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Sample records for acid-3 receptor-mediated feed-forward

  1. Additive Feed Forward Control with Neural Networks

    Sørensen, O.

    1999-01-01

    suitable 'shaped' (low-pass filtered) reference is used to overcome problems with excessive control action when using a controller acting as the inverse process model. The control concept is Additive Feed Forward Control, where the trained neural network controller, acting as the inverse process model, is...

  2. Propagating Synchrony in Feed-Forward Networks

    Sven eJahnke

    2013-11-01

    Full Text Available Coordinated patterns of precisely timed action potentials (spikes emerge in a variety of neural circuits but their dynamical originis still not well understood. One hypothesis states that synchronous activity propagating through feed-forward chains of groups of neurons (synfire chains may dynamically generate such spike patterns. Additionally, synfire chains offer the possibility to enable reliable signal transmission. So far, mostly densely connected chains, often with all-to-all connectivity between groups, have been theoretically and computationally studied. Yet, such prominent feed-forward structures have not been observed experimentally. Here we analytically and numerically investigate under which conditions diluted feed-forward chains may exhibit synchrony propagation. In addition to conventional linear input summation, we study the impact of nonlinear, non-additive summation accounting for the effect of fast dendritic spikes. The non-linearities promote synchronous inputs to generate precisely timed spikes. We identify how non-additive coupling relaxes the conditions on connectivity such that it enables synchrony propagation at connectivities substantially lower than required for linearly coupled chains. Although the analytical treatment is based on a simple leaky integrate-and-fire neuron model, we show how to generalize our methods to biologically more detailed neuron models and verify our results by numerical simulations with, e.g., Hodgkin Huxley type neurons.

  3. Feed forward control: An implementation at CIRFEL

    Krishnaswamy, J.; Lehrman, I.S.; Hartley, R. [Northrop Grumman Advanced Technology and Development Center, Princeton, NJ (United States)] [and others

    1995-12-31

    An integral part of the Compact InfraRed Free Electron LASER (CIRFEL) is control of the phase and amplitude stability in the RF power system. We have implemented such a Feed Forward system using the LabView software package, by National Instruments. We will discuss implementation and performance data of the Feed Forward control of the RF power system at CIRFEL. We will also briefly discuss some conditions under which the problem is ill-conditioned, and what idealizations can be made to remedy these ill-conditioned systems. Using an arbitrary function generator, we generate a driving signal for a voltage-controlled attenuator at the input side of the RF system, and we monitor the RF voltage in cell I of the photocathode gun using a digital storage oscilliscope in averaging mode. The system is stable enough to use data from one shot to modify the inputs for future shots. After downloading the averaged data to a personal computer via a GPIB (IEEE 488) bus, we use a simple linear transformation on the difference waveform between the current shot and the target to produce a correction signal. This signal is added to the driving signal in the arbitrary function generator, and the process is repeated until we get the flatness we need in the output signals from cell 1. The system for phase control is similar, with a voltage-controlled phase shifter replacing the attenuator, and monitoring of the RF phase in cell I replacing the monitoring of RF voltage. By repeatedly alternating between correcting the RF voltage (equivalent to correcting the RF power) and RF phase in cell 1, we are able to achieve simultaneous phase variations of <{+-}1{degrees} and amplitude variations of <{+-}0.1% over a 3{mu}sec pulse.

  4. Feed Forward Neural Network Algorithm for Frequent Patterns Mining

    Dr. K.R.Pardasani; Sanjay Sharma; Amit Bhagat

    2010-01-01

    Association rule mining is used to find relationships among items in large data sets. Frequent patterns mining is an important aspect in association rule mining. In this paper, an efficient algorithm named Apriori-Feed Forward(AFF) based on Apriori algorithm and the Feed Forward Neural Network is presented to mine frequent patterns. Apriori algorithm scans database many times to generate frequent itemsets whereas Apriori-Feed Forward(AFF) algorithm scans database Only Once. Computational resu...

  5. Adaptive feed-forward loop connection based on error signal

    Hidaka, Koichi

    2005-12-01

    In this paper, we investigate effect of changing the connection of feed-forward loop based on error signal. Our motivation of this work is solution to progress of human skill. For the skill model, we study a human simple action such as arm motion. Many models that describe the human arm dynamics have been proposed in recent year. While one type does not need an inverse model of human dynamics, the system based on the model does not include feed-forward loop. On the other hand, another type model has a feed-forward loop and feedback loop systems. This type assumes feed-forward element includes an internal model by repeating action or training and this loop progress our skill. Then we usually have to exercise to get a good performance. This says that we design the internal motion model by training and we move on prediction for motion. Under the assumption, Kawato model is well known. The model proposed that learning of feed-forward element is promoted in brain so that the error of feedback loop decreases. Furthermore, we assume the connections in feedback loop and feed-forward loop are changed. We show numerical simulations and consider that the position error given by our vision changes the skill element and we confirm that the position error is the one of the estimate function for the improvement in our skill.

  6. A brief review of feed-forward neural networks

    SAZLI, Murat Hüsnü

    2006-01-01

    Artificial neural networks, or shortly neural networks, find applications in a very wide spectrum. In this paper, following a brief presentation of the basic aspects of feed-forward neural networks, their mostly used learning/training algorithm, the so-called back-propagation algorithm, have been described.

  7. Adaptive feed forward in the LANL RF control system

    This paper describes an adaptive feed forward system that corrects repetitive errors in the amplitude and phase of the RF field of a pulsed accelerator. High-frequency disturbances that are beyond the effective bandwidth of the RF-field feedback control system can be eliminated with a feed forward system. Many RF-field disturbances for a pulsed accelerator are repetitive, occurring at the same relative time in every pulse. This design employs digital signal processing hardware to adaptively determine and track the control signals required to eliminate the repetitive errors in the feedback control system. In order to provide the necessary high-frequency response, the adaptive feed forward hardware provides the calculated control signal prior to the repetitive disturbance that it corrects. This system has been demonstrated to reduce the transient disturbances caused by beam pulses. Furthermore, it has been shown to negate high-frequency phase and amplitude oscillations in a high-power klystron amplifier caused by PFN ripple on the high-voltage. The design and results of the adaptive feed forward system are presented. (Author) 3 figs., 2 refs

  8. A new C++ implemented feed forward neural network simulator

    J. Sütő

    2013-12-01

    Full Text Available This paper presents the implementation of a simulator application for feed forward neural networks which was made in Qt application framework. The paper demonstrates the object oriented design and the performance of the software. The main topics cover the class organization and some test results where the Matlab neural network toolbox was used as reference.

  9. Learning Process of a Stochastic Feed-Forward Neural Network

    Fujiki, Sumiyoshi; Fujiki, Nahomi

    1995-03-01

    A positive reinforcement type learning algorithm is formulated for a stochastic feed-forward neural network by minimizing a relative entropic measure, and a learning equation similar to that of the Boltzmann machine is obtained. The learning of the network actually shows a similar result to that of the Boltzmann machine in the classification problems of AND and XOR, by numerical experiments.

  10. Feed-Forward Neural Networks and Minimal Search Space Learning

    Neruda, Roman

    2005-01-01

    Roč. 4, č. 12 (2005), s. 1867-1872. ISSN 1109-2750 R&D Projects: GA ČR GA201/05/0557 Institutional research plan: CEZ:AV0Z10300504 Keywords : search space * feed-forward networks * genetic algorithm s Subject RIV: BA - General Mathematics

  11. Quantum teleportation over 143 kilometres using active feed-forward.

    Ma, Xiao-Song; Herbst, Thomas; Scheidl, Thomas; Wang, Daqing; Kropatschek, Sebastian; Naylor, William; Wittmann, Bernhard; Mech, Alexandra; Kofler, Johannes; Anisimova, Elena; Makarov, Vadim; Jennewein, Thomas; Ursin, Rupert; Zeilinger, Anton

    2012-09-13

    The quantum internet is predicted to be the next-generation information processing platform, promising secure communication and an exponential speed-up in distributed computation. The distribution of single qubits over large distances via quantum teleportation is a key ingredient for realizing such a global platform. By using quantum teleportation, unknown quantum states can be transferred over arbitrary distances to a party whose location is unknown. Since the first experimental demonstrations of quantum teleportation of independent external qubits, an internal qubit and squeezed states, researchers have progressively extended the communication distance. Usually this occurs without active feed-forward of the classical Bell-state measurement result, which is an essential ingredient in future applications such as communication between quantum computers. The benchmark for a global quantum internet is quantum teleportation of independent qubits over a free-space link whose attenuation corresponds to the path between a satellite and a ground station. Here we report such an experiment, using active feed-forward in real time. The experiment uses two free-space optical links, quantum and classical, over 143 kilometres between the two Canary Islands of La Palma and Tenerife. To achieve this, we combine advanced techniques involving a frequency-uncorrelated polarization-entangled photon pair source, ultra-low-noise single-photon detectors and entanglement-assisted clock synchronization. The average teleported state fidelity is well beyond the classical limit of two-thirds. Furthermore, we confirm the quality of the quantum teleportation procedure without feed-forward by complete quantum process tomography. Our experiment verifies the maturity and applicability of such technologies in real-world scenarios, in particular for future satellite-based quantum teleportation. PMID:22951967

  12. Feed Forward Neural Network for Solid Waste Image Classification

    Zailah, W.; Hannan, M. A.; Abdulla Al Mamun

    2013-01-01

    This study deals with the Feed Forward Neutral Network (FFNN) model to classify the level content of waste based on teaching and learning concept. An FFNN with twenty images is used for testing the input samples through the neural network learning to compute the sum squared error to ensure the performance of the model. After several training the neural network was able to learn and match the target. Thirty images for each class are used as a fullest of inputs samples for classifying. Result f...

  13. Topological reversibility and causality in feed-forward networks

    Corominas-Murtra, Bernat; RodrIguez-Caso, Carlos; Sole, Ricard [ICREA-Complex Systems Lab, Universitat Pompeu Fabra (Parc de Recerca Biomedica de Barcelona), Dr Aiguader 88, 08003 Barcelona (Spain); Goni, JoaquIn, E-mail: bernat.corominas@upf.ed [Functional Neuroimaging Laboratory, Department of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona (Spain)

    2010-11-15

    Systems whose organization displays causal asymmetry constraints, from evolutionary trees to river basins or transport networks, can often be described in terms of directed paths on a discrete set of arbitrary units including states in state spaces, feed-forward neural nets, the evolutionary history of a given collection of events or the chart of computational states visited along a complex computation. Such a set of paths defines a feed-forward, acyclic network. A key problem associated with these systems involves characterizing their intrinsic degree of path reversibility: given an end node in the graph, what is the uncertainty of recovering the process backwards until the origin? Here, we propose a novel concept, topological reversibility, which is a measure of the complexity of the net that rigorously weights such uncertainty in path dependency, quantifying the minimum amount of information required to successfully reverse a causal path. Within the proposed framework, we also analytically characterize limit cases for both topologically reversible and maximally entropic structures. The relevance of these measures within the context of evolutionary dynamics is highlighted.

  14. Noise propagation with interlinked feed-forward pathways

    Chepyala, Surendhar Reddy; Chen, Yi-Chen; Yan, Ching-Cher Sanders; Lu, Chun-Yi David; Wu, Yi-Chun; Hsu, Chao-Ping

    2016-01-01

    Functionally similar pathways are often seen in biological systems, forming feed-forward controls. The robustness in network motifs such as feed-forward loops (FFLs) has been reported previously. In this work, we studied noise propagation in a development network that has multiple interlinked FFLs. A FFL has the potential of asymmetric noise-filtering (i.e., it works at either the “ON” or the “OFF” state in the target gene). With multiple, interlinked FFLs, we show that the propagated noises are largely filtered regardless of the states in the input genes. The noise-filtering property of an interlinked FFL can be largely derived from that of the individual FFLs, and with interlinked FFLs, it is possible to filter noises in both “ON” and “OFF” states in the output. We demonstrated the noise filtering effect in the developmental regulatory network of Caenorhabditis elegans that controls the timing of distal tip cell (DTC) migration. The roles of positive feedback loops involving blmp-1 and the degradation regulation of DRE-1 also studied. Our analyses allow for better inference from network structures to noise-filtering properties, and provide insights into the mechanisms behind the precise DTC migration controls in space and time. PMID:27029397

  15. Feed forward neural networks modeling for K-P interactions

    Artificial intelligence techniques involving neural networks became vital modeling tools where model dynamics are difficult to track with conventional techniques. The paper make use of the feed forward neural networks (FFNN) to model the charged multiplicity distribution of K-P interactions at high energies. The FFNN was trained using experimental data for the multiplicity distributions at different lab momenta. Results of the FFNN model were compared to that generated using the parton two fireball model and the experimental data. The proposed FFNN model results showed good fitting to the experimental data. The neural network model performance was also tested at non-trained space and was found to be in good agreement with the experimental data

  16. Comparative study of gas sections of heavy water production plant based on gas feed forward and liquid feed forward

    Deuterium, an isotope of hydrogen, present in natural water in almost negligible amount but it is used for numerous purposes (both civil and defense). Special techniques are used to separate the negligible amount of deuterium contents from natural water and thereafter to 99.99 percent purity. Girdler Sulfide (GS) process is based on the exchange technique between two phases i.e. liquid (water) and gas (H/sub 2/S) and this technique was developed in 40s and also being used in the present era. The work is being done to analyze the performance of heavy water enrichment method based on original GS process termed as Liquid Feed Forward (LFF) and slight modification in the original design termed as Gas Feed Forward (GFF). The comparison on the material balance flow sheets, recovery, economy, efficiency and requirement of number of plates in both the processes is provided as adequate information to the readers to comprehend the differences in both the processes. In the original process i.e LFF water is pumped directly to 2nd stage from 1st stage but in the modified design i.e. GFF water is not directly pumped to 2nd stage to 1st stage and being circulated in a close cycle. The comparison is being done by the material balance results for both processes by keeping the recovery constant for both processes and determining the Number of Plates (Np). For the recovery of 0.505 Kg mol/hr; Np for 2nd stage Hot Tower (HT) required was 91 and for 2nd stage Cold Towers (CT) required was 55 for LFF and Np required was 65 and 53 respectively for GFF. Hence it is possible to achieve the desired enrichment with slight modification and improvement in performance by adopting the GFF. (author)

  17. Review of feed forward neural network classification preprocessing techniques

    Asadi, Roya; Kareem, Sameem Abdul

    2014-06-01

    The best feature of artificial intelligent Feed Forward Neural Network (FFNN) classification models is learning of input data through their weights. Data preprocessing and pre-training are the contributing factors in developing efficient techniques for low training time and high accuracy of classification. In this study, we investigate and review the powerful preprocessing functions of the FFNN models. Currently initialization of the weights is at random which is the main source of problems. Multilayer auto-encoder networks as the latest technique like other related techniques is unable to solve the problems. Weight Linear Analysis (WLA) is a combination of data pre-processing and pre-training to generate real weights through the use of normalized input values. The FFNN model by using the WLA increases classification accuracy and improve training time in a single epoch without any training cycle, the gradient of the mean square error function, updating the weights. The results of comparison and evaluation show that the WLA is a powerful technique in the FFNN classification area yet.

  18. Feed-Forward Control of Kite Power Systems

    Fechner, Uwe; Schmehl, Roland

    2014-06-01

    Kite power technology is a novel solution to harvest wind energy from altitudes that can not be reached by conventional wind turbines. The use of a lightweight but strong tether in place of an expensive tower provides an additional cost advantage, next to the higher capacity factor. This paper describes a method to estimate the wind velocity at the kite using measurement data at the kite and at the ground. Focussing on a kite power system, which is converting the traction power of a kite in a pumping mode of operation, a reel-out speed predictor is presented for use in feed-forward control of the tether reel-out speed of the winch. The results show, that the developed feedforward controller improves the force control accuracy by a factor of two compared to the previously used feedback controller. This allows to use a higher set force during the reel-out phase which in turn increases the average power output by more than 4%. Due to its straightforward implementation and low computational requirements feedforward control is considered a promising technique for the reliable and efficient operation of traction-based kite power systems.

  19. Feed-Forward Control of Kite Power Systems

    Kite power technology is a novel solution to harvest wind energy from altitudes that can not be reached by conventional wind turbines. The use of a lightweight but strong tether in place of an expensive tower provides an additional cost advantage, next to the higher capacity factor. This paper describes a method to estimate the wind velocity at the kite using measurement data at the kite and at the ground. Focussing on a kite power system, which is converting the traction power of a kite in a pumping mode of operation, a reel-out speed predictor is presented for use in feed-forward control of the tether reel-out speed of the winch. The results show, that the developed feedforward controller improves the force control accuracy by a factor of two compared to the previously used feedback controller. This allows to use a higher set force during the reel-out phase which in turn increases the average power output by more than 4%. Due to its straightforward implementation and low computational requirements feedforward control is considered a promising technique for the reliable and efficient operation of traction-based kite power systems

  20. Adaptive Feed-Forward Control of Low Frequency Interior Noise

    Kletschkowski, Thomas

    2012-01-01

    This book presents a mechatronic approach to Active Noise Control (ANC). It describes the required elements of system theory, engineering acoustics, electroacoustics and adaptive signal processing in a comprehensive, consistent and systematic manner using a unified notation. Furthermore, it includes a design methodology for ANC-systems, explains its application and describes tools to be used for ANC-system design. From the research point of view, the book presents new approaches to sound source localization in weakly damped interiors. One is based on the inverse finite element method, the other is based on a sound intensity probe with an active free field. Furthermore, a prototype of an ANC-system able to reach the physical limits of local (feed-forward) ANC is described. This is one example for applied research in ANC-system design. Other examples are given for (i) local ANC in a semi-enclosed subspace of an aircraft cargo hold and (ii) for the combination of audio entertainment with ANC.

  1. Prediction of metal corrosion using feed-forward neural networks

    The reliable prediction of corrosion behavior for the effective control of corrosion is a fundamental requirement. Since real world corrosion never seems to involve quite the same conditions that have previously been tested, using corrosion literature does not provide the necessary answers. In order to provide a methodology for predicting corrosion in real and complex situations, artificial neural networks can be utilized. Feed-forward artificial neural network (FFANN) is an information-processing paradigm inspired by the way the densely interconnected, parallel structure of the human brain process information.The aim of the present work is to predict corrosion behavior in critical conditions, such as industrial applications, based on some laboratory experimental data. Electrochemical behavior of stainless steel in different conditions were studied, using polarization technique and Tafel curves. Back-propagation neural networks models were developed to predict the corrosion behavior. The trained networks result in predicted value in good comparison to the experimental data. They have generally been claimed to be successful in modeling the corrosion behavior. The results are presented in two tables. Table 1 gives corrosion behavior of stainless-steel as a function of pH and CuSO4 concentration and table 2 gives corrosion behavior of stainless - steel as a function of electrode surface area and CuSO4 concentration. (authors)

  2. A Feed-forward Geometrical Compensation and Adaptive Feedback Control Algorithm for Hydraulic Robot Manipulators

    Conrad, Finn; Zhou, Jianjun; Gabacik, Andrzej; Stecki, Jacek

    1998-01-01

    Invited paper presents a new control algorithm based on feed-forward geometrical compensation strategy combined with adaptive feedback control.......Invited paper presents a new control algorithm based on feed-forward geometrical compensation strategy combined with adaptive feedback control....

  3. Feed-Forward: Students Gaining More from Assessment via Deeper Engagement in Video-Recorded Presentations

    Murphy, Karen; Barry, Shane

    2016-01-01

    Presentation feedback can be limited in its feed-forward value, as students do not have their actual presentation available for review whilst reflecting upon the feedback. This study reports on students' perceptions of the learning and feed-forward value of an oral presentation assessment. Students self-marked their performance immediately after…

  4. Feed-forward motor control of ultrafast, ballistic movements.

    Kagaya, K; Patek, S N

    2016-02-01

    To circumvent the limits of muscle, ultrafast movements achieve high power through the use of springs and latches. The time scale of these movements is too short for control through typical neuromuscular mechanisms, thus ultrafast movements are either invariant or controlled prior to movement. We tested whether mantis shrimp (Stomatopoda: Neogonodactylus bredini) vary their ultrafast smashing strikes and, if so, how this control is achieved prior to movement. We collected high-speed images of strike mechanics and electromyograms of the extensor and flexor muscles that control spring compression and latch release. During spring compression, lateral extensor and flexor units were co-activated. The strike initiated several milliseconds after the flexor units ceased, suggesting that flexor activity prevents spring release and determines the timing of strike initiation. We used linear mixed models and Akaike's information criterion to serially evaluate multiple hypotheses for control mechanisms. We found that variation in spring compression and strike angular velocity were statistically explained by spike activity of the extensor muscle. The results show that mantis shrimp can generate kinematically variable strikes and that their kinematics can be changed through adjustments to motor activity prior to the movement, thus supporting an upstream, central-nervous-system-based control of ultrafast movement. Based on these and other findings, we present a shishiodoshi model that illustrates alternative models of control in biological ballistic systems. The discovery of feed-forward control in mantis shrimp sets the stage for the assessment of targets, strategic variation in kinematics and the role of learning in ultrafast animals. PMID:26643091

  5. Gaussian and feed-forward neural network classifiers for shower recognition, generalization and parallel implementation

    The performance of Gaussian and feed-forward neural network classifiers, is compared with respect to the recognition of energy deposition patterns in a calorimeter. Implementation aspects of these classifiers for a multi-processor architecture are discussed

  6. Feed-Forward versus Feedback Inhibition in a Basic Olfactory Circuit

    Tiffany Kee; Pavel Sanda; Nitin Gupta; Mark Stopfer; Maxim Bazhenov

    2015-01-01

    Inhibitory interneurons play critical roles in shaping the firing patterns of principal neurons in many brain systems. Despite difference in the anatomy or functions of neuronal circuits containing inhibition, two basic motifs repeatedly emerge: feed-forward and feedback. In the locust, it was proposed that a subset of lateral horn interneurons (LHNs), provide feed-forward inhibition onto Kenyon cells (KCs) to maintain their sparse firing--a property critical for olfactory learning and memory...

  7. Simple Digital Feed-Forward Circuit to Compensate for AOM Thermal Lensing

    Hill, Joshua; Aman, James; Killian, Thomas; Neutral Experiment Team

    2016-05-01

    I demonstrate a simple digital feed-forward circuit which, when combined with two-frequency radio frequency (RF) electronics, maintains constant total RF power driving an acousto-optic modulator (AOM). Consistency in total power is desirable to mitigate thermal lensing effects that otherwise displace and misshape the laser beam when the primary frequency drive RF power is changed to, for example, alter the laser power in a diffracted beam. The Arduino-based feed-forward circuit is cost-effective, quick to implement, and easily modified.

  8. Feed Forward Orbit Correction in the CLIC Ring to Main LINAC Transfer lines

    Apsimon, R; Schulte, D; Uythoven, J

    2014-01-01

    The emittance growth in the betatron collimation system of the 27 km long transfer lines between the CLIC damping rings and the main LINAC depends strongly on the transverse orbit jitter. The resulting stability requirements of the damping ring extraction elements seem extremely difficult to achieve. Position and angle feed forward systems in these long transfer lines bring the specified parameters of the extraction elements within reach. The designs of the optics and feed forward hardware are presented together with tracking simulations of the systems.

  9. Endothelin receptor-mediated vasodilatation

    Nilsson, David; Wackenfors, Angelica; Gustafsson, Lotta;

    2008-01-01

    Culture of intact arteries is a frequently employed experimental model for investigating the mechanisms governing the regulation of vascular endothelin receptors. Endothelin type A (ET(A)) and type B (ET(B)) receptors on vascular smooth muscle cells are up-regulated in organ culture and the...... enhanced vasoconstriction mimics the changes that occur in cardiovascular disease. The effect of organ culture on endothelial dilatory endothelin ET(B) receptors is not known. We hypothesize that organ culture decreases the endothelin receptor-mediated dilatation and that this is one possible mechanism by...... denudation. The increase in sarafotoxin 6c contraction after removal of the endothelium was more pronounced before than after organ culture, suggesting down-regulated endothelial endothelin ET(B) receptors. Also, the immunofluorescence staining intensities for endothelial endothelin ET(B) receptors were...

  10. Modulation of spike and burst rate in a minimal neuronal circuit with feed-forward inhibition

    F. Zeldenrust; W.J. Wadman

    2013-01-01

    Pyramidal cells perform computations on their inputs within the context of the local network. The present computational study investigates the consequences of feed-forward inhibition for the firing rate and reliability of a typical hippocampal pyramidal neuron that can respond with single spikes as

  11. Application of self-adaptive feed-forward control in linac systems

    In this paper, the basis of the self-adaptive feed-forward RF control (SAFF) is discussed and its analytical formulation introduced. It is adopted in Beijing Free Electron Laser facility (BFEL) to control the beam loading effect of the thermionic cathode RF gun and proves to be effective. Other possible applications of SAFF in linac are also discussed

  12. Using Hybrid Algorithm to Improve Intrusion Detection in Multi Layer Feed Forward Neural Networks

    Ray, Loye Lynn

    2014-01-01

    The need for detecting malicious behavior on a computer networks continued to be important to maintaining a safe and secure environment. The purpose of this study was to determine the relationship of multilayer feed forward neural network architecture to the ability of detecting abnormal behavior in networks. This involved building, training, and…

  13. Instantaneous Gradient Based Dual Mode Feed-Forward Neural Network Blind Equalization Algorithm

    Ying Xiao

    2013-01-01

    Full Text Available To further improve the performance of feed-forward neural network blind equalization based on Constant Modulus Algorithm (CMA cost function, an instantaneous gradient based dual mode between Modified Constant Modulus Algorithm (MCMA and Decision Directed (DD algorithm was proposed. The neural network weights change quantity of the adjacent iterative process is defined as instantaneous gradient. After the network converges, the weights of neural network to achieve a stable energy state and the instantaneous gradient would be zero. Therefore dual mode algorithm can be realized by criterion which set according to the instantaneous gradient. Computer simulation results show that the dual mode feed-forward neural network blind equalization algorithm proposed in this study improves the convergence rate and convergence precision effectively, at the same time, has good restart and tracking ability under channel burst interference condition.

  14. Entangling Color-Different Photons via Time-Resolved Measurement and Active Feed-Forward

    Zhao, Tian-Ming; Yang, Jian; Sang, Zi-Ru; Jiang, Xiao; Bao, Xiao-Hui; Pan, Jian-Wei

    2015-01-01

    Entangling independent photons is not only of fundamental interest but also of crucial importance for quantum information science. Two-photon interference is a major method to entangle independent identical photons. If two photons are color-different, perfect two-photon coalescence cannot happen anymore, which makes the entangling of color-different photons difficult to realize. In this letter by exploring and developing time-resolved measurement and active feed-forward, we have entangled two independent photons of different colors for the first time. We find that entanglement with a varying form can be identified for different two-photon temporal modes through time-resolved measurement. By using active feed-forward we are able to convert the varying entanglement into uniform. Adopting these measures, we have successfully entangled two photons with a frequency separation of 16 times larger than their linewidths. In addition to its fundamental interest, our work also provides an approach to solve the frequency...

  15. Feed-Forward Corrections for Tune and Chromaticity Injection Decay During 2015 LHC Operation

    Solfaroli Camillocci, Matteo; Lamont, Mike; Schaumann, Michaela; Todesco, Ezio; Wenninger, Jorg

    2016-01-01

    After two years of shutdown, the Large Hadron Collider (LHC) has been operated in 2015 at 6.5 TeV, close to its designed energy. When the current is stable at low field, the harmonic components of the main circuits are subject to a dynamic variation induced by current redistribution on the superconducting cables. The Field Description of the LHC (FiDel) foresaw an increase of the decay at injection of tune (quadrupolar components) and chromaticity (sextupolar components) of about 50% with respect to LHC Run1 due to the higher operational current. This paper discusses the beam-based measurements of the decay during the injection plateau and the implementation and accuracy of the feed-forward corrections as present in 2015. Moreover, the observed tune shift proportional to the circulating beam intensity and it's foreseen feed-forward correction are covered.

  16. Quantum teleportation using active feed-forward between two Canary Islands

    Ma, Xiao-song; Scheidl, Thomas; Wang, Daqing; Kropatschek, Sebastian; Naylor, William; Mech, Alexandra; Wittmann, Bernhard; Kofler, Johannes; Anisimova, Elena; Makarov, Vadim; Jennewein, Thomas; Ursin, Rupert; Zeilinger, Anton

    2012-01-01

    Quantum teleportation [1] is a quintessential prerequisite of many quantum information processing protocols [2-4]. By using quantum teleportation, one can circumvent the no-cloning theorem [5] and faithfully transfer unknown quantum states to a party whose location is even unknown over arbitrary distances. Ever since the first experimental demonstrations of quantum teleportation of independent qubits [6] and of squeezed states [7], researchers have progressively extended the communication distance in teleportation, usually without active feed-forward of the classical Bell-state measurement result which is an essential ingredient in future applications such as communication between quantum computers. Here we report the first long-distance quantum teleportation experiment with active feed-forward in real time. The experiment employed two optical links, quantum and classical, over 143 km free space between the two Canary Islands of La Palma and Tenerife. To achieve this, the experiment had to employ novel techni...

  17. DESIGNING PHYSICAL EDUCATION LESSONS IN PRIMARY SCHOOL BY CONTENT TYPE FEED-FORWARD

    Cojanu Florin

    2010-01-01

    In actual didactic design is need to anticipate problems that may arise during implementation of proposed interdisciplinary content in the physical education lesson in class, by projecting sequential forward type of content, there by ensuring quality and efficiency. Its necessary to include in the design content of physical education lessons in primary sequence type of feed-forward, to increase the quality and effectiveness of physical education lessons at the operational objectives achieved....

  18. In-Orbit Magnetic Disturbance Compensation using Feed Forward Control in Nano-JASMINE Mission

    Inamori, Takaya

    2008-01-01

    Nano-JASMINE is planned as a nano astrometry satellite at the ISSL lab, University of Tokyo in cooperation with the National Astronomical Observatory of Japan (NAOJ). This research presents the method for controlling the attitude using a feed forward controller. During Nano-JASMINE’s operation in space, magnetic disturbances are dominant and must be canceled to ensure astrometric observations and measurements. This paper concludes that the use of magnetic disturbance compensation is indispens...

  19. A mixed incoherent feed-forward loop contributes to the regulation of bacterial photosynthesis genes

    Mank, Nils N.; Berghoff, Bork A.; Klug, Gabriele

    2013-01-01

    Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes. In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand. Recently, we identified a mixed incoherent feed-forward loop comprising the transcription factor PrrA, the sRNA PcrZ and photosyn...

  20. Automatic Identification of Tomato Maturation Using Multilayer Feed Forward Neural Network with Genetic Algorithms (GA)

    FANG Jun-long; ZHANG Chang-li; WANG Shu-wen

    2004-01-01

    We set up computer vision system for tomato images. By using this system, the RGB value of tomato image was converted into HIS value whose H was used to acquire the color character of the surface of tomato. To use multilayer feed forward neural network with GA can finish automatic identification of tomato maturation. The results of experiment showed that the accuracy was upto 94%.

  1. Determining the Efficient Structure of Feed-Forward Neural Network to Classify Breast Cancer Dataset

    Ahmed Khalid; Noureldien A. Noureldien

    2014-01-01

    Classification is one of the most frequently encountered problems in data mining. A classification problem occurs when an object needs to be assigned in predefined classes based on a number of observed attributes related to that object. Neural networks have emerged as one of the tools that can handle the classification problem. Feed-forward Neural Networks (FNN's) have been widely applied in many different fields as a classification tool. Designing an efficient FNN structure with optimum numb...

  2. Feed forward neural networks and genetic algorithms for automated financial time series modelling

    Kingdon, J. C.

    1995-01-01

    This thesis presents an automated system for financial time series modelling. Formal and applied methods are investigated for combining feed-forward Neural Networks and Genetic Algorithms (GAs) into a single adaptive/learning system for automated time series forecasting. Four important research contributions arise from this investigation: i) novel forms of GAs are introduced which are designed to counter the representational bias associated with the conventional Holland GA, ii) an...

