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Sample records for increases channel open

  1. Opening of pannexin- and connexin-based channels increases the excitability of nodose ganglion sensory neurons.

    Science.gov (United States)

    Retamal, Mauricio A; Alcayaga, Julio; Verdugo, Christian A; Bultynck, Geert; Leybaert, Luc; Sáez, Pablo J; Fernández, Ricardo; León, Luis E; Sáez, Juan C

    2014-01-01

    Satellite glial cells (SGCs) are the main glia in sensory ganglia. They surround neuronal bodies and form a cap that prevents the formation of chemical or electrical synapses between neighboring neurons. SGCs have been suggested to establish bidirectional paracrine communication with sensory neurons. However, the molecular mechanism involved in this cellular communication is unknown. In the central nervous system (CNS), astrocytes present connexin43 (Cx43) hemichannels and pannexin1 (Panx1) channels, and the opening of these channels allows the release of signal molecules, such as ATP and glutamate. We propose that these channels could play a role in glia-neuron communication in sensory ganglia. Therefore, we studied the expression and function of Cx43 and Panx1 in rat and mouse nodose-petrosal-jugular complexes (NPJcs) using confocal immunofluorescence, molecular and electrophysiological techniques. Cx43 and Panx1 were detected in SGCs and in sensory neurons, respectively. In the rat and mouse, the electrical activity of vagal nerve increased significantly after nodose neurons were exposed to a Ca(2+)/Mg(2+)-free solution, a condition that increases the open probability of Cx hemichannels. This response was partially mimicked by a cell-permeable peptide corresponding to the last 10 amino acids of Cx43 (TAT-Cx43CT). Enhanced neuronal activity was reduced by Cx hemichannel, Panx1 channel and P2X7 receptor blockers. Moreover, the role of Panx1 was confirmed in NPJc, because in those from Panx1 knockout mice showed a reduced increase of neuronal activity induced by Ca(2+)/Mg(2+)-free extracellular conditions. The data suggest that Cx hemichannels and Panx channels serve as paracrine communication pathways between SGCs and neurons by modulating the excitability of sensory neurons.

  2. Opening of pannexin and connexin based-channels increases the excitability of nodose ganglion sensory neurons.

    Directory of Open Access Journals (Sweden)

    Mauricio Antonio Retamal

    2014-06-01

    Full Text Available Satellite glial cells (SGCs are the main glia in sensory ganglia. They surround neuronal bodies and form a cap that prevents the formation of chemical or electrical synapses between neighboring neurons. SGCs have been suggested to establish bidirectional paracrine communication with sensory neurons. However, the molecular mechanism involved in this cellular communication is unknown. In the central nervous system, astrocytes present connexin43 (Cx43 hemichannels and pannexin1 (Panx1 channels, and their opening allows the release of signal molecules, such as ATP and glutamate. We propose that these channels could play a role in the glia-neuron communication in sensory ganglia. Therefore, we studied the expression and function of Cx43 and Panx1 in rat and mouse nodose-petrosal-jugular complex (NPJc by confocal immunofluorescence, molecular and electrophysiological techniques. Cx43 and Panx1 were detected in SGCs and sensory neurons, respectively. In the rat and mouse, the electrical activity of vagal nerve increased significantly after nodose neurons were exposed to Ca2+/ Mg2+-free solution, a condition that increases the open probability of Cx hemichannels. This response was partially mimicked by a cell-permeable peptide corresponding to the last 10 amino acids of Cx43 (TAT-Cx43CT. Enhanced neuronal activity was reduced by Cx hemichannel, Panx1 channel and P2X7 receptor blockers. Moreover, the role of Panx1 was confirmed in NPJc, because Panx1 knockout mouse showed a reduced increase of neuronal activity induced by Ca2+/Mg2+-free extracellular conditions. Data suggest that Cx hemichannels and Panx channels serve as paracrine communication pathways between SGCs and neurons by modulating the excitability of sensory neurons.

