WorldWideScience

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

  1. Additive Feed Forward Control with Neural Networks

    DEFF Research Database (Denmark)

    Sørensen, O.

    1999-01-01

    This paper demonstrates a method to control a non-linear, multivariable, noisy process using trained neural networks. The basis for the method is a trained neural network controller acting as the inverse process model. A training method for obtaining such an inverse process model is applied....... A 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 placed in a supplementary pure feed-forward path to an existing feedback controller. This concept benefits from the fact, that an existing, traditional designed, feedback controller can be retained without any modifications, and after training the connection of the neural network feed-forward controller...

  2. Propagating Synchrony in Feed-Forward Networks

    Directory of Open Access Journals (Sweden)

    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

    Energy Technology Data Exchange (ETDEWEB)

    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. Somatosensory integration controlled by dynamic thalamocortical feed-forward inhibition.

    Science.gov (United States)

    Gabernet, Laetitia; Jadhav, Shantanu P; Feldman, Daniel E; Carandini, Matteo; Scanziani, Massimo

    2005-10-20

    The temporal features of tactile stimuli are faithfully represented by the activity of neurons in the somatosensory cortex. However, the cellular mechanisms that enable cortical neurons to report accurate temporal information are not known. Here, we show that in the rodent barrel cortex, the temporal window for integration of thalamic inputs is under the control of thalamocortical feed-forward inhibition and can vary from 1 to 10 ms. A single thalamic fiber can trigger feed-forward inhibition and contacts both excitatory and inhibitory cortical neurons. The dynamics of feed-forward inhibition exceed those of each individual synapse in the circuit and are captured by a simple disynaptic model of the thalamocortical projection. The variations in the integration window produce changes in the temporal precision of cortical responses to whisker stimulation. Hence, feed-forward inhibitory circuits, classically known to sharpen spatial contrast of tactile inputs, also increase the temporal resolution in the somatosensory cortex.

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

    Science.gov (United States)

    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. Learning Process of a Stochastic Feed-Forward Neural Network

    Science.gov (United States)

    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.

  7. A brief review of feed-forward neural networks

    OpenAIRE

    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.

  8. Flow of Information in Feed-Forward Deep Neural Networks

    OpenAIRE

    Khadivi, Pejman; Tandon, Ravi; Ramakrishnan, Naren

    2016-01-01

    Feed-forward deep neural networks have been used extensively in various machine learning applications. Developing a precise understanding of the underling behavior of neural networks is crucial for their efficient deployment. In this paper, we use an information theoretic approach to study the flow of information in a neural network and to determine how entropy of information changes between consecutive layers. Moreover, using the Information Bottleneck principle, we develop a constrained opt...

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

    Science.gov (United States)

    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

  10. Feed Forward Neural Network for Solid Waste Image Classification

    OpenAIRE

    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...

  11. Noise propagation with interlinked feed-forward pathways

    Science.gov (United States)

    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

  12. Feed-forward control of a redundant motor system.

    Science.gov (United States)

    Goodman, Simon R; Latash, Mark L

    2006-09-01

    We describe a model of feed-forward control of a redundant motor system and validate it using, as examples, tasks of multi-finger force production. The model assumes the existence of two input signals at an upper level of the control hierarchy, related and unrelated to a task variable. Knowledge of the Jacobian of the system is assumed at the level of generation of elemental variables (variables at the level of effectors). Variance at the level of elemental variables is considered as the sum of two components, related and unrelated to variability in the task variable. An index of stabilization of the task variable is similarly introduced as to how it was done in several studies using the framework of the uncontrolled manifold hypothesis. Several phenomena have been simulated including data point distributions corresponding to presence and absence of force-stabilizing synergies in two-finger tasks, changes in synergies with practice, and changes in synergy indices in preparation to a fast action. The model is discussed in comparison to other models of control of multi-element systems based on feedback processes. It shows that patterns of structured variability in the space of elemental variables can result from feed-forward processes. Relations of the model to the equilibrium-point hypothesis are also discussed. PMID:16838148

  13. Topological reversibility and causality in feed-forward networks

    Energy Technology Data Exchange (ETDEWEB)

    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. Feed forward neural networks modeling for K-P interactions

    International Nuclear Information System (INIS)

    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

  15. PSO optimized Feed Forward Neural Network for offline Signature Classification

    Directory of Open Access Journals (Sweden)

    Pratik R. Hajare

    2015-07-01

    Full Text Available The paper is based on feed forward neural network (FFNN optimization by particle swarm intelligence (PSI used to provide initial weights and biases to train neural network. Once the weights and biases are found using Particle swarm optimization (PSO with neural network used as training algorithm for specified epoch, the same are used to train the neural network for training and classification of benchmark problems. Further the approach is tested for offline signature classifications. A comparison is made between normal FFNN with random weights and biases and FFNN with particle swarm optimized weights and biases. Firstly, the performance is tested on two benchmark databases for neural network, The Breast Cancer Database and the Diabetic Database. Result shows that neural network performs better with initial weights and biases obtained by Particle Swarm optimization. The network converges faster with PSO obtained initial weights and biases for FFNN and classification accuracy is increased.

  16. The mechanism of synchronization in feed-forward neuronal networks

    Energy Technology Data Exchange (ETDEWEB)

    Goedeke, S; Diesmann, M [Bernstein Center for Computational Neuroscience, Albert-Ludwigs-University, Freiburg (Germany)], E-mail: diesmann@brain.riken.jp

    2008-01-15

    Synchronization in feed-forward subnetworks of the brain has been proposed to explain the precisely timed spike patterns observed in experiments. While the attractor dynamics of these networks is now well understood, the underlying single neuron mechanisms remain unexplained. Previous attempts have captured the effects of the highly fluctuating membrane potential by relating spike intensity f(U) to the instantaneous voltage U generated by the input. This article shows that f is high during the rise and low during the decay of U(t), demonstrating that the U-dot-dependence of f, not refractoriness, is essential for synchronization. Moreover, the bifurcation scenario is quantitatively described by a simple f(U,U-dot) relationship. These findings suggest f(U,U-dot) as the relevant model class for the investigation of neural synchronization phenomena in a noisy environment.

  17. Feed-Forward Control of Kite Power Systems

    International Nuclear Information System (INIS)

    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

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

    CERN Document Server

    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.

  19. Feed-Forward Control of Kite Power Systems

    Science.gov (United States)

    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.

  20. Feed-forward regulation of phagocytosis by Entamoeba histolytica.

    Science.gov (United States)

    Sateriale, Adam; Vaithilingam, Archana; Donnelly, Liam; Miller, Peter; Huston, Christopher D

    2012-12-01

    The parasitic protozoan Entamoeba histolytica is aptly named for its capacity to destroy host tissue. When E. histolytica trophozoites invade the lamina propria of a host colon, extracellular matrices are degraded while host cells are killed and phagocytosed. The ability of E. histolytica to phagocytose host cells correlates with virulence in vivo. In order to better understand the mechanism of phagocytosis, we used an E. histolytica Affymetrix microarray chip to measure the total gene expression of phagocytic and nonphagocytic subpopulations. Using paramagnetic beads coated with a known host ligand that stimulates phagocytosis, phagocytic and nonphagocytic amoebae from a single culture were purified. Microarray analysis of the subpopulations identified 121 genes with >2-fold higher expression in phagocytic than in nonphagocytic amoebae. Functional annotation identified genes encoding proteins involved in actin binding and cytoskeletal organization as highly enriched gene clusters. Post hoc analyses of selected genes showed that the gene expression profile identified in the microarray experiment did not exist prior to cell sorting but rather was stimulated through phagocytosis. Further, these expression profiles correlated with an increase in phagocytic ability, as E. histolytica cultures exposed to an initial stimulus of phagocytosis showed increased phagocytic ability upon a second stimulus. To our knowledge, this is the first description of such feed-forward regulation of gene expression and phagocytic ability in a phagocyte.

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

    International Nuclear Information System (INIS)

    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. Review of feed forward neural network classification preprocessing techniques

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

    Science.gov (United States)

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

    OpenAIRE

    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...

  6. Endothelin receptor-mediated vasodilatation

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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

    CERN Document Server

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

    International Nuclear Information System (INIS)

    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

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

    NARCIS (Netherlands)

    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. High-speed linear optics quantum computing using active feed-forward.

    Science.gov (United States)

    Prevedel, Robert; Walther, Philip; Tiefenbacher, Felix; Böhi, Pascal; Kaltenbaek, Rainer; Jennewein, Thomas; Zeilinger, Anton

    2007-01-01

    As information carriers in quantum computing, photonic qubits have the advantage of undergoing negligible decoherence. However, the absence of any significant photon-photon interaction is problematic for the realization of non-trivial two-qubit gates. One solution is to introduce an effective nonlinearity by measurements resulting in probabilistic gate operations. In one-way quantum computation, the random quantum measurement error can be overcome by applying a feed-forward technique, such that the future measurement basis depends on earlier measurement results. This technique is crucial for achieving deterministic quantum computation once a cluster state (the highly entangled multiparticle state on which one-way quantum computation is based) is prepared. Here we realize a concatenated scheme of measurement and active feed-forward in a one-way quantum computing experiment. We demonstrate that, for a perfect cluster state and no photon loss, our quantum computation scheme would operate with good fidelity and that our feed-forward components function with very high speed and low error for detected photons. With present technology, the individual computational step (in our case the individual feed-forward cycle) can be operated in less than 150 ns using electro-optical modulators. This is an important result for the future development of one-way quantum computers, whose large-scale implementation will depend on advances in the production and detection of the required highly entangled cluster states.

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

    Science.gov (United States)

    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

    Directory of Open Access Journals (Sweden)

    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. Development of a combined feed forward-feedback system for an electron Linac

    Energy Technology Data Exchange (ETDEWEB)

    Meier, E. [School of Physics, Monash University, Wellington Rd, Clayton VIC 3800 (Australia) and Australian Synchrotron, 800 Blackburn Rd, Clayton VIC 3168 (Australia); FERMI-Elettra, Sincrotrone Trieste, S.S. 14km 163.5 in AREA Science Park, 34012 Basovizza, Trieste (Italy)], E-mail: evelyne.meier@synchrotron.org.au; Biedron, S.G. [Department of Defense Project Office, Argonne National Laboratory, IL 60439 (United States); FERMI-Elettra, Sincrotrone Trieste, S.S. 14km 163.5 in AREA Science Park, 34012 Basovizza, Trieste (Italy)], E-mail: biedron@anl.gov; LeBlanc, G. [Australian Synchrotron, 800 Blackburn Rd, Clayton VIC 3168 (Australia)], E-mail: Greg.LeBlanc@synchrotron.org.au; Morgan, M.J. [School of Physics, Monash University, Wellington Rd, Clayton VIC 3800 (Australia)], E-mail: Michael.Morgan@sci.monash.edu.au; Wu, J. [LCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Rd, Menlo Park, CA 94025 (United States)], E-mail: jhwu@slac.stanford.edu

    2009-10-11

    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.

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

    CERN Document Server

    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...

  16. Feed-forward inhibition: a novel cellular mechanism for the analgesic effect of substance P

    Directory of Open Access Journals (Sweden)

    Yoshimura Megumu

    2005-11-01

    Full Text Available Abstract Substance P (SP is a neuropeptide well known for its contribution to pain transmission in the spinal cord, however, less is known about the possible modulatory effects of SP. A new study by Gu and colleagues, published in Molecular Pain (2005, 1:20, describes its potential role in feed-forward inhibition in lamina V of the dorsal horn of the spinal cord. This inhibition seems to function through a direct excitation of GABAergic interneurons by substance P released from primary afferent fibers and has a distinct temporal phase of action from the well-described glutamate-dependent feed-forward inhibition. It is believed that through this inhibition, substance P can balance nociceptive output from the spinal cord.

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

    CERN Document Server

    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.

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

    OpenAIRE

    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....

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

    Institute of Scientific and Technical Information of China (English)

    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%.

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  2. Evidence Feed Forward Hidden Markov Model: A New Type Of Hidden Markov Model

    Directory of Open Access Journals (Sweden)

    Michael Del Rose

    2011-01-01

    Full Text Available The ability to predict the intentions of people based solely on their visual actions is a skill only performed by humans and animals. The intelligence of current computer algorithms has not reached this level of complexity, but there are several research efforts that are working towards it. With the number of classification algorithms available, it is hard to determine which algorithm works best for a particular situation. In classification of visual human intent data, Hidden Markov Models (HMM, and their variants, are leading candidates. The inability of HMMs to provide a probability in the observation to observation linkages is a big downfall in this classification technique. If a person is visually identifying an action of another person, they monitor patterns in the observations. By estimating the next observation, people have the ability to summarize the actions, and thus determine, with pretty good accuracy, the intention of the person performing the action. These visual cues and linkages are important in creating intelligent algorithms for determining human actions based on visual observations. The Evidence Feed Forward Hidden Markov Model is a newly developed algorithm which provides observation to observation linkages. The following research addresses the theory behind Evidence Feed Forward HMMs, provides mathematical proofs of their learning of these parameters to optimize the likelihood of observations with a Evidence Feed Forwards HMM, which is important in all computational intelligence algorithm, and gives comparative examples with standard HMMs in classification of both visual action data and measurement data; thus providing a strong base for Evidence Feed Forward HMMs in classification of many types of problems.

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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. Higher order feed-forward control of reticle writing error fingerprints

    Science.gov (United States)

    van Haren, Richard; Cekli, Hakki Ergun; Beltman, Jan; Pastol, Anne; Sundermann, Frank; Gatefait, Maxime

    2015-10-01

    The understanding and control of the intra-field overlay budget becomes crucial particularly after the introduction of multi-patterning applications. The intra-field overlay budget is built-up out of many contributors, each with its own characteristic. Some of them are (semi-)static like the reticle writing error (RWE) fingerprint, the scanner lens fingerprint, or the intra-field processing signature. Others are more dynamic. Examples are reticle heating and lens heating due to the absorption of a small portion of the exposure light. Ideally, all overlay contributors that are understood and known could be taken out of the feed-back control loop and send as feed-forward corrections to the scanner. As a consequence, only non-correctable overlay residuals are measured on the wafer. In the current work, we have studied the possibility to characterize the reticle writing error fingerprint by an off-line position measurement tool and use this information to send feed-forward corrections to the ASML TWINSCANTM exposure tool. The current work is an extension of the work we published earlier. To this end, we have selected a reticle pair out of 50 production reticles that are used to manufacture a 28-nm technology device. These two reticles are special in the sense that the delta fingerprint contains a significant higher order RWE signature. While previously only the linear parameters were sent as feed-forward corrections to the ASML TWINSCANTM exposure tool, this time we additionally demonstrate the capability to correct for the non-linear terms as well. Since the concept heavily relies on the quality of the off-line mask registration measurements, a state-of-the-art reticle registration tool was chosen. Special care was taken to eliminate any effects of the tool induced shifts that may affect the quality of the measurements. The on-wafer overlay verification measurements were performed on an ASML YieldStar metrology tool as well as on a different vendor tool. In conclusion

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

    Institute of Scientific and Technical Information of China (English)

    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.

  9. Control of transcriptional variability by overlapping feed-forward regulatory motifs.

    Science.gov (United States)

    Ratushny, Alexander V; Ramsey, Stephen A; Roda, Oriol; Wan, Yakun; Smith, Jennifer J; Aitchison, John D

    2008-10-01

    In yeast, beta-oxidation of fatty acids (FAs) takes place in the peroxisome, an organelle whose size and number are controlled in response to environmental cues. The expression of genes required for peroxisome assembly and function is controlled by a transcriptional regulatory network that is induced by FAs such as oleate. The core FA-responsive transcriptional network consists of carbon source-sensing transcription factors that regulate key target genes through an overlapping feed-forward network motif (OFFNM). However, a systems-level understanding of the function of this network architecture in regulating dynamic FA-induced gene expression is lacking. The specific role of the OFFNM in regulating the dynamic and cell-population transcriptional response to oleate was investigated using a kinetic model comprised of four core transcription factor genes (ADR1, OAF1, PIP2, and OAF3) and two reporter genes (CTA1 and POT1) that are indicative of peroxisome induction. Simulations of the model suggest that 1), the intrinsic Adr1p-driven feed-forward loop reduces the steady-state expression variability of target genes; 2), the parallel Oaf3p-driven inhibitory feed-forward loop modulates the dynamic response of target genes to a transiently varying oleate concentration; and 3), heterodimerization of Oaf1p and Pip2p does not appear to have a noise-reducing function in the context of oleate-dependent expression of target genes. The OFFNM is highly overrepresented in the yeast regulome, suggesting that the specific functions described for the OFFNM, or other properties of this motif, provide a selective advantage. PMID:18621837

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

    International Nuclear Information System (INIS)

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

    CERN Document Server

    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.

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

    OpenAIRE

    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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Feed-forward control of a solid oxide fuel cell system with anode offgas recycle

    Science.gov (United States)

    Carré, Maxime; Brandenburger, Ralf; Friede, Wolfgang; Lapicque, François; Limbeck, Uwe; da Silva, Pedro

    2015-05-01

    In this work a combined heat and power unit (CHP unit) based on the solid oxide fuel cell (SOFC) technology is analysed. This unit has a special feature: the anode offgas is partially recycled to the anode inlet. Thus it is possible to increase the electrical efficiency and the system can be operated without external water feeding. A feed-forward control concept which allows secure operating conditions of the CHP unit as well as a maximization of its electrical efficiency is introduced and validated experimentally. The control algorithm requires a limited number of measurement values and few deterministic relations for its description.

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

    CERN Document Server

    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.

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

    Science.gov (United States)

    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.

  18. Top-level dynamics and the regulated gene response of feed-forward loop transcriptional motifs

    Science.gov (United States)

    Mayo, Michael; Abdelzaher, Ahmed; Perkins, Edward J.; Ghosh, Preetam

    2014-09-01

    Feed-forward loops are hierarchical three-node transcriptional subnetworks, wherein a top-level protein regulates the activity of a target gene via two paths: a direct-regulatory path, and an indirect route, whereby the top-level proteins act implicitly through an intermediate transcription factor. Using a transcriptional network of the model bacterium Escherichia coli, we confirmed that nearly all types of feed-forward loop were significantly overrepresented in the bacterial network. We then used mathematical modeling to study their dynamics by manipulating the rise times of the top-level protein concentration, termed the induction time, through alteration of the protein destruction rates. Rise times of the regulated proteins exhibited two qualitatively different regimes, depending on whether top-level inductions were "fast" or "slow." In the fast regime, rise times were nearly independent of rapid top-level inductions, indicative of biological robustness, and occurred when RNA production rate-limits the protein yield. Alternatively, the protein rise times were dependent upon slower top-level inductions, greater than approximately one bacterial cell cycle. An equation is given for this crossover, which depends upon three parameters of the direct-regulatory path: transcriptional cooperation at the DNA-binding site, a protein-DNA dissociation constant, and the relative magnitude of the top-level protien concentration.

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

    Science.gov (United States)

    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

    International Nuclear Information System (INIS)

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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)

  3. Noise performance of a feed-forward scheme for carrier-envelope phase stabilization

    Science.gov (United States)

    Koke, S.; Anderson, A.; Frei, H.; Assion, A.; Steinmeyer, G.

    2011-09-01

    The noise performance of a feed-forward scheme for carrier-envelope phase stabilization is discussed. This scheme uses an acousto-optic frequency shifter to directly correct for fluctuations of the carrier-envelope phase in a pulse train emitted by a mode-locked laser without manipulating the intracavity dispersion. Generation of zero-offset frequency combs is demonstrated. Furthermore, it is shown that pump laser noise has only a minor effect on the achievable performance. Limited only by the travel time of the acoustic wave in the shifter, pump laser noise can be corrected up to near-megahertz frequencies, which yields superior noise performance compared to traditional feedback operation. Residual phase jitters down to 45 mrad are experimentally verified.

  4. Learning in feed-forward neural networks by improving the performance

    Science.gov (United States)

    Gordon, Mirta B.; Pereto, Pierre; Rodriguez-Girones, Miguel

    1992-06-01

    Statistical mechanics is used to derive a new learning rule for a feed-forward neural network with one hidden layer. Generalization to multilayer neural networks is straightforward, and proceeds in the same way as backpropagation. We consider a neural network as a physical system, that can be in different states. There are as many possible states as patterns in the learning set. The energy of each level is proportional to the stability of the corresponding pattern. The statistical mechanics free energy of the system, which we call performance, is a maximum for the synaptic strengths that stabilize all the patterns. We propose a learning algorithm that looks for synaptic strengths that maximize the network's performance. Patterns with lower stabilities are more effective in driving the learning process because they have a higher statistical weight. Taking different temperatures for different layers improves the results.

  5. Design of Phase Feed Forward System in CTF3 and Performance of Fast Beam Phase Monitors

    CERN Document Server

    Skowronski, P K; Ghigo, A; Marcellini, F; Burrows, PN; Christian, GB; Perry, C; Gerbershagen, A; Roberts, J; Ikarios, E

    2013-01-01

    The CLIC two beam acceleration technology requires a drive beam phase stability better than 0.3 deg rms at 12 GHz, corresponding to a timing stability below 50 fs rms. For this reason the CLIC design includes a phase stabilization feed-forward system. It relies on precise beam phase measurements and their subsequent correction in a chicane with the help of fast kickers. A prototype of such a system is being installed in the CLIC Test Facility CTF3. In this paper its design and implementation is described in detail. Additionally, the performance of the precision phase monitor prototypes installed at the end of the CTF3 linac, as measured with the drive beam, is presented.

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

    Directory of Open Access Journals (Sweden)

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  14. Assessing the stability of an ALPAO deformable mirror for feed-forward operation.

    Science.gov (United States)

    Bitenc, Urban; Bharmal, Nazim A; Morris, Timothy J; Myers, Richard M

    2014-05-19

    A deformable mirror (DM) is a mirror whose surface can be deformed in order to correct for optical aberrations. If a DM is used in a feed-forward operation (i.e. without feed-back, also known as open-loop) it is, among other requirements, crucial that a set of actuator commands repeatedly results in the same surface shape. We have tested an ALPAO DM against this criterion, by repeatedly applying a set of actuator commands over hours and monitoring the DM shape with an interferometer. We found that if the surface shape was held to shape A for several hours, then changed to a second shape, ℬ, the DM surface will drift from this new shape over the course of several hours. During this period the root-mean-square (RMS) of the deviation from shape ℬ can exceed 30% of the RMS of the difference between shapes A and ℬ. This can correspond to a surface deviation with RMS of several hundred nanometers, and would severely impact the resulting performance of an AO system using such a DM in a feed-forward operation. We have developed a model to correct for the time-varying surface shape in software by continuously adapting the actuator commands over the stabilization period. Application of the stabilisation procedure allows the surface to remain stable to within 4 nm RMS after a period of 6 minutes. We also provide a suggestion on how to improve the repeatability of surface response to different sets of actuator commands, which can be affected by the surface drift. PMID:24921361

  15. Mitigation of ground motion effects in linear accelerators via feed-forward control

    Science.gov (United States)

    Pfingstner, J.; Artoos, K.; Charrondiere, C.; Janssens, St.; Patecki, M.; Renier, Y.; Schulte, D.; Tomás, R.; Jeremie, A.; Kubo, K.; Kuroda, S.; Naito, T.; Okugi, T.; Tauchi, T.; Terunuma, N.

    2014-12-01

    Ground motion is a severe problem for many particle accelerators, since it excites beam oscillations, which decrease the beam quality and create beam-beam offset (at colliders). Orbit feedback systems can only compensate ground motion effects at frequencies significantly smaller than the beam repetition rate. In linear colliders, where the repetition rate is low, additional counter measures have to be put in place. For this reason, a ground motion mitigation method based on feed-forward control is presented in this paper. It has several advantages compared to other techniques (stabilization systems and intratrain feedback systems) such as cost reduction and potential performance improvement. An analytical model is presented that allows the derivation of hardware specification and performance estimates for a specific accelerator and ground motion model. At the Accelerator Test Facility (ATF2), ground motion sensors have been installed to verify the feasibility of important parts of the mitigation strategy. In experimental studies, it has been shown that beam excitations due to ground motion can be predicted from ground motion measurements on a pulse-to-pulse basis. Correlations of up to 80% between the estimated and measured orbit jitter have been observed. Additionally, an orbit jitter source was identified and has been removed, which halved the orbit jitter power at ATF2 and shows that the feed-forward scheme is also very useful for the detection of installation issues. We believe that the presented mitigation method has the potential to reduce costs and improve the performance of linear colliders and potentially other linear accelerators.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    DEFF Research Database (Denmark)

    Wang, Haojie; Han, Minxiao; Yan, Wenli;

    2016-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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…

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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,

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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.)

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

    Institute of Scientific and Technical Information of China (English)

    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.

  7. Feed-forward carrier phase recovery for offset-QAM Nyquist WDM transmission.

    Science.gov (United States)

    Tang, Haoyuan; Xiang, Meng; Fu, Songnian; Tang, Ming; Shum, Perry; Liu, Deming

    2015-03-01

    Due to the half symbol delay between in-phase and quadrature components for offset quadrature amplitude modulation (OQAM) signal, phase noise cannot only lead to constellation rotation but also introduce additional crosstalk. Therefore, OQAM signal has very poor tolerance to the laser linewidth. Here, we carry out a semi-analytical investigation of phase noise induced crosstalk during OQAM Nyquist WDM transmission, and find that the carrier phase recovery (CPR) has to be implemented prior to the inter-symbol-interference (ISI) equalization. Then, after a function separation of polarization de-multiplexing and ISI equalization, we propose a new DSP flow with a linewidth-tolerant blind feed-forward CPR scheme for OQAM signal. Its effectiveness is verified under the scenario of 5-channel 28-Gbaud polarization multiplexing (PM) OQAM Nyquist WDM systems. A tolerance of linewidth and symbol duration products of 6.5×10(-4) and 1.1×10(-4) is secured for 4-OQAM and 16-OQAM, respectively, given 1-dB required-OSNR penalty at BER = 10(-3).

  8. Optimal Feed Forward MLPArchitecture for Off-Line Cursive Numeral Recognition

    Directory of Open Access Journals (Sweden)

    Vijaypal Singh Dhaka

    2010-01-01

    Full Text Available The purpose of this work is to analyze the performance of back-propagation feed-forward algorithm using various different activation functions for the neurons of hidden and output layer and varying the number of neurons in the hidden layer. For sample creation, 250 numerals were gathered form 35 people of different ages including male and female. After binarization, these numerals were clubbed together to form training patterns for the neural network. Network was trained to learn its behavior by adjusting the connection strengths at every iteration. The conjugate gradient descent of each presented training pattern was calculated to identify the minima on the error surface for each training pattern. Experiments were performed by selecting different combinations of two activation functions out of the three activation functions logsig, tansig and purelin for the neurons of the hidden and output layers and the results revealed that as the number of neurons in the hidden layer is increased, the network gets trained in small number of epochs and the percentage recognition accuracy of the neural network was observed to increase up to certain level and then it starts decreasing when number of hidden neurons exceeds a certain level.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Flatness-based model inverse for feed-forward braking control

    Science.gov (United States)

    de Vries, Edwin; Fehn, Achim; Rixen, Daniel

    2010-12-01

    For modern cars an increasing number of driver assistance systems have been developed. Some of these systems interfere/assist with the braking of a car. Here, a brake actuation algorithm for each individual wheel that can respond to both driver inputs and artificial vehicle deceleration set points is developed. The algorithm consists of a feed-forward control that ensures, within the modelled system plant, the optimal behaviour of the vehicle. For the quarter-car model with LuGre-tyre behavioural model, an inverse model can be derived using v x as the 'flat output', that is, the input for the inverse model. A number of time derivatives of the flat output are required to calculate the model input, brake torque. Polynomial trajectory planning provides the needed time derivatives of the deceleration request. The transition time of the planning can be adjusted to meet actuator constraints. It is shown that the output of the trajectory planning would ripple and introduce a time delay when a gradual continuous increase of deceleration is requested by the driver. Derivative filters are then considered: the Bessel filter provides the best symmetry in its step response. A filter of same order and with negative real-poles is also used, exhibiting no overshoot nor ringing. For these reasons, the 'real-poles' filter would be preferred over the Bessel filter. The half-car model can be used to predict the change in normal load on the front and rear axle due to the pitching of the vehicle. The anticipated dynamic variation of the wheel load can be included in the inverse model, even though it is based on a quarter-car. Brake force distribution proportional to normal load is established. It provides more natural and simpler equations than a fixed force ratio strategy.

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

    Science.gov (United States)

    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

  12. Two-layer tree-connected feed-forward neural network model for neural cryptography

    Science.gov (United States)

    Lei, Xinyu; Liao, Xiaofeng; Chen, Fei; Huang, Tingwen

    2013-03-01

    Neural synchronization by means of mutual learning provides an avenue to design public key exchange protocols, bringing about what is known as neural cryptography. Two identically structured neural networks learn from each other and reach full synchronization eventually. The full synchronization enables two networks to have the same weight, which can be used as a secret key for many subsequent cryptographic purposes. It is striking to observe that after the first decade of neural cryptography, the tree parity machine (TPM) network with hidden unit K=3 appears to be the sole network that is suitable for a neural protocol. No convincingly secure neural protocol is well designed by using other network structures despite considerable research efforts. With the goal of overcoming the limitations of a suitable network structure, in this paper we develop a two-layer tree-connected feed-forward neural network (TTFNN) model for a neural protocol. The TTFNN model captures the notion that two partners are capable of exchanging a vector with multiple bits in each time step. An in-depth study of the dynamic process of TTFNN-based protocols is then undertaken, based upon which a feasible condition is theoretically obtained to seek applicable protocols. Afterward, according to two analytically derived heuristic rules, a complete methodology for designing feasible TTFNN-based protocols is elaborated. A variety of feasible neural protocols are constructed, which exhibit the effectiveness and benefits of the proposed model. With another look from the perspective of application, TTFNN-based instances, which can outperform the conventional TPM-based protocol with respect to synchronization speed, are also experimentally confirmed.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Luz, Yotam; Shamir, Maoz

    2016-01-01

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  3. Prediction of gas hydrate saturation throughout the seismic section in Krishna Godavari basin using multivariate linear regression and multi-layer feed forward neural network approach

    Digital Repository Service at National Institute of Oceanography (India)

    Singh, Y.; Nair, R.R.; Singh, H.; Datta, P.; Jaiswal, P.; Dewangan, P.; Ramprasad, T.

    Stepwise linear regression, multi-layer feed forward neural (MLFN) network method was used to predict the 2D distribution of P-wave velocity, resistivity, porosity, and gas hydrate saturation throughout seismic section NGHP-01 in the Krishna...

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

    OpenAIRE

    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...

  5. Exploiting low-gap beam position monitors in orbit stabilization feedback and feed-forward systems at ELETTRA

    Energy Technology Data Exchange (ETDEWEB)

    Bulfone, D.; Forchi, V.; Gaio, G.; Lonza, M. [Sincrotrone Trieste, Trieste (Italy)

    2003-07-01

    Two low-gap electron Beam Position Monitors (BPMs) equipped with digital detector electronics have been installed either side of an Insertion Device (ID) long straight section at ELETTRA. The new BPMs have been integrated in a fast local orbit feedback system that stabilizes the electron beam orbit at the center of the ID. They also provide the basic measurements that are used by a feed-forward correction system compensating for the orbit distortion produced by an Electromagnetic Elliptical Wiggler (EEW) operated at high switching frequencies (up to 100 Hz) of the horizontal field. The main results achieved are presented. (author)

  6. Exploiting low-gap beam position monitors in orbit stabilization feedback and feed-forward systems at ELETTRA

    CERN Document Server

    Bulfone, D; Gaio, G; Lonza, M

    2003-01-01

    Two low-gap electron Beam Position Monitors (BPMs) equipped with digital detector electronics have been installed either side of an Insertion Device (ID) long straight section at ELETTRA. The new BPMs have been integrated in a fast local orbit feedback system that stabilizes the electron beam orbit at the center of the ID. They also provide the basic measurements that are used by a feed-forward correction system compensating for the orbit distortion produced by an Electromagnetic Elliptical Wiggler (EEW) operated at high switching frequencies (up to 100 Hz) of the horizontal field. The main results achieved are presented. (author)

  7. Long-term carrier-envelope-phase-stable few-cycle pulses by use of the feed-forward method.

    Science.gov (United States)

    Lücking, Fabian; Assion, Andreas; Apolonski, Alexander; Krausz, Ferenc; Steinmeyer, Günter

    2012-06-01

    The feed-forward technique has recently revolutionized carrier-envelope phase (CEP) stabilization, enabling unprecedented values of residual phase jitter. Nevertheless, its demonstrations have hitherto remained in a proof-of-principle state. Here we show that pulse quality and power issues can be solved, leading to few-cycle pulses with good beam quality. Making use of stable interferometers, we achieve day-long CEP-stable operation of the setup. Out-of-loop RMS phase noise amounts to less than 30 mrad in 20 s, with more than 24 h of CEP-locked operation being demonstrated. PMID:22660126

  8. Analysis of the feed-forward method for the referencing of a CW laser to a frequency comb.

    Science.gov (United States)

    Gatti, D; Sala, T; Gambetta, A; Coluccelli, N; Conti, G Nunzi; Galzerano, G; Laporta, P; Marangoni, M

    2012-10-22

    We report on a comprehensive theoretical and experimental analysis of the feed-forward method for external frequency stabilization of a continuous wave laser against a frequency comb. Application of the method to a distributed feedback diode laser at 1.55 μm allows line narrowing from 800 to 10 kHz, with frequency noise reduction by more than 2 decades up to a Fourier frequency of 100 kHz and a maximum control bandwidth of 0.8 MHz. The results are consistent with a relative phase fluctuation of 1.4 rad rms, as limited by uncompensated high-frequency noise of the slave laser. PMID:23187255

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

    OpenAIRE

    Afsaneh Salehi; Farzin Piltan; Mahmoud Mousavi; Arzhang Khajeh; Mohammad Reza Rashidian

    2013-01-01

    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 ...

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Improvement of multi-parameter-based feed-forward coagulant dosing control systems with feed-back functionalities.

    Science.gov (United States)

    Liu, W; Ratnaweera, H

    2016-01-01

    Coagulant dosing control in drinking and wastewater treatment plants (WWTPs) is often limited to flow proportional concepts. The advanced multi-parameter-based dosing control systems have significantly reduced coagulant consumption and improved outlet qualities. Due to the long retention time in separation stages, these models are mostly based on feed-forward (FF) models. This paper demonstrates the improvement of such models with feed-back (FB) concepts with simplifications, making it possible to use even in systems with long separation stages. Full-scale case studies from a drinking water treatment plant and a WWTP are presented. The model qualities were improved by the dosage adjustment of the FB model, ranging from 66% to 197% of the FF model. Hence, the outlet qualities became more stable and coagulant consumption was further reduced in the range of 3.7%-15.5%.

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

    Science.gov (United States)

    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.

  17. Regulation of apoptotic c-Jun N-terminal kinase signaling by a stabilization-based feed-forward loop.

    Science.gov (United States)

    Xu, Zhiheng; Kukekov, Nikolay V; Greene, Lloyd A

    2005-11-01

    A sequential kinase cascade culminating in activation of c-Jun N-terminal kinases (JNKs) plays a fundamental role in promoting apoptotic death in many cellular contexts. The mechanisms by which this pathway is engaged in response to apoptotic stimuli and suppressed in viable cells are largely unknown. Here, we show that apoptotic stimuli increase endogenous cellular levels of pathway components, including POSH, mixed lineage kinases (MLKs), and JNK interacting protein 1, and that this effect occurs through protein stabilization and requires the presence of POSH as well as activation of MLKs and JNKs. Our findings suggest a self-amplifying, feed-forward loop mechanism by which apoptotic stimuli promote the stabilization of JNK pathway components, thereby contributing to cell death. PMID:16260609

  18. Regulation of Apoptotic c-Jun N-Terminal Kinase Signaling by a Stabilization-Based Feed-Forward Loop†

    Science.gov (United States)

    Xu, Zhiheng; Kukekov, Nikolay V.; Greene, Lloyd A.

    2005-01-01

    A sequential kinase cascade culminating in activation of c-Jun N-terminal kinases (JNKs) plays a fundamental role in promoting apoptotic death in many cellular contexts. The mechanisms by which this pathway is engaged in response to apoptotic stimuli and suppressed in viable cells are largely unknown. Here, we show that apoptotic stimuli increase endogenous cellular levels of pathway components, including POSH, mixed lineage kinases (MLKs), and JNK interacting protein 1, and that this effect occurs through protein stabilization and requires the presence of POSH as well as activation of MLKs and JNKs. Our findings suggest a self-amplifying, feed-forward loop mechanism by which apoptotic stimuli promote the stabilization of JNK pathway components, thereby contributing to cell death. PMID:16260609

  19. Long-term CEP-stable high energy few-cycle pulses using the feed-forward method

    Science.gov (United States)

    Lücking, Fabian; Anderson, Alexandria; Apolonskiy, Alexander; Krausz, Ferenc; Steinmeyer, Günter; Tempea, Gabriel; Assion, Andreas

    2012-03-01

    The feed-forward technique has recently revolutionized carrier-envelope phase stabilization, enabling unprecedented values of residual phase jitter. Nevertheless, in its original demonstrations the stabilized beam exhibited angular and temporal dispersion. We demonstrate that these problems can be solved, resulting in few-cycle pulses with good beam quality. This in turn enables the use of monolithic interferometers, providing excellent long-term stability of the system. Out-of-loop RMS phase noise of less than 80 mrad over 33 minutes (0.5 mHz to 5 kHz) is measured, i.e., a value that has previously been reported for a few seconds integration time. The current method promises to enable reliable operation of CEP-stable systems over several days.

  20. Spectral multiplexing for scalable quantum photonics using an atomic frequency comb quantum memory and feed-forward control.

    Science.gov (United States)

    Sinclair, Neil; Saglamyurek, Erhan; Mallahzadeh, Hassan; Slater, Joshua A; George, Mathew; Ricken, Raimund; Hedges, Morgan P; Oblak, Daniel; Simon, Christoph; Sohler, Wolfgang; Tittel, Wolfgang

    2014-08-01

    Future multiphoton applications of quantum optics and quantum information science require quantum memories that simultaneously store many photon states, each encoded into a different optical mode, and enable one to select the mapping between any input and a specific retrieved mode during storage. Here we show, with the example of a quantum repeater, how to employ spectrally multiplexed states and memories with fixed storage times that allow such mapping between spectral modes. Furthermore, using a Ti:Tm:LiNbO_{3} waveguide cooled to 3 K, a phase modulator, and a spectral filter, we demonstrate storage followed by the required feed-forward-controlled frequency manipulation with time-bin qubits encoded into up to 26 multiplexed spectral modes and 97% fidelity.

  1. Feed-forward and visual feedback control of head roll orientation in wasps (Polistes humilis, Vespidae, Hymenoptera).

    Science.gov (United States)

    Viollet, Stéphane; Zeil, Jochen

    2013-04-01

    Flying insects keep their visual system horizontally aligned, suggesting that gaze stabilization is a crucial first step in flight control. Unlike flies, hymenopteran insects such as bees and wasps do not have halteres that provide fast, feed-forward angular rate information to stabilize head orientation in the presence of body rotations. We tested whether hymenopteran insects use inertial (mechanosensory) information to control head orientation from other sources, such as the wings, by applying periodic roll perturbations to male Polistes humilis wasps flying in tether under different visual conditions indoors and in natural outdoor conditions. We oscillated the thorax of the insects with frequency-modulated sinusoids (chirps) with frequencies increasing from 0.2 to 2 Hz at a maximal amplitude of 50 deg peak-to-peak and maximal angular velocity of ±245 deg s(-1). We found that head roll stabilization is best outdoors, but completely absent in uniform visual conditions and in darkness. Step responses confirm that compensatory head roll movements are purely visually driven. Modelling step responses indicates that head roll stabilization is achieved by merging information on head angular velocity, presumably provided by motion-sensitive neurons and information on head orientation, presumably provided by light level integration across the compound eyes and/or ocelli (dorsal light response). Body roll in free flight reaches amplitudes of ±40 deg and angular velocities greater than 1000 deg s(-1), while head orientation remains horizontal for most of the time to within ±10 deg. In free flight, we did not find a delay between spontaneous body roll and compensatory head movements, and suggest that this is evidence for the contribution of a feed-forward control to head stabilization.

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

    Science.gov (United States)

    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.

  3. Feed-forward and visual feedback control of head roll orientation in wasps (Polistes humilis, Vespidae, Hymenoptera).

    Science.gov (United States)

    Viollet, Stéphane; Zeil, Jochen

    2013-04-01

    Flying insects keep their visual system horizontally aligned, suggesting that gaze stabilization is a crucial first step in flight control. Unlike flies, hymenopteran insects such as bees and wasps do not have halteres that provide fast, feed-forward angular rate information to stabilize head orientation in the presence of body rotations. We tested whether hymenopteran insects use inertial (mechanosensory) information to control head orientation from other sources, such as the wings, by applying periodic roll perturbations to male Polistes humilis wasps flying in tether under different visual conditions indoors and in natural outdoor conditions. We oscillated the thorax of the insects with frequency-modulated sinusoids (chirps) with frequencies increasing from 0.2 to 2 Hz at a maximal amplitude of 50 deg peak-to-peak and maximal angular velocity of ±245 deg s(-1). We found that head roll stabilization is best outdoors, but completely absent in uniform visual conditions and in darkness. Step responses confirm that compensatory head roll movements are purely visually driven. Modelling step responses indicates that head roll stabilization is achieved by merging information on head angular velocity, presumably provided by motion-sensitive neurons and information on head orientation, presumably provided by light level integration across the compound eyes and/or ocelli (dorsal light response). Body roll in free flight reaches amplitudes of ±40 deg and angular velocities greater than 1000 deg s(-1), while head orientation remains horizontal for most of the time to within ±10 deg. In free flight, we did not find a delay between spontaneous body roll and compensatory head movements, and suggest that this is evidence for the contribution of a feed-forward control to head stabilization. PMID:23239889

  4. A feed-forward Hopfield neural network algorithm (FHNNA) with a colour satellite image for water quality mapping

    Science.gov (United States)

    Asal Kzar, Ahmed; Mat Jafri, M. Z.; Hwee San, Lim; Al-Zuky, Ali A.; Mutter, Kussay N.; Hassan Al-Saleh, Anwar

    2016-06-01

    There are many techniques that have been given for water quality problem, but the remote sensing techniques have proven their success, especially when the artificial neural networks are used as mathematical models with these techniques. Hopfield neural network is one type of artificial neural networks which is common, fast, simple, and efficient, but it when it deals with images that have more than two colours such as remote sensing images. This work has attempted to solve this problem via modifying the network that deals with colour remote sensing images for water quality mapping. A Feed-forward Hopfield Neural Network Algorithm (FHNNA) was modified and used with a satellite colour image from type of Thailand earth observation system (THEOS) for TSS mapping in the Penang strait, Malaysia, through the classification of TSS concentrations. The new algorithm is based essentially on three modifications: using HNN as feed-forward network, considering the weights of bitplanes, and non-self-architecture or zero diagonal of weight matrix, in addition, it depends on a validation data. The achieved map was colour-coded for visual interpretation. The efficiency of the new algorithm has found out by the higher correlation coefficient (R=0.979) and the lower root mean square error (RMSE=4.301) between the validation data that were divided into two groups. One used for the algorithm and the other used for validating the results. The comparison was with the minimum distance classifier. Therefore, TSS mapping of polluted water in Penang strait, Malaysia, can be performed using FHNNA with remote sensing technique (THEOS). It is a new and useful application of HNN, so it is a new model with remote sensing techniques for water quality mapping which is considered important environmental problem.