  3. Learning algorithms and probability distributions in feed-forward and feed-back networks

    Hopfield, J J

    1987-01-01

    Learning algorithms have been used both on feed-forward deterministic networks and on feed-back statistical networks to capture input-output relations and do pattern classification. These learning algorithms are examined for a class of problems characterized by noisy or statistical data, in which the networks learn the relation between input data and probability distributions of answers. In simple but nontrivial networks the two learning rules are closely related. Under some circumstances the...

  4. Feed-forward and feedback projections of midbrain reticular formation neurons in the cat

    Eddie Perkins; May, Paul J.; Susan Warren

    2014-01-01

    Gaze changes involving the eyes and head are orchestrated by brainstem gaze centers found within the superior colliculus (SC), paramedian pontine reticular formation (PPRF), and medullary reticular formation (MdRF). The mesencephalic reticular formation (MRF) also plays a role in gaze. It receives a major input from the ipsilateral SC and contains cells that fire in relation to gaze changes. Moreover, it provides a feedback projection to the SC and feed-forward projections to the PPRF and MdR...

  5. An Open Loop Feed-Forward Control Scheme for Bioinspired Artificial Hair Cell Sensors

    Crowley, Kevin Michael

    2015-01-01

    This research documents the creation and use of an open-loop feed forward control scheme designed to manipulate the DC potential across lipid bilayer membranes in artificial hair cell sensors. Inspired by the human cochlea's non-linear gain phenomenon, whereby the cochlea can increase or decrease the effective gain of the auditory system, this controller is the first step in developing more sophisticated signal processing schemes for use with future bio-inspired artificial hair cell developme...

  6. Aversive Learning and Appetitive Motivation Toggle Feed-Forward Inhibition in the Drosophila Mushroom Body.

    Perisse, Emmanuel; Owald, David; Barnstedt, Oliver; Talbot, Clifford B; Huetteroth, Wolf; Waddell, Scott

    2016-06-01

    In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach. PMID:27210550

  7. Feed-forward and feedback projections of midbrain reticular formation neurons in the cat

    Eddie Perkins

    2014-01-01

    Full Text Available Gaze changes involving the eyes and head are orchestrated by brainstem gaze centers found within the superior colliculus (SC, paramedian pontine reticular formation (PPRF, and medullary reticular formation (MdRF. The mesencephalic reticular formation (MRF also plays a role in gaze. It receives a major input from the ipsilateral SC and contains cells that fire in relation to gaze changes. Moreover, it provides a feedback projection to the SC and feed-forward projections to the PPRF and MdRF. We sought to determine whether these MRF feedback and feed-forward projections originate from the same or different neuronal populations by utilizing paired fluorescent retrograde tracers in cats. Specifically, we tested: 1. whether MRF neurons that control eye movements form a single population by injecting the SC and PPRF with different tracers, and 2. whether MRF neurons that control head movements form a single population by injecting the SC and MdRF with different tracers. In neither case were double labeled neurons observed, indicating that feedback and feed-forward projections originate from separate MRF populations. In both cases, the labeled reticulotectal and reticuloreticular neurons were distributed bilaterally in the MRF. However, neurons projecting to the MdRF were generally constrained to the medial half of the MRF, while those projecting to the PPRF, like MRF reticulotectal neurons, were spread throughout the mediolateral axis. Thus, the medial MRF may be specialized for control of head movements, with control of eye movements being more widespread in this structure.

  8. Evolvability of feed-forward loop architecture biases its abundance in transcription networks

    Widder Stefanie

    2012-01-01

    Full Text Available Abstract Background Transcription networks define the core of the regulatory machinery of cellular life and are largely responsible for information processing and decision making. At the small scale, interaction motifs have been characterized based on their abundance and some seemingly general patterns have been described. In particular, the abundance of different feed-forward loop motifs in gene regulatory networks displays systematic biases towards some particular topologies, which are much more common than others. The causative process of this pattern is still matter of debate. Results We analyzed the entire motif-function landscape of the feed-forward loop using the formalism developed in a previous work. We evaluated the probabilities to implement possible functions for each motif and found that the kurtosis of these distributions correlate well with the natural abundance pattern. Kurtosis is a standard measure for the peakedness of probability distributions. Furthermore, we examined the functional robustness of the motifs facing mutational pressure in silico and observed that the abundance pattern is biased by the degree of their evolvability. Conclusions The natural abundance pattern of the feed-forward loop can be reconstructed concerning its intrinsic plasticity. Intrinsic plasticity is associated to each motif in terms of its capacity of implementing a repertoire of possible functions and it is directly linked to the motif's evolvability. Since evolvability is defined as the potential phenotypic variation of the motif upon mutation, the link plausibly explains the abundance pattern.

  9. Near-infrared Spectral Detection of the Content of Soybean Fat Acids Based on Genetic Multilayer Feed forward Neural Network

    CHAI Yu-hua; PAN Wei; NING Hai-long

    2005-01-01

    In the paper, a method of building mathematic model employing genetic multilayer feed forward neural network is presented, and the quantitative relationship of chemical measured values and near-infrared spectral data is established. In the paper, quantitative mathematic model related chemical assayed values and near-infrared spectral data is established by means of genetic multilayer feed forward neural network, acquired near-infrared spectral data are taken as input of network with the content of five kinds of fat acids tested from chemical method as output,weight values of multilayer feed forward neural network are trained by genetic algorithms and detection model of neural network of soybean is built. A kind of multilayer feed forward neural network trained by genetic algorithms is designed in the paper. Through experiments, all the related coefficients of five fat acids can approach 0.9 which satisfies the preliminary test of soybean breeding.

  10. A data-driven feed-forward decision framework for building clusters operation under uncertainty

    Highlights: • A self-tuned and noise-tolerant building clusters model is developed. • A feed-forward decision framework is proposed for building clusters operation. • Four data fusion techniques are compared in terms of accuracy and robustness. • Operation decision obtained by the proposed framework can achieve more cost saving. - Abstract: Building plays a significant role for energy consumption and carbon dioxide emission in the United States. Extensive researches are conducted to develop effective operation strategy for the building system. However, less study is to investigate the energy sharing among a cluster of multiple buildings (aka building clusters) under uncertainty. In this research, we propose to develop a data-driven feed-forward decision framework for building clusters operation, through the use of noise-tolerant data fusion techniques. Three stages are implemented in the proposed framework which include: (1) decisions generation stage that employs an augmented multi-objective particle swarm optimization based decision framework to obtain operation decisions for the next future L hours; (2) execution stage that implements the first l hours decisions; and (3) calibration stage that employs data fusion techniques to calibrate the building clusters model in a l′ hour scale. The calibrated model is fed back to the decisions generation stage for the next period decisions. Unscented Kalman filter which is demonstrated to outperform other data fusion techniques in terms of accuracy, robustness and computational efficiency based on our experimental results is employed in the calibration stage. To evaluate the performance of the proposed framework, we compare the operation decisions with and without calibration stage. It is demonstrated that the proposed feed-forward framework can obtain operation decisions to achieve more cost savings. The impacts of different time lengths l in the execution stage are investigated which indicate the selection of l

  11. Selection of hadronic W-decays in DELPHI with feed forward neural networks - An update

    Becks, K H; Müller, U; Wahlen, H

    2003-01-01

    Since 1998 feed forward neural networks have been successfully applied to select candidates of hadronic W-decays measured at different center of mass-energies by the DELPHI collaboration at the Large Electron Positron collider at CERN. To prepare the final publication, the neural network was adapted to all center of mass- energies. Detailed studies were performed concerning the level of preselection, the choice of network parameters and especially of the network architecture. The number of hidden nodes was optimized by testing different pruning methods. All studies and results will be discussed.

  12. DESIGNING PHYSICAL EDUCATION LESSONS IN PRIMARY SCHOOL BY CONTENT TYPE FEED-FORWARD

    Cojanu Florin

    2010-06-01

    Full Text Available In actual didactic design is need to anticipate problems that may arise during implementation of proposed interdisciplinary content in the physical education lesson in class, by projecting sequential forward type of content, there by ensuring quality and efficiency. Its necessary to include in the design content of physical education lessons in primary sequence type of feed-forward, to increase the quality and effectiveness of physical education lessons at the operational objectives achieved. To development modern didactics of physical education we can keep some purchases of traditionalteaching, but still with emphasis currently reconsidering its entire system on the content, forms, methods of education.

  13. Feed forward neural network for prediction of end blow oxygen in LD converter steel making

    Narra Rajesh; Malaya Ranjan Khare; Shyamal Kumar Pabi

    2010-01-01

    A multi layered feed forward neural network model is being developed for the prediction of end blow oxygen in the LD converter using a two step process. In the first step intermediate stopping temperature is being predicted and using this as an input the end blow oxygen is predicted. In both the cases two hidden layers had given the best results compared to the single layer neural network. Intermediate and end blow temperatures played a vital role in end blow oxygen and intermediate stopping ...

  14. Feed forward neural network for prediction of end blow oxygen in LD converter steel making

    Narra Rajesh

    2010-03-01

    Full Text Available A multi layered feed forward neural network model is being developed for the prediction of end blow oxygen in the LD converter using a two step process. In the first step intermediate stopping temperature is being predicted and using this as an input the end blow oxygen is predicted. In both the cases two hidden layers had given the best results compared to the single layer neural network. Intermediate and end blow temperatures played a vital role in end blow oxygen and intermediate stopping temperature predictions. The model acts a guide for the operator and thereby enhances the yield of the converter steel making process.

  15. Compressive sensing reconstruction of feed-forward connectivity in pulse-coupled nonlinear networks

    Barranca, Victor J.; Zhou, Douglas; Cai, David

    2016-06-01

    Utilizing the sparsity ubiquitous in real-world network connectivity, we develop a theoretical framework for efficiently reconstructing sparse feed-forward connections in a pulse-coupled nonlinear network through its output activities. Using only a small ensemble of random inputs, we solve this inverse problem through the compressive sensing theory based on a hidden linear structure intrinsic to the nonlinear network dynamics. The accuracy of the reconstruction is further verified by the fact that complex inputs can be well recovered using the reconstructed connectivity. We expect this Rapid Communication provides a new perspective for understanding the structure-function relationship as well as compressive sensing principle in nonlinear network dynamics.

  16. Global Feed-Forward Vibration Isolation in a km scale Interferometer

    DeRosa, Ryan; Atkinson, Dani; Miao, Haixing; Frolov, Valery; Landry, Michael; Giaime, Joseph; Adhikari, Rana

    2012-01-01

    Using a network of seismometers and sets of optimal filters, we implemented a feed-forward control technique to minimize the seismic contribution to multiple interferometric degrees of freedom of the LIGO interferometers. The filters are constructed by using the Levinson-Durbin recursion relation to approximate the optimal Wiener filter. By reducing the RMS of the interferometer feedback signals below \\sim10 Hz, we have improved the stability and duty cycle of the joint network of gravitational wave detectors. By suppressing the large control forces and mirror motions, we have dramatically reduced the rate of non-Gaussian transients in the gravitational wave signal stream.

  17. The application of feed-forward neural network for the X-ray image fusion

    Under the current urgent circumstances of the aviation security, all countries are intensifying the security inspection. In the view of the specialty of dangerous goods, simulating the X-ray images of the superimposed objects to train inspectors, would become a convenient and effective way to strengthen the inspectors' priori knowledge of threatening ones. In this paper, depending on the learning algorithm 'OWO-HWO', we design a three layers feed-forward neural network. The characteristics and advantages of the neural network on the field of X-ray image fusion are completely analyzed in the paper.

  18. Feed-forward neural networks for shower recognition: construction and generalization

    Strictly layered feed-forward neural networks are explored as recognition tools for energy deposition patterns in a calorimeter. This study is motivated by possible applications for on-line event selection. Networks consisting of linear threshold units are generated by a constructive learning algorithm, the Patch algorithm. As a non-constructive counterpart the back-propagation algorithm is applied. This algorithm makes use of analogue neurons. The generalization capabilities of the neural networks resulting from both methods are compared to those of nearest-neighbour classifiers and of Probabilistic Neural Networks implementing Parzen-windows. The latter non-parametric statistical method is applied to estimate the optimal Bayesian classifier. For all methods the generalization capabilities are determined for different ways of pre-processing of the input data. The complexity of the feed-forward neural networks studied does not grow with the training set size. This favours a hardwired implementation of these neural networks as any implementation of the other two methods grows linearly with the training set size. ((orig.))

  19. Input Voltage Feed Forward Of Secondary Side Controlled Half-Bridge Converter

    Strogerer, Franz; Kreid, Fritz

    2011-10-01

    Sensitive electronic equipment supplied by a disturbed power bus requires a power converter featuring a good line rejection. This can be ensured by a well designed input and output filter together with a fast control loop. However, due to the limitation of board space and weight, high density power converter are mandatory requesting lowest possible size of the input and output filter components. The implementation of an input voltage feed forward can help to improve the line rejection without increasing input or output filter size. Using a half-bridge topology on the primary side, the implementation of peak current mode for high control dynamics may be in conflict with the stability of the half-bridge capacitor voltage. In this Paper, a feed forward technique of a half-bridge converter with current doubler is presented featuring a stable half-bridge capacitor voltage in peak current control mode and ensuring a good line rejection. The theoretically work is supported by experimental results gained from a flight representative hardware.

  20. An energy harvester using self-powered feed forward converter charging approach

    The paper proposes a stand-alone energy harvester system that considers economical, environmental, and technological implications. The applications of this paper are maintenance free, low cost and environmentally friendly commercial devices. The stand-alone system contains a self starting/self powering circuitry which allows the system power to be turned off while not in use. This proposed system requires neither batteries nor a power supply unit; it constitutes a true stand-alone, low maintenance and pollution free system. Additionally, it proposes a feed forward charging scheme to eliminate the needs of using voltage feedback, current feedback, or both, and hence reduces electronic complexity and cost of the charger. A detailed analysis of the feed forward charger, and the self-starting/self power circuitry was carried out to obtain the relationship between the system parameters and the outputs of the system. This paper also presents simulation results and experimental data to reveal performance of the charger and the self-starting/self powering circuitry. - Highlights: ► We frame an energy harvester that requires neither batteries nor a power supply unit. ► The harvester can avoid impacting the lifetime quality of energy storage elements. ► We show a thorough operation analysis for both ideal and non-ideal cases. ► The harvester possesses simplicity, low cost, and commercialization potential. ► Design concept integrates technical, economic and environmental concerns

  1. Visual language recognition with a feed-forward network of spiking neurons

    Rasmussen, Craig E [Los Alamos National Laboratory; Garrett, Kenyan [Los Alamos National Laboratory; Sottile, Matthew [GALOIS; Shreyas, Ns [INDIANA UNIV.

    2010-01-01

    An analogy is made and exploited between the recognition of visual objects and language parsing. A subset of regular languages is used to define a one-dimensional 'visual' language, in which the words are translational and scale invariant. This allows an exploration of the viewpoint invariant languages that can be solved by a network of concurrent, hierarchically connected processors. A language family is defined that is hierarchically tiling system recognizable (HREC). As inspired by nature, an algorithm is presented that constructs a cellular automaton that recognizes strings from a language in the HREC family. It is demonstrated how a language recognizer can be implemented from the cellular automaton using a feed-forward network of spiking neurons. This parser recognizes fixed-length strings from the language in parallel and as the computation is pipelined, a new string can be parsed in each new interval of time. The analogy with formal language theory allows inferences to be drawn regarding what class of objects can be recognized by visual cortex operating in purely feed-forward fashion and what class of objects requires a more complicated network architecture.

  2. A modified feed-forward control system at the Accelerator Test Facility

    A modified feed-forward control system has been operated at the Brookhaven Accelerator Test Facility to control the phase and amplitude of two high power klystron rf systems used to power a photocathode rf gun and a traveling wave electron linac. The changes to the control algorithm include an improved handling of cross coupling between the amplitude and the phase channels, an improved calibration routine that allows for changes in the matrix elements due to the variable base-line and improved filtering. The modifications to the software include modularity, portability, and user-friendliness. Improvements to the hardware include a linearized phase and amplitude controller with dc biasing for an improved dynamic range. The feed-forward system can handle nonlinear and noninstantaneous systems. With simultaneous regulation of two channels, the phase and the amplitude fluctuations over a time span of more than 3 μS were reduced to less than ±0.2 degree and ±0.2%, from the initial ±2.7 degree and ±1.8%, respectively. copyright 1997 American Institute of Physics

  3. Robust design of feedback feed-forward iterative learning control based on 2D system theory for linear uncertain systems

    Li, Zhifu; Hu, Yueming; Li, Di

    2016-08-01

    For a class of linear discrete-time uncertain systems, a feedback feed-forward iterative learning control (ILC) scheme is proposed, which is comprised of an iterative learning controller and two current iteration feedback controllers. The iterative learning controller is used to improve the performance along the iteration direction and the feedback controllers are used to improve the performance along the time direction. First of all, the uncertain feedback feed-forward ILC system is presented by an uncertain two-dimensional Roesser model system. Then, two robust control schemes are proposed. One can ensure that the feedback feed-forward ILC system is bounded-input bounded-output stable along time direction, and the other can ensure that the feedback feed-forward ILC system is asymptotically stable along time direction. Both schemes can guarantee the system is robust monotonically convergent along the iteration direction. Third, the robust convergent sufficient conditions are given, which contains a linear matrix inequality (LMI). Moreover, the LMI can be used to determine the gain matrix of the feedback feed-forward iterative learning controller. Finally, the simulation results are presented to demonstrate the effectiveness of the proposed schemes.

  4. Field Testing LIDAR Based Feed-Forward Controls on the NREL Controls Advanced Research Turbine: Preprint

    Scholbrock, A. K.; Fleming, P. A.; Fingersh, L. J.; Wright, A. D.; Schlipf, D.; Haizmann, F.; Belen, F.

    2013-01-01

    Wind turbines are complex, nonlinear, dynamic systems driven by aerodynamic, gravitational, centrifugal, and gyroscopic forces. The aerodynamics of wind turbines are nonlinear, unsteady, and complex. Turbine rotors are subjected to a chaotic three-dimensional (3-D) turbulent wind inflow field with imbedded coherent vortices that drive fatigue loads and reduce lifetime. In order to reduce cost of energy, future large multimegawatt turbines must be designed with lighter weight structures, using active controls to mitigate fatigue loads, maximize energy capture, and add active damping to maintain stability for these dynamically active structures operating in a complex environment. Researchers at the National Renewable Energy Laboratory (NREL) and University of Stuttgart are designing, implementing, and testing advanced feed-back and feed-forward controls in order to reduce the cost of energy for wind turbines.

  5. Efficient Generation of Large Number-Path Entanglement Using Only Linear Optics and Feed-Forward

    We show how an idealized measurement procedure can condense photons from two modes into one and how, by feeding forward the results of the measurement, it is possible to generate efficiently superposition states commonly called N00N states. For the basic procedure sources of number states leak onto a beam splitter, and the output ports are monitored by photodetectors. We find that detecting a fixed fraction of the input at one output port suffices to direct the remainder to the same port, with high probability, however large the initial state. When instead photons are detected at both ports, macroscopic quantum superposition states are produced. We describe a linear-optical circuit for making the components of such a state orthogonal, and another to convert the output to a N00N state. Our approach scales exponentially better than existing proposals. Important applications include quantum imaging and metrology

  6. Feed-forward segmentation of figure-ground and assignment of border-ownership.

    Hans Supèr

    Full Text Available Figure-ground is the segmentation of visual information into objects and their surrounding backgrounds. Two main processes herein are boundary assignment and surface segregation, which rely on the integration of global scene information. Recurrent processing either by intrinsic horizontal connections that connect surrounding neurons or by feedback projections from higher visual areas provide such information, and are considered to be the neural substrate for figure-ground segmentation. On the contrary, a role of feedforward projections in figure-ground segmentation is unknown. To have a better understanding of a role of feedforward connections in figure-ground organization, we constructed a feedforward spiking model using a biologically plausible neuron model. By means of surround inhibition our simple 3-layered model performs figure-ground segmentation and one-sided border-ownership coding. We propose that the visual system uses feed forward suppression for figure-ground segmentation and border-ownership assignment.

  7. A Feed-Forward Controlled AC-DC Boost Converter for Biomedical Implants

    Jiang, Hao; Lan, Di; Lin, Dahsien;

    2012-01-01

    than 2.1% of its mean. The measured load regulation is 0.4 V/kΩ. The estimated conversion efficiency excluding the power consumption of the control circuits reaches 75%. The converter in this paper has the potential to reduce the size of the receiving coil and yet achieve desirable DC output voltage...... employed to deliver electrical power wirelessly. In this approach, a rectifier is needed to convert the received RF power to a stable DC one. To achieve high efficiency, the induced voltage of the receiving coil must be much higher than the turn-on voltage of the rectifying diode (which could be an active...... 100 Hz) because of the superior magnetic strength produced by rare-earth magnets [2]. Taking the advantage of the low operating frequency, an innovative feed-forward controlled AC to DC boost converter has been demonstrated for the first time to accomplish the following two tasks simultaneously: (1...

  8. Soliton generation from a fundamentally mode-locked fiber laser with a feed-forward path

    We demonstrate for the first time to our knowledge, the soliton generation from a mode-locked erbium-doped fiber laser using a novel saturable absorber (SA), which is realized by combining a dual-drive modulator and an intensity feed-forward path. The laser is fundamentally mode-locked under high-frequency RF signal modulation. Experimentally, the actively mode-locked laser produces a 16.7 MHz repetition rate pulse train with a 1.4 ps pulse width, and the spectrum bandwidth is 2.17 nm. The results demonstrate that the SA supports soliton pulse shaping in the cavity at the fundamental frequency. (letter)

  9. Entry, Descent and Landing Systems Analysis: Exploration Feed Forward Internal Peer Review Slide Package

    Dwyer Cianciolo, Alicia M. (Editor)

    2011-01-01

    NASA senior management commissioned the Entry, Descent and Landing Systems Analysis (EDL-SA) Study in 2008 to identify and roadmap the Entry, Descent and Landing (EDL) technology investments that the agency needed to successfully land large payloads at Mars for both robotic and human-scale missions. Year 1 of the study focused on technologies required for Exploration-class missions to land payloads of 10 to 50 mt. Inflatable decelerators, rigid aeroshell and supersonic retro-propulsion emerged as the top candidate technologies. In Year 2 of the study, low TRL technologies identified in Year 1, inflatables aeroshells and supersonic retropropulsion, were combined to create a demonstration precursor robotic mission. This part of the EDL-SA Year 2 effort, called Exploration Feed Forward (EFF), took much of the systems analysis simulation and component model development from Year 1 to the next level of detail.

  10. Entry, Descent and Landing Systems Analysis Study: Phase 2 Report on Exploration Feed-Forward Systems

    Dwyer Ciancolo, Alicia M.; Davis, Jody L.; Engelund, Walter C.; Komar, D. R.; Queen, Eric M.; Samareh, Jamshid A.; Way, David W.; Zang, Thomas A.; Murch, Jeff G.; Krizan, Shawn A.; Olds, Aaron D.; Powell, Richard W.; Shidner, Jeremy D.; Kinney, Daivd J.; McGuire, M. Kathleen; Arnold, James O.; Covington, M. Alan; Sostaric, Ronald R.; Zumwalt, Carlie H.; Llama, Eduardo G.

    2011-01-01

    NASA senior management commissioned the Entry, Descent and Landing Systems Analysis (EDL-SA) Study in 2008 to identify and roadmap the Entry, Descent and Landing (EDL) technology investments that the agency needed to successfully land large payloads at Mars for both robotic and human-scale missions. Year 1 of the study focused on technologies required for Exploration-class missions to land payloads of 10 to 50 t. Inflatable decelerators, rigid aeroshell and supersonic retro-propulsion emerged as the top candidate technologies. In Year 2 of the study, low TRL technologies identified in Year 1, inflatables aeroshells and supersonic retropropulsion, were combined to create a demonstration precursor robotic mission. This part of the EDL-SA Year 2 effort, called Exploration Feed Forward (EFF), took much of the systems analysis simulation and component model development from Year 1 to the next level of detail.

  11. Overview of the NASA Entry, Descent and Landing Systems Analysis Exploration Feed-Forward Study

    DwyerCianciolo, Alicia M.; Zang, Thomas A.; Sostaric, Ronald R.; McGuire, M. Kathy

    2011-01-01

    Technology required to land large payloads (20 to 50 mt) on Mars remains elusive. In an effort to identify the most viable investment path, NASA and others have been studying various concepts. One such study, the Entry, Descent and Landing Systems Analysis (EDLSA) Study [1] identified three potential options: the rigid aeroshell, the inflatable aeroshell and supersonic retropropulsion (SRP). In an effort to drive out additional levels of design detail, a smaller demonstrator, or exploration feed-forward (EFF), robotic mission was devised that utilized two of the three (inflatable aeroshell and SRP) high potential technologies in a configuration to demonstrate landing a two to four metric ton payload on Mars. This paper presents and overview of the maximum landed mass, inflatable aeroshell controllability and sensor suite capability assessments of the selected technologies and recommends specific technology areas for additional work.

  12. LEARNING ALGORITHM EFFECT ON MULTILAYER FEED FORWARD ARTIFICIAL NEURAL NETWORK PERFORMANCE IN IMAGE CODING

    OMER MAHMOUD

    2007-08-01

    Full Text Available One of the essential factors that affect the performance of Artificial Neural Networks is the learning algorithm. The performance of Multilayer Feed Forward Artificial Neural Network performance in image compression using different learning algorithms is examined in this paper. Based on Gradient Descent, Conjugate Gradient, Quasi-Newton techniques three different error back propagation algorithms have been developed for use in training two types of neural networks, a single hidden layer network and three hidden layers network. The essence of this study is to investigate the most efficient and effective training methods for use in image compression and its subsequent applications. The obtained results show that the Quasi-Newton based algorithm has better performance as compared to the other two algorithms.

  13. Modeling of an industrial process of pleuromutilin fermentation using feed-forward neural networks

    L. Khaouane

    2013-03-01

    Full Text Available This work investigates the use of artificial neural networks in modeling an industrial fermentation process of Pleuromutilin produced by Pleurotus mutilus in a fed-batch mode. Three feed-forward neural network models characterized by a similar structure (five neurons in the input layer, one hidden layer and one neuron in the output layer are constructed and optimized with the aim to predict the evolution of three main bioprocess variables: biomass, substrate and product. Results show a good fit between the predicted and experimental values for each model (the root mean squared errors were 0.4624% - 0.1234 g/L and 0.0016 mg/g respectively. Furthermore, the comparison between the optimized models and the unstructured kinetic models in terms of simulation results shows that neural network models gave more significant results. These results encourage further studies to integrate the mathematical formulae extracted from these models into an industrial control loop of the process.

  14. Energy dissipation drives the gradient signal amplification through an incoherent type-1 feed-forward loop

    Lan, Ganhui

    2015-09-01

    We present here the analytical relation between the gain of eukaryotic gradient sensing network and the associated thermodynamic cost. By analyzing a general incoherent type-1 feed-forward loop, we derive the gain function (G ) through the reaction network and explicitly show that G depends on the nonequilibrium factor (0 ≤γ ≤1 with γ =0 and 1 representing irreversible and equilibrium reaction systems, respectively), the Michaelis constant (KM), and the turnover ratio (rcat) of the participating enzymes. We further find the maximum possible gain is intrinsically determined by KM/Gmax=(1 /KM+2 ) /4 . Our model also indicates that the dissipated energy (measured by -lnγ ), from the intracellular energy-bearing bioparticles (e.g., ATP), is used to generate a force field Fγ∝(1 -√{γ }) that reshapes and disables the effective potential around the zero gain region, which leads to the ultrasensitive response to external chemical gradients.

  15. Deterministic quantum teleportation with feed-forward in a solid state system.

    Steffen, L; Salathe, Y; Oppliger, M; Kurpiers, P; Baur, M; Lang, C; Eichler, C; Puebla-Hellmann, G; Fedorov, A; Wallraff, A

    2013-08-15

    Engineered macroscopic quantum systems based on superconducting electronic circuits are attractive for experimentally exploring diverse questions in quantum information science. At the current state of the art, quantum bits (qubits) are fabricated, initialized, controlled, read out and coupled to each other in simple circuits. This enables the realization of basic logic gates, the creation of complex entangled states and the demonstration of algorithms or error correction. Using different variants of low-noise parametric amplifiers, dispersive quantum non-demolition single-shot readout of single-qubit states with high fidelity has enabled continuous and discrete feedback control of single qubits. Here we realize full deterministic quantum teleportation with feed-forward in a chip-based superconducting circuit architecture. We use a set of two parametric amplifiers for both joint two-qubit and individual qubit single-shot readout, combined with flexible real-time digital electronics. Our device uses a crossed quantum bus technology that allows us to create complex networks with arbitrary connecting topology in a planar architecture. The deterministic teleportation process succeeds with order unit probability for any input state, as we prepare maximally entangled two-qubit states as a resource and distinguish all Bell states in a single two-qubit measurement with high efficiency and high fidelity. We teleport quantum states between two macroscopic systems separated by 6 mm at a rate of 10(4) s(-1), exceeding other reported implementations. The low transmission loss of superconducting waveguides is likely to enable the range of this and other schemes to be extended to significantly larger distances, enabling tests of non-locality and the realization of elements for quantum communication at microwave frequencies. The demonstrated feed-forward may also find application in error correction schemes. PMID:23955231

  16. A Feed-Forward Control Realizing Fast Response for Three-Branch Interleaved DC-DC Converter in DC Microgrid

    Haojie Wang

    2016-07-01

    Full Text Available It is a common practice for storage batteries to be connected to DC microgrid buses through DC-DC converters for voltage support on islanded operation mode. A feed-forward control based dual-loop constant voltage PI control for three-branch interleaved DC-DC converters (TIDC is proposed for storage batteries in DC microgrids. The working principle of TIDC is analyzed, and the factors influencing the response rate based on the dual-loop constant voltage control for TIDC are discussed, and then the method of feed-forward control for TIDC is studied to improve the response rate for load changing. A prototype of the TIDC is developed and an experimental platform is built. The experiment results show that DC bus voltage sags or swells caused by load changing can be reduced and the time for voltage recovery can be decreased significantly with the proposed feed-forward control.

  17. Development of an Accurate Feed-Forward Temperature Control Tankless Water Heater

    David Yuill

    2008-06-30

    The following document is the final report for DE-FC26-05NT42327: Development of an Accurate Feed-Forward Temperature Control Tankless Water Heater. This work was carried out under a cooperative agreement from the Department of Energy's National Energy Technology Laboratory, with additional funding from Keltech, Inc. The objective of the project was to improve the temperature control performance of an electric tankless water heater (TWH). The reason for doing this is to minimize or eliminate one of the barriers to wider adoption of the TWH. TWH use less energy than typical (storage) water heaters because of the elimination of standby losses, so wider adoption will lead to reduced energy consumption. The project was carried out by Building Solutions, Inc. (BSI), a small business based in Omaha, Nebraska. BSI partnered with Keltech, Inc., a manufacturer of electric tankless water heaters based in Delton, Michigan. Additional work was carried out by the University of Nebraska and Mike Coward. A background study revealed several advantages and disadvantages to TWH. Besides using less energy than storage heaters, TWH provide an endless supply of hot water, have a longer life, use less floor space, can be used at point-of-use, and are suitable as boosters to enable alternative water heating technologies, such as solar or heat-pump water heaters. Their disadvantages are their higher cost, large instantaneous power requirement, and poor temperature control. A test method was developed to quantify performance under a representative range of disturbances to flow rate and inlet temperature. A device capable of conducting this test was designed and built. Some heaters currently on the market were tested, and were found to perform quite poorly. A new controller was designed using model predictive control (MPC). This control method required an accurate dynamic model to be created and required significant tuning to the controller before good control was achieved. The MPC

  18. Intelligent Robust Feed-forward Fuzzy Feedback Linearization Estimation of PID Control with Application to Continuum Robot

    Afsaneh Salehi

    2013-05-01

    Full Text Available Refer to this paper, an intelligent-fuzzy feed-forward computed torque estimator for Proportional-Integral-Derivative (PID controller is proposed for highly nonlinear continuum robot manipulator. In the absence of robot knowledge, PID may be the best controller, because it is model-free, and its parameters can be adjusted easily and separately and it is the most used in robot manipulators. In order to remove steady-state error caused by uncertainties and noise, the integrator gain has to be increased. This leads to worse transient performance, even destroys the stability. The integrator in a PID controller also reduces the bandwidth of the closed-loop system. Model-based compensation for PD control is an alternative method to substitute PID control. Computed torque compensation is one of the nonlinear compensator. The main problem of the pure computed torque compensator (CTC was highly nonlinear dynamic parameters which related to system’s dynamic parameters in certain and uncertain systems. The nonlinear equivalent dynamic problem in uncertain system is solved by using feed-forward fuzzy inference system. To eliminate the continuum robot manipulator system’s dynamic; Mamdani fuzzy inference system is design and applied to CTC. This methodology is based on design feed-forward fuzzy inference system and applied to CTC. The results demonstrate that the model base feed-forward fuzzy CTC estimator works well to compensate linear PID controller in presence of partly uncertainty system (e.g., continuum robot.