  3. All channels open

    NARCIS (Netherlands)

    Frank Huysmans; Jos de Haan

    2010-01-01

    Original title: Alle kanalen staan open. The rapid changes taking place in the media landscape in the Netherlands - characterised by digitisation and convergence of media technologies - raise the question of how the Dutch are dealing with the many new opportunities that have opened up. All channels

  4. The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state.

    Science.gov (United States)

    Lynch, J W; Han, N L; Haddrill, J; Pierce, K D; Schofield, P R

    2001-04-15

    Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

  5. Opening Channels of Communication

    Directory of Open Access Journals (Sweden)

    Clarice Moura Costa

    2009-03-01

    Full Text Available Psychosis, as described through a psychodynamic perspective, is conceptualized as an attempt to deny the enveloping reality to avoid contact with the other. Music therapy is a way to break this barrier of non-communication raised by the patients. The music therapy process is configured as a trinomial – action (making music/ relationship (action with the other/communication (musical or verbal voluntary expression of feelings and conflicts, which, although intrinsically connected, is perceived in a sequential process. Aulagnier asserts that psychic activity represents the conjunction of three modes of functioning: the original process, the primary process and the secondary process. The perception of sound passes through three phases, corresponding to each manner of functioning of the psychic system – the pleasure of hearing, the desire to listen (to the other and the imperative of meaning. The music therapy process offers a significant similarity with the theory proposed by Aulagnier. We propose the hypothesis that in music therapy, there is an opportunity to (reexperience very archaic phases in the constitution of the ego, but in a new manner, so helping to open communication channels. This theoretical hypothesis is illustrated by real examples of patients.

  6. Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels

    Science.gov (United States)

    Meighan, Peter C.; Peng, Changhong; Varnum, Michael D.

    2015-01-01

    Cyclic nucleotide gated (CNG) channels are a critical component of the visual transduction cascade in the vertebrate retina. Mutations in the genes encoding these channels have been associated with a spectrum of inherited retinal disorders. To gain insight into their pathophysiological mechanisms, we have investigated the functional consequences of several CNGB3 mutations, previously associated with macular degeneration (Y469D and L595F) or complete achromatopsia (S156F, P309L, and G558C), by expressing these subunits in combination with wild-type CNGA3 in Xenopus oocytes and characterizing them using patch-clamp recordings in the inside-out configuration. These mutations did not prevent the formation of functional heteromeric channels, as indicated by sensitivity to block by L-cis-diltiazem. With the exception of S156F, each of the mutant channels displayed electrophysiological properties reflecting enhanced channel activity at physiological concentrations of cGMP (i.e., a gain-of-function phenotype). The increased channel activity produced by these mutations resulted from either increased functional expression levels, or increased sensitivity to cyclic nucleotides. Furthermore, L595F increased the spontaneous open probability in the absence of activating ligand, signifying a ligand independent gain-of-function change. In addition to the CNGB3 disease-associate mutations, we characterized the effects of several common CNGB3 and CNGA3 single-nucleotide polymorphisms (SNPs) on heteromeric CNGA3+CNGB3 channel function. Two of the SNPs examined (A3-T153M, and B3-W234C) produced decreased ligand sensitivity for heteromeric CNG channels. These changes may contribute to background disease susceptibility when combined with other genetic or non-genetic factors. Together, these studies help to define the underlying molecular phenotype for mutations relating to CNG channel disease pathogenesis. PMID:26106334

  7. Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels.

    Directory of Open Access Journals (Sweden)

    Peter eMeighan

    2015-06-01

    Full Text Available Cyclic nucleotide gated (CNG channels are a critical component of the visual transduction cascade in the vertebrate retina. Mutations in the genes encoding these channels have been associated with a spectrum of inherited retinal disorders. To gain insight into their pathophysiological mechanisms, we have investigated the functional consequences of several CNGB3 mutations, previously associated with macular degeneration (Y469D and L595F or complete achromatopsia (S156F, P309L, and G558C, by expressing these subunits in combination with wild-type CNGA3 in Xenopus oocytes and characterizing them using patch-clamp recordings in the inside-out configuration. These mutations did not prevent the formation of functional heteromeric channels, as indicated by sensitivity to block by L-cis-diltiazem. With the exception of S156F, each of the mutant channels displayed electrophysiological properties reflecting enhanced channel activity at physiological concentrations of cGMP (i.e., a gain-of-function phenotype. The increased channel activity produced by these mutations resulted from either increased functional expression levels, or increased sensitivity to cyclic nucleotides. Furthermore, L595F increased the spontaneous open probability in the absence of activating ligand, signifying a ligand independent gain-of-function change. In addition to the CNGB3 disease-associate mutations, we characterized the effects of several common CNGB3 and CNGA3 single-nucleotide polymorphisms (SNPs on heteromeric CNGA3+CNGB3 channel function. Two of the SNPs examined (A3-T153M, and B3-W234C produced decreased ligand sensitivity for heteromeric CNG channels. These changes may contribute to background disease susceptibility when combined with other genetic or nongenetic factors. Together, these studies help to define the underlying molecular phenotype for mutations relating to CNG channel disease pathogenesis.