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

    Science.gov (United States)

    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

  6. RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation

    Science.gov (United States)

    Nishimoto, Satoko; Wilde, Susan M.; Wood, Sophie; Logan, Malcolm P.O.

    2015-01-01

    Summary The retinoic acid (RA)- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors. PMID:26212321

  7. RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation

    Directory of Open Access Journals (Sweden)

    Satoko Nishimoto

    2015-08-01

    Full Text Available The retinoic acid (RA- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors.

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Dim star fringe stabilization demonstration using pathlength feed-forward on the SIM testbed 3 (STB3)

    Science.gov (United States)

    Goullioud, Renaud; Alvarez-Salazar, Oscar S.; Nemati, Bijan

    2003-02-01

    Future space-based optical interferometers such as the Space Interferometer Mission require fringe stabilization to the level of nanometers in order to produce astrometric data at the micro-arc-second level. Even the best attitude control system available to date will not be able to stabilize the attitude of a several thousand pound spacecraft to a few milli-arc-seconds. Active pathlength control is usually implemented to compensate for attitude drift of the spacecraft. This issue has been addressed in previous experiments while tracking bright stars. In the case of dim stars, as the sensor bandwidth falls below one hertz, feedback control will not provide sufficient rejection. However, stabilization of the fringes from a dim-star down to the nanometer level can be done open loop using information from additional interferometers looking at bright guide stars. The STB3 testbed developed at the Jet Propulsion Laboratory features three optical interferometers sharing a common baseline, dynamically representative to the SIM interferometer. An artificial star feeding the interferometers is installed on a separate optics bench. Voice coils are used to simulate the attitude motion of the spacecraft by moving the entire bench. Data measured on STB3 show that fringe motion of a dim star due to spacecraft attitude changes can be attenuated by 80 dB at 0.1Hz without feedback control, using only information from two guide stars. This paper describes the STB3 setup, the pathlength feed-forward architecture, implementation issues and data collected with the system.

  12. Simultaneously precise frequency transfer and time synchronization using feed-forward compensation technique via 120 km fiber link

    Science.gov (United States)

    Chen, Xing; Lu, Jinlong; Cui, Yifan; Zhang, Jian; Lu, Xing; Tian, Xusheng; Ci, Cheng; Liu, Bo; Wu, Hong; Tang, Tingsong; Shi, Kebin; Zhang, Zhigang

    2015-12-01

    Precision time synchronization between two remote sites is desired in many applications such as global positioning satellite systems, long-baseline interferometry, coherent radar detection and fundamental physics constant measurements. The recently developed frequency dissemination technologies based on optical fiber link have improved the transfer instability to the level of 10-19/day at remote location. Therefore it is possible to keep clock oscillation at remote locations continuously corrected, or to reproduce a “virtual” clock on the remote location. However the initial alignment and the correction of 1 pps timing signal from time to time are still required, besides the highly stabilized clock frequency transfer between distant locations. Here we demonstrate a time synchronization based on an ultra-stable frequency transfer system via 120-km commercial fiber link by transferring an optical frequency comb. Both the phase noise compensation in frequency dissemination and temporal basis alignment in time synchronization were implemented by a feed-forward digital compensation (FFDC) technique. The fractional frequency instability was measured to be 6.18 × 10-20 at 2000 s. The timing deviation of time synchronization was measured to be 0.6 ps in 1500 s. This technique also can be applied in multi-node fiber network topology.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Role of Feed Forward Neural Networks Coupled with Genetic Algorithm in Capitalizing of Intracellular Alpha-Galactosidase Production by Acinetobacter sp.

    Directory of Open Access Journals (Sweden)

    Sirisha Edupuganti

    2014-01-01

    Full Text Available Alpha-galactosidase production in submerged fermentation by Acinetobacter sp. was optimized using feed forward neural networks and genetic algorithm (FFNN-GA. Six different parameters, pH, temperature, agitation speed, carbon source (raffinose, nitrogen source (tryptone, and K2HPO4, were chosen and used to construct 6-10-1 topology of feed forward neural network to study interactions between fermentation parameters and enzyme yield. The predicted values were further optimized by genetic algorithm (GA. The predictability of neural networks was further analysed by using mean squared error (MSE, root mean squared error (RMSE, mean absolute error (MAE, mean absolute percentage error (MAPE, and R2-value for training and testing data. Using hybrid neural networks and genetic algorithm, alpha-galactosidase production was improved from 7.5 U/mL to 10.2 U/mL.

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

    Energy Technology Data Exchange (ETDEWEB)

    Meier, E., E-mail: evelyne.meier@synchrotron.org.a [School of Physics, Monash University, Wellington Rd, Clayton, VIC 3800 (Australia) and Australian Synchrotron, 800 Blackburn Rd, Clayton, VIC 3168 (Australia) and FERMI-Elettra, Sincrotrone Trieste, S.S. 14km 163.5 in AREA Science Park, 34012 Basovizza, Trieste (Italy); Biedron, S.G., E-mail: biedron@anl.go [Department of Defense Project Office, Argonne National Laboratory, IL 60439 (United States); FERMI-Elettra, Sincrotrone Trieste, S.S. 14km 163.5 in AREA Science Park, 34012 Basovizza, Trieste (Italy); LeBlanc, G., E-mail: Greg.LeBlanc@synchrotron.org.a [Australian Synchrotron, 800 Blackburn Rd, Clayton, VIC 3168 (Australia); Morgan, M.J., E-mail: Michael.Morgan@sci.monash.edu.a [School of Physics, Monash University, Wellington Rd, Clayton, VIC 3800 (Australia); Wu, J., E-mail: jhwu@slac.stanford.ed [LCLS, SLAC National Accelerator Laboratory, 2575 Sand Hill Rd, Menlo Park, CA 94025 (United States)

    2009-11-11

    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.

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

    International Nuclear Information System (INIS)

    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

  2. A feed-forward circuit linking wingless, fat-dachsous signaling, and the warts-hippo pathway to Drosophila wing growth.

    Directory of Open Access Journals (Sweden)

    Myriam Zecca

    Full Text Available During development, the Drosophila wing primordium undergoes a dramatic increase in cell number and mass under the control of the long-range morphogens Wingless (Wg, a Wnt and Decapentaplegic (Dpp, a BMP. This process depends in part on the capacity of wing cells to recruit neighboring, non-wing cells into the wing primordium. Wing cells are defined by activity of the selector gene vestigial (vg and recruitment entails the production of a vg-dependent "feed-forward signal" that acts together with morphogen to induce vg expression in neighboring non-wing cells. Here, we identify the protocadherins Fat (Ft and Dachsous (Ds, the Warts-Hippo tumor suppressor pathway, and the transcriptional co-activator Yorkie (Yki, a YES associated protein, or YAP as components of the feed-forward signaling mechanism, and we show how this mechanism promotes wing growth in response to Wg. We find that vg generates the feed-forward signal by creating a steep differential in Ft-Ds signaling between wing and non-wing cells. This differential down-regulates Warts-Hippo pathway activity in non-wing cells, leading to a burst of Yki activity and the induction of vg in response to Wg. We posit that Wg propels wing growth at least in part by fueling a wave front of Ft-Ds signaling that propagates vg expression from one cell to the next.

  3. Deep learning in the small sample size setting: cascaded feed forward neural networks for medical image segmentation

    Science.gov (United States)

    Gaonkar, Bilwaj; Hovda, David; Martin, Neil; Macyszyn, Luke

    2016-03-01

    Deep Learning, refers to large set of neural network based algorithms, have emerged as promising machine- learning tools in the general imaging and computer vision domains. Convolutional neural networks (CNNs), a specific class of deep learning algorithms, have been extremely effective in object recognition and localization in natural images. A characteristic feature of CNNs, is the use of a locally connected multi layer topology that is inspired by the animal visual cortex (the most powerful vision system in existence). While CNNs, perform admirably in object identification and localization tasks, typically require training on extremely large datasets. Unfortunately, in medical image analysis, large datasets are either unavailable or are extremely expensive to obtain. Further, the primary tasks in medical imaging are organ identification and segmentation from 3D scans, which are different from the standard computer vision tasks of object recognition. Thus, in order to translate the advantages of deep learning to medical image analysis, there is a need to develop deep network topologies and training methodologies, that are geared towards medical imaging related tasks and can work in a setting where dataset sizes are relatively small. In this paper, we present a technique for stacked supervised training of deep feed forward neural networks for segmenting organs from medical scans. Each `neural network layer' in the stack is trained to identify a sub region of the original image, that contains the organ of interest. By layering several such stacks together a very deep neural network is constructed. Such a network can be used to identify extremely small regions of interest in extremely large images, inspite of a lack of clear contrast in the signal or easily identifiable shape characteristics. What is even more intriguing is that the network stack achieves accurate segmentation even when it is trained on a single image with manually labelled ground truth. We validate

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

    Directory of Open Access Journals (Sweden)

    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/.

  5. Asialoglycoprotein receptor mediated hepatocyte targeting - strategies and applications.

    Science.gov (United States)

    D'Souza, Anisha A; Devarajan, Padma V

    2015-04-10

    Hepatocyte resident afflictions continue to affect the human population unabated. The asialoglycoprotein receptor (ASGPR) is primarily expressed on hepatocytes and minimally on extra-hepatic cells. This makes it specifically attractive for receptor-mediated drug delivery with minimum concerns of toxicity. ASGPR facilitates internalization by clathrin-mediated endocytosis and exhibits high affinity for carbohydrates specifically galactose, N-acetylgalactosamine and glucose. Isomeric forms of sugar, galactose density and branching, spatial geometry and galactose linkages are key factors influencing ligand-receptor binding. Popular ligands for ASGPR mediated targeting are carbohydrate polymers, arabinogalactan and pullulan. Other ligands include galactose-bearing glycoproteins, glycopeptides and galactose modified polymers and lipids. Drug-ligand conjugates provide a viable strategy; nevertheless ligand-anchored nanocarriers provide an attractive option for ASGPR targeted delivery and are widely explored. The present review details various ligands and nanocarriers exploited for ASGPR mediated delivery of drugs to hepatocytes. Nanocarrier properties affecting ASGPR mediated uptake are discussed at length. The review also highlights the clinical relevance of ASGPR mediated targeting and applications in diagnostics. ASGPR mediated hepatocyte targeting provides great promise for improved therapy of hepatic afflictions.

  6. Cerebellar vermis H₂ receptors mediate fear memory consolidation in mice.

    Science.gov (United States)

    Gianlorenço, A C L; Riboldi, A M; Silva-Marques, B; Mattioli, R

    2015-02-01

    Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have a high density in the vermis and flocullus. Evidence supports that the cerebellar histaminergic system is involved in memory consolidation. Our recent study showed that histamine injections facilitate the retention of an inhibitory avoidance task, which was abolished by pretreatment with an H2 receptor antagonist. In the present study, we investigated the effects of intracerebellar post training injections of H1 and H2 receptor antagonists as well as the selective H2 receptor agonist on fear memory consolidation. The cerebellar vermi of male mice were implanted with guide cannulae, and after three days of recovery, the inhibitory avoidance test was performed. Immediately after a training session, animals received a microinjection of the following histaminergic drugs: experiment 1, saline or chlorpheniramine (0.016, 0.052 or 0.16 nmol); experiment 2, saline or ranitidine (0.57, 2.85 or 5.07 nmol); and experiment 3, saline or dimaprit (1, 2 or 4 nmol). Twenty-four hours later, a retention test was performed. The data were analyzed using one-way analysis of variance (ANOVA) and Duncan's tests. Animals microinjected with chlorpheniramine did not show any behavioral effects at the doses that we used. Intra-cerebellar injection of the H2 receptor antagonist ranitidine inhibited, while the selective H2 receptor agonist dimaprit facilitated, memory consolidation, suggesting that H2 receptors mediate memory consolidation in the inhibitory avoidance task in mice.

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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

  10. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. 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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  17. High-Speed Tracking Method Using Zero Phase Error Tracking-Feed-Forward (ZPET-FF) Control for High-Data-Transfer-Rate Optical Disk Drives

    Science.gov (United States)

    Koide, Daiichi; Yanagisawa, Hitoshi; Tokumaru, Haruki; Nakamura, Shoichi; Ohishi, Kiyoshi; Inomata, Koichi; Miyazaki, Toshimasa

    2004-07-01

    We describe the effectiveness of feed-forward control using the zero phase error tracking method (ZPET-FF control) of the tracking servo for high-data-transfer-rate optical disk drives, as we are developing an optical disk system to replace the conventional professional videotape recorder for recording high-definition television signals for news gathering or producing broadcast contents. The optical disk system requires a high-data-transfer-rate of more than 200 Mbps and large recording capacity. Therefore, fast and precise track-following control is indispensable. Here, we compare the characteristics of ZPET-FF control with those of conventional feedback control or repetitive control. Experimental results show that ZPET-FF control is more precise than feedback control, and the residual tracking error level is achieved with a tolerance of 10 nm at a linear velocity of 26 m/s in the experimental setup using a blue-violet laser optical head and high-density media. The feasibility of achieving precise ZPET-FF control at 15000 rpm is also presented.

  18. Analysis of speedup as function of block size and cluster size for parallel feed-forward neural networks on a Beowulf cluster.

    Science.gov (United States)

    Mörchen, Fabian

    2004-03-01

    The performance of feed-forward neural networks trained with the backpropagation algorithm on a dedicated Beowulf cluster is analyzed. The concept of training set parallelism is applied. A new model for run time and speedup prediction is developed. With the model the speedup and efficiency of one iteration of the neural networks can be estimated as a function of block size and cluster size. The model is applied to three example problems representing different applications and network architectures. The estimation of the model has a higher accuracy than traditional methods for run time estimation and can be efficiently calculated. Experiments show that speedup of one iteration does not necessarily translate to a shorter training time toward a given error level. To overcome this problem a heuristic extension to training set parallelism called weight averaging is developed. The results show that training in parallel should only be done on clusters with high performance network connections or a multiprocessor machine. A rule of thumb is given for how much network performance of the cluster is needed to achieve speedup of the training time for a neural network.

  19. Comparative determination of phosphate and silicate using molybdenum blue by radial basis function and feed-forward neural networks assisted by principal component analysis.

    Science.gov (United States)

    Afkhami, Abbas; Abbasi-Tarighat, Maryam

    2008-06-01

    In the present study, chemometric analysis of visible spectral data of phospho-and silico-molybdenum blue complexes was used to develop artificial neural networks (ANNs) for the simultaneous determination of the phosphate and silicate. Combinations of principal component analysis (PCA) with feed-forward neural networks (FFNNs) and radial basis function networks (RBFNs) were built and investigated. The structures of the models were simplified by using the corresponding important principal components as input instead of the original spectra. Number of inputs and hidden nodes, learning rate, transfer functions and number of epochs and SPREAD values were optimized. Performances of methods were tested with root mean square errors prediction (RMSEP, %), using synthetic solutions. The obtained satisfactory results indicate the applicability of this ANN approach based on PCA input selection for determination in highly spectral overlapping. The results obtained by FFNNs and by RBF networks were compared. The applicability of methods was investigated for synthetic samples, for detergent formulations, and for a river water sample.

  20. FoxM1 Drives a Feed-forward STAT3-activation Signaling Loop that Promotes the Self-renewal and Tumorigenicity of Glioblastoma Stem-like Cells

    Science.gov (United States)

    Gong, Ai-hua; Wei, Ping; Zhang, Sicong; Yao, Jun; Yuan, Ying; Zhou, Ai-dong; Lang, Frederick F.; Heimberger, Amy B.; Rao, Ganesh; Huang, Suyun

    2015-01-01

    The growth factor PDGF controls the development of glioblastoma (GBM) but its contribution to the function of GBM stem-like cells (GSC) has been little studied. Here we report that the transcription factor FoxM1 promotes PDGFA-STAT3 signaling to drive GSC self-renewal and tumorigenicity. In GBM we found a positive correlation between expression of FoxM1 and PDGF-A. In GSC and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. Analysis of the human cancer genomic database TCGA revealed that GBM express higher levels of STAT3, a PDGF-A effector signaling molecule, as compared with normal brain. FoxM1 regulated STAT3 transcription through interactions with the β-catenin/TCF4 complex. FoxM1 deficiency inhibited PDGF-A and STAT3 expression in neural stem cells and GSC, abolishing their stem-like and tumorigenic properties. Further mechanistic investigations defined a FoxM1-PDGFA-STAT3 feed-forward pathway that was sufficient to confer stem-like properties to glioma cells. Collectively, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells. PMID:25832656

  1. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

    Directory of Open Access Journals (Sweden)

    Cátia Vieira

    2014-01-01

    Full Text Available Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis lacks adenosine neuromodulation, which may contribute to acceleration of gastrointestinal transit. The loss of adenosine neuromodulation results from deficient accumulation of the nucleoside at the myenteric synapse despite the fact that the increases in ATP release were observed. Disparity between ATP outflow and adenosine deficit in postinflammatory ileitis is ascribed to feed-forward inhibition of ecto-5′-nucleotidase/CD73 by high extracellular ATP and/or ADP. Redistribution of NTPDase2, but not of NTPDase3, from ganglion cell bodies to myenteric nerve terminals leads to preferential ADP accumulation from released ATP, thus contributing to the prolonged inhibition of muscle-bound ecto-5′-nucleotidase/CD73 and to the delay of adenosine formation at the inflamed neuromuscular synapse. On the other hand, depression of endogenous adenosine accumulation may also occur due to enhancement of adenosine deaminase activity. Both membrane-bound and soluble forms of ecto-5′-nucleotidase/CD73 and adenosine deaminase were detected in the inflamed myenteric plexus. These findings provide novel therapeutic targets for inflammatory gut motility disorders.

  2. Feed-forward control of pressure of recycled gas main pipe%回炉煤气主管压力的前反馈控制

    Institute of Scientific and Technical Information of China (English)

    刘超; 宁芳青; 程抱友; 梅学书; 周游

    2015-01-01

    根据煤气主管压力调节阀的特性曲线,构建出压力调节阀改变量的数学模型,并在此模型的基础上,针对调节阀的特性及焦炉加热系统的工艺要求,利用前反馈的控制方法消除系统的阶跃干扰,使得回炉煤气主管压力能够稳定在给定压力上,系统现场运行效果良好.%According to the characteristics curve of the pressure control valve on gas main pipe,this paper establishes a mathematical model of variables of pressure control valve. On that basis,step dis-turbance of the system is removed with feed-forward control method according to the characteristic of control valve and process requirement of coke oven heating system,so that the pressure of recycled gas main pipe could be stabilized at the prescribed value,and the system has been well operated at site.

  3. A 2nd-Order Feed-Forward ∑-△ Modulator%一种2阶前馈方式∑-△调制器

    Institute of Scientific and Technical Information of China (English)

    李新; 杨森林; 梁洁

    2012-01-01

    The principle of Σ-Δ modulator was described. A 2nd-order feed-forwardΣ-Δ modulator was designed. The system function and zero pole distribution were analyzed to verify system characteristics, such as system stability, signal-to-noise ratio (SNR), spurious free dynamic range (SFDR) and effective number of bits (EOB). Behavioral modeling and simulation were made to validate the design. Test results showed that the circuit could realize conversion from analog signal to digital signal in the ADC path, which ensured reliability of the circuit%详细论述了∑-△调制器的工作原理,在此基础上设计了一种2阶前馈方式∑-△调制器.分析了系统函数以及零极点的分布情况,确认了系统稳定性、信噪比、无杂散动态范围、有效位数等系统特性.采用行为级建模与仿真,验证了设计的正确性.性能测试表明,芯片的ADC通路可以很好地实现模拟信号向数字信号的转换,保证了电路的可靠性.

  4. The Arabidopsis Transcription Factor NAC016 Promotes Drought Stress Responses by Repressing AREB1 Transcription through a Trifurcate Feed-Forward Regulatory Loop Involving NAP.

    Science.gov (United States)

    Sakuraba, Yasuhito; Kim, Ye-Sol; Han, Su-Hyun; Lee, Byoung-Doo; Paek, Nam-Chon

    2015-06-01

    Drought and other abiotic stresses negatively affect plant growth and development and thus reduce productivity. The plant-specific NAM/ATAF1/2/CUC2 (NAC) transcription factors have important roles in abiotic stress-responsive signaling. Here, we show that Arabidopsis thaliana NAC016 is involved in drought stress responses; nac016 mutants have high drought tolerance, and NAC016-overexpressing (NAC016-OX) plants have low drought tolerance. Using genome-wide gene expression microarray analysis and MEME motif searches, we identified the NAC016-specific binding motif (NAC16BM), GATTGGAT[AT]CA, in the promoters of genes downregulated in nac016-1 mutants. The NAC16BM sequence does not contain the core NAC binding motif CACG (or its reverse complement CGTG). NAC016 directly binds to the NAC16BM in the promoter of ABSCISIC ACID-RESPONSIVE ELEMENT BINDING PROTEIN1 (AREB1), which encodes a central transcription factor in the stress-responsive abscisic acid signaling pathway and represses AREB1 transcription. We found that knockout mutants of the NAC016 target gene NAC-LIKE, ACTIVATED BY AP3/PI (NAP) also exhibited strong drought tolerance; moreover, NAP binds to the AREB1 promoter and suppresses AREB1 transcription. Taking these results together, we propose that a trifurcate feed-forward pathway involving NAC016, NAP, and AREB1 functions in the drought stress response, in addition to affecting leaf senescence in Arabidopsis. PMID:26059204

  5. DMPD: Modulation of Toll-interleukin 1 receptor mediated signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15662540 Modulation of Toll-interleukin 1 receptor mediated signaling. Li X, Qin J....iated signaling. PubmedID 15662540 Title Modulation of Toll-interleukin 1 receptor media... J Mol Med. 2005 Apr;83(4):258-66. Epub 2005 Jan 21. (.png) (.svg) (.html) (.csml) Show Modulation of Toll-interleukin 1 receptor med

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

    OpenAIRE

    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...

  7. Experimental workflow for developing a feed forward strategy to control biomass growth and exploit maximum specific methane productivity of Methanothermobacter marburgensis in a biological methane production process (BMPP

    Directory of Open Access Journals (Sweden)

    Alexander Krajete

    2016-08-01

    Full Text Available Recently, interests for new biofuel generations allowing conversion of gaseous substrate(s to gaseous product(s arose for power to gas and waste to value applications. An example is biological methane production process (BMPP with Methanothermobacter marburgensis. The latter, can convert carbon dioxide (CO2 and hydrogen (H2, having different origins and purities, to methane (CH4, water and biomass. However, these gas converting bioprocesses are tendentiously gas limited processes and the specific methane productivity per biomass amount (qCH4 tends to be low. Therefore, this contribution proposes a workflow for the development of a feed forward strategy to control biomass, growth (rx and qCH4 in a continuous gas limited BMPP. The proposed workflow starts with a design of experiment (DoE to optimize media composition and search for a liquid based limitation to control selectively growth. From the DoE it came out that controlling biomass growth was possible independently of the dilution and gassing rate applied while not affecting methane evolution rates (MERs. This was done by shifting the process from a natural gas limited state to a controlled liquid limited growth. The latter allowed exploiting the maximum biocatalytic activity for methane formation of Methanothermobacter marburgensis. An increase of qCH4 from 42 to 129 mmolCH4 g−1 h−1 was achieved by applying a liquid limitation compare with the reference state. Finally, a verification experiment was done to verify the feeding strategy transferability to a different process configuration. This evidenced the ratio of the fed KH2PO4 to rx (R(FKH2PO4/rx has an appropriate parameter for scaling feeds in a continuous gas limited BMPP. In the verification experiment CH4 was produced in a single bioreactor step at a methane evolution rate (MER of   132 mmolCH4*L−1*h−1 at a CH4 purity of 93 [Vol.%].

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  10. 自适应前馈神经网络结构优化设计%An adaptive algorithm for designing optimal feed-forward neural network architecture

    Institute of Scientific and Technical Information of China (English)

    张昭昭; 乔俊飞; 杨刚

    2011-01-01

    针对多数前馈神经网络结构设计算法采取贪婪搜索策略而易陷入局部最优结构的问题,提出一种自适应前馈神经网络结构设计算法.该算法在网络训练过程中采取自适应寻优策略合并和分裂隐节点,达到设计最优神经网络结构的目的.在合并操作中,以互信息为准则对输出线性相关的隐节点进行合并;在分裂操作中,引入变异系数,有助于跳出局部最优网络结构.算法将合并和分裂操作之后的权值调整与网络对样本的学习过程结合,减少了网络对样本的学习次数,提高了网络的学习速度,增强了网络的泛化性能.非线性函数逼近结果表明,所提算法能得到更小的检测误差,最终网络结构紧凑.%Due to the fact that most algorithms use a greedy strategy in designing artificial neural networks which are susceptible to becoming trapped at the architectural local optimal point, an adaptive algorithm for designing an optimal feed-forward neural network was proposed. During the training process of the neural network, the adaptive optimization strategy was adopted to merge and split the hidden unit to design optimal neural network architecture. In the merge operation, the hidden units were merged based on mutual information criterion. In the split operation, a mutation coefficient was introduced to help jump out of locally optimal network. The process of adjusting the connection weight after merge and split operations was combined with the process of training the neural network. Therefore, the number of training samples was reduced, the training speed was increased, and the generalization performance was improved. The results of approximating non-linear functions show that the proposed algorithm can limit testing errors and a compact neural network structure.

  11. A Novel Feed-forward Voltage Control Strategy of the Boost Converter%一种新型Boost变换器前馈控制策略

    Institute of Scientific and Technical Information of China (English)

    王海波; 许路广; 朱胜辉; 杨秀; 桂谊; 夏晗

    2015-01-01

    In the stand-alone photovoltaic system with DC(direct current) bus-bar, stabilizing the DC bus volt-age is an important method to guarantee the efficient operation of the system, high power quality and long life of the battery. A novel topology that the MPPT of PV (maximum power point tracking of photovoltaic) boost converter and the DC bus are connected by another boost converter is proposed. Moreover, a new feed-for-ward control strategy is applied to the boost converter to stabilize the DC bus voltage: based on the voltage outer loop and current inner loop control, the input voltage and load current feed-forward loops are introduced to eliminate the fluctuation of DC bus voltage due to the change of the two factors mentioned above to improve the voltage-stabilizing performance of the system. The simulation compares DC bus voltage of double-loop con-trol and the control mentioned in this paper in case of voltage leap and verifies effectiveness of the above-mentioned control strategy.%在通过直流母线汇流的独立光伏发电系统中,维持直流母线电压恒定是保证系统的高效运行、较高的电能质量以及延长蓄电池的使用寿命的重要手段。提出一种在光伏MPPT Boost变换器后通过再一级Boost变换器与直流母线连接的网络结构,并采用新型的前馈控制策略实现对直流母线电压的稳定控制。该控制方法为,在原有的电流内环电压外环双环控制基础上引入负荷电流与输入电压的前馈环节,削除因二者的变动引起的直流母线电压波动,提高了系统的动态稳压性能。仿真比较了双环控制与本文所提控制在负荷电流与输入电压跃变情况下的直流母线电压,验证了所提控制策略的有效性。

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    RNA 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..., phosphorylation of ERK1/2 proteins and elevation of intracellular calcium level are required for endothelin ET(B) receptor-mediated contraction in rat mesenteric artery....

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

    DEFF Research Database (Denmark)

    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......(+)-solution was not modified after 1 day in culture medium. The experiments indicate that organ culture of rat coronary arteries upregulate endothelin ET(B) receptor-mediated contraction by inducing synthesis of new protein....... descending coronary arteries isolated from hearts of rats as response to application of the selective endothelin ET(B) receptor agonist, Sarafotoxin 6c and endothelin-1. In segments cultured 1 day in serum free Dulbecco's Modified Eagle's Medium, Sarafotoxin 6c induced a concentration dependent contraction...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  16. Research on Improving Machining Precision of CNC Machine Based on Velocity Feed-forward of FANUC System%基于FANUC系统速度前馈提高CNC机床加工精度的研究

    Institute of Scientific and Technical Information of China (English)

    刘萍; 王民权; 王劲

    2013-01-01

    CNC servo system has time delay in machine process of high-speed and high-precision which would cause form error because of deviation between instruction and real trajectory. Feed-forward control was introduced into servo system of CNC machine. Through theoretical analysis, it is shown that the form error can be effectively reduced by adopting proper feed-forward controller. CNC machine test results show; by adjusting the speed feed-forward coefficient, the speed loop gain can be improved, the form error due to changing acceleration is reduced, so surface quality and form precision are increased. Further the precision of CNC machine tools is improved.%针对高速高精加工过程中,因数控伺服系统时滞而导致的指令轨迹与实际轨迹存在偏差、进而导致形状误差的问题,将前馈控制引入数控机床伺服系统.通过理论分析可知:选用适当的前馈控制器,可以有效减小形状误差.数控机床测试结果表明:通过调整速度前馈系数,可以提高速度环的增益,从而减小因加速度变化引起的形状误差,改善表面精度和加工形状精度,进而提高CNC机床的加工精度.

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

    Science.gov (United States)

    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

  18. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway

    DEFF Research Database (Denmark)

    Madsen, Daniel H; Leonard, Daniel; Masedunskas, Andrius;

    2013-01-01

    routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation...... of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies...

  19. Artificial neural networks for determination of enantiomeric composition of alpha-phenylglycine using UV spectra of cyclodextrin host-guest complexes: comparison of feed-forward and radial basis function networks.

    Science.gov (United States)

    Afkhami, Abbas; Abbasi-Tarighat, Maryam; Bahram, Morteza

    2008-03-15

    In this work feed-forward neural networks and radial basis function networks were used for the determination of enantiomeric composition of alpha-phenylglycine using UV spectra of cyclodextrin host-guest complexes and the data provided by two techniques were compared. Wavelet transformation (WT) and principal component analysis (PCA) were used for data compression prior to neural network construction and their efficiencies were compared. The structures of the wavelet transformation-radial basis function networks (WT-RBFNs) and wavelet transformation-feed-forward neural networks (WT-FFNNs), were simplified by using the corresponding wavelet coefficients of three mother wavelets (Mexican hat, daubechies and symlets). Dilation parameters, number of inputs, hidden nodes, learning rate, transfer functions, number of epochs and SPREAD values were optimized. Performances of the proposed methods were tested with regard to root mean square errors of prediction (RMSE%), using synthetic solutions containing a fixed concentration of beta-cyclodextrin (beta-CD) and fixed concentration of alpha-phenylglycine (alpha-Gly) with different enantiomeric compositions. Although satisfactory results with regard to some statistical parameters were obtained for all the investigated methods but the best results were achieved by WT-RBFNs.

  20. Feed-Forward Decoupling Control and Simulation of Three-Phase PWM Rectifier%三相PWM整流器的前馈解耦控制与仿真研究

    Institute of Scientific and Technical Information of China (English)

    唐玉良

    2012-01-01

    基于前馈解耦控制策略,研究了三相电压型PWM整流器的建模与控制问题。首先,在d-q旋转坐标系下建立了三相电压型PWM整流器的数学模型,给出了三相电压型PWM整流器的双闭环控制结构,按此方法确定了电压、电流PI调节器的设计方法。仿真结果表明该方法能使所设计的PWM整流器运行于单位功率因数,输出的直流电压稳定在期望值且具有快速的动态响应,满足了设计要求。%Based on feed-forward decoupling control strategy, the model and controller of three-phase voltage source PWM rectifier are presented. First of all, a mathematical model of three-phase voltage source PWM rectifier is established in the d-q rotation frames. The double loop system is designed based on feed-forward decoupling strategy, and three PI controllers are designed. The simulation results show that this method can make PWM rectifier run with unit power factor, the output DC voltage stabilize on the desired value with the fast dynamic response. The characteristics meet the design demands.

  1. Wind control of cigarette process based on T-S model combined with feed-forward%基于T-S模型模糊混合前馈的卷烟工艺风力控制

    Institute of Scientific and Technical Information of China (English)

    谢钟翔; 成佳庆; 张立勋; 张振峰

    2013-01-01

    为解决扁式布袋除尘器中脉冲喷吹对工艺风力除尘系统管道的负压造成的定时扰动问题,提出一种基于 T-S模糊模型的模糊控制结合脉冲喷吹和压力波动前馈的混合前馈控制方法。从山东和其他一些地方的集中工艺风力系统生产环境中的运行效果可以看出,它有效地减弱了脉冲喷吹对于管道负压造成的扰动,简化了控制,具有良好的稳定性和鲁棒性。%A mixed feed-forward control method based on T-S fuzzy model combined with pulse jet and pressure fluctuation feed-forward is proposed to decrease the timing disturbance on the negative pressure of wind dust removal pipeline caused by pulse jet in flat bag dedusting system. The proposed method is applied in the practical production environments with concentrated wind power processes in Shandong and other provinces. The operation results indicate that, it can effectively weaken the disturbance on pipeline negative pressure caused by pulse jet, and simplify the control with good stability and robustness.

  2. DMPD: Translational mini-review series on Toll-like receptors: networks regulated byToll-like receptors mediate innate and adaptive immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available e receptors: networks regulated byToll-like receptors mediate innate and adaptive...ed byToll-like receptors mediate innate and adaptive immunity. Authors Parker LC, Prince LR, Sabroe I. Publi...d byToll-like receptors mediate innate and adaptive immunity. Parker LC, Prince LR, Sabroe I. Clin Exp Immun...17223959 Translational mini-review series on Toll-like receptors: networks regulate

  3. Muscarinic receptor-mediated calcium changes in a rat model of facial nerve nucleus injury

    Institute of Scientific and Technical Information of China (English)

    Dawei Sun; Huamin Liu; Fugao Zhu; Yanqing Wang; Junfeng Wen; Rui Zhou; Yanjun Wang; Banghua Liu

    2010-01-01

    The muscarinic receptor modulates intracellular free calcium ion levels in the facial nerve nucleus via different channels.In the present study,muscarinic receptor-mediated free calcium ions levels were detected by confocal laser microscopy in the facial nerve nucleus following facial nerve injury in rats.There was no significant difference in muscarinic receptor expression at the affected facial nerve nucleus compared with expression prior to injury,but muscarinic receptor-mediated free calcium ion levels increased in the affected side following facial nerve injury(P < 0.01).At day 30after facial nerve injury,50 μmol/L muscarinic-mediated free calcium ion levels were significantly inhibited at the affected facial nerve nucleus in calcium-free artificial cerebrospinal fluid,and the change range was 82% of artificial cerebrospinal fluid(P < 0.05).These results suggest that increased free calcium ion concentrations are achieved by intracellular calcium ion release,and that the transmembrane flow of calcium ions is also involved in this process.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  5. Melanocortin MC(4) receptor-mediated feeding and grooming in rodents.

    Science.gov (United States)

    Mul, Joram D; Spruijt, Berry M; Brakkee, Jan H; Adan, Roger A H

    2013-11-01

    Decades ago it was recognized that the pharmacological profile of melanocortin ligands that stimulated grooming behavior in rats was strikingly similar to that of Xenopus laevis melanophore pigment dispersion. After cloning of the melanocortin MC1 receptor, expressed in melanocytes, and the melanocortin MC4 receptor, expressed mainly in brain, the pharmacological profiles of these receptors appeared to be very similar and it was demonstrated that these receptors mediate melanocortin-induced pigmentation and grooming respectively. Grooming is a low priority behavior that is concerned with care of body surface. Activation of central melanocortin MC4 receptors is also associated with meal termination, and continued postprandial stimulation of melanocortin MC4 receptors may stimulate natural postprandial grooming behavior as part of the behavioral satiety sequence. Indeed, melanocortins fail to suppress food intake or induce grooming behavior in melanocortin MC4 receptor-deficient rats. This review will focus on how melanocortins affect grooming behavior through the melanocortin MC4 receptor, and how melanocortin MC4 receptors mediate feeding behavior. This review also illustrates how melanocortins were the most likely candidates to mediate grooming and feeding based on the natural behaviors they induced.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  8. 基于模型预测前馈的滚转稳定伺服系统控制研究%Research on Roll Stabilized Servo Platform Based on Model Predictive Feed-Forward Control

    Institute of Scientific and Technical Information of China (English)

    许叙遥; 林辉

    2012-01-01

    Roll stabilized platform based on gyro is a kind of inertia stable device applied to roll carrier. It demands not only higher position control precision but also higher speed control precision to meet the gyro measurement range. After a-nalysis of the platform,the system transfer function was built,and model predictive feed-forward controller on the basis of PID feedback control was designed. The experimental results show that the new model predictive feed-forward control method improves greatly the platform stabilized precision when the carrier roll speed rise fast and it run higher.%速率陀螺式滚转稳定平台是一种应用于旋转载体中的惯性稳定装置,不仅要求有较高的位置控制精度,为满足陀螺测量范围,还要求很高的速度控制精度.通过对稳定平台的分析,详细推导了系统的传递函数模型,在PID反馈控制的基础上,设计了由模型预测控制单元组成前馈环节的预测前馈复合控制器.实验结果表明在载体滚转速度快速上升以及大速度稳定滚转情况下,模型预测前馈控制大大提高了稳定平台的控制精度.

  9. Dynamic Positioning of Dredgers Using Nonlinear Dynamic Surface Control and Feed-Forward Compensation%结合非线性动态面和前馈补偿的挖泥船动力定位控制

    Institute of Scientific and Technical Information of China (English)

    张宇华; 姜建国; 郜登科

    2012-01-01

    针对挖泥船受挖泥强干扰作用的特点,提出采用前馈补偿与非线性动态面相结合的控制方法,解决挖泥船动力定位的控制问题.挖泥干扰的前馈补偿与动态面控制算法相结合的控制方法能保证挖泥船动力定位系统的渐近稳定.在反步控制的设计中加入一阶低通滤波器形成的动态面控制,避免了对非线性模型的多次微分,简化了控制器的设计.仿真结果表明,该方法对挖泥船动力定位有较好的控制效果.%To deal with difficulties in the control of dynamic positioning of dredgers under large dredging forces reaction, a method of combining dynamic surface control and feed-forward compensation is proposed to be used in dynamic positioning of dredgers. Dredging forces can be feed-forward compensated by sensors, and the dynamic surface controller guarantees global asymptotic stability of the closed-loop system. A first-order low-pass filter in the back-stepping design process allows the dynamic surface control technique to be implemented without differentiating any model nonlinearities, which can significantly simplify the design. Simulation results show that the proposed method has satisfactory performance.

  10. Drum water level control method based on fuzzy control and feed-forward compensation%基于模糊方法和前馈补偿的汽包水位控制方法

    Institute of Scientific and Technical Information of China (English)

    张向; 陆继东; 卢志民; 董美蓉

    2012-01-01

    将入口烟气流量和温度参数引入到余热锅炉汽包水位的控制算法中进行前馈补偿,采用模糊控制方法,设计了2个模糊控制器.控制器的流量修正值与传统蒸汽流量前馈修正值一起,对水位调节回路上的传统串级三冲量PID控制器的给水流量值进行修正.在纯低温余热发电站上以二级控制的方式进行试验,结果表明:该方法在水泥余热锅炉入口烟气温度和流量的大幅变化条件下仍能保持汽包水位的稳定,稳定性明显高于传统PID控制.%The flow rate and temperature were introduced into the control algorithm of drum water level of waste heat boiler. Based on fuzzy control, two fuzzy controllers were designed. In this scheme, the output amendments of water flow from the two controllers and the feed-forward amend- ment of main steam flow modify the water flow setting value from traditional cascade three impulses PID proportional-integral-derivative controller in the water level regulation loop. It was applied and tested in a waste heat power generation plane. The result demonstrates that the stability of the drum water level can still maintain in the substantial changes of the cement waste heat boiler inlet flue gas temperature and flow conditions. The control result of drum water level in fuzzy feed-forward control is better than in conventional PID control.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  12. 微阵列制备机器人分向前馈误差补偿控制%Two-way feed-forward error compensation control of a microarray production robot

    Institute of Scientific and Technical Information of China (English)

    刘飞; 吴丹; 陈恳; 宋立滨; 潘玉龙

    2011-01-01

    为了提高半闭环微阵列制备机器人的定位精度,根据机器人运动误差具有方向性的特点,提出了分向前馈误差补偿技术。建立了微阵列制备机器人系统误差前馈补偿的传递函数模型,对系统的准确性、快速性与稳定性进行分析,从理论上证明该方法在提高机器人精度方面是可行有效的。研究并实施了回程误差与其他非线性误差的分向补偿算法。在清华大学开发的THU-biorobot微阵列制备机器人上进行了实验研究。结果表明:补偿后机器人的定位精度在±5μm以内,系统动态性能也有显著提高,能够满足微阵列制备要求。%The positioning accuracy of a semi-closed control loop for a robot to produce microarrays was improved by a two-way feed-forward error compensation method based on the fact that the motion errors of the robot are directional.The motion control transfer function including the feed-forward compensation block was used to analyze the accuracy,speed and stability of the robotic system.This showed that error compensation method can significantly improve the accuracy.Two-way error compensation was then developed for the hysteresis error and other nonlinear errors.Tests on the THU-biorobot microarray production system demonstrated by Tsinghua University that the positioning error was reduced to less than ±5 μm,with the dynamic performance significantly improved by the error compensation method.

  13. 一种功率前馈的鲁棒预测无差拍并网控制方法%A Robust Predictive Deadbeat Grid-connected Control Method Based on Power Feed-forward Control

    Institute of Scientific and Technical Information of China (English)

    陈燕东; 罗安; 周乐明; 谢宁; 金国彬; 吕志鹏

    2013-01-01

    在光伏并网控制中,延时和滤波电感量变化会影响系统响应速度、稳定性及并网电流畸变率。对此,该文提出一种功率前馈的鲁棒预测无差拍并网控制方法。通过引入功率前馈控制加快系统的响应速度。鲁棒预测无差拍控制方法被提出用于并网电流控制,以增强系统的鲁棒性,降低因控制延时和电感量偏差对并网电流造成的畸变。分析带延迟环节的z域无差拍控制模型,并讨论延时和电感量取值对系统稳定性的影响。给出鲁棒预测无差拍控制的设计方法,并根据z域内的传递函数对其进行稳定性分析,确定控制参数的选取范围。仿真与实验结果证明了所提控制方法的有效性。%In photovoltaic grid-connected control system, the delay and the filtering inductance variation affect the system response speed, stability, and the current distortion. In this paper, a robust predictive deadbeat grid-connected control method based on power feed-forward is proposed. Power feed-forward control is introduced to speed up the system response. For the grid-connected current controller, a robust predictive deadbeat control method is proposed to enhance system robustness and to reduce the current distortion due to the control delay and inductance deviation. A delayed z-domain deadbeat control model was analyzed, and the delay and inductance effects on system stability were discussed. The design of the proposed robust predictive deadbeat control was given. In z-domain, the system transfer function was derived, and the system stability was analyzed, and the control parameters were selected. Simulation and experimental results verified the validity of the proposed control method.

  14. Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina.

    Science.gov (United States)

    Borghuis, Bart G; Looger, Loren L; Tomita, Susumu; Demb, Jonathan B

    2014-04-30

    A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Cryptococcus neoformans is internalized by receptor-mediated or 'triggered' phagocytosis, dependent on actin recruitment.