  19. Application of Formalised Developmental Feedback for Feed-Forward to Foster Student Ownership of the Learning Process

    Todd, Valerie J.; McIlroy, David

    2014-01-01

    There has been considerable criticism of assessment methods because of inconsistencies across modules and a focus on the measurement of learning rather than assessment for learning. The aim of the current study was to formalise the process of assessment feedback to feed-forward, and assess the impact on student learning. A cohort of undergraduate…

  20. Accumbal core: Essential link in feed-forward spiraling striato-nigro-striatal in series connected loop

    Ikeda, H.; Koshikawa, N.; Cools, A.R.

    2013-01-01

    The goal of the present study was to establish the behavioral role of the nucleus accumbens (Nacc) core in the feed-forward spiraling striato-nigro-striatal circuitry that transmits information from the Nacc shell toward the dorsal subregion of the neostriatum (DS) in freely moving rats. Unilateral

  1. Spiraling dopaminergic circuitry from the ventral striatum to dorsal striatum is an effective feed-forward loop

    Ikeda, H.; Saigusa, T.; Kamei, J.; Koshikawa, N.; Cools, A.R.

    2013-01-01

    Central dopamine systems are key players in the cerebral organization of behavior and in various neurological and psychiatric diseases. We demonstrate the presence of a neurochemical feed-forward loop characterized by region-specific changes in dopamine efflux in serially connected striatal regions,

  2. A feed-forward loop coupling extracellular BMP transport and morphogenesis in Drosophila wing.

    Shinya Matsuda

    2013-03-01

    Full Text Available A variety of extracellular factors regulate morphogenesis during development. However, coordination between extracellular signaling and dynamic morphogenesis is largely unexplored. We address the fundamental question by studying posterior crossvein (PCV development in Drosophila as a model, in which long-range BMP transport from the longitudinal veins plays a critical role during the pupal stages. Here, we show that RhoGAP Crossveinless-C (Cv-C is induced at the PCV primordial cells by BMP signaling and mediates PCV morphogenesis cell-autonomously by inactivating members of the Rho-type small GTPases. Intriguingly, we find that Cv-C is also required non-cell-autonomously for BMP transport into the PCV region, while a long-range BMP transport is guided toward ectopic wing vein regions by loss of the Rho-type small GTPases. We present evidence that low level of ß-integrin accumulation at the basal side of PCV epithelial cells regulated by Cv-C provides an optimal extracellular environment for guiding BMP transport. These data suggest that BMP transport and PCV morphogenesis are tightly coupled. Our study reveals a feed-forward mechanism that coordinates the spatial distribution of extracellular instructive cues and morphogenesis. The coupling mechanism may be widely utilized to achieve precise morphogenesis during development and homeostasis.

  3. A feed forward neural network for classification of bull's-eye myocardial perfusion images

    Identification of hypoperfused areas in myocardial perfusion single-photon emission tomography studies can be aided by bull's-eye representation of raw counts, lesion extent and lesion severity, the latter two being produced by comparison of the raw bull's-eye data with a normal data base. An artificial intelligence technique which is presently becoming widely popular and which is particularly suitable for pattern recognition is that of artificial neural network. We have studied the ability of feed forward neural networks to extract patterns from bull's-eye data by assessing their capability to predict lesion presence without direct comparison with a normal data base. Studies were undertaken on both simulation data and on real stress-rest data obtained from 410 male patients undergoing routine thallium-201 myocardial perfusion scintigraphy. The ability of trained neural networks to predict lesion presence was quantified by calculating the areas under receiver operating characteristic curves. Figures as high as 0.96 for non-preclassified patient data were obtained, corresponding to an accuracy of 92%. The results demonstrate that neural networks can accurately classify patterns from bull's-eye myocardial perfusion images and detect the presence of hypoperfused areas without the need for comparison with a normal data base. Preliminary work suggests that this technique could be used to study perfusion patterns in the myocardium and their correlation with clinical parameters. (orig.)

  4. Towards a GPS-based TEC prediction model for Southern Africa with feed forward networks

    Habarulema, John Bosco; McKinnell, Lee-Anne; Opperman, Ben D. L.

    2009-07-01

    In this paper, first results from a national Global Positioning System (GPS) based total electron content (TEC) prediction model over South Africa are presented. Data for 10 GPS receiver stations distributed through out the country were used to train a feed forward neural network (NN) over an interval of at most five years. In the NN training, validating and testing processes, five factors which are well known to influence TEC variability namely diurnal variation, seasonal variation, magnetic activity, solar activity and the geographic position of the GPS receivers were included in the NN model. The database consisted of 1-min data and therefore the NN model developed can be used to forecast TEC values 1 min in advance. Results from the NN national model (NM) were compared with hourly TEC values generated by the earlier developed NN single station models (SSMs) at Sutherland (32.38°S, 20.81°E) and Springbok (29.67°S, 17.88°E), to predict TEC variations over the Cape Town (33.95°S, 18.47°E) and Upington (28.41°S, 21.26°E) stations, respectively, during equinoxes and solstices. This revealed that, on average, the NM led to an improvement in TEC prediction accuracy compared to the SSMs for the considered testing periods.

  5. PRE-DIAGNOSIS OF LUNG CANCER USING FEED FORWARD NEURAL NETWORK AND BACK PROPAGATION ALGORITHM

    Mr. Abhinav Vishwa

    2011-09-01

    Full Text Available Cancer is the most important cause of death for both men and women. The early detection of cancer can be helpful in curing the disease completely. So the requirement of techniques to detect the occurrence of cancer nodule in early stage is increasing. A disease that is commonly misdiagnosed is lung cancer. Artificial Neural Networks (ANNs play a vital role in the medical field in solving various health problems like acute diseases and even other mild diseases. Earlier diagnosis of Lung Cancer saves enormous lives, failing which may lead to other severe problems causing sudden fatal end. Its cure rate and prognosis depends mainly on the early detection and diagnosis of the disease. This paper provides a Feed Forward Artificial Neural Network Model for early detection of lung cancer. The model consists of an input layer, a hidden layer and an output layer. The network is trained with one hidden layer and one output layer by giving twelve inputs. One of the most common forms of medical malpractices globally is an error in diagnosis. The paper provides a formula for Error Detection and on the basis of error weights are adjusted and system is improved. Aim of the paper is to propose a model for early detection and correct diagnosis of the disease which will help the doctor in saving the life of the patient.

  6. Content Based Image Retrieval using Novel Gaussian Fuzzy Feed Forward-Neural Network

    C. R.B. Durai

    2011-01-01

    Full Text Available Problem statement: With extensive digitization of images, diagrams and paintings, traditional keyword based search has been found to be inefficient for retrieval of the required data. Content-Based Image Retrieval (CBIR system responds to image queries as input and relies on image content, using techniques from computer vision and image processing to interpret and understand it, while using techniques from information retrieval and databases to rapidly locate and retrieve images suiting an input query. CBIR finds extensive applications in the field of medicine as it assists a doctor to make better decisions by referring the CBIR system and gain confidence. Approach: Various methods have been proposed for CBIR using image low level image features like histogram, color layout, texture and analysis of the image in the frequency domain. Similarly various classification algorithms like Naïve Bayes classifier, Support Vector Machine, Decision tree induction algorithms and Neural Network based classifiers have been studied extensively. We proposed to extract features from an image using Discrete Cosine Transform, extract relevant features using information gain and Gaussian Fuzzy Feed Forward Neural Network algorithm for classification. Results and Conclusion: We apply our proposed procedure to 180 brain MRI images of which 72 images were used for testing and the remaining for training. The classification accuracy obtained was 95.83% for a three class problem. This research focused on a narrow search, where further investigation is needed to evaluate larger classes.

  7. Combined use of SOM-classification and Feed-Forward Networks for multinetwork streamflow forecasting

    Toth, E.

    2009-04-01

    The contribution presents the results of a modular approach for real-time streamflow forecasting, that applies different rainfall-runoff models, on the basis of the hydro-meteorological situation characterising each forecast instant. Modular neural networks or multi-network modelling for streamflow forecasting have been successfully applied in the recent years (e.g. Abrahart and See, 2000; Corzo and Solomatine, 2007; Parasuraman and Elshorbagy 2007). The hydrological and meteorological conditions of the watershed in the instant in which the forecast is issued determine, in fact, which hydrological processes will be dominant in the following period: the future evolution of the streamflow values is then simulated with a rainfall-runoff model that is specific for each forecast instant, parameterised on the basis of the evolution of the similar situations observed in the past. In the present work, the hydro-meteorological conditions are classified with a clustering technique based on unsupervised artificial neural networks, namely self-organisation maps (SOMs) or Kohonen networks. Following the SOM classification, the streamflow forecasts for an Italian mid-sized mountain watershed are issued by specific multilayer feed-forward artificial neural network (FFN). The results confirm that an adequate distinction of the hydro-meteorological conditions characterising the basin at the forecast instant, thus including additional knowledge on the forthcoming hydrological processes, may considerably improve the rainfall-runoff modelling performance.

  8. ADAPTIVE FEED-FORWARD COMPENSATOR FOR HARMONIC CANCELLATION IN ELECTRO- HYDRAULIC SERVO SYSTEM

    YAO Jianjun; WANG Liquan; JIANG Hongzhou; WU Zhenshun; HAN Junwei

    2008-01-01

    Since the dead zone phenomenon occurs in electro-hydraulic servo system, the output of the system corresponding to a sinusoidal input contains higher harmonic besides the fundamental input, which causes harmonic distortion of the output signal. The method for harmonic cancellation based on adaptive filter is proposed. The task is accomplished by generating reference signals with frequency that should be eliminated from the output. The reference inputs are weighted by the adaptive filter in such a way that it closely matches the harmonic. The output of the adaptive filter is a harmonic replica and is injected to the fundamental signal such that the output harmonic is cancelled leaving the desired signal alone, and the total harmonic distortion (THD) is greatly reduced. The weights of filter are adjusted on-line according to the control error by using least-mean-square (LMS) algorithm. Simulation results performed with a hydraulic system demonstrate the efficiency and validity of the proposed adaptive feed-forward compensator (AFC) control scheme.

  9. Predictive zero-dimensional combustion model for DI diesel engine feed-forward control

    Highlights: → Zero-dimensional low-throughput combustion model for real-time control in diesel engine applications. → Feed-forward control of MFB50, pmax and IMEP in both conventional and PCCI combustion modes. → Capability of resolving the contribution to HRR of each injection pulse in multiple injection schedule. → Ignition delay and model parameters estimated through physically consistent and easy-to-tune correlations. - Abstract: An innovative zero-dimensional predictive combustion model has been developed for the estimation of HRR (heat release rate) and in-cylinder pressure traces. This model has been assessed and applied to conventional and PCCI (premixed charge compression ignition) DI diesel engines for model-based feed-forward control purposes. The injection rate profile is calculated on the basis of the injected fuel quantities and on the injection parameters, such as SOI (start of injection), ET (energizing time), and DT (dwell time), taking the injector NOD (nozzle opening delay) and NCD (nozzle closure delay) into account. The injection rate profile in turn allows the released chemical energy Qch to be estimated. The approach starts from the assumption that, at each time instant, the HRR is proportional to the energy associated with the accumulated fuel mass in the combustion chamber. The main novelties of the proposed approach consist of the method that is adopted to estimate the fuel ignition delay and of injection rate splitting for HRR estimation. The procedure allows an accurate calculation to be made of the different combustion parameters that are important for engine calibration, such as SOC (start of combustion) and MFB50 (50% of fuel mass fraction burned angle). On the basis of an estimation of the fuel released chemical energy, of the heat globally exchanged from the charge with the walls and of the energy associated with the fuel evaporation, the charge net energy is calculated, for a subsequent evaluation of the in-chamber pressure

  10. Predictive zero-dimensional combustion model for DI diesel engine feed-forward control

    Catania, Andrea Emilio; Finesso, Roberto [IC Engines Advanced Laboratory, Politecnico di Torino, c.so Duca degli Abruzzi 24, 10129 Torino (Italy); Spessa, Ezio, E-mail: ezio.spessa@polito.it [IC Engines Advanced Laboratory, Politecnico di Torino, c.so Duca degli Abruzzi 24, 10129 Torino (Italy)

    2011-09-15

    Highlights: {yields} Zero-dimensional low-throughput combustion model for real-time control in diesel engine applications. {yields} Feed-forward control of MFB50, p{sub max} and IMEP in both conventional and PCCI combustion modes. {yields} Capability of resolving the contribution to HRR of each injection pulse in multiple injection schedule. {yields} Ignition delay and model parameters estimated through physically consistent and easy-to-tune correlations. - Abstract: An innovative zero-dimensional predictive combustion model has been developed for the estimation of HRR (heat release rate) and in-cylinder pressure traces. This model has been assessed and applied to conventional and PCCI (premixed charge compression ignition) DI diesel engines for model-based feed-forward control purposes. The injection rate profile is calculated on the basis of the injected fuel quantities and on the injection parameters, such as SOI (start of injection), ET (energizing time), and DT (dwell time), taking the injector NOD (nozzle opening delay) and NCD (nozzle closure delay) into account. The injection rate profile in turn allows the released chemical energy Q{sub ch} to be estimated. The approach starts from the assumption that, at each time instant, the HRR is proportional to the energy associated with the accumulated fuel mass in the combustion chamber. The main novelties of the proposed approach consist of the method that is adopted to estimate the fuel ignition delay and of injection rate splitting for HRR estimation. The procedure allows an accurate calculation to be made of the different combustion parameters that are important for engine calibration, such as SOC (start of combustion) and MFB50 (50% of fuel mass fraction burned angle). On the basis of an estimation of the fuel released chemical energy, of the heat globally exchanged from the charge with the walls and of the energy associated with the fuel evaporation, the charge net energy is calculated, for a subsequent

  11. A feed-forward controlled AC-DC boost converter for biomedical implants.

    Jiang, Hao; Lan, Di; Lin, Dahsien; Zhang, Junmin; Liou, Shyshenq; Shahnasser, Hamid; Shen, Ming; Harrison, Michael; Roy, Shuvo

    2012-01-01

    Miniaturization is important to make implants clinic friendly. Wireless power transfer is an essential technology to miniaturize implants by reducing their battery size or completely eliminating their batteries. Traditionally, a pair of inductively-coupled coils operating at radio-frequency (RF) is employed to deliver electrical power wirelessly. In this approach, a rectifier is needed to convert the received RF power to a stable DC one. To achieve high efficiency, the induced voltage of the receiving coil must be much higher than the turn-on voltage of the rectifying diode (which could be an active circuit for low turn-on voltage) [1]. In order to have a high induced voltage, the size of the receiving coil often is significantly larger than rest of the implant. A rotating magnets based wireless power transfer has been demonstrated to deliver the same amount of power at much lower frequency (around 100 Hz) because of the superior magnetic strength produced by rare-earth magnets [2]. Taking the advantage of the low operating frequency, an innovative feed-forward controlled AC to DC boost converter has been demonstrated for the first time to accomplish the following two tasks simultaneously: (1) rectifying the AC power whose amplitude (500 mV) is less than the rectifier's turn-on voltage (1.44 V) and (2) boosting the DC output voltage to a much higher level (5 V). Within a range, the output DC voltage can be selected by the control circuit. The standard deviation of the output DC voltage is less than 2.1% of its mean. The measured load regulation is 0.4 V/kΩ. The estimated conversion efficiency excluding the power consumption of the control circuits reaches 75%. The converter in this paper has the potential to reduce the size of the receiving coil and yet achieve desirable DC output voltage for powering biomedical implants. PMID:23366230

  12. Oscillations via Spike-Timing Dependent Plasticity in a Feed-Forward Model.

    Luz, Yotam; Shamir, Maoz

    2016-04-01

    Neuronal oscillatory activity has been reported in relation to a wide range of cognitive processes including the encoding of external stimuli, attention, and learning. Although the specific role of these oscillations has yet to be determined, it is clear that neuronal oscillations are abundant in the central nervous system. This raises the question of the origin of these oscillations: are the mechanisms for generating these oscillations genetically hard-wired or can they be acquired via a learning process? Here, we study the conditions under which oscillatory activity emerges through a process of spike timing dependent plasticity (STDP) in a feed-forward architecture. First, we analyze the effect of oscillations on STDP-driven synaptic dynamics of a single synapse, and study how the parameters that characterize the STDP rule and the oscillations affect the resultant synaptic weight. Next, we analyze STDP-driven synaptic dynamics of a pre-synaptic population of neurons onto a single post-synaptic cell. The pre-synaptic neural population is assumed to be oscillating at the same frequency, albeit with different phases, such that the net activity of the pre-synaptic population is constant in time. Thus, in the homogeneous case in which all synapses are equal, the post-synaptic neuron receives constant input and hence does not oscillate. To investigate the transition to oscillatory activity, we develop a mean-field Fokker-Planck approximation of the synaptic dynamics. We analyze the conditions causing the homogeneous solution to lose its stability. The findings show that oscillatory activity appears through a mechanism of spontaneous symmetry breaking. However, in the general case the homogeneous solution is unstable, and the synaptic dynamics does not converge to a different fixed point, but rather to a limit cycle. We show how the temporal structure of the STDP rule determines the stability of the homogeneous solution and the drift velocity of the limit cycle. PMID

  13. Spike-timing computation properties of a feed-forward neural network model

    Drew Benjamin Sinha

    2014-01-01

    Full Text Available Brain function is characterized by dynamical interactions among networks of neurons. These interactions are mediated by network topology at many scales ranging from microcircuits to brain areas. Understanding how networks operate can be aided by understanding how the transformation of inputs depends upon network connectivity patterns, e.g. serial and parallel pathways. To tractably determine how single synapses or groups of synapses in such pathways shape transformations, we modeled feed-forward networks of 7-22 neurons in which synaptic strength changed according to a spike-timing dependent plasticity rule. We investigated how activity varied when dynamics were perturbed by an activity-dependent electrical stimulation protocol (spike-triggered stimulation; STS in networks of different topologies and background input correlations. STS can successfully reorganize functional brain networks in vivo, but with a variability in effectiveness that may derive partially from the underlying network topology. In a simulated network with a single disynaptic pathway driven by uncorrelated background activity, structured spike-timing relationships between polysynaptically connected neurons were not observed. When background activity was correlated or parallel disynaptic pathways were added, however, robust polysynaptic spike timing relationships were observed, and application of STS yielded predictable changes in synaptic strengths and spike-timing relationships. These observations suggest that precise input-related or topologically induced temporal relationships in network activity are necessary for polysynaptic signal propagation. Such constraints for polysynaptic computation suggest potential roles for higher-order topological structure in network organization, such as maintaining polysynaptic correlation in the face of relatively weak synapses.

  14. Oscillations via Spike-Timing Dependent Plasticity in a Feed-Forward Model.

    Yotam Luz

    2016-04-01

    Full Text Available Neuronal oscillatory activity has been reported in relation to a wide range of cognitive processes including the encoding of external stimuli, attention, and learning. Although the specific role of these oscillations has yet to be determined, it is clear that neuronal oscillations are abundant in the central nervous system. This raises the question of the origin of these oscillations: are the mechanisms for generating these oscillations genetically hard-wired or can they be acquired via a learning process? Here, we study the conditions under which oscillatory activity emerges through a process of spike timing dependent plasticity (STDP in a feed-forward architecture. First, we analyze the effect of oscillations on STDP-driven synaptic dynamics of a single synapse, and study how the parameters that characterize the STDP rule and the oscillations affect the resultant synaptic weight. Next, we analyze STDP-driven synaptic dynamics of a pre-synaptic population of neurons onto a single post-synaptic cell. The pre-synaptic neural population is assumed to be oscillating at the same frequency, albeit with different phases, such that the net activity of the pre-synaptic population is constant in time. Thus, in the homogeneous case in which all synapses are equal, the post-synaptic neuron receives constant input and hence does not oscillate. To investigate the transition to oscillatory activity, we develop a mean-field Fokker-Planck approximation of the synaptic dynamics. We analyze the conditions causing the homogeneous solution to lose its stability. The findings show that oscillatory activity appears through a mechanism of spontaneous symmetry breaking. However, in the general case the homogeneous solution is unstable, and the synaptic dynamics does not converge to a different fixed point, but rather to a limit cycle. We show how the temporal structure of the STDP rule determines the stability of the homogeneous solution and the drift velocity of the

  15. A Positive Buck Boost Converter with Mode Select Circuit and Feed Forward Techniques Using Fuzzy Logic Controller

    Latha. S. C

    2014-11-01

    Full Text Available The portable devices development of semiconductor manufacturing technology, conversion efficiency, power consumption, and the size of devices have become the most important design criteria of switching power converters. For portable applications better conveniences extension of battery life and improves the conversion efficiency of power converters .It is essential to develop accurate switching power converters, which can reduce more wasted power energy. The proposed topology can achieve faster transient responses when the supply voltages are changed for the converter by making use of the feed forward network .With mode select circuit the conduction & switching losses are reduced the positive buck–boost converter operate in buck, buck–boost, or boost converter. By adding feed-forward techniques, the proposed converter can improve transient response when the supply voltages are changed. The designing, modeling & experimental results were verified in MATLAB/ Simulink. The fuzzy logic controller is used as controller.

  16. Genome-Wide Survey of MicroRNA - Transcription Factor Feed-Forward Regulatory Circuits in Human

    Re, Angela; Cora, Davide; Taverna, Daniela; Caselle, Michele

    2009-01-01

    In this work, we describe a computational framework for the genome-wide identification and characterization of mixed transcriptional/post-transcriptional regulatory circuits in humans. We concentrated in particular on feed-forward loops (FFL), in which a master transcription factor regulates a microRNA, and together with it, a set of joint target protein coding genes. The circuits were assembled with a two step procedure. We first constructed separately the transcriptional and post-transcript...

  17. Feed-forward active contour analysis for improved brachial artery reactivity testing.

    Pugliese, Daniel N; Sehgal, Chandra M; Sultan, Laith R; Reamer, Courtney B; Mohler, Emile R

    2016-08-01

    The object of this study was to utilize a novel feed-forward active contour (FFAC) algorithm to find a reproducible technique for analysis of brachial artery reactivity. Flow-mediated dilation (FMD) is an important marker of vascular endothelial function but has not been adopted for widespread clinical use given its technical limitations, including inter-observer variability and differences in technique across clinical sites. We developed a novel FFAC algorithm with the goal of validating a more reliable standard. Forty-six healthy volunteers underwent FMD measurement according to the standard technique. Ultrasound videos lasting 5-10 seconds each were obtained pre-cuff inflation and at minutes 1 through 5 post-cuff deflation in longitudinal and transverse views. Automated segmentation using the FFAC algorithm with initial boundary definition from three different observers was used to analyze the images to measure diameter/cross-sectional area over the cardiac cycle. The %FMD was calculated for average, minimum, and maximum diameters/areas. Using the FFAC algorithm, the population-specific coefficient of variation (CV) at end-diastole was 3.24% for transverse compared to 9.96% for longitudinal measurements; the subject-specific CV was 15.03% compared to 57.41%, respectively. For longitudinal measurements made via the conventional method, the population-specific CV was 4.77% and subject-specific CV was 117.79%. The intraclass correlation coefficient (ICC) for transverse measurements was 0.97 (95% CI: 0.95-0.98) compared to 0.90 (95% CI: 0.84-0.94) for longitudinal measurements with FFAC and 0.72 (95% CI: 0.51-0.84) for conventional measurements. In conclusion, transverse views using the novel FFAC method provide less inter-observer variability than traditional longitudinal views. Improved reproducibility may allow adoption of FMD testing in a clinical setting. The FFAC algorithm is a robust technique that should be evaluated further for its ability to replace the

  18. Structural basis for feed-forward transcriptional regulation of membrane lipid homeostasis in Staphylococcus aureus.

    Daniela Albanesi

    2013-01-01

    Full Text Available The biosynthesis of membrane lipids is an essential pathway for virtually all bacteria. Despite its potential importance for the development of novel antibiotics, little is known about the underlying signaling mechanisms that allow bacteria to control their membrane lipid composition within narrow limits. Recent studies disclosed an elaborate feed-forward system that senses the levels of malonyl-CoA and modulates the transcription of genes that mediate fatty acid and phospholipid synthesis in many Gram-positive bacteria including several human pathogens. A key component of this network is FapR, a transcriptional regulator that binds malonyl-CoA, but whose mode of action remains enigmatic. We report here the crystal structures of FapR from Staphylococcus aureus (SaFapR in three relevant states of its regulation cycle. The repressor-DNA complex reveals that the operator binds two SaFapR homodimers with different affinities, involving sequence-specific contacts from the helix-turn-helix motifs to the major and minor grooves of DNA. In contrast with the elongated conformation observed for the DNA-bound FapR homodimer, binding of malonyl-CoA stabilizes a different, more compact, quaternary arrangement of the repressor, in which the two DNA-binding domains are attached to either side of the central thioesterase-like domain, resulting in a non-productive overall conformation that precludes DNA binding. The structural transition between the DNA-bound and malonyl-CoA-bound states of SaFapR involves substantial changes and large (>30 Å inter-domain movements; however, both conformational states can be populated by the ligand-free repressor species, as confirmed by the structure of SaFapR in two distinct crystal forms. Disruption of the ability of SaFapR to monitor malonyl-CoA compromises cell growth, revealing the essentiality of membrane lipid homeostasis for S. aureus survival and uncovering novel opportunities for the development of antibiotics

  19. Option pricing: The empirical tests of the black-scholes pricing formula and the feed-forward network

    Vlasáková Baruníková, Michaela

    2009-01-01

    In this article we evaluate the pricing performance of the rather simple but revolutionary Black-Scholes model and one of the more complex techniques (neural networks) on the European-style S&P Index call and put options over the period of 1.6.2006 till 8.6.2007. Our results on call options show that generally Black-Scholes model performs better than simple generalized feed-forward networks. On the other hand neural networks performance is improving as the option goes deep in the money and as...

  20. A prediction-based self-adaptive feed-forward control system for thermionic cathode microwave electron gun

    Beijing Free Electron Laser Facility (BFEL) adopts a thermionic cathode microwave electron gun as its RF linac injector. For relatively long macro-pulse operation, the back-bombardment effect deteriorates the characteristics of the accelerated electron beam. So the authors developed a prediction-based self-adaptive feed-forward control system to compensate for the beam-loading. The system is operational and some experimental results have been obtained, which suggests that the system is effective to improve the beam quality, and that it's capable of dealing with complicated systems whose response is time-variable, non-linear and of long delay

  1. Design Feed Forward Neural network for solving two dimension singularly perturbed integro-differential and integral equation

    Eman Ali Hussain

    2012-11-01

    Full Text Available Recently, there has been an increasing interest in the study of singular and perturbed systems. In this paper design fast feed forward neural network to present a method to solve two dimensions singularly perturbed integro-differential and integral equations. Using a multi-layer having one hidden layer with 7 hidden units (neurons and one linear output unit the sigmoid activation of each unit is radial basis function and Levenberg – Marquardt (trainlm training algorithm. Finally the results of numerical experiments are compared with the exact solution in illustrative examples to confirm the accuracy and efficiency of the presented scheme.

  2. Beam stability improvement of the HIMAC synchrotron using a feed-forward system for magnet power supplies

    In order to realize a precise dose distribution in heavy-ion cancer therapy, high beam stability is required for the accelerator complex. Owing to load fluctuation caused by the upper ring, which is one of the two rings in HIMAC, current dips of ≈5–10 Hz were observed in the power supply for the bending/quadrupole magnet of the other lower ring. The parameters of the beam stability, such as the spill variation, the beam position, and the size, were adversely affected by the current dips. In order to suppress these current dips, we developed a new feed-forward system in the magnet power supply. We verified the performance of the feed-forward system by measuring the suppression of the current dips. We also performed beam experiments to measure the variation of the horizontal tune and the structure of the beam spill, which is slowly extracted by the resonance method. The experimental result showed that the current dips were successfully reduced by the system to ΔI/I ∼ 10−6. It was also confirmed that the horizontal tune and the spill structure could be stabilized by the current dip suppression.

  3. Beam stability improvement of the HIMAC synchrotron using a feed-forward system for magnet power supplies

    Katagiri, K.; Furukawa, T.; Mizushima, K.; Uchiyama, H.; Takeshita, E.; Himukai, T.; Sato, S.; Iwata, Y.; Shirai, T.; Noda, K.

    2011-12-01

    In order to realize a precise dose distribution in heavy-ion cancer therapy, high beam stability is required for the accelerator complex. Owing to load fluctuation caused by the upper ring, which is one of the two rings in HIMAC, current dips of ≈5-10 Hz were observed in the power supply for the bending/quadrupole magnet of the other lower ring. The parameters of the beam stability, such as the spill variation, the beam position, and the size, were adversely affected by the current dips. In order to suppress these current dips, we developed a new feed-forward system in the magnet power supply. We verified the performance of the feed-forward system by measuring the suppression of the current dips. We also performed beam experiments to measure the variation of the horizontal tune and the structure of the beam spill, which is slowly extracted by the resonance method. The experimental result showed that the current dips were successfully reduced by the system to Δ I/ I ˜ 10 -6. It was also confirmed that the horizontal tune and the spill structure could be stabilized by the current dip suppression.

  4. Optimization of pigment dyeing process of high performance fibers using feed-forward bottleneck neural networks mapping technique

    Fjodorova, Natalja, E-mail: natalja.fjodorova@ki.si [National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana (Slovenia); Novic, Marjana [National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana (Slovenia); Diankova, Tamara [St-Petersburg State University of Technology and Design, Bolshaya Morskaya st. 18, 191186, St. Petersburg (Russian Federation)

    2011-10-31

    Highlights: {yields} Optimum conditions of pigment dying process of high performance fibers were proposed. {yields} The feed-forward bottleneck neural network (FFBN) as a mapping technique was implemented. {yields} We showed the influence of different factors (parameters of pigment dying) on different output responses (quality of pigment dying). - Abstract: Process optimization involves the minimization (or maximization) of an objective function, that can be established from a technical and (or) economic viewpoint taking into account safety of process. The basic idea of the optimization method using neural network (NN) is to replace the model equations (which traditionally obtained using, for example, the surface response design or others methods) by an equivalent NN. The feed-forward bottleneck neural network (FFBN) as a mapping technique is described and evaluated. From the 2D maps the optimal parameters of pigment dyeing of high performance fibers on the bases of poly-amide benzimidazole (PABI) and polyimide (arimid) are discussed. The studied fibers were treated in 32 experiments under the conditions as proposed by the Design of Experiment (DOE), varying five influencing factors. Neural network mapping method enables visualization of process and shows the influence of different factors on different output responses. Optimum parameters were selected upon compromise decision.

  5. Optimization of pigment dyeing process of high performance fibers using feed-forward bottleneck neural networks mapping technique

    Highlights: → Optimum conditions of pigment dying process of high performance fibers were proposed. → The feed-forward bottleneck neural network (FFBN) as a mapping technique was implemented. → We showed the influence of different factors (parameters of pigment dying) on different output responses (quality of pigment dying). - Abstract: Process optimization involves the minimization (or maximization) of an objective function, that can be established from a technical and (or) economic viewpoint taking into account safety of process. The basic idea of the optimization method using neural network (NN) is to replace the model equations (which traditionally obtained using, for example, the surface response design or others methods) by an equivalent NN. The feed-forward bottleneck neural network (FFBN) as a mapping technique is described and evaluated. From the 2D maps the optimal parameters of pigment dyeing of high performance fibers on the bases of poly-amide benzimidazole (PABI) and polyimide (arimid) are discussed. The studied fibers were treated in 32 experiments under the conditions as proposed by the Design of Experiment (DOE), varying five influencing factors. Neural network mapping method enables visualization of process and shows the influence of different factors on different output responses. Optimum parameters were selected upon compromise decision.