  8. Evaporative Lithography in Open Microfluidic Channel Networks

    KAUST Repository

    Lone, Saifullah

    2017-02-24

    We demonstrate a direct capillary-driven method based on wetting and evaporation of various suspensions to fabricate regular two-dimensional wires in an open microfluidic channel through continuous deposition of micro- or nanoparticles under evaporative lithography, akin to the coffee-ring effect. The suspension is gently placed in a loading reservoir connected to the main open microchannel groove on a PDMS substrate. Hydrophilic conditions ensure rapid spreading of the suspension from the loading reservoir to fill the entire channel length. Evaporation during the spreading and after the channel is full increases the particle concentration toward the end of the channel. This evaporation-induced convective transport brings particles from the loading reservoir toward the channel end where this flow deposits a continuous multilayered particle structure. The particle deposition front propagates backward over the entire channel length. The final dry deposit of the particles is thereby much thicker than the initial volume fraction of the suspension. The deposition depth is characterized using a 3D imaging profiler, whereas the deposition topography is revealed using a scanning electron microscope. The patterning technology described here is robust and passive and hence operates without an external field. This work may well become a launching pad to construct low-cost and large-scale thin optoelectronic films with variable thicknesses and interspacing distances.

  9. Evaporative Lithography in Open Microfluidic Channel Networks.

    Science.gov (United States)

    Lone, Saifullah; Zhang, Jia Ming; Vakarelski, Ivan U; Li, Er Qiang; Thoroddsen, Sigurdur T

    2017-03-13

    We demonstrate a direct capillary-driven method based on wetting and evaporation of various suspensions to fabricate regular two-dimensional wires in an open microfluidic channel through continuous deposition of micro- or nanoparticles under evaporative lithography, akin to the coffee-ring effect. The suspension is gently placed in a loading reservoir connected to the main open microchannel groove on a PDMS substrate. Hydrophilic conditions ensure rapid spreading of the suspension from the loading reservoir to fill the entire channel length. Evaporation during the spreading and after the channel is full increases the particle concentration toward the end of the channel. This evaporation-induced convective transport brings particles from the loading reservoir toward the channel end where this flow deposits a continuous multilayered particle structure. The particle deposition front propagates backward over the entire channel length. The final dry deposit of the particles is thereby much thicker than the initial volume fraction of the suspension. The deposition depth is characterized using a 3D imaging profiler, whereas the deposition topography is revealed using a scanning electron microscope. The patterning technology described here is robust and passive and hence operates without an external field. This work may well become a launching pad to construct low-cost and large-scale thin optoelectronic films with variable thicknesses and interspacing distances.

  10. Stability of flowing open fluidic channels

    Directory of Open Access Journals (Sweden)

    Jue Nee Tan

    2013-02-01

    Full Text Available Open fluidic systems have a distinct advantage over enclosed channels in that the fluids exposed nature makes for easy external interaction, this finds uses in introduction of samples by adding liquid droplets or from the surrounding gaseous medium. This work investigates flowing open channels and films, which can potentially make use of the open section of the system as an external interface, before bringing the sample into an enclosed channel. Clearly, in this scenario a key factor is the stability of the flowing open fluid. The open channels investigated include a straight open channel defined by a narrow strip of solid surface, the edges of which allow large contact angle hysteresis, and a wider structure allowing for multiple inputs and outputs. A model is developed for fluid flow, and the findings used to describe the process of failure in both cases.