    Directory of Open Access Journals (Sweden)

    Caroline Rezende Guerra

    Full Text Available Cryptococcosis by the encapsulated yeast Cryptococcus neoformans affects mostly immunocompromised individuals and is a frequent neurological complication in AIDS patients. Recent studies support the idea that intracellular survival of Cryptococcus yeast cells is important for the pathogenesis of cryptococcosis. However, the initial steps of Cryptococcus internalization by host cells remain poorly understood. Here, we investigate the mechanism of Cryptococcus neoformans phagocytosis by peritoneal macrophages using confocal and electron microscopy techniques, as well as flow cytometry quantification, evaluating the importance of fungal capsule production and of host cell cytoskeletal elements for fungal phagocytosis. Electron microscopy analyses revealed that capsular and acapsular strains of C. neoformans are internalized by macrophages via both 'zipper' (receptor-mediated and 'trigger' (membrane ruffle-dependent phagocytosis mechanisms. Actin filaments surrounded phagosomes of capsular and acapsular yeasts, and the actin depolymerizing drugs cytochalasin D and latrunculin B inhibited yeast internalization and actin recruitment to the phagosome area. In contrast, nocodazole and paclitaxel, inhibitors of microtubule dynamics decreased internalization but did not prevent actin recruitment to the site of phagocytosis. Our results show that different uptake mechanisms, dependent on both actin and tubulin dynamics occur during yeast internalization by macrophages, and that capsule production does not affect the mode of Cryptococcus uptake by host cells.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Receptor-Mediated and Fluid-Phase Transcytosis of Horseradish Peroxidase across Rat Hepatocytes

    Directory of Open Access Journals (Sweden)

    Isabella Ellinger

    2010-01-01

    Full Text Available Horseradish peroxidase (HRP is often used as a fluid-phase marker to characterize endocytic and transcytotic processes. Likewise, it has been applied to investigate the mechanisms of biliary secretion of fluid in rat liver hepatocytes. However, HRP contains mannose residues and thus binds to mannose receptors (MRs on liver cells, including hepatocytes. To study the role of MR-mediated endocytosis of HRP transport in hepatocytes, we determined the influence of the oligosaccharid mannan on HRP biliary secretion in the isolated perfused rat liver. A 1-minute pulse of HRP was applied followed by marker-free perfusion. HRP appeared in bile with biphasic kinetics: a first peak at 7 minutes and a second peak at 15 minutes after labeling. Perfusion with 0.8 mg/mL HRP in the presence of a twofold excess of mannan reduced the first peak by 41% without effect on the second one. Together with recently published data on MR expression in rat hepatocytes this demonstrates two different mechanisms for HRP transcytosis: a rapid, receptor-mediated transport and a slower fluid-phase transport.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  2. Research on Feed Forward Decoupling Algorism of Active Power Filter%有源电力滤波器的前馈解耦控制策略研究

    Institute of Scientific and Technical Information of China (English)

    许彦; 冯宇; 张晓; 李德路

    2012-01-01

    In connection with current control in APF control system; this paper puts forward a new feed forward decoupling algorithm which traced given current with two PI controllers in current loop; and stabilized DC-voltage with PI controllers in voltage loop. Finally; referent voltage of SVPWM which is the output of current loop controlled the inverter. This method is simple; reliable and easy to be realized in project. This approach is proved to be feasibility by experiment based on DSP.%目前流行的预测控制算法存在计算量大、对系统参数依赖性大、未考虑三相电路耦合关系等问题.基于此,本文提出了一种新型的前馈解耦算法,该算法通过电流环的两个PI控制器对指令电流进行跟踪,通过电压环的PI控制器对直流侧电压进行稳定,电流环的输出结果作为SVPWM的参考电压对逆变器进行控制.方法控制简单,便于工程实现,很好的解决了预测控制所存在的问题.基于DSP的实验证明了其可行性.

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

    Science.gov (United States)

    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

  4. Learning feed-forward multi-nets

    NARCIS (Netherlands)

    Venema, RS; Spaanenburg, L; Kurkova,; Steele, NC; Neruda, R; Karny, M

    2001-01-01

    Multi-nets promise an improved performance over monolithic neural networks by virtue of their distributed implementation. This potential lacks popularity as, without precautions, the learning rate has to drop considerably to eliminate the occurrence of unlearning. This paper introduces extensions of

  5. Feed up, Feedback, and Feed Forward

    Science.gov (United States)

    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…

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

    Directory of Open Access Journals (Sweden)

    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

  7. α1A-adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat

    Institute of Scientific and Technical Information of China (English)

    XU Qi; ZHU Weizhong; L(U) Zhizhen; ZHANG Youyi; HAN Qide

    2004-01-01

    To determine which subtype of α1A-adrenergic receptors plays a role in the regulation of blood pressure, with α1A-adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various α1A-adrenergic receptor selective antagonists on the vasopressure responses to phenylephrine between the mean arterial pressure and hindlimb perfusion pressure in anesthetized rats. In Normotensive Wistar rats, the results showed that the inhibitory effects (dose ratios of ED50, Dr) of α1A-adrenoceptor selective antagonist (prazosin, Dr 13.5 ± 3.6 vs.15.1 ± 4.3, n = 11), α1A-adrenoceptor selective antagonist (5- methyl-urapidil, Dr 2.4 ± 0.9 vs. 3.7 ± 2.3, n = 12; RS-17053, Dr 3.2 ± 1.6 vs. 4.4 ± 3.3, n =12) and α1D- adrenoceptor selective antagonist (BMY7378, Dr 1.9 ± 0.9 vs. 2.2 ± 0.8, n = 8) on phenylephrine- induced increases of perfusion pressure in the autoperfused femoral beds were the same as that in the mean arterial blood pressure in normotensive Wistar rats. The inhibitory effects of antagonists (RS-17053, Dr 3.4 ± 0.6 vs. 4.3 ± 0.9, n = 5; BMY7378, Dr 1.7±0.5 vs. 1.7 ± 0.5, n = 8) in spontaneous hypertensive rats were similar with the Wistar rats. These results suggest that the mean arterial pressure induced by phenylephrine was mainly mediated by α1A-adrenergic receptor in both the anesthetized Wistar rats and spontaneous hypertensive rats.

  8. Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro

    Science.gov (United States)

    Phelan, K. D.; Gallagher, J. P.

    1992-01-01

    We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

  9. 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

    Institute of Scientific and Technical Information of China (English)

    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

  10. 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.

    Science.gov (United States)

    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 in Synechocystis sp. 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 the psrR1 gene among cyanobacterial species. Gel mobility shift assay revealed that RpaB binds to the HLR1 sequence of psrR1 in vitro. RNA gel blot analysis together with chromatin affinity purification (ChAP) analysis suggested that PSI genes are activated and the psrR1 gene 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 of psrR1 gene 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.

  11. 一种利用前馈电容改善瞬态响应的LDO%Optimization of the Transient Response for LDO with Feed-Forward Capacitance

    Institute of Scientific and Technical Information of China (English)

    任国栋; 王永顺; 汪再兴; 王道斌; 冯有才; 武钢

    2011-01-01

    The LDO is a device of high ripple reject and low noise, and is wide used in low in-out differential pressure and RF. At the situation of a large range of the load current, a dynamic compensation was chosen. Based on CSMC 0. 5 μm CMOS process, a dynamic compensation LDO with the MOS gate-source capacitance was designed. The well capacitance was simulated by a reverse-bias diode to imitate the effect on the system stability, and the stability of the system was optimized through reducing the bandwidth. The feed-forward capacitance was designed for quick response to improve the transient response characteristic. The experiment result shows that the circuit realizes the high PSRR and quick response, it is suitable for the portable devices.%LDO具有高的纹波抑制和低噪声特点,在低输入输出压差以及RF领域应用广泛.在负载电流变化范围大的情况下,动态补偿成为必然选择.基于CSMC 0.5μm CMOS工艺,设计了一种利用MOS栅源电容实现动态补偿的LDO.采用反偏二极管模拟了寄生阱电容对系统稳定性的影响,并提出减小系统带宽、优化系统稳定性的方案.为了实现快速动态响应,设计前馈电容优化了系统.实验表明,设计的电路具有高PSRR和快速响应能力,适用于便携式设备供电.

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 基于蓄电池负载DC/DC变换器的数字式前馈控制器仿真分析%Simulation Analysis on Digital Feed-Forward Contoller for DC/DC Converter with Battery Load

    Institute of Scientific and Technical Information of China (English)

    张小勇; 谢伟; 李梅

    2012-01-01

    采用前馈控制的方式,可以提高带蓄电池负载的DC/DC变换器的动态性能.针对列车上采用的半桥式DC/DC电源装置设计了与其相适应的前馈控制器,并且对该系统进行了仿真.仿真分析表明,这种前馈控制方式能够大大改善系统的动态性能以及稳定精度.%Dynamic performance of DC/DC converter with battery load could be enhanced by adopting feed-forward control method. Feed-forward controller for vehicle supply based on half-bridge topological DC/DC converter was designed and simulated, which was proved to greatly enhance the dynamic and stability performance of the system.

  15. 基于简约学习前馈补偿的永磁直线同步电机跟踪控制%Tracking control for permanent-magnet linear synchronous motor based on parsimonious learning feed-forward control

    Institute of Scientific and Technical Information of China (English)

    刘莉莉

    2011-01-01

    针对永磁直线同步电机易受端部效应、负载扰动和参数不确定等因素影响的特点,提出一种使用学习滤波器的简约学习前馈补偿控制策略.为消除端部效应的影响,设计多个低维B样条网络进行学习前馈补偿,从而达到良好的补偿效果;为保证系统的稳定性,在学习前馈控制中增加学习滤波器.仿真结果表明,该策略对非周期性输入信号具有良好的跟踪特性,同时有效解决了学习前馈补偿控制中的"维数灾难".%For the characteristics of permanent-magnet linear synchronous motor(PMLSM) suffering from the effects of end effect, load disturbances and parameter variations and so on, the parsimonious learning feed-forward control(LFFC) with learning filter was designed. The learning feed-forward compensation based on several lower-dimensional B-spline networks was adopted to overcome the influence of the end-effect, and a learning filter was added to the learning feed-forward controller to ensure stability of the system. Simulation results show that the proposed strategy enables servo system to have accurate tracking performance for non-periodic input signal, while solves effectively the "curse of dimensionality" in learning feed-forward control.

  16. Decoupling and PLC Controller Design in Greenhouse Based on Feed Forward Compensation Algorithm%基于前馈补偿算法温室解耦及 PLC 控制器设计

    Institute of Scientific and Technical Information of China (English)

    付焕森; 李元贵

    2016-01-01

    The feed forward compensation algorithm based on the greenhouse has been studied in this paper with the pur-pose resolving the problem that the key factors are difficult and inefficient to control because of its nonlinear, time-delay and decoupling characteristics.According to this algorithm, the two dimensional inputs of temperature and humidity have been decoupled and simulated in the Matlab with the results that the algorithm has a good quality of practice and effi-ciency.Based on the theoretical results, the PID decoupling controller and display interface have been designed.Several typical greenhouse examples are employed to demonstrate effectiveness and simplicity of this design controller ensuring stability of the key factors in control processes.%为解决温室系统由于非线性、大时滞和强耦合等特点引起的关键因子难以控制和效率低下的问题,研究了前馈补偿解耦算法。通过该算法实现了温室系统温度和湿度二维变量系统的解耦,并在MatLab 仿真模型中验证了该算法的实用性和高效性。利用MatLab GUI ( graphical user interface )强大的数据计算能力,设计了上位机控制界面,克服了常规的工业控制器难以编写复杂算法的缺点;再结合PLC执行稳定的优点,设计了 PID 解耦控制器。实践验证表明:该解耦控制器克服了单一温度和湿度控制的缺点,提高了系统的整体工作效率,保障了关键生长因子控制的稳定。

  17. Implementation of a Brushless Excitation System With Current Feed-Forward Control for Medium Frequency Electrical System%具有电流前馈的中频无刷励磁控制系统及其实现

    Institute of Scientific and Technical Information of China (English)

    周德佳; 庄亚平; 冀路明; 徐定海; 李江

    2011-01-01

    精密品质的400Hz船用中频供电系统是特种装备可靠运行的重要保障,研究高性能的中频同步发电机励磁控制策略和工程应用非常重要。本文分析了中频供电系统瞬变电压调整特性,提出了具有电流前馈的中频无刷励磁系统PID控制算法,能够对励磁机的时间常数进行一定的补偿,降低其滞后效果,因此增加了励磁系统小信号响应带宽的能力,以满足中频供电系统在突加或突卸负载的工况下,中频发电机机端输出瞬变电压具有快速的恢复时间。实验结果与仿真相符合,系统输出电压具有良好的动稳态性能,表明了所提出的控制方案是有效的。%It is very important to study medium frequency synchronous generator's excitation control strategy and application in shipboard,for it can guarantee the safe operation of special equipment in high quality 400Hz medium frequency electrical system.In order to make the medium frequency synchronous generator terminal's transient voltage restores as quickly as possible under the circumstances of suddenly increased and decreased load,this paper analyzes regulating property of the transient voltage of medium frequency electrical system and puts forward PID with current feed-forward controlling algorithm for medium frequency brushless excitation system,which compensates the exciter time constant to some extent,decreases its delaying effect,and increases the small signal response bandwidth of the excitation system.The simulation and experimental results verify the effectiveness of the proposed algorithm,which demonstrate that the proposed control system has good dynamic stability and steady-state performance.

  18. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Clustered DC Voltage Balancing Control of Star-Connected Cascaded STATCOM Based on Negative Current Feed-Forward Control%基于负序电流前馈的星型链式STATCOM链间均压策略

    Institute of Scientific and Technical Information of China (English)

    冯宇鹏; 王先为; 吴金龙; 王林; 左广杰; 潘爱强

    2016-01-01

    ABSTRACT:For DC bus voltage imbalance between clusters of star-connected STATCOM under unbalanced grid voltage faults, mechanism of negative sequence current injection method is analyzed. Relationship between negative sequence d-q axis current and active power of clusters is derived. Negative sequence d-q axis current under steady-state is calculated and a new dc voltage balance control strategy among clusters is proposed, composed of feed-forward control and closed-loop control. Results of simulation and industrial prototype experiments show that dc voltage of clusters becomes balanced under unbalanced faults with the proposed control strategy. Besides, the strategy is characterized with easy realization, fast response, and small dc bus voltage fluctuation and current surge.%针对星型链式静止同步补偿器(static synchronous compensator,STATCOM)在电网电压不平衡故障下链间直流母线电压不均衡的问题,首先对负序电流注入法的链间均压机理进行了理论分析,然后推导了负序dq轴电流与换流链有功功率的关系,求解了负序dq轴电流的稳态表达式;提出了一种新的基于负序电流前馈加闭环的链间均压控制策略。仿真分析与工业样机实验结果表明,所提出的链间均压策略达到了电网不平衡故障下换流链间直流母线电压平衡的目的,并且具有实现简单,响应速度快,直流母线电压动态波动小和电流冲击小的特点。

  20. Nicotine alpha 4 beta 2 receptor-mediated free calcium in an animal model of facial nucleus injury

    Institute of Scientific and Technical Information of China (English)

    Dawei Sun; Wenhai Sun; Yanqing Wang; Fugao Zhu; Rui Zhou; Yanjun Wang; Banghua Liu; Xiuming Wan; Huamin Liu

    2010-01-01

    Previous studies have demonstrated that the cholinergic system,via nicotinic receptors,regulates intracellular free calcium levels in the facial nucleus under normal physiological conditions.However,the regulation of nicotinic receptors on free calcium levels following facial nerve injury remains unclear.In the present study,an animal model of facial nerve injury was established,and changes in nicotinic receptor expression following facial nerve injury in rats were detected using reverse transcription polymerase chain reaction.Nicotinic receptor-mediated changes of free calcium levels following facial nucleus injury were determined by laser confocal microscopy.Results showed no significant difference in nicotinic receptor expression between the normal group and the affected facial nerve nucleus.The nicotinic receptor α4β2 subtype increased free calcium levels following facial nerve injury by promoting calcium transmembrane influx,and L-type voltage-gated calcium channel-mediated influx of calcium ions played an important role in promoting calcium transmembrane influx.The nicotinic receptor-mediated increase of free calcium levels following facial nerve injury provides an important mechanism for the repair of facial nerve injury.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. 动态属性权重智能前馈神经网络电力控制方法%Power Control Method Based on Intelligence Feed Forward Neural Network with Dynamic Attribute Weights

    Institute of Scientific and Technical Information of China (English)

    洪天星; 李斌勋

    2014-01-01

    According to the power control of grid connected photovoltaic industrial park, power control driven process has oscillation effect, it affects the system response speed and stability. A power control method for dynamic attribute weights of artificial intelligence based on the feed forward neural network is proposed, it improves industrial park photovoltaic grid connected power control performance. In the design of the control system, two PI controllers are used, combined with the use of flux controller and speed controller, a magnetic field in the rotor coordinate system is obtained. Using the affine PARK transform, make industrial photovoltaic grid connected power system control of all operations in the rotor magnetic field coordinates. Dynamic attribute weights is proposed to predictive current control technique for compensating the delay, the deadbeat control and sinusoidal pulse width modulation is realized. System test shows that, by using the control method to control the power industrial park, the distortion and control delay can be effectively restrained, it has high stability and robustness of the control system.%在工业园区光伏并网控制中,电力控制驱动过程中呈现阻尼振荡,影响系统响应速度和稳定性。提出一种改进的基于动态属性权重人工智能前馈神经网络的电力控制方法,提高工业园区光伏并网电力控制性能。控制系统设计中,采用两个PI控制器,并结合使用磁链控制器和转速控制器,在转子磁场坐标系下,利用仿射PARK变换,使得工业光伏并网控制电力系统所有运算在转子磁场坐标系下实现。构建人工智能前馈神经网络,通过功率前馈控制加快并网系统的响应速度,采用动态属性权重预测电流控制技术补偿延时,实现无差拍控制和正弦脉宽调制。系统测试表明,采用该控制方法进行工业园区光伏并网电力控制,能有效抑制控制延时和电感量偏

  3. An Application of Nonlinear Filter in the Feed-forward Control of Coordinated Control System%一种非线性滤波器在协调控制系统前馈控制中的应用

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    西北电网联络线调度下AGC指令复杂多变对火电机组稳定运行不利,为了改善火电机组协调控制前馈系统在AGC指令频繁小幅度波动时造成锅炉燃料量大幅度摆动的问题,研究了一种可变滤波时间的非线性滤波器;依据AGC指令变化幅度设计一种变滤波时间的非线性滤波器,对其动态微分部分输出信号进行增益修正和滤波处理;采集西北某电厂660 MW 24 h AGC指令进行算例分析,通过对比改进前后的燃料量指令证明该非线性滤波器可以实现: AGC指令大幅度变化时,前馈足额快速输出,以维持机前压力稳定; AGC指令小幅度频繁波动时,减小前馈输出幅值并增加滤波时间以减少燃料量波动。通过对比改进前后的燃料量指令,证明了可变滤波时间系数的滤波器具有应用价值。%Under the dispatch of linking-up road, the complexity and variability of AGC command affect the stabil-ity of thermal power units .In order to solve the problem that the amount of boiler fuel swings severely when AGC command fluctuations in a small amplitude , this paper explores a filter-time-variant nonlinear filter , which imple-ments gain correction and filtering implementation on the dynamic differential part of output signal according to the variation amplitude of AGC command .In addition, 24 hours’ AGC command of a 660 MW unit from a power plant in northwest China was collected to analyze the algorithm .After comparing the improved and non-improved fuel command we found the filter-time-variant nonlinear filter can realize the follow effects: when AGC command fluctu-ations in a small amplitude frequently , it reduces feed-forward output amplitude and increases filtering time to re-duce the fluctuation of fuel amount .Thus, the result shows that this filter has a considerable effect on the coordina-ted control system of a 660MW unit.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    CERN Document Server

    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...

  7. Loss of progesterone receptor-mediated actions induce preterm cellular and structural remodeling of the cervix and premature birth.

    Directory of Open Access Journals (Sweden)

    Steven M Yellon

    Full Text Available A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone, or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes

    Science.gov (United States)

    Ruiz, A; Matute, C; Alberdi, E

    2010-01-01

    Overactivation of ionotropic glutamate receptors in oligodendrocytes induces cytosolic Ca2+ overload and excitotoxic death, a process that contributes to demyelination and multiple sclerosis. Excitotoxic insults cause well-characterized mitochondrial alterations and endoplasmic reticulum (ER) dysfunction, which is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine receptors (RyRs) and inositol triphosphate receptors (IP3Rs) to excitotoxicity in oligodendrocytes in vitro. First, we observed that oligodendrocytes express all previously characterized RyRs and IP3Rs. Blockade of Ca2+-induced Ca2+ release by TMB-8 following α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated insults attenuated both oligodendrocyte death and cytosolic Ca2+ overload. In turn, RyR inhibition by ryanodine reduced as well the Ca2+ overload whereas IP3R inhibition was ineffective. Furthermore, AMPA-triggered mitochondrial membrane depolarization, oxidative stress and activation of caspase-3, which in all instances was diminished by RyR inhibition. In addition, we observed that AMPA induced an ER stress response as revealed by α subunit of the eukaryotic initiation factor 2α phosphorylation, overexpression of GRP chaperones and RyR-dependent cleavage of caspase-12. Finally, attenuating ER stress with salubrinal protected oligodendrocytes from AMPA excitotoxicity. Together, these results show that Ca2+ release through RyRs contributes to cytosolic Ca2+ overload, mitochondrial dysfunction, ER stress and cell death following AMPA receptor-mediated excitotoxicity in oligodendrocytes. PMID:21364659

  10. Plasma membrane Ca2+ pumping plays a prominent role in adenosine A(1) receptor mediated changes in [Ca2+](i) in DDT1 MF-2 cells

    NARCIS (Netherlands)

    Sipma, H; Fredholm, BB; DenHertog, A; Nelemans, A

    1996-01-01

    Adenosine A(1) receptor mediated formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) and accumulation of cytoplasmic Ca2+ ([Ca2+](i)) were investigated in DDT1 MF-2 smooth muscle cells. A strong reduction of the adenosine and N-6-cyclopentyladenosine (CPA) induced rise in [Ca2+](i) was observe

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

    Directory of Open Access Journals (Sweden)

    Romain eNardou

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

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

    Science.gov (United States)

    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

  15. 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

    Institute of Scientific and Technical Information of China (English)

    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。

  16. Histaminergic H1 receptors mediate L-histidine-induced anxiety in elevated plus-maze test in mice.

    Science.gov (United States)

    Kumar, Kuchibhotla Vijaya; Krishna, Devarakonda Rama; Palit, Gautam

    2007-05-01

    The central histaminergic system is reported to mediate behavioural, hormonal and physiological homeostasis of living organisms. Recent reports indicate its prominent role in various neurobehavioural disorders such as depression and psychosis. This study evaluated the effect of activation of the central histaminergic system in anxiety-like conditions, using the elevated plus-maze test in mice, and elucidated the role of different histaminergic receptors mediating such effects. Peripheral administration of L-histidine (L-His), in a dose-dependent manner, significantly decreased the exploration time in open arms and number of entries into open arms without modifying the number of entries into closed arms of the elevated plus-maze, indicating anxiogenesis. Further, such effects of central histamine were significantly attenuated, in a dose-dependent manner, by pretreatment with pyrilamine (H1 receptor antagonist). Pretreatment with either zolantidine (H2 receptor antagonist) or thioperamide (H3 receptor antagonist), however, failed to attenuate the L-His-induced anxiogenesis. Our results indicate that anxiogenic effects of central histaminergic system appear to be mediated prominently by activation of H1 receptors.

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

    International Nuclear Information System (INIS)

    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

  18. An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer.

    Science.gov (United States)

    Lu, Meng-Han; Hu, Ling-Yun; Du, Xin-Xin; Yang, Min; Zhang, Wei-Yi; Huang, Ke; Li, Li-An; Jiang, Shu-Fang; Li, Ya-Li

    2015-01-01

    High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People's liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable.

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

    KAUST Repository

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  3. Receptor-mediated membrane adhesion of lipid-polymer hybrid (LPH) nanoparticles studied by dissipative particle dynamics simulations

    Science.gov (United States)

    Li, Zhenlong; Gorfe, Alemayehu A.

    2014-12-01

    Lipid-polymer hybrid (LPH) nanoparticles represent a novel class of targeted drug delivery platforms that combine the advantages of liposomes and biodegradable polymeric nanoparticles. However, the molecular details of the interaction between LPHs and their target cell membranes remain poorly understood. We have investigated the receptor-mediated membrane adhesion process of a ligand-tethered LPH nanoparticle using extensive dissipative particle dynamics (DPD) simulations. We found that the spontaneous adhesion process follows a first-order kinetics characterized by two distinct stages: a rapid nanoparticle-membrane engagement, followed by a slow growth in the number of ligand-receptor pairs coupled with structural re-organization of both the nanoparticle and the membrane. The number of ligand-receptor pairs increases with the dynamic segregation of ligands and receptors toward the adhesion zone causing an out-of-plane deformation of the membrane. Moreover, the fluidity of the lipid shell allows for strong nanoparticle-membrane interactions to occur even when the ligand density is low. The LPH-membrane avidity is enhanced by the increased stability of each receptor-ligand pair due to the geometric confinement and the cooperative effect arising from multiple binding events. Thus, our results reveal the unique advantages of LPH nanoparticles as active cell-targeting nanocarriers and provide some general principles governing nanoparticle-cell interactions that may aid future design of LPHs with improved affinity and specificity for a given target of interest.

  4. Preparation and characterization of folate-poly(ethylene glycol)-grafted-trimethylchitosan for intracellular transport of protein through folate receptor-mediated endocytosis.

    Science.gov (United States)

    Zheng, Yu; Song, Xiangrong; Darby, Michael; Liang, Yufeng; He, Ling; Cai, Zheng; Chen, Qiuhong; Bi, Yueqi; Yang, Xiaojuan; Xu, Jiapeng; Li, Yuanbo; Sun, Yiyi; Lee, Robert J; Hou, Shixiang

    2010-01-01

    To develop a receptor-mediated intracellular delivery system that can transport therapeutic proteins to specific tumor cells, folate-poly(ethylene glycol)-grafted-trimethylchitosan (folate-PEG-g-TMC) was synthesized. Nano-scaled spherical polyelectrolyte complexes between the folate-PEG-g-TMC and fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) were prepared under suitable weight ratio of copolymer to FITC-BSA by ionic interaction between the positively charged copolymers and the negatively charged FITC-BSA. Intracellular uptake of FITC-BSA was specifically enhanced in SKOV3 cells (folate receptor over-expressing cell line) through folate receptor-mediated endocytosis compared with A549 cells (folate receptor deficient cell line). Folate-PEG-g-TMC shows promise for intracellular transport of negatively charged therapeutic proteins into folate receptor over-expressing tumor cells.

  5. Monoacylglycerol lipase promotes Fcγ receptor-mediated phagocytosis in microglia but does not regulate LPS-induced upregulation of inflammatory cytokines.

    Science.gov (United States)

    Kouchi, Zen

    2015-08-21

    Monoacylglycerol lipase (MAGL) is important for neuroinflammation. However, the regulatory mechanisms underlying its expression and function remain unknown. Lipopolysaccharide (LPS) treatment post-translationally upregulated MAGL expression, whereas it downregulated MAGL transcription through a Stat6-mediated mechanism in microglia. Neither MAGL knockdown nor JZL-184, a selective MAGL inhibitor, suppressed LPS-induced upregulation of inflammatory cytokines in microglia. Moreover, exogenous expression of MAGL in BV-2 microglial cell line, which lacks endogenous MAGL, did not promote the induction of inflammatory cytokines by LPS treatment. Interestingly, MAGL knockdown reduced Fcγ receptor-mediated phagocytosis in primary microglia, and introduction of MAGL into the BV-2 cells increased Fcγ receptor-mediated phagocytosis. Collectively, these results suggest that MAGL regulates phagocytosis, but not LPS-mediated cytokine induction in microglia.

  6. Long-term exposure to IL-1beta enhances Toll-IL-1 receptor-mediated inflammatory signaling in murine airway hyperresponsiveness

    DEFF Research Database (Denmark)

    Zhang, Yaping; Xu, Cang-Bao; Cardell, Lars-Olaf

    2009-01-01

    Toll-interleukin-1 (Toll-IL-1) receptor signaling may play a key role in the development of airway hyperreactivity (AHR) and chronic airway inflammatory diseases such as asthma. Previously, we have demonstrated that pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin......RNA expression following IL-1beta treatment. Immunohistochemistry confirmed that protein expression for CD14, RP105, MCP-1 and phosphorylated IkappaB-alpha were increased in both the airway epithelial and smooth muscle cells. In order to link the activation of Toll-IL-1 receptor-mediated inflammatory signal......-1beta (IL-1beta), induce AHR. However, the underlying intracellular signaling mechanisms that lead to AHR remain elusive. In order to see if the Toll-IL-1 receptor-mediated inflammatory signal pathways are involved in the development of AHR, the present study was designed to use a real-time PCR...

  7. 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

    OpenAIRE

    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,...

  8. 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

    OpenAIRE

    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,...

  9. The application effect of feed forward control in chemohyperthermia combined with extracorporeal high-frequency hyperthermia%前馈控制在热灌注化疗联合体外高频热疗中的应用效果

    Institute of Scientific and Technical Information of China (English)

    黎逢弟; 梁梅琼; 张翔; 杜梅芬; 梁红梅

    2014-01-01

    目的 采用前馈控制管理方法,降低体腔热灌注化疗联合体外高频深部热疗治疗恶性胸腔、腹腔积液护理不良事件的发生率.方法 按患者治疗的时间顺序将60例患者分为对照组和实验组,实验组对体腔热灌注化疗联合热疗的治疗风险环节进行前馈控制管理,对照组采用传统管理方法.结果 实验组在护理不良事件发生率、考核成绩、设备管理质量及消毒隔离质量方面,与对照组比较,差异具有统计学意义(P<0.05).结论实施前馈控制管理能有效避免和减少新治疗技术护理不良事件的发生,提高护士的风险管理意识与护理质量管理水平.%Objective To reduce the occurrence of adverse events by adopting feed forward control method in chemohyperthermia combined with extracorporeal high-frequency hyperthermia in the treatment of malignant pleural effusion and malignant peritoneal effusion.Methods 60 patients were divided into control group and experimental group according to the therapeutic sequence.Experimental group used feed forward control method to manage risk links,while control group used traditional management method.Result There were statistically significant difference in the rate of nursing adverse events,test results,equipment management quality and disinfection and isolation quality between two groups (P < 0.05).Conclusion Feed forward control method can effectively prevent and reduce nursing adverse events in new technological treatment,improve the consciousness of risk management and nursing quality management level of nurses.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Exploring the contextual sensitivity of factors that determine cell-to-cell variability in receptor-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Suzanne Gaudet

    Full Text Available Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype. For TRAIL (TNF-related apoptosis-inducing ligand variability manifests itself as dramatic differences in the time between ligand exposure and the sudden activation of the effector caspases that kill cells. However, the contribution of individual proteins to phenotypic variability has not been explored in detail. In this paper we use feature-based sensitivity analysis as a means to estimate the impact of variation in key apoptosis regulators on variability in the dynamics of cell death. We use Monte Carlo sampling from measured protein concentration distributions in combination with a previously validated ordinary differential equation model of apoptosis to simulate the dynamics of receptor-mediated apoptosis. We find that variation in the concentrations of some proteins matters much more than variation in others and that precisely which proteins matter depends both on the concentrations of other proteins and on whether correlations in protein levels are taken into account. A prediction from simulation that we confirm experimentally is that variability in fate is sensitive to even small increases in the levels of Bcl-2. We also show that sensitivity to Bcl-2 levels is itself sensitive to the levels of interacting proteins. The contextual dependency is implicit in the mathematical formulation of sensitivity, but our data show that it is also important for biologically relevant parameter values. Our work provides a conceptual and practical means to study and understand the impact of cell-to-cell variability in protein expression levels on cell fate using deterministic models and sampling from parameter distributions.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  14. Receptor-mediated hepatic uptake of M6P-BSA-conjugated triplex-forming oligonucleotides in rats.

    Science.gov (United States)

    Ye, Zhaoyang; Cheng, Kun; Guntaka, Ramareddy V; Mahato, Ram I

    2006-01-01

    Excessive production of extracellular matrix, predominantly type I collagen, results in liver fibrosis. Earlier we synthesized mannose 6-phosphate-bovine serum albumin (M6P-BSA) and conjugated to the type I collagen specific triplex-forming oligonucleotide (TFO) for its enhanced delivery to hepatic stellate cells (HSCs), which is the principal liver fibrogenic cell. In this report, we demonstrate a time-dependent cellular uptake of M6P-BSA-33P-TFO by HSC-T6 cells. Both cellular uptake and nuclear deposition of M6P-BSA-33P-TFO were significantly higher than those of 33P-TFO, leading to enhanced inhibition of type I collagen transcription. Following systemic administration into rats, hepatic accumulation of M6P-BSA-33P-TFO increased from 55% to 68% with the number of M6P per BSA from 14 to 27. Unlike 33P-TFO, there was no significant decrease in the hepatic uptake of (M6P)20-BSA-33P-TFO in fibrotic rats. Prior administration of excess M6P-BSA decreased the hepatic uptake of (M6P)20-BSA-33P-TFO from 66% to 40% in normal rats, and from 60% to 15% in fibrotic rats, suggesting M6P/insulin-like growth factor II (M6P/IGF II) receptor-mediated endocytosis of M6P-BSA-33P-TFO by HSCs. Almost 82% of the total liver uptake in fibrotic rats was contributed by HSCs. In conclusion, by conjugation with M6P-BSA, the TFO could be potentially used for the treatment of liver fibrosis.

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

    International Nuclear Information System (INIS)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  17. Pentosan polysulfate regulates scavenger receptor-mediated, but not fluid-phase, endocytosis in immortalized cerebral endothelial cells.

    Science.gov (United States)

    Deli, M A; Abrahám, C S; Takahata, H; Katamine, S; Niwa, M

    2000-12-01

    1. Effects of pentosan polysulfate (PPS) and the structurally related sulfated polyanions dextran sulfate, fucoidan, and heparin on the scavenger receptor-mediated and fluidphase endocytosis in GP8 immortalized rat brain endothelial cells were investigated. 2. Using 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarboxyamine perchlorate-labeled acetylated low-density lipoprotein (DiI-AcLDL), we found a binding site with high affinity and low binding capacity, and another one with low affinity and high binding capacity. Increasing ligand concentrations could not saturate DiI-AcLDL uptake. DiI-AcLDL uptake, but not binding, was sensitive to pretreatment with filipin, an inhibitor of caveola formation. 3. PPS (20-200 microg/ml) significantly reduced the binding of DiI-AcLDL after coincubation for 3 hr, though this effect was less expressed after 18 hr. Among other polyanions, only fucoidan decreased the DiI-AcLDL binding after 3 hr, whereas dextran sulfate significantly increased it after 18 hr. PPS treatment induced an increase in DiI-AcLDL uptake, whereas other polysulfated compounds caused a significant reduction. 4. Fluid-phase endocytosis determined by the accumulation of Lucifer yellow was concentration and time dependent in GP8 cells. Coincubation with PPS or other sulfated polyanions could not significantly alter the rate of Lucifer yellow uptake. 5. In conclusion. PPS decreased the binding and increased the uptake of DiI-AcLDL in cerebral endothelial cells, an effect not mimicked by the other polyanions investigated.

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

    Energy Technology Data Exchange (ETDEWEB)

    Magno, Aaron L. [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia); Ingley, Evan [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Brown, Suzanne J. [Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia); Conigrave, Arthur D. [School of Molecular Bioscience, University of Sydney, New South Wales 2000 (Australia); Ratajczak, Thomas [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia); Ward, Bryan K., E-mail: bryanw@cyllene.uwa.edu.au [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia)

    2011-09-09

    Highlights: {yields} A yeast two-hybrid screen revealed testin bound to the calcium-sensing receptor. {yields} The second zinc finger of LIM domain 1 of testin is critical for interaction. {yields} Testin bound to a region of the receptor tail important for cell signalling. {yields} Testin and receptor interaction was confirmed in mammalian (HEK293) cells. {yields} 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.

  19. Urotensin Ⅱ inhibits electrical activity of hippocampal CA1 neurons by potentiating the GABAA receptor-mediated Cl- current

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To examine the effects of urotensin Ⅱ (UII) on the discharges of neurons in CA1 area of hippocampal slices by using extracellular recording technique. Results① In response to the application of UII (0.3, 3.0,30.0, 300.0 nmol/L, n =77) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 63/77 (81.8%) neurons were significantly decreased in a dose-dependent manner. ②Pretreatment with bicuculline( BIC, 100 μmol/L) , a specific GABAA receptor antagonist, led to a marked increase in the SDR of 6/7 (85.71% ) neurons in an epileptiform pattern. The increased discharges were not significantly changed after UII (30.0 nmol/L) was applied into the perfusate for 2 min. ③ Pretreatment with picrotoxin (PIC, 50 μmol/L) , a selective blocker of Cl- channel, led to an increase in the SDR of all 8/8 (100%) neurons. The increased discharges were not influenced by the UII (30.0 nmol/L) applied.④Application of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L) into the perfusate for 2 min also significantly augmented the SDR of 14/16 (87.5%) neurons , then UII (30.0 nmol/L) applied into the perfusate reduced the increased the SDR of all 14/14 ( 100% ) neurons. Conclusion These results suggest that UII may decrease neuronal activity by potentiating GABAA receptor-mediated Cl- current in hippocampal CA1 neurons, and involved with the mediation of nitric oxide.

  20. Modulation of the input-output function by GABAA receptor-mediated currents in rat oculomotor nucleus motoneurons.

    Science.gov (United States)

    Torres-Torrelo, Julio; Torres, Blas; Carrascal, Livia

    2014-11-15

    The neuronal input-output function depends on recruitment threshold and gain of the firing frequency-current (f-I) relationship. These two parameters are positively correlated in ocular motoneurons (MNs) recorded in alert preparation and inhibitory inputs could contribute to this correlation. Phasic inhibition mediated by γ-amino butyric acid (GABA) occurs when a high concentration of GABA at the synaptic cleft activates postsynaptic GABAA receptors, allowing neuronal information transfer. In some neuronal populations, low concentrations of GABA activate non-synaptic GABAA receptors and generate a tonic inhibition, which modulates cell excitability. This study determined how ambient GABA concentrations modulate the input-output relationship of rat oculomotor nucleus MNs. Superfusion of brain slices with GABA (100 μm) produced a GABAA receptor-mediated current that reduced the input resistance, increased the recruitment threshold and shifted the f-I relationship rightward without any change in gain. These modifications did not depend on MN size. In absence of exogenous GABA, gabazine (20 μm; antagonist of GABAA receptors) abolished spontaneous inhibitory postsynaptic currents and revealed a tonic current in MNs. Gabazine increased input resistance and decreased recruitment threshold mainly in larger MNs. The f-I relationship shifted to the left, without any change in gain. Gabazine effects were chiefly due to MN tonic inhibition because tonic current amplitude was five-fold greater than phasic. This study demonstrates a tonic inhibition in ocular MNs that modulates cell excitability depending on cell size. We suggest that GABAA tonic inhibition acting concurrently with glutamate receptors activation could reproduce the positive covariation between threshold and gain reported in alert preparation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Türkiye’de Enflasyonun İleri ve Geri Beslemeli Yapay Sinir Ağlarının Melez Yaklaşımı ile Öngörüsü = Forecasting of Turkey Inflation with Hybrid of Feed Forward and Recurrent Artifical Neural Networks

    Directory of Open Access Journals (Sweden)

    V. Rezan USLU

    2010-01-01

    Full Text Available Obtaining the inflation prediction is an important problem. Having this prediction accurately will lead to more accurate decisions. Various time series techniques have been used in the literature for inflation prediction. Recently, Artificial Neural Network (ANN is being preferred in the time series prediction problem due to its flexible modeling capacity. Artificial neural network can be applied easily to any time series since it does not require prior conditions such as a linear or curved specific model pattern, stationary and normal distribution. In this study, the predictions have been obtained using the feed forward and recurrent artificial neural network for the Consumer Price Index (CPI. A new combined forecast has been proposed based on ANN in which the ANN model predictions employed in analysis were used as data.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  5. Development of drug loaded nanoparticles for tumor targeting. Part 2: Enhancement of tumor penetration through receptor mediated transcytosis in 3D tumor models

    Science.gov (United States)

    El-Dakdouki, Mohammad H.; Puré, Ellen; Huang, Xuefei

    2013-04-01

    We report that receptor mediated transcytosis can be utilized to facilitate tumor penetration by drug loaded nanoparticles (NPs). We synthesized hyaluronan (HA) coated silica nanoparticles (SNPs) containing a highly fluorescent core to target CD44 expressed on the cancer cell surface. Although prior studies have primarily focused on CD44 mediated endocytosis to facilitate cellular uptake of HA-NPs by cancer cells, we discovered that, once internalized, the HA-SNPs could be transported out of the cells with their cargo. The exported NPs could be taken up by neighboring cells. This enabled the HA-SNPs to penetrate deeper inside tumors and reach a much greater number of tumor cells in 3D tumor models, presumably through tandem cycles of CD44 mediated endocytosis and exocytosis. When doxorubicin (DOX) was loaded onto the NPs, better penetration of multilayered tumor cells was observed with much improved cytotoxicities against both drug sensitive and drug resistant cancer spheroids compared to the free drug. Thus, targeting receptors such as CD44 that can readily undergo recycling between the cell surface and interior of the cells can become a useful strategy to enhance the tumor penetration potential of NPs and the efficiency of drug delivery through receptor mediated transcytosis.We report that receptor mediated transcytosis can be utilized to facilitate tumor penetration by drug loaded nanoparticles (NPs). We synthesized hyaluronan (HA) coated silica nanoparticles (SNPs) containing a highly fluorescent core to target CD44 expressed on the cancer cell surface. Although prior studies have primarily focused on CD44 mediated endocytosis to facilitate cellular uptake of HA-NPs by cancer cells, we discovered that, once internalized, the HA-SNPs could be transported out of the cells with their cargo. The exported NPs could be taken up by neighboring cells. This enabled the HA-SNPs to penetrate deeper inside tumors and reach a much greater number of tumor cells in 3D tumor

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  12. 抑制直流母线电压波动的四象限级联型变频器前馈控制策略%A Feed-Forward Scheme for A Four-Quadrant Cascade Converter to Restrain DC Bus Voltage Ripple

    Institute of Scientific and Technical Information of China (English)

    邱长青; 黄声华

    2015-01-01

    四象限级联型变频器功率单元 H 桥的瞬时输出功率以2倍和4倍频率脉动,使得直流母线产生2次和4次纹波电压。单个功率单元输入端PWM整流器采用前馈控制策略能有效抑制母线电压波动,且总的并网电流无低次谐波。从功率单元的数学模型出发,推导出输入输出的瞬时有功功率,提出了基于瞬时 abc 理论的瞬时有功电流前馈控制来抑制直流母线电压波动,同时建立了基于Kalman滤波的负载电流估计模型。最后通过功率单元实验测试,验证了控制策略的可行性。%The instantaneous output power of the power cell H-bridge in four-quadrant cascade converter pulsates at twice and quadruple the output frequency, generating the second and fourth harmonic DC bus voltage. Using feed-forward control scheme in PWM rectifier of single power cell can effectively restrain DC bus voltage ripple and make the total grid-connected current without low-order harmonics. From the mathematical model of power cell, the instantaneous active power is derived. Based on instantaneous abc theory, instantaneous active current feed-forward control have been proposed to restrain the DC bus voltage ripple. Moreover, load current estimation model based on Kalman theory is established. Finally, the experimental results are given to prove the effectiveness of the proposed control scheme.