  6. Beam stability improvement of the HIMAC synchrotron using a feed-forward system for magnet power supplies

    Katagiri, K., E-mail: tag410@nirs.go.jp [National Institute of Radiological Sciences (NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Furukawa, T.; Mizushima, K. [National Institute of Radiological Sciences (NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Uchiyama, H. [Accelerator Engineering Corporation (AEC), 3-8-5 Konakadai, Inage, Chiba 263-0043 (Japan); Takeshita, E.; Himukai, T.; Sato, S.; Iwata, Y.; Shirai, T.; Noda, K. [National Institute of Radiological Sciences (NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2011-12-15

    In order to realize a precise dose distribution in heavy-ion cancer therapy, high beam stability is required for the accelerator complex. Owing to load fluctuation caused by the upper ring, which is one of the two rings in HIMAC, current dips of Almost-Equal-To 5-10 Hz were observed in the power supply for the bending/quadrupole magnet of the other lower ring. The parameters of the beam stability, such as the spill variation, the beam position, and the size, were adversely affected by the current dips. In order to suppress these current dips, we developed a new feed-forward system in the magnet power supply. We verified the performance of the feed-forward system by measuring the suppression of the current dips. We also performed beam experiments to measure the variation of the horizontal tune and the structure of the beam spill, which is slowly extracted by the resonance method. The experimental result showed that the current dips were successfully reduced by the system to {Delta}I/I {approx} 10{sup -6}. It was also confirmed that the horizontal tune and the spill structure could be stabilized by the current dip suppression.

  7. Modeling of PEM Fuel Cell Stack System using Feed-forward and Recurrent Neural Networks for Automotive Applications

    Mr. M. Karthik

    2014-05-01

    Full Text Available Artificial Neural Network (ANN has become a significant modeling tool for predicting the performance of complex systems that provide appropriate mapping between input-output variables without acquiring any empirical relationship due to the intrinsic properties. This paper is focussed towards the modeling of Proton Exchange Membrane (PEM Fuel Cell system using Artificial Neural Networks especially for automotive applications. Three different neural networks such as Static Feed Forward Network (SFFN, Cascaded Feed Forward Network (CFFN & Fully Connected Dynamic Recurrent Network (FCRN are discussed in this paper for modeling the PEM Fuel Cell System. The numerical analysis is carried out between the three Neural Network architectures for predicting the output performance of the PEM Fuel Cell. The performance of the proposed Networks is evaluated using various error criteria such as Mean Square Error, Mean Absolute Percentage Error, Mean Absolute Error, Coefficient of correlation and Iteration Values. The optimum network with high performance indices (low prediction error values and iteration values can be used as an ancillary model in developing the PEM Fuel Cell powered vehicle system. The development of the fuel cell driven vehicle model also incorporates the modeling of DC-DC Power Converter and Vehicle Dynamics. Finally the Performance of the Electric vehicle model is analyzed for two different drive cycle such as M-NEDC & M-UDDS.

  8. Performance evaluation of MLP and RBF feed forward neural network for the recognition of off-line handwritten characters

    Rishi, Rahul; Choudhary, Amit; Singh, Ravinder; Dhaka, Vijaypal Singh; Ahlawat, Savita; Rao, Mukta

    2010-02-01

    In this paper we propose a system for classification problem of handwritten text. The system is composed of preprocessing module, supervised learning module and recognition module on a very broad level. The preprocessing module digitizes the documents and extracts features (tangent values) for each character. The radial basis function network is used in the learning and recognition modules. The objective is to analyze and improve the performance of Multi Layer Perceptron (MLP) using RBF transfer functions over Logarithmic Sigmoid Function. The results of 35 experiments indicate that the Feed Forward MLP performs accurately and exhaustively with RBF. With the change in weight update mechanism and feature-drawn preprocessing module, the proposed system is competent with good recognition show.

  9. Feed-Forward Propagation of Temporal and Rate Information between Cortical Populations during Coherent Activation in Engineered In Vitro Networks

    DeMarse, Thomas B.; Pan, Liangbin; Alagapan, Sankaraleengam; Brewer, Gregory J.; Wheeler, Bruce C.

    2016-01-01

    Transient propagation of information across neuronal assembles is thought to underlie many cognitive processes. However, the nature of the neural code that is embedded within these transmissions remains uncertain. Much of our understanding of how information is transmitted among these assemblies has been derived from computational models. While these models have been instrumental in understanding these processes they often make simplifying assumptions about the biophysical properties of neurons that may influence the nature and properties expressed. To address this issue we created an in vitro analog of a feed-forward network composed of two small populations (also referred to as assemblies or layers) of living dissociated rat cortical neurons. The populations were separated by, and communicated through, a microelectromechanical systems (MEMS) device containing a strip of microscale tunnels. Delayed culturing of one population in the first layer followed by the second a few days later induced the unidirectional growth of axons through the microtunnels resulting in a primarily feed-forward communication between these two small neural populations. In this study we systematically manipulated the number of tunnels that connected each layer and hence, the number of axons providing communication between those populations. We then assess the effect of reducing the number of tunnels has upon the properties of between-layer communication capacity and fidelity of neural transmission among spike trains transmitted across and within layers. We show evidence based on Victor-Purpura’s and van Rossum’s spike train similarity metrics supporting the presence of both rate and temporal information embedded within these transmissions whose fidelity increased during communication both between and within layers when the number of tunnels are increased. We also provide evidence reinforcing the role of synchronized activity upon transmission fidelity during the spontaneous

  10. Fictitious Reference Tuning of the Feed-Forward Controller in a Two-Degree-of-Freedom Control System

    Kaneko, Osamu; Yamashina, Yusuke; Yamamoto, Shigeru

    In this paper, we provide a new effective tuning method to obtain the optimal parameter of the feed-forward controller in a two-degree-of-freedom (2DOF) control system for the purpose of achieving the desired response without using a mathematical model of a plant. The first author proposed “fictitious reference iterative tuning” (which is abbreviated to FRIT) as an effective method for the tuning of parameters of a controller by using only one-shot experimental data instead of using mathematical models of a plant. Here, we extend FRIT to the tuning of the feed-forward controller in a 2DOF control system and develop the off-line computation so as to be done by the least squares method. For these purposes, we introduce a new cost function consisting of the fictitious reference and the actual data (since we do not have to do iterative computation in the least squares method, we call the proposed method here as “fictitious reference tuning”). Since the new cost function is quadratically-parameterized, it is possible to analyze how far the obtained parameter is apart from the desired one. Thus, we then derive a pre-filter which is applied to the actual data so as to guarantee that the obtained parameter is close to the desired one. We also show that the proposed method is applicable to the case in which the initial experiment is performed in the conventional 1DOF control system. Finally, we illustrate experimental results in order to show the utility and the validity of the proposed method.

  11. Targeted gene delivery via N-acetylglucosamine receptor mediated endocytosis.

    Singh, Bijay; Maharjan, Sushila; Kim, You-Kyoung; Jiang, Tai; Islam, Mohammad Ariful; Kang, Sang-Kee; Cho, Myung-Haing; Choi, Yun-Jaie; Cho, Chong-Su

    2014-11-01

    Receptor-mediated endocytosis is a promising approach of gene delivery into the target cells via receptor-ligand interaction. Vimentins at the cell surface are recently known to bind N-acetylglucosamine (GlcNAc) residue, therefore, the cell surfaces of vimentin-expressing cells could be targeted by using the GlcNAc residue as a specific ligand for receptor-mediated gene delivery. Here, we have developed polymeric gene delivery vectors, based on poly(ethylene oxide)(PEO) and poly(aspartamide), namely poly[(aspartamide)(diethylenetriamine)]-b-[PEO-(GlcNAc)] (PADPG) and poly[(aspartamide)(diethylenetriamine)]-b-[PEO] (PADP) to elucidate the efficiency of GlcNAc ligand for gene delivery through receptor mediated endocytosis. To determine the efficiency of these polymeric vectors for specific gene delivery, the DNA condensation ability of PADPG and PADP and the subsequent formation of polymeric nanoparticles were confirmed by gel retardation assay and transmission electron microscopy respectively. Both PADPG and PADP had lower cytotoxicity than polyethylenimine 25 K (PEI 25 K). However, their transfection efficiency was comparatively lower than PEI 25 K due to hydrophilic property of PEO in the vectors. To observe the stability of polymeric nanoparticles, the transfection of PADPG and PADP was carried out in the presence of serum. Favorably, the interfering effect of serum on the transfection efficiency of PADPG and PADP was also very low. Finally, when the cell specificity of these polymeric vectors was investigated, PADPG had high gene transfection in vimentin-expressing cells than vimentin-deficiency cells. The high transfection efficiency of PADPG was attributed to the GlcNAc in the polymeric vector which interact specifically with vimentin in the cells for the receptor-mediated endocytosis. The competitive inhibition assay further proved the receptor-mediated endocytosis of PADPG. Thus, this study demonstrates that conjugation of GlcNAc is an effective and rational

  12. Hybrid evolutionary techniques in feed forward neural network with distributed error for classification of handwritten Hindi `SWARS'

    Kumar, Somesh; Pratap Singh, Manu; Goel, Rajkumar; Lavania, Rajesh

    2013-12-01

    In this work, the performance of feedforward neural network with a descent gradient of distributed error and the genetic algorithm (GA) is evaluated for the recognition of handwritten 'SWARS' of Hindi curve script. The performance index for the feedforward multilayer neural networks is considered here with distributed instantaneous unknown error i.e. different error for different layers. The objective of the GA is to make the search process more efficient to determine the optimal weight vectors from the population. The GA is applied with the distributed error. The fitness function of the GA is considered as the mean of square distributed error that is different for each layer. Hence the convergence is obtained only when the minimum of different errors is determined. It has been analysed that the proposed method of a descent gradient of distributed error with the GA known as hybrid distributed evolutionary technique for the multilayer feed forward neural performs better in terms of accuracy, epochs and the number of optimal solutions for the given training and test pattern sets of the pattern recognition problem.

  13. Automatic Segmentation of Colon in 3D CT Images and Removal of Opacified Fluid Using Cascade Feed Forward Neural Network

    K. Gayathri Devi

    2015-01-01

    Full Text Available Purpose. Colon segmentation is an essential step in the development of computer-aided diagnosis systems based on computed tomography (CT images. The requirement for the detection of the polyps which lie on the walls of the colon is much needed in the field of medical imaging for diagnosis of colorectal cancer. Methods. The proposed work is focused on designing an efficient automatic colon segmentation algorithm from abdominal slices consisting of colons, partial volume effect, bowels, and lungs. The challenge lies in determining the exact colon enhanced with partial volume effect of the slice. In this work, adaptive thresholding technique is proposed for the segmentation of air packets, machine learning based cascade feed forward neural network enhanced with boundary detection algorithms are used which differentiate the segments of the lung and the fluids which are sediment at the side wall of colon and by rejecting bowels based on the slice difference removal method. The proposed neural network method is trained with Bayesian regulation algorithm to determine the partial volume effect. Results. Experiment was conducted on CT database images which results in 98% accuracy and minimal error rate. Conclusions. The main contribution of this work is the exploitation of neural network algorithm for removal of opacified fluid to attain desired colon segmentation result.

  14. Using an extended Kalman filter learning algorithm for feed-forward neural networks to describe tracer correlations

    D. J. Lary

    2004-06-01

    Full Text Available In this study a new extended Kalman filter (EKF learning algorithm for feed-forward neural networks (FFN is used. With the EKF approach, the training of the FFN can be seen as state estimation for a non-linear stationary process. The EKF method gives excellent convergence performances provided that there is enough computer core memory and that the machine precision is high. Neural networks are ideally suited to describe the spatial and temporal dependence of tracer-tracer correlations. The neural network performs well even in regions where the correlations are less compact and normally a family of correlation curves would be required. For example, the CH4-N2O correlation can be well described using a neural network trained with the latitude, pressure, time of year, and CH4 volume mixing ratio (v.m.r.. The neural network was able to reproduce the CH4-N2O correlation with a correlation coefficient between simulated and training values of 0.9997. The neural network Fortran code used is available for download.

  15. Using an Extended Kalman Filter Learning Algorithm for Feed-Forward Neural Networks to Describe Tracer Correlations

    Lary, David J.; Mussa, Yussuf

    2004-01-01

    In this study a new extended Kalman filter (EKF) learning algorithm for feed-forward neural networks (FFN) is used. With the EKF approach, the training of the FFN can be seen as state estimation for a non-linear stationary process. The EKF method gives excellent convergence performances provided that there is enough computer core memory and that the machine precision is high. Neural networks are ideally suited to describe the spatial and temporal dependence of tracer-tracer correlations. The neural network performs well even in regions where the correlations are less compact and normally a family of correlation curves would be required. For example, the CH4-N2O correlation can be well described using a neural network trained with the latitude, pressure, time of year, and CH4 volume mixing ratio (v.m.r.). The neural network was able to reproduce the CH4-N2O correlation with a correlation coefficient between simulated and training values of 0.9997. The neural network Fortran code used is available for download.

  16. A current mode feed-forward gain control system for a 0.8 V CMOS hearing aid

    A current mode feed-forward gain control (CMFGC) technique is presented, which is applied in the front-end system of a hearing aid chip. Compared with conventional automatic gain control (AGC), CMFGC significantly improves the total harmonic distortion (THD) by digital gain control. To attain the digital gain control codes according to the extremely weak output signal from the microphone, a rectifier and a state controller implemented in current mode are proposed. A prototype chip has been designed based on a 0.13 μm standard CMOS process. The measurement results show that the supply voltage can be as low as 0.6 V. And with the 0.8 V supply voltage, the THD is improved and below 0.06% (-64 dB) at the output level of 500 mVp-p, yet the power consumption is limited to 40 μW. In addition, the input referred noise is only 4 μVrms and the maximum gain is maintained at 33 dB. (semiconductor integrated circuits)

  17. A current mode feed-forward gain control system for a 0.8 V CMOS hearing aid*

    Li Fanyang; Yang Haigang; Liu Fei; Yin Tao

    2011-01-01

    A current mode feed-forward gain control (CMFGC) technique is presented, which is applied in the front-end system of a heating aid chip. Compared with conventional automatic gain control (AGC), CMFGC significantly improves the total harmonic distortion (THD) by digital gain control. To attain the digital gain control codes according to the extremely weak output signal from the microphone, a rectifier and a state controller implemented in current mode are proposed. A prototype chip has been designed based on a 0.13μm standard CMOS process. The measurement results show that the supply voltage can be as low as 0.6 V. And with the 0.8 V supply voltage, the THD is improved and below 0.06% (-64 dB) at the output level of 500 mVp-p, yet the power consumption is limited to 40μW. In addition, the input referred noise is only 4μVrms and the maximum gain is maintained at 33 dB.

  18. A current mode feed-forward gain control system for a 0.8 V CMOS hearing aid

    Fanyang, Li; Haigang, Yang; Fei, Liu; Tao, Yin

    2011-06-01

    A current mode feed-forward gain control (CMFGC) technique is presented, which is applied in the front-end system of a hearing aid chip. Compared with conventional automatic gain control (AGC), CMFGC significantly improves the total harmonic distortion (THD) by digital gain control. To attain the digital gain control codes according to the extremely weak output signal from the microphone, a rectifier and a state controller implemented in current mode are proposed. A prototype chip has been designed based on a 0.13 μm standard CMOS process. The measurement results show that the supply voltage can be as low as 0.6 V. And with the 0.8 V supply voltage, the THD is improved and below 0.06% (-64 dB) at the output level of 500 mVp-p, yet the power consumption is limited to 40 μW. In addition, the input referred noise is only 4 μVrms and the maximum gain is maintained at 33 dB.

  19. Feed-forward and reciprocal inhibition for gain and phase timing control in a computational model of repetitive cough.

    Pitts, Teresa; Morris, Kendall F; Segers, Lauren S; Poliacek, Ivan; Rose, Melanie J; Lindsey, Bruce G; Davenport, Paul W; Howland, Dena R; Bolser, Donald C

    2016-07-01

    We investigated the hypothesis, motivated in part by a coordinated computational cough network model, that second-order neurons in the nucleus tractus solitarius (NTS) act as a filter and shape afferent input to the respiratory network during the production of cough. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms of the parasternal (inspiratory) and rectus abdominis (expiratory) muscles and esophageal pressure were recorded. In vivo data revealed that expiratory motor drive during bouts of repetitive coughs is variable: peak expulsive amplitude increases from the first cough, peaks about the eighth or ninth cough, and then decreases through the remainder of the bout. Model simulations indicated that feed-forward inhibition of a single second-order neuron population is not sufficient to account for this dynamic feature of a repetitive cough bout. When a single second-order population was split into two subpopulations (inspiratory and expiratory), the resultant model produced simulated expiratory motor bursts that were comparable to in vivo data. However, expiratory phase durations during these simulations of repetitive coughing had less variance than those in vivo. Simulations in which reciprocal inhibitory processes between inspiratory-decrementing and expiratory-augmenting-late neurons were introduced exhibited increased variance in the expiratory phase durations. These results support the prediction that serial and parallel processing of airway afferent signals in the NTS play a role in generation of the motor pattern for cough. PMID:27283917

  20. Characterization of GABA/sub A/ receptor-mediated 36chloride uptake in rat brain synaptoneurosomes

    γ-Aminobutyric acid (GABA) receptor-mediated 36chloride (36Cl-) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated 36Cl- uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated 36Cl- uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated 36Cl- uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br->Cl-≥NO3->I-≥SCN->>C3H5OO-≥ClO4->F-, consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl- channel. 43 references, 4 figures, 3 tables

  1. Feed-forward regulation of bile acid detoxification by CYP3A4: studies in humanized transgenic mice.

    Stedman, Catherine; Robertson, Graham; Coulter, Sally; Liddle, Christopher

    2004-03-19

    Bile acids are potentially toxic end products of cholesterol metabolism and their concentrations must be tightly regulated. Homeostasis is maintained by both feed-forward regulation and feedback regulation. We used humanized transgenic mice incorporating 13 kb of the 5' regulatory flanking sequence of CYP3A4 linked to a lacZ reporter gene to explore the in vivo relationship between bile acids and physiological adaptive CYP3A gene regulation in acute cholestasis after bile duct ligation (BDL). Male transgenic mice were subjected to BDL or sham surgery prior to sacrifice on days 3, 6, and 10, and others were injected with intraperitoneal lithocholic acid (LCA) or vehicle alone. BDL resulted in marked hepatic activation of the CYP3A4/lacZ transgene in pericentral hepatocytes, with an 80-fold increase in transgene activation by day 10. Individual bile acids were quantified by liquid chromatography/mass spectrometry. Serum 6beta-hydroxylated bile acids were increased following BDL, confirming the physiological relevance of endogenous Cyp3a induction to bile acid detoxification. Although concentrations of conjugated primary bile acids increased after BDL, there was no increase in LCA, a putative PXR ligand, indicating that this cannot be the only endogenous bile acid mediating this protective response. Moreover, in LCA-treated animals, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining showed hepatic activation of the CYP3A4 transgene only on the liver capsular surface, and minimal parenchymal induction, despite significant liver injury. This study demonstrates that CYP3A up-regulation is a significant in vivo adaptive response to cholestasis. However, this up-regulation is not dependent on increases in circulating LCA and the role of other bile acids as regulatory molecules requires further exploration. PMID:14681232

  2. Feed-Forward Control Strategy for the VSC of DVR for Smooth and Clean Power Flow to Load

    Aamir Hanif

    2012-04-01

    Full Text Available VSC (Voltage Source Converter feed-forward control strategy of DVR (Dynamic Voltage Restorer for an in-phase voltage injection scheme is proposed in this paper to tackle not only voltage sags and swells in the utility supply but also phase jumps as well. The proposed strategy utilizes a time based ramp at a clock rate of 50Hz to obtain a 3-phase reference signal that is compared with actual 3-phase utility voltage to obtain an error signal. If the error in each phase of the utility voltage is greater than zero then appropriate control signals are generated. The switching devices in VSC are switched accordingly to compensate voltage sags, swells and phase jumps in the utility voltage that propagates to load. For the mitigation of voltage sags, swells and phase jumps, the unipolar SPWM control is used. The proposed control system response time to compensate voltage sag, swell and phase jump through switching of VSC devices is less than 10ms whereas ITIC curve and SEMI-F-47 standard suggest a target of 20ms. Load voltage THD is below 5% as per IEEE Std. 519-1992. These results show that employed control strategy has an excellent capability of voltage restoration with acceptable harmonic distortion, within specified time frame for smooth and clean power flow to load. MATLAB/Simulink SimpowerSystem tool box has been used to obtain simulation results to verify the effectiveness and validity of the proposed control strategy to improve the quality of the power delivered to the load.

  3. Electron beam energy and bunch length feed forward control studies using an artificial neural network at the Linac coherent light source

    This paper describes the results of an advanced control algorithm for the stabilization of electron beam energy in a Linac. The approach combines a conventional Proportional-Integral (PI) controller with a neural network (NNET) feed forward algorithm; it utilizes the robustness of PI control and the ability of a feed forward system in order to exert control over a wider range of frequencies. The NNET is trained to recognize jitter occurring in the phase and voltage of one of the klystrons, based on a record of these parameters, and predicts future energy deviations. A systematic approach is developed to determine the optimal NNET parameters that are then applied to the Australian Synchrotron Linac. The system's capability to fully cancel multi-frequency jitter is demonstrated. The NNET system is then augmented with the PI algorithm, and further jitter attenuation is achieved when the NNET is not operating optimally.

  4. The liver taxis of receptor mediated lactosaminated human growth hormone

    Radiography imaging is used to assess liver taxis mechanism of anti-dwarfism drug lactosaminated human growth hormone (L-rhGH). Both L-rhGH and rhGH labelled with 131I are used to study their biodistribution in animals (including rabbits, cocks and rats). The results show that L-rhGH is of specific hepatic targeting property, and the maximum hepatic concentration rate is 76.8%, which is two times of rhGH. Its hepatic binding is receptor mediated

  5. PANET: a GPU-based tool for fast parallel analysis of robustness dynamics and feed-forward/feedback loop structures in large-scale biological networks.

    Hung-Cuong Trinh

    Full Text Available It has been a challenge in systems biology to unravel relationships between structural properties and dynamic behaviors of biological networks. A Cytoscape plugin named NetDS was recently proposed to analyze the robustness-related dynamics and feed-forward/feedback loop structures of biological networks. Despite such a useful function, limitations on the network size that can be analyzed exist due to high computational costs. In addition, the plugin cannot verify an intrinsic property which can be induced by an observed result because it has no function to simulate the observation on a large number of random networks. To overcome these limitations, we have developed a novel software tool, PANET. First, the time-consuming parts of NetDS were redesigned to be processed in parallel using the OpenCL library. This approach utilizes the full computing power of multi-core central processing units and graphics processing units. Eventually, this made it possible to investigate a large-scale network such as a human signaling network with 1,609 nodes and 5,063 links. We also developed a new function to perform a batch-mode simulation where it generates a lot of random networks and conducts robustness calculations and feed-forward/feedback loop examinations of them. This helps us to determine if the findings in real biological networks are valid in arbitrary random networks or not. We tested our plugin in two case studies based on two large-scale signaling networks and found interesting results regarding relationships between coherently coupled feed-forward/feedback loops and robustness. In addition, we verified whether or not those findings are consistently conserved in random networks through batch-mode simulations. Taken together, our plugin is expected to effectively investigate various relationships between dynamics and structural properties in large-scale networks. Our software tool, user manual and example datasets are freely available at http://panet-csc.sourceforge.net/.

  6. A Quantitative Model of Glucose Signaling in Yeast Reveals an Incoherent Feed Forward Loop Leading to a Specific, Transient Pulse of Transcription

    Kuttykrishnan, Sooraj; Sabina, Jeffrey; Langton, Laura; Johnston, Mark; Brent, Michael R.

    The ability to design and engineer organisms demands the ability to predict kinetic responses of novel regulatory networks built from well-characterized biological components. Surprisingly, few validated kinetic models of complex regulatory networks have been derived by combining models of the network components. A major bottleneck in producing such models is the difficulty of measuring in vivo rate constants for components of complex networks. We demonstrate that a simple, genetic approach to measuring rate constants in vivo produces an accurate kinetic model of the complex network that Saccharomyces cerevisiae employs to regulate the expression of genes encoding glucose transporters. The model predicts a transient pulse of transcription of HXT4 (but not HXT2 or HXT3) in response to addition of a small amount of glucose to cells, an outcome we observed experimentally. Our model also provides a mechanistic explanation for this result: HXT24 are governed by a type 2, incoherent feed forward regulatory loop involving the Rgt1 and Mig2 transcriptional repressors. The efficiency with which Rgt1 and Mig2 repress expression of each HXT gene determines which of them have a pulse of transcription in response to glucose. Finally, the model correctly predicts how lesions in the feed forward loop change the kinetics of induction of HXT4 expression.

  7. Inhibition by the tetramine disulphide, benextramine, of cardiac chronotropic histamine H2-receptor-mediated effects.

    Belleau, B.; Benfey, B. G.; Benfey, T. J.; Melchiorre, C.

    1982-01-01

    1 Benextramine (N,N1-bis[o-methoxybenzylamino)-n-hexyl]cystamine), which irreversibly blocks alpha-adrenoceptors and does not inhibit the H1-receptor-mediated contractile effect of histamine on guinea-pig isolated ileum, also did not inhibit the H1-receptor-mediated inotropic effect of histamine on guinea-pig isolated atrium. 2 Benextramine irreversibly inhibited the H2-receptor-mediated chronotropic effect of histamine on guinea-pig isolated atrium. 3 Since its combination with the competiti...

  8. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

    In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, ''new'' radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy. (orig.)

  9. Feed-Forward Neural Network Soft-Sensor Modeling of Flotation Process Based on Particle Swarm Optimization and Gravitational Search Algorithm

    Wang, Jie-Sheng; Han, Shuang

    2015-01-01

    For predicting the key technology indicators (concentrate grade and tailings recovery rate) of flotation process, a feed-forward neural network (FNN) based soft-sensor model optimized by the hybrid algorithm combining particle swarm optimization (PSO) algorithm and gravitational search algorithm (GSA) is proposed. Although GSA has better optimization capability, it has slow convergence velocity and is easy to fall into local optimum. So in this paper, the velocity vector and position vector of GSA are adjusted by PSO algorithm in order to improve its convergence speed and prediction accuracy. Finally, the proposed hybrid algorithm is adopted to optimize the parameters of FNN soft-sensor model. Simulation results show that the model has better generalization and prediction accuracy for the concentrate grade and tailings recovery rate to meet the online soft-sensor requirements of the real-time control in the flotation process. PMID:26583034

  10. Analysis and prediction of aperiodic hydrodynamic oscillatory time series by feed-forward neural networks, fuzzy logic, and a local nonlinear predictor

    Gentili, Pier Luigi, E-mail: pierluigi.gentili@unipg.it [Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia (Italy); Gotoda, Hiroshi [Department of Mechanical Engineering, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu-shi, Shiga 525-8577 (Japan); Dolnik, Milos; Epstein, Irving R. [Department of Chemistry, Brandeis University, Waltham, Massachusetts 02454-9110 (United States)

    2015-01-15

    Forecasting of aperiodic time series is a compelling challenge for science. In this work, we analyze aperiodic spectrophotometric data, proportional to the concentrations of two forms of a thermoreversible photochromic spiro-oxazine, that are generated when a cuvette containing a solution of the spiro-oxazine undergoes photoreaction and convection due to localized ultraviolet illumination. We construct the phase space for the system using Takens' theorem and we calculate the Lyapunov exponents and the correlation dimensions to ascertain the chaotic character of the time series. Finally, we predict the time series using three distinct methods: a feed-forward neural network, fuzzy logic, and a local nonlinear predictor. We compare the performances of these three methods.

  11. A Kind of Second-Order Learning Algorithm Based on Generalized Cost Criteria in Multi-Layer Feed-Forward Neural Networks

    张长江; 付梦印; 金梅

    2003-01-01

    A kind of second-order algorithm--recursive approximate Newton algorithm was given by Karayiannis. The algorithm was simplified when it was formulated. Especially, the simplification to matrix Hessian was very reluctant, which led to the loss of valuable information and affected performance of the algorithm to certain extent. For multi-layer feed-forward neural networks, the second-order back-propagation recursive algorithm based generalized cost criteria was proposed. It is proved that it is equivalent to Newton recursive algorithm and has a second-order convergent rate. The performance and application prospect are analyzed. Lots of simulation experiments indicate that the calculation of the new algorithm is almost equivalent to the recursive least square multiple algorithm. The algorithm and selection of networks parameters are significant and the performance is more excellent than BP algorithm and the second-order learning algorithm that was given by Karayiannis.

  12. Analysis and prediction of aperiodic hydrodynamic oscillatory time series by feed-forward neural networks, fuzzy logic, and a local nonlinear predictor

    Forecasting of aperiodic time series is a compelling challenge for science. In this work, we analyze aperiodic spectrophotometric data, proportional to the concentrations of two forms of a thermoreversible photochromic spiro-oxazine, that are generated when a cuvette containing a solution of the spiro-oxazine undergoes photoreaction and convection due to localized ultraviolet illumination. We construct the phase space for the system using Takens' theorem and we calculate the Lyapunov exponents and the correlation dimensions to ascertain the chaotic character of the time series. Finally, we predict the time series using three distinct methods: a feed-forward neural network, fuzzy logic, and a local nonlinear predictor. We compare the performances of these three methods

  13. Realization of nonlinear PID with feed-forward controller for 3-DOF flight simulator and hardware-in-the-loop simulation

    Duan Haibin; Wang Daobo; Yu Xiufen

    2008-01-01

    As friction, intrinsic steady-state nonlinearity poses a challenging dilemma to the control system of 3-DOF (three degree of freedom) flight simulator, a novel hybrid control strategy of nonlinear PID (proportional-integral-derivative) with additional FFC (feed-forward controller) is proposed, and the hardware-in-the-loop simu-lation results are also given. Based on the description of 3-DOF flight simulator, a novel nonlinear PID theory is well introduced. Then a nonlinear PID controller with additional FFC is designed. Subsequently, the loop structure of 3-DOF flight simulator is also designed. Finally, a series of hardware-in-the-loop simulation experiments are undertaken to verify the feasibility and effectiveness of the proposed nonlinear FID controller with additional FFC for 3-DOF flight simulator.

  14. 基于LM5025的有源箝位反激变换器的前馈控制%Feed-Forward Control of the Active Clamp Flyback Converters Based on LM5025

    雷明; 程善美; 于孟春; 申勇哲

    2012-01-01

    在有源箝位反激变换器负载基本恒定的情况下采用前馈控制既可以减小变换器体积,又可降低变换器的成本。文中在分析有源箝位反激变换器工作原理的基础上,结合LM5025器件的前馈控制特性,深入研究了基于LM5025的有源箝位反激变换器前馈控制的实现方案,设计了前馈控制电路的参数,完成了有源前馈反激变换器电路设计。在此基础上进行了实验研究,实验结果证明了有源箝位反激变换器前馈控制的有效性和实用性。%Feed-forward control can both reduce the size of the converter volume and reduce the cost of the converter when the active clamp flyback converter load is almost constant. On the basis of the analysis of the active clamp flyback converter working principle, and combined with the feed-forward features of the LM5025 device, the implementation of feed-forward control used in active clamp flyback converter is deeply studied based on the LM5025, and the parameters of the feed-forward control circuit is designed, and the active feed forward flyback converter circuit is implemented. On this basis, the experimental study is earried, and the experimental results show the effectiveness and practicality of the feed-forward control of the active clamp flyback converter.

  15. Characterization of GABA/sub A/ receptor-mediated /sup 36/chloride uptake in rat brain synaptoneurosomes

    Luu, M.D.; Morrow, A.L.; Paul, S.M.; Schwartz, R.D.