  11. Mathematical Modeling on Open Limestone Channel

    CERN Document Server

    Bandstra, Joel; Wu, Naiyi

    2014-01-01

    Acid mine drainage (AMD) is the outflow of acidic water from metal mines or coal mines. When exposed to air and water, metal sulfides from the deposits of the mines are oxidized and produce acid, metal ions and sulfate, which lower the pH value of the water. An open limestone channel (OLC) is a passive and low cost way to neutralize AMD. The dissolution of calcium into the water increases the pH value of the solution. A differential equation model is numerically solved to predict the variation of concentration of each species in the OLC solution. The diffusion of Calcium due to iron precipitates is modeled by a linear equation. The results give the variation of pH value and the concentration of Calcium.

  12. Backstepping feedback control of open channel flow

    OpenAIRE

    Huo, Mandy; Malek, Sami

    2014-01-01

    We derive a feedback control law for the control of the downstream flow in a 1-D open channel by manipulating the water flow at an upstream location. We use backstepping for controller design and Lyapunov techniques for stability analysis. Finally, the controller is verified with simulations.

  13. Localization in chaotic systems with a single-channel opening.

    Science.gov (United States)

    Lippolis, Domenico; Ryu, Jung-Wan; Kim, Sang Wook

    2015-07-01

    We introduce a single-channel opening in a random Hamiltonian and a quantized chaotic map: localization on the opening occurs as a sensible deviation of the wave-function statistics from the predictions of random matrix theory, even in the semiclassical limit. Increasing the coupling to the open channel in the quantum model, we observe a similar picture to resonance trapping, made of a few fast-decaying states, whose left (right) eigenfunctions are entirely localized on the (preimage of the) opening, and plentiful long-lived states, whose probability density is instead suppressed at the opening. For the latter, we derive and test a linear relation between the wave-function intensities and the decay rates, similar to the Breit-Wigner law. We then analyze the statistics of the eigenfunctions of the corresponding (discretized) classical propagator, finding a similar behavior to the quantum system only in the weak-coupling regime.

  14. Numerical Investigation of Developing Velocity Distributions in Open Channel Flows

    Directory of Open Access Journals (Sweden)

    Usman Ghani

    2014-04-01

    Full Text Available The velocity profiles in open channel flows start developing after entering into the channel for quite some length. All types of laboratory experiments for open channel flows are carried out in the fully developed flow regions which exist at some length downstream the inlet. In this research work an attempt has been made to investigate the impact of roughness and slope of the channel bed on the length required for establishment of fully developed flow in an open channel. A range of different roughness values along with various slopes were considered for this purpose. It was observed that an increase in roughness results in reduction of development length; and development length reduces drastically when roughness reaches to the range normally encountered in open channel flows with emergent vegetation or natural river flows. However, it was observed that the change of slope did not have any noticeable effect on development length. This work suggests that CFD (Computational Fluid Dynamics technique can be used for getting a reliable development length before performing an experimental work

  15. Frequency width of open channels in multiple scattering media.

    Science.gov (United States)

    Bosch, Jeroen; Goorden, Sebastianus A; Mosk, Allard P

    2016-11-14

    We report optical measurements of the spectral width of open transmission channels in a three-dimensional diffusive medium. The light transmission through a sample is enhanced by efficiently coupling to open transmission channels using repeated digital optical phase conjugation. The spectral properties are investigated by enhancing the transmission, fixing the incident wavefront and scanning the wavelength of the laser. We measure the transmitted field to extract the field correlation function and the enhancement of the total transmission. We find that optimizing the total transmission leads to a significant increase in the frequency width of the field correlation function. Additionally we find that the enhanced transmission persists over an even larger frequency bandwidth. This result shows open channels in the diffusive regime are spectrally much wider than previous measurements in the localized regime suggest.

  16. Pathlengths of open channels in multiple scattering media

    CERN Document Server

    Bosch, Jeroen; Mosk, Allard P

    2016-01-01

    We report optical measurements of the spectral width of open transmission channels in a three-dimensional diffusive medium. The light transmission through a sample is enhanced by efficiently coupling to open transmission channels using repeated digital optical phase conjugation. The spectral properties are investigated by enhancing the transmission, fixing the incident wavefront and scanning the wavelength of the laser. We measure the transmitted field to extract the field correlation function and the enhancement of the total transmission. We find that optimizing the total transmission leads to a significant increase in the frequency width of the field correlation function. Additionally we find that the enhanced transmission persists over an even larger frequency bandwidth. This result shows open channels in the diffusive regime are spectrally much wider than previous measurements in the localized regime suggest.