  13. A CONTROL METHOD FOR SPLIT RANGE INDIVIDUAL PITCH BASED ON FEED-FORWARD AZIMUTH ANGLE WEIGHT NUMBER ASSIGNMENT%基于前馈补偿方位角权系数的分程独立变桨距控制研究

    Institute of Scientific and Technical Information of China (English)

    姚兴佳; 刘玥; 郭庆鼎

    2012-01-01

    依据风速特性及桨叶的空气动力学分析得到独立变桨距控制的基本控制规律,提出基于前馈补偿的方位角权系数分程独立变桨距控制,此控制方法采用方位角权系数分配分别对3个桨叶的桨距角进行调整,实现独立变桨距控制,然后根据前馈补偿理论对变桨距过程进行分程独立变桨距控制.在Matlab中进行仿真.仿真结果表明,该控制方法不仅可实现风力机的独立变桨,在稳定输出功率的同时减小桨叶的拍打振动,且可避免由于全程独立变桨距桨叶调节频繁所引起的电动变桨执行电机因过热损坏的问题.控制方法简单,更适合用于独立动作的电动变桨距执行机构.%The individual control law was obtained by analyzing of wind characteristics and wind turbine aerodynamics.A control method for split range individual pitch was proposed based on feed-forward compensator azimuth angle weight number assignment.The separate distribution for pitch angle of blades using azimuth angle weight number assignment was adopted to achieve individual pitch control.Then,the split range individual pitch control with feed-forward compensator was used to control wind turbine.The simulation results show that this control strategy can make the output power keep stable and the flapwise fluctuation be reduced at the same time.Moreover,the method can prevent the blades from adjusting frequently and the actuator motor superheating damage.The method is easy to control and more suitable for electric pitch regulated mechanism.

  14. Optimization of Feed-forward and Feed-back Control System for Oxygen Venting in Residual Oil Gasifier of Synthesis Ammonia Plant%合成氨渣油气化炉氧气放空前馈-反馈控制系统优化

    Institute of Scientific and Technical Information of China (English)

    郝丽荣; 王亚凤; 许刚

    2014-01-01

    Aiming at the fact that in a synthetic ammonia plant , two residual oil gasifiers share an oxygen-ven-ting regulation system and the pressure control of oxygen system becomes difficult in a miss -operation single furnace, the Yokogawa CS3000 R3 DCS was employed to complete feed-forward control so as to stabilize the oxygen pressure and to ensure both safe and stable operation of the another gasifier , as well as to reduce any non-planned shutdown .%针对合成氨两台渣油气化炉共用一套氧气放空调节系统,单炉跳车氧气系统压力控制难度大的特点,利用日本横河电机公司CS3000 R3集散控制系统,对单炉跳车情况下的氧气放空进行前馈控制,稳定氧气系统压力,确保另一台气化炉安全稳定运行,减少非计划停车。

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. Unlearning in feed-forward multi-nets

    NARCIS (Netherlands)

    Spaanenburg, L; Kurkova,; Steele, NC; Neruda, R; Karny, M

    2001-01-01

    Multi-nets promise an improved performance over monolithic neural networks by virtue of their distributed implementation. Modular neural networks are multi-nets based on an judicious assembly of functionally different parts. This can be viewed as again a monolithic network, but with more complex neu

  20. Orthogonal Bases used for Feed Forward Control of Wind Turbines

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Stoustrup, Jakob

    2011-01-01

    In optimizing wind turbines it can be of a large help to use information of wind speeds at upwind turbine for the control of downwind turbines, it is, however, problematic to use these measurements directly since they are highly influenced by turbulence behind the wind turbine rotor plane. In this...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Ontogeny of catecholamine and adenosine receptor-mediated cAMP signaling of embryonic red blood cells: role of cGMP-inhibited phosphodiesterase 3 and hemoglobin.

    Science.gov (United States)

    Baumann, R; Blass, C; Götz, R; Dragon, S

    1999-12-15

    We have previously shown that the cAMP signaling pathway controls major aspects of embryonic red blood cell (RBC) function in avian embryos (Glombitza et al, Am J Physiol 271:R973, 1996; and Dragon et al, Am J Physiol 271:R982, 1996) that are important for adaptation of the RBC gas transport properties to the progressive hypercapnia and hypoxia of later stages of avian embryonic development. Data about the ontogeny of receptor-mediated cAMP signaling are lacking. We have analyzed the response of primitive and definitive chick embryo RBC harvested from day 3 to 18 of development towards forskolin, beta-adrenergic, and A2 receptor agonists. The results show a strong response of immature definitive and primitive RBC to adenosine A2 and beta-adrenergic receptor agonists, which is drastically reduced in the last stage of development, coincident with the appearance of mature, transcriptionally inactive RBC. Modulation of cGMP-inhibited phosphodiesterase 3 (PDE3) has a controlling influence on cAMP accumulation in definitive RBC. Under physiological conditions, PDE3 is inhibited due to activation of soluble guanylyl cyclase (sGC). Inhibition of sGC with the specific inhibitor ODQ decreases receptor-mediated stimulation of cAMP production; this effect is reversed by the PDE3 inhibitor milrinone. sGC is acitivated by nitric oxide (NO), but we found no evidence for production of NO by erythrocyte NO-synthase. However, embryonic hemoglobin releases NO in an oxygen-linked manner that may activate guanylyl cyclase.

  3. GABAA receptor-mediated feedforward and feedback inhibition differentially modulate the gain and the neural code transformation in hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Jang, Hyun Jae; Park, Kyerl; Lee, Jaedong; Kim, Hyuncheol; Han, Kyu Hun; Kwag, Jeehyun

    2015-12-01

    Diverse variety of hippocampal interneurons exists in the CA1 area, which provides either feedforward (FF) or feedback (FB) inhibition to CA1 pyramidal cell (PC). However, how the two different inhibitory network architectures modulate the computational mode of CA1 PC is unknown. By investigating the CA3 PC rate-driven input-output function of CA1 PC using in vitro electrophysiology, in vitro-simulation of inhibitory network, and in silico computational modeling, we demonstrated for the first time that GABAA receptor-mediated FF and FB inhibition differentially modulate the gain, the spike precision, the neural code transformation and the information capacity of CA1 PC. Recruitment of FF inhibition buffered the CA1 PC spikes to theta-frequency regardless of the input frequency, abolishing the gain and making CA1 PC insensitive to its inputs. Instead, temporal variability of the CA1 PC spikes was increased, promoting the rate-to-temporal code transformation to enhance the information capacity of CA1 PC. In contrast, the recruitment of FB inhibition sub-linearly transformed the input rate to spike output rate with high gain and low spike temporal variability, promoting the rate-to-rate code transformation. These results suggest that GABAA receptor-mediated FF and FB inhibitory circuits could serve as network mechanisms for differentially modulating the gain of CA1 PC, allowing CA1 PC to switch between different computational modes using rate and temporal codes ad hoc. Such switch will allow CA1 PC to efficiently respond to spatio-temporally dynamic inputs and expand its computational capacity during different behavioral and neuromodulatory states in vivo.

  4. A Full Grid Voltage Feed-forward Control Strategy With Inverter-side Current Feedback for LCL Grid-connected Inverters%逆变器侧电流反馈的LCL并网逆变器电网电压前馈控制策略

    Institute of Scientific and Technical Information of China (English)

    吴云亚; 谢少军; 阚加荣; 过亮

    2013-01-01

    逆变器侧电流反馈的具有稳定性强、单闭环控制、参数设计简单和系统成本较低的优点,但是其属于电网电流间接控制,造成并网功率因数较低,此外,电网电流中还包含由电网电压引起的低次谐波电流.为保留其优点并克服其缺点,提出一种适用于逆变器侧电流反馈LCL并网逆变器的完全电网电压前馈控制策略,该策略能完全消除电网电压对电网电流的影响,并且并网功率因数得到了大大的提升.仿真与实验结果表明,所提控制策略正确、有效.%The LCL grid-connected inverter, which uses the inverter-side current as feedback parameter, has many advantages, such as stronger stability, single-current loop, easy design for control parameters and its low cost. However, the grid current is controlled indirectly, which causes the power factor at grid-side is less than 1. Moreover, the grid current contains a lot of low-order harmonic, which results from low-order harmonic in grid voltage. A full grid-voltage feed-forward was proposed to overcome its shortcomings and reserve its merits, which can cancels out the effect of grid voltage on grid current and the power factor at grid-side is approximately equal to l.The simulation and experimental results verify that the performance of proposed control strategy is excellent.

  5. Fuzzy Neural Network Control Combined with Feed-forward Compensation for a Double Invert Pendulum Based on PSO-SA%基于PSO—SA的二级倒立摆前馈补偿模糊神经网络控制

    Institute of Scientific and Technical Information of China (English)

    张秀玲; 田力勇; 李晓辉

    2012-01-01

    以模糊神经网络为基础,结合误差前馈补偿完成了二级倒立摆系统的稳定控制,并采用模拟退火粒子群算法对控制参数进行全局寻优。与基于状态变量合成的模糊神经网络控制器相比,该控制方法豢仅解决了多变量系统模糊控制器的“规则爆炸”问题,并且。由于所有状态变量直接参与控制输出,控制精度亦有所提高。仿真结果表明,该控制方案所需规则数目少,响应速度快,有良好的鲁棒性和非线性适应能力。%The stability control of the double invert pendulum system was completed based on a fuzzy neural network and combined with the error feed-forward compensation in this paper and,an algorithm of particle swarm optimiza- tion combined with simulated annealing (PSO-SA) was used in global optimizing of control parameters. Compared with the fuzzy controller based on the synthesis of state variables this control scheme has not only solved the rule number explosion problem of multi-variable system fuzzy controller, but also has improved the control accuracy be- cause of the direct participation of control output by all state variables. Simulation results show that this control scheme has the advantages of less rules,fast response speed,good robustness and strong nonlinear adaptive ability.

  6. RESEARCH OF GRID-SIDE CONVERTER PROPORTIONAL-RESONANT WITH FEED-FORWARD CONTROL STRATEGY FOR VARIABLE-SPEED CONSTANT-FREQUENCY WIND POWER GENERATOR SYSTEM%变速恒频风力发电网侧变流器比例谐振和前馈控制研究

    Institute of Scientific and Technical Information of China (English)

    马浩淼; 高勇; 杨媛

    2012-01-01

    Proportional-resonant control with high precision and simple algorithm was applied to the grid side converter for variable-speed constant-frequency wind power generator system, but its stability is easy to be disturbed by load and grid voltage disturbance. Under this condition, based on the analysis of proportional resonant control algorithm structure of grid side converter, an improved feed-forward control strategy including the information of both grid voltage and rotor current differential signal was proposed according to the input and output power balance relationship. Power balance between the input and output can be maintained by adjusting rotor current differential signal. Compared to conventional proportional-resonant control, the robustness of the grid side converter to the disturbance of both grid voltage and rotor converter load was improved by the proposed control strategy, and the dynamic performance of the system was also be greatly enhanced. Simulation and experiment results verify the correctness and effectiveness of the proposed control strategy.%在分析网侧变流器比例谐振控制算法结构的基础上,根据双馈变流器输入输出之间的功率平衡关系,提出一种包括电网电压和转子电流微分信号的前馈控制策略,通过电流微分快速调节网侧电流以维持系统功率平衡.与传统的比例谐振控制相比,前馈控制引入能有效提高系统对电网波动和转子变流器负载扰动的抗干扰能力,加快系统动态性能,仿真和实验验证了所提控制策略的正确性和有效性.

  7. Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor-Mediated Endocytosis

    Science.gov (United States)

    Brosson, Sébastien; Fontaine, Frédéric; Vermeersch, Marjorie; Perez-Morga, David; Pays, Etienne; Bousbata, Sabrina; Salmon, Didier

    2016-01-01

    Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and β-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N-linked glycans binding to both ricin and TL. Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. PMID:27685262

  8. Cell Type-Specific Delivery of RNAi by Ligand-Functionalized Curdlan Nanoparticles: Balancing the Receptor Mediation and the Charge Motivation.

    Science.gov (United States)

    Wu, Yinga; Cai, Jia; Han, Jingfen; Baigude, Huricha

    2015-09-30

    Tissue-specific delivery of therapeutic RNAi has great potential for clinical applications. Receptor-mediated endocytosis plays a crucial role in targeted delivery of biotherapeutics including short interfering RNA (siRNA). Previously we reported a novel Curdlan-based nanoparticle for intracellular delivery of siRNA. Here we designed a nanoparticle based on ligand-functionalized Curdlan. Disaccharides were site-specifically conjugated to 6-deoxy-6-amino Curdlan, and the cell line specificity, cellular uptake, cytotoxicity, and siRNA delivery efficiency of the corresponding disaccharide-modified 6-deoxy-6-amino-Curdlan were investigated. Observation by fluorescence microscopy as well as flow cytometry showed that galactose-containing Curdlan derivatives delivered fluorescently labeled short nucleic acid to HepG2 cells expressing ASGPR receptor but not in other cells lacking surface ASGPR protein. Moreover, highly galactose-substituted Curdlan derivatives delivered siRNA specifically to ASGPR-expressing cells and induced RNAi activities, silencing endogenous GAPDH gene expression. Our data demonstrated that galactose-functionalized 6-deoxy-6-amino-Curdlan is a promising carrier for short therapeutic nucleic acids for clinical applications.

  9. CD36 is not involved in scavenger receptor-mediated endocytic uptake of glycolaldehyde- and methylglyoxal-modified proteins by liver endothelial cells.

    Science.gov (United States)

    Nakajou, Keisuke; Horiuchi, Seikoh; Sakai, Masakazu; Hirata, Kenshiro; Tanaka, Makiko; Takeya, Motohiro; Kai, Toshiya; Otagiri, Masaki

    2005-05-01

    Circulating proteins modified by advanced glycation end-products (AGE) are mainly taken up by liver endothelial cells (LECs) via scavenger receptor-mediated endocytosis. Endocytic uptake of chemically modified proteins by macrophages and macrophage-derived cells is mediated by class A scavenger receptor (SR-A) and CD36. In a previous study using SR-A knockout mice, we demonstrated that SR-A is not involved in endocytic uptake of AGE proteins by LECs [Matsumoto et al. (2000) Biochem. J. 352, 233-240]. The present study was conducted to determine the contribution of CD36 to this process. Glycolaldehyde-modified BSA (GA-BSA) and methylglyoxal-modified BSA (MG-BSA) were used as AGE proteins. 125I-GA-BSA and 125I-MG-BSA underwent endocytic degradation by these cells at 37 degrees C, and this process was inhibited by several ligands for the scavenger receptors. However, this endocytic uptake of 125I-GA-BSA by LECs was not inhibited by a neutralizing anti-CD36 antibody. Similarly, hepatic uptake of (111)In-GA-BSA after its intravenous injection was not significantly attenuated by co-administration of the anti-CD36 antibody. These results clarify that CD36 does not play a significant role in elimination of GA-BSA and MG-BSA from the circulation, suggesting that the receptor involved in endocytic uptake of circulating AGE proteins by LEC is not SR-A or CD36.

  10. The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Benn, Marianne; Christensen, Pernille Møller;

    2012-01-01

    ApoM is mainly associated with HDL. Nevertheless, we have consistently observed positive correlations of apoM with plasma LDL cholesterol in humans. Moreover, LDL receptor deficiency is associated with increased plasma apoM in mice. Here, we tested the idea that plasma apoM concentrations...... are affected by the rate of LDL receptor-mediated clearance of apoB-containing particles. We measured apoM in humans each carrying one of three different LDL receptor mutations (n = 9) or the apoB3500 mutation (n = 12). These carriers had increased plasma apoM (1.34 ± 0.13 µM, P = 0.003, and 1.23 ± 0.10 µM, P...... = 0.02, respectively) as compared with noncarriers (0.93 ± 0.04 µM). When we injected human apoM-containing HDL into Wt (n = 6) or LDL receptor-deficient mice (n = 6), the removal of HDL-associated human apoM was delayed in the LDL receptor-deficient mice. After 2 h, 54 ± 5% versus 90 ± 8% (P

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  14. Somatostatin Receptor-Mediated Tumor-Targeting Nanocarriers Based on Octreotide-PEG Conjugated Nanographene Oxide for Combined Chemo and Photothermal Therapy.

    Science.gov (United States)

    Zhang, Xuyuan; Yang, Chongyin; Zhou, Jianping; Huo, Meirong

    2016-07-01

    Nano-sized in vivo active targeting drug delivery systems have been developed to a high anti-tumor efficacy strategy against certain cancer-cells-specific. Graphene based nanocarriers with unique physical and chemical properties have shown significant potentials in this aspect. Here, octreotide (OCT), an efficient biotarget molecule, is conjugated to PEGylated nanographene oxide (NGO) drug carriers for the first time. The obtained NGO-PEG-OCT complex shows low toxicity and excellent stability in vivo and is able to achieve somatostatin receptor-mediated tumor-specific targeting delivery. Owing to the high loading efficiency and accurate targeting delivery of anti-cancer drug doxorubicin (DOX), our DOX loaded NGO-PEG-OCT complex offers a remarkably improved cancer-cell-specific cellular uptake, chemo-cytotoxicity, and decreased systemic toxicity compared to free DOX or NGO-PEG. More importantly, due to its strong near-infrared absorption, the NGO-PEG-OCT complex further enhances efficient photothermal ablation of tumors, delivering combined chemo and photothermal therapeutic effect against cancer cells. PMID:27244649

  15. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  17. ERK/Egr-1 signaling pathway is involved in CysLT2 receptor-mediated IL-8 production in HEK293 cells.

    Science.gov (United States)

    Lin, Kana; Fang, Sanhua; Cai, Beilei; Huang, Xueqin; Zhang, Xiayan; Lu, Yunbi; Zhang, Weiping; Wei, Erqing

    2014-07-01

    The CysLT2 receptor is involved in myocardial ischemia/reperfusion injury, differentiation of colorectal cancers, bleomycin-induced pulmonary inflammation and fibrosis. However, the signal transduction of cysteinyl leukotriene receptor 2 (CysLT2) in inflammatory responses remains to be clarified. In HEK293 cells stably expressing hCysLT1, hCysLT2 and rGPR17, we determined the signaling pathways for interleukin-8 (IL-8) production after CysLT2 receptor activation. HEK293 cells were stably transfected with the recombinant plasmids of pcDNA3.1(+)-hCysLT1, pcDNA3.1(+)-hCysLT2 and pcDNA3.1-rGPR17. Leukotriene C4 (LTC4) and LTD4 were used as the agonists to induce IL-8 production and the related changes in signal molecules. We found that LTC4 and LTD4 significantly induced IL-8 promoter activation in the HEK293 cells stably expressing hCysLT2, but not in those expressing hCysLT1 and rGPR17. In hCysLT2-HEK293 cells, LTC4 induced elevation of intracellular calcium, ERK1/2 phosphorylation and Egr-1 expression, and stimulated IL-8 expression and release. These responses were blocked by the selective CysLT2 receptor antagonist HAMI3379. The ERK1/2 inhibitor U0126 inhibited Egr-1 and IL-8 expression as well as IL-8 release, but the JNK and p38 inhibitors did not have the inhibitory effects. Down-regulation of Egr-1 by RNA interference with its siRNA inhibited the LTC4-induced IL-8 expression and release. In conclusion, these findings indicate the ERK-Egr-1 pathway of CysLT2 receptors mediates IL-8 production induced by the pro-inflammatory mediators LTC4 and LTD4.

  18. Brain tumor-targeted therapy by systemic delivery of siRNA with Transferrin receptor-mediated core-shell nanoparticles.

    Science.gov (United States)

    Wei, Lin; Guo, Xi-Ying; Yang, Ting; Yu, Min-Zhi; Chen, Da-Wei; Wang, Jian-Cheng

    2016-08-20

    Treatment of brain tumor remains a great challenge worldwide. Development of a stable, safe, and effective siRNA delivery system which is able to cross the impermeable blood-brain barrier (BBB) and target glioma cells is necessary. This study aims to investigate the therapeutic effects of intravenous administration of T7 peptide modified core-shell nanoparticles (named T7-LPC/siRNA NPs) on brain tumors. Layer-by-layer assembling of protamine/chondroitin sulfate/siRNA/cationic liposomes followed by T7 peptide modification has been carried out in order to obtain a targeted siRNA delivery system. In vitro cellular uptake experiments demonstrated a higher intracellular fluorescence intensity of siRNA in brain microvascular endothelial cells (BMVECs) and U87 glioma cells when treated with T7-LPC/siRNA NPs compared with PEG-LPC/siRNA NPs. In the co-culture model of BMVECs and U87 cells, a significant down-regulation of EGFR protein expression occurred in the U87 glioma cells after treatment with the T7-LPC/siEGFR NPs. Moreover, the T7-LPC/siRNA NPs had an advantage in penetrating into a deep region of the tumor spheroid compared with PEG-LPC/siRNA NPs. In vivo imaging revealed that T7-LPC/siRNA NPs accumulated more specifically in brain tumor tissues than the non-targeted NPs. Also, in vivo tumor therapy experiments demonstrated that the longest survival period along with the greatest downregulation of EGFR expression in tumor tissues was observed in mice with an intracranial U87 glioma treated with T7-LPC/siEGFR NPs compared with mice receiving other formulations. Therefore, we believe that these transferrin receptor-mediated core-shell nanoparticles are an important potential siRNA delivery system for brain tumor-targeted therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Science.gov (United States)

    Izzo, Nicholas J; Xu, Jinbin; Zeng, Chenbo; Kirk, Molly J; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Cruchaga, Carlos; Goate, Alison; Cahill, Michael A; Arancio, Ottavio; Mach, Robert H; Craven, Rolf; Head, Elizabeth; LeVine, Harry; Spires-Jones, Tara L; Catalano, Susan M

    2014-01-01

    Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of

  1. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Directory of Open Access Journals (Sweden)

    Nicholas J Izzo

    Full Text Available Amyloid beta (Abeta 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD. We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1 protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological

  2. Does ligand-receptor mediated competitive effect or penetrating effect of iRGD peptide when co-administration with iRGD-modified SSL?

    Science.gov (United States)

    Zhang, Wei-Qiang; Yu, Ke-Fu; Zhong, Ting; Luo, Li-Min; Du, Ruo; Ren, Wei; Huang, Dan; Song, Ping; Li, Dan; Zhao, Yang; Wang, Chao; Zhang, Xuan

    2015-12-01

    Ligand-mediated targeting of anticancer therapeutic agents is a useful strategy for improving anti-tumor efficacy. It has been reported that co-administration of a tumor-penetrating peptide iRGD (CRGDK/RGPD/EC) enhances the efficacy of anticancer drugs. Here, we designed an experiment involving co-administration of iRGD-SSL-DOX with free iRGD to B16-F10 tumor bearing mice to examine the action of free iRGD. We also designed an experiment to investigate the location of iRGD-modified SSL when co-administered with free iRGD or free RGD to B16-F10 tumor bearing nude mice. Considering the sequence of iRGD, we selected the GPDC, RGD and CRGDK as targeting ligands to investigate the targeting effect of these peptides compared with iRGD on B16-F10 and MCF-7 cells, with or without enzymatic degradation. Finally, we selected free RGD, free CRGDK and free iRGD as ligand to investigate the inhibitory effect on RGD-, CRGDK- or iRGD-modified SSL on B16-F10 or MCF-7 cells. Our results indicated that iRGD targeting to tumor cells was ligand-receptor mediated involving RGD to αv-integrin receptor and CRGDK to NRP-1 receptor. Being competitive effect, the administration of free iRGD would not be able to further enhance the anti-tumor activity of iRGD-modified SSL. There is no need to co-administrate of free iRGD with the iRGD-modified nanoparticles for further therapeutic benefit.

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

    Science.gov (United States)

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

    International Nuclear Information System (INIS)

    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.

  5. 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

    Institute of Scientific and Technical Information of China (English)

    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

  6. 一种自适应前向均衡与判决均衡组合结构及变步长改进算法∗%The novel feed forward and decision feedback equalizer structures and improved variable step algorithm

    Institute of Scientific and Technical Information of China (English)

    郝学元; 颜晓红; 钱丽霞

    2015-01-01

    Skin effect and dielectric loss in super-long cable will cause nonlinear attenuation at different signal frequency, and in addition, coupling noise and thermal noise also cause signal distortion at the receiver end. These factors seriously affect the signal transmission speed in the super-long cable. Especially, in the field of exploration of shale gas and bed methane, the transmission cable is also used to transport high-precision synchronization pulse signal, and the synchronization pulse must reach the microsecond accuracy, which is used for data phase calibration. A synchronization signal is a high frequency signal, which suffers more severe attenuation and noise interference. At the receiving end, the sync pulse signal will be drowned in the noise environment, and so it is difficult to restore the original signal. Although fiber can achieve a high transfer rate, but the fiber cable cannot transmit power energy;in addition, the tensile strength and heat resistance of the fiber are much worse than copper cable, these weaknesses limit its application in such industry. Therefore, an effective balancing algorithm is necessary to overcome the propagation effects and interference in a super-long copper cable. However, conventional equalization techniques have well-balanced effect for the short-range communications, but for the long-distance communication, they often have poorly balanced results. In order to solve the above problem and improve the long cable signal transmission speed, this paper presents a new balanced portfolio structure;the new structure uses feed-forward equalizer (FFE) as the pre-stage, and decision-feedback equalizer (DFE) as the post stage to form a new structure. The combination structures can effectively utilize the flexibility of FFE and overcome the problem of error diffusion in DFE. By mathematical modeling and simulation, this paper gives the best combination factors. Furthermore, based on the improved structure, a new convergence

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

    Science.gov (United States)

    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

  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

    DEFF Research Database (Denmark)

    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...... ETB receptor agonist sarafotoxin 6c. The involvement of extracellular regulated kinase (ERK) 1/2 and focal adhesion kinase (FAK) were studied by their specific inhibitors U0126 and PF-228, respectively. Compared to their stretched counterparts, un-stretched MCA segments showed a significantly...

  9. Construction of a comprehensive quality management system for PIVAS by feed forward control theory%运用前馈控制理论全面构建静脉用药调配中心质量控制体系

    Institute of Scientific and Technical Information of China (English)

    李明娥; 王梅林; 王雁林; 许红梅; 陈晓琳

    2015-01-01

    methods of feed forward control and delicacy management,by establishing and completing three-grade-quality management organization,defining the quality control indicators,selecting and demonstrating with the application of expert meeting method and Delphi method,a scientific quality control system was formed.Statistics on unreasonable prescriptions,adverse drug reaction of intravenous infusion,defect of pharmacy intravenous admixture and satisfaction of medical staff and patients were compiled and evaluated throughout the implementation of the practice changes in 38 wards.Results Significant differences were observed in various indicators,comparing statistics collected during 6 months of the same season throughout the implementation of the practice changes.x2 value was 160.54,21.39 and 10.29 by comparison of unreasonable prescriptions,adverse drug reaction and number of drug preparation errors.The satisfaction degree of medical staff and patients improved evidently,x2 value was 14.34 and 26.76.Conclusions The construction and implementation of three-grade-quality management system adapt to high-risk,high strength,high sense of responsibility,process-oriented and intensive management of PIVAS.The impact on the continuous improvement PIVAS quality and assurance in safety of intravenous infusion is remarkable.

  10. Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands

    DEFF Research Database (Denmark)

    Hudson, Brian D; Christiansen, Elisabeth; Murdoch, Hannah;

    2014-01-01

    Analysis of the roles of the short chain fatty acid receptor, free fatty acid 3 receptor (FFA3), has been severely limited by the low potency of its endogenous ligands, the crossover of function of these on the closely related free fatty acid 2 receptor, and a dearth of FFA3-selective synthetic l...

  11. 甲状腺激素非经典核受体作用途径的研究进展%Progress in the Study of Non-classical Nuclear Receptor Mediated Mechanism of Thyroid Hormone

    Institute of Scientific and Technical Information of China (English)

    王浩华

    2012-01-01

    甲状腺激素是维持机体功能活动的基础性激素,在机体产热、新陈代谢、组织分化和器官发育等方面具有重要的调节作用,一般认为甲状腺激素结合靶细胞核内甲状腺激素受体,启动特异性甲状腺激素应答基因的转录表达,发挥生物学效应.近年来研究发现,某些甲状腺激素引起的生物反应迅速,而且不受基因转录与翻译相关抑制剂的影响,提示甲状腺激素存在非经典核受体作用途径,甲状腺激素介导的非经典核受体作用途径在心肌细胞、人神经胶质细胞、人成纤维细胞和成骨细胞等已被证实.%Thyroid hormone( TH )is a basal hormone which maintains the body's functional activity and has a critical role in energy utilization, metabolism, tissue differentiation and organ growth. It's generally considered that most thyroid hormone effects are mediated by direct transcriptional effects of thyroid hormone bound to nuclear thyroid hormone receptors( TRs ). Recently, a new mechanism of thyroid hormone action is identified which is very rapid and not affected by RNA and protein synthesis inhibitor, indicating a non-classical nuclear receptor mediated action. Besides,the non-classical nuclear receptor mediated action of thyroid hormone has been verified in cardiomyocyte, human glioma,human fibroblasts, osteoblast and so on.

  12. Potential of Gibberellic Acid 3 (GA3) for Enhancing the Phytoremediation Efficiency of Solanum nigrum L.

    Science.gov (United States)

    Ji, Puhui; Tang, Xiwang; Jiang, Yongji; Tong, Yan'an; Gao, Pengcheng; Han, Wenshe

    2015-12-01

    A microcosm experiment with artificially contaminated soils was conducted in a greenhouse to evaluate the effect of gibberellic acid 3 (GA3) on phytoremediation efficiency of Solanum nigrum L. The GA3 was applied at three different concentrations (10, 100, 1000 mg L(-1)) to S. nigrum. Results indicated that GA3 can significantly (p phytoremediation efficiency of S. nigrum.

  13. 40 CFR 721.1705 - Benzoic acid, 3-amino-, diazotized, coupled with 6-amino-4-hydroxy-2-naphthalenesulfonic acid...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzoic acid, 3-amino-, diazotized, coupled with 6-amino-4-hydroxy-2-naphthalenesulfonic acid, diazotized, (3-aminophenyl)phosphonic acid and... Significant New Uses for Specific Chemical Substances § 721.1705 Benzoic acid, 3-amino-, diazotized,...

  14. Receptor-mediated delivery of all-trans-retinoic acid (ATRA) to hepatocytes from ATRA-loaded poly(N-p-vinylbenzyl-4-o-{beta}-D-galactopyranosyl-D-gluconamide) nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Seog-Jin [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Moon, Hyun-Seuk [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Guo, Ding-Ding [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Kim, Sang-Heon [Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of) ; Akaike, Toshihiro [Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama 226-8501 (Japan); Cho, Chong-Su [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ]. E-mail: chocs@plaza.snu.ac.kr

    2006-01-15

    All-trans-retinoic acid (ATRA) plays a role in regulating CYP26 gene expression in hepatocytes. Poly(N-p-vinylbenzyl-4-o-{beta}-D-galactopyranosyl-D-gluconamide) (PVLA) nanoparticles have been used as hepatocyte-specific targeting candidates. The objective of this study was to investigate receptor-mediated delivery of ATRA using PVLA nanoparticles. ATRA-loaded PVLA nanoparticles were confirmed by {sup 1}H-nuclear magnetic resonance ({sup 1}H-NMR) and powder X-ray diffraction (XRD). In the {sup 1}H-NMR study, the proton signals of ATRA disappeared in the spectrum of ATRA-loaded PVLA nanoparticles in D{sub 2}O, whereas in dimethylsulfoxide-d{sub 6}, the spectrum seemed like an addition of the respective spectrum of each of the pure components. The crystalline peaks of ATRA disappeared in the XRD pattern of ATRA-loaded PVLA nanoparticles after ATRA was loaded into PVLA nanoparticles. In the measurement of size distribution, diameter of PVLA and ATRA-loaded PVLA nanoparticles in aqueous solution was 6.9 and 61.2 nm in number average, respectively. Flow cytometric analysis showed that the internalization of FITC-PVLA nanoparticles by hepatocytes in the absence of a competitive inhibitor was larger than preincubated with galactose. In reverse transcription-polymerase chain reaction (RT-PCR) analysis, ATRA-loaded PVLA nanoparticles induced CYP26A1 gene in hepatocytes in the absence of a competitive inhibitor but not preincubated with galactose. The results indicate that the ATRA-loaded PVLA nanoparticle can induce CYP26A1 gene in aqueous phase by an asialoglycoprotein receptor (ASGPR)-mediated delivery system.

  15. Implementation of multi-layer feed forward neural network on PIC16F877 microcontroller

    International Nuclear Information System (INIS)

    Artificial Neural Network (ANN) is an electronic model based on the neural structure of the brain. Similar to human brain, ANN consists of interconnected simple processing units or neurons that process input to generate output signals. ANN operation is divided into 2 categories; training mode and service mode. This project aims to implement ANN on PIC micro-controller that enable on-chip or stand alone training and service mode. The input can varies from sensors or switches, while the output can be used to control valves, motors, light source and a lot more. As partial development of the project, this paper reports the current status and results of the implemented ANN. The hardware fraction of this project incorporates Microchip PIC16F877A microcontrollers along with uM-FPU math co-processor. uM-FPU is a 32-bit floating point co-processor utilized to execute complex calculation requires by the sigmoid activation function for neuron. ANN algorithm is converted to software program written in assembly language. The implemented ANN structure is three layer with one hidden layer, and five neurons with two hidden neurons. To prove the operability and functionality, the network is trained to solve three common logic gate operations; AND, OR, and XOR. This paper concludes that the ANN had been successfully implemented on PIC16F877a and uM-FPU math co-processor hardware that works accordingly on both training and service mode. (Author)

  16. Effective enhancement of classification of respiratory states using feed forward back propagation neural networks

    Indian Academy of Sciences (India)

    A Bhavani Sankar; J Arputha Vijaya Selvi; D Kumar; K Seetha Lakshmi

    2013-06-01

    In biomedical signal analysis, Artificial Neural Networks are frequently used for classification, owing to their capability to resolve nonlinearly separable problems and the flexibility to implement them on-chip processor, competently. Artificial Neural Network for a classification task attempts to hand design a network topology and to find a set of network parameters using a back propagation training algorithm. This work presents an intelligent diagnosis system using artificial neural network. Features were extracted from respiratory effort signal based on the threshold-based scheme and the respiratory states were classified into normal, sleep apnea and motion artifacts. The introduced neural classifier was then trained with different back propagation training algorithms and the classified output was compared with the hand designed results. Five different back propagation training algorithms were used for training, such as Levenberg–Marquardt, scaled conjugate gradient, BFGS algorithm, one step secant and Powell–Beale restarts. Our results revealed that the system could correctly classify at an average of 98.7%, when the LM training method was used. Receiver Operating Characteristic (ROC) analysis and confusion matrix showed that the LM method conferred a more balanced and an apt classification of sleep apnea and normal states.

  17. Training a Feed-Forward Neural Network with Artificial Bee Colony based Backpropagation Method

    Directory of Open Access Journals (Sweden)

    Sudarshan Nandy

    2012-09-01

    Full Text Available Back-propagation algorithm is one of the most widely used and popular techniques to optimize the feedforward neural network training. Nature inspired meta-heuristic algorithms also provide derivative-freesolution to optimize complex problem. Artificial bee colony algorithm is a nature inspired meta-heuristicalgorithm, mimicking the foraging or food source searching behaviour of bees in a bee colony and thisalgorithm is implemented in several applications for an improved optimized outcome. The proposedmethod in this paper includes an improved artificial bee colony algorithm based back-propagation neuralnetwork training method for fast and improved convergence rate of the hybrid neural network learningmethod. The result is analysed with the genetic algorithm based back-propagation method, and it isanother hybridized procedure of its kind. Analysis is performed over standard data sets, reflecting the lightof efficiency of proposed method in terms of convergence speed and rate.

  18. Feed forward and feedback control for over-ground locomotion in anaesthetized cats

    Science.gov (United States)

    Mazurek, K. A.; Holinski, B. J.; Everaert, D. G.; Stein, R. B.; Etienne-Cummings, R.; Mushahwar, V. K.

    2012-04-01

    The biological central pattern generator (CPG) integrates open and closed loop control to produce over-ground walking. The goal of this study was to develop a physiologically based algorithm capable of mimicking the biological system to control multiple joints in the lower extremities for producing over-ground walking. The algorithm used state-based models of the step cycle each of which produced different stimulation patterns. Two configurations were implemented to restore over-ground walking in five adult anaesthetized cats using intramuscular stimulation (IMS) of the main hip, knee and ankle flexor and extensor muscles in the hind limbs. An open loop controller relied only on intrinsic timing while a hybrid-CPG controller added sensory feedback from force plates (representing limb loading), and accelerometers and gyroscopes (representing limb position). Stimulation applied to hind limb muscles caused extension or flexion in the hips, knees and ankles. A total of 113 walking trials were obtained across all experiments. Of these, 74 were successful in which the cats traversed 75% of the 3.5 m over-ground walkway. In these trials, the average peak step length decreased from 24.9 ± 8.4 to 21.8 ± 7.5 (normalized units) and the median number of steps per trial increased from 7 (Q1 = 6, Q3 = 9) to 9 (8, 11) with the hybrid-CPG controller. Moreover, within these trials, the hybrid-CPG controller produced more successful steps (step length ≤ 20 cm ground reaction force ≥ 12.5% body weight) than the open loop controller: 372 of 544 steps (68%) versus 65 of 134 steps (49%), respectively. This supports our previous preliminary findings, and affirms that physiologically based hybrid-CPG approaches produce more successful stepping than open loop controllers. The algorithm provides the foundation for a neural prosthetic controller and a framework to implement more detailed control of locomotion in the future.

  19. A feed-forward loop amplifies nutritional regulation of PNPLA3

    OpenAIRE

    Huang, Yongcheng; He, Shaoqing; Li, John Zhong; Seo, Young-Kyo; Osborne, Timothy F; Cohen, Jonathan C.; Hobbs, Helen H.

    2010-01-01

    The upsurge in prevalence of obesity has spawned an epidemic of nonalcoholic fatty liver disease (NAFLD). Previously, we identified a sequence variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) that confers susceptibility to both hepatic triglyceride (TG) deposition and liver injury. To glean insights into the biological role of PNPLA3, we examined the molecular mechanisms by which nutrient status controls hepatic expression of PNPLA3. PNPLA3 mRNA levels, which...

  20. Mitigation of ground motion effects in linear accelerators via feed-forward control

    OpenAIRE

    Pfingstner, J.; Artoos, K.; Charrondiere, C.; Janssens, St.; Patecki, M.; Renier, Y.; Schulte, D.; Tomás, R.; Jérémie, A.; Kubo, K; Kuroda, S.; Naito, T.; Okugi, T.; Tauchi, T.; Terunuma, N.

    2014-01-01

    International audience; Ground motion is a severe problem for many particle accelerators, since it excites beam oscillations, which decrease the beam quality and create beam-beam offset (at colliders). Orbit feedback systems can only compensate ground motion effects at frequencies significantly smaller than the beam repetition rate. In linear colliders, where the repetition rate is low, additional counter measures have to be put in place. For this reason, a ground motion mitigation method bas...

  1. Developing a supervised training algorithm for limited precision feed-forward spiking neural networks

    CERN Document Server

    Stromatias, Evangelos

    2011-01-01

    Spiking neural networks have been referred to as the third generation of artificial neural networks where the information is coded as time of the spikes. There are a number of different spiking neuron models available and they are categorized based on their level of abstraction. In addition, there are two known learning methods, unsupervised and supervised learning. This thesis focuses on supervised learning where a new algorithm is proposed, based on genetic algorithms. The proposed algorithm is able to train both synaptic weights and delays and also allow each neuron to emit multiple spikes thus taking full advantage of the spatial-temporal coding power of the spiking neurons. In addition, limited synaptic precision is applied; only six bits are used to describe and train a synapse, three bits for the weights and three bits for the delays. Two limited precision schemes are investigated. The proposed algorithm is tested on the XOR classification problem where it produces better results for even smaller netwo...

  2. Up/Down Converter Linear Model with Feed Forward and Feedback Stability Analysis

    Directory of Open Access Journals (Sweden)

    Ziad Sobih

    2014-01-01

    Full Text Available After knowing most power electronics circuits, we can say that the operation that we expected are under ideal conditions. The goal of power conversion was achieved by proper circuit configuration and proper switching. Our electronics circuits are treated under ideal conditions and operate in a nominal way. The steady state in most power electronics circuit is periodic steady state. Usually the focus is in operation were the behavior is the same from cycle to cycle. In this paper we will deal with disturbances that will cause the power electronics circuit to deviate from nominal. This includes unexpected changes in the input or load. Also we look at the transient due to start. This deviation from nominal is called dynamic behavior. If this dynamic behavior do not change the desired output significantly we do not do any corrective action. This is rarely the case, however. We have to design the system in order not to deviate from the desired nominal conditions. We need a control system recover to desired specifications. The compensator must operate to restore nominal conditions. second, it must maintain the circuit and guide it to nominal conditions by advancing or delaying the switching time. In this paper we are going to analyze the dynamic behavior due to disturbances or fault and how to control and guide the system to normal. The focus in this paper is dynamics and control and an appropriate model for the non linear circuit to apply this control. From our experience we conceder faults that the system might fall into and we consider treatment from these situations. In our treatment we consider more parameters and more elements to have more flexibility to control the system. The cost of falling in one of these faults might be too high so we have to think of a solution.

  3. A Modified Structure for Feed Forward Active Noise Control Systems With Improved Performa

    Directory of Open Access Journals (Sweden)

    P.Babu

    2010-09-01

    Full Text Available Several approaches have been introduced in literature for active noise control (ANC systems. SinceFxLMS algorithm appears to be the best choice as a controller filter, researchers tend to improveperformance of ANC systems by enhancing and modifying this algorithm. In this paper, the existingFxLMS algorithm is modified which provides a new structure for improving the noise reduction andconvergence rate. Here the proposed method uses two variable step sizes, one for control filter andanother for modelling filter. The control filter step size is varied based on the secondary path thresholdsignal l dˆ . The modelling filter step size is varied based on error signal f (n . It is shown that in theproposed method ANC system noise reduction rate and convergence rate are improved dynamically thanthe FxLMS variable step size methods. The computer simulations results indicate effectiveness of theproposed method.

  4. Evidence Feed Forward Hidden Markov Model: A New Type of Hidden Markov Model

    CERN Document Server

    DelRose, Michael; Frederick, Philip; 10.5121/ijaia.2011.2101

    2011-01-01

    The ability to predict the intentions of people based solely on their visual actions is a skill only performed by humans and animals. The intelligence of current computer algorithms has not reached this level of complexity, but there are several research efforts that are working towards it. With the number of classification algorithms available, it is hard to determine which algorithm works best for a particular situation. In classification of visual human intent data, Hidden Markov Models (HMM), and their variants, are leading candidates. The inability of HMMs to provide a probability in the observation to observation linkages is a big downfall in this classification technique. If a person is visually identifying an action of another person, they monitor patterns in the observations. By estimating the next observation, people have the ability to summarize the actions, and thus determine, with pretty good accuracy, the intention of the person performing the action. These visual cues and linkages are important...

  5. Flat acoustic sources with frequency response correction based on feedback and feed-forward distributed control

    NARCIS (Netherlands)

    Ho, Jen-Hsuan; Berkhoff, A.P.

    2015-01-01

    This paper presents an acoustic source with a small thickness and high bending stiffness. The high bending stiffness is obtained with a sandwich structure in which the face of the sandwich structure internal to the source is perforated to increase the acoustic compliance, thereby leading to increase

  6. Feed-Forward and Feed-Backward Amplification Model from Cochlear Cytoarchitecture: An Interspecies Comparison

    OpenAIRE

    Yoon, Yong-Jin; Steele, Charles R.; Puria, Sunil

    2011-01-01

    The high sensitivity and wide bandwidth of mammalian hearing are thought to derive from an active process involving the somatic and hair-bundle motility of the thousands of outer hair cells uniquely found in mammalian cochleae. To better understand this, a biophysical three-dimensional cochlear fluid model was developed for gerbil, chinchilla, cat, and human, featuring an active “push-pull” cochlear amplifier mechanism based on the cytoarchitecture of the organ of Corti and using the time-ave...