    1987-09-07

    ..gamma..-Aminobutyric acid (GABA) receptor-mediated /sup 36/chloride (/sup 36/Cl/sup -/) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated /sup 36/Cl/sup -/ uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated /sup 36/Cl/sup -/ uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated /sup 36/Cl/sup -/ uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br/sup -/>Cl/sup -/greater than or equal toNO/sub 3//sup -/>I/sup -/greater than or equal toSCN/sup -/>>C/sub 3/H/sub 5/OO/sup -/greater than or equal toClO/sub 4//sup -/>F/sup -/, consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl/sup -/ channel. 43 references, 4 figures, 3 tables.

  16. Dopamine receptor-mediated regulation of neuronal "clock" gene expression.

    Imbesi, M; Yildiz, S; Dirim Arslan, A; Sharma, R; Manev, H; Uz, T

    2009-01-23

    Using a transgenic mice model (i.e. "clock" knockouts), clock transcription factors have been suggested as critical regulators of dopaminergic behaviors induced by drugs of abuse. Moreover, it has been shown that systemic administration of psychostimulants, such as cocaine and methamphetamine regulates the striatal expression of clock genes. However, it is not known whether dopamine receptors mediate these regulatory effects of psychostimulants at the cellular level. Primary striatal neurons in culture express dopamine receptors as well as clock genes and have been successfully used in studying dopamine receptor functioning. Therefore, we investigated the role of dopamine receptors on neuronal clock gene expression in this model using specific receptor agonists. We found an inhibitory effect on the expression of mClock and mPer1 genes with the D2-class (i.e. D2/D3) receptor agonist quinpirole. We also found a generalized stimulatory effect on the expression of clock genes mPer1, mClock, mNPAS2 (neuronal PAS domain protein 2), and mBmal1 with the D1-class (i.e. D1) receptor agonist SKF38393. Further, we tested whether systemic administration of dopamine receptor agonists causes similar changes in striatal clock gene expression in vivo. We found quinpirole-induced alterations in mPER1 protein levels in the mouse striatum (i.e. rhythm shift). Collectively, our results indicate that the dopamine receptor system may mediate psychostimulant-induced changes in clock gene expression. Using striatal neurons in culture as a model, further research is needed to better understand how dopamine signaling modulates the expression dynamics of clock genes (i.e. intracellular signaling pathways) and thereby influences neuronal gene expression, neuronal transmission, and brain functioning. PMID:19017537

  17. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  18. Kinetic model-based feed-forward controlled fed-batch fermentation of Lactobacillus rhamnosus for the production of lactic acid from Arabic date juice.

    Choi, Minsung; Al-Zahrani, Saeed M; Lee, Sang Yup

    2014-06-01

    Arabic date is overproduced in Arabic countries such as Saudi Arabia and Iraq and is mostly composed of sugars (70-80 wt%). Here we developed a fed-batch fermentation process by using a kinetic model for the efficient production of lactic acid to a high concentration from Arabic date juice. First, a kinetic model of Lactobacillus rhamnosus grown on date juice in batch fermentation was constructed in EXCEL so that the estimation of parameters and simulation of the model can be easily performed. Then, several fed-batch fermentations were conducted by employing different feeding strategies including pulsed feeding, exponential feeding, and modified exponential feeding. Based on the results of fed-batch fermentations, the kinetic model for fed-batch fermentation was also developed. This new model was used to perform feed-forward controlled fed-batch fermentation, which resulted in the production of 171.79 g l(-1) of lactic acid with the productivity and yield of 1.58 and 0.87 g l(-1) h(-1), respectively. PMID:24100793

  19. A Feed-Forward Circuit of Endogenous PGC-1α and Estrogen Related Receptor α Regulates the Neuronal Electron Transport Chain.

    Bakshi, Rachit; Mittal, Shuchi; Liao, Zhixiang; Scherzer, Clemens R

    2016-01-01

    Peroxisome proliferator-activated receptor  γ coactivator 1α (PGC-1α) is a central regulator of cellular and mitochondrial metabolism. Cellular bioenergetics are critically important in "energy-guzzling" neurons, but the components and wiring of the transcriptional circuit through which PGC-1α regulates the neuronal electron transport chain have not been established. This information may be vital for restoring neuronal bioenergetics gene expression that is compromised during incipient Parkinson's neuropathology and in aging-dependent brain diseases. Here we delineate a neuronal transcriptional circuit controlled by endogenous PGC-1α. We show that a feed-forward circuit of endogenous neuronal PGC-1α and the orphan nuclear estrogen-related receptor α (ERRα) activates the nuclear-encoded mitochondrial electron transport chain. PGC-1α not only trans-activated expression of ERRα, but also coactivated ERRα target genes in complexes I, II, IV, and V of the neuronal electron transport chain via association with evolutionary conserved ERRα promoter binding motifs. Chemical activation of this transcriptional program induced transcription of the neuronal electron transport chain. These data highlight a neuronal transcriptional circuit regulated by PGC-1α that can be therapeutically targeted for Parkinson's and other neurodegenerative diseases. PMID:27088034

  20. Trypanosoma cruzi: antigen-receptor mediated endocytosis of antibody

    Judith Abelha

    1981-06-01

    Full Text Available Trypanomastigote forms of Trypanosoma cruzi were derived from tissue culture and incubated with immune and non-immune human sera. All immune sera showed high titers of specific humoral antibodies of the IgM or the IgG type. Agglutination and swelling of parasites were observed after incubation at 37ºC, but many trypomastigotes remained free-swimming in the sera for two to three days. The quantitiy of immune serum capable of lysing a maximum of 10 x 10 [raised to the power of 6] sensitized red cells was not capable of lysing 4 x 10 [raised to the power of 3] tripomastigotes. Typically, the parasites underwent cyclical changes with the formation of clumps of amastigotes and the appearance of epimastigote forms. Multiplication of the parasites was observed in immune sera. Further, the infectivity of the parasites to susceptible mice was not lost. All sera used produced similar general effects on the growth of the parasite. The antibody bound to T. cruzi appeard to enter cells by antigen-receptor mediated endocytosis. The ferritin-conjugated antibody was internalized and delivered to phagolysosomes where they might be completely degraded to amino-acids. This seemed to be a coupled process by which the immunoglobulin is first bound to specific parasite surface receptor and then rapidly endocytosed by the cell.Formas tripomastigotas de Trypanosoma cruzi derivadas de cultura de tecido foram encubadas com soros humanos imunes e não-imunes.Todos os soros humanos usados tinham títulos elevados de anticorpos das classes IgM ou IgG. Aglutinação e entumescimento dos parasitos eram observados apos encubação a 37ºC mas muitos tripomastigotas permaneceram circulando livremente nos soros por dois a três dias. A quantidade de soro imune capaz de lisar um máximo de 10 x 10 [elevado a 6] hemácias sensibilizadas não foi capaz de lisar 4 x 10 [elevado a 3] tripomastigotas. Tipicamente, os parasitos apresentavam alterações cíclicas com formação de

  1. C-terminal Src kinase-mediated EPIYA phosphorylation of Pragmin creates a feed-forward C-terminal Src kinase activation loop that promotes cell motility.

    Senda, Yoshie; Murata-Kamiya, Naoko; Hatakeyama, Masanori

    2016-07-01

    Pragmin is one of the few mammalian proteins containing the Glu-Pro-Ile-Tyr-Ala (EPIYA) tyrosine-phosphorylation motif that was originally discovered in the Helicobacter pylori CagA oncoprotein. Following delivery into gastric epithelial cells by type IV secretion and subsequent tyrosine phosphorylation at the EPIYA motifs, CagA serves as an oncogenic scaffold/adaptor that promiscuously interacts with SH2 domain-containing mammalian proteins such as the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) and the C-terminal Src kinase (Csk), a negative regulator of Src family kinases. Like CagA, Pragmin also forms a physical complex with Csk. In the present study, we found that Pragmin directly binds to Csk by the tyrosine-phosphorylated EPIYA motif. The complex formation potentiates kinase activity of Csk, which in turn phosphorylates Pragmin on tyrosine-238 (Y238), Y343, and Y391. As Y391 of Pragmin comprises the EPIYA motif, Pragmin-Csk interaction creates a feed-forward regulatory loop of Csk activation. Together with the finding that Pragmin and Csk are colocalized to focal adhesions, these observations indicate that the Pragmin-Csk interaction, triggered by Pragmin EPIYA phosphorylation, robustly stimulates the kinase activity of Csk at focal adhesions, which direct cell-matrix adhesion that regulates cell morphology and cell motility. As a consequence, expression of Pragmin and/or Csk in epithelial cells induces an elongated cell shape with elevated cell scattering in a manner that is mutually dependent on Pragmin and Csk. Deregulation of the Pragmin-Csk axis may therefore induce aberrant cell migration that contributes to tumor invasion and metastasis. PMID:27116701

  2. Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl/Hes genes.

    Ben E Housden

    Full Text Available Dynamic activity of signaling pathways, such as Notch, is vital to achieve correct development and homeostasis. However, most studies assess output many hours or days after initiation of signaling, once the outcome has been consolidated. Here we analyze genome-wide changes in transcript levels, binding of the Notch pathway transcription factor, CSL [Suppressor of Hairless, Su(H, in Drosophila], and RNA Polymerase II (Pol II immediately following a short pulse of Notch stimulation. A total of 154 genes showed significant differential expression (DE over time, and their expression profiles stratified into 14 clusters based on the timing, magnitude, and direction of DE. E(spl genes were the most rapidly upregulated, with Su(H, Pol II, and transcript levels increasing within 5-10 minutes. Other genes had a more delayed response, the timing of which was largely unaffected by more prolonged Notch activation. Neither Su(H binding nor poised Pol II could fully explain the differences between profiles. Instead, our data indicate that regulatory interactions, driven by the early-responding E(splbHLH genes, are required. Proposed cross-regulatory relationships were validated in vivo and in cell culture, supporting the view that feed-forward repression by E(splbHLH/Hes shapes the response of late-responding genes. Based on these data, we propose a model in which Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts.

  3. Upregulation of endothelin ETB receptor-mediated vasoconstriction in rat coronary artery after organ culture

    Eskesen, Karen; Edvinsson, Lars

    2006-01-01

    The aim of this study was to examine if endothelin ET(B) receptor-mediated contraction occurred in isolated segments of rat coronary arteries during organ culture. Presence of contractile endothelin ET(B) receptors was studied by measuring the change in isometric tension in rings of left anterior...

  4. Bombesin receptor-mediated imaging and cytotoxicity: review and current status

    Sancho, Veronica; Di Florio, Alessia; Moody, Terry W.; Jensen, Robert T.

    2011-01-01

    The three mammalian bombesin (Bn) receptors (gastrin-releasing peptide [GRP] receptor, neuromedin B [NMB] receptor, BRS-3) are one of the classes of G protein-coupled receptors that are most frequently over-express/ectopically expressed by common, important malignancies. Because of the clinical success of somatostatin receptor-mediated imaging and cytotoxicity with neuroendocrine...

  5. Downregulation of adenosine and P2X receptor-mediated cardiovascular responses in heart failure rats

    Zhao, Xin; Sun, X Y; Erlinge, D;

    2000-01-01

    degradation product adenosine, experiments were performed in a rat model of ischaemic CHF. In this model, ischaemia was induced in rats by ligation of the left coronary artery. Our results demonstrate that there is a selective downregulation of P2X receptor-mediated pressor effects, while the hypotensive...

  6. Dopamine receptor-mediated regulation of neuronal “clock” gene expression

    Imbesi, Marta; Yildiz, Sevim; Arslan, Ahmet Dirim; Sharma, Rajiv; Manev, Hari; Uz, Tolga

    2008-01-01

    Using transgenic mice model (i.e., “clock” knockouts), clock transcription factors have been suggested as critical regulators of dopaminergic behaviors induced by drugs of abuse. Moreover, it has been shown that systemic administration of psychostimulants, such as cocaine and methamphetamine regulate the striatal expression of clock genes. However, it is not known whether dopamine receptors mediate these regulatory effects of psychostimulants at the cellular level. Primary striatal neurons in...

  7. Human immunodeficiency virus infection of T cells and monocytes proceeds via receptor-mediated endocytosis

    1988-01-01

    The rates of internalization and uncoating of 32P-labelled human immunodeficiency virus (HIV) in the human T lymphoid cell line CEM are consonant with a receptor-mediated endocytosis mechanism of entry. This interpretation was affirmed by electron microscopic observation of virions within endosomes. Virus binding and infectivity were inhibited to the same extent by pretreatment with OKT4A antibody, therefore, the CD4 receptor-dependent pathway of internalization appears to be the infectious r...

  8. Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats

    Fu, Jinjuan; Han, Yu; Wang, Hongyong; Wang, Zhen; Liu, Yukai; Chen, Xingjian; Cai, Yue; Guan, Weiwei; Yang, Di; Asico, Laureano D.; ZHOU, Lin; Jose, Pedro A; Zeng, Chunyu

    2014-01-01

    Background Obesity plays an important role in the pathogenesis of hypertension. Renal dopamine D1-like receptor-mediated diuresis and natriuresis are impaired in the obese Zucker rat, an obesity-related hypertensive rat model. The role of arterial D1 receptors in the hypertension of obese Zucker rats is not clear. Methods Plasma glucose and insulin concentrations and blood pressure were measured. The vasodilatory response of isolated mesenteric arteries was evaluated using a small vessel myog...

  9. [Molecular physiology of receptor mediated endocytosis and its role in overcoming multidrug resistance].

    Severin, E S; Posypanova, G A

    2011-06-01

    Receptor-mediated endocytosis plays important role in the selective uptake of proteins at the plasma membrane of eukaryotic cells. Endocytosis regulates many processes of cell signalling by controlling the number of functional receptors on the cell surface. The article reviews the mechanism of clathrin-dependent endocytosis and the possibility of using this phenomenon for the targeted delivery of drugs. Use of certain proteins as targeting component of drug delivery systems can significantly improve the selectivity of this drug, as well as to overcome the multidrug resistance of cells resulting from the activity of the ABC-transporters. PMID:21874867

  10. Receptor-Mediated Drug Delivery to Macrophages in Chemotherapy of Leishmaniasis

    Mukhopadhyay, Amitabha; Chaudhuri, Gautam; Arora, Sunil K.; Sehgal, Shobha; Basu, Sandip K.

    1989-05-01

    Methotrexate coupled to maleylated bovine serum albumin was taken up efficiently through the ``scavenger'' receptors present on macrophages and led to selective killing of intracellular Leishmania mexicana amazonensis amastigotes in cultured hamster peritoneal macrophages. The drug conjugate was nearly 100 times as effective as free methotrexate in eliminating the intracellular parasites. Furthermore, in a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days. In contrast, the free drug at a similar concentration did not significantly affect lesion size. These studies demonstrate the potential of receptor-mediated drug delivery in the therapy of macrophage-associated diseases.

  11. TRAIL receptor mediates inflammatory cytokine release in an NF-κB-dependent manner

    Wanhu Tang; Weimin Wang; Yaxi Zhang; Shilian Liu; Yanxin Liu; Dexian Zheng

    2009-01-01

    In the present article, we report that DR4 or DR5 overexpression dramatically activates the release of the inflam-matory cytokines IL-8, TNF-α, CCL20, MIP-2 and MIP-1β in an NF-κB-dependent manner in 293T, MDA-MB-231 and HCT-116 cells. We showed that death receptor-mediated signals were extracellular domain-independent, where-as the effect of overexpression of the DR4 intracellular domain was much less potent. The TRADD-TRAF2-NIK-IKKα/β signaling cascade, which plays an essential role in TNF-induced NF-κB activation, was found to be involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-mediated signal transduction. The FADD-caspase signaling pathway, which has been reported to be mostly related to apoptosis, was identified as be-ing essential for DR4 or DR5 overexpression-mediated NF-κB activation and cytokine secretion and crosstalks with the TRADD-TRAF2-NIK-IKKα/β signaling cascade. Furthermore, a DR5 agonistic antibody (AD5-10) triggered the inflammatory cytokine release. These data, together with previous reports, provide strong evidence that TRAIL and TRAIL receptors play an important role in inflammation.

  12. Vascular endothelin ET(B) receptor-mediated contraction requires phosphorylation of ERK1/2 proteins

    Luo, Guogang; Jamali, Roya; Cao, Yong-Xiao;

    2006-01-01

    In cardiovascular diseases, endothelin type B (ET(B)) receptors in arterial smooth muscle cells are upregulated. The present study revealed that organ culture of rat mesenteric artery segments enhanced endothelin ET(B) receptor-mediated contraction paralleled with increase in the receptor mRNA and...... protein expressions. The endothelin ET(B) receptor-mediated contraction was associated with increase in phosphorylation of extracellular regulation kinase 1 and 2 (ERK1/2) proteins and elevated levels of intracellular calcium. The elevation curve of intracellular calcium consisted of two phases: one rapid...... and one sustained. Inhibition of ERK1/2 phosphorylation by SB386023 or blockage of calcium channels by nifedipine significantly reduced the endothelin ET(B) receptor-mediated contraction (P<0.05) and decreased the sustained phase of intracellular calcium level, but not the rapid phase. Thus...

  13. Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison).

    Folland, William R; Newsted, John L; Fitzgerald, Scott D; Fuchsman, Phyllis C; Bradley, Patrick W; Kern, John; Kannan, Kurunthachalam; Zwiernik, Matthew J

    2016-03-01

    Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with

  14. Transferrin protein nanospheres: a nanoplatform for receptor-mediated cancer cell labeling and gene delivery

    McDonald, Michael A.; Spurlin, Tighe A.; Tona, Alessandro; Elliott, John T.; Halter, Michael; Plant, Anne L.

    2010-02-01

    This paper presents preliminary results on the use of transferrin protein nanospheres (TfpNS) for targeting cancer cells in vitro. Protein nanospheres represent an easily prepared and modifiable nanoplatform for receptor-specific targeting, molecular imaging and gene delivery. Rhodamine B isothiocyanate conjugated TfpNS (RBITC-TfpNS) show significantly enhanced uptake in vitro in SK-MEL-28 human malignant melanoma cells known to overexpress transferrin receptors compared to controls. RBITCTfpNS labeling of the cancer cells is due to transferrin receptor-mediated uptake, as demonstrated by competitive inhibition with native transferrin. Initial fluorescence microscopy studies indicate GFP plasmid can be transfected into melanoma cells via GFP plasmid encapsulated by TfpNS.

  15. Potentiation of NMDA receptor-mediated transmission in striatal cholinergic interneurons.

    Oswald, Manfred J; Schulz, Jan M; Kelsch, Wolfgang; Oorschot, Dorothy E; Reynolds, John N J

    2015-01-01

    Pauses in the tonic firing of striatal cholinergic interneurons (CINs) emerge during reward-related learning in response to conditioning of a neutral cue. We have previously reported that augmenting the postsynaptic response to cortical afferents in CINs is coupled to the emergence of a cell-intrinsic afterhyperpolarization (AHP) underlying pauses in tonic activity. Here we investigated in a bihemispheric rat-brain slice preparation the mechanisms of synaptic plasticity of excitatory afferents to CINs and the association with changes in the AHP. We found that high frequency stimulation (HFS) of commissural corticostriatal afferents from the contralateral hemisphere induced a robust long-term depression (LTD) of postsynaptic potentials (PSP) in CINs. Depression of the PSP of smaller magnitude and duration was observed in response to HFS of the ipsilateral white matter or cerebral cortex. In Mg(2+)-free solution HFS induced NMDA receptor-dependent potentiation of the PSP, evident in both the maximal slope and amplitude of the PSP. The increase in maximal slope corroborates previous findings, and was blocked by antagonism of either D1-like dopamine receptors with SCH23390 or D2-like dopamine receptors with sulpiride during HFS in Mg(2+)-free solution. Potentiation of the slower PSP amplitude component was due to augmentation of the NMDA receptor-mediated potential as this was completely reversed on subsequent application of the NMDA receptor antagonist AP5. HFS similarly potentiated NMDA receptor currents isolated by blockade of AMPA/kainate receptors with CNQX. The plasticity-induced increase in the slow PSP component was directly associated with an increase in the subsequent AHP. Thus plasticity of cortical afferent synapses is ideally suited to influence the cue-induced firing dynamics of CINs, particularly through potentiation of NMDA receptor-mediated synaptic transmission. PMID:25914618

  16. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    Junker, L.H.; Davis, R.A. (Univ. of Colorado Health Sciences Center, Denver (USA))

    1989-12-01

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of (14C)cholesterol from (2-14C)acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of (14C)cholesterol from (2-14C)acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis.

  17. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of [14C]cholesterol from [2-14C]acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of [14C]cholesterol from [2-14C]acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis

  18. SYK TYROSINE KINASE INVOLVEMENT IN COMPLEMENT RECEPTOR-MEDIATED SIGNALING LEADING TO AN OXIDATIVE BURST IN CHICKEN HETEROPHILS

    We have previously reported the inhibition of Fc receptor-mediated degranulation in avian heterophils by the syk tyrosine kinase inhibitor piceatannol. The present studies investigated whether attachment of complement opsonized bacteria to complement receptors also involve the syk tyrosine kinase p...

  19. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    Klika, Václav; Baker, R. E.; Headon, D.; Gaffney, E. A.

    2012-01-01

    Roč. 74, č. 4 (2012), s. 935-957. ISSN 0092-8240 Institutional research plan: CEZ:AV0Z20760514 Keywords : reaction-diffusion * receptor-mediated patterning * turing models Subject RIV: BO - Biophysics Impact factor: 2.023, year: 2012 http://www.springerlink.com/content/9713544x6871w4n6/?MUD=MP

  20. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  1. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B2 receptor agonist) and des-Arg9-bradykinin- (selective B1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE2. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg9-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B2 receptors, but not those on B1. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma. - Highlights:

  2. Fluid shear stress sensitizes cancer cells to receptor-mediated apoptosis via trimeric death receptors

    Cancer metastasis, the process of cancer cell migration from a primary to distal location, typically leads to a poor patient prognosis. Hematogenous metastasis is initiated by intravasation of circulating tumor cells (CTCs) into the bloodstream, which are then believed to adhere to the luminal surface of the endothelium and extravasate into distal locations. Apoptotic agents such as tumor necrosis factor apoptosis-inducing ligand (TRAIL), whether in soluble ligand form or expressed on the surface of natural killer cells, have shown promise in treating CTCs to reduce the probability of metastasis. The role of hemodynamic shear forces in altering the cancer cell response to apoptotic agents has not been previously investigated. Here, we report that human colon cancer COLO 205 and prostate cancer PC-3 cells exposed to a uniform fluid shear stress in a cone-and-plate viscometer become sensitized to TRAIL-induced apoptosis. Shear-induced sensitization directly correlates with the application of fluid shear stress, and TRAIL-induced apoptosis increases in a fluid shear stress force- and time-dependent manner. In contrast, TRAIL-induced necrosis is not affected by the application fluid shear stress. Interestingly, fluid shear stress does not sensitize cancer cells to apoptosis when treated with doxorubicin, which also induces apoptosis in cancer cells. Caspase inhibition experiments reveal that shear stress-induced sensitization to TRAIL occurs via caspase-dependent apoptosis. These results suggest that physiological fluid shear forces can modulate receptor-mediated apoptosis of cancer cells in the presence of apoptotic agents. (paper)

  3. Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery

    Majumdar, S.; Basu, S.K. (Institute of Microbial Technology, Chandigarh (India))

    1991-01-01

    p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections.

  4. Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila.

    Liu, Bo; Zheng, Yonggang; Yin, Feng; Yu, Jianzhong; Silverman, Neal; Pan, Duojia

    2016-01-28

    The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innate immunity whereby Yorkie directly regulates the transcription of the Drosophila IκB homolog, Cactus, in Toll receptor-mediated antimicrobial response. Loss of Hippo pathway tumor suppressors or activation of Yorkie in fat bodies, the Drosophila immune organ, leads to elevated cactus mRNA levels, decreased expression of antimicrobial peptides, and vulnerability to infection by Gram-positive bacteria. Furthermore, Gram-positive bacteria acutely activate Hippo-Yorkie signaling in fat bodies via the Toll-Myd88-Pelle cascade through Pelle-mediated phosphorylation and degradation of the Cka subunit of the Hippo-inhibitory STRIPAK PP2A complex. Our studies elucidate a Toll-mediated Hippo signaling pathway in antimicrobial response, highlight the importance of regulating IκB/Cactus transcription in innate immunity, and identify Gram-positive bacteria as extracellular stimuli of Hippo signaling under physiological settings. PMID:26824654

  5. Receptor-mediated effects of a PGH2 analogue (U 46619) on human platelets

    The specific effects of U 46619 (9,11-dideoxy,9α-11α-methanoepoxy-prostaglandin F2α), thromboxane A2-prostaglandin H2 (TxA2/PGH2) analogue, on human platelet shape change, myosin light-chain phosphorylation, serotonin release, fibrinogen receptor exposure, and platelet aggregation were measured and compared with binding of [3H]U 46619 to platelets. Shape change and myosin light-chain phosphorylation were found to be saturable and dose dependent. These two effects were competitively inhibited by specific antagonists of TxA2/PGH2 receptors indicating that they are receptor mediated. Binding of [3H]U 46619 showed two components. The authors proposed that a second component represents a second, low-affinity site. Mean EC50 values for U 46619-induced serotonin release platelet aggregation, and fibrinogen receptor exposure were 0.54 ± 0.13, 1.31 ± 0.34, and 0.53 ± 0.21 μM, respectively. Therefore, the platelet release reaction was not directly correlated with occupancy of high-affinity receptors but could be related to the second binding component of U 46619. Fibrinogen receptor exposure and platelet aggregation caused by U 46619 appeared to be events mediated by the release of adenosine diphosphate from platelet-dense granules

  6. The effect of vanadate on receptor-mediated endocytosis of asialoorosomucoid in rat liver parenchymal cells

    Vanadate is a phosphate analogue that inhibits enzymes involved in phosphate release and transfer reactions. Since such reactions may play important roles in endocytosis, we studied the effects of vanadate on various steps in receptor-mediated endocytosis of asialoorosomucoid labeled with 125I-tyramine-cellobiose (125I-TC-AOM). The labeled degradation products formed from 125I-TC-AOM are trapped in the lysosomes and may therefore serve as lysosomal markers in subcellular fractionation studies. Vanadate reduced the amount of active surface asialoglycoprotein receptors approximately 70%, but had no effect on the rate of internalization and retroendocytosis of ligand. The amount of surface asialoglycoprotein receptors can be reduced by lowering the incubation temperature gradually from 37 to 15 degrees C; vanadate affected only the temperature--sensitive receptors. Vanadate inhibited degradation of 125I-TC-AOM 70-80%. Degradation was much more sensitive to vanadate than binding; half-maximal effects were seen at approximately 1 mM vanadate for binding and approximately 0.1 mM vanadate for degradation. By subcellular fractionation in sucrose and Nycodenz gradients, it was shown that vanadate completely prevented the transfer of 125I-TC-AOM from endosomes to lysosomes. Therefore, the inhibition of degradation by vanadate was indirect; in the presence of vanadate, ligand did not gain access to the lysosomes. The limited degradation in the presence of vanadate took place in a prelysosomal compartment. Vanadate did not affect cell viability and ATP content

  7. Sucrose-induced analgesia in mice: Role of nitric oxide and opioid receptor-mediated system

    Abtin Shahlaee

    2013-01-01

    Full Text Available Background: The mechanism of action of sweet substance-induced analgesia is thought to involve activation of the endogenous opioid system. The nitric oxide (NO pathway has a pivotal role in pain modulation of analgesic compounds such as opioids. Objectives: We investigated the role of NO and the opioid receptor-mediated system in the analgesic effect of sucrose ingestion in mice. Materials and Methods: We evaluated the effect of intraperitoneal administration of 10 mg/kg of NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME and 20 mg/kg of opioid receptor antagonist, naltrexone on the tail flick response in sucrose ingesting mice. Results: Sucrose ingestion for 12 days induced a statistically significant increase in the latency of tail flick response which was unmodified by L-NAME, but partially inhibited by naltrexone administration. Conclusions: Sucrose-induced nociception may be explained by facilitating the release of endogenous opioid peptides. Contrary to some previously studied pain models, the NO/cyclic guanosine monophosphate (cGMP pathway had no role in thermal hyperalgesia in our study. We recommend further studies on the involvement of NO in other animals and pain models.

  8. Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria

    E.V. Seliverstova

    2015-04-01

    Full Text Available The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes, and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals.

  9. Progesterone stimulates respiration through a central nervous system steroid receptor-mediated mechanism in cat.

    Bayliss, D A; Millhorn, D E; Gallman, E A; Cidlowski, J A

    1987-11-01

    We have examined the effect on respiration of the steroid hormone progesterone, administered either intravenously or directly into the medulla oblongata in anesthetized and paralyzed male and female cats. The carotid sinus and vagus nerves were cut, and end-tidal PCO2 and temperature were kept constant with servo-controllers. Phrenic nerve activity was used to quantitate central respiratory activity. Repeated doses of progesterone (from 0.1 to 2.0 micrograms/kg, cumulative) caused a sustained (greater than 45 min) facilitation of phrenic nerve activity in female and male cats; however, the response was much more variable in females. Progesterone injected into the region of nucleus tractus solitarii, a respiratory-related area in the medulla oblongata, also caused a prolonged stimulation of respiration. Progesterone administration at high concentration by both routes also caused a substantial hypotension. Identical i.v. doses of other classes of steroid hormones (17 beta-estradiol, testosterone, and cortisol) did not elicit the same respiratory effect. Pretreatment with RU 486, a progesterone-receptor antagonist, blocked the facilitatory effect of progesterone. We conclude that progesterone acts centrally through a steroid receptor-mediated mechanism to facilitate respiration. PMID:3478727

  10. Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery

    p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections

  11. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    Sun, Hongfan

    2010-01-01

    Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH) receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposome...

  12. Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn of the rat spinal cord.

    Baba, H; Doubell, T P; Moore, K A; Woolf, C J

    2000-02-01

    In vitro whole cell patch-clamp recording techniques were utilized to study silent pure-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses in lamina II (substantia gelatinosa, SG) and lamina III of the spinal dorsal horn. To clarify whether these synapses are present in the adult and contribute to neuropathic pain, transverse lumbar spinal cord slices were prepared from neonatal, naive adult and adult sciatic nerve transected rats. In neonatal rats, pure-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were elicited in SG neurons either by focal intraspinal stimulation (n = 15 of 20 neurons) or focal stimulation of the dorsal root (n = 2 of 7 neurons). In contrast, in slices from naive adult rats, no silent pure-NMDA EPSCs were recorded in SG neurons following focal intraspinal stimulation (n = 27), and only one pure-NMDA EPSC was observed in lamina III (n = 23). Furthermore, in rats with chronic sciatic nerve transection, pure-NMDA EPSCs were elicited by focal intraspinal stimulation in only 2 of 45 SG neurons. Although a large increase in Abeta fiber evoked mixed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptor-mediated synapses was detected after sciatic nerve injury, Abeta fiber-mediated pure-NMDA EPSCs were not evoked in SG neurons by dorsal root stimulation. Pure-NMDA receptor-mediated EPSCs are therefore a transient, developmentally regulated phenomenon, and, although they may have a role in synaptic refinement in the immature dorsal horn, they are unlikely to be involved in receptive field plasticity in the adult. PMID:10669507

  13. Fc receptor-mediated, antibody-dependent enhancement of bacteriophage lambda-mediated gene transfer in mammalian cells

    Sapinoro, Ramil; Volcy, Ketna; Shanaka, W.W.; Rodrigo, I.; Schlesinger, Jacob J.; Dewhurst, Stephen

    2008-01-01

    Lambda phage vectors mediate gene transfer in cultured mammalian cells and in live mice, and in vivo phage-mediated gene expression is increased when mice are pre-immunized with bacteriophage lambda. We now show that, like eukaryotic viruses, bacteriophage vectors are subject to Fc receptor-mediated, antibody-dependent enhancement of infection in mammalian cells. Antibody-dependent enhancement of phage gene transfer required FcγRI, but not its associated γ chain, and was not supported by othe...