  17. VELOCITY PROFILES OF TURBULENT OPEN CHANNEL FLOWS

    Institute of Scientific and Technical Information of China (English)

    WANG Dianchang; WANG Xingkui; YU Mingzhong; LI Danxun

    2001-01-01

    The log-law and the wake law of velocity profile for open channel flows are discussed and compared in this paper. Experimental data from eight sources are used to verify the velocity distribution models.The effect of bed level on the velocity profile is analyzed. A formula to calculate the maximum velocity is proposed. In the region of y <δm , the velocity profile approximately follows the log-law. For the region of y >δm , the effect of the aspect ratio is considered. A new velocity profile model on the basis of log-law that can unify all of the hydraulic bed roughness is presented.

  18. Identification of resonance waves in open water channels

    Science.gov (United States)

    This article presents a procedure to determine the characteristics of open water channels required for controller and filter design, with special focus on the resonance waves. Also, a new simplified model structure for open water channels is proposed. The procedure applies System Identification tool...

  19. Frequency width of open channels in multiple scattering media

    NARCIS (Netherlands)

    Bosch, J.; Goorden, S.A.; Mosk, Allard

    2016-01-01

    We report optical measurements of the spectral width of open transmission channels in a three-dimensional diffusive medium. The light transmission through a sample is enhanced by efficiently coupling to open transmission channels using repeated digital optical phase conjugation. The spectral

  20. NONUNIFORM OPEN CHANNEL FLOW WITH UPWARD SEEPAGE THROUGH LOOSE BEDS

    Institute of Scientific and Technical Information of China (English)

    Subhasish DEY

    2003-01-01

    The Reynolds stress and bed shear stress are important parameters in fluvial hydraulics. Steadynonuniform flow in open channels with streamwise sloping beds having upward seepage through loose beds is theoretically analyzed to estimate the Reynolds stress and bed shear stress. Equations of the Reynolds stress and bed shear stress are developed, assuming a modified logarithmic velocity distribution law due to upward seepage, and using the Reynolds and continuity equations of twodimensional flow in open channels.

  1. Computation of gradually varied flow in compound open channel networks

    Indian Academy of Sciences (India)

    H Prashanth Reddy; M Hanif Chaudhry; Jasim Imran

    2014-12-01

    Although, natural channels are rarely rectangular or trapezoidal in cross section, these cross sections are assumed for the computation of steady, gradually varied flow in open channel networks. The accuracy of the computed results, therefore, becomes questionable due to differences in the hydraulic and geometric characteristics of the main channel and floodplains. To overcome these limitations, an algorithm is presented in this paper to compute steady, gradually varied flow in an open-channel network with compound cross sections. As compared to the presently available methods, the methodology is more general and suitable for application to compound and trapezoidal channel cross sections in series channels, tree-type or looped networks. In this method, the energy and continuity equations are solved for steady, gradually varied flow by the Newton–Raphson method and the proposed methodology is applied to tree-type and looped-channel networks. An algorithm is presented to determine multiple critical depths in a compound channel. Modifications in channel geometry are presented to avoid the occurrence of multiple critical depths. The occurrence of only one critical depth in a compound cross section with modified geometry is demonstrated for a tree-type channel network.

  2. Variability of hydrologic regimes and morphology in constructed open-ditch channels

    Science.gov (United States)

    Strock, J.S.; Magner, J.A.; Richardson, W.B.; Sadowsky, M.J.; Sands, G.R.; Venterea, R.T.; ,