  7. Incoherent feed-forward regulatory loops control segregation of C-mechanoreceptors, nociceptors, and pruriceptors.

    Science.gov (United States)

    Lou, Shan; Pan, Xiaoxin; Huang, Tianwen; Duan, Bo; Yang, Fu-Chia; Yang, Juan; Xiong, Mulin; Liu, Yang; Ma, Qiufu

    2015-04-01

    Mammalian skin is innervated by diverse, unmyelinated C fibers that are associated with senses of pain, itch, temperature, or touch. A key developmental question is how this neuronal cell diversity is generated during development. We reported previously that the runt domain transcription factor Runx1 is required to coordinate the development of these unmyelinated cutaneous sensory neurons, including VGLUT3(+) low-threshold c-mechanoreceptors (CLTMs), MrgprD(+) polymodal nociceptors, MrgprA3(+) pruriceptors, MrgprB4(+) c-mechanoreceptors, and others. However, how these Runx1-dependent cutaneous sensory neurons are further segregated is poorly illustrated. Here, we find that the Runx1-dependent transcription factor gene Zfp521 is expressed in, and required for establishing molecular features that define, VGLUT3(+) CLTMs. Furthermore, Runx1 and Zfp521 form a classic incoherent feedforward loop (I-FFL) in controlling molecular identities that normally belong to MrgprD(+) neurons, with Runx1 and Zfp51 playing activator and repressor roles, respectively (in genetic terms). A knock-out of Zfp521 allows prospective VGLUT3 lineage neurons to acquire MrgprD(+) neuron identities. Furthermore, Runx1 might form other I-FFLs to regulate the expression of MrgprA3 and MrgprB4, a mechanism preventing these genes from being expressed in Runx1-persistent VGLUT3(+) and MrgprD(+) neurons. The evolvement of these I-FFLs provides an explanation for how modality-selective sensory subtypes are formed during development and may also have intriguing implications for sensory neuron evolution and sensory coding.

  8. Sensor based robot laser welding - based on feed forward and gain sceduling algorithms

    DEFF Research Database (Denmark)

    Andersen, Henrik John

    2001-01-01

    A real-time control system forlaser welding of thick steel plates are developed and tested in a industrial environment. The robotic execution of the laser welding process is based on measure weld joint geometry and impirically established welding procedures. The influence of industrial production...

  9. Deep Networks Can Resemble Human Feed-forward Vision in Invariant Object Recognition

    Science.gov (United States)

    Kheradpisheh, Saeed Reza; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

    2016-09-01

    Deep convolutional neural networks (DCNNs) have attracted much attention recently, and have shown to be able to recognize thousands of object categories in natural image databases. Their architecture is somewhat similar to that of the human visual system: both use restricted receptive fields, and a hierarchy of layers which progressively extract more and more abstracted features. Yet it is unknown whether DCNNs match human performance at the task of view-invariant object recognition, whether they make similar errors and use similar representations for this task, and whether the answers depend on the magnitude of the viewpoint variations. To investigate these issues, we benchmarked eight state-of-the-art DCNNs, the HMAX model, and a baseline shallow model and compared their results to those of humans with backward masking. Unlike in all previous DCNN studies, we carefully controlled the magnitude of the viewpoint variations to demonstrate that shallow nets can outperform deep nets and humans when variations are weak. When facing larger variations, however, more layers were needed to match human performance and error distributions, and to have representations that are consistent with human behavior. A very deep net with 18 layers even outperformed humans at the highest variation level, using the most human-like representations.

  10. Sensor based robot laser welding - based on feed forward and gain sceduling algorithms

    OpenAIRE

    Andersen, Henrik John

    2001-01-01

    A real-time control system forlaser welding of thick steel plates are developed and tested in a industrial environment. The robotic execution of the laser welding process is based on measure weld joint geometry and impirically established welding procedures. The influence of industrial production environment and manufacturing tolerences of the workpieces are evaluated.

  11. Combining synaptic and cellular resonance in a feed-forward neuronal network

    OpenAIRE

    Jonathan D Drover; Tohidi, Vahid; Bose, Amitabha; Nadim, Farzan

    2007-01-01

    We derive a mathematical theory to explain the subthreshold resonance response of a neuron to synaptic input. The theory shows how a neuron combines information from its intrinsic resonant properties with those of the synapse to determine the neuron’s generalized resonance response. Our results show that the maximal response of a postsynaptic neuron can lie between the preferred intrinsic frequency of the neuron and the synaptic resonance frequency. We compare our theoretical results to paral...

  12. Noiseless phase quadrature amplification via an electro-optic feed-forward technique

    CERN Document Server

    Buchler, B C; Ralph, T C; Buchler, Ben C.; Huntington, Elanor H.; Ralph, Timothy C.

    1999-01-01

    Theoretical results are presented which show that noiseless phase quadrature amplification is possible, and limited experimentally only by the efficiency of the phase detection system. Experimental results obtained using a Nd:YAG laser show a signal gain of 10dB and a signal transfer ratio of T_s=0.9. This result easily exceeds the standard quantum limit for signal transfer. The results also explicitly demonstrate the phase sensitive nature of the amplification process.

  13. Feature Extraction of Olive Ridley Sea Turtle Using Feed Forward neural Network

    Directory of Open Access Journals (Sweden)

    Capt. Dr.S.Santhosh Baboo

    2014-10-01

    Full Text Available The paper deals with the computer based auto detection of particular species of sea turtles. In this process, three parameters have been taken and trained in artificial neural network for detecting the particular species among the popular seven species of the world. The existing algorithm for auto photo identification of detecting the particular species is much complicated due to classification process in the algorithm. To improve this algorithm, new technique has been used in feature extraction of the image and there are 10 images where trained and then finally particular species Olive Ridely is retrieved. These images are trained through artificial neural network and result of the images is plotted in the graphs.

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

    OpenAIRE

    Luz, Yotam; Shamir, Maoz

    2016-01-01

    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 lea...

  15. Deep Networks Can Resemble Human Feed-forward Vision in Invariant Object Recognition

    Science.gov (United States)

    Kheradpisheh, Saeed Reza; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

    2016-01-01

    Deep convolutional neural networks (DCNNs) have attracted much attention recently, and have shown to be able to recognize thousands of object categories in natural image databases. Their architecture is somewhat similar to that of the human visual system: both use restricted receptive fields, and a hierarchy of layers which progressively extract more and more abstracted features. Yet it is unknown whether DCNNs match human performance at the task of view-invariant object recognition, whether they make similar errors and use similar representations for this task, and whether the answers depend on the magnitude of the viewpoint variations. To investigate these issues, we benchmarked eight state-of-the-art DCNNs, the HMAX model, and a baseline shallow model and compared their results to those of humans with backward masking. Unlike in all previous DCNN studies, we carefully controlled the magnitude of the viewpoint variations to demonstrate that shallow nets can outperform deep nets and humans when variations are weak. When facing larger variations, however, more layers were needed to match human performance and error distributions, and to have representations that are consistent with human behavior. A very deep net with 18 layers even outperformed humans at the highest variation level, using the most human-like representations. PMID:27601096

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

    DEFF Research Database (Denmark)

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

    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) ...

  17. Cell cycle regulation by feed-forward loops coupling transcription and phosphorylation

    DEFF Research Database (Denmark)

    Csikász-Nagy, Attila; Kapuy, Orsolya; Tóth, Attila;

    2009-01-01

    ) from Cdk1. By mathematical modelling, we show that such FFLs can activate EPs at different phases of the cell cycle depending of the effective signs (+ or -) of the regulatory steps of the FFL. We provide several case studies of EPs that are controlled by FFLs exactly as our models predict. The signal......-transduction properties of FFLs allow one (or a few) Cdk signal(s) to drive a host of cell cycle responses in correct temporal sequence.......The eukaryotic cell cycle requires precise temporal coordination of the activities of hundreds of 'executor' proteins (EPs) involved in cell growth and division. Cyclin-dependent protein kinases (Cdks) play central roles in regulating the production, activation, inactivation and destruction...

  18. 3β-Acetyl Tormentic Acid (3ATA a Novel Modulator of ABCC Proteins Activity

    Directory of Open Access Journals (Sweden)

    Cerli Rocha Gattass

    2012-06-01

    Full Text Available Multidrug resistance (MDR is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport and circumventing MDR, a great amount of work has been dedicated to identifying pharmacological inhibitors of specific ABC transporters. We recently showed that 3β-acetyl tormentic acid (3ATA had no effect on P-gp/ABCB1 activity. Herein, we show that 3ATA strongly inhibited the activity of MRP1/ABCC1. In the B16/F10 and Ma104 cell lines, this effect was either 20X higher or similar to that observed with MK571, respectively. Nevertheless, the low inhibitory effect of 3ATA on A549, a cell line that expresses MRP1-5, suggests that it may not inhibit other MRPs. The use of cells transfected with ABCC2, ABCC3 or ABCC4 showed that 3ATA was also able to modulate these transporters, though with an inhibition ratio lower than that observed for MRP1/ABCC1. These data point to 3ATA as a new ABCC inhibitor and call attention to its potential use as a tool to investigate the function of MRP/ABCC proteins or as a co-adjuvant in the treatment of MDR tumors.

  19. Crystal Structure of Nicotinic Acid(3,5-dinitrobenzoic Acid Organic Adduct

    Institute of Scientific and Technical Information of China (English)

    朱军; 郑吉民

    2004-01-01

    The title compound nicotinic acid(3,5-dinitrobenzoic acid(NDNT)has been obtained by the reaction of nicotinic acid with 3,5-dinitrobenzoic acid in deionic water at room temperature.The crystal is of monoclinic,space group P21/n with a=14.053(6),b=5.046(2),c=20.105(8)A,β=103.573(8)°,C13H9N3O8,Mr=335.23,Z=4,V=1385.8(10)A3,Dc=1.607g/cm3,μ(MoKα)=0.137 mm-1,F(000)=688,R=0.0435 and wR=0.0993 for 1239 observed reflections (I>2σ(I)).In the crystals,the asymmetric unit contains one nicotinic acid (C6H5NO2)and one 3,5-dinitrobenzoic acid (C7H4N2O6)molecules which are linked by some hydrogen bonds to form a twenty-membered hydrogen-bonded ring and an extended linear structure.

  20. NMDA receptors mediate synaptic competition in culture.

    Directory of Open Access Journals (Sweden)

    Kevin She

    Full Text Available BACKGROUND: Activity through NMDA type glutamate receptors sculpts connectivity in the developing nervous system. This topic is typically studied in the visual system in vivo, where activity of inputs can be differentially regulated, but in which individual synapses are difficult to visualize and mechanisms governing synaptic competition can be difficult to ascertain. Here, we develop a model of NMDA-receptor dependent synaptic competition in dissociated cultured hippocampal neurons. METHODOLOGY/PRINCIPAL FINDINGS: GluN1 -/- (KO mouse hippocampal neurons lacking the essential NMDA receptor subunit were cultured alone or cultured in defined ratios with wild type (WT neurons. The absence of functional NMDA receptors did not alter neuron survival. Synapse development was assessed by immunofluorescence for postsynaptic PSD-95 family scaffold and apposed presynaptic vesicular glutamate transporter VGlut1. Synapse density was specifically enhanced onto minority wild type neurons co-cultured with a majority of GluN1 -/- neighbour neurons, both relative to the GluN1 -/- neighbours and relative to sister pure wild type cultures. This form of synaptic competition was dependent on NMDA receptor activity and not conferred by the mere physical presence of GluN1. In contrast to these results in 10% WT and 90% KO co-cultures, synapse density did not differ by genotype in 50% WT and 50% KO co-cultures or in 90% WT and 10% KO co-cultures. CONCLUSIONS/SIGNIFICANCE: The enhanced synaptic density onto NMDA receptor-competent neurons in minority coculture with GluN1 -/- neurons represents a cell culture paradigm for studying synaptic competition. Mechanisms involved may include a retrograde 'reward' signal generated by WT neurons, although in this paradigm there was no 'punishment' signal against GluN1 -/- neurons. Cell culture assays involving such defined circuits may help uncover the rules and mechanisms of activity-dependent synaptic competition in the developing nervous system.

  1. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Lara eCosta

    2015-03-01

    Full Text Available Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD in wild-type (wt and in Fmr1 KO mice, a mouse model of Fragile X syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices.Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions.The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of

  2. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome.

    Science.gov (United States)

    Costa, Lara; Sardone, Lara M; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

  3. Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    International Nuclear Information System (INIS)

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe1-Tyr3-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T1/2 =9.5 hr; β+=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67Ga- and 68Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPETTM images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0±0.7, 13.2±2.1 and 9.8±1.5 for 66Ga-, 67Ga-, and 68Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio 1.64), and high kidney uptake must be eliminated

  4. In vitro antifungal potentials of bioactive compound oleic acid, 3-(octadecyloxy) propyl ester isolated from Lepidagathis cristata Willd. (Acanthaceae) inflorescence

    Institute of Scientific and Technical Information of China (English)

    Maghdu Nainamohamed Abubacker; Palaniyappan Kamala Devi

    2014-01-01

    Objective: To identify bioactive compound oleic acid, 3-(octadecyloxy) propyl ester from Lepidagathis cristata Willd. (L. cristata) and to assess antifungal potentials of the isolated compound. Methods: Aqueous extracts of L. cristata inflorescence were used for this study. The major bioactive compound isolated was tested for antifungal activities. Results: The major bioactive compound oleic acid, 3-(octadecyloxy) propyl ester was isolated from the inflorescence of L. cristata. The bioactive compound was tested for antifungal potentials and found to be highly effective to plant pathogenic fungi Colletotrichum fulcatum NCBT 146, Fusarium oxysporum NCBT 156 and Rhizoctonia solani NCBT 196 as well as for the human pathogenic fungi Curvularia lunata MTCC 2030 and Microsporum canis MTCC 2820. Conclusions: The results justify the antifungal potentials of both plant and human pathogenic fungi. The plant bioactive compound will be helpful in herbal antifungal formulations.

  5. Synthesis of pteroylglutamic acid-3',5'-2H2 by trifluoroacetic acid catalyzed exchange with deuterium oxide

    International Nuclear Information System (INIS)

    Pteroylglutamic acid (PGA) was deuterated by trifluoroacetic acid catalyzed exchange with deuterium oxide. The product, pteroylglutamic acid-3',5'-2H2, was specifically deuterated in the aromatic protons of the p-aminobenzoyl (PABA) moiety; the protons on C7 and C9 and in the glutamic acid residue were not exchanged. Deuterium incorporation was measured by chemical ionization mass spectrometry (CI-MS). Pteroylglutamates were cleaved by a base-catalyzed, oxidative hydrolysis to PABA, which was converted to the methyl ester, N-trifluoroacetate for analysis by gas chromatography-chemical ionization-mass spectrometry. Products from the exchange typically contained 1 percent 2H1 and 90 percent 2H2 species. The procedure may be used to label specifically various analogs of PGA with deuterium in the PABA portion of the molecule

  6. Photovoltaic Properties of Poly (3-Hexylthiophene: [6, 6]-Phenyl C61-Butyric Acid 3-Ethylthiophene Thin Films

    Directory of Open Access Journals (Sweden)

    B.M. Omer

    2013-07-01

    Full Text Available We fabricated and studied the electrical and photovoltaic properties of organic solar cell based on poly (3-hexylthiophene (P3HT as an electron donor blended with the acceptor [6, 6]-Phenyl C61-Butyric Acid 3-Ethylthiophene Ester (modified fullerene. The active layer composed of (3:1, w/w mixture of P3HT and the modified fullerene was sandwiched between indium tin oxide (ITO and aluminum (Al. The ideality factor n and barrier hight b values were determined from the dark current density-voltage characteristics and found as 2.45 and 0.78 eV, respectively. The device shows photovoltaic behavior with an open circuit voltage of 400 mV, short circuit current of 22.9 A/cm2 and fill factor 0.32 under 2.8 mW/cm2 light intensity.

  7. Microbial Production of Glycyrrhetic Acid 3-O-mono-βββ-D-glucuronide From Glycyrrhizin by Aspergillus terreus

    Directory of Open Access Journals (Sweden)

    Amin, H. A.

    2010-01-01

    Full Text Available Among seven fungi (three Aspergilli and four Penicilli have been screened for production of glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG from glycyrrhizin (GL, Aspergillus terreus was found to be the most potent GAMG producer. This strain was capable of expressing two intracellular β-D-glucuronidase forms, one responsible for partial hydrolysis of GL to GAMG and the other one for hydrolysis of GL to glycyrrhetic acid (GA. The highest yield of GAMG was achieved when the reaction mixture was incubated at pH 6 at 40 °C for 1 h using GL (0.1%, w/v as a substrate. The maximum hydrolytic activity for production of GAMG (396 U/mL was obtained using production medium composed of (g%, w/v: corn steep liquor 2.5, soybean flour 3.5, glucose 0.5 and CaCO3 0.5; pH 6.0. The medium was inoculated with 15% (v/v inoculum and incubated at 27 °C for 3 days. Under these optimal conditions, GAMG yield became about 2 times higher than GA yield and the cells bioconversion efficiency increased from 24.6 to 78.3%.

  8. Induced resistance by cresotic acid (3-hydroxy-4-methyl methylbenzoic acid) against wilt disease of melon and cotton

    International Nuclear Information System (INIS)

    Cresotic acid (3-hydroxy-4-methylbenzoic acid) was proved be active in controlling wilt diseases of melon and cotton plants grown in the house. Soil drench with 200-1000 ppm cresotic acid induced 62-77 %, 69-79 % and 50-60 % protection against Fusarium oxysporum f.sp melonis (FOM) in melon, Fusarium oxysporum f.sp vasinfectum (FOV) and Verticillium dahliae in cotton, respectively. Since no inhibitory effect of cresotic acid on mycelial growth of these three fungual pathogens was observed in vitro, it is suggested that control of these wilt diseases with cresotic acid resulted from induced resistance. Cresotic acid induced resistance in melon plants not only against race 0, race 1, race 2 and race 1,2, but also against a mixture of these four races of FOM, suggesting a non-race- specific resistance. Level of induced resistance by cresotic acid against FOM depended on inoculum pressure applied to melon plants. At 25 day after inoculation with FOM, percentage protection induced by cresotic acid under low inoculum pressure retained a level of 51 %, while under high inoculum pressure percentage protection decreased to only 10 %. High concentrations of cresotic acid significantly reduced plant growth. Reduction in fresh weight of melon (36-51%) and cotton (42-71%) was obtained with 500-1000 ppm cresotic acid, while only less than 8% reduction occurred with 100-200 ppm. (author)

  9. A feed-forward artificial neural network with enhanced feature selection for power system transient stability assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sawhney, Harinder; Jeyasurya, B. [Faculty of Engineering and Applied Science, Memorial University of Newfoundland, St. John' s, Newfoundland (Canada A1B3X5)

    2006-08-15

    This paper describes an approach where an artificial neural network is used to predict the stability status of the power system. This efficient and robust approach combines the advantages of the time-domain integration schemes and artificial neural network for on-line transient stability assessment of the power system. The transient stability index has been obtained by the extended equal area criterion method and is used as an output of the neural network. Two feature selection techniques have been used to identify the input variables best suitable for training. The proposed technique predicts the transient stability index correctly, without any false alarm. In addition, the transient stability index as an output of the neural network helps to implement possible control actions. The results obtained demonstrate the potential for neural network to be a part of any on-line dynamic security assessment tool. (author)

  10. Regulation of Apoptotic c-Jun N-Terminal Kinase Signaling by a Stabilization-Based Feed-Forward Loop†

    OpenAIRE

    Xu, Zhiheng; Kukekov, Nikolay V.; Greene, Lloyd A.

    2005-01-01

    A sequential kinase cascade culminating in activation of c-Jun N-terminal kinases (JNKs) plays a fundamental role in promoting apoptotic death in many cellular contexts. The mechanisms by which this pathway is engaged in response to apoptotic stimuli and suppressed in viable cells are largely unknown. Here, we show that apoptotic stimuli increase endogenous cellular levels of pathway components, including POSH, mixed lineage kinases (MLKs), and JNK interacting protein 1, and that this effect ...

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

    OpenAIRE

    Latha. S. C; Dr. Venugopal .N

    2014-01-01

    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 ...

  12. A comparison between the performance of feed forward neural networks and the supervised growing neural gas algorithm

    Science.gov (United States)

    Berlich, Rüdiger; Kunze, Marcel

    1997-02-01

    The Supervised Growing Neural Gas algorithm (SGNG) provides an interesting alternative to standard Multi-Layer Perceptrons (MLP). A comparison is drawn between the performance of SGNG and MLP in the domain of function mapping. A further field of interest is classification power, which has been investigated with real data taken by PS197 at CERN. The characteristics of the two network models will be discussed from a practical point of view as well as their advantages and disadvantages.

  13. Conglomeration of Hand Shapes and Texture Information for Recognizing Gestures of Indian Sign Language Using Feed forward Neural Networks

    Directory of Open Access Journals (Sweden)

    P.V.V.Kishore

    2013-10-01

    Full Text Available This research paper highlights the use of shape and texture information for recognizing gestures of Indian sign language. The proposed method involves extracting the hand segments from theoriginal color gesture images and subjecting them to further processing. In the next stage texture information of the hands in extracted using gabor filter. Again from the segmented hand portions shape is modeled using Chan-Vese(CV active contour model. Finally both the shape and texture information are merged together to produce a feature vector that essentially represents a sign in Indian SignLanguage. To reduce the dimensionality of the feature matrix principle component analysis is applied on the feature matrix. The obtained feature matrix will train a artificial neural network the learns using error back propagation algorithm. Indian sign language database was created for around 36 signs with 10 different signers. For training 4 sets gesture images were used and the remaining 6 sets were used for testing. After extensive testing under various conditions the average recognition rate stands at 98.2%.

  14. Sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}ester a recyclable catalyst for the synthesis of 2-aryl-1-arylmethyl- 1H-1,3-benzimidazole derivatives

    Institute of Scientific and Technical Information of China (English)

    Nasir Iravani; Negar Safikhani Mohammadzade; Khodabakhsh Niknam

    2011-01-01

    A highly selective synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles from the reaction of o-phenylenediamine and aromatic aldehydes in the presence of sulfuric acid {[3-(3-silicapropyl)sulfanyl]propyl}Jester (SASPSPE) in water and at 80 ℃ in good to excellent yields.

  15. 苯丙酸诺龙对烫伤模型大鼠雄激素受体介导靶基因转录调控的影响%Effect of nandrolone phenylpropionate on androgen receptor-mediated transcriptional regulation of target genes in rat scald models

    Institute of Scientific and Technical Information of China (English)

    李凯; 岑瑛

    2015-01-01

    BACKGROUND:Moderate to severe burn and trauma, treatment of which has been paid equal attention to wound surface, is always a difficulty of clinical systemic treatment and has a poor prognosis. Anabolic hormones have acquired secure and good results in the treatment of burns in both animals and clinical patients. Although use of anabolic hormones is restricted by the doping management, but its androgen receptor and nuclear receptor coregulators are the newly emerging areas of interests in the field of gene regulation mechanism in recent years. OBJECTIVE:To investigate the effect of nandrolone phenylpropionate on androgen receptor-mediated transcriptional regulation of target gene in rat scald models. METHODS: Thirty-six rats were randomly divided into nandrolone phenylpropionate, model and control groups. In the nandrolone phenylpropionate and model groups, rats were subjected to a 20% total body surface area second-degree scald injury by hot water. Two days after model preparation, rats in these two groups were intramuscularly injected with nandrolone phenylpropionate and saline, once every other day, for a total of 21 days. RESULTS AND CONCLUSION:The gene expression levels of steroid receptor coactivator-1 and insulin-like growth factor 1 in the rat livers and gonads (testes, ovaries) were significantly different between the nandrolone phenylpropionate and model groups (P 0.05)。说明在不同组织不同生理病理条件下苯丙酸诺龙对类固醇受体辅助活化因子1、c-myc、胰岛素样生长因子1基因表达的作用是不同的。

  16. Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines.

    Directory of Open Access Journals (Sweden)

    Ashiq Hussain

    2016-05-01

    Full Text Available The ability to find and consume nutrient-rich diets for successful reproduction and survival is fundamental to animal life. Among the nutrients important for all animals are polyamines, a class of pungent smelling compounds required in numerous cellular and organismic processes. Polyamine deficiency or excess has detrimental effects on health, cognitive function, reproduction, and lifespan. Here, we show that a diet high in polyamine is beneficial and increases reproductive success of flies, and we unravel the sensory mechanisms that attract Drosophila to polyamine-rich food and egg-laying substrates. Using a combination of behavioral genetics and in vivo calcium imaging, we demonstrate that Drosophila uses multisensory detection to find and evaluate polyamines present in overripe and fermenting fruit, their favored feeding and egg-laying substrate. In the olfactory system, two coexpressed ionotropic receptors (IRs, IR76b and IR41a, mediate the long-range attraction to the odor. In the gustatory system, multimodal taste sensation by IR76b receptor and GR66a bitter receptor neurons is used to evaluate quality and valence of the polyamine providing a mechanism for the fly's high attraction to polyamine-rich and sweet decaying fruit. Given their universal and highly conserved biological roles, we propose that the ability to evaluate food for polyamine content may impact health and reproductive success also of other animals including humans.

  17. Aryl hydrocarbon receptor mediates benzene-induced hematotoxicity.

    Science.gov (United States)

    Yoon, Byung-Il; Hirabayashi, Yoko; Kawasaki, Yasushi; Kodama, Yukio; Kaneko, Toyozo; Kanno, Jun; Kim, Dae-Yong; Fujii-Kuriyama, Yoshiaki; Inoue, Tohru

    2002-11-01

    Benzene can induce hematotoxicity and leukemia in humans and mice. Since a review of the literature shows that the CYP2E1 knockout mouse is not known to possess any benzene toxicity, the metabolism of benzene by CYP2E1 in the liver is regarded to be prerequisite for its cytotoxicity and genotoxicity, although the mechanism is not fully understood yet. Because it was found some years ago that benzene was also a substrate for CYP1A1, we investigated the involvement of the aryl hydrocarbon receptor (AhR) in benzene hematotoxicity using AhR wild-type (AhR(+/+)), heterozygous (AhR(+/-)), and homozygous (AhR(-/-)) male mice. Interestingly, following a 2-week inhalation of 300 ppm benzene (a potent dose for leukemogenicity), no hematotoxicity was induced in AhR(-/-) mice. Further, there were no changes in cellularity of peripheral blood and bone marrow (BM), nor in levels of granulocyte-macrophage colony-forming units in BM. This lack of hematotoxicity was associated with the lack of p21 overexpression, which was regularly seen in the wild-type mice following benzene inhalation. Combined treatment with two major benzene metabolites, phenol and hydroquinone, induced hemopoietic toxicity, although it was not known whether this happened due to a surprising lack of expression of CYP2E1 by AhR knockout, or due to a lack of other AhR-mediated CYP enzymes, including 1A1 (i.e., a possible alternative pathway of benzene metabolism). The former possibility, evaluated in the present study, failed to show a significant relationship between AhR and the expression of CYP2E1. Furthermore, a subsequent evaluation of AhR expression after benzene inhalation tended to show higher but less significant expression in the liver, and none in the BM, compared with sham control. Although this study failed to identify the more likely of the above-mentioned two possibilities, the study using AhR knockout mice on benzene inhalation presents the unique possibility that the benzene toxicity may be regulated by AhR signaling.

  18. Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis

    Directory of Open Access Journals (Sweden)

    J. Sardinha

    2014-01-01

    Full Text Available Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics. The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS in mice and intestinal microcirculation was assessed through intravital microscopy. We found that HU308 (CB2 receptor agonist reduced the number of adherent leukocytes in submucosal venules but did not restore muscular and mucosal villi FCD in endotoxemic mice. AM630 (CB2 receptor antagonist maintained the level of adherent leukocytes induced by LPS but further reduced muscular and mucosal villi FCD. URB597 (FAAH inhibitor and JZL184 (MAGL inhibitor both reduced the number of adherent leukocytes in submucosal venules but did not restore the mucosal villi FCD. Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.

  19. Receptor-mediated regional sympathetic nerve activation by leptin.

    OpenAIRE

    Haynes, W G; Morgan, D A; Walsh, S A; Mark, A L; Sivitz, W I

    1997-01-01

    Leptin is a peptide hormone produced by adipose tissue which acts centrally to decrease appetite and increase energy expenditure. Although leptin increases norepinephrine turnover in thermogenic tissues, the effects of leptin on directly measured sympathetic nerve activity to thermogenic and other tissues are not known. We examined the effects of intravenous leptin and vehicle on sympathetic nerve activity to brown adipose tissue, kidney, hindlimb, and adrenal gland in anesthetized Sprague-Da...

  20. Nucleus incertus Orexin2 receptors mediate alcohol seeking in rats.

    Science.gov (United States)

    Kastman, Hanna E; Blasiak, Anna; Walker, Leigh; Siwiec, Marcin; Krstew, Elena V; Gundlach, Andrew L; Lawrence, Andrew J

    2016-11-01

    Alcoholism is a chronic relapsing disorder and a major global health problem. Stress is a key precipitant of relapse in human alcoholics and in animal models of alcohol seeking. The brainstem nucleus incertus (NI) contains a population of relaxin-3 neurons that are highly responsive to psychological stressors; and the ascending NI relaxin-3/RXFP3 signalling system is implicated in stress-induced reinstatement of alcohol seeking. The NI receives orexinergic innervation and expresses orexin1 (OX1) and orexin2 (OX2) receptor mRNA. In alcohol-preferring (iP) rats, we examined the impact of yohimbine-induced reinstatement of alcohol seeking on orexin neuronal activation, and the effect of bilateral injections into NI of the OX1 receptor antagonist, SB-334867 (n = 16) or the OX2 receptor antagonist, TCS-OX2-29 (n = 8) on stress-induced reinstatement of alcohol seeking. We also assessed the effects of orexin-A on NI neuronal activity and the involvement of OX1 and OX2 receptors using whole cell patch-clamp recordings in rat brain slices. Yohimbine-induced reinstatement of alcohol seeking activated orexin neurons. Bilateral NI injections of TCS-OX2-29 attenuated yohimbine-induced reinstatement of alcohol seeking. In contrast, intra-NI injection of SB-334867 had no significant effect. In line with these data, orexin-A (600 nM) depolarized a majority of NI neurons recorded in coronal brain slices (18/28 cells), effects prevented by bath application of TCS-OX2-29 (10 μM), but not SB-334867 (10 μM). These data suggest an excitatory orexinergic input to NI contributes to yohimbine-induced reinstatement of alcohol seeking, predominantly via OX2 receptor signalling. PMID:27395787

  1. Accepted: 2008-11-05Delivery and immunologic efficacy of CpG ODN targeting B lymphocytes of umbilical cord blood by CD40 ligand-receptor-mediated carrier%CD40配体-受体载体介导的CpG ODN靶向脐血B淋巴细胞的特异传递及其免疫效应

    Institute of Scientific and Technical Information of China (English)

    曾慧兰; 蒋建伟; 郑梅珍; 古晨; 韩新爱; 曾耀英; 狄静芳; 严玉霞

    2009-01-01

    cells and degradation by nuclease blocks its clinical application. OBJECTIVE: To explore the specific delivery and its immunologic efficacy of CpG ODN targeting B lymphocytes of umbilical cord blood by CD40 ligand-receptor-mediated carrier system. DESIGN, TIME AND SETTING: An observation and control experiment was performed at the Department of Hematology, and Department of Pediatric, the First Affiliated Hospital of Jinan University from April 2004 to October 2007. MATERIALS: Fresh umbilical cord blood with heparin was obtained from healthy, natal infant. Informed consent was obtained from his parents, and the experiment was approved by the hospital Ethics Committee. METHODS: CD40 ligand (CD40L)-EDC-PLL-CpG ODN conjugated complex was prepared. Mononuclear cells (MNCs) from umbilical cord blood were co-cultured with conjugated complexes. Uptake rate, mean fluorescence intensity of FAM marked CpG ODN, expressions of MNCs, proliferations of lymphocytes and the IgG levels of culture supematants were detected by flow cytometry, fluorescence techniques, MTT assay and ELISA, respectively. MAIN OUTCOME MEASURES: The uptake rate, the mean fluorescence intensity of CpG ODN by MNCs, subgroups and proliferations of lymphocytes, and IgG levels of culture supematants. RESULTS: Compared to the pure CpG ODN group, the uptake rate of the conjugated complexes group was higher (98%), the peak level of up-taking occurred earlier, and intracellular fluorescence intensity maintained much more stable. Expressions of CD19+, CD22+, and CD20+ was increased, A value and IgG levels in supematants were all higher than that of the control group. CONCLUSION: CD40 tigand-receptor-mediated carrier system is helpful for CpG ODN delivery targeting to B lymphocyte, enhancing its immunological efficiency.

  2. 胖Zucker大鼠肠系膜动脉多巴胺D1受体介导的血管舒张功能受损及其机制%Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats and its underlying mechanisms

    Institute of Scientific and Technical Information of China (English)

    符金娟; 韩愈; 王震; 关蔚蔚; 刘渔凯; 杨迪; 黄河飞; 杨素菲; 曾春雨

    2014-01-01

    目的 观察多巴胺D1受体激动剂Fenoldopam介导的血管舒张反应性在胖、瘦Zucker大鼠中的差异.方法 取12~14周健康雄性胖、瘦Zucker大鼠(n=12),采用鼠尾动脉无创测压法测定血压;采用离体微血管张力测定系统,观察雄性胖、瘦Zucker大鼠肠系膜三级动脉在内皮完整与去除后,Fenoldopam(1×10-8~3×10-6 mol/L)对苯肾上腺素(PHE,1×10-5 mol/L)预收缩血管的舒张作用.用多巴胺D1受体拮抗剂SCH23390(10-7 mol/L)预孵育Zucker大鼠肠系膜动脉30 min,观察Fenoldopam通过多巴胺D1受体舒张血管的特异性.采用蛋白免疫印迹法测定胖、瘦Zucker大鼠肠系膜组织多巴胺D1受体表达量的差异.结果 与瘦Zucker大鼠相比,胖Zucker大鼠的血压增高.在Fenoldopam 3×10-6mol/L时,瘦Zucker大鼠肠系膜动脉的舒张效应明显强于胖Zucker大鼠[(63.43±13.79)%比(20.75±8.60)%,P<0.01].去内皮前后,胖、瘦Zucker大鼠肠系膜动脉对Fenoldopam的舒张效应比较,差异无统计学意义(均P>0.05).SCH23390可以拮抗Fenoldopam对胖、瘦Zucker大鼠血管的舒张效应.蛋白免疫印迹结果显示,瘦Zucker大鼠肠系膜组织多巴胺D1受体表达量高于胖Zucker大鼠[(1.26±0.04)%比(0.74±0.06)%,P<0.01].结论 与瘦Zucker大鼠相比,胖Zucker大鼠血压增高;增高的血压可能与肠系膜动脉多巴胺D1受体表达量下降引起的Fenoldopam的血管舒张效应下降有关.%Objective To investigate the difference of dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries between obese and lean Zucker rats,as well as its underlying mechanisms.Methods The blood pressures of obese and lean Zucker rats (12-14 weeks) were measured at tail artery (n=12).In an in-vitro microvascular tension measurement system,the relaxation effect of Fenoldopam (1 × 10-8 to 3 × 10-6 mol/L) on mesenteric arteries from all rats,with or without intact endothelium,was evaluated in a setting of phenylephedrine (PHE,1

  3. Optical Properties of MEH-PPV and MEH-PPV/ [6,6]-Phenyl C61-butyric Acid 3-ethylthiophene Ester Thin Films

    Directory of Open Access Journals (Sweden)

    B.M. Omer

    2012-12-01

    Full Text Available Thin films of Poly [2-methoxy-5-(2-ethylhexyloxy-1,4-phenylenevinylene] (MEH-PPV were prepared from chloroform, 1,2-dichlorobenzene and toluene solutions by spin coating technique on quartz substrates. Absorption and photoluminescence (PL spectra of the polymer thin films prepared from different solvents were measured. It was concluded from the UV-Vis absorption and PL spectra that the optical properties of MEH-PPV films strongly affected by solvents used for spin coating. A strong photoluminescence quenching was observed in (1:4 MEH-PPV: [6,6]-Phenyl C61-butyric Acid 3-ethylthiophene Ester (Modified Fullerene composite which provides evidence of photoinduced charge transfer. Further, with Atomic Force Microscope (AFM it has been demonstrated that the surface morphology of the MEH-PPV: Modified fullerene thin films are strongly dependent on the preparation condition (solvents.

  4. Sulfuric Acid ([3-(3-Silicapropyl)sulfanyl]propyl)ester as a Recyclable Catalyst for the Synthesis of 4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols)%Sulfuric Acid ([3-(3-Silicapropyl)sulfanyl]propyl)ester as a Recyclable Catalyst for the Synthesis of4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols)

    Institute of Scientific and Technical Information of China (English)

    Shekoofeh TAYEBI; Mojtaba BAGHERNEJAD; Dariush SABERI; Khodabakhsh NI KNAM

    2011-01-01

    Sulfuric acid ([3-(3-silicapropyl)sulfanyl]propyl)ester is employed as a recyclable catalyst for the condensation reaction between aromatic aldehydes and 3-methyl-l-phenyl-5-pyrazolone.This condensation reaction was performed in ethanol under refluxing conditions giving 4,4-alkylmethylene-bis(3-methyl-5-pyrazolones) in 74-90% yields.The heterogeneous catalyst was recycled and used in eleven runs for the reaction between benzaldehyde and 3-methyl-l-phenyl-5-pyrazolone without losing catalytic activity.

  5. Synthesis and Molecular Structure of Acetic Acid-3,5-diacetoxy-2-acetoxymethyl-6-(4-quinoxalin-2-yl-phenoxy)-tetrahydro-pyran-4-yl-ester

    Institute of Scientific and Technical Information of China (English)

    WEI Hui-Qin; ZENG Run-Sheng; WU Gui-Ping; WANG Bao-An; ZOU Jian-Ping

    2006-01-01

    The title compound, acetic acid-3,5-diacetoxy-2-acetoxymethyl-6-(4-quinoxalin-2-yl-phenoxy)-tetrahydro-pyran-4-yl-ester 8 (C28H28N2O10, Mr = 552.54), has been synthesized and its crystal structure was determined by X-ray diffraction analysis. It crystallizes in monoclinic,space group P21, a = 10.060(8), b = 5.648(4), c=24.11(2)(A), β=91.078(10)O, Z = 2, V =1369.9(19)(A)3, Dc = 1.339 g/cm3,μ(MoKα) = 1.03 cm-1, F(000) = 580.00, T=193.1 K,θmax =25.03, (△/σ)max = 0.0000, Flack = -0.0(24), the final R = 0.0680 and wR= 0.140 (w =1/[0.0016Fo2+ 1.0000σ(Fo2)]/(4Fo2)) for 3126 observed reflections (I>2σ(I)). The pyranoid ring adopts chair conformation in the sugar moiety, and all of the acetyl groups are in the e bond of the pyranoid ring, so the sugar moiety is very stable.

  6. Protective effect of minocycline, a semi-synthetic second-generation tetracycline against 3-nitropropionic acid (3-NP)-induced neurotoxicity

    International Nuclear Information System (INIS)

    3-Nitropropionic acid (3-NP) is an irreversible inhibitor of the electron transport enzyme succinate dehydrogenase, a mitochondrial Complex II enzyme. Minocycline is a semi-synthetic second-generation tetracycline with neuroprotective activity and has the capability to effectively cross the blood-brain barrier. We investigated the effects of minocycline on behavioral, biochemical, inflammation related and neurochemical alterations induced by the sub-chronic administration of 3-nitropropionic acid to rats. Chronic pre-administration of minocycline (50 and 100 mg/kg) dose dependently prevented 3-NP-induced dysfunction behavioral (hypoactivity, memory retention, locomotor and rota-rod activity). In addition, 3-NP produced a marked increase in lipid peroxidation levels whereas decreased the activities of catalase and succinate dehydrogenase. In contrast, pretreatment of 3-NP injected rats with minocycline resulted in the attenuation of all these alterations. A marked increase in an inflammatory cytokine TNF-α by 3-NP was also decreased by minocycline treatment. Neurochemically, the administration of 3-NP significantly decreased the levels of catecholamines in the brain homogenates (dopamine, norepinephrine and serotonin) which were reversed by pretreatment of minocycline. The present finding explains the neuroprotective effect of minocycline against 3-NP toxicity by virtue of its antioxidant and anti-inflammatory activity

  7. Protective effect of minocycline, a semi-synthetic second-generation tetracycline against 3-nitropropionic acid (3-NP)-induced neurotoxicity.

    Science.gov (United States)

    Ahuja, Manuj; Bishnoi, Mahendra; Chopra, Kanwaljit

    2008-02-28

    3-Nitropropionic acid (3-NP) is an irreversible inhibitor of the electron transport enzyme succinate dehydrogenase, a mitochondrial Complex II enzyme. Minocycline is a semi-synthetic second-generation tetracycline with neuroprotective activity and has the capability to effectively cross the blood-brain barrier. We investigated the effects of minocycline on behavioral, biochemical, inflammation related and neurochemical alterations induced by the sub-chronic administration of 3-nitropropionic acid to rats. Chronic pre-administration of minocycline (50 and 100mg/kg) dose dependently prevented 3-NP-induced dysfunction behavioral (hypoactivity, memory retention, locomotor and rota-rod activity). In addition, 3-NP produced a marked increase in lipid peroxidation levels whereas decreased the activities of catalase and succinate dehydrogenase. In contrast, pretreatment of 3-NP injected rats with minocycline resulted in the attenuation of all these alterations. A marked increase in an inflammatory cytokine TNF-alpha by 3-NP was also decreased by minocycline treatment. Neurochemically, the administration of 3-NP significantly decreased the levels of catecholamines in the brain homogenates (dopamine, norepinephrine and serotonin) which were reversed by pretreatment of minocycline. The present finding explains the neuroprotective effect of minocycline against 3-NP toxicity by virtue of its antioxidant and anti-inflammatory activity. PMID:18164115

  8. 叶酸受体新技术及细胞学检查对宫颈癌筛查应用价值的评估%Evaluation of the application of folate receptor mediated (FRD) multifunctional acetic acid white solution inspection with liquid based cytology screening for cervical cancer

    Institute of Scientific and Technical Information of China (English)

    邓翠; 康佳丽; 蒋文燕; 聂妙玲; 黄晓晖

    2014-01-01

    Objective To explore the folate receptor mediated (FRD) check and multi-function acetic acid white solution liquid based cervical cytology (TCT) application value in cervical cancer screening.Methods A total of 602 cases of patients was tested with FRD multi-function acetic acid white solution check,and TCT and cervical biopsy pathology examination.With the used of histopathological results as the gold standard,FRD multi-function acetic acid white analysis was compared with the TCT screening inspection results.Results For a total 602 patients with TCT screening,the positive rate was 21.8% (131/602),including 36 cases of CIN Ⅰ level,41 cases of CIN Ⅱ level,24 cases of CIN Ⅲ level,and 30 cases of cervical invasive carcinoma.For the FRD multifunction white acetate solution screening,its positive rate was 23.8% (143/602).No statistically significant difference was found between TCT and FRD screening (P > 0.05).The missed diagnosis rate of FRD multi-function white acetate solution screening was 2.6% in inflammation,and 21.1% in cervical invasive cancer,and 3.8 % in CIN.The missed diagnosis rate of TCT screening was 7.2% in inflammation,5.3% in CIN Ⅰ,4.9% in CIN Ⅱ,and 58.6% in CIN Ⅲ]; whereas,its detection coincidence rate was 100% in squamous cells carcinoma (SCC) and adenocarcinoma (AC).FRD multi-function acetic acid white solution screening had a sensitivity 80.92%,specificity 92.14%,positive predictive value 74.13%,and negative predictive value 95.59%.TCT examination had a sensitivity 90.84%,specificity 90.23%,positive predictive value 72.12%,and negative predictive value 97.25%.No significant difference was found between FRD and TCT methods (P > 0.05).Conclusions FRD and TCT methods were both efficient in screening and evaluation for cervical lesions and cervical cancer.Because FRD method is limited in the deep tube for examination of cervical lesions; it cannot completely replace the TCT examination

  9. Enhanced production of glycyrrhetic acid 3-O-mono-β-D-glucuronide by fed-batch fermentation using pH and dissolved oxygen as feedback parameters☆

    Institute of Scientific and Technical Information of China (English)

    Bo Lü; Xiaogang Yang; Xudong Feng; Chun Li

    2016-01-01

    Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG), the major functional ingredient in licorice, has widespread applications in food, pharmacy and cosmetics industry. The production of GAMG through Penicil ium purpurogenum Li-3 cultivation was for the first time performed through both batch and fed-batch processes in bioreactors. In batch process, under optimal conditions (pH 5.0, temperature 32 °C, agitation speed 100 r·min−1), 3.55 g·L−1 GAMG was obtained in a 2.5 L fermentor. To further enhance GAMG production, a fine fed-batch process was developed by using pH and DO as feedback parameters. Starting from 48 h, 100 ml 90 g·L−1 substrate Glycyrrhizin (GL) was fed each time when pH increased to above 5.0 and DO was increased to above 80%. This strategy can significantly enhance GAMG production:the achieved GL conversion was 95.34%with GAMG yield of 95.15%, and GAMG concentration was 16.62 g·L−1 which was 5 times higher than that of batch. Then, a two-step separation strat-egy was established to separate GAMG from fermentation broth by crude extraction of 15 ml column packed with D101 resin followed by fine purification with preparative C18 chromatography. The obtained GAMG purity was 95.79%. This study provides a new insight into the industrial bioprocess of high-level GAMG production.