  14. The Orphan Nuclear Receptor ERRγ Regulates Hepatic CB1 Receptor-Mediated Fibroblast Growth Factor 21 Gene Expression

    Jung, Yoon Seok; Lee, Ji-Min; Kim, Don-Kyu; Lee, Yong-Soo; Kim, Ki-Sun; Kim, Yong-Hoon; Kim, Jina; Lee, Myung-Shik; Lee, In-Kyu; Kim, Seong Heon; Cho, Sung Jin; Jeong, Won-Il; Lee, Chul-Ho; Harris, Robert A.; Choi, Hueng-Sik

    2016-01-01

    Background Fibroblast growth factor 21 (FGF21), a stress inducible hepatokine, is synthesized in the liver and plays important roles in glucose and lipid metabolism. However, the mechanism of hepatic cannabinoid type 1 (CB1) receptor-mediated induction of FGF21 gene expression is largely unknown. Results Activation of the hepatic CB1 receptor by arachidonyl-2’-chloroethylamide (ACEA), a CB1 receptor selective agonist, significantly increased FGF21 gene expression. Overexpression of estrogen-related receptor (ERR) γ increased FGF21 gene expression and secretion both in hepatocytes and mice, whereas knockdown of ERRγ decreased ACEA-mediated FGF21 gene expression and secretion. Moreover, ERRγ, but not ERRα and ERRβ, induced FGF21 gene promoter activity. In addition, deletion and mutation analysis of the FGF21 promoter identified a putative ERRγ-binding motif (AGGTGC, a near-consensus response element). A chromatin immunoprecipitation assay revealed direct binding of ERRγ to the FGF21 gene promoter. Finally, GSK5182, an ERRγ inverse agonist, significantly inhibited hepatic CB1 receptor-mediated FGF21 gene expression and secretion. Conclusion Based on our data, we conclude that ERRγ plays a key role in hepatic CB1 receptor-mediated induction of FGF21 gene expression and secretion. PMID:27455076

  15. Feed up, Feedback, and Feed Forward

    Fisher, Douglas; Frey, Nancy

    2011-01-01

    "Feeding up" establishes a substantive line of inquiry that compels learners to engage in investigation and inquire. It also forms the basis for the assessments that follow. Once students understand the purpose and begin to work, they receive "feedback" that is timely and scaffolds their understanding. Based on their responses, the teacher gains a…

  16. Modification of ionotropic glutamate receptor-mediated processes in the rat hippocampus following repeated, brief seizures.

    Borbély, S; Dobó, E; Czégé, D; Molnár, E; Bakos, M; Szucs, B; Vincze, A; Világi, I; Mihály, A

    2009-03-01

    The seizure-induced molecular and functional alterations of glutamatergic transmission in the hippocampus have been investigated. Daily repeated epileptic seizures were induced for 12 days by intraperitoneal administration of 4-aminopyridine (4-AP; 4.5 mg/kg) in adult Wistar rats. The seizure symptoms were evaluated on the Racine's scale. One day after the last injection, the brains were removed for in vitro electrophysiological experiments and immunohistochemical analysis. The glutamate receptor subunits NR1, NR2A, NR2B, GluR1, GluR1(flop), GluR2, and KA-2 were studied using the histoblotting method. The semi-quantitative analysis of subunit immunoreactivities in hippocampal layers was performed with densitometry. In the hippocampus, increase of GluR1, GluR1(flop) and NR2B immunostaining was observed in most of the areas and layers. The significant decrease of GluR2 staining intensity was observed in the CA1 and dentate gyrus. Calcium permeability of hippocampal neurons was tested by a cobalt uptake assay in hippocampal slices. The uptake of cobalt increased in the CA1 area and dentate gyrus, but not in the CA3 region following 4-AP treatment. Effects of AMPA and NMDA (N-methyl-d-aspartate) glutamate receptor antagonists (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) and D-APV respectively) were measured in hippocampal slices using extracellular recording. Analysis of the population spikes revealed the reduced effectiveness of the AMPA receptor antagonist GYKI 52466, while the effect of the NMDA receptor antagonist d-(2R)-amino-5-phosphonovaleric acid was similar to controls. The results demonstrated that repeated convulsions induced structural and functional changes in AMPA receptor-mediated transmission, while NMDA and kainate receptor systems displayed only alterations in receptor subunit composition. PMID:19154779

  17. High dose of spinal morphine produce a nonopiate receptor-mediated hyperesthesia: clinical and theoretic implications.

    Yaksh, T L; Harty, G J; Onofrio, B M

    1986-05-01

    In rats with chronically implanted intrathecal catheters, high concentrations of morphine (3 microliters of 50 mg/ml: 150 micrograms) yielded a reliable and striking syndrome of pain behavior that involved intermittent bouts of biting and scratching at the dermatomes innervated by levels of the spinal cord proximal to the catheter tip. In addition, during intervals between bouts of agitation, the animals displayed a clear, marked hyperesthesia where an otherwise innocuous stimuli (brush stroke) evoked significant signs of discomfort and consequent aggressive behavior. These effects were exaggerated rather than reversed by high doses of naltrexone. The effect, perfectly mimicked by a considerably lower dose of morphine-3-glucuronide (15 micrograms) or the glycine antagonist strychnine (30 micrograms), was not produced by equimolar concentrations of sodium sulfate, glucuronide, methadone, or sufentanil. In halothane-anesthetized cats, light brushing of the hindpaw and tail or low-intensity stimulation of the sciatic nerves resulted in prominent elevations in blood pressure and pupil diameter following the intrathecal administration of high concentrations (50 mg/ml; 0.1 ml) of morphine sulfate. This effect, exaggerated by naloxone, was produced by a lower concentration of intrathecal morphine-3-glucuronide (5 mg/ml; 0.1 ml) but not by intrathecal saline. These results suggest the possibility that the effects of high doses of morphine may be characterized by a nonopiate receptor-mediated effect that alters the coding of sensory information in the spinal cord. The authors speculate that high concentrations of spinal opiates, as may be employed in tolerant terminal-cancer patients, could exert an action that physiologically antagonizes the analgesic effects otherwise mediated by the action of morphine on the spinal opiate receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2938524

  18. Receptor-mediated endocytosis of low density lipoproteins in aortic endothelial cells

    Lipoprotein binding and metabolism in actively-dividing (subconfluent) and quiescent (postconfluent) bovine aortic endothelial cells (ECs) were qualitatively investigated by fluorescence microscopy using dioctadecylindocarbocyanine-labelled lipoproteins and by indirect immunofluorescence microscopy. LDL and acetylated-LDL (AcLDL) were seen bound to the surfaces of subconfluent ECs (at 4 degrees C or at 37 degrees C), as a random distribution of punctate foci. ECs therefore closely resembled fibroblasts in the distribution of LDL receptors on their surfaces. No binding of LDL was seen on postconfluent EC surfaces by either direct or indirect fluorescence microscopy. The patterns of AcLDL binding on postconfluent ECs resembled those on subconfluent ECs. Intracellular LDL and AcLDL occurred as perinuclear accumulations of large fluorescent disc-shaped profiles in subconfluent ECs. These accumulations were shown to arise from surface-bound material by pulse-chase experiments. Intracellular LDL was absent in the majority of postconfluent ECs, while AcLDL accumulation was massive. 'Wounding' of cultures allowed simultaneous assessment of lipoprotein metabolism in quiescent and actively-dividing areas of the same culture. It is concluded that postconfluent quiescent bovine aortic ECs in vitro metabolise virtually no LDL via the LDL-receptor pathway due to a vanishingly low number of LDL receptors. This contrasts with the ability of postconfluent cells to metabolise relatively large amounts of AcLDL via a receptor-mediated mechanism. The significance of these conclusions is discussed with respect to the interaction of plasma lipoproteins with the endothelium in vivo. 301 refs

  19. P2X receptor-mediated ATP purinergic signaling in health and disease

    Jiang LH

    2012-09-01

    Full Text Available Lin-Hua JiangSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAbstract: Purinergic P2X receptors are plasma membrane proteins present in a wide range of mammalian cells where they act as a cellular sensor, enabling cells to detect and respond to extracellular adenosine triphosphate (ATP, an important signaling molecule. P2X receptors function as ligand-gated Ca2+-permeable cationic channels that open upon ATP binding to elevate intracellular Ca2+ concentrations and cause membrane depolarization. In response to sustained activation, P2X receptors induce formation of a pore permeable to large molecules. P2X receptors also interact with distinct functional proteins and membrane lipids to form specialized signaling complexes. Studies have provided compelling evidence to show that such P2X receptor-mediated ATP-signaling mechanisms determine and regulate a growing number and diversity of important physiological processes, including neurotransmission, muscle contraction, and cytokine release. There is accumulating evidence to support strong causative relationships of altered receptor expression and function with chronic pain, inflammatory diseases, cancers, and other pathologies or diseases. Numerous high throughput screening drug discovery programs and preclinical studies have thus far demonstrated the proof of concepts that the P2X receptors are druggable targets and selective receptor antagonism is a promising therapeutics approach. This review will discuss the recent progress in understanding the mammalian P2X receptors with respect to the ATP-signaling mechanisms, physiological and pathophysiological roles, and development and preclinical studies of receptor antagonists.Keywords: extracellular ATP, ion channel, large pore, signaling complex, chronic pain, inflammatory diseases

  20. Triple Feed-forward APIOBPCS Based Resilience and Operational Costs Assessment of Supply Chain%基于三前馈APIOBPCS的供应链弹性与运作成本评估

    许波桅; 杨勇生; 杨斌; 李军军

    2015-01-01

    为兼顾供应链系统的弹性和运作成本,提出三前馈自动渠道的、基于库存和定购的生产控制系统(Triple feed-forward automatic pipeline, inventory and order-based production control system, TFF-APIOBPCS)。在自动渠道的、基于库存和定购的生产控制系统模型中,增加一阶微分前馈环节,以部分抵消需求波动对库存的影响。在零稳态误差情况下针对生产控制系统的不同极点分布,分析一阶微分前馈环节的参数与供应链弹性的关系。综合考虑库存成本及生产调节成本,构造供应链系统的运作成本模型。通过阶跃需求、随机需求下的供应链系统仿真,评估一阶前馈环节参数对供应链弹性及运作成本的影响,验证三前馈自动渠道的、基于库存和定购的生产控制系统的有效性。结果表明,针对不同波动程度的需求,合理设置一阶微分前馈环节的参数,可以获得弹性与运作成本的良好均衡。%In order to trade off between supply chain resilience and operational cost, a sort of triple feed-forward automatic pipeline, inventory and order-based production control system(TFF-APIOBPCS) is presented. A first order differential feedforward unit, introduced to production control model APIOBPCS, enables the model to mitigate the impact of fluctuations in demand on actual inventory. Aiming at different pole distribution of the production control system, analysis of the relationship between the parameters of first order differential feedforward and resilience are conducted under zero steady-state error. Supply chain operational cost model is constructed by comprehensive consideration of inventory cost and production regulation cost. Supply chain system simulations with a unit step signal and a stochastic signal as the customer demand evaluate the effect of the first order differential feedforward parameters on supply chain resilience and operational cost, and reveal the

  1. A Feed-Forward Loop Consisting of the Response Regulator RpaB and the Small RNA PsrR1 Controls Light Acclimation of Photosystem I Gene Expression in the Cyanobacterium Synechocystis sp. PCC 6803.

    Kadowaki, Taro; Nagayama, Ryuta; Georg, Jens; Nishiyama, Yoshitaka; Wilde, Annegret; Hess, Wolfgang R; Hihara, Yukako

    2016-04-01

    Since cyanobacteria need to decrease PSI content to avoid absorption of excess light energy, down-regulation of PSI gene expression is one of the key characteristics of the high-light (HL) acclimation response. The transcriptional regulator RpaB and the small RNA PsrR1 (photosynthesis regulatory RNA1) have been suggested to be the two most critical factors for this response inSynechocystissp. PCC 6803. In this study, we found that the HLR1 DNA-binding motif, the recognition sequence for RpaB, is highly conserved in the core promoter region of thepsrR1gene among cyanobacterial species. Gel mobility shift assay revealed that RpaB binds to the HLR1 sequence ofpsrR1in vitro. RNA gel blot analysis together with chromatin affinity purification (ChAP) analysis suggested that PSI genes are activated and thepsrR1gene is repressed by the binding of RpaB under low-light (LL) conditions. A decrease in DNA binding affinity of RpaB occurs within 5 min after the shift from LL to HL conditions, leading to the prompt decrease in PSI promoter activity together with derepression ofpsrR1gene expression. Accumulating PsrR1 molecules then prevent translation from pre-existing PSI transcripts. By this dual repression at transcriptional and post-transcriptional levels, rapid and strict down-regulation of PSI expression under HL is secured. Our findings suggest that RpaB and PsrR1 constitute a feed-forward loop for the regulation of PSI gene expression to achieve a rapid acclimation response to the damaging HL conditions. PMID:26872833

  2. GABAA and GABAB receptor-mediated effects in guinea-pig ileum.

    Giotti, A; Luzzi, S; Spagnesi, S; Zilletti, L

    1983-03-01

    1 The effects of gamma-aminobutyric acid (GABA) and related substances were examined in guinea-pig ileum longitudinal muscle.2 GABA at doses ranging from 10(-7) M to 3 x 10(-6) M elicited a relaxation while at higher doses (3 x 10(-6) M - 10(-4) M), as previously described, it caused a contraction followed by relaxation.3 GABA-induced relaxation was bicuculline-insensitive, was mimicked by (-)-baclofen but not by homotaurine and muscimol. The effect of baclofen was stereospecific. GABA- and (-)-baclofen-induced relaxations were dose-dependent and their ED(50) values were similar. A specific cross-desensitization occurred between GABA and (-)-baclofen.4 The bicuculline-insensitive relaxation induced by GABA and (-)-baclofen was prevented by tetrodotoxin and hyoscine but not by phentolamine plus propranolol, naloxone or theophylline.5 In preparations in which the muscle tone was raised by histamine or prostaglandin F(2alpha), GABA and (-)-baclofen induced relaxation to the same extent as before increasing the tone. If the tone was raised by DMPP, a greater bicuculline-insensitive relaxation occurred.6 Contraction caused by GABA was bicuculline-sensitive and was mimicked by homotaurine and muscimol. Contraction was dose-dependent and muscimol was about three times more potent than GABA or homotaurine. A specific cross-desensitization occurred between the contractile effects of GABA and those of homotaurine or muscimol.7 Bicuculline competitively antagonized the contractile effects of GABA, homotaurine and muscimol and gave closely similar pA(2) values. The slope of the Schild plot for the above drugs was near 1, confirming the competitive nature of the antagonism.8 The bicuculline-sensitive contraction induced by GABA, homotaurine and muscimol was abolished by tetrodotoxin and was non-competitively antagonized by hyoscine, while it was unaffected by hexamethonium, mepyramine and methysergide.9 It is concluded that two receptors mediate the GABA effects in guinea

  3. Pharmacological and biochemical characterization of the D-1 dopamine receptor mediating acetylcholine release in rabbit retina

    Hensler, J.G.; Cotterell, D.J.; Dubocovich, M.L.

    1987-12-01

    Superfusion with dopamine (0.1 microM-10 mM) evokes calcium-dependent (/sup 3/H)acetylcholine release from rabbit retina labeled in vitro with (/sup 3/H)choline. This effect is antagonized by the D-1 dopamine receptor antagonist SCH 23390. Activation or blockade of D-2 dopamine, alpha-2 or beta receptors did not stimulate or attenuate the release of (/sup 3/H)acetylcholine from rabbit retina. Dopamine receptor agonists evoke the release of (/sup 3/H)acetylcholine with the following order of potency: apomorphine less than or equal to SKF(R)82526 < SKF 85174 < SKF(R)38393 less than or equal to pergolide less than or equal to dopamine (EC50 = 4.5 microM) < SKF(S)82526 less than or equal to SKF(S)38393. Dopamine receptor antagonists inhibited the dopamine-evoked release of (/sup 3/H)acetylcholine: SCH 23390 (IC50 = 1 nM) < (+)-butaclamol less than or equal to cis-flupenthixol < fluphenazine < perphenazine < trans-flupenthixol < R-sulpiride. The potencies of dopamine receptor agonists and antagonists at the dopamine receptor mediating (/sup 3/H)acetylcholine release is characteristic of the D-1 dopamine receptor. These potencies were correlated with the potencies of dopamine receptor agonists and antagonists at the D-1 dopamine receptor in rabbit retina as labeled by (/sup 3/H)SCH 23390, or as determined by adenylate cyclase activity. (/sup 3/H)SCH 23390 binding in rabbit retinal membranes was stable, saturable and reversible. Scatchard analysis of (/sup 3/H)SCH 23390 saturation data revealed a single high affinity binding site (Kd = 0.175 +/- 0.002 nM) with a maximum binding of 482 +/- 12 fmol/mg of protein. The potencies of dopamine receptor agonists to stimulate (/sup 3/H)acetylcholine release were correlated with their potencies to stimulate adenylate cyclase (r = 0.784, P less than .05, n = 7) and with their affinities at (/sup 3/H)SCH 23390 binding sites (r = 0.755, P < .05, n = 8).

  4. Astrocytes protect neurons against methylmercury via ATP/P2Y(1 receptor-mediated pathways in astrocytes.

    Yusuke Noguchi

    Full Text Available Methylmercury (MeHg is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we report that MeHg triggers ATP/P2Y1 receptor signals in astrocytes, thereby protecting neurons against MeHg via interleukin-6 (IL-6-mediated pathways. MeHg increased several mRNAs in astrocytes, among which IL-6 was the highest. For this, ATP/P2Y1 receptor-mediated mechanisms were required because the IL-6 production was (i inhibited by a P2Y1 receptor antagonist, MRS2179, (ii abolished in astrocytes obtained from P2Y1 receptor-knockout mice, and (iii mimicked by exogenously applied ATP. In addition, (iv MeHg released ATP by exocytosis from astrocytes. As for the intracellular mechanisms responsible for IL-6 production, p38 MAP kinase was involved. MeHg-treated astrocyte-conditioned medium (ACM showed neuro-protective effects against MeHg, which was blocked by anti-IL-6 antibody and was mimicked by the application of recombinant IL-6. As for the mechanism of neuro-protection by IL-6, an adenosine A1 receptor-mediated pathway in neurons seems to be involved. Taken together, when astrocytes sense MeHg, they release ATP that autostimulates P2Y1 receptors to upregulate IL-6, thereby leading to A1 receptor-mediated neuro-protection against MeHg.

  5. alpha 2-macroglobulin adsorbed to colloidal gold: a new probe in the study of receptor-mediated endocytosis

    1981-01-01

    alpha 2-Macroglobulin (alpha 2 M) was adsorbed to colloidal gold and used as a new tool in the study of receptor-mediated endocytosis. alpha 2 M-gold is easy to prepare and is clearly visualized at the electron microscope level. When cells were incubated with alpha 2 M-gold at 0 degrees C, gold was visualized both diffusely over the cell surface and concentrated in coated pits. After cells to which alpha 2 M-gold had been bound at 0 degrees C were warmed, the gold was rapidly internalized int...

  6. Multivariable System with Multi-Delays Decoupling based-on Feed-forward Compensation and IMC-PID Control%多变量多时滞系统的前馈补偿解耦及IMC-PID控制

    李兴春; 刘智勇; 李兴高

    2012-01-01

    多变量系统控制器设计中遇到的主要难题是多时滞和强铰链耦合问题;对于非奇异方阵系统,根据解耦理论通过串级前馈时滞补偿器将原系统解耦为多个单变量小时滞系统,运用模型降阶技术,将解耦后的复杂单变量小时滞系统逼近为FOPDT(一阶环节十延时)形式,采用IMC控制策略实现多个单变量系统单位反馈控制,运用了麦克劳林级数展开式,通过相应项系数的比对得到了传统PID控制器;仿真分析表明了该方法能够有效性地补偿系统时滞,同时现实解耦;解决了多变量多时滞系统控制器设计复杂性的难题,有一定的工程参考价值.%The main problems encountered in multivariable system controllers design is multiple delays and strong coupling. For a nonsin-gular square system, the original system will be decoupled to many single variable system with little delays through cascade feed forward delay compensators according to the decoupling theory. The complex decoupling single variable system will be approximated to FOPDT form by the model reduction technique. Multiple single variable system with unit feedback control will be realized by adopting IMC control strategy. The traditional PTD controller comes into being by Maclaurin series expansion. The simulation analysis shows that the effectiveness of the proposed method. The system time delay is compensated and decoupling is realized. The complexity of controller design of multivariable system with multi - delay has been solved. This technique has certain reference to engineering design.

  7. EGF-Receptor-Mediated Mammary Epithelial Cell Migration is Driven by Sustained ERK Signaling from Autocrine Stimulation

    Joslin, Elizabeth J.; Opresko, Lee; Wells, Alan; Wiley, H. S.; Lauffenburger, Douglas A.

    2007-10-15

    Aberrant expression of epidermal growth factor (EGF) receptor family ligands, as well as the receptors themselves, has been implicated in various types of cancers. EGF family ligands are synthesized as membrane-anchored proteins requiring proteolytic release to form the mature soluble factor. Despite the pathophysiological importance of autocrine systems, how the rate of protease-mediated ligand release quantitatively influences receptor-mediated signaling and consequent cell behavior is poorly understood. Therefore, we explored the relationship between autocrine EGF release rates and receptor-mediated ERK activation and migration in human mammary epithelial cells. A quantitative spectrum of EGF release rates was achieved using a set of chimeric transmembrane EGF ligand precursors modulated by the addition of the metalloprotease inhibitor batimastat. We found that ERK activation increased with increasing ligand release rates despite concomitant EGF receptor downregulation. Cell migration speed depended linearly on the steady-state phospho-ERK level obtained from either autocrine or exogenous ligand, but was much greater at any given phospho-ERK level for autocrine compared to exogenous stimulation. In contrast, cell proliferation rates were relatively constant across the various treatment conditions. Thus, in these cells, ERK-mediated migration stimulated by EGF receptor signaling is most sensitively regulated by autocrine ligand control mechanisms.

  8. Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

    Datz, Stefan; Gattner, Michael; Weiss, Veronika; Brunner, Korbinian; Bretzler, Johanna; von Schirnding, Constantin; Spada, Fabio; Engelke, Hanna; Vrabel, Milan; Bräuchle, Christoph; Carell, Thomas; Bein, Thomas

    2015-01-01

    Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the development of precisely controllable and highly modular theranos...

  9. The influence of receptor-mediated interactions on reaction-diffusion mechanisms of cellular self-organisation.

    Klika, Václav; Baker, Ruth E; Headon, Denis; Gaffney, Eamonn A

    2012-04-01

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. PMID:22072186

  10. Multi-functionalized hyaluronic acid nanogels crosslinked with carbon dots as dual receptor-mediated targeting tumor theranostics.

    Jia, Xu; Han, Yu; Pei, Mingliang; Zhao, Xubo; Tian, Kun; Zhou, Tingting; Liu, Peng

    2016-11-01

    Hyaluronic acid (HA)-based theranostic nanogels were designed for the tumor diagnosis and chemotherapy, by crosslinking the folate-terminated poly(ethylene glycol) modified hyaluronic acid (FA-PEG-HA) with carbon dots (CDs) for the first time. Due to the extraordinary fluorescence property of the integrated CDs, the theranostic nanogels could be used for the real-time and noninvasive location tracking to cancer cells. HA could load Doxorubicin (DOX) via electrostatic interaction with a drug-loading capacity (DLC) of 32.5%. The nanogels possessed an ideal release of DOX in the weak acid environment, while it was restrained in the neutral media, demonstrating the pH-responsive controlled release behavior. The cytotoxicity and cellular uptake results clearly illustrated that most DOX was released and accumulated in the cell nuclei and killed the cancer cells efficaciously, due to their dual receptor-mediated targeting characteristics. PMID:27516286

  11. Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

    Huang Li-Yen

    2007-08-01

    Full Text Available Abstract Prostaglandin E2 (PGE2 is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

  12. Phenobarbital but not diazepam reduces AMPA/Kainate receptor mediated currents and exerts opposite actions on initial seizures in the neonatal rat hippocampus

    Romain Nardou

    2011-07-01

    Full Text Available Diazepam (DZP and phenobarbital (PB are extensively used as first and second line drugs to treat acute seizures in neonates and their actions are thought to be mediated by increasing the actions of GABAergic signals. Yet, their efficacy is variable with occasional failure or even aggravation of recurrent seizures questioning whether other mechanisms are not involved in their actions. We have now compared the effects of DZP and PB on ictal-like events (ILEs in an in vitro model of mirror focus (MF. Using the three-compartment chamber with the two immature hippocampi and their commissural fibers placed in 3 different compartments, kainate was applied to one hippocampus and PB or DZP to the contralateral one, either after one ILE or after many recurrent ILEs that produce an epileptogenic MF. We report that in contrast to PB, DZP aggravated propagating ILEs from the start and did not prevent the formation of MF. PB reduced and DZP increased the network driven Giant Depolarising Potentials suggesting that PB may exert additional actions that are not mediated by GABA signalling. In keeping with this, PB but not DZP reduced field potentials recorded in the presence of GABA and NMDA receptor antagonists. These effects are mediated by a direct action on AMPA/Kainate receptors since PB: i reduced AMPA/Kainate receptor mediated currents induced by focal applications of glutamate ; ii reduced the amplitude and the frequency of AMPA but not NMDA receptor mediated miniature EPSCs; iii augmented the number of AMPA receptor mediated EPSCs failures evoked by minimal stimulation. These effects persisted in MF. Therefore, PB exerts its anticonvulsive actions partly by reducing AMPA/Kainate receptors mediated EPSCs in addition to the pro-GABA effects. We suggest that PB may have advantage over DZP in the treatment of initial neonatal seizures since the additional reduction of glutamate receptors mediated signals may reduce the severity of neonatal seizures.

  13. The Hypolipidemic Agent Guggulsterone Regulates the Expression of Human Bile Salt Export Pump: Dominance of Transactivation over Farsenoid X Receptor-Mediated Antagonism

    Deng, Ruitang; Yang, Dongfang; Radke, Amy; Yang, Jian; Yan, Bingfang

    2006-01-01

    Conversion of cholesterol to bile acids in the liver is initiated by the rate-limiting enzyme cholesterol 7α-hydroxylase (CYP7A1) and excretion of bile acids from the liver is mediated by the bile salt export pump (BSEP). The expression of CYP7A1 and BSEP is coordinately regulated by a negative feedback and positive feed-forward mechanism, respectively, through bile acid-mediated activation of farsenoid X receptor (FXR). It is well established that hypolipidemic agent guggulsterone is an FXR ...

  14. 文化前馈指导下动作技能学习的领会教学法--以投掷铅球动作技能学习为例%The method of comprehension teaching guided by cultural feed forward in movement skill learning--Taking shot put movement skill learning for example

    和立新; 朱立新

    2014-01-01

    Based on the three-layer cultural structure theory, the authors expatiated on the cultural attribute of movement skills, and analyzed the sign of missing of some cultural constituent elements in the process of teaching and learning, ex-plained the function of feed forward control according to the characteristics of movement skills showed at various stages, put forward the principles to be followed in using cultural form as feed forward information for movement skill learning:learning migration theory and knowledge structure integrity, analyzed the characteristics of implementation of the method of comprehension teaching, and explained it by taking shot put movement skill learning for example.%依文化三层次结构论,阐述了动作技能的文化属性,并解析了传习过程中部分文化构成要素的遗失现象;结合动作技能形成的特点,对前馈控制作用进行说明,提出以文化形态作为动作技能学习前馈信息遵循的原理:学习迁移理论、知识结构的完整性;分析领会教学法的实施特点,并以推铅球动作技能学习为例说明。

  15. Glycine and GABAA receptors mediate tonic and phasic inhibitory processes that contribute to prepulse inhibition in the goldfish startle network

    Paul C.P. Curtin

    2015-03-01

    Full Text Available Prepulse inhibition (PPI is understood as an inhibitory process that attenuates sensory flow during early stages (20-1000ms of information processing. Here, we applied in vivo electrophysiology and pharmacology to determine if prepulse inhibition (PPI is mediated by glycine receptors (GlyRs and/or GABAA receptors (GABAARs in the goldfish auditory startle circuit. Specifically, we used selective antagonists to dissect the contributions of target receptors on sound-evoked postsynaptic potentials (PSPs recorded in the neurons that initiate startle, the Mauthner-cells (M-cell. We found that strychnine, a GlyR antagonist, disrupted a fast-activated (5 ms and rapidly (< 50ms decaying (feed-forward inhibitory process that disrupts PPI at 20 ms prepulse/pulse inter-stimulus intervals (ISI. Additionally we observed increases of the evoked postsynaptic potential (PSP peak amplitude (+87.43 ± 21.53%; N=9 and duration (+204 ± 48.91%, N=9. In contrast, treatment with bicuculline, a GABAAR antagonist, caused a general reduction in PPI across all tested ISIs (20-500 ms, essentially eliminating PPI at ISIs from 20-100 ms. Bicuculline also increased PSP peak amplitude (+133.8 ± 10.3%, N=5 and PSP duration (+284.95 ± 65.64%, N=5. Treatment with either antagonist also tonically increased post-synaptic excitability in the M-cells, reflected by an increase in the magnitude of antidromically-evoked action potentials (APs by 15.07 ± 3.21%, N=7 and 16.23 ± 7.08%, N=5 for strychnine and bicuculline, respectively. These results suggest that GABAARs and GlyRs are functionally segregated to short- and longer-lasting sound-evoked (phasic inhibitory processes that contribute to PPI, with the mediation of tonic inhibition by both receptor systems being critical for gain control within the M-cell startle circuit.

  16. Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

    Datz, Stefan; Argyo, Christian; Gattner, Michael; Weiss, Veronika; Brunner, Korbinian; Bretzler, Johanna; von Schirnding, Constantin; Torrano, Adriano A.; Spada, Fabio; Vrabel, Milan; Engelke, Hanna; Bräuchle, Christoph; Carell, Thomas; Bein, Thomas

    2016-04-01

    Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the development of precisely controllable and highly modular theranostic systems.Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the

  17. The overexpressed human 46-kDa mannose 6-phosphate receptor mediates endocytosis and sorting of β-glucuronidase

    The authors studied the function of the human small (46-kDa) mannose 6-phosphate receptor (SMPR) in transfected mouse L cells that do not express the larger insulin-like growth factor II/mannose 6-phosphate receptor. Cells overexpressing human SMPR were studied for enzyme binding to cell surface receptors, for binding to intracellular receptors in permeabilized cells, and for receptor-mediated endocytosis of recombinant human β-glucuronidase. Specific binding to human SMPR in permeabilized cells showed a pH optimum between pH 6.0 and pH 6.5. Binding was significant in the present of EDTA but was enhanced by added divalent cations. Up to 2.3% of the total functional receptor could be detected on the cell surface by enzyme binding. They present experiments showing that at very high levels of overexpression, and at pH 6.5, human SMPR mediated the endocytosis of β-glucuronidase. At pH 7.5, the rate of endocytosis was only 14% the rate seen at pH 6.5. Cells overexpressing human SMPR also showed reduced secretion of newly synthesized β-glucuronidase when compared to cells transfected with vector only, suggesting that overexpressed human SMPR can participate in sorting of newly synthesized β-glucuronidase and partially correct the sorting defect in mouse L cells that do not express the insulin-like growth factor II/mannose 6-phosphate receptor

  18. Polypeptide hormone receptor phosphorylation: is there a role in receptor-mediated endocytosis of human growth hormone

    To determine whether receptor phosphorylation is a critical step in the internalization of polypeptide hormones and their receptors, the authors have studied a model system wherein insulin stimulates phosphorylation of its receptor and is also internalized. Using insulin as a positive control, they found that it stimulated a partially purified plasma membrane preparation of IM-9 lymphocytes to autophosphorylate its receptor and to catalyze the phosphorylation of a tyrosine-containing substrate. The human GH (hGH) receptor of the IM-9 lymphocytes, when coupled to [125I]iodo-hGH, migrated as a 140,000-dalton protein on polyacrylamide gel electrophoresis. This protein, in contrast to the insulin receptor, was not phosphorylated by the addition of hGH, nor did hGH stimulate this preparation to phosphorylate the tyrosine-containing substrate poly-(GluNa,Tyr)4:1, casein, or histone f2b under a variety of conditions. The authors conclude that receptor phosphorylation is not a critical intermediate in the receptor-mediated endocytosis of hGH and probably other polypeptide hormones and growth factors

  19. Interrogating the Role of Receptor-Mediated Mechanisms: Biological Fate of Peptide-Functionalized Radiolabeled Gold Nanoparticles in Tumor Mice.