    2004-01-01

    Open-ditch ecosystems are potential transporters of considerable loads of nutrients, sediment, pathogens and pesticides from direct inflow from agricultural land to small streams and larger rivers. Our objective was to compare hydrology and channel morphology between two experimental open-ditch channels. An open-ditch research facility incorporating a paired design was constructed during 2002 near Lamberton, MN. A200-m reach of existing drainage channel was converted into a system of four parallel channels. The facility was equipped with water level control devices and instrumentation for flow monitoring and water sample collection on upstream and downstream ends of the system. Hydrographs from simulated flow during year one indicated that paired open-ditch channels responded similarly to changes in inflow. Variability in hydrologic response between open-ditches was attributed to differences in open-ditch channel bottom elevation and vegetation density. No chemical, biological, or atmospheric measurements were made during 2003. Potential future benefits of this research include improved biological diversity and integrity of open-ditch ecosystems, reduce flood peaks and increased flow during critical low-flow periods, improved and more efficient nitrogen retention within the open-ditch ecosystem, and decreased maintenance cost associated with reduced frequency of open-ditch maintenance.

  3. Cooperative transition between open and closed conformations in potassium channels.

    Directory of Open Access Journals (Sweden)

    Turkan Haliloglu

    Full Text Available Potassium (K+ ion channels switch between open and closed conformations. The nature of this important transition was revealed by comparing the X-ray crystal structures of the MthK channel from Methanobacterium thermoautotrophicum, obtained in its open conformation, and the KcsA channel from Streptomyces lividans, obtained in its closed conformation. We analyzed the dynamic characteristics and energetics of these homotetrameric structures in order to study the role of the intersubunit cooperativity in this transition. For this, elastic models and in silico alanine-scanning mutagenesis were used, respectively. Reassuringly, the calculations manifested motion from the open (closed towards the closed (open conformation. The calculations also revealed a network of dynamically and energetically coupled residues. Interestingly, the network suggests coupling between the selectivity filter and the gate, which are located at the two ends of the channel pore. Coupling between these two regions was not observed in calculations that were conducted with the monomer, which emphasizes the importance of the intersubunit interactions within the tetrameric structure for the cooperative gating behavior of the channel.

  4. The complete structure of an activated open sodium channel

    Science.gov (United States)

    Sula, Altin; Booker, Jennifer; Ng, Leo C. T.; Naylor, Claire E.; DeCaen, Paul G.; Wallace, B. A.

    2017-01-01

    Voltage-gated sodium channels (Navs) play essential roles in excitable tissues, with their activation and opening resulting in the initial phase of the action potential. The cycling of Navs through open, closed and inactivated states, and their closely choreographed relationships with the activities of other ion channels lead to exquisite control of intracellular ion concentrations in both prokaryotes and eukaryotes. Here we present the 2.45 Å resolution crystal structure of the complete NavMs prokaryotic sodium channel in a fully open conformation. A canonical activated conformation of the voltage sensor S4 helix, an open selectivity filter leading to an open activation gate at the intracellular membrane surface and the intracellular C-terminal domain are visible in the structure. It includes a heretofore unseen interaction motif between W77 of S3, the S4–S5 interdomain linker, and the C-terminus, which is associated with regulation of opening and closing of the intracellular gate. PMID:28205548

  5. Effect Of Flow Resistance In Open Rectangular Channel

    Directory of Open Access Journals (Sweden)

    Ahmad Noor Aliza

    2017-01-01

    Full Text Available The determination of flow resistance for open channels remains a challenge in practices. In this research, an experimental study was carried out to investigate the hydraulic roughness characteristics in an open channel. The experimental flume (10 m length, 0.30 m width and 0.46 height was carried out with two conditions ; contain gravel bed and without gravel bed (as controller. Blocks of concrete foam were fabricated and laid on the bed surface for providing uniformly roughened along the open channel. A velocity flow meter was used to quantify the average velocity, and other parameters such as cross-section, hydraulic radius, wetted perimeter, and channel slopes were also calculated. Finally, the flow resistance, n obtained using the flume with gravel bed surface is higher than the flume without gravel bed surface. The flow conditions were declared as subcritical as the Froude number is less than 1 for both conditions in the flume. As a conclusion, it was identified that the hydraulic roughness n, was influenced by the type bed roughness, flow rate and channel slope.

  6. Secondary flow in sharp open-channel bends

    NARCIS (Netherlands)

    Blanckaert, K.; De Vriend, H.J.