  10. A Positive Feed-forward Loop Associating EGR1 and PDGFA Promotes Proliferation and Self-renewal in Glioblastoma Stem Cells.

    Science.gov (United States)

    Sakakini, Nathalie; Turchi, Laurent; Bergon, Aurélie; Holota, Hélène; Rekima, Samah; Lopez, Fabrice; Paquis, Philipe; Almairac, Fabien; Fontaine, Denys; Baeza-Kallee, Nathalie; Van Obberghen-Schilling, Ellen; Junier, Marie-Pierre; Chneiweiss, Hervé; Figarella-Branger, Dominique; Burel-Vandenbos, Fanny; Imbert, Jean; Virolle, Thierry

    2016-05-13

    Glioblastomas are the most common primary brain tumors, highly vascularized, infiltrating, and resistant to current therapies. This cancer leads to a fatal outcome in less than 18 months. The aggressive behavior of glioblastomas, including resistance to current treatments and tumor recurrence, has been attributed to glioma stemlike/progenitor cells. The transcription factor EGR1 (early growth response 1), a member of a zinc finger transcription factor family, has been described as tumor suppressor in gliomas when ectopically overexpressed. Although EGR1 expression in human glioblastomas has been associated with patient survival, its precise location in tumor territories as well as its contribution to glioblastoma progression remain elusive. In the present study, we show that EGR1-expressing cells are more frequent in high grade gliomas where the nuclear expression of EGR1 is restricted to proliferating/progenitor cells. We show in primary cultures of glioma stemlike cells that EGR1 contributes to stemness marker expression and proliferation by orchestrating a PDGFA-dependent growth-stimulatory loop. In addition, we demonstrate that EGR1 acts as a positive regulator of several important genes, including SHH, GLI1, GLI2, and PDGFA, previously linked to the maintenance and proliferation of glioma stemlike cells.

  11. CircuitsDB: a database of mixed microRNA/transcription factor feed-forward regulatory circuits in human and mouse

    OpenAIRE

    Friard Olivier; Re Angela; Taverna Daniela; De Bortoli Michele; Corá Davide

    2010-01-01

    Abstract Background Transcription Factors (TFs) and microRNAs (miRNAs) are key players for gene expression regulation in higher eukaryotes. In the last years, a large amount of bioinformatic studies were devoted to the elucidation of transcriptional and post-transcriptional (mostly miRNA-mediated) regulatory interactions, but little is known about the interplay between them. Description Here we describe a dynamic web-accessible database, CircuitsDB, supporting a genome-wide transcriptional an...

  12. Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells.

    Science.gov (United States)

    Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen; Schneider, Robert J

    2015-08-01

    Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity.

  13. 惯性稳定平台自适应前馈控制%Adaptive feed-forward control for inertially stabilized platform

    Institute of Scientific and Technical Information of China (English)

    朱明超; 刘慧; 张鑫; 贾宏光

    2015-01-01

    结合反馈控制提出了一种自适应前馈控制方法来提高惯性稳定平台稳定控制的指令跟踪性能.应用子空间辨识算法,由输入输出数据辨识稳定平台动态模型的状态空间描述;采用频域回路成型方法设计反馈回路控制器,用于抑制外部扰动.应用递推最小二乘(RLS)自适应滤波器构建反馈控制回路逆模型,构造指令信号的全通特性,提高指令跟踪能力.针对不同的指令信号进行跟踪实验,验证了自适应前馈控制方法的有效性.实验结果表明:提出的自适应前馈方法对阶跃指令响应快,超调量可由反馈控制的30%降低至4.5%,对30 Hz正弦信号的响应幅值无衰减,相位滞后由反馈控制的90°降低至54°.得到的结果显著提高了系统的暂态性能,控制性能优于单独的反馈控制回路.

  14. Electron bunch energy and phase feed-forward stabilization system for the Mark V RF-linac free-electron laser

    CERN Document Server

    Hadmack, M R; Kowalczyk, J M D; Lienert, B R; Madey, J M J; Szarmes, E B

    2013-01-01

    An amplitude and phase compensation system has been developed and tested at the University of Hawai`i for the optimization of the RF drive system to the Mark V Free-Electron Laser. Temporal uniformity of the RF drive is essential to the generation of an electron beam suitable for optimal free-electron laser performance and the operation of an inverse Compton scattering x-ray source. The design of the RF measurement and compensation system is described in detail and the results of RF phase compensation are presented. Performance of the free-electron laser was evaluated by comparing the measured effects of phase compensation with the results of a computer simulation. Finally, preliminary results are presented for the effects of amplitude compensation on the performance of the complete system.

  15. Electron bunch energy and phase feed-forward stabilization system for the Mark V RF-linac free-electron laser

    Science.gov (United States)

    Hadmack, M. R.; Jacobson, B. T.; Kowalczyk, J. M. D.; Lienert, B. R.; Madey, J. M. J.; Szarmes, E. B.

    2013-06-01

    An amplitude and phase compensation system has been developed and tested at the University of Hawai`i for the optimization of the RF drive system to the Mark V free-electron laser. Temporal uniformity of the RF drive is essential to the generation of an electron beam suitable for optimal free-electron laser performance and the operation of an inverse Compton scattering x-ray source. The design of the RF measurement and compensation system is described in detail and the results of RF phase compensation are presented. Performance of the free-electron laser was evaluated by comparing the measured effects of phase compensation with the results of a computer simulation. Finally, preliminary results are presented for the effects of amplitude compensation on the performance of the complete system.

  16. Electron bunch energy and phase feed-forward stabilization system for the Mark V RF-linac free-electron laser

    OpenAIRE

    Hadmack, M. R.; Jacobson, B. T.; Kowalczyk, J. M. D.; Lienert, B. R.; Madey, J.M.J.; Szarmes, E. B.

    2013-01-01

    An amplitude and phase compensation system has been developed and tested at the University of Hawai`i for the optimization of the RF drive system to the Mark V Free-Electron Laser. Temporal uniformity of the RF drive is essential to the generation of an electron beam suitable for optimal free-electron laser performance and the operation of an inverse Compton scattering x-ray source. The design of the RF measurement and compensation system is described in detail and the results of RF phase com...

  17. Electron bunch energy and phase feed-forward stabilization system for the Mark V RF-linac free-electron laser

    Energy Technology Data Exchange (ETDEWEB)

    Hadmack, M. R.; Kowalczyk, J. M. D.; Lienert, B. R.; Madey, J. M. J.; Szarmes, E. B. [Department of Physics and Astronomy, University of Hawai' i at Manoa, Honolulu, Hawaii 96822 (United States); Jacobson, B. T. [RadiaBeam Technologies, Santa Monica, California 90404 (United States)

    2013-06-15

    An amplitude and phase compensation system has been developed and tested at the University of Hawai'i for the optimization of the RF drive system to the Mark V free-electron laser. Temporal uniformity of the RF drive is essential to the generation of an electron beam suitable for optimal free-electron laser performance and the operation of an inverse Compton scattering x-ray source. The design of the RF measurement and compensation system is described in detail and the results of RF phase compensation are presented. Performance of the free-electron laser was evaluated by comparing the measured effects of phase compensation with the results of a computer simulation. Finally, preliminary results are presented for the effects of amplitude compensation on the performance of the complete system.

  18. Feed-forward control to stabilize optical axis based on accelerometer%基于加速度信息的光轴稳定控制

    Institute of Scientific and Technical Information of China (English)

    王虎; 陈娟

    2010-01-01

    将惯导原件加速度计应用于伺服系统的复合控制中,进行了基于加速度信息的等效复合控制实验研究.实验结果表明,在方位伺服系统以最大角速度50°/s、最大角加速度30°/s2工作时,引入加速度信息后,最大稳态跟踪误差为1.08′,精度提高了近6倍.

  19. A gain-of-function mutant p53–HSF1 feed forward circuit governs adaptation of cancer cells to proteotoxic stress

    OpenAIRE

    D. Li(Hunan University, Changsha 410082, People's Republic of China); Yallowitz, A; Ozog, L; Marchenko, N

    2014-01-01

    To overcome proteotoxic stress inherent to malignant transformation, cancer cells induce a range of adaptive mechanisms, with the master transcription factor heat-shock factor 1 (HSF1)-orchestrated response taking center stage. Here we define a novel gain-of-function of mutant p53 (mutp53), whereby mutp53-overexpressing cancer cells acquire superior tolerance to proteotoxic stress. mutp53 via constitutive stimulation of EGFR and ErbB2 signaling hyperactivates the MAPK and PI3K cascades, which...

  20. Inverted Pendulum Control Based on Feed- forward backpropagation Algorithm of ANN%基于前馈BP网的倒立摆控制

    Institute of Scientific and Technical Information of China (English)

    张滔; 谢宗安

    2004-01-01

    本文分析了直线一级倒立摆的受力情况,建立状态空间数学模型,构造4输入1输出的三层前馈BP网络.运用引入动量项的改进BP算法对网络进行训练,并将这一网络对倒立摆进行实时控制.实验结果表明BP算法具有算法精度高,实现快,鲁棒性好等优点,应用前景广阔.

  1. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

    OpenAIRE

    Cátia Vieira; Maria Teresa Magalhães-Cardoso; Fátima Ferreirinha; Isabel Silva; Ana Sofia Dias; Julie Pelletier; Jean Sévigny; Paulo Correia-de-Sá

    2014-01-01

    Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis ...

  2. A HEURISTIC MOVING VEHICLE LOCATION PREDICTION TECHNIQUE VIA OPTIMAL PATHS SELECTION WITH AID OF GENETIC ALGORITHM AND FEED FORWARD BACK PROPAGATION NEURAL NETWORK

    Directory of Open Access Journals (Sweden)

    K. Duraiswamy

    2012-01-01

    Full Text Available The moving object or vehicle location prediction based on their spatial and temporal information is an important task in many applications. Different methods were utilized for performing the vehicle movement detection and prediction process. In such works, there is a lack of analysis in predicting the vehicles location in current as well as in future. Moreover, such methods compute the vehicles movement by finding the topological relationships among trajectories and locations, whereas the representative GPS points are determined by the 30 m circular window. Due to this process, the performance of the method is degraded because such 30 m circular window is selected by calculating the error range in the given input image and such error range may vary from image to image. To reduce the drawback presented in the existing method, in this study a heuristic moving vehicle location prediction algorithm is proposed. The proposed heuristic algorithm mainly comprises two techniques namely, optimization GA algorithm and FFBNN. In this proposed technique, initially the vehicles frequent paths are collected by monitoring all the vehicles movement in a specific period. Among the frequent paths, the vehicles optimal paths are computed by the GA algorithm. The selected optimal paths for each vehicle are utilized to train the FFBNN. The well trained FFBNN is then utilized to find the vehicle movement from the current location. By combining the proposed heuristic algorithm with GA and FFBNN, the vehicles location is predicted efficiently. The implementation result shows the effectiveness of the proposed heuristic algorithm in predicting the vehicles future location from the current location. The performance of the heuristic algorithm is evaluated by comparing the result with the RBF classifier. The comparison result shows our proposed technique acquires an accurate vehicle location prediction ratio than the RBF prediction ratio, in terms of accuracy.

  3. Effects of self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane and dopamine on the corrosion behaviors and biocompatibility of a magnesium alloy.

    Science.gov (United States)

    Pan, Chang-Jiang; Hou, Yu; Wang, Ya-Nan; Gao, Fei; Liu, Tao; Hou, Yan-Hua; Zhu, Yu-Fu; Ye, Wei; Wang, Ling-Ren

    2016-10-01

    Magnesium based alloys are attracting tremendous interests as the novel biodegradable metallic biomaterials. However, the rapid in vivo degradation and the limited surface biocompatibility restrict their clinical applications. Surface modification represents one of the important approaches to control the corrosion rate of Mg based alloys and to enhance the biocompatibility. In the present study, in order to improve the corrosion resistance and surface biocompatibility, magnesium alloy (AZ31B) was modified by the alkali heating treatment followed by the self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane (APTMS) and dopamine, respectively. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectra (XPS) indicated that the molecules were successfully immobilized on the magnesium alloy surface by the self-assembly. An excellent hydrophilic surface was obtained after the alkali heating treatment and the water contact angle increased to some degree after the self-assembly of dopamine, APTMS and 3-phosphonopropionic acid, however, the hydrophilicity of the modified samples was better than that of the pristine magnesium substrate. Due to the formation of the passivation layer after the alkali heating treatment, the corrosion resistance of the magnesium alloy was obviously improved. The corrosion rate further decreased to varying degrees after the self-assembly surface modification. The blood compatibility of the pristine magnesium was significantly improved after the surface modification. The hemolysis rate was reduced from 56% of the blank magnesium alloy to 18% of the alkali heating treated sample and the values were further reduced to about 10% of dopamine-modified sample and 7% of APTMS-modified sample. The hemolysis rate was below 5% for the 3-phosphonopropionic acid modified sample. As compared to the pristine magnesium alloy, fewer platelets were attached and activated on the

  4. 18-碳酸-3,4-呋喃二酯对小鼠精子超微结构的影响%Ultrastructural Effect of Octadecanoic Acid-3,4-Furanodiyl Ester on Sperm in Male Mice

    Institute of Scientific and Technical Information of China (English)

    殷中琼; 吴成奎; 张新申; 万固存; 刘毅; 俞德顺; 杨军; 莫彬彬; 田弋夫

    2006-01-01

    The effects of octadecanoic acid-3,4-furanodiyl ester on Kunming male mice sperm ultra-structural characteristics were studied in vitro. Kill 10 healthy fertile mice and collect the testicle, and, with a swim-up technique, a sperm suspension of high motility and purity was extract of neem oil,and the sperm pellets were fixed in 2.5% glutaraldehyde (pH was 7.2) and observed in electron microscope. Octadecanoic acid-3,4-furanodiyl ester can kill all sperm of Kunming mice in vitro in less than 20 s at the concentration of 4 g/L. On electron microscope, the acrosome and karyotheca of spermatids had been damaged. Small-to-large damaged areas which seemed to have been bitten by worms could be observed at the edge of the cytoplasmic membrane. In some cases, membrane and the peripheral mitochondria were virtually absent and the entire cytoplasm was medullary degenerated and vacuolated. The octadecanoic acid-3,4-furanodiyl ester has strong sperm-killing activity in vitro. There are evident histological changes due to octadecanoic acid-3,4-furanodiyl ester in sperm of male Kunming mice.%研究了18-碳酸-3,4-呋喃二酯对昆明小鼠精子超微结构的影响.处死10只健康有生育力的雄性小鼠,取睾丸组织,获取具有高活力的精子悬浮液,测定18-碳酸-3,4-呋喃二酯的瞬间杀精活性;然后将经过处理的精子团块固定在2.5%的戊二醛溶液中,电镜观察.结果表明,18-碳酸-3,4-呋喃二酯的瞬间杀精浓度为4 g·L-1.在电镜下,精子头部顶体与核膜被破坏,在核质膜周边形成大小不一的虫蚀状缺痕,严重者,细胞核膜破裂/缺损,核染色质不均匀,呈颗粒样改变,有空泡形成.由此可见,18-碳酸-3,4-呋喃二酯有很强的体外杀精作用.

  5. A High-efficiency Preparation, Properties and Structure of (R, S )- and (S, S )-Pyrrolidine-2-carboxylic Acid 3,5-Dioxa-4-boracyclohepta [ 2, 1-a; 3,4-a′] dinaphthalen-4-yl Esters

    Institute of Scientific and Technical Information of China (English)

    SHAN Zi-Xing; LIU, Si-Min; LIU, De-Jun

    2003-01-01

    A highly-efficient preparative procedure for ( R, S )- and ( S,S ) -pyrrolidine-2-carboxylic acid 3,5-dioxa-4-boracyclohepta [2,1-a; 3,4-a′ ] dinaphthalen-4-yl esters [ namely ( R, S )-BNBAP and (S, S )-BNBAP] is described and the crystal structure of (R, S ) -BNBAP was obtained. The data indicate that ( R, S )-BNBAP is a spirocyclic inner borate salt with almost normal tetrahedral configuration. This structural form may be the basic reason for their high chemical, optical and thermodynamic stability.

  6. Optical Properties of Poly (3-hexylthiophene-2,5-diyl and Poly (3-hexylthiophene-2,5-diyl / [6,6]-Phenyl C61-butyric Acid 3-ethylthiophene Ester Thin Films

    Directory of Open Access Journals (Sweden)

    B.M. Omer

    2013-07-01

    Full Text Available Thin films of Poly(3-hexylthiophene-2,5-diyl (P3HT were prepared from chloroform, 1,2 dichlorobenzene and toluene solutions by spin coating technique on quartz substrates. The absorption and photoluminescence (PL measurements were performed on the P3HT films to investigate the influence of solvent on the optical properties of the films. The results shows that the UV-vis absorption of P3HT film spin-coated from toluene is red shifted compared to the spectra of the films spin-coated from either chloroform or 1,2 dichlorobenzene. The surface morphology of P3HT: [6, 6]-Phenyl C61-butyric Acid 3-ethylthiophene Ester (Modified Fullerene thin films spin-coated from different solvents were studied using Atomic Force Microscope (AFM, the thin film spin-coated from 1,2 dichlorobenzene show the smoother surface.

  7. β-Receptor-mediated increase in cerebral blood flow during hypoglycemia

    International Nuclear Information System (INIS)

    The authors tested the hypothesis that β-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin; normoglycemic control rates were given saline. Propranolol was administered to some control and some hypoglycemic rats to block the β-adrenergic receptors. Regional CBF was measured using 4-[N-methyl-14C]iodoantipyrine. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied from ∼60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. They conclude that β-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia

  8. beta. -Receptor-mediated increase in cerebral blood flow during hypoglycemia

    Energy Technology Data Exchange (ETDEWEB)

    Hollinger, B.R.; Bryan, R.M. (Pennsylvania State Univ., Hershey (USA))

    1987-10-01

    The authors tested the hypothesis that {beta}-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin; normoglycemic control rates were given saline. Propranolol was administered to some control and some hypoglycemic rats to block the {beta}-adrenergic receptors. Regional CBF was measured using 4-(N-methyl-{sup 14}C)iodoantipyrine. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied from {approximately}60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. They conclude that {beta}-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia.

  9. Receptor-mediated sorting of soluble vacuolar proteins: myths, facts, and a new model.

    Science.gov (United States)

    Robinson, David G; Neuhaus, Jean-Marc

    2016-08-01

    To prevent their being released to the cell exterior, acid hydrolases are recognized by receptors at some point in the secretory pathway and diverted towards the lytic compartment of the cell (lysosome or vacuole). In animal cells, the receptor is called the mannosyl 6-phosphate receptor (MPR) and it binds hydrolase ligands in the trans-Golgi network (TGN). These ligands are then sequestered into clathrin-coated vesicles (CCVs) because of motifs in the cytosolic tail of the MPR which interact first with monomeric adaptors (Golgi-localized, Gamma-ear-containing, ARF-binding proteins, GGAs) and then with tetrameric (adaptin) adaptor complexes. The CCVs then fuse with an early endosome, whose more acidic lumen causes the ligands to dissociate. The MPRs are then recycled back to the TGN via retromer-coated carriers. Plants have vacuolar sorting receptors (VSRs) which were originally identified in CCVs isolated from pea (Pisum sativum L.) cotyledons. It was therefore assumed that VSRs would have an analogous function in plants to MPRs in animals. Although this dogma has enjoyed wide support over the last 20 years there are many inconsistencies. Recently, results have been published which are quite contrary to it. It now emerges that VSRs and their ligands can interact very early in the secretory pathway, and dissociate in the TGN, which, in contrast to its mammalian counterpart, has a pH of 5.5. Multivesicular endosomes in plants lack proton pump complexes and consequently have an almost neutral internal pH, which discounts them as organelles of pH-dependent receptor-ligand dissociation. These data force a critical re-evaluation of the role of CCVs at the TGN, especially considering that vacuolar cargo ligands have never been identified in them. We propose that one population of TGN-derived CCVs participate in retrograde transport of VSRs from the TGN. We also present a new model to explain how secretory and vacuolar cargo proteins are effectively separated after entering the late Golgi/TGN compartments.

  10. Receptor-Mediated and Lectin-Like Activities of Carp (Cyprinus carpio) TNF-¿

    NARCIS (Netherlands)

    Forlenza, M.; Magez, S.; Scharsack, J.P.; Westphal, A.H.; Savelkoul, H.F.J.; Wiegertjes, G.F.

    2009-01-01

    Functional characterization of TNF- in species other than mammalian vertebrates is limited, and TNF- has been studied in a limited number of fish species, primarily in vitro using recombinant proteins. Studies on TNF- from different fish species so far pointed to several inconsistencies, in particul

  11. Receptor-mediated sorting of soluble vacuolar proteins: myths, facts, and a new model.

    Science.gov (United States)

    Robinson, David G; Neuhaus, Jean-Marc

    2016-08-01

    To prevent their being released to the cell exterior, acid hydrolases are recognized by receptors at some point in the secretory pathway and diverted towards the lytic compartment of the cell (lysosome or vacuole). In animal cells, the receptor is called the mannosyl 6-phosphate receptor (MPR) and it binds hydrolase ligands in the trans-Golgi network (TGN). These ligands are then sequestered into clathrin-coated vesicles (CCVs) because of motifs in the cytosolic tail of the MPR which interact first with monomeric adaptors (Golgi-localized, Gamma-ear-containing, ARF-binding proteins, GGAs) and then with tetrameric (adaptin) adaptor complexes. The CCVs then fuse with an early endosome, whose more acidic lumen causes the ligands to dissociate. The MPRs are then recycled back to the TGN via retromer-coated carriers. Plants have vacuolar sorting receptors (VSRs) which were originally identified in CCVs isolated from pea (Pisum sativum L.) cotyledons. It was therefore assumed that VSRs would have an analogous function in plants to MPRs in animals. Although this dogma has enjoyed wide support over the last 20 years there are many inconsistencies. Recently, results have been published which are quite contrary to it. It now emerges that VSRs and their ligands can interact very early in the secretory pathway, and dissociate in the TGN, which, in contrast to its mammalian counterpart, has a pH of 5.5. Multivesicular endosomes in plants lack proton pump complexes and consequently have an almost neutral internal pH, which discounts them as organelles of pH-dependent receptor-ligand dissociation. These data force a critical re-evaluation of the role of CCVs at the TGN, especially considering that vacuolar cargo ligands have never been identified in them. We propose that one population of TGN-derived CCVs participate in retrograde transport of VSRs from the TGN. We also present a new model to explain how secretory and vacuolar cargo proteins are effectively separated after entering the late Golgi/TGN compartments. PMID:27262127

  12. Interaction between thyrotropin-releasing hormone (TRH) and NMDA-receptor-mediated responses in hypoglossal motoneurones

    DEFF Research Database (Denmark)

    Rekling, J C

    1992-01-01

    The effect of thyrotropin-releasing hormone (TRH) on the responses to excitatory amino acids was investigated in hypoglossal motoneurones in an in vitro preparation of the brainstem from guinea pigs using current clamp and discontinuous single electrode voltage clamp (dSEVC). Bath application of 20......-50 microM TRH markedly potentiated the response to iontophoretically applied NMDA, whereas no potentiation of the response to glutamate, aspartate or quisqualic acid was seen. Voltage clamp experiments showed that TRH did not increase the current flowing through NMDA channels, thus a direct modulatory role...... of TRH on NMDA channels was not a likely explanation of the potentiation. Voltage clamp studies of the current-voltage relationship showed that the potentiation of the response to NMDA and lack of potentiation of the response to quisqualic acid was a result of an interaction between the actions of TRH...

  13. Asialoglycoprotein Receptor-Mediated Gene Delivery to Hepatocytes Using Galactosylated Polymers.

    Science.gov (United States)

    Thapa, Bindu; Kumar, Piyush; Zeng, Hongbo; Narain, Ravin

    2015-09-14

    Highly efficient, specific, and nontoxic gene delivery vector is required for gene therapy to the liver. Hepatocytes exclusively express asialoglycoprotein receptor (ASGPR), which can recognize and bind to galactose or N-acetylgalactosamine. Galactosylated polymers are therefore explored for targeted gene delivery to the liver. A library of safe and stable galactose-based glycopolymers that can specifically deliver genes to hepatocytes were synthesized having different architectures, compositions, and molecular weights via the reversible addition-fragmentation chain transfer process. The physical and chemical properties of these polymers have a great impact on gene delivery efficacy into hepatocytes, as such block copolymers are found to form more stable complexes with plasmid and have high gene delivery efficiency into ASGPR expressing hepatocytes. Transfection efficiency and uptake of polyplexes with these polymers decreased significantly by preincubation of hepatocytes with free asialofetuin or by adding free asialofetuin together with polyplexes into hepatocytes. The results confirmed that polyplexes with these polymers were taken up specifically by hepatocytes via ASGPR-mediated endocytosis. The results from transfection efficiency and uptake of these polymers in cells without ASGPR, such as SK Hep1 and HeLa cells, further support this mechanism. Since in vitro cytotoxicity assays prove these glycopolymers to be nontoxic, they may be useful for delivery of clinically important genes specifically to the liver.

  14. BURN-INDUCED ALTERATIONS IN TOLL-LIKE RECEPTOR-MEDIATED RESPONSES BY BRONCHOALVEOLAR LAVAGE CELLS

    OpenAIRE

    Richard F. Oppeltz; Rani, Meenakshi; Zhang, Qiong; Schwacha, Martin G.

    2011-01-01

    Burn is associated with profound inflammation and activation of the innate immune system in multiple organ beds, including the lung. Similarly, toll-like receptors (TLR) are associated with innate immune activation. Nonetheless, it is unclear what impact burn has on TLR-induced inflammatory responses in the lung.

  15. Application of an in silico liver model to determine nuclear receptor mediated pathways in liver cancer

    Science.gov (United States)

    Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs in rodents can result in increased incidence of liver tumors. These are generally thought to develop through a non-genotoxic mechanism with...

  16. Loss of receptor-mediated 86Rb efflux from pig aortic endothelial cells in culture.

    OpenAIRE

    Ager, A.; Martin, W

    1983-01-01

    The responsiveness of freshly-isolated and subcultured pig aortic endothelial cells to adenosine triphosphate (ATP), bradykinin and ionophore A23187 was compared by monitoring agonist-induced 86Rb efflux. ATP, bradykinin and ionophore A23187 stimulated 86Rb efflux from freshly-isolated cells. ATP and bradykinin, which act via specific receptors, were less effective at inducing 86Rb efflux from subcultured cells but ionophore A23187 was as effective on subcultured as on freshly-isolated cells....

  17. Estrogen receptor-mediated transcription involves the activation of multiple kinase pathways in neuroblastoma cells.

    Science.gov (United States)

    Clark, Sara; Rainville, Jennifer; Zhao, Xing; Katzenellenbogen, Benita S; Pfaff, Donald; Vasudevan, Nandini

    2014-01-01

    While many physiological effects of estrogens (E) are due to regulation of gene transcription by liganded estrogen receptors (ERs), several effects are also mediated, at least in part, by rapid non-genomic actions of E. Though the relative importance of rapid versus genomic effects in the central nervous system is controversial, we showed previously that membrane-limited effects of E, initiated by an estradiol bovine serum albumin conjugate (E2-BSA), could potentiate transcriptional effects of 17β-estradiol from an estrogen response element (ERE)-reporter in neuroblastoma cells. Here, using specific inhibitors and activators in a pharmacological approach, we show that activation of phosphatidylinositol-3-phosphate kinase (PI3K) and mitogen activated protein kinase (MAPK) pathways, dependent on a Gαq coupled receptor signaling are important in this transcriptional potentiation. We further demonstrate, using ERα phospho-deficient mutants, that E2-BSA mediated phosphorylation of ERα is one mechanism to potentiate transcription from an ERE reporter construct. This study provides a possible mechanism by which signaling from the membrane is coupled to transcription in the nucleus, providing an integrated view of hormone signaling in the brain.

  18. Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis

    Directory of Open Access Journals (Sweden)

    Tomonari Kasai

    2012-01-01

    Full Text Available Chlorotoxin is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion venom, which has been shown to inhibit low-conductance chloride channels in colonic epithelial cells. Chlorotoxin also binds to matrix metalloproteinase-2 and other proteins on glioma cell surfaces. Glioma cells are considered to require the activation of matrix metalloproteinase-2 during invasion and migration. In this study, for targeting glioma, we designed two types of recombinant chlorotoxin fused to human IgG-Fcs with/without a hinge region. Chlorotoxin fused to IgG-Fcs was designed as a dimer of 60 kDa with a hinge region and a monomer of 30 kDa without a hinge region. The monomeric and dimeric forms of chlorotoxin inhibited cell proliferation at 300 nM and induced internalization in human glioma A172 cells. The monomer had a greater inhibitory effect than the dimer; therefore, monomeric chlorotoxin fused to IgG-Fc was multivalently displayed on the surface of bionanocapsules to develop a drug delivery system that targeted matrix metalloproteinase-2. The target-dependent internalization of bionanocapsules in A172 cells was observed when chlorotoxin was displayed on the bionanocapsules. This study indicates that chlorotoxin fused to IgG-Fcs could be useful for the active targeting of glioblastoma cells.

  19. Different pools of glutamate receptors mediate sensitivity to ambient glutamate in the cochlear nucleus.

    Science.gov (United States)

    Yang, Yang; Xu-Friedman, Matthew A

    2015-06-01

    Ambient glutamate plays an important role in pathological conditions, such as stroke, but its role during normal activity is not clear. In addition, it is not clear how ambient glutamate acts on glutamate receptors with varying affinities or subcellular localizations. To address this, we studied "endbulb of Held" synapses, which are formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus. When ambient glutamate was increased by applying the glutamate reuptake inhibitor TFB-TBOA, BCs depolarized as a result of activation of N-methyl-D-aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs). Application of antagonists against NMDARs (in 0 Mg(2+)) or mGluRs caused hyperpolarization, indicating that these receptors were bound by a tonic source of glutamate. AMPA receptors did not show these effects, consistent with their lower glutamate affinity. We also evaluated the subcellular localization of the receptors activated by ambient glutamate. The mGluRs were not activated by synaptic stimulation and thus appear to be exclusively extrasynaptic. By contrast, NMDARs in both synaptic and extrasynaptic compartments were activated by ambient glutamate, as shown using the use-dependent antagonist MK-801. Levels of ambient glutamate appeared to be regulated in a spike-independent manner, and glia likely play a major role. These low levels of ambient glutamate likely have functional consequences, as even low concentrations of TBOA caused significant increases in BC spiking following synaptic stimulation. These results indicate that normal resting potential appears to be poised in the region of maximal sensitivity to small changes in ambient glutamate. PMID:25855696

  20. Regulation of VH replacement by B cell receptor-mediated signaling in human immature B cells.

    Science.gov (United States)

    Liu, Jing; Lange, Miles D; Hong, Sang Yong; Xie, Wanqin; Xu, Kerui; Huang, Lin; Yu, Yangsheng; Ehrhardt, Götz R A; Zemlin, Michael; Burrows, Peter D; Su, Kaihong; Carter, Robert H; Zhang, Zhixin

    2013-06-01

    VH replacement provides a unique RAG-mediated recombination mechanism to edit nonfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversification of Ab repertoire in the mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. In this article, we show that cross-linking BCRs induces VH replacement in human EU12 μHC(+) cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling-induced VH replacement is dependent on the activation of Syk and Src kinases but is inhibited by CD19 costimulation, presumably through activation of the PI3K pathway. These results show that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.

  1. Molecular and Biochemical Effects of a Kola Nut Extract on Androgen Receptor-Mediated Pathways

    International Nuclear Information System (INIS)

    The low incidence of prostate cancer in Asians has been attributed to chemo preventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemo preventative properties of the Jamaican bush tea Bizzy using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI50) of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the pro apoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC50) of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.

  2. CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus.

    Science.gov (United States)

    Scerif, Miski; Füzesi, Tamás; Thomas, Julia D; Kola, Blerina; Grossman, Ashley B; Fekete, Csaba; Korbonits, Márta

    2013-10-01

    AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy homeostasis, can be influenced by several hormones. Tissue-specific alteration of AMPK activity by glucocorticoids may explain the increase in appetite, the accumulation of lipids in adipose tissues, and the detrimental cardiac effects of Cushing's syndrome. Endocannabinoids are known to mediate the effects of various hormones and to influence AMPK activity. Cannabinoids have central orexigenic and direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In our preliminary experiments, WT mice received implants of a corticosterone-containing pellet to establish a mouse model of Cushing's syndrome. Subsequently, WT and Cb1 (Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight gain and of increase in hypothalamic and hepatic AMPK activity. In adipose tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid-induced drop was observed, similar to that observed in WT mice. Cardiac AMPK levels were reduced in CB1-KO mice, but while WT mice showed significantly reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a paradoxical increase. Our findings indicate the importance of the CB1 receptor in the central orexigenic effect of glucocorticoid-induced activation of hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur independently of the CB1 receptor, but the receptor appears to alter the responsiveness of the liver and myocardial tissues to glucocorticoids. In conclusion, our data suggest that an intact cannabinoid pathway is required for the full metabolic effects of chronic glucocorticoid excess.

  3. Basolateral amygdala CB1 cannabinoid receptors mediate nicotine-induced place preference.

    Science.gov (United States)

    Hashemizadeh, Shiva; Sardari, Maryam; Rezayof, Ameneh

    2014-06-01

    In the present study, the effects of bilateral microinjections of cannabinoid CB1 receptor agonist and antagonist into the basolateral amygdala (intra-BLA) on nicotine-induced place preference were examined in rats. A conditioned place preference (CPP) apparatus was used for the assessment of rewarding effects of the drugs in adult male Wistar rats. Subcutaneous (s.c.) administration of nicotine (0.2mg/kg) induced a significant CPP, without any effect on the locomotor activity during the testing phase. Intra-BLA microinjection of a non-selective cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (0.1-0.5 μg/rat) with an ineffective dose of nicotine (0.1mg/kg, s.c.) induced a significant place preference. On the other hand, intra-BLA administration of AM251 (20-60 ng/rat), a selective cannabinoid CB1 receptor antagonist inhibited the acquisition of nicotine-induced place preference. It should be considered that the microinjection of the same doses of WIN 55,212-2 or AM251 into the BLA, by itself had no effect on the CPP score. The administration of a higher dose of AM251 (60 ng/rat) during the acquisition decreased the locomotor activity of animals on the testing phase. Interestingly, the microinjection of AM251 (20 and 40 ng/rat), but not WIN55,212-2 (0.1-0.5 μg/rat), into the BLA inhibited the expression of nicotine-induced place preference without any effect on the locomotor activity. Taken together, these findings support the possible role of endogenous cannabinoid system of the BLA in the acquisition and the expression of nicotine-induced place preference. Furthermore, it seems that there is a functional interaction between the BLA cannabinoid receptors and nicotine in producing the rewarding effects.

  4. Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity.

    Science.gov (United States)

    Reich, C G; Mihalik, G R; Iskander, A N; Seckler, J C; Weiss, M S

    2013-12-01

    Endocannabinoids (eCBs) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders. Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is unknown how this stress-induced change in CB1 levels affects eCB-mediated neurotransmission. In vitro, field potential recordings from CMS-exposed (21-days) rats were performed to assess the effects of stress on eCB-regulated glutamatergic neurotransmission in/on hippocampal area CA1. We observed that application of the CB1 agonist, WIN 55,212-5 (1 μM), in stress animals resulted in a ∼135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ∼30% decrease. However, during blockade of GABA(A) neurotransmission with picrotoxin, CB1 activation yielded a ∼35% decrease in stress animals. These findings indicate that CMS does not directly affect glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic terminals, leading to less inhibition and an increase in excitatory neurotransmission. This finding is reinforced in that induction of weak long-term-potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals. These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity.

  5. Pax6 represses androgen receptor-mediated transactivation by inhibiting recruitment of the coactivator SPBP.

    Directory of Open Access Journals (Sweden)

    Julianne Elvenes

    Full Text Available The androgen receptor (AR has a central role in development and maintenance of the male reproductive system and in the etiology of prostate cancer. The transcription factor Pax6 has recently been reported to act as a repressor of AR and to be hypermethylated in prostate cancer cells. SPBP is a transcriptional regulator that previously has been shown to enhance the activity of Pax6. In this study we have identified SPBP to act as a transcriptional coactivator of AR. We also show that Pax6 inhibits SPBP-mediated enhancement of AR activity on the AR target gene probasin promoter, a repression that was partly reversed by increased expression of SPBP. Enhanced expression of Pax6 reduced the amount of SPBP associated with the probasin promoter when assayed by ChIP in HeLa cells. We mapped the interaction between both AR and SPBP, and AR and Pax6 to the DNA-binding domains of the involved proteins. Further binding studies revealed that Pax6 and SPBP compete for binding to AR. These results suggest that Pax6 represses AR activity by displacing and/or inhibiting recruitment of coactivators to AR target promoters. Understanding the mechanism for inhibition of AR coactivators can give rise to molecular targeted drugs for treatment of prostate cancer.

  6. How toxic is oil? Investigating specific receptor-mediated toxic effects of crude and refined oils

    NARCIS (Netherlands)

    Vrabie, C.M.

    2011-01-01

    Crude oils and refined oil products are major pollutants of the environment. Large oil spills, such as the recent blowout of the Deepwater Horizon in the Gulf of Mexico, raise concerns about the long term health effects of petroleum hydrocarbon exposure on wildlife and humans. In the environmental r

  7. Bidirectional regulation of angiogenesis by phytoestrogens through estrogen receptor-mediated signaling networks.

    Science.gov (United States)

    Liu, Hai-Xin; Wang, Yu; Lu, Qing; Yang, Ming-Zhu; Fan, Guan-Wei; Karas, Richard H; Gao, Xiu-Mei; Zhu, Yan

    2016-04-01

    Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERα and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERα and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERα, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERα and ERβ may be critical in the balance of pro- or anti-angiogenesis process. PMID:27114311

  8. Direct and indirect endocrine disruption : aromatase and estrogen receptor-mediated processes in breast cancer development

    NARCIS (Netherlands)

    Heneweer, Marjoke

    2005-01-01

    Endocrine disrupting chemicals (EDCs) have been defined by the World Health Organization as: “exogenous substances or mixtures that alters function(s) of the endocrine system and causes adverse health effects in an intact organism, or its progeny, or (sub)populations”. Synthetic, as well as, natura

  9. Formulating tumor-homing peptides as regular nanoparticles enhances receptor-mediated cell penetrability

    OpenAIRE

    Xu, Zhikun; Unzueta Elorza, Ugutz; Roldán, Mónica; Mangues, Ramón; Sánchez Chardi, Alejandro; Ferrer Miralles, Neus; Villaverde Corrales, Antonio; Vázquez Gómez, Esther

    2015-01-01

    The authors acknowledge the financial support granted to E.V. (PI12/00327) and R.M. (PI12/01861) from FIS, to E.V. (TV32013-133930) and to R.M. and A.V. (TV32013-132031) from La Marató de TV3 (416/C/2013), to A.V. from MINECO (Grant BIO2013-41019-P) and from the Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina (NANOPROTHER and NANOCOMETS projects). We are grateful to the Protein Production Platform (CIBER-BBN-UAB) for protein production and purif...

  10. Modulation of Toll-like receptor-mediated activation of Microglia

    NARCIS (Netherlands)

    Putten, C. M.-T. van der

    2015-01-01

    Microglia are the resident macrophages of the central nervous system (CNS). Like other tissue macrophages, microglia have many different functions under physiological as well as pathological conditions. Microglia can contribute to the initiation, progression and resolution of disease processes and m

  11. Rapidly activated epidermal growth factor receptor mediates lipopolysaccharide-triggered migration of microglia.

    Science.gov (United States)

    Qu, Wen-Sheng; Liu, Jun-Li; Li, Chun-Yu; Li, Xiao; Xie, Min-Jie; Wang, Wei; Tian, Dai-Shi

    2015-11-01

    Previous reports have suggested that epidermal growth factor receptor (EGFR) is involved in microglia activation characterized by cell morphology changes, cytokine production and cell migration; and the biochemical regulation of the microglia migration is a potential therapeutic target following CNS inflammatory damages. However, the role of EGFR in microglia motility after inflammatory stimulation remains unknown. In the present study, lipopolysaccharide (LPS) was found to trigger rapid EGFR phosphorylation within 10 min, which was sustained during long-term stimulation in both primary microglial cells and the cultured BV2 microglial cells, furthermore, blocking EGFR phosphorylation by AG1478 significantly attenuated the LPS-induced chemotactic and chemokinetic migration of microglia. In addition, LPS could initiate calcium oscillation in microglia during live-cell recording, however, an intracellular calcium chelator and a selective inhibitor of calcium/calmodulin-dependent protein kinase II, but not an extracellular calcium chelator, remarkably suppressed the LPS-induced EGFR phosphorylation in BV2 microglia cells. As EGFR is not a traditional receptor for LPS, these findings suggest that the rapid phosphorylation of EGFR is attributed to the LPS-triggered intracellular calcium mobilization. By examining the downstream signals of EGFR, we further proved that extracellular signal-regulated kinase (ERK) is essential for EGFR-mediated microglia migration, because ERK inhibition attenuated the chemotactic and chemokinetic migration of microglia that had been induced by either LPS or EGF. Collectively, these results suggest that LPS could trigger the rapid phosphorylation of EGFR and subsequent ERK activation through mobilizing calcium activity, which underlies the microglia migration in an inflammatory condition.