    Silva, Francisco; Zambre, Ajit; Campello, Maria Paula Cabral; Gano, Lurdes; Santos, Isabel; Ferraria, Ana Maria; Ferreira, Maria João; Singh, Amolak; Upendran, Anandhi; Paulo, António; Kannan, Raghuraman

    2016-04-20

    To get a better insight on the transport mechanism of peptide-conjugated nanoparticles to tumors, we performed in vivo biological studies of bombesin (BBN) peptide functionalized gold nanoparticles (AuNPs) in human prostate tumor bearing mice. Initially, we sought to compare AuNPs with thiol derivatives of acyclic and macrocyclic chelators of DTPA and DOTA types. The DTPA derivatives were unable to provide a stable coordination of (67)Ga, and therefore, the functionalization with the BBN analogues was pursued for the DOTA-containing AuNPs. The DOTA-coated AuNPs were functionalized with BBN[7-14] using a unidentate cysteine group or a bidentate thioctic group to attach the peptide. AuNPs functionalized with thioctic-BBN displayed the highest in vitro cellular internalization (≈ 25%, 15 min) in gastrin releasing peptide (GRP) receptor expressing cancer cells. However, these results fail to translate to in vivo tumor uptake. Biodistribution studies following intravenous (IV) and intraperitoneal (IP) administration of nanoconjugates in tumor bearing mice indicated that the presence of BBN influences to some degree the biological profile of the nanoconstructs. For IV administration, the receptor-mediated pathway appears to be outweighed by the EPR effect. By contrast, in IP administration, it is reasoned that the GRPr-mediated mechanism plays a role in pancreas uptake. PMID:27003101

  20. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    Klika, Václav

    2011-11-10

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. © 2011 Society for Mathematical Biology.

  1. Receptor interconversion model of hormone action. 3. Estrogen receptor mediated repression of reporter gene activity in A431 cells.

    Nag, A; Park, I; Krust, A; Smith, R G

    1990-03-20

    The chicken estrogen receptor exists in three interconvertible forms, two of which bind estradiol with high affinity and one which lacks the capacity to bind estradiol. Interconversion is regulated by reactions involving ATP/Mg2+. By cotransfecting into A431 cells estrogen receptor cDNA in an expression vector together with the pA2 (-821/-87) tk-CAT vitellogenin construct, we demonstrate that constitutive expression of chloramphenicol acetyltransferase (CAT) activity can be regulated either by selection of ligand or by modifying phosphorylation reactions in the recipient cells. In the presence of estrogen receptors, constitutive expression of CAT activity is inhibited in three situations: (i) in the absence of an estrogenic ligand; (ii) in the presence of an anti-estrogen; and (iii) in the presence of an estrogenic ligand together with 12-O-tetradecanoylphorbol 13-acetate (TPA). Estrogen receptor mediated repression of constitutive CAT activity is not observed with the pA2 (-331/-87) tk-CAT construct, indicating that DNA sequences required for repression are located between -821 and -331 base pairs upstream of the transcription initiation site. PMID:2346742

  2. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Highlights: ► We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. ► Zfat-deficiency leads to reduction in the number of the peripheral T cells. ► Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. ► Decreased expression of IL-7Rα, IL-2Rα and IL-2 in Zfat-deficient peripheral T cells. ► Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  3. Human epidermal Langerhans cells cointernalize by receptor-mediated endocytosis "nonclassical" major histocompatibility complex class I molecules (T6 antigens) and class II molecules (HLA-DR antigens).

    Hanau, D.; Fabre, M.; Schmitt, D A; Garaud, J C; Pauly, G; Tongio, M M; Mayer, S.; Cazenave, J. P.

    1987-01-01

    HLA-DR and T6 surface antigens are expressed only by Langerhans cells and indeterminate cells in normal human epidermis. We have previously demonstrated that T6 antigens are internalized in Langerhans cells and indeterminate cells by receptor-mediated endocytosis. This process is induced by the binding of BL6, a monoclonal antibody directed against T6 antigens. In the present study, using a monoclonal antibody directed against HLA-DR antigens, on human epidermal cells in suspension, we show t...

  4. Optogenetic evocation of field inhibitory postsynaptic potentials in hippocampal slices: a simple and reliable approach for studying pharmacological effects on GABAA and GABAB receptor-mediated neurotransmission

    Dine, Julien; Kühne, Claudia; Deussing, Jan M.; Eder, Matthias

    2014-01-01

    The GABAergic system is the main source of inhibition in the mammalian brain. Consequently, much effort is still made to develop new modulators of GABAergic synaptic transmission. In contrast to glutamatergic postsynaptic potentials (PSPs), accurate monitoring of GABA receptor-mediated PSPs (GABAR-PSPs) and their pharmacological modulation in brain tissue invariably requires the use of intracellular recording techniques. However, these techniques are expensive, time- and labor-consuming, and,...

  5. Optogenetic Evocation of Field Inhibitory Postsynaptic Potentials in Hippocampal Slices: A Simple and Reliable Approach for Studying Pharmacological Effects on GABAA and GABAB Receptor-Mediated Neurotransmission

    Julien eDine; Claudia eKühne; Deussing, Jan M.; Matthias eEder

    2014-01-01

    The GABAergic system is the main source of inhibition in the mammalian brain. Consequently, much effort is still made to develop new modulators of GABAergic synaptic transmission. In contrast to glutamatergic postsynaptic potentials (PSPs), accurate monitoring of GABA receptor-mediated PSPs (GABAR-PSPs) and their pharmacological modulation in brain tissue invariably requires the use of intracellular recording techniques. However, these techniques are expensive, time- and labor-consuming, and,...

  6. Methamphetamine exposure antagonizes N-methyl-D-aspartate receptor-mediated neurotoxicity in organotypic hippocampal slice cultures.

    Smith, Katherine J; Self, Rachel L; Butler, Tracy R; Mullins, Michael M; Ghayoumi, Layla; Holley, Robert C; Littleton, John M; Prendergast, Mark A

    2007-07-01

    Glutamatergic systems have been increasingly recognized as mediators of methamphetamine's (METH) pharmacological effects though little is known about the means by which METH interacts with glutamate receptors. The present studies examined effects of METH (0.1-100 microM) on [3H]MK-801 binding to membranes prepared from adult rat cortex, hippocampus and cerebellum, as well as the neurotoxicity produced by 24-h exposure to N-methyl-D-aspartate (5-10 microM; NMDA) employing organotypic hippocampal slice cultures of neonatal rat. Co-incubation of [3H]MK-801 with METH (0.1-100 microM) did not reduce dextromethorphan (1 mM)-displaceable ligand binding. Exposure of slice cultures to NMDA for 24-h produced increases in uptake of the non-vital fluorescent marker propidium iodide (PI) of 150-500% above control levels, most notably, in the CA1 region pyramidal cell layer. Co-exposure to METH (>1.0 microM) with NMDA (5 microM) reduced PI uptake by approximately 50% in each subregion, though the CA1 pyramidal cell layer was markedly more sensitive to the protective effects of METH exposure. In contrast, METH exposure did not reduce PI uptake stimulated by 24-h exposure to 10 microM NMDA. Co-exposure to the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (20 microM) prevented toxicity produced by exposure to 5 or 10 microM NMDA. These findings indicate that the pharmacological effects of short-term METH exposure involve inhibition of NMDA receptor-mediated neuronal signaling, not reflective of direct channel inhibition at an MK-801-sensitive site. PMID:17524372

  7. Possible role of death receptor-mediated apoptosis by the E3 ubiquitin ligases Siah2 and POSH

    Schwarze Steven R

    2011-05-01

    Full Text Available Abstract Background A functioning ubiquitin proteasome system (UPS is essential for a number of diverse cellular processes and maintenance of overall cellular homeostasis. The ability of proteasome inhibitors, such as Velcade, to promote extrinsic apoptotic effects illustrates the importance of the ubiquitin proteasome system in the regulation of death receptor signaling. Here, we set out to define the UPS machinery, particularly the E3 ubiquitin ligases, that repress apoptosis through the extrinsic pathway. A cell-based genome-wide E3 ligase siRNA screen was established to monitor caspase-8 activity following the addition of TRAIL. Results Data from the high-throughput screen revealed that targeting the RING-finger containing E3 ligase Siah2 as well as the signaling platform molecule POSH (SH3RF1 conferred robust caspase-8 activation in response to TRAIL stimulus. Silencing Siah2 or POSH in prostate cancer cells led to increased caspase activity and apoptosis in response to both TRAIL and Fas ligand. The E3 activity of Siah2 was responsible for mediating apoptosis resistance; while POSH protein levels were critical for maintaining viability. Further characterization of Siah2 revealed it to function downstream of early death receptor events in the apoptotic pathway. The observed apoptosis resistance provides one biological explanation for the induction of Siah2 and POSH reported in lung and prostate cancer, respectively. Expanding on an initial yeast-two-hybrid screen we have confirmed a physical interaction between E3 ligases Siah2 and POSH. Utilizing a yeast-two-hybrid mapping approach we have defined the spacer region of POSH, more specifically the RPxAxVxP motif encompassing amino acids 601-607, to be the site of Siah2 binding. Conclusions The data presented here define POSH and Siah2 as important mediators of death receptor mediated apoptosis and suggest targeting the interaction of these two E3 ligases is a promising novel cancer

  8. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    Yingna He

    2010-09-01

    Full Text Available Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposomes were prepared by lipid film hydration and an ultrasound dispersion process. Thiolated gonadorelin with affinity for the LHRH receptor was chemically coupled to N-[(3-maleimide-1-oxopropyl aminopropyl polyethylene glycol-carbamyl] distearoyl-l-phosphatidyl-ethanolamine via a thioether bond and subsequently inserted into polyethylene glycol-grafted liposomes. The liposome was characterized in terms of its size, ligand density, drug loading, and leakage properties. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured MCF-7 breast cancer cells. A protein assay of ligand coupling to the liposomal surface indicated that more than 60% of the LHRH peptides were inserted into the liposome bilayer. Up to 1.0 mg/mL of stable liposomal mitoxantrone loading was achieved, with approximately 98% of this being entrapped within the liposomes. In vitro cell culture studies revealed that the gonadorelin-modified liposomes bound to their target cells had significantly higher affinity and better antitumor efficiency than generic drug-loaded liposomes. These events were presumed to occur through specific interactions of the LHRH with its cognate receptors on the cell surface. It was concluded that the targeting properties of the delivery system would potentially improve the therapeutic benefits of mitoxantrone, as compared with nontargeted liposomes.Keywords: mitoxantrone, liposome, luteinizing hormone-releasing hormone receptor

  9. Role of various kinases in muscarinic M3 receptor-mediated contraction of longitudinal muscle of rat colon

    Anderson, Charles D.; Kendig, Derek M.; Al-Qudah, Mohammad; Mahavadi, Sunila; Murthy, Karnam S.; Grider, John R.

    2016-01-01

    The longitudinal muscle layer in gut is the functional opponent to the circular muscle layer during peristalsis. Differences in innervation of the layers allow for the contraction of one layer concurrently with the relaxation of the other, enabling the passage of gut contents in a controlled fashion. Differences in development have given the cells of the two layers differences in receptor populations, membrane lipid handling, and calcium handling profiles/behaviors. The contractile activity of the longitudinal muscle is largely mediated by cholinergic neural input from myenteric plexus. Activation of muscarinic receptors leads to rapid activation of several kinases including MLC kinase, ERK1/2, CaMKII and Rho kinase. Phosphorylation of myosin light chain (MLC20) by MLC kinase (MLCK) is a prerequisite for contraction in both circular and longitudinal muscle cells. In rat colonic longitudinal muscle strips, we measured muscarinic receptor-mediated contraction following incubation with kinase inhibitors. Basal tension was differentially regulated by Rho kinase, ERK1/2, CaMKII and CaMKK. Selective inhibitors of Rho kinase, ERK1/2, CaMKK/AMPK, and CaMKII each reduced carbachol-induced contraction in the innervated muscle strips. These inhibitors had no direct effect on MLCK activity. Thus unlike previously reported for isolated muscle cells where CaMKII and ERK1/2 are not involved in contraction, we conclude that the regulation of carbachol-induced contraction in innervated longitudinal muscle strips involves the interplay of Rho kinase, ERK1/2, CaMKK/AMPK, and CAMKII. PMID:25891767

  10. Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling

    Highlights: → A yeast two-hybrid screen revealed testin bound to the calcium-sensing receptor. → The second zinc finger of LIM domain 1 of testin is critical for interaction. → Testin bound to a region of the receptor tail important for cell signalling. → Testin and receptor interaction was confirmed in mammalian (HEK293) cells. → Overexpression of testin enhanced receptor-mediated Rho signalling in HEK293 cells. -- Abstract: The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin. Testin has not previously been shown to interact with cell surface receptors. The sites of interaction between the CaR and testin were mapped to the membrane proximal region of the receptor tail and the second zinc-finger of LIM domain 1 of testin, the integrity of which was found to be critical for the CaR-testin interaction. The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation and confocal microscopy studies. Ectopic expression of testin in HEK293 cells stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect on CaR-stimulated ERK signalling. These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton.

  11. Histamine is required for H3 receptor-mediated alcohol reward inhibition, but not for alcohol consumption or stimulation

    Vanhanen, J; Nuutinen, S; Lintunen, M; Mäki, T; Rämö, J; Karlstedt, K; Panula, P

    2013-01-01

    Background and Purpose Conflicting data have been published on whether histamine is inhibitory to the rewarding effects of abused drugs. The purpose of this study was to clarify the role of neuronal histamine and, in particular, H3 receptors in alcohol dependence-related behaviours, which represent the addictive effects of alcohol. Experimental Approach Alcohol-induced conditioned place preference (alcohol-CPP) was used to measure alcohol reward. Alcohol-induced locomotor stimulation, alcohol consumption and kinetics were also assessed. mRNA levels were quantified using radioactive in situ hybridization. Key Results Low doses of H3 receptor antagonists, JNJ-10181457 and JNJ-39220675, inhibited alcohol reward in wild-type (WT) mice. However, these H3 receptor antagonists did not inhibit alcohol reward in histidine decarboxylase knock-out (HDC KO) mice and a lack of histamine did not alter alcohol consumption. Thus H3 receptor antagonists inhibited alcohol reward in a histamine-dependent manner. Furthermore, WT and HDC KO mice were similarly stimulated by alcohol. The expression levels of dopamine D1 and D2 receptors, STEP61 and DARPP-32 mRNA in striatal subregions were unaltered in HDC KO mice. No differences were seen in alcohol kinetics in HDC KO compared to WT control animals. In addition, JNJ-39220675 had no effect on alcohol kinetics in WT mice. Conclusions and Implications These data suggest that histamine is required for the H3 receptor-mediated inhibition of alcohol-CPP and support the hypothesis that the brain histaminergic system has an inhibitory role in alcohol reward. Increasing neuronal histamine release via H3 receptor blockade could therefore be a novel way of treating alcohol dependence. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 PMID:23489295

  12. Amyloid β-protein differentially affects NMDA receptor- and GABAA receptor-mediated currents in rat hippocampal CA1 neurons

    Junfang Zhang; Lei Hou; Xiuping Gao; Fen Guo; Wei Jing; Jinshun Qi; Jiantian Qiao

    2009-01-01

    Although the aggregated amyloid β-protein (Aβ) in senile plaques is one of the key neuropathological features of Alzheimer's disease (AD), soluble forms of Aβ also interfere with synaptic plasticity at the early stage of AD. The suppressive action of acute application of Aβ on hippocampal long-term potentiation (LTP) has been reported widely, whereas the mechanism underlying the effects of Aβ is still mostly unknown. The present study, using the whole-cell patch clamp technique, investigated the effects of Aβ fragments (Aβ25-35 and Aβ31-35) on the LTP induction-related postsynaptic ligand-gated channel currents in isolated hippocampal CA1 neurons. The results showed a rapid but opposite action of both peptides on excitatory and inhibitory receptor currents. Glutamate application-induced currents were suppressed by A β25-35 in a dose-dependent manner, and further N-methyl-I>aspartate (NMDA) receptor-mediated currents were selec-tively inhibited. In contrast, pretreatment with Aβ fragments potentiated γ-aminobutyric acid (GABA)-induced whole-cell currents. As a control, Aβ35-31 the reversed sequence of Aβ35-31 showed no effect on the currents induced by glutamate, NMDA or GABA. These results may partly explain the impaired effects of Aβ on hippocampal LTP, and suggest that the functional down-regulation of N M DA receptors and up-regulation of GABAA receptors may play an important role in remodeling the hippocampal synaptic plasticity in early AD.

  13. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Doi, Keiko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka (Japan); Fujimoto, Takahiro [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Okamura, Tadashi [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ogawa, Masahiro [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tanaka, Yoko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Mototani, Yasumasa; Goto, Motohito [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ota, Takeharu; Matsuzaki, Hiroshi [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Kuroki, Masahide [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tsunoda, Toshiyuki [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Sasazuki, Takehiko [Institute for Advanced Study, Kyushu University, Fukuoka (Japan); Shirasawa, Senji, E-mail: sshirasa@fukuoka-u.ac.jp [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7R{alpha} and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2R{alpha} expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  14. Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006

    Wakiguchi Hiroshi

    2003-07-01

    Full Text Available Abstract Background Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN are known to exert a strong adjuvant effect on Th1 immune responses. Although several genes have been reported, no comprehensive study of the gene expression profiles in human cells after stimulation with CpG ODN has been reported. Results This study was designed to identify a CpG-inducible gene cluster that potentially predicts for the molecular mechanisms of clinical efficacy of CpG ODN, by determining mRNA expression in human PBMC after stimulation with CpG ODN. PBMCs were obtained from the peripheral blood of healthy volunteers and cultured in the presence or absence of CpG ODN 2006 for up to 24 hours. The mRNA expression profile was evaluated using a high-density oligonucleotide probe array, GeneChip®. Using hierarchical clustering-analysis, out of a total of 10,000 genes we identified a cluster containing 77 genes as having been up-regulated by CpG ODN. This cluster was further divided into two sub-clusters by means of time-kinetics. (1 Inflammatory cytokines such as IL-6 and GM-CSF were up-regulated predominantly 3 to 6 hours after stimulation with CpG ODN, presumably through activation of a transcription factor, NF-κB. (2 Interferon (IFN-inducible anti-viral proteins, including IFIT1, OAS1 and Mx1, and Th1 chemoattractant IP-10, were up-regulated predominantly 6 to 24 hours after stimulation. Blocking with mAb against IFN-α/β receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN. Conclusion This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-α/β receptor-mediated paracrine pathway.

  15. The Role of cGMP on Adenosine A1 Receptor-mediated Inhibition of Synaptic Transmission at the Hippocampus

    Pinto, Isa; Serpa, André; Sebastião, Ana M.; Cascalheira, José F.

    2016-01-01

    Both adenosine A1 receptor and cGMP inhibit synaptic transmission at the hippocampus and recently it was found that A1 receptor increased cGMP levels in hippocampus, but the role of cGMP on A1 receptor-mediated inhibition of synaptic transmission remains to be established. In the present work we investigated if blocking the NOS/sGC/cGMP/PKG pathway using nitric oxide synthase (NOS), protein kinase G (PKG), and soluble guanylyl cyclase (sGC) inhibitors modify the A1 receptor effect on synaptic transmission. Neurotransmission was evaluated by measuring the slope of field excitatory postsynaptic potentials (fEPSPs) evoked by electrical stimulation at hippocampal slices. N6-cyclopentyladenosine (CPA, 15 nM), a selective A1 receptor agonist, reversibly decreased the fEPSPs by 54 ± 5%. Incubation of the slices with an inhibitor of NOS (L-NAME, 200 μM) decreased the CPA effect on fEPSPs by 57 ± 9% in female rats. In males, ODQ (10 μM), an sGC inhibitor, decreased the CPA inhibitory effect on fEPSPs by 23 ± 6%, but only when adenosine deaminase (ADA,1 U/ml) was present; similar results were found in females, where ODQ decreased CPA-induced inhibition of fEPSP slope by 23 ± 7%. In male rats, the presence of the PKG inhibitor (KT5823, 1 nM) decreased the CPA effect by 45.0 ± 9%; similar results were obtained in females, where KT5823 caused a 32 ± 9% decrease on the CPA effect. In conclusion, the results suggest that the inhibitory action of adenosine A1 receptors on synaptic transmission at hippocampus is, in part, mediated by the NOS/sGC/cGMP/PKG pathway.

  16. Two types of functionally different GABAA receptors mediate GABA modulation of cholinergic transmission in cat terminal ileum.

    Radomirov, R; Pencheva, N

    1995-08-01

    1. The effects of GABA (1 microM-2 mM) on longitudinally or circularly oriented organ bath preparations of cat terminal ileum consisted of a relaxation phase with an inhibition of the rhythmic spontaneous phasic contractions, followed by a phase of contractions characterized by an elevation in basal tone and an increase in amplitude of the spontaneous phasic contractions. 2. Muscimol (100 microM), but not baclofen (100 microM), mimicked the relaxation phase of the response to applied GABA (100 microM) in all tissue preparations. In addition, muscimol induced a phase of contractile activity in the circular muscle layer whilst baclofen exerted a 'GABA-like' contractile effect on the longitudinal muscle layer. Bicuculline (30 microM) or picrotoxinin (30 microM) antagonized the GABA- or muscimol-induced relaxations in all preparations and decreased the GABA- but not the baclofen-induced contractions of the longitudinal muscle layer. 3. Tetrodotoxin (0.5 microM) or atropine (0.1 microM) prevented the bicuculline-sensitive phases of the GABA or muscimol effects on both muscle layers but not the contractile effect of baclofen on the longitudinal muscle layer. 4. The bicuculline-sensitive phases of the GABA effect on both muscle layers were almost completely eliminated by 1 nM pirenzepine. At this concentration pirenzepine did not affect the electrically-evoked cholinergic twitch contractions or contractile responses to applied acetylcholine of both muscle layers. 5. During electrically-evoked cholinergic twitch contractions of both muscle layers, GABA (100 microM) had an inhibitory effect. The inhibition occurred in the presence of pirenzepine (1 nM) but not of bicuculline (30 microM). 6. It is suggested that two types of functionally different bicuculline-sensitive GABAA receptors mediate an exitatory presynaptic and an inhibitory prejunctional action of GABA on the cholinergic transmission in cat terminal ileum. PMID:8576270

  17. α4 nicotinic acetylcholine receptor modulated by galantamine on nigrostriatal terminals regulates dopamine receptor-mediated rotational behavior.

    Inden, Masatoshi; Takata, Kazuyuki; Yanagisawa, Daijiro; Ashihara, Eishi; Tooyama, Ikuo; Shimohama, Shun; Kitamura, Yoshihisa

    2016-03-01

    Galantamine, an acetylcholine esterase (AChE) inhibitor used to treat dementia symptoms, also acts as an allosteric potentiating ligand (APL) at nicotinic acetylcholine receptors (nAChRs). This study was designed to evaluate the allosteric effect of galantamine on nAChR regulation of nigrostrial dopaminergic neuronal function in the hemiparkinsonian rat model established by unilateral nigral 6-hydroxydopamine (6-OHDA) injection. Methamphetamine, a dopamine releaser, induced ipsilateral rotation, whereas dopamine agonists apomorphine (a non-selective dopamine receptor agonist), SKF38393 (a selective dopamine D1 receptor agonist), and quinpirole (a selective dopamine D2 receptor agonist) induced contralateral rotation. When 6-OHDA-injected rats were co-treated with nomifensine, a dopamine transporter inhibitor, a more pronounced and a remarkable effect of nicotine and galantamine was observed. Under these conditions, the combination of nomifensine with nicotine or galantamine induced the ipsilateral rotation similar to the methamphetamine-induced rotational behavior, indicating that nicotine and galantamine also induce dopamine release from striatal terminals. Both nicotine- and galantamine-induced rotations were significantly blocked by flupenthixol (an antagonist of both D1 and D2 dopamine receptors) and mecamylamine (an antagonist of nAChRs), suggesting that galantamine modulation of nAChRs on striatal dopaminergic terminals regulates dopamine receptor-mediated movement. Immunohistochemical staining showed that α4 nAChRs were highly expressed on striatal dopaminergic terminals, while no α7 nAChRs were detected. Pretreatment with the α4 nAChR antagonist dihydroxy-β-erythroidine significantly inhibited nicotine- and galantamine-induced rotational behaviors, whereas pretreatment with the α7 nAChR antagonist methyllycaconitine was ineffective. Moreover, the α4 nAChR agonist ABT-418 induced ipsilateral rotation, while the α7 nAChR agonist PNU282987 had no

  18. Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute NO-deficiency in rats.

    Béla Horváth

    Full Text Available BACKGROUND: Low frequency (4-12 cpm spontaneous fluctuations of the cerebrovascular tone (vasomotion and oscillations of the cerebral blood flow (CBF have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO suppresses constitutively the release and vascular effects of thromboxane A(2 (TXA(2, NO-deficiency is often associated with activation of thromboxane receptors (TP. In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. METHODOLOGY/PRINCIPAL FINDINGS: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 µg/kg i.v. to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.v. resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 148±2 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA(2 synthesis by ozagrel (10 mg/kg i.v. attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 µM Y-27632. CONCLUSION/SIGNIFICANCE: These results suggest that hypersensitivity of the TP

  19. The Critical Role Of VP1 In Forming The Necessary Cavities For Receptor-mediated Entry Of FMDV To The Host Cell

    Jahanshah Ashkani; Rees, D. J. G.

    2016-01-01

    The antigenic inconsistency of the foot-and-mouth disease virus (FMDV) is very broad, such that a vaccine made from one isolate will not offer protection against infection with other isolates from the same serotype. Viral particles (VPs) or surface exposed capsid proteins, VP1–VP3, of FMDV determine both the antigenicity of the virus and its receptor-mediated entry into the host cell. Therefore, modifications of these structural proteins may alter the properties of the virus. Here we show put...

  20. Alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. Possible parallel activation of phospholipase C and phospholipase A2

    alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are mediated by a single population of alpha 1-adrenergic receptors. However, we find that the kinetics of the two responses are quite different, PGE2 production occurring more rapidly and transiently than the hydrolysis of phosphoinositides. The antibiotic neomycin selectively decreases alpha 1-receptor-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis without decreasing alpha 1-receptor-mediated arachidonic acid release and PGE2 generation. In addition, receptor-mediated inositol trisphosphate formation is independent of extracellular calcium, whereas release of labeled arachidonic acid is largely calcium-dependent. Moreover, based on studies obtained with labeled arachidonic acid, receptor-mediated generation of arachidonic acid cannot be accounted for by breakdown of phosphatidylinositol monophosphate, phosphatidylinositol bisphosphate, or phosphatidic acid. Further studies indicate that epinephrine produces changes in formation or turnover of several classes of membrane phospholipids in MDCK cells. We conclude that alpha 1-adrenergic receptors in MDCK cells appear to regulate phospholipid metabolism by the parallel activation of phospholipase C and phospholipase A2. This parallel activation of phospholipases contrasts with models described in other systems which imply sequential activation of phospholipase C and diacylglycerol lipase or phospholipase A2

  1. The Critical Role Of VP1 In Forming The Necessary Cavities For Receptor-mediated Entry Of FMDV To The Host Cell.

    Ashkani, Jahanshah; Rees, D J G

    2016-01-01

    The antigenic inconsistency of the foot-and-mouth disease virus (FMDV) is very broad, such that a vaccine made from one isolate will not offer protection against infection with other isolates from the same serotype. Viral particles (VPs) or surface exposed capsid proteins, VP1-VP3, of FMDV determine both the antigenicity of the virus and its receptor-mediated entry into the host cell. Therefore, modifications of these structural proteins may alter the properties of the virus. Here we show putative cavities on the FMDV-SAT1 (FMDV Southern African Territories1) capsid as possible binding sites for the receptor-mediated viral entry into the host cell. We identified three possible cavities on the FMDV capsid surface, from which the largest one (C2) is shaped in the contact regions of VP1-VP3. Our results demonstrate the significance of VP1, in the formation of FMDV-SAT1 surface cavities, which is the main component in all the identified cavities. Our findings can have profound implications in the protein engineering of FMDV in the contact region of VP1-VP3 found to be embedded in several cavities. Such information is of great significance in the context of vaccine design, as it provides the ground for future improvement of synthetic vaccines to control FMD caused by FMDV-SAT1 serotypes. PMID:27249937

  2. The Critical Role Of VP1 In Forming The Necessary Cavities For Receptor-mediated Entry Of FMDV To The Host Cell

    Ashkani, Jahanshah; Rees, D. J. G.

    2016-01-01

    The antigenic inconsistency of the foot-and-mouth disease virus (FMDV) is very broad, such that a vaccine made from one isolate will not offer protection against infection with other isolates from the same serotype. Viral particles (VPs) or surface exposed capsid proteins, VP1–VP3, of FMDV determine both the antigenicity of the virus and its receptor-mediated entry into the host cell. Therefore, modifications of these structural proteins may alter the properties of the virus. Here we show putative cavities on the FMDV-SAT1 (FMDV Southern African Territories1) capsid as possible binding sites for the receptor-mediated viral entry into the host cell. We identified three possible cavities on the FMDV capsid surface, from which the largest one (C2) is shaped in the contact regions of VP1–VP3. Our results demonstrate the significance of VP1, in the formation of FMDV-SAT1 surface cavities, which is the main component in all the identified cavities. Our findings can have profound implications in the protein engineering of FMDV in the contact region of VP1–VP3 found to be embedded in several cavities. Such information is of great significance in the context of vaccine design, as it provides the ground for future improvement of synthetic vaccines to control FMD caused by FMDV-SAT1 serotypes. PMID:27249937

  3. Differential modulation of expression of nuclear receptor mediated genes by tris(2-butoxyethyl) phosphate (TBOEP) on early life stages of zebrafish (Danio rerio).

    Ma, Zhiyuan; Yu, Yijun; Tang, Song; Liu, Hongling; Su, Guanyong; Xie, Yuwei; Giesy, John P; Hecker, Markus; Yu, Hongxia

    2015-12-01

    As one substitute for phased-out brominated flame retardants (BFRs), tris(2-butoxyethyl) phosphate (TBOEP) is frequently detected in aquatic organisms. However, knowledge about endocrine disrupting mechanisms associated with nuclear receptors caused by TBOEP remained restricted to results from in vitro studies with mammalian cells. In the study, results of which are presented here, embryos/larvae of zebrafish (Danio rerio) were exposed to 0.02, 0.1 or 0.5μM TBOEP to investigate expression of genes under control of several nuclear hormone receptors (estrogen receptors (ERs), androgen receptor (AR), thyroid hormone receptor alpha (TRα), mineralocorticoid receptor (MR), glucocorticoid receptor (GR), aryl hydrocarbon (AhR), peroxisome proliferator-activated receptor alpha (PPARα), and pregnane×receptor (P×R)) pathways at 120hpf. Exposure to 0.5μM TBOEP significantly (peffects on AR- and AhR-mediated pathways. In mammalian cells, none of these pathways were affected by TBOEP at the concentrations studied. Receptor-mediated responses (in vivo) and mammalian cell lines receptor binding assay (in vitro) combined with published information suggest that TBOEP can modulate receptor-mediated, endocrine process (in vivo/in vitro), particularly ER and MR. PMID:26562049

  4. Dopamine D1 receptor-mediated NMDA receptor insertion depends on Fyn but not Src kinase pathway in prefrontal cortical neurons

    Hu Jian-Li

    2010-06-01

    Full Text Available Abstract Background Interactions between dopamine and glutamate in the prefrontal cortex are essential for cognitive functions such as working memory. Modulation of N-methyl-D-aspartic acid (NMDA receptor functions by dopamine D1 receptor is believed to play a critical role in these functions. The aim of the work reported here is to explore the signaling pathway underlying D1 receptor-mediated trafficking of NMDA receptors in cultured rat prefrontal cortical neurons. Results Activation of D1 receptor by selective agonist SKF-81297 significantly increased the expression of NR2B subunits. This effect was completely blocked by small interfering RNA knockdown of Fyn, but not Src. Under control conditions, neither Fyn nor Src knockdown exhibited significant effect on basal NR2B expression. D1 stimulation significantly enhanced NR2B insertion into plasma membrane in cultured PFC neurons, a process obstructed by Fyn, but not Src, knockdown. Conclusions Dopamine D1 receptor-mediated increase of NMDA receptors is thus Fyn kinase dependent. Targeting this signaling pathway may be useful in treating drug addiction and schizophrenia.