    2004-01-01

    Secondary currents are a characteristic feature of flow in open-channel bends. Besides the classical helical motion (centre-region cell), a weaker and smaller counter-rotating circulation cell (outer-bank cell) is often observed near the outer bank, which is believed to play an important role in ban

  7. Minoxidil opens mitochondrial KATP channels and confers cardioprotection

    Science.gov (United States)

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

    2003-01-01

    ATP-sensitive potassium channel in the mitochondrial inner membrane (mitoKATP channel) rather than in the sarcolemma (sarcKATP channel) appears to play an important role in cardioprotection. We examined the effect of minoxidil, a potent antihypertensive agent and hair growth stimulator, on sarcKATP and mitoKATP channels in guinea-pig ventricular myocytes. Minoxidil activated a glybenclamide-sensitive sarcKATP channel current in the whole-cell recording mode with an EC50 of 182.6 μM. Minoxidil reversibly increased the flavoprotein oxidation, an index of mitoKATP channel activity, in a concentration-dependent manner. The EC50 for mitoKATP channel activation was estimated to be 7.3 μM; this value was notably ≈25-fold lower than that for sarcKATP channel activation. Minoxidil (10 μM) significantly attenuated the ouabain-induced increase of mitochondrial Ca2+ concentration, which was measured by loading cells with rhod-2 fluorescence. Furthermore, pretreatment with minoxidil (10 μM) before 20-min no-flow ischaemia significantly improved the recovery of developed tension measured after 60 min of reperfusion in coronary perfused guinea-pig ventricular muscles. These cardioprotective effects of minoxidil were completely abolished by the mitoKATP channel blocker 5-hydroxydecanoate (500 μM). Our results indicate that minoxidil exerts a direct cardioprotective effect on heart muscle cells, an effect mediated by the selective activation of mitoKATP channels. PMID:14691056

  8. Pharmacodynamics of potassium channel openers in cultured neuronal networks.

    Science.gov (United States)

    Wu, Calvin; V Gopal, Kamakshi; Lukas, Thomas J; Gross, Guenter W; Moore, Ernest J

    2014-06-01

    A novel class of drugs - potassium (K(+)) channel openers or activators - has recently been shown to cause anticonvulsive and neuroprotective effects by activating hyperpolarizing K(+) currents, and therefore, may show efficacy for treating tinnitus. This study presents measurements of the modulatory effects of four K(+) channel openers on the spontaneous activity and action potential waveforms of neuronal networks. The networks were derived from mouse embryonic auditory cortices and grown on microelectrode arrays. Pentylenetetrazol was used to create hyperactivity states in the neuronal networks as a first approximation for mimicking tinnitus or tinnitus-like activity. We then compared the pharmacodynamics of the four channel activators, retigabine and flupirtine (voltage-gated K(+) channel KV7 activators), NS1619 and isopimaric acid ("big potassium" BK channel activators). The EC50 of retigabine, flupirtine, NS1619, and isopimaric acid were 8.0, 4.0, 5.8, and 7.8µM, respectively. The reduction of hyperactivity compared to the reference activity was significant. The present results highlight the notion of re-purposing the K(+) channel activators for reducing hyperactivity of spontaneously active auditory networks, serving as a platform for these drugs to show efficacy toward target identification, prevention, as well as treatment of tinnitus.

  9. LARGE EDDY SIMULATION OF PULSATING TURBULENT OPEN CHANNEL FLOW

    Institute of Scientific and Technical Information of China (English)

    ZOU Li-yong; LIU Nan-sheng; LU Xi-yun

    2004-01-01

    Pulsating turbulent open channel flow has been investigated by the use of Large Eddy Simulation (LES) technique coupled with dynamic Sub-Grid-Scale (SGS) model for turbulent SGS stress to closure the governing equations. Three-dimensional filtered Navier-Stokes equations are numerically solved by a fractional-step method. The objective of this study is to deal with the behavior of the pulsating turbulent open channel flow and to examine the reliability of the LES approach for predicting the pulsating turbulent flow. In this study, the Reynolds number (Reτ ) is chosen as 180 based on the friction velocity and the channel depth. The frequency of the driving pressure gradient for the pulsating turbulent flow ranges low, medium and high value. Statistical turbulence quantities as well as the flow structures are analyzed.

  10. Microfluidic mixing