  12. Melanocortin receptor-mediated effects on obesity are distributed over specific hypothalamic regions

    NARCIS (Netherlands)

    M.W.A. de Backer; S.E. la Fleur; M.A.D. Brans; A.J. van Rozen; M.C.M. Luijendijk; M. Merkestein; K.M. Garner; E.M. van der Zwaal; R.A.H. Adan

    2011-01-01

    Objective:Reduction of melanocortin signaling in the brain results in obesity. However, where in the brain reduced melanocortin signaling mediates this effect is poorly understood.Design:We determined the effects of long-term inhibition of melanocortin receptor activity in specific brain regions of

  13. beta. -adrenergic receptor-mediated hepatic glycogenolysis is increased in aged male rats

    Energy Technology Data Exchange (ETDEWEB)

    Herring, P.A.; Graham, S.M.; Arinze, I.J.

    1986-03-05

    The effect of age on catecholamine-stimulated glycogenolysis was studied in isolated hepatocytes prepared from 3, 12, and 24 month-old rats. Glucose release was stimulated by epinephrine and norepinephrine, this was inhibited by phentolamine and prazosin. Isoproterenol (ISO) stimulated glycogenolysis only in cells from 24 month-old rats, this was blocked by propranolol. In liver plasma membranes, binding of (/sup 3/H)yohimbine (100-130 fmol/mg protein) did not change with age, whereas (/sup 3/H)prazosin binding decreased from 870 fmol/mg at 3 months to 435 fmol/mg at 12 months, but subsequently rose to 656 fmol/mg at 24 months. (/sup 125/I)Cyanopindolol binding increased from 8 fmol/mg at 3 months to 19 fmol/mg at 24 months. The proportion of ..beta..-receptors in the high affinity state increased from 28% at 3 months to 42% at 24 months. ISO stimulated adenylate cyclase at 24 months but not at 3 months. Basal, fluoride-, GTP-, and Gpp(NH)p-stimulated activities were 1.4- to 2.4-fold greater at 24 months than at 3 months. These results suggest an age-related increase in the sensitivity of adenylate cyclase to ..beta..-receptor stimulation.

  14. Identification of Novel Pathways That Control Farnesoid X Receptor-mediated Hypocholesterolemia*

    OpenAIRE

    Zhang, Yanqiao; Yin, Liya; Anderson, Jody; Ma, Huiyan; Gonzalez, Frank J.; Willson, Timothy M.; Edwards, Peter A.

    2009-01-01

    Farnesoid X receptor (FXR) plays important regulatory roles in bile acid, lipoprotein, and glucose homeostasis. Here, we have utilized Fxr−/− mice and mice deficient in scavenger receptor class B type I (SR-BI), together with an FXR-specific agonist and adenovirus expressing hepatocyte nuclear factor 4α or constitutively active FXR, to identify the mechanisms by which activation of FXR results in hypocholesterolemia. We identify a novel pathway linking FXR to changes in hepatic p-JNK, hepatoc...

  15. A Boolean Network Model of Nuclear Receptor Mediated Cell Cycle Progression

    Science.gov (United States)

    Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad range of cellular processes. Hormones, lipids and xenobiotics have been shown to activate NRs with a range of consequences on development, metabolism, oxidative stress, apoptosis, and prolif...

  16. Modeling Nuclear Receptor-Mediated Activity and Hepatotoxicity with Boolean Networks

    Science.gov (United States)

    Predicting the human health risk of chronic exposure to environmental contaminants remains an open problem. Chronic exposure to a wide array of chemicals – e.g., conazoles, perfluourinated chemicals and phthalates – has been associated with a range of hepatic lesions in rodents t...

  17. A Boolean Network Model of Nuclear Receptor Mediated Cell Cycle Progression (S)

    Science.gov (United States)

    Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad range of cellular processes. Hormones, lipids and xenobiotics have been shown to activate NRs with a range of consequences on development, metabolism, oxidative stress, apoptosis, and prolif...

  18. Ionotropic glutamate receptors mediate inducible defense in the water flea Daphnia pulex.

    Directory of Open Access Journals (Sweden)

    Hitoshi Miyakawa

    Full Text Available Phenotypic plasticity is the ability held in many organisms to produce different phenotypes with a given genome in response to environmental stimuli, such as temperature, nutrition and various biological interactions. It seems likely that environmental signals induce a variety of mechanistic responses that influence ontogenetic processes. Inducible defenses, in which prey animals alter their morphology, behavior and/or other traits to help protect against direct or latent predation threats, are among the most striking examples of phenotypic plasticity. The freshwater microcrustacean Daphnia pulex forms tooth-like defensive structures, "neckteeth," in response to chemical cues or signals, referred to as "kairomones," in this case released from phantom midge larvae, a predator of D. pulex. To identify factors involved in the reception and/or transmission of a kairomone, we used microarray analysis to identify genes up-regulated following a short period of exposure to the midge kairomone. In addition to identifying differentially expressed genes of unknown function, we also found significant up-regulation of genes encoding ionotropic glutamate receptors, which are known to be involved in neurotransmission in many animal species. Specific antagonists of these receptors strongly inhibit the formation of neckteeth in D. pulex, although agonists did not induce neckteeth by themselves, indicating that ionotropic glutamate receptors are necessary but not sufficient for early steps of neckteeth formation in D. pulex. Moreover, using co-exposure of D. pulex to antagonists and juvenile hormone (JH, which physiologically mediates neckteeth formation, we found evidence suggesting that the inhibitory effect of antagonists is not due to direct inhibition of JH synthesis/secretion. Our findings not only provide a candidate molecule required for the inducible defense response in D. pulex, but also will contribute to the understanding of complex mechanisms underlying the recognition of environmental changes, which form the basis of phenotypic plasticity.

  19. IL-1 Receptors Mediate Persistent, but Not Acute, Airway Hyperreactivity to Ozone in Guinea Pigs

    OpenAIRE

    Verhein, Kirsten C.; Jacoby, David B.; Allison D Fryer

    2008-01-01

    Ozone exposure in the lab and environment causes airway hyperreactivity lasting at least 3 days in humans and animals. In guinea pigs 1 day after ozone exposure, airway hyperreactivity is mediated by eosinophils that block neuronal M2 muscarinic receptor function, thus increasing acetylcholine release from airway parasympathetic nerves. However, mechanisms of ozone-induced airway hyperreactivity change over time, so that depleting eosinophils 3 days after ozone makes airway hyperreactivity wo...

  20. Cholecystokinin-2 receptor mediated gene expression in neuronal PC12 cells

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Borup, Rehannah; Marstrand, Troels;

    2007-01-01

    Cholecystokinin (CCK) is abundantly expressed in the CNS, in which it regulates feeding behavior and long-term memory. Moreover, CCK has been implicated in mental disorders, such as anxiety and schizophrenia. Despite its manifest physiological and pathophysiological role, the molecular targets...... could be identified. Comparison with forskolin- and nerve growth factor (NGF)-treated PC12 cells showed that CCK induced a separate set of target genes. Taken together, we propose that neuronal CCK may have a role in the regulation of the circadian rhythm, the metabolism of cerebral cholesterol...

  1. Techniques to Study Specific Cell-Surface Receptor-Mediated Cellular Vitamin A Uptake

    OpenAIRE

    KAWAGUCHI, RIKI; Sun, Hui

    2010-01-01

    STRA6 is a multitransmembrane domain protein that was recently identified as the cell-surface receptor for plasma retinol binding protein (RBP), the vitamin A carrier protein in the blood. STRA6 binds to RBP with high affinity and mediates cellular uptake of vitamin A from RBP. It is not homologous to any known receptors, transporters, and channels, and it represents a new class of membrane transport protein. Consistent with the diverse physiological functions of vitamin A, STRA6 is widely ex...

  2. Dopamine D2 Receptor-Mediated Regulation of Pancreatic β Cell Mass

    Directory of Open Access Journals (Sweden)

    Daisuke Sakano

    2016-07-01

    Full Text Available Understanding the molecular mechanisms that regulate β cell mass and proliferation is important for the treatment of diabetes. Here, we identified domperidone (DPD, a dopamine D2 receptor (DRD2 antagonist that enhances β cell mass. Over time, islet β cell loss occurs in dissociation cultures, and this was inhibited by DPD. DPD increased proliferation and decreased apoptosis of β cells through increasing intracellular cAMP. DPD prevented β cell dedifferentiation, which together highly contributed to the increased β cell mass. DRD2 knockdown phenocopied the effects of domperidone and increased the number of β cells. Drd2 overexpression sensitized the dopamine responsiveness of β cells and increased apoptosis. Further analysis revealed that the adenosine agonist 5′-N-ethylcarboxamidoadenosine, a previously identified promoter of β cell proliferation, acted with DPD to increase the number of β cells. In humans, dopamine also modulates β cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling.

  3. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

    KAUST Repository

    Gao, Virginia

    2016-07-12

    Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

  4. Acid-responsive PEGylated doxorubicin prodrug nanoparticles for neuropilin-1 receptor-mediated targeted drug delivery.

    Science.gov (United States)

    Song, Huijuan; Zhang, Ju; Wang, Weiwei; Huang, Pingsheng; Zhang, Yumin; Liu, Jianfeng; Li, Chen; Kong, Deling

    2015-12-01

    Self-assembled prodrug nanoparticles have demonstrated great promise in cancer chemotherapy. In the present study, we developed a new kind of prodrug nanoparticles for targeted drug delivery. PEGylated doxorubicin conjugate with an acid-cleavable cis-aconityl spacer was prepared. Then it was functionalized with a tumor-penetrating peptide, Cys-Arg-Gly-Asp-Lys (CRGDK), providing the prodrug nanoparticles with the specific binding ability to neurophilin-1 receptor. In acid mediums, doxorubicin could be released from the prodrug nanoparticles with an accumulative release around 60% through the acid-triggered hydrolysis of cis-aconityl bond and nanoparticle disassembly. Whereas, drug release was slow under a neutral pH and the accumulative drug release was less than 16%. In the cell culture tests, our prodrug nanoparticles showed enhanced endocytosis and cytotoxicity in cancer cells including HepG2, MCF-7 and MDA-MB-231 cells, but lower cytotoxicity in human cardiomyocyte H2C9. In the animal experiments, the prodrug nanoparticles were intravenously injected into Balb/c nude mice bearing MDA-MB-231 tumors. Enhanced drug penetration and accumulation in tumors, accompanying with a rapid early tumor-binding behavior, was observed after intravenous injection of the peptide modified prodrug nanoparticles. These data suggests that the acid-sensitive and tumor-targeting PEGylated doxorubicin prodrug nanoparticle may be an efficient drug delivery system for cancer chemotherapy.

  5. Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes

    DEFF Research Database (Denmark)

    Haxholm, Gitte Wolfsberg; Nikolajsen, Louise Fletcher; Olsen, Johan Gotthardt;

    2015-01-01

    Class 1 cytokine receptors regulate essential biological processes through complex intracellular signaling networks. However, the structural platform for understanding their functions is currently incomplete as structure-function studies of the intracellular domains (ICDs) are critically lacking...... of the inner plasma membrane leaflet through conserved motifs resembling immuno T-cell receptor activation motifs(ITAMs). However, contrary to the observations made for ITAMs, lipid association of the prolactin and growth hormone receptor ICDs was shown to be unaccompanied by changes in transient secondary...... structure and independent of tyrosine phosphorylation. The data presented here provides a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signaling....

  6. Mechanisms of G Protein-Coupled Estrogen Receptor-Mediated Spinal Nociception

    DEFF Research Database (Denmark)

    Deliu, Elena; Brailoiu, G. Cristina; Arterburn, Jeffrey B.;

    2012-01-01

    Human and animal studies suggest that estrogens are involved in the processing of nociceptive sensory information and analgesic responses in the central nervous system. Rapid pronociceptive estrogenic effects have been reported, some of which likely involve G protein-coupled estrogen receptor (GPER...... in spinal nociceptive processing. Intrathecal challenging of mice with the GPER agonist G-1 results in pain-related behaviors. GPER antagonism with G15 reduces the G-1-induced response. Electrophysiological recordings from superficial dorsal horn neurons indicate neuronal membrane depolarization with G-1...... application, which is G15 sensitive. In cultured spinal sensory neurons, G-1 increases intracellular calcium concentration and induces mitochondrial and cytosolic ROS accumulation. In the presence of G15, G-1 does not elicit the calcium and ROS responses, confirming specific GPER involvement in this process...

  7. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Harmit S. Ranhotra

    2016-07-01

    Full Text Available The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.

  8. The nuclear architectural protein HMGA1a triggers receptor-mediated endocytosis.

    Science.gov (United States)

    Wu, Wuwei; Wan, Wei; Li, Alexander D Q

    2009-11-01

    High mobility group proteins A (HMGA), nuclear architectural factors, locate in the cell nuclei and mostly execute gene-regulation function. However, our results reveal that a HMGA member (HMGA1a) has a unique plasma membrane receptor; this receptor specifically binds to HMGA-decorated species, effectively mediates endocytosis, and internalizes extracellular HMGA-functionalized cargoes. Indeed, dyes or nanoparticles labeled with HMGA1a protein readily enter Hela cells. Using a stratagem chemical cross-linker, we covalently bonded the HMGA receptor to the HMGA1a-GFP fusion protein, thus capturing the plasma membrane receptor. Subsequent Western blots and SDS-PAGE gel revealed that the HMGA receptor is a 26-kDa protein. Confocal live-cell microscopic imaging was used to monitor the whole endocytic process, in which the internalized HMGA1a-decorated species are transported by motor proteins on microtubules and eventually arrive at the late endosomes/lysosomes. Cell viability assays also suggested that extracellular HMGA1a protein directly influences the survival ability of Hela cells in a dose-dependent manner, implying versatility of HMGA1a protein and its potent role to suppress cancer cell survivability and to regulate growth. PMID:19739099

  9. pp90rsk1 Regulates Estrogen Receptor-Mediated Transcription through Phosphorylation of Ser-167

    OpenAIRE

    Joel, Peteranne B.; Smith, Jeffrey; Sturgill, Thomas W.; Fisher, Tracey L.; Blenis, John; Lannigan, Deborah A.

    1998-01-01

    The estrogen receptor α (ER), a member of the steroid receptor superfamily, contains an N-terminal hormone-independent transcriptional activation function (AF-1) and a C-terminal hormone-dependent transcriptional activation function (AF-2). Here, we used in-gel kinase assays to determine that pp90rsk1 activated by either epidermal growth factor (EGF) or phorbol myristate acetate specifically phosphorylates Ser-167 within AF-1. In vitro kinase assays demonstrated that pp90rsk1 phosphorylates t...

  10. How toxic is oil? Investigating specific receptor-mediated toxic effects of crude and refined oils

    OpenAIRE

    Vrabie, C.M.

    2011-01-01

    Crude oils and refined oil products are major pollutants of the environment. Large oil spills, such as the recent blowout of the Deepwater Horizon in the Gulf of Mexico, raise concerns about the long term health effects of petroleum hydrocarbon exposure on wildlife and humans. In the environmental risk assessment of oils, narcosis (the disruption of an organism’s membrane structure) is the only mode of action assumed to determine the toxicity of petroleum hydrocarbons. However, several crude ...

  11. Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide

    International Nuclear Information System (INIS)

    A newly developed somatostatin radioligand, DOTA-[D-Phe1-Tyr3]-octreotide (DOTATOC), has been synthesised for therapeutic purposes, because of its stable and easy labelling with yttrium-90. The aim of this study was to determine the dosage, safety profile and therapeutic efficacy of 90Y-DOTATOC in patients with cancers expressing somatostatin receptors. We recruited 30 patients with histologically confirmed cancer. The main inclusion criterion was the presence of somatostatin receptors as documented by 111In-DOTATOC scintigraphy. 90Y-DOTATOC was injected intravenously using a horizontal protocol: patients received equivalent-activity doses in each of three cycles over 6 months. The first six patients received 1.11 GBq per cycle and the four successive groups of six patients received doses increasing in 0.37-GBq steps. Toxicity was evaluated according to WHO criteria. No patient had acute or delayed adverse reactions up to 2.59 GBq 90Y-DOTATOC per cycle (total 7.77 GBq). After a total dose of 3.33 GBq, one patient developed grade II renal toxicity 6 months later. The maximum tolerated dose per cycle has not yet been reached, although transient lymphocytopenia has been observed. Total injectable activity is limited by the fact that the maximum dose tolerated by the kidneys has been estimated at 20-25 Gy. Complete or partial tumour mass reduction occurred in 23% of patients; 64% had stable and 13% progressive disease. It is concluded that high activities of 90Y-DOTATOC can be administered with a low risk of myelotoxicity, although the cumulative radiation dose to the kidneys is a limiting factor and requires careful evaluation. Objective therapeutic responses have been observed. (orig.)

  12. Vacuolar Sorting Receptor-Mediated Trafficking of Soluble Vacuolar Proteins in Plant Cells

    Directory of Open Access Journals (Sweden)

    Hyangju Kang

    2014-08-01

    Full Text Available Vacuoles are one of the most prominent organelles in plant cells, and they play various important roles, such as degradation of waste materials, storage of ions and metabolites, and maintaining turgor. During the past two decades, numerous advances have been made in understanding how proteins are specifically delivered to the vacuole. One of the most crucial steps in this process is specific sorting of soluble vacuolar proteins. Vacuolar sorting receptors (VSRs, which are type I membrane proteins, are involved in the sorting and packaging of soluble vacuolar proteins into transport vesicles with the help of various accessory proteins. To date, large amounts of data have led to the development of two different models describing VSR-mediated vacuolar trafficking that are radically different in multiple ways, particularly regarding the location of cargo binding to, and release from, the VSR and the types of carriers utilized. In this review, we summarize current literature aimed at elucidating VSR-mediated vacuolar trafficking and compare the two models with respect to the sorting signals of vacuolar proteins, as well as the molecular machinery involved in VSR-mediated vacuolar trafficking and its action mechanisms.

  13. Hypothyroidism Affects D2 Receptor-mediated Breathing without altering D2 Receptor Expression

    OpenAIRE

    Schlenker, Evelyn H; Rio, Rodrigo Del; Schultz, Harold D.

    2014-01-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age- matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a periphera...

  14. Role of desensitization and subunit expression for kainate receptor-mediated neurotoxicity in murine neocortical cultures

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S;

    1999-01-01

    The neurotoxic actions of kainate and domoate were studied in cultured murine neocortical neurons at various days in culture and found to be developmentally regulated involving three components of neurotoxicity: (1) toxicity via indirect activation of N-methyl-D-aspartate (NMDA) receptors, (2) to...... produced by kainate receptors in mature cultures. Examining the subunit expression of the kainate receptor subunits GluR6/7 and KA2 did, however, not reveal any major change during development of the cultures....

  15. THIP, a hypnotic and antinociceptive drug, enhances a tonic GABAA receptor mediated conductance in mouse neocortex

    DEFF Research Database (Denmark)

    Drasbek, Kim Ryun; Jensen, Kimmo

    2006-01-01

    THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a selective GABA(A) receptor agonist with a preference for delta-subunit containing GABA(A) receptors. THIP is currently being tested in human trials for its hypnotic effects, displaying advantageous tolerance and addiction properties. Since...

  16. Potential insight for drug discovery from high fidelity receptor-mediated transduction mechanisms in insects

    Science.gov (United States)

    Raffa, Robert B.; Raffa, Kenneth F.

    2011-01-01

    Introduction There is a pervasive and growing concern about the small number of new pharmaceutical agents. There are many proposed explanations for this trend that do not involve the drug-discovery process per se, but the discovery process itself has also come under scrutiny. If the current paradigms are indeed not working, where are novel ideas to come from? Perhaps it is time to look to novel sources. Areas covered The receptor-signaling and 2nd-messenger transduction processes present in insects are quite similar to those in mammals (involving G proteins, ion channels, etc.). However, a review of these systems reveals an unprecedented degree of high potency and receptor selectivity to an extent greater than that modeled in most current drug-discovery approaches. Expert opinion A better understanding of insect receptor pharmacology could stimulate novel theoretical and practical ideas in mammalian pharmacology (drug discovery) and, conversely, the application of pharmacology and medicinal chemistry principles could stimulate novel advances in entomology (safer and more targeted control of pest species). PMID:21984882

  17. Monoolein-based nanocarriers for enhanced folate receptor-mediated RNA delivery to cancer cells.

    Science.gov (United States)

    Lopes, Ivo; C N Oliveira, Ana; P Sárria, Marisa; P Neves Silva, João; Gonçalves, Odete; Gomes, Andreia C; Real Oliveira, Maria Elisabete C D

    2016-09-01

    We report the development and characterization of a novel nanometric system for specific delivery of therapeutic siRNA for cancer treatment. This vector is based on a binary mixture of the cationic surfactant dioctadecyldimethylammonium chloride (DODAC) and the helper lipid monoolein (MO). These liposomes were previously validated by our research group as promising non-viral vectors for nucleic acid delivery. In this work, the DODAC:MO vesicles were for the first time functionalized with polyethylene glycol and PEG-folate conjugates to achieve both maximal stability in biological fluids and increase selectivity toward folate receptor α expressing cells. The produced DODAC:MO:PEG liposomes were highly effective in RNA complexation (close to 100%), and the resulting lipoplexes also demonstrated high stability in conditions simulating their administration by intravenous injection (physiological pH, high NaCl, heparin and fetal bovine serum concentrations). In addition, cell uptake of the PEG-folate-coated lipoplexes was significantly greater in folate receptor α positive breast cancer cells (39% for 25 µg/mL of lipid and 31% for 40 µg/mL) when compared with folate receptor α negative cells (31% for 25 µg/mL of lipid and 23% for 40 µg/mL) and to systems without PEG-folate (≈13% to 16% for all tested conditions), supporting their selectivity towards the receptor. Overall, the results support these systems as appealing vectors for selective delivery of siRNA to cancer cells by folate receptor α-mediated internalization, aiming at future therapeutic applications of interest. PMID:26340109

  18. Role of receptor-mediated endocytosis, endosomal acidification and cathepsin D in cholera toxin cytotoxicity.

    Science.gov (United States)

    El Hage, Tatiana; Merlen, Clémence; Fabrega, Sylvie; Authier, François

    2007-05-01

    Using the in situ liver model system, we have recently shown that, after cholera toxin binding to hepatic cells, cholera toxin accumulates in a low-density endosomal compartment, and then undergoes endosomal proteolysis by the aspartic acid protease cathepsin-D [Merlen C, Fayol-Messaoudi D, Fabrega S, El Hage T, Servin A, Authier F (2005) FEBS J272, 4385-4397]. Here, we have used a subcellular fractionation approach to address the in vivo compartmentalization and cytotoxic action of cholera toxin in rat liver parenchyma. Following administration of a saturating dose of cholera toxin to rats, rapid endocytosis of both cholera toxin subunits was observed, coincident with massive internalization of both the 45 kDa and 47 kDa Gsalpha proteins. These events coincided with the endosomal recruitment of ADP-ribosylation factor proteins, especially ADP-ribosylation factor-6, with a time course identical to that of toxin and the A subunit of the stimulatory G protein (Gsalpha) translocation. After an initial lag phase of 30 min, these constituents were linked to NAD-dependent ADP-ribosylation of endogenous Gsalpha, with maximum accumulation observed at 30-60 min postinjection. Assessment of the subsequent postendosomal fate of internalized Gsalpha revealed sustained endolysosomal transfer of the two Gsalpha isoforms. Concomitantly, cholera toxin increased in vivo endosome acidification rates driven by the ATP-dependent H(+)-ATPase pump and in vitro vacuolar acidification in hepatoma HepG2 cells. The vacuolar H(+)-ATPase inhibitor bafilomycin and the cathepsin D inhibitor pepstatin A partially inhibited, both in vivo and in vitro, the cAMP response to cholera toxin. This cathepsin D-dependent action of cholera toxin under the control of endosomal acidity was confirmed using cellular systems in which modification of the expression levels of cathepsin D, either by transfection of the cathepsin D gene or small interfering RNA, was followed by parallel changes in the cytotoxic response to cholera toxin. Thus, in hepatic cells, a unique endocytic pathway was revealed following cholera toxin administration, with regulation specificity most probably occurring at the locus of the endosome and implicating endosomal proteases, such as cathepsin D, as well as organelle acidification. PMID:17451437

  19. Evidence that 5-hydroxytryptamine/sub 3/ receptors mediate cytotoxic drug and radiation-evoked emesis

    Energy Technology Data Exchange (ETDEWEB)

    Miner, W.D.; Sanger, G.J.; Turner, D.H.

    1987-08-01

    The involvement of 5-hydroxytryptamine (5-HT) 5-HT/sub 3/ receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT/sub 3/ receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT/sub 3/ receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT/sub 3/ receptors in the mechanisms mediating severely emetogenic cancer treatment therapies.

  20. Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain.

    Science.gov (United States)

    Jhaveri, Maulik D; Sagar, Devi R; Elmes, Steven J R; Kendall, David A; Chapman, Victoria

    2007-08-01

    The endocannabinoid system consists of cannabinoid CB(1) and CB(2) receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB(1) receptors. Following the recent evidence for CB(2) receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB(2) receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB(2) receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB(2) receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action.

  1. Androgen Receptors Mediate Masculinization of Astrocytes in the Rat Posterodorsal Medial Amygdala During Puberty

    OpenAIRE

    JOHNSON, RYAN T.; Breedlove, S. Marc; Jordan, Cynthia L.

    2013-01-01

    Astrocytes in the posterodorsal portion of the medial amygdala (MePD) are sexually dimorphic in adult rats: males have more astrocytes in the right MePD and more elaborate processes in the left MePD than do females. Functional androgen receptors (ARs) are required for masculinization of MePD astrocytes, as these measures are demasculinized in adult genetic males carrying the testicular feminization mutation (Tfm) of the AR gene, which renders AR dysfunctional. We now report that the number of...

  2. Orexin-1 Receptor Mediation of Cocaine Seeking in Male and Female Rats

    OpenAIRE

    Zhou, Luyi; Ghee, Shannon M.; Chan, Clifford; Lin, Li; Cameron, Michael D.; Kenny, Paul J.; See, Ronald E.

    2012-01-01

    Previous studies have shown that female rats exhibit enhanced cocaine seeking during multiple phases of cocaine addiction compared with males. The orexin/hypocretin system recently has been implicated in drug addiction in male rats. Based on the known sex differences in cocaine addiction, in the current study we examined orexin-mediated cocaine seeking during self-administration, extinction, and reinstatement in age-matched male (initial weight 250–300 g) and female (initial weight 175–225 g)...

  3. Adiponectin increases secretion of rat submandibular gland via adiponectin receptors-mediated AMPK signaling.

    Directory of Open Access Journals (Sweden)

    Chong Ding

    Full Text Available Adiponectin and adiponectin receptors (AdipoR1/2 are expressed in various tissues and are involved in the regulation of multiple functions such as energy metabolism and inflammatory responses. However, the effect of adiponectin and AdipoRs in submandibular glands has not been fully evaluated. In the present study, we found that mRNA and protein of both adiponectin and AdipoR1/2 were expressed in rat submandibular glands and in the SMG-C6 cell line, as evidenced by RT-PCR and Western blot analysis. Immunofluorescence staining showed that adiponectin was diffused in the cytoplasm, while AdipoR1/2 was concentrated in the membrane of acinar cells. Saliva flow was significantly increased by full length adiponectin (fAd or globular adiponectin (gAd perfusion in isolated rat submandibular glands. 5-Aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR, an adenosine monophosphate activated protein kinase (AMPK activator, also increased saliva secretion. fAd, gAd, and AICAR all increased the average width of apical tight junctions in perfused submandibular glands, and decreased transepithelial electrical resistance (TER in SMG-C6 cells, suggesting that adiponectin promoted secretion by modulating paracellular permeability. fAd and gAd increased p-AMPK levels, while AraA, an AMPK antagonist, abolished fAd- and gAd-induced changes in secretion, tight junction ultrastructure, and TER. Moreover, both AdipoR1 and AdipoR2 were required for fAd- or gAd-induced p-AMPK and TER responses, suggesting from their inhibition following AdipoR1 or AdipoR2 knockdown, and co-knockdown of AdipoRs by RNA interference. Our results suggest that adiponectin functions as a promoter of salivary secretion in rat submandibular glands via activation of AdipoRs, AMPK, and paracellular permeability.

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

    OpenAIRE

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

    1987-01-01

    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...

  5. Role of the Ventral Tegmental Area in Methamphetamine Extinction: AMPA Receptor-Mediated Neuroplasticity

    Science.gov (United States)

    Chen Han-Ting; Chen, Jin-Chung

    2015-01-01

    The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned…

  6. 5-Hydroxytryptamine Receptors Mediating Carotid and Systemic Haemodynamic Effects: The Relation to Acute Antimigraine Therapy

    NARCIS (Netherlands)

    P. de Vries (Peter)

    1999-01-01

    textabstractThe presence of a vasoconstrictor substance in blood was suspected for 130 years (Ludwig & Schmidt, 1868) and, 50 years ago, Page and associates at the Cleveland Clinic (Cleveland, Ohio, USA) succeeded in isolating 'serotonin' from the blood (Rapport et al., 1948). Within the next 3 year

  7. Histamine H(3 receptor-mediated signaling protects mice from cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Walid Beghdadi

    Full Text Available BACKGROUND: Histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. In humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. We reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (CM in mice infected with Plasmodium berghei ANKA. Histamine exerts its biological effects through four different receptors designated H1R, H2R, H3R, and H4R. PRINCIPAL FINDINGS: In the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R in the pathogenesis of murine CM. We observed that the lack of H3R expression (H3R(-/- mice accelerates the onset of CM and this was correlated with enhanced brain pathology and earlier and more pronounced loss of blood brain barrier integrity than in wild type mice. Additionally tele-methylhistamine, the major histamine metabolite in the brain, that was initially present at a higher level in the brain of H3R(-/- mice was depleted more quickly post-infection in H3R(-/- mice as compared to wild-type counterparts. CONCLUSIONS: Our data suggest that histamine regulation through the H3R in the brain suppresses the development of CM. Thus modulating histamine signaling in the central nervous system, in combination with standard therapies, may represent a novel strategy to reduce the risk of progression to cerebral malaria.

  8. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

    OpenAIRE

    Kontny, U; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  9. MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

    DEFF Research Database (Denmark)

    Kocerha, Jannet; Faghihi, Mohammad Ali; Lopez-Toledano, Miguel A;

    2009-01-01

    N-methyl-D-aspartate (NMDA) glutamate receptors are regulators of fast neurotransmission and synaptic plasticity in the brain. Disruption of NMDA-mediated glutamate signaling has been linked to behavioral deficits displayed in psychiatric disorders such as schizophrenia. Recently, noncoding RNA...... significantly modulated behavioral responses associated with disrupted NMDA receptor transmission. Furthermore, pretreatment with the antipsychotic drugs haloperidol and clozapine prevented dizocilpine-induced effects on miR-219. Taken together, these data support an integral role for miR-219 in the expression...

  10. Valerian inhibits rat hepatocarcinogenesis by activating GABA(A) receptor-mediated signaling.

    Science.gov (United States)

    Kakehashi, Anna; Kato, Ayumi; Ishii, Naomi; Wei, Min; Morimura, Keiichirou; Fukushima, Shoji; Wanibuchi, Hideki

    2014-01-01

    Valerian is widely used as a traditional medicine to improve the quality of sleep due to interaction of several active components with the γ-aminobutyric acid (GABA) A receptor (GABA(A)R) system. Recently, activation of GABA signaling in stem cells has been reported to suppress cell cycle progression in vivo. Furthermore, possible inhibitory effects of GABA(A)R agonists on hepatocarcinogenesis have been reported. The present study was performed to investigate modulating effects of Valerian on hepatocarcinogenesis using a medium-term rat liver bioassay. Male F344 rats were treated with one of the most powerful Valerian species (Valeriana sitchensis) at doses of 0, 50, 500 and 5000 ppm in their drinking water after initiation of hepatocarcinogenesis with diethylnitrosamine (DEN). Formation of glutathione S-transferase placental form positive (GST-P(+)) foci was significantly inhibited by Valerian at all applied doses compared with DEN initiation control rats. Generation of 8-hydroxy-2'-deoxyguanosine in the rat liver was significantly suppressed by all doses of Valerian, likely due to suppression of Nrf2, CYP7A1 and induction of catalase expression. Cell proliferation was significantly inhibited, while apoptosis was induced in areas of GST-P(+) foci of Valerian groups associated with suppression of c-myc, Mafb, cyclin D1 and induction of p21(Waf1/Cip1), p53 and Bax mRNA expression. Interestingly, expression of the GABA(A)R alpha 1 subunit was observed in GST-P(+) foci of DEN control rats, with significant elevation associated with Valerian treatment. These results indicate that Valerian exhibits inhibitory effects on rat hepatocarcinogenesis by inhibiting oxidative DNA damage, suppressing cell proliferation and inducing apoptosis in GST-P(+) foci by activating GABA(A)R-mediated signaling. PMID:25419570

  11. Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

    Institute of Scientific and Technical Information of China (English)

    Jian-xin SHEN; Jerrel L YAKEL

    2009-01-01

    Based on the composition of the five subunits forming functional neuronal nicotinic acetylcholine receptors (nAChRs), they are grouped into either heteromeric (comprising both α and β subunits) or homomeric (comprising only α subunits) recep-tors. The nAChRs are known to be differentially permeable to calcium ions, with the α7 nAChR subtype having one of the highest permeabilities to calcium. Calcium influx through nAChRs, particularly through the α-bungarotoxin-sensitive α7-containing nAChRs, is a very efficient way to raise cytoplasmic calcium levels. The activation of nAChRs can mediate three types of cytoplasmic calcium signals: (1) direct calcium influx through the nAChRs, (2) indirect calcium influx through voltage-dependent calcium channels (VDCCs) which are activated by the nAChR-mediated depolarization, and (3) calcium-induced calcium release (CICR) (triggered by the first two sources) from the endoplasmic reticulum (ER) through the ryanodine receptors and inositol (1,4,5)-triphosphate receptors (IP3Rs). Downstream signaling events mediated by nAChR-mediated calcium responses can be grouped into instantaneous effects (such as neurotransmitter release, which can occur in milliseconds after nAChR activation), short-term effects (such as the recovery of nAChR desensitization through cellular signaling cascades), and long-term effects (such as neuroprotection via gene expression). In addition, nAChR activity can be regulated by cytoplasmic calcium levels, suggesting a complex reciprocal relationship. Further advances in imaging techniques, animal models, and more potent and subtype-selective ligands for neuronal nAChRs would help in understand-ing the neuronal nAChR-mediated calcium signaling, and lead to the development of improved therapeutic treatments.

  12. A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.

    Science.gov (United States)

    Frecska, Ede; Szabo, Attila; Winkelman, Michael J; Luna, Luis E; McKenna, Dennis J

    2013-09-01

    N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies. PMID:23619992

  13. Characterization of the 5-HT4 receptor mediating tachycardia in piglet isolated right atrium.

    OpenAIRE

    Medhurst, A. D.; Kaumann, A J

    1993-01-01

    1. In order to explore whether 5-HT4 receptor subtypes exist, we have characterized further the 5-HT4 receptor that mediates tachycardia in the piglet isolated right atrium. All experiments were carried out in the presence of propranolol (400 nM) and cocaine (6 microM). We used tryptamine derivatives, substituted benzamides and benzimidazolone derivatives as pharmacological tools. 2. Tachycardia responses to 5-hydroxytryptamine (5-HT) were mimicked by other tryptamine derivatives with the fol...

  14. Signal transduction in cultered cardiomyocytes : alpha1-adrenergic and endothelin receptor mediated responses

    NARCIS (Netherlands)

    H.W. de Jonge (Jet)

    1996-01-01

    textabstractAlready in ancient times the Greek were aware of the heart in the human body and they gave it the name kardia, which is still in use in words as cardiac, myocardial, tachycardia and bradycardia. In those times the importance of the heart was appraised by Aristotle (384-322 B.C.), who tho

  15. Emodin isolated from Polygoni Multiflori Ramulus inhibits melanogenesis through the liver X receptor-mediated pathway.

    Science.gov (United States)

    Kim, Mi Ok; Park, Yong Seek; Nho, Youn Hwa; Yun, Seok Kyun; Kim, Youngsoo; Jung, Eunsun; Paik, Jean Kyung; Kim, Minhee; Cho, Il-Hoon; Lee, Jongsung

    2016-04-25

    Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role against skin photocarcinogenesis. We investigated the effects of a Polygoni Multiflori Ramulus extract on melanogenesis and isolated emodin from Polygoni Multiflori as an active compound. In addition, the possible mechanisms of action were examined. We found that emodin inhibited both melanin content and tyrosinase activity concentration and time dependently. Tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 mRNA levels decreased following emodin treatment. However, while the mRNA levels of microphthalmia-associated transcription factor (MITF) were not affected by emodin, emodin reduced MITF protein levels. Furthermore, expression of the liver X-receptor (LXR) α gene, but not the LXR β gene was upregulated by emodin. Moreover, emodin regulated melanogenesis by promoting degradation of the MITF protein by upregulating the LXR α gene. The emodin effects on MITF was found to be mediated by phosphorylation of p42/44 MAPK. Taken together, these findings indicate that the inhibition of melanogenesis by emodin occurs through reduced MITF protein expression, which is mediated by upregulation of the LXR α gene and suggest that emodin may be useful as a hyperpigmentation inhibitor. PMID:26972667

  16. Capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo

    OpenAIRE

    Liu, Shihui; Crown, Devorah; Miller-Randolph, Sharmina; Moayeri, Mahtab; Wang, Hailun; Hu, Haijing; Morley, Thomas; Leppla, Stephen H.

    2009-01-01

    Anthrax toxin, a major virulence factor of Bacillus anthracis, gains entry into target cells by binding to either of 2 von Willebrand factor A domain-containing proteins, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2). The wide tissue expression of TEM8 and CMG2 suggest that both receptors could play a role in anthrax pathogenesis. To explore the roles of TEM8 and CMG2 in normal physiology, as well as in anthrax pathogenesis, we generated TEM8- and CMG2-null mi...

  17. Kappa Opioid Receptors Mediate where Fear Is Expressed Following Extinction Training

    Science.gov (United States)

    Cole, Sindy; Richardson, Rick; McNally, Gavan P.

    2011-01-01

    Six experiments used a within-subjects renewal design to examine the involvement of kappa opioid receptors (KORs) in regulating the expression and recovery of extinguished fear. Rats were trained to fear a tone conditioned stimulus (CS) via pairings with foot shock in a distinctive context (A). This was followed by extinction training of the CS in…

  18. CXCR4 Chemokine Receptor Mediates Prostate Tumor Cell Adhesion through α5 and β3 Integrins

    Directory of Open Access Journals (Sweden)

    Tobias Engl

    2006-04-01

    Full Text Available The mechanisms leading to prostate cancer metastasis are not understood completely. Although there is evidence that the CXC chemokine receptor (CXCR 4 and its ligand CXCL12 may regulate tumor dissemination, their role in prostate cancer is controversial. We examined CXCR4 expression and functionality, and explored CXCL12-triggered adhesion of prostate tumor cells to human endothelium or to extracellular matrix proteins laminin, collagen, and fibronectin. Although little CXCR4 was expressed on LNCaP and DU-145 prostate tumor cells, CXCR4 was still active, enabling the cells to migrate toward a CXCL12 gradient. CXCL12 induced elevated adhesion to the endothelial cell monolayer and to immobilized fibronectin, laminin, and collagen. Anti-CXCR4 antibodies or CXCR4 knock out significantly impaired CXCL 12-triggered tumor cell binding. The effects observed did not depend on CXCR4 surface expression level. Rather, CXCR4-mediated adhesion was established by α5 and β3 integrin subunits and took place in the presence of reduced p38 and p38 phosphorylation. These data show that chemoattractive mechanisms are involved in adhesion processes of prostate cancer cells, and that binding of CXCL12 to its receptor leads to enhanced expression of α5 and β3. The findings provide a link between chemokine receptor expression and integrin-triggered tumor dissemination.

  19. Molecular and Biochemical Effects of a Kola Nut Extract on Androgen Receptor-Mediated Pathways

    Directory of Open Access Journals (Sweden)

    Rajasree Solipuram

    2009-01-01

    Full Text Available The low incidence of prostate cancer in Asians has been attributed to chemopreventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemopreventative properties of the Jamaican bush tea “Bizzy,” using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI50 of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the proapoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC50 of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.

  20. CB1 cannabinoid receptor-mediated modulation of food intake in mice

    OpenAIRE

    Wiley, Jenny L; Burston, James J.; Leggett, Darnica C; Alekseeva, Olga O; Razdan, Raj K.; Mahadevan, Anu; Martin, Billy R

    2005-01-01

    Marijuana's appetite-increasing effects have long been known. Recent research suggests that the CB1 cannabinoid receptor antagonist SR141716A may suppress appetite. This study represents a further, systematic investigation of the role of CB1 cannabinoid receptors in the pharmacological effects of cannabinoids on food intake.Mice were food-restricted for 24 h and then allowed access to their regular rodent chow for 1 h. Whereas the CB1 antagonist SR141716A dose-dependently decreased food consu...

  1. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils

    Institute of Scientific and Technical Information of China (English)

    Nariman A B Balenga; Maria Waldhoer; Elma Aflaki; Julia Kargl; Wolfgang Platzer; Ralf Schr(o)der; Stefanie Bl(a)ttermann; Evi Kostenis; Andrew J Brown; Akos Heinemann

    2011-01-01

    The directional migration of neutrophils towards inflammatory mediators,such as chemokines and cannabinoids,occurs via the activation of seven transmembrane G protein coupled receptors (7TM/GPCRs) and is a highly organized process.A crucial role for controlling neutrophil migration has been ascribed to the cannabinoid CB2 receptor (CB2R),but additional modulatory sites distinct from CB2R have recently been suggested to impact CB2R-mediated effector functions in neutrophils.Here,we provide evidence that the recently de-orphanized 7TM/GPCR GPR55potently modulates CB2R-mediated responses.We show that GPR55 is expressed in human blood neutrophils and its activation augments the migratory response towards the CB2R agonist 2-arachidonoylglycerol (2-AG),while inhibiting neutrophil degranulation and reactive oxygen species (ROS) production.Using HEK293 and HL60 cell lines,along with primary neutrophils,we show that GPR55 and CB2R interfere with each other's signaling pathways at the level of small GTPases,such as Rac2 and Cdc42.This ultimately leads to cellular polarization and efficient migration as well as abrogation of degranulation and ROS formation in neutrophils.Therefore,GPR55 limits the tissueinjuring inflammatory responses mediated by CB2R,while it synergizes with CB2R in recruiting neutrophils to sites of inflammation.

  2. Icariin Stimulates Differentiation and Suppresses Adipocytic Transdifferentiation of Primary Osteoblasts Through Estrogen Receptor-Mediated Pathway.