  5. Changes in synaptic and extrasynaptic N-methyl-D-aspartate receptor-mediated currents at early-stage epileptogenesis in adult mice

    Juegang Ju; Sheng-tian Li

    2011-01-01

    Previous reports have shown that N-methyl-D-aspartate (NMDA) receptors are extensively involved in epilepsy genesis and recurrence.Recent studies have shown that synaptic and extrasynaptic NMDA receptors play different, or even opposing, roles in various signaling pathways, including synaptic plasticity and neuronal death.The present study analyzed changes in synaptic and extrasynaptic NMDA receptor-mediated currents during epilepsy onset.Mouse models of lithium chloride pilocarpine-induced epilepsy were established, and hippocampal slices were prepared at 24 hours after the onset of status epilepticus.Synaptic and extrasynaptic NMDA receptor-mediated excitatory post-synaptic currents (NMDA-EPSCs) were recorded in CA1 pyramidal neurons by whole-cell patch clamp technique.Results demonstrated no significant difference in rise and delay time of synaptic NMDA-EPSCs compared with normal neurons.Peak amplitude, area-to-peak ratio,and rising time of extrasynaptic NMDA-EPSCs remained unchanged, but decay of extrasynaptic NMDA-EPSCs was faster than that of normal neurons.These results suggest that extrasynaptic NMDA receptors play a role in epileptogenesis.

  6. Mu-Opioid (MOP) receptor mediated G-protein signaling is impaired in specific brain regions in a rat model of schizophrenia.

    Szűcs, Edina; Büki, Alexandra; Kékesi, Gabriella; Horváth, Gyöngyi; Benyhe, Sándor

    2016-04-21

    Schizophrenia is a complex mental health disorder. Clinical reports suggest that many patients with schizophrenia are less sensitive to pain than other individuals. Animal models do not interpret schizophrenia completely, but they can model a number of symptoms of the disease, including decreased pain sensitivities and increased pain thresholds of various modalities. Opioid receptors and endogenous opioid peptides have a substantial role in analgesia. In this biochemical study we investigated changes in the signaling properties of the mu-opioid (MOP) receptor in different brain regions, which are involved in the pain transmission, i.e., thalamus, olfactory bulb, prefrontal cortex and hippocampus. Our goal was to compare the transmembrane signaling mediated by MOP receptors in control rats and in a recently developed rat model of schizophrenia. Regulatory G-protein activation via MOP receptors were measured in [(35)S]GTPγS binding assays in the presence of a highly selective MOP receptor peptide agonist, DAMGO. It was found that the MOP receptor mediated activation of G-proteins was substantially lower in membranes prepared from the 'schizophrenic' model rats than in control animals. The potency of DAMGO to activate MOP receptor was also decreased in all brain regions studied. Taken together in our rat model of schizophrenia, MOP receptor mediated G-proteins have a reduced stimulatory activity compared to membrane preparations taken from control animals. The observed distinct changes of opioid receptor functions in different areas of the brain do not explain the augmented nociceptive threshold described in these animals. PMID:26946106

  7. mu Opioid receptor-mediated G-protein activation by heroin metabolites: evidence for greater efficacy of 6-monoacetylmorphine compared with morphine.

    Selley, D E; Cao, C C; Sexton, T; Schwegel, J A; Martin, T J; Childers, S R

    2001-08-15

    The efficacy of heroin metabolites for the stimulation of mu opioid receptor-mediated G-protein activation was investigated using agonist-stimulated [(35)S]guanosine-5'-O-(gamma-thio)-triphosphate binding. In rat thalamic membranes, heroin and its primary metabolite, 6-monoacetylmorphine (6-MAM), were more efficacious than morphine or morphine-6-beta D-glucuronide. This increased efficacy was not due to increased action of heroin and 6-MAM at delta receptors, as determined by competitive antagonism by naloxone, lack of antagonism by naltrindole, and competitive partial antagonism with morphine. In agreement with this interpretation, the same relative efficacy profile of heroin and its metabolites was observed at the cloned human mu opioid receptor expressed in C6 glioma cells. Moreover, these efficacy differences were GDP-dependent in a manner consistent with accepted mechanisms of receptor-mediated G-protein activation. The activity of heroin was attributed to in vitro deacetylation to 6-MAM, as confirmed by HPLC analysis. These results indicate that the heroin metabolite 6-MAM possesses higher efficacy than other heroin metabolites at mu opioid receptors, which may contribute to the higher efficacy of heroin compared with morphine in certain behavioral paradigms in vivo. PMID:11448454

  8. Reduced Mechanical Stretch Induces Enhanced Endothelin B Receptor-mediated Contractility via Activation of Focal Adhesion Kinase and Extra Cellular-regulated Kinase 1/2 in Cerebral Arteries from Rat

    Rasmussen, Marianne N P; Spray, Stine; Skovsted, Gry F;

    2016-01-01

    Cerebral ischaemia results in enhanced endothelin B (ETB ) receptor-mediated contraction and receptor protein expression in the affected cerebrovascular smooth muscle cells (SMC). Organ culture of cerebral arteries is a method to induce similar alterations in ETB receptor expression. We hypothesize......-mediated contractility via triggering of an early mechanosensitive signalling pathway involving ERK1/2 and FAK signalling. A mechanism likely to be an initiating factor for the increased ETB receptor-mediated contractility found after cerebral ischaemia. This article is protected by copyright. All rights reserved....

  9. Modeling and Feed-Forward Control of Structural Elastic Robots

    Reiner, M.; Otter, M.; Ulbrich, H.

    2010-09-01

    In this paper an approach for modeling and control of robots with elasticities in power trains and in structural parts is presented and experimentally verified. For this purpose object-oriented, nonlinear models are developed in the modeling language Modelica. A system theoretical study of the generated models shows that a direct inversion of the models, due to the unstable zero dynamics, is not possible. Therefore an algorithm for the approximate inversion is developed. With this inversion method an approximate inverse model considering structural elasticity for a 6-axis robot is created and verified for the control of the robot. The new control leads to a considerable improvement of the driving characteristics of the robot in the experiment.

  10. Neural network based feed-forward high density associative memory

    Daud, T.; Moopenn, A.; Lamb, J. L.; Ramesham, R.; Thakoor, A. P.

    1987-01-01

    A novel thin film approach to neural-network-based high-density associative memory is described. The information is stored locally in a memory matrix of passive, nonvolatile, binary connection elements with a potential to achieve a storage density of 10 to the 9th bits/sq cm. Microswitches based on memory switching in thin film hydrogenated amorphous silicon, and alternatively in manganese oxide, have been used as programmable read-only memory elements. Low-energy switching has been ascertained in both these materials. Fabrication and testing of memory matrix is described. High-speed associative recall approaching 10 to the 7th bits/sec and high storage capacity in such a connection matrix memory system is also described.

  11. Improved Cuckoo Search Algorithm for Feed forward Neural Network Training

    Ehsan Valian; Shahram Mohanna; Saeed Tavakoli

    2011-01-01

    The cuckoo search algorithm is a recently developed meta-heuristic optimization algorithm, which is suitable for solving optimization problems. To enhance the accuracy and convergence rate of this algorithm, an improved cuckoo search algorithm is proposed in this paper. Normally, the parameters of the cuckoo search are kept constant. This may lead to decreasing the efficiency of the algorithm. To cope with this issue, a proper strategy for tuning the cuckoo search parameters is pr...

  12. Improved Cuckoo Search Algorithm for Feed forward Neural Network Training

    Ehsan Valian

    2011-07-01

    Full Text Available The cuckoo search algorithm is a recently developed meta-heuristic optimization algorithm, which is suitable for solving optimization problems. To enhance the accuracy and convergence rate of this algorithm, an improved cuckoo search algorithm is proposed in this paper. Normally, the parameters of the cuckoo search are kept constant. This may lead to decreasing the efficiency of the algorithm. To cope with this issue, a proper strategy for tuning the cuckoo search parameters is presented. Then, it is employed for training feedforward neural networks for two benchmark classification problems. Finally, the performance of the proposed algorithm is compared with that of the standard cuckoo search. Simulation results demonstrate the effectiveness of the proposed algorithm.

  13. Inhibition of P2Y6 receptor-mediated phospholipase C activation and Ca(2+) signalling by prostaglandin E2 in J774 murine macrophages.

    Ito, Masaaki; Matsuoka, Isao

    2015-02-15

    Extracellular nucleotides act as inflammatory mediators through activation of multiple purinoceptors. Under inflammatory conditions, the purinergic signalling is affected by various inflammatory mediators. We previously showed that prostaglandin (PG) E2 suppressed the elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) stimulated by P2X4, P2Y2, and P2Y6 receptors in J774 murine macrophages. In this study, we examined the mechanism of PGE2 inhibitory effects on P2Y6 receptor-mediated function in J774 cells. The P2Y6 receptor agonist UDP induced a sustained elevation of [Ca(2+)]i by stimulating the phospholipase C (PLC) signalling pathway. PGE2 inhibited [Ca(2+)]i elevation and phosphatidylinositol (PI) hydrolysis in a concentration-dependent manner. J774 cells highly expressed the E-type prostanoid 2 (EP2) receptor subtype, a Gs-coupled receptor. PGE2 and a selective EP2 receptor agonist caused cyclic AMP (cAMP) accumulation in J774 cells. The inhibitory effects of PGE2 on P2Y6 receptor-mediated responses were mimicked by the selective EP2 receptor agonist. Although EP2 receptor is linked to adenylyl cyclase activation, PGE2-induced inhibition of Ca(2+) response and PI hydrolysis could not be mimicked by a lipophilic cAMP derivative, dibutyryl cAMP, or an adenylyl cyclase activator, forskolin. The inhibition of UDP-induced PLC activation by PGE2 was not affected by down-regulation of protein kinase C by phorbol-12-myristate-13-acetate treatment. PGE2 inhibited PLC activation induced by aluminium fluoride, but not by the Ca(2+)-ionophore, ionomycin. Finally, the inhibition of UDP-induced PLC activation by PGE2 was impaired by Gs knockdown using siRNA. These results suggest that EP2 receptor activation in macrophages negatively controls the Gq/11-PLC signalling through a Gs-mediated, but cAMP-independent signalling mechanism. PMID:25614334

  14. Single residues in the surface subunits of oncogenic sheep retrovirus envelopes distinguish receptor-mediated triggering for fusion at low pH and infection

    Cote, Marceline [Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada); Zheng, Yi-Min [Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211-7310 (United States); Albritton, Lorraine M. [Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Liu, Shan-Lu, E-mail: liushan@missouri.edu [Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada); Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211-7310 (United States)

    2011-12-20

    Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are two closely related oncogenic retroviruses that share the same cellular receptor yet exhibit distinct fusogenicity and infectivity. Here, we find that the low fusogenicity of ENTV envelope protein (Env) is not because of receptor binding, but lies in its intrinsic insensitivity to receptor-mediated triggering for fusion at low pH. Distinct from JSRV, shedding of ENTV surface (SU) subunit into culture medium was not enhanced by a soluble form of receptor, Hyal2 (sHyal2), and sHyal2 was unable to effectively inactivate the ENTV pseudovirions. Remarkably, replacing either of the two amino acid residues, N191 or S195, located in the ENTV SU with the corresponding JSRV residues, H191 or G195, markedly increased the Env-mediated membrane fusion activity and infection. Reciprocal amino acid substitutions also partly switched the sensitivities of ENTV and JSRV pseudovirions to sHyal2-mediated SU shedding and inactivation. While N191 is responsible for an extra N-linked glycosylation of ENTV SU relative to that of JSRV, S195 possibly forms a hydrogen bond with a surrounding amino acid residue. Molecular modeling of the pre-fusion structure of JSRV Env predicts that the segment of SU that contains H191 to G195 contacts the fusion peptide and suggests that the H191N and G195S changes seen in ENTV may stabilize its pre-fusion structure against receptor priming and therefore modulate fusion activation by Hyal2. In summary, our study reveals critical determinants in the SU subunits of JSRV and ENTV Env proteins that likely regulate their local structures and thereby differential receptor-mediated fusion activation at low pH, and these findings explain, at least in part, their distinct viral infectivity.

  15. Single residues in the surface subunits of oncogenic sheep retrovirus envelopes distinguish receptor-mediated triggering for fusion at low pH and infection

    Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are two closely related oncogenic retroviruses that share the same cellular receptor yet exhibit distinct fusogenicity and infectivity. Here, we find that the low fusogenicity of ENTV envelope protein (Env) is not because of receptor binding, but lies in its intrinsic insensitivity to receptor-mediated triggering for fusion at low pH. Distinct from JSRV, shedding of ENTV surface (SU) subunit into culture medium was not enhanced by a soluble form of receptor, Hyal2 (sHyal2), and sHyal2 was unable to effectively inactivate the ENTV pseudovirions. Remarkably, replacing either of the two amino acid residues, N191 or S195, located in the ENTV SU with the corresponding JSRV residues, H191 or G195, markedly increased the Env-mediated membrane fusion activity and infection. Reciprocal amino acid substitutions also partly switched the sensitivities of ENTV and JSRV pseudovirions to sHyal2-mediated SU shedding and inactivation. While N191 is responsible for an extra N-linked glycosylation of ENTV SU relative to that of JSRV, S195 possibly forms a hydrogen bond with a surrounding amino acid residue. Molecular modeling of the pre-fusion structure of JSRV Env predicts that the segment of SU that contains H191 to G195 contacts the fusion peptide and suggests that the H191N and G195S changes seen in ENTV may stabilize its pre-fusion structure against receptor priming and therefore modulate fusion activation by Hyal2. In summary, our study reveals critical determinants in the SU subunits of JSRV and ENTV Env proteins that likely regulate their local structures and thereby differential receptor-mediated fusion activation at low pH, and these findings explain, at least in part, their distinct viral infectivity.

  16. Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1 receptor-mediated p38MAP kinase independently of angiotensin II.

    Li Lin

    Full Text Available Angiotensin II (Ang II type 1 (AT1 receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6 mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment of cardiomyocyte autophagy using LC3b-II. Losartan, an AT1 receptor blocker, but not PD123319, the AT2 inhibitor, was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy was significantly inhibited by Losartan in the absence of Ang II. Taken together, our results indicate that mechanical stress triggers cardiomyocyte autophagy through AT1 receptor-mediated activation of p38MAP kinase independently of Ang II.

  17. Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway.

    Wang, Yan-Juan; Ren, Qing-Guo; Gong, Wei-Gang; Wu, Di; Tang, Xiang; Li, Xiao-Li; Wu, Fang-Fang; Bai, Feng; Xu, Lin; Zhang, Zhi-Jun

    2016-03-22

    Tau hyperphosphorylation is an important pathological feature of Alzheimer's disease (AD). To investigate whether escitalopram could inhibit amyloid-β (Aβ)-induced tau hyperphosphorylation and the underlying mechanisms, we treated the rat primary hippocampal neurons with Aβ1-42 and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aβ1-42-induced tau hyperphosphorylation. In addition, escitalopram activated the Akt/GSK-3β pathway, and the PI3K inhibitor LY294002 blocked the attenuation of tau hyperphosphorylation induced by escitalopram. Moreover, the 5-HT1A receptor agonist 8-OH-DPAT also activated the Akt/GSK-3β pathway and decreased Aβ1-42-induced tau hyperphosphorylation. Furthermore, the 5-HT1A receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3β pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aβ1-42 induced impairment of neurite outgrowth and spine density, and reversed Aβ1-42 induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aβ1-42-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway. PMID:26950279

  18. Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to β Amyloid via Protein Kinase C

    Ji Jia

    2016-01-01

    Full Text Available Background. Reducing β amyloid- (Aβ- induced microglial activation is considered to be effective in treating Alzheimer’s disease (AD. Nicotine attenuates Aβ-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state or alternative activated state (M2 state; the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aβ-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process. Methods. We used Aβ1–42 to activate N9 microglial cells and observed nicotine-induced effects on microglial M1 and M2 biomarkers by using western blot, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA. Results. We found that nicotine reduced the levels of M1 state markers, including inducible nitric oxide synthase (iNOS expression and tumor necrosis factor α (TNF-α and interleukin- (IL- 6 releases; meanwhile, it increased the levels of M2 state markers, including arginase-1 (Arg-1 expression and brain-derived neurotrophic factor (BDNF release, in the Aβ-stimulated microglia. Coadministration of cannabinoid CB2 receptor antagonist or protein kinase C (PKC inhibitor partially abolished the nicotine-induced effects. Conclusion. These findings indicated that cannabinoid CB2 receptor mediates nicotine-induced anti-inflammation in microglia exposed to Aβ via PKC.

  19. Metabolism of glycosylated human salivary amylase: in vivo plasma clearance by rat hepatic endothelial cells and in vitro receptor mediated pinocytosis by rat macrophages

    Niesen, T.E.; Alpers, D.H.; Stahl, P.D.; Rosenblum, J.L.

    1984-09-01

    Salivary-type amylase normally comprises about 60% of the amylase activity in human serum, but only a small fraction is a glycosylated isoenzyme (amylase A). In contrast, 1/3 of amylase in human saliva is glycosylated. Since glycosylation can affect circulatory clearance, we studied the clearance of amylase A in rats and its uptake by rat alveolar macrophages. Following intravenous injection, /sup 125/I-labeled amylase A disappeared rapidly from plasma (t 1/2 . 9 min) and accumulated in the liver. Simultaneous injection of mannose-albumin slowed its clearance to a rate comparable to that of /sup 125/I-labeled nonglycosylated salivary amylase (t 1/2 . 45 min). In contrast, galactose-albumin had no effect. Electron microscope autoradiography of the liver following injection of /sup 125/I-labeled amylase A revealed a localization of grains over the hepatic endothelial cells. In vitro studies indicated that amylase A is taken up by alveolar macrophages via receptor-mediated pinocytosis. Uptake was linear over time, saturable, and inhibited by mannan and mannose-albumin, but not by galactose-albumin. We conclude that amylase A, which is a naturally occurring human glycoprotein with at most three terminal L-fucose residues per molecule, is recognized in rats by a mannose receptor located on hepatic endothelial cells. We speculate that this receptor, by rapidly clearing circulating amylase A, may be responsible for the low level of amylase A in human serum.

  20. Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia.

    Pamenter, Matthew E; Dzal, Yvonne A; Milsom, William K

    2015-02-01

    Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O₂ for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 ± 2.9 to 12.1 ± 0.3 ml O₂ min(-1) kg(-1), and 1412 ± 244 to 417 ± 62 ml min(-1) kg(-1), respectively; p tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR. PMID:25520355

  1. Optogenetic Evocation of Field Inhibitory Postsynaptic Potentials in Hippocampal Slices: A Simple and Reliable Approach for Studying Pharmacological Effects on GABAA and GABAB Receptor-Mediated Neurotransmission

    Julien eDine

    2014-01-01

    Full Text Available The GABAergic system is the main source of inhibition in the mammalian brain. Consequently, much effort is still made to develop new modulators of GABAergic synaptic transmission. In contrast to glutamatergic postsynaptic potentials (PSPs, accurate monitoring of GABA receptor-mediated PSPs (GABAR-PSPs and their pharmacological modulation in brain tissue invariably requires the use of intracellular recording techniques. However, these techniques are expensive, time- and labor-consuming, and, in case of the frequently employed whole-cell patch-clamp configuration, impact on intracellular ion concentrations, signaling cascades, and pH buffering systems. Here, we describe a novel approach to circumvent these drawbacks. In particular, we demonstrate in mouse hippocampal slices that selective optogenetic activation of interneurons leads to prominent field inhibitory GABAAR- and GABABR-PSPs in area CA1 which are easily and reliably detectable by a single extracellular recording electrode. The field PSPs exhibit typical temporal and pharmacological characteristics, display pronounced paired-pulse depression, and remain stable over many consecutive evocations. Additionally validating the methodological value of this approach, we further show that the neuroactive steroid 5-THDOC (5 µM shifts the inhibitory GABAAR-PSPs towards excitatory ones.

  2. Application of feed-forward control in management of sudden outbreak of influenza A H1N1 virus infection%前馈控制应用于甲型H1N1流感突发疫情的护理管理

    程红; 王霞

    2011-01-01

    目的 探讨综合医院突发疫情护理管理的方法和措施,避免工作的盲目性,提高防控医院感染的应急能力和安全性.方法 通过网络平台和本地疾控中心收集相关信息,制定甲型H1N1流感应急预案,组织护理人员培训,准备相关物资与技术;在应对疫情过程中,不断完善应急预案和工作流程,加强质量控制.结果 2009年5~12月,我院共救治确诊甲型H1N1流感病例21例,其中危重患者8例,全部治愈出院,无一例死亡,未发生医院感染.结论 建立和落实前馈控制管理,可以使护理人员在突发疫情到达之前掌握相关信息,进行相关知识的学习和操作演练;护理管理者提前对可能出现的问题进行预测,并采取预防措施,保证护理安全.%Objective To explore management of sudden outbreak of infectious diseases in general hospitals, to avoid blindness in work, to improve medical staff's response capability in handling emergency and to guarantee safety of medical care. Methods We collected relevant information through network platform and local disease control centers, formulated a contingency plan of managing influenza A H1N1 virus infection, applied the plan in training program for the staff, and prepared related materials and technologies. In handling the H1N1 epidemic, we continued to make better adjustment of the emergency plan and work processes, and reinforced quality control of nursing service. Results From May to December of 2009, we admitted 21 cases of confirmed influenza A H1N1 infections; among them, 8 cases were critically ill. All patients were cured and discharged without death cases. Nosocomial infection did not occur. Conclusion Establishment and implementation of feed-forward control helps nurses grasp a picture of related information before the arrival of an epidemic contingency, enable them to learn related knowledge and to start the drill of nursing skills. Nurse managers are able to predict potential

  3. Increased desensitization of dopamine D₂ receptor-mediated response in the ventral tegmental area in the absence of adenosine A(2A) receptors.

    Al-Hasani, R; Foster, J D; Metaxas, A; Ledent, C; Hourani, S M O; Kitchen, I; Chen, Y

    2011-09-01

    G-protein coupled receptors interact to provide additional regulatory mechanisms for neurotransmitter signaling. Adenosine A(2A) receptors are expressed at a high density in striatal neurons, where they closely interact with dopamine D₂ receptors and modulate effects of dopamine and responses to psychostimulants. A(2A) receptors are expressed at much lower densities in other forebrain neurons but play a more prominent yet opposing role to striatal receptors in response to psychostimulants in mice. It is, therefore, possible that A(2A) receptors expressed at low levels elsewhere in the brain may also regulate neurotransmitter systems and modulate neuronal functions. Dopamine D₂ receptors play an important role in autoinhibition of neuronal firing in dopamine neurons of the ventral tegmental area (VTA) and dopamine release in other brain areas. Here, we examined the effect of A(2A) receptor deletion on D₂ receptor-mediated inhibition of neuronal firing in dopamine neurons in the VTA. Spontaneous activity of dopamine neurons was recorded in midbrain slices, and concentration-dependent effects of the dopamine D₂ receptor agonist, quinpirole, was compared between wild-type and A(2A) knockout mice. The potency of quinpirole applied in single concentrations and the expression of D₂ receptors were not altered in the VTA of the knockout mice. However, quinpirole applied in stepwise escalating concentrations caused significantly reduced maximal inhibition in A(2A) knockout mice, indicating an enhanced agonist-induced desensitization of D₂ receptors in the absence of A(2A) receptors. The A(2A) receptor agonist, CGS21680, did not exert any effect on dopamine neuron firing or response to quinpirole, revealing a novel non-pharmacological interaction between adenosine A(2A) receptors and dopaminergic neurotransmission in midbrain dopamine neurons. Altered D₂ receptor desensitization may result in changes in dopamine neuron firing rate and pattern and dopamine

  4. Exposure to 50 Hz magnetic field modulates GABAA currents in cerebellar granule neurons through an EP receptor-mediated PKC pathway.

    Yang, Guang; Ren, Zhen; Mei, Yan-Ai

    2015-10-01

    Previous work from both our lab and others have indicated that exposure to 50 Hz magnetic fields (ELF-MF) was able to modify ion channel functions. However, very few studies have investigated the effects of MF on γ-aminobutyric acid (GABA) type A receptors (GABA(A) Rs) channel functioning, which are fundamental to overall neuronal excitability. Here, our major goal is to reveal the potential effects of ELF-MF on GABA(A) Rs activity in rat cerebellar granule neurons (CGNs). Our results indicated that exposing CGNs to 1 mT ELF-MF for 60 min. significantly increased GABA(A) R currents without modifying sensitivity to GABA. However, activation of PKA by db-cAMP failed to do so, but led to a slight decrease instead. On the other hand, PKC activation or inhibition by PMA or Bis and Docosahexaenoic acid (DHA) mimicked or eliminated the field-induced-increase of GABA(A) R currents. Western blot analysis indicated that the intracellular levels of phosphorylated PKC (pPKC) were significantly elevated after 60 min. of ELF-MF exposure, which was subsequently blocked by application of DHA or EP1 receptor-specific (prostaglandin E receptor 1) antagonist (SC19220), but not by EP2-EP4 receptor-specific antagonists. SC19220 also significantly inhibited the ELF-MF-induced elevation on GABA(A) R currents. Together, these data obviously demonstrated for the first time that neuronal GABA(A) currents are significantly increased by ELF-MF exposure, and also suggest that these effects are mediated via an EP1 receptor-mediated PKC pathway. Future work will focus on a more comprehensive analysis of the physiological and/or pathological consequences of these effects. PMID:26176998

  5. Exposure to 50 Hz magnetic field modulates GABAA currents in cerebellar granule neurons through an EP receptor-mediated PKC pathway

    Yang, Guang; Ren, Zhen; Mei, Yan-Ai

    2015-01-01

    Previous work from both our lab and others have indicated that exposure to 50 Hz magnetic fields (ELF-MF) was able to modify ion channel functions. However, very few studies have investigated the effects of MF on γ-aminobutyric acid (GABA) type A receptors (GABAARs) channel functioning, which are fundamental to overall neuronal excitability. Here, our major goal is to reveal the potential effects of ELF-MF on GABAARs activity in rat cerebellar granule neurons (CGNs). Our results indicated that exposing CGNs to 1 mT ELF-MF for 60 min. significantly increased GABAAR currents without modifying sensitivity to GABA. However, activation of PKA by db-cAMP failed to do so, but led to a slight decrease instead. On the other hand, PKC activation or inhibition by PMA or Bis and Docosahexaenoic acid (DHA) mimicked or eliminated the field-induced-increase of GABAAR currents. Western blot analysis indicated that the intracellular levels of phosphorylated PKC (pPKC) were significantly elevated after 60 min. of ELF-MF exposure, which was subsequently blocked by application of DHA or EP1 receptor-specific (prostaglandin E receptor 1) antagonist (SC19220), but not by EP2-EP4 receptor-specific antagonists. SC19220 also significantly inhibited the ELF-MF-induced elevation on GABAAR currents. Together, these data obviously demonstrated for the first time that neuronal GABAA currents are significantly increased by ELF-MF exposure, and also suggest that these effects are mediated via an EP1 receptor-mediated PKC pathway. Future work will focus on a more comprehensive analysis of the physiological and/or pathological consequences of these effects. PMID:26176998

  6. Striatal adenosine A{sub 2A} receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [{sup 18}F]-MRS5425

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Shinkre, Bidhan [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Ma Ying [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Niu Gang [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Trenkle, William C. [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jacobson, Kenneth A. [Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Chen Xiaoyuan [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Kiesewetter, Dale O., E-mail: dk7k@nih.gov [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States)

    2011-08-15

    Introduction: A{sub 2A} receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an {sup 18}F-labeled A{sub 2A} analog radiotracer ([{sup 18}F]-MRS5425) for A{sub 2A} receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A{sub 2A} receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [{sup 18}F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D{sub 2} agonist quinpirole (1.0 mg/kg) or D{sub 2} antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A{sub 2A} receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  7. Striatal adenosine A2A receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [18F]-MRS5425

    Introduction: A2A receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an 18F-labeled A2A analog radiotracer ([18F]-MRS5425) for A2A receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A2A receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [18F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D2 agonist quinpirole (1.0 mg/kg) or D2 antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A2A receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  8. Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

    Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased 45Ca2+ uptake into the cell monolayer, and (f) increased 86Rb+ uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca2+ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca2+-mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca2+ gating

  9. Activation of the sigma receptor 1 modulates AMPA receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells.

    Liu, Lei-Lei; Deng, Qin-Qin; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

    2016-09-22

    Sigma receptor (σR), a unique receptor family, is classified into three subtypes: σR1, σR2 and σR3. It was previously shown that σR1 activation induced by 1μM SKF10047 (SKF) suppressed N-methyl-d-aspartate (NMDA) receptor-mediated responses of rat retinal ganglion cells (GCs) and the suppression was mediated by a distinct Ca(2+)-dependent phospholipase C (PLC)-protein kinase C (PKC) pathway. In the present work, using whole-cell patch-clamp techniques in rat retinal slice preparations, we further demonstrate that SKF of higher dosage (50μM) significantly suppressed AMPA receptor (AMPAR)-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) of retinal ON-type GCs (ON GCs), and the effect was reversed by the σR1 antagonist BD1047, suggesting the involvement of σR1. The SKF (50μM) effect was unlikely due to a change in glutamate release from bipolar cells, as suggested by the unaltered paired-pulse ratio (PPR) of AMPAR-mediated EPSCs of ON GCs. SKF (50μM) did not change L-EPSCs of ON GCs when the G protein inhibitor GDP-β-S or the protein kinase G (PKG) inhibitor KT5823 was intracellularly infused. Calcium imaging further revealed that SKF (50μM) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50μM) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50μM) effect is Ca(2+)-independent, PKG-dependent, but not involving PKA, PI-PLC pathways. PMID:27373906

  10. Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated.

    Kennett, G A; Trail, B; Bright, F

    1998-12-01

    The 5-HT2B receptor agonist, BW 723C86 (10, 30(mg/kg i.p. 30 min pre-test), increased the number of punishments accepted in a rat Vogel drinking conflict paradigm over 3 min, as did the benzodiazepine anxiolytics, chlordiazepoxide (2.5-10 mg/kg p.o. 1 h pre-test) and alprazolam (0.2-5 mg/kg p.o. 1 h pre-test), but not the 5-HT2C/2B receptor agonist, m-chlorophenylpiperazine (mCPP, 0.3-3 mg/kg i.p) or the 5-HT1A receptor agonist, buspirone (5-20 mg/kg p.o. 1 h pre-test). The effect of BW 723C86 was unlikely to be secondary to enhanced thirst, as BW 723C86 did not increase the time that rats with free access to water spent drinking, nor did it reduce sensitivity to shock in the apparatus. The anti-punishment effect of BW 723C86 was opposed by prior treatment with the 5-HT2/2B receptor antagonist, SB-206553 (10 and 20 mg/kg p.o. 1 h pre-test), and the selective 5-HT2B receptor antagonist, SB-215505 (1 and 3 mg/kg p.o. 1 h pre-test), but not by the selective 5-HT2C receptor antagonist, SB-242084 (5 mg/kg p.o.), or the 5-HT1A receptor antagonist, WAY 100635 (0.1 or 0.3 mg/kg s.c. 30 min pre-test). Thus, the anti-punishment action of BW 723C86 is likely to be 5-HT2B receptor mediated. This is consistent with previous reports that BW 723C86 exhibited anxiolytic-like properties in both the social interaction and Geller-Seifter conflict tests. PMID:9886683