    Science.gov (United States)

    Zhang, Dawei; Fong, Chichun; Jia, Zhenbin; Cui, Liao; Yao, Xinsheng; Yang, Mengsu

    2016-08-01

    Icariin, the main constituent of Herba Epimedii, appears to be a promising alternative to classic drugs used to treat osteoporosis. However, the detailed molecular mechanisms of its action and the role of icariin in the cross-talk between osteoblasts and adipocytes remain unclear. The present study was designed to investigate the gene expression profile of primary osteoblasts in the presence of icariin, and the effects of icariin on the differentiation and adipogenic transdifferentiation of osteoblasts. Cellular and molecular markers expressed during osteoblastic differentiation were assessed by cytochemical analysis, real-time quantitative PCR, Western blotting, and cDNA microarray analysis. Results indicated that icariin up-regulated the expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (Bmp2), and collagen type 1 (Col1) genes, and down-regulated the expression of the peroxisome proliferator-activated receptor γ (Pparg) and CCAAT/enhancer-binding protein β (Cebpb) genes. These effects were blocked by ICI 182,780, suggesting that icariin may be acting via the estrogen receptor (ER). Results also demonstrated that the ratio of osteoprotegerin (Opg)/receptor activator of nuclear factor kappa B ligand (Rankl) expression was up-regulated following treatment with icariin. In total, osteoblastic gene expression profile analysis suggested that 33 genes were affected by icariin; these could be sub-divided into nine functional categories. It appears that icariin could stimulate the differentiation and mineralization of osteoblasts, regulate the differentiation of osteoclasts, and inhibit the adipogenic transdifferentiation of osteoblasts, therefore increasing the number of osteoblasts undergoing differentiation to mature osteoblasts, via an ER-mediated pathway. In summary, icariin may exhibit beneficial effects on bone health, especially for patients with osteoporosis and obesity. PMID:27061090

  3. ARRHYTHMOGENIC CALMODULIN MUTATIONS AFFECT THE ACTIVATION AND TERMINATION OF CARDIAC RYANODINE RECEPTOR MEDIATED CA2+ RELEASE

    DEFF Research Database (Denmark)

    Søndergaard, Mads Toft; Chazin, Walter J.; Chen, Wayne S.R.;

    We recently identified the first two human missense mutations in a calmodulin (CaM) gene (CALM1) and linked these to catecholaminergic polymorphic ventricular tachycardia (CPVT) and sudden cardiac death in young individuals1. More CaM mutations have since been identified in CALM1 and also...... in the other two CaM genes (CALM2 and CALM3). All CaM mutations are associated with severe ventricular arrhythmias. CaM regulates several key proteins governing cardiac excitation-contraction coupling (ECC), including the cardiac ryanodine receptor (RyR2) Ca2+ release channel. RyR2 mutations also dominantly...... cause CPVT, where the mutations increase the channel sensitivity to activation and enhance the propensity for pro-arrhythmogenic spontaneous Ca2+ release. Here we investigated the effect of CPVT-linked CaM mutations (N53I and N97S) and two CaM mutations identified in individuals with early onset severe...

  4. P2X7 receptor-mediated analgesia in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; D. Schwab, Samantha; Frøsig-Jørgensen, Majbrit;

    2015-01-01

    to low intensity or electrical stimulation. In contrast, A839977 had no effect on the tested parameters in naïve or sham animals. In awake animals, 40mg/kg A839977 (i.p) significantly reduced both early and late stage pain behavior. In contrast, no effect was observed in sham or vehicle-treated animals....... The results suggest that the P2X7R is involved in the mechanisms of cancer-induced bone pain, and that P2X7R antagonism might be a useful analgesic target. No effect was observed in sham or naïve animals, indicating that the P2X7R-mediated effect is state-dependent, and might therefore be an advantageous......Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique...

  5. Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and HBD3 ligands

    OpenAIRE

    Beaumont, Kimberley A.; Smit, Darren J.; Liu, Yan Yan; Chai, Eric; Patel, Mira P.; Millhauser, Glenn L.; Smith, Jennifer J.; Alewood, Paul F.; Sturm, Richard A.

    2012-01-01

    Binding of melanocortin peptide agonists to the melanocortin-1 receptor of melanocytes results in eumelanin production, whereas binding of the agouti signalling protein inverse agonist results in pheomelanin synthesis. Recently, a novel melanocortin-1 receptor ligand was reported. A β-defensin gene mutation was found to beresponsible for black coat colour in domestic dogs. Notably, the human equivalent, β-defensin 3, was found to bind with high affinity to the melanocortin-1 receptor; however...

  6. Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

    DEFF Research Database (Denmark)

    Møller, Cathrine Laustrup; Raun, Kirsten; Jacobsen, Marianne Lambert;

    2011-01-01

    The melanocortin receptors (MCRs) belong to the G-protein coupled receptors (family A). So far, 5 different subtypes have been described (MC1R-MC5R) and of these MC2R and MC5R have been proposed to act directly in adipocytes and regulate lipolysis in rodents. Using ACTH and a-melanocyte stimulating...

  7. Opioid Receptors Mediate Direct Predictive Fear Learning: Evidence from One-Trial Blocking

    Science.gov (United States)

    Cole, Sindy; McNally, Gavan P.

    2007-01-01

    Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including [mu]-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear…

  8. System theoretical investigation of human epidermal growth factor receptor-mediated signalling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi; Shankaran, Harish; Opresko, Lee; Resat, Haluk

    2008-09-01

    The partitioning of biological networks into coupled functional modules is gaining increasing attention in the biological sciences. This approach has the advantage that predicting a system level response does not require a mechanistic description of the internal dynamics of each module. Identification of the input-output characteristics of the network modules and the connectivity between the modules provide the necessary quantitative representation of system dynamics. However, determination of the input-output relationships of the modules is not trivial; it requires the controlled perturbation of module inputs and systematic analysis of experimental data. In this report, we apply a system theoretical analysis approach to derive the causal input-output relationships of the functional module for the human epidermal growth factor receptor (HER) mediated Erk and Akt signaling pathways. Using a library of cell lines expressing varying levels of EGFR and HER2, we show that a transfer function-based representation can be successfully applied to quantitatively characterize information transfer in this system.

  9. A novel gliotic P2 receptor mediating cyclooxygenase-2 induction in rat and human astrocytes.

    Science.gov (United States)

    Brambilla, R; Ceruti, S; Malorni, W; Cattabeni, F; Abbracchio, M P

    2000-07-01

    In astrocytic cultures maintained in vitro, a brief challenge with the ATP analog alpha,beta methyleneATP (alpha,betameATP) results, 3 days later, in marked elongation of astrocytic processes, an event that resembles the astrocytic hypertrophy known to occur in vivo during reactive astrogliosis. alpha,beta meATP-induced effects were observed in primary astrocytes obtained from both rat striatum and cortex (a brain area highly involved in chronic neurodegenerative pathologies), as well as in human astrocytoma cells (ADF cells). Purine-induced gliosis could be reversed by the non-selective P2X/P2Y receptor antagonist pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS), but not by oxidized ATP (an antagonist of the P2X(7) receptor), in line with previous studies of our laboratory suggesting the involvement of a P2Y receptor subtype. Induction of reactive gliosis was preceded by increased expression of cyclooxygenase-2 (COX-2), an enzyme whose excessive activation has been implicated in both acute and chronic neurodegenerative diseases. The selective COX-2 inhibitor NS-398 prevented both purine-induced astrogliosis and the associated COX-2 induction, suggesting that inhibition of the transcription of the COX-2 gene may also contribute to the anti-inflammatory properties of this agent. Significant blockade of both alpha,beta meATP-mediated reactive gliosis and COX-2 induction was also observed with PPADS. These data suggest that COX-2 mediates P2Y receptor-induced reactive astrogliosis, and that antagonists selective for this receptor subtype may represent a novel class of anti-inflammatory agents of potential interest in acute and chronic neurological disorders characterized by an inflammatory component and reactive gliosis.

  10. P2X receptors mediate ATP-induced primary nociceptive neurone activation.

    Science.gov (United States)

    Bland-Ward, P A; Humphrey, P P

    2000-07-01

    ATP-gated P2X ion-channel receptors are localised throughout the mammalian nervous system and have been identified on neurones which participate in conduction of nociceptive information from the periphery to, and within, the CNS. This article briefly reviews recently published research describing the role that ATP and P2X receptors may play in pain perception, highlighting the importance of the P2X(3) receptor in this process. The P2X(3) receptor subunit is almost exclusively expressed on a subset of small and medium diameter sensory neurones innervating cutaneous and visceral tissue. Activation of P2X receptors present on the peripheral terminals of primary afferents results in neuronal depolarisation and, in conscious animals, leads to the manifestation of acute nociceptive behaviour. Recent animal studies have also shown that P2X(3) receptor expression is increased in sensory ganglia following acute neuronal injury, hinting that similar plasticity in the expression of this receptor subtype could underlie the mechanisms involved in a range of conditions characterised by sensory hypersensitivity in man. It is apparent from the evidence available that functional antagonists at specific P2X receptor subtypes could represent an important class of novel analgesic agents.

  11. Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

    Science.gov (United States)

    De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

    2016-01-01

    While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments.

  12. Thyrotropin modulates receptor-mediated processing of the atrial natriuretic peptide receptor in cultured thyroid cells

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Y.L.; Burman, K.D.; Lahiri, S.; Abdelrahim, M.M.; D' Avis, J.C.; Wartofsky, L. (Walter Reed Army Medical Center, Washington, DC (USA))

    1991-03-01

    In a prior study of atrial natriuretic peptide (ANP) binding to cultured thyroid cells, we reported that at 4 C, more than 95% of bound ANP is recovered on cell membranes, with negligible ANP internalization observed. Since ANP binding was inhibited by TSH, we have further studied TSH effects on postbinding ANP processing to determine whether this phenomenon reflects enhanced endocytosis of the ANP-receptor complex. An ANP chase study was initiated by binding (125I) ANP to thyroid cells at 4 C for 2 h, followed by incubation at 37 C. ANP processing was then traced by following 125I activity at various time intervals in three fractions: cell surface membranes, incubation medium, and inside the cells. Radioactivity released into medium represented processed ANP rather than ANP dissociated from surface membranes, since prebound (125I)ANP could not be competitively dissociated by a high concentration of ANP (1 mumol/L) at 37 C. Chase study results showed that prebound ANP quickly disappeared from cell membranes down to 34% by 30 min. Internalized ANP peaked at 10 min, with 21% of initial prebound ANP found inside the cells. At the same time, radioactivity recovered in incubation medium sharply increased between 10-30 min from 8% to 52%. Preincubation of cells with chloroquine (which blocks degradation of the ANP-receptor complex by inhibiting lysosomal hydrolase) caused a 146% increase in internalized (125I)ANP by 30 min (39% compared to 15% control), while medium radioactivity decreased from 52% to 16%, suggesting that processing of the receptor complex is mediated via lysosomal enzymes. In chase studies employing cells pretreated with chloroquine, TSH stimulated the internalization rate of ANP-receptor complex. By 30 min, TSH significantly reduced the membrane-bound ANP, and the decrease was inversely correlated to the increase in internalized radioactivity.

  13. Muscarinic acetylcholine receptor-mediated stimulation of retinal ganglion cell photoreceptors.

    Science.gov (United States)

    Sodhi, Puneet; Hartwick, Andrew T E

    2016-09-01

    Melanopsin-dependent phototransduction in intrinsically photosensitive retinal ganglion cells (ipRGCs) involves a Gq-coupled phospholipase C (PLC) signaling cascade. Acetylcholine, released in the mammalian retina by starburst amacrine cells, can also activate Gq-PLC pathways through certain muscarinic acetylcholine receptors (mAChRs). Using multielectrode array recordings of rat retinas, we demonstrate that robust spiking responses can be evoked in neonatal and adult ipRGCs after bath application of the muscarinic agonist carbachol. The stimulatory action of carbachol on ipRGCs was a direct effect, as confirmed through calcium imaging experiments on isolated ipRGCs in purified cultures. Using flickering (6 Hz) yellow light stimuli at irradiances below the threshold for melanopsin activation, spiking responses could be elicited in ipRGCs that were suppressed by mAChR antagonism. Therefore, this work identified a novel melanopsin-independent pathway for stimulating sustained spiking in ganglion cell photoreceptors. This mAChR-mediated pathway could enhance ipRGC spiking responses in conditions known to evoke retinal acetylcholine release, such as those involving flickering or moving visual stimuli. Furthermore, this work identifies a pharmacological approach for light-independent ipRGC stimulation that could be targeted by mAChR agonists. PMID:27055770

  14. The Fc and not CD4 Receptor Mediates Antibody Enhancement of HIV Infection in Human Cells

    Science.gov (United States)

    Homsy, Jacques; Meyer, Mia; Tateno, Masatoshi; Clarkson, Sarah; Levy, Jay A.

    1989-06-01

    Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.

  15. Rab20 regulates phagosome maturation in RAW264 macrophages during Fc gamma receptor-mediated phagocytosis.

    Directory of Open Access Journals (Sweden)

    Youhei Egami

    Full Text Available Rab20, a member of the Rab GTPase family, is known to be involved in membrane trafficking, however its implication in FcγR-mediated phagocytosis is unclear. We examined the spatiotemporal localization of Rab20 during phagocytosis of IgG-opsonized erythrocytes (IgG-Es in RAW264 macrophages. By the live-cell imaging of fluorescent protein-fused Rab20, it was shown that Rab20 was transiently associated with the phagosomal membranes. During the early stage of phagosome formation, Rab20 was not localized on the membranes of phagocytic cups, but was gradually recruited to the newly formed phagosomes. Although Rab20 was colocalized with Rab5 to some extent, the association of Rab20 with the phagosomes persisted even after the loss of Rab5 from the phagosomal membranes. Then, Rab20 was colocalized with Rab7 and Lamp1, late endosomal/lysosomal markers, on the internalized phagosomes. Moreover, our analysis of Rab20 mutant expression revealed that the maturation of phagosomes was significantly delayed in cells expressing the GDP-bound mutant Rab20-T19N. These data suggest that Rab20 is an important component of phagosome and regulates the phagosome maturation during FcγR-mediated phagocytosis.

  16. Protein kinase C regulates tonic GABAA receptor-mediated inhibition in the hippocampus and thalamus

    Science.gov (United States)

    Bright, Damian P; Smart, Trevor G

    2013-01-01

    Tonic inhibition mediated by extrasynaptic GABAA receptors (GABAARs) is an important regulator of neuronal excitability. Phosphorylation by protein kinase C (PKC) provides a key mode of regulation for synaptic GABAARs underlying phasic inhibition; however, less attention has been focused on the plasticity of tonic inhibition and whether this can also be modulated by receptor phosphorylation. To address this issue, we used whole-cell patch clamp recording in acute murine brain slices at both room and physiological temperatures to examine the effects of PKC-mediated phosphorylation on tonic inhibition. Recordings from dentate gyrus granule cells in the hippocampus and dorsal lateral geniculate relay neurons in the thalamus demonstrated that PKC activation caused downregulation of tonic GABAAR-mediated inhibition. Conversely, inhibition of PKC resulted in an increase in tonic GABAAR activity. These findings were corroborated by experiments on human embryonic kidney 293 cells expressing recombinant α4β2δ GABAARs, which represent a key extrasynaptic GABAAR isoform in the hippocampus and thalamus. Using bath application of low GABA concentrations to mimic activation by ambient neurotransmitter, we demonstrated a similar inhibition of receptor function following PKC activation at physiological temperature. Live cell imaging revealed that this was correlated with a loss of cell surface GABAARs. The inhibitory effects of PKC activation on α4β2δ GABAAR activity appeared to be mediated by direct phosphorylation at a previously identified site on the β2 subunit, serine 410. These results indicate that PKC-mediated phosphorylation can be an important physiological regulator of tonic GABAAR-mediated inhibition. PMID:24102973

  17. Antibody therapy of cancer : Fc receptor-mediated mechanisms of action

    NARCIS (Netherlands)

    Overdijk, M.B.

    2013-01-01

    Cancer, a class of malignant diseases characterized by unregulated cell growth, is still a leading cause of death worldwide. The high specificity of antibodies combined with the ability to engage multiple mechanisms of action (MoA) and minimal side-effects makes them attractive agents for targeted t

  18. Insulin receptors mediate growth effects in cultured fetal neurons. I. Rapid stimulation of protein synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, K.A.; Toledo, S.P. (Univ. of California-San Diego, La Jolla (USA))

    1989-09-01

    In this study we have examined the effects of insulin on protein synthesis in cultured fetal chick neurons. Protein synthesis was monitored by measuring the incorporation of (3H)leucine (3H-leu) into trichloroacetic acid (TCA)-precipitable protein. Upon addition of 3H-leu, there was a 5-min lag before radioactivity occurred in protein. During this period cell-associated radioactivity reached equilibrium and was totally recovered in the TCA-soluble fraction. After 5 min, the incorporation of 3H-leu into protein was linear for 2 h and was inhibited (98%) by the inclusion of 10 micrograms/ml cycloheximide. After 24 h of serum deprivation, insulin increased 3H-leu incorporation into protein by approximately 2-fold. The stimulation of protein synthesis by insulin was dose dependent (ED50 = 70 pM) and seen within 30 min. Proinsulin was approximately 10-fold less potent than insulin on a molar basis in stimulating neuronal protein synthesis. Insulin had no effect on the TCA-soluble fraction of 3H-leu at any time and did not influence the uptake of (3H)aminoisobutyric acid into neurons. The isotope ratio of 3H-leu/14C-leu in the leucyl tRNA pool was the same in control and insulin-treated neurons. Analysis of newly synthesized proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that insulin uniformly increased the incorporation of 14C-leu into all of the resolved neuronal proteins. We conclude from these data that (1) insulin rapidly stimulates overall protein synthesis in fetal neurons independent of amino acid uptake and aminoacyl tRNA precursor pools; (2) stimulation of protein synthesis is mediated by the brain subtype of insulin receptor; and (3) insulin is potentially an important in vivo growth factor for fetal central nervous system neurons.

  19. Insulin receptors mediate growth effects in cultured fetal neurons. I. Rapid stimulation of protein synthesis

    International Nuclear Information System (INIS)

    In this study we have examined the effects of insulin on protein synthesis in cultured fetal chick neurons. Protein synthesis was monitored by measuring the incorporation of [3H]leucine (3H-leu) into trichloroacetic acid (TCA)-precipitable protein. Upon addition of 3H-leu, there was a 5-min lag before radioactivity occurred in protein. During this period cell-associated radioactivity reached equilibrium and was totally recovered in the TCA-soluble fraction. After 5 min, the incorporation of 3H-leu into protein was linear for 2 h and was inhibited (98%) by the inclusion of 10 micrograms/ml cycloheximide. After 24 h of serum deprivation, insulin increased 3H-leu incorporation into protein by approximately 2-fold. The stimulation of protein synthesis by insulin was dose dependent (ED50 = 70 pM) and seen within 30 min. Proinsulin was approximately 10-fold less potent than insulin on a molar basis in stimulating neuronal protein synthesis. Insulin had no effect on the TCA-soluble fraction of 3H-leu at any time and did not influence the uptake of [3H]aminoisobutyric acid into neurons. The isotope ratio of 3H-leu/14C-leu in the leucyl tRNA pool was the same in control and insulin-treated neurons. Analysis of newly synthesized proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that insulin uniformly increased the incorporation of 14C-leu into all of the resolved neuronal proteins. We conclude from these data that (1) insulin rapidly stimulates overall protein synthesis in fetal neurons independent of amino acid uptake and aminoacyl tRNA precursor pools; (2) stimulation of protein synthesis is mediated by the brain subtype of insulin receptor; and (3) insulin is potentially an important in vivo growth factor for fetal central nervous system neurons

  20. Benzodiazepine receptor-mediated behavioral effects of nitrous oxide in the rat social interaction test.

    Science.gov (United States)

    Quock, R M; Wetzel, P J; Maillefer, R H; Hodges, B L; Curtis, B A; Czech, D A

    1993-09-01

    The present study was conducted to ascertain whether an anxiolytic effect of nitrous oxide was demonstrable in rats using the social interaction test and whether this drug effect might be mediated by benzodiazepine receptors. Compared to behavior of vehicle-pretreated, room air-exposed rats, rat pairs exposed to nitrous oxide showed a generally inverted U-shaped dose-response curve with the maximum increase in social interaction encounters occurring at 25% and significant increase in time of active social interaction at 15-35%; higher concentrations produced a sedative effect that reduced social interaction. Treatment with 5.0 mg/kg of the anxiolytic benzodiazepine chlordiazepoxide also increased social interaction. Pretreatment with 10 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, significantly antagonized the social interaction-increasing effects of both nitrous oxide and chlordiazepoxide. In summary, these findings suggest that nitrous oxide produces a flumazenil-sensitive effect comparable to that of chlordiazepoxide and implicate central benzodiazepine mechanisms in mediation of the anxiolytic effect of nitrous oxide.

  1. Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies

    Directory of Open Access Journals (Sweden)

    Francisco J. Carvajal

    2016-01-01

    Full Text Available N-Methyl-D-aspartate receptors (NMDARs have two opposing roles in the brain. On the one hand, NMDARs control critical events in the formation and development of synaptic organization and synaptic plasticity. On the other hand, the overactivation of NMDARs can promote neuronal death in neuropathological conditions. Ca2+ influx acts as a primary modulator after NMDAR channel activation. An imbalance in Ca2+ homeostasis is associated with several neurological diseases including schizophrenia, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These chronic conditions have a lengthy progression depending on internal and external factors. External factors such as acute episodes of brain damage are associated with an earlier onset of several of these chronic mental conditions. Here, we will review some of the current evidence of how traumatic brain injury can hasten the onset of several neurological conditions, focusing on the role of NMDAR distribution and the functional consequences in calcium homeostasis associated with synaptic dysfunction and neuronal death present in this group of chronic diseases.

  2. Swim stress differentially blocks CRF receptor mediated responses in dorsal raphe nucleus.

    Science.gov (United States)

    Lamy, Christophe M; Beck, Sheryl G

    2010-10-01

    Modulation of the serotonergic (5-HT) neurotransmitter system arising from the dorsal raphe nucleus (DR) is thought to support the behavioral effects of swim stress, i.e., immobility. In vivo pharmacological and anatomical studies suggest that corticotropin-releasing factor (CRF) and γ-aminobutyric acid (GABA) synaptic transmission closely interact to set the response of the DR to swim stress. To investigate the cellular basis of these physiological mechanisms the effects of ovine CRF (oCRF) on GABA(A)-dependent miniature inhibitory postsynaptic currents (mIPSCs) in 5-HT and non-5-HT DR neurons in acute mesencephalic slices obtained from rats either naïve or 24h after a 15 min swim stress session were tested. In this study, the effect of swim stress alone was to decrease the holding current, i.e., hyperpolarize the neuron, and to increase the amplitude and charge of mIPSCs recorded from non-5-HT neurons. Ovine CRF (10 nM) induced an increase in mIPSC frequency in 5-HT neurons recorded from naïve rats, an effect that was suppressed by swim stress. The inward current elicited by oCRF in both 5-HT and non-5-HT neurons was also blocked by swim stress. Ovine CRF increased mIPSCs amplitude and charge in both 5-HT and non-5-HT neurons, but this effect was not modified by swim stress. In concert with our previous findings that swim stress decreased input resistance, action potential threshold and action potential duration and increased glutamatergic synaptic activity the overall primary effect of swim stress is to increase the excitability of 5-HT neurons. These data provide a mechanism at the cellular level for the immobility induced by swim stress and identifies critical components of the raphe circuitry responsible for the altered output of 5-HT neurons induced by swim stress.

  3. Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers.

    Science.gov (United States)

    Marzec, Paulina; Armenise, Claudia; Pérot, Gaëlle; Roumelioti, Fani-Marlen; Basyuk, Eugenia; Gagos, Sarantis; Chibon, Frédéric; Déjardin, Jérôme

    2015-02-26

    The breakage-fusion-bridge cycle is a classical mechanism of telomere-driven genome instability in which dysfunctional telomeres are fused to other chromosomal extremities, creating dicentric chromosomes that eventually break at mitosis. Here, we uncover a distinct pathway of telomere-driven genome instability, specifically occurring in cells that maintain telomeres with the alternative lengthening of telomeres mechanism. We show that, in these cells, telomeric DNA is added to multiple discrete sites throughout the genome, corresponding to regions regulated by NR2C/F transcription factors. These proteins drive local telomere DNA addition by recruiting telomeric chromatin. This mechanism, which we name targeted telomere insertion (TTI), generates potential common fragile sites that destabilize the genome. We propose that TTI driven by NR2C/F proteins contributes to the formation of complex karyotypes in ALT tumors. PMID:25723166

  4. Gamma-secretase activity of presenilin 1 regulates acetylcholine muscarinic receptor-mediated signal transduction

    DEFF Research Database (Denmark)

    Popescu, Bogdan O; Cedazo-Minguez, Angel; Benedikz, Eirikur;

    2004-01-01

    Familial Alzheimer's disease (FAD) presenilin 1 (PS1) mutations give enhanced calcium responses upon different stimuli, attenuated capacitative calcium entry, an increased sensitivity of cells to undergo apoptosis, and increased gamma-secretase activity. We previously showed that the FAD mutation...

  5. Toll-like receptor-mediated immune response inhibits prion propagation.

    Science.gov (United States)

    Kang, Sang-Gyun; Kim, Chiye; Cortez, Leonardo M; Carmen Garza, María; Yang, Jing; Wille, Holger; Sim, Valerie L; Westaway, David; McKenzie, Debbie; Aiken, Judd

    2016-06-01

    Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion diseases is neuroinflammation characterized by activation of neuroglia surrounding prion deposition. The cause and effect of this cellular response, however, is unclear. We investigated innate immune defenses against prion infection using primary mixed neuronal and glial cultures. Conditional prion propagation occurred in glial cultures depending on their immune status. Preconditioning of the cells with the toll-like receptor (TLR) ligand, lipopolysaccharide, resulted in a reduction in prion propagation, whereas suppression of the immune responses with the synthetic glucocorticoid, dexamethasone, increased prion propagation. In response to recombinant prion fibrils, glial cells up-regulated TLRs (TLR1 and TLR2) expression and secreted cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6, granulocyte-macrophage colony-stimulating factor, and interferon-β). Preconditioning of neuronal and glial cultures with recombinant prion fibrils inhibited prion replication and altered microglial and astrocytic populations. Our results provide evidence that, in early stages of prion infection, glial cells respond to prion infection through TLR-mediated innate immunity. GLIA 2016;64:937-951. PMID:26880394

  6. Role of receptor-mediated endocytosis, endosomal acidification and cathepsin D in cholera toxin cytotoxicity.

    Science.gov (United States)

    El Hage, Tatiana; Merlen, Clémence; Fabrega, Sylvie; Authier, François

    2007-05-01

    Using the in situ liver model system, we have recently shown that, after cholera toxin binding to hepatic cells, cholera toxin accumulates in a low-density endosomal compartment, and then undergoes endosomal proteolysis by the aspartic acid protease cathepsin-D [Merlen C, Fayol-Messaoudi D, Fabrega S, El Hage T, Servin A, Authier F (2005) FEBS J272, 4385-4397]. Here, we have used a subcellular fractionation approach to address the in vivo compartmentalization and cytotoxic action of cholera toxin in rat liver parenchyma. Following administration of a saturating dose of cholera toxin to rats, rapid endocytosis of both cholera toxin subunits was observed, coincident with massive internalization of both the 45 kDa and 47 kDa Gsalpha proteins. These events coincided with the endosomal recruitment of ADP-ribosylation factor proteins, especially ADP-ribosylation factor-6, with a time course identical to that of toxin and the A subunit of the stimulatory G protein (Gsalpha) translocation. After an initial lag phase of 30 min, these constituents were linked to NAD-dependent ADP-ribosylation of endogenous Gsalpha, with maximum accumulation observed at 30-60 min postinjection. Assessment of the subsequent postendosomal fate of internalized Gsalpha revealed sustained endolysosomal transfer of the two Gsalpha isoforms. Concomitantly, cholera toxin increased in vivo endosome acidification rates driven by the ATP-dependent H(+)-ATPase pump and in vitro vacuolar acidification in hepatoma HepG2 cells. The vacuolar H(+)-ATPase inhibitor bafilomycin and the cathepsin D inhibitor pepstatin A partially inhibited, both in vivo and in vitro, the cAMP response to cholera toxin. This cathepsin D-dependent action of cholera toxin under the control of endosomal acidity was confirmed using cellular systems in which modification of the expression levels of cathepsin D, either by transfection of the cathepsin D gene or small interfering RNA, was followed by parallel changes in the cytotoxic response to cholera toxin. Thus, in hepatic cells, a unique endocytic pathway was revealed following cholera toxin administration, with regulation specificity most probably occurring at the locus of the endosome and implicating endosomal proteases, such as cathepsin D, as well as organelle acidification.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    Neurohormonal changes in congestive heart failure (CHF) include an enhanced peripheral sympathetic nerve activity which results in increased release of noradrenaline, neuropeptide Y and ATP. To examine if such changes in CHF would modulate peripheral pre- and postsynaptic receptors of ATP and its...... effects mediated by the endothelial P2Y receptors are unaffected in CHF. Moreover, the adenosine-mediated inhibitory effects on heart rate and blood pressure were also attenuated in the CHF rats. The most important changes in adenosine and P2-receptor function induced by ischaemic CHF were the reduced...... pressor effect mediated by the P2X receptor and the increased heart rate due to an attenuated inhibitory effect of adenosine....

  8. Alpha-latrotoxin modulates the secretory machinery via receptor-mediated activation of protein kinase C.

    Science.gov (United States)

    Liu, Jie; Wan, Qunfang; Lin, Xianguang; Zhu, Hongliang; Volynski, Kirill; Ushkaryov, Yuri; Xu, Tao

    2005-09-01

    The hypothesis whether alpha-latrotoxin (LTX) could directly regulate the secretory machinery was tested in pancreatic beta cells using combined techniques of membrane capacitance (Cm) measurement and Ca2+ uncaging. Employing ramp increase in [Ca2+]i to stimulate exocytosis, we found that LTX lowers the Ca2+ threshold required for exocytosis without affecting the size of the readily releasable pool (RRP). The burst component of exocytosis in response to step-like [Ca2+]i increase generated by flash photolysis of caged Ca2+ was also speeded up by LTX treatment. LTX increased the maximum rate of exocytosis compared with control responses with similar postflash [Ca2+]i and shifted the Ca2+ dependence of the exocytotic machinery toward lower Ca2+ concentrations. LTXN4C, a LTX mutant which cannot form membrane pores or penetrate through the plasma membrane but has similar affinity for the receptors as the wild-type LTX, mimicked the effect of LTX. Moreover, the effects of both LTX and LTXN4C) were independent of intracellular or extracellular Ca2+ but required extracellular Mg2+. Our data propose that LTX, by binding to the membrane receptors, sensitizes the fusion machinery to Ca2+ and, hence, may permit release at low [Ca2+]i level. This sensitization is mediated by activation of protein kinase C. PMID:16101679

  9. Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  10. Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  11. Angiotensin II Type 1 Receptor-Mediated Electrical Remodeling in Mouse Cardiac Myocytes.

    Directory of Open Access Journals (Sweden)

    Jeremy Kim

    Full Text Available We recently characterized an autocrine renin angiotensin system (RAS in canine heart. Activation of Angiotensin II Type 1 Receptors (AT1Rs induced electrical remodeling, including inhibition of the transient outward potassium current Ito, prolongation of the action potential (AP, increased calcium entry and increased contractility. Electrical properties of the mouse heart are very different from those of dog heart, but if a similar system existed in mouse, it could be uniquely studied through genetic manipulations. To investigate the presence of a RAS in mouse, we measured APs and Ito in isolated myocytes. Application of angiotensin II (A2 for 2 or more hours reduced Ito magnitude, without affecting voltage dependence, and prolonged APs in a dose-dependent manner. Based on dose-inhibition curves, the fast and slow components of Ito (Ito,fast and IK,slow appeared to be coherently regulated by [A2], with 50% inhibition at an A2 concentration of about 400 nM. This very high K0.5 is inconsistent with systemic A2 effects, but is consistent with an autocrine RAS in mouse heart. Pre-application of the microtubule destabilizing agent colchicine eliminated A2 effects on Ito and AP duration, suggesting these effects depend on intracellular trafficking. Application of the biased agonist SII ([Sar1-Ile4-Ile8]A2, which stimulates receptor internalization without G protein activation, caused Ito reduction and AP prolongation similar to A2-induced changes. These data demonstrate AT1R mediated regulation of Ito in mouse heart. Moreover, all measured properties parallel those measured in dog heart, suggesting an autocrine RAS may be a fundamental feedback system that is present across species.

  12. Glucocorticoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro

    Science.gov (United States)

    Max, Stephen R.; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa; Konagaya, Masaaki

    1987-01-01

    The regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture is studied. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.

  13. T-Cell Tumor Elimination as a Result of T-Cell Receptor-Mediated Activation

    Science.gov (United States)

    Ashwell, Jonathan D.; Longo, Dan L.; Bridges, Sandra H.

    1987-07-01

    It has recently been shown that activation of murine T-cell hybridomas with antigen inhibits their growth in vitro. The ``suicide'' of these neoplastic T cells upon stimulation with antigen suggested the possibility that activation via the antigen-specific receptor could also inhibit the growth of neoplastic T cells in vivo. To test this, mice were subcutaneously inoculated with antigen-specific T-cell hybridomas and then treated intraperitoneally with antigen. Administration of the appropriate antigen immediately after inoculation with the T-cell hybridoma abrogated tumor formation; antigen administered after tumors had become established decreased the tumor burden and, in a substantial fraction of animals, led to long-term survival. The efficacy of antigen therapy was due to both a direct inhibitory effect on tumor growth and the induction of host immunity. These studies demonstrate the utility of cellular activation as a means of inhibiting neoplastic T-cell growth in vivo and provide a rationale for studying the use of less selective reagents that can mimic the activating properties of antigen, such as monoclonal antibodies, in the treatment of T-cell neoplasms of unknown antigen specificity.

  14. Metabotropic glutamate receptor-mediated signaling dampens the HPA axis response to restraint stress.

    Science.gov (United States)

    Evanson, Nathan K; Herman, James P

    2015-10-15

    Glutamate is an important neurotransmitter in the regulation of the neural portion of hypothalamus-pituitary-adrenal (HPA) axis activity, and signals through ionotropic and metabotropic receptors. In the current studies we investigated the role of hypothalamic paraventricular group I metabotropic glutamate receptors in the regulation of the HPA axis response to restraint stress in rats. Direct injection of the group I metabotropic glutamate receptor agonist 3,5-dihydroxyphenylglycine (DHPG) into the PVN prior to restraint leads to blunting of the HPA axis response in awake animals. Consistent with this result, infusion of the group I receptor antagonist hexyl-homoibotenic acid (HIBO) potentiates the HPA axis response to restraint. The excitatory effect of blocking paraventricular group I metabotropic glutamate signaling is blocked by co-administration of dexamethasone into the PVN. However, the inhibitory effect of DHPG is not affected by co-administration of the cannabinoid CB1 receptor antagonist AM-251 into the PVN. Together, these results suggest that paraventricular group I metabotropic glutamate receptor signaling acts to dampen HPA axis reactivity. This effect appears to be similar to the rapid inhibitory effect of glucocorticoids at the PVN, but is not mediated by endocannabinoid signaling.

  15. Receptor-mediated endocytosis of diphtheria toxin by cells in culture.

    OpenAIRE

    Keen, J H; Maxfield, F R; Hardegree, M C; Habig, W H

    1982-01-01

    The binding and uptake of fluorescently labeled diphtheria toxin by cells in culture has been examined by using epifluorescence video intensification microscopy. Rhodamine-labeled diphtheria toxin retained significant toxicity on bioassay and in cell culture and was tested for uptake by human WI-38 and mouse 3T3 fibroblasts grown in culture. When added to cells at 37 degrees C, toxin was observed to become concentrated and internalized in discrete vesicles in both cell lines. The appearance o...

  16. Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

    Science.gov (United States)

    De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

    2016-01-01

    While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments. PMID:26522737

  17. Valerian inhibits rat hepatocarcinogenesis by activating GABA(A receptor-mediated signaling.

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    Full Text Available Valerian is widely used as a traditional medicine to improve the quality of sleep due to interaction of several active components with the γ-aminobutyric acid (GABA A receptor (GABA(AR system. Recently, activation of GABA signaling in stem cells has been reported to suppress cell cycle progression in vivo. Furthermore, possible inhibitory effects of GABA(AR agonists on hepatocarcinogenesis have been reported. The present study was performed to investigate modulating effects of Valerian on hepatocarcinogenesis using a medium-term rat liver bioassay. Male F344 rats were treated with one of the most powerful Valerian species (Valeriana sitchensis at doses of 0, 50, 500 and 5000 ppm in their drinking water after initiation of hepatocarcinogenesis with diethylnitrosamine (DEN. Formation of glutathione S-transferase placental form positive (GST-P(+ foci was significantly inhibited by Valerian at all applied doses compared with DEN initiation control rats. Generation of 8-hydroxy-2'-deoxyguanosine in the rat liver was significantly suppressed by all doses of Valerian, likely due to suppression of Nrf2, CYP7A1 and induction of catalase expression. Cell proliferation was significantly inhibited, while apoptosis was induced in areas of GST-P(+ foci of Valerian groups associated with suppression of c-myc, Mafb, cyclin D1 and induction of p21(Waf1/Cip1, p53 and Bax mRNA expression. Interestingly, expression of the GABA(AR alpha 1 subunit was observed in GST-P(+ foci of DEN control rats, with significant elevation associated with Valerian treatment. These results indicate that Valerian exhibits inhibitory effects on rat hepatocarcinogenesis by inhibiting oxidative DNA damage, suppressing cell proliferation and inducing apoptosis in GST-P(+ foci by activating GABA(AR-mediated signaling.

  18. Human neutrophil Fc receptor-mediated adhesion under flow: a hollow fibre model of intravascular arrest.

    Science.gov (United States)

    D'Arrigo, C; Candal-Couto, J J; Greer, M; Veale, D J; Woof, J M

    1995-04-01

    Human polymorphonuclear cells (PMN) were found to adhere to a novel model of blood vessel wall-associated IgG. The internal surfaces of cellulose acetate hollow fibres, of comparable internal diameter to small blood vessels, were coated with normal serum human IgG, heat-aggregated IgG (HAIgG), laminin or fibrinogen. Under conditions of flow mimicking those in a small vessel, PMN were found to adhere markedly only to immunoglobulin-coated fibres. Arrest on HAIgG was inhibited by excess soluble IgG but not by bovine serum albumin (BSA), demonstrating that the adhesion was IgG-specific and presumably mediated by Fc gamma R on the PMN surface. Pre-adsorption of serum components onto HAIgG-coated fibres enhanced PMN arrest, due most probably to fixation of complement components by immobilized HAIgG, resulting in additional potential to entrap PMN via complement receptors such as CR3. Treatment of PMN with the regulatory neuropeptide substance P also enhanced adhesion to HAIgG-coated fibres and caused increased surface expression of Fc gamma RI, Fc gamma RII and Fc gamma RIII. A mouse cell line derived from L cells, hR4C6, stably transfected with human Fc gamma RII, was found to adhere under flow to HAIgG-coated fibres, whilst untransfected parent L cells did not. This adhesion was similarly inhibited by excess soluble IgG, confirming the capability of Fc gamma R to mediate cell arrest. The study strongly suggests that Fc gamma R may play an important role in intravascular PMN arrest and we speculate that in inflammatory diseases PMN may adhere via Fc gamma R to immobilized immunoglobulin on the vascular endothelium, with subsequent degranulation and tissue damage. PMID:7535210

  19. Inhibitory nature of tiagabine-augmented GABAA receptor-mediated depolarizing responses in hippocampal pyramidal cells.

    Science.gov (United States)

    Jackson, M F; Esplin, B; Capek, R

    1999-03-01

    Tiagabine is a potent GABA uptake inhibitor with demonstrated anticonvulsant activity. GABA uptake inhibitors are believed to produce their anticonvulsant effects by prolonging the postsynaptic actions of GABA, released during episodes of neuronal hyperexcitability. However, tiagabine has recently been reported to facilitate the depolarizing actions of GABA in the CNS of adult rats following the stimulation of inhibitory pathways at a frequency (100 Hz) intended to mimic interneuronal activation during epileptiform activity. In the present study, we performed extracellular and whole cell recordings from CA1 pyramidal neurons in rat hippocampal slices to examine the functional consequences of tiagabine-augmented GABA-mediated depolarizing responses. Orthodromic population spikes (PSs), elicited from the stratum radiatum, were inhibited following the activation of recurrent inhibitory pathways by antidromic conditioning stimulation of the alveus, which consisted of either a single stimulus or a train of stimuli delivered at high-frequency (100 Hz, 200 ms). The inhibition of orthodromic PSs produced by high-frequency conditioning stimulation (HFS), which was always of much greater strength and duration than that produced by a single conditioning stimulus, was greatly enhanced following the bath application of tiagabine (2-100 microM). Thus, in the presence of tiagabine (20 microM), orthodromic PSs, evoked 200 and 800 ms following HFS, were inhibited to 7.8 +/- 2.6% (mean +/- SE) and 34.4 +/- 18.5% of their unconditioned amplitudes compared with only 35.4 +/- 12.7% and 98.8 +/- 12.4% in control. Whole cell recordings revealed that the bath application of tiagabine (20 microM) either caused the appearance or greatly enhanced the amplitude of GABA-mediated depolarizing responses (DR). Excitatory postsynaptic potentials (EPSPs) evoked from stratum radiatum at time points that coincided with the DR were inhibited to below the threshold for action-potential firing. Independently of the stimulus intensity with which they were evoked, the charge transferred to the soma by excitatory postsynaptic currents (EPSCs), elicited in the presence of tiagabine (20 microM) during the large (1,428 +/- 331 pA) inward currents that underlie the DRs, was decreased on the average by 90.8 +/- 1.7%. Such inhibition occurred despite the presence of the GABAB receptor antagonist, CGP 52 432 (10 microM), indicating that GABAB heteroreceptors, located on glutamatergic terminals, do not mediate the observed reduction in the amplitude of excitatory postsynaptic responses. The present results suggest that despite facilitating the induction of GABA-mediated depolarizations, tiagabine application may nevertheless increase the effectiveness of synaptic inhibition during the synchronous high-frequency activation of inhibitory interneurons by enhanced shunting.

  20. Glucocorticoid receptor mediated the propofol self-administration by dopamine D1 receptor in nucleus accumbens.

    Science.gov (United States)

    Wu, Binbin; Liang, Yuyuan; Dong, Zhanglei; Chen, Zhichuan; Zhang, Gaolong; Lin, Wenxuan; Wang, Sicong; Wang, Benfu; Ge, Ren-Shan; Lian, Qingquan

    2016-07-22

    Propofol, a widely used anesthetic, can cause addictive behaviors in both human and experimental animals. In the present study, we examined the involvement of glucocorticoid receptor (GR) signaling in the molecular process by which propofol may cause addiction. The propofol self-administration model was established by a fixed ratio 1 (FR1) schedule of reinforced dosing over successive 14days in rats. On day 15, the rats were treated with dexamethasone, a GR agonist (10-100μg/kg), or RU486, a GR antagonist (10-100μg/kg) at 1h prior to the last training. The animal behaviors were recorded automatically by the computer. The expression of dopamine D1 receptor in the nucleus accumbens (NAc) was examined by Western blot and the concentrations of plasma corticosterone were measured by enzyme-linked immunosorbent assay (ELISA). To further examine the specificity of GR in the process, mineralocorticoid receptor (MR) antagonist, spironolactone, and dexamethasone plus MR agonist, aldosterone, were also tested. Administration of dexamethasone (100μg/kg) or RU486 (⩾10mg/kg) significantly attenuated the rate of propofol maintained active nose-poke responses and infusions, which were accompanied by reductions in both plasma corticosterone level and the expression of D1 receptor in the NAc. Neither spironolactone alone nor dexamethasone combined with aldosterone affected the propofol-maintaining self-administrative behavior, indicating GR, but not MR, modulates the propofol reward in rats. In addition, neither the food-maintaining sucrose responses under FR1 schedule nor the locomotor activity was affected by any doses of dexamethasone or RU486 tested. These findings provide evidence that GR signaling may play an important role in propofol reward. PMID:27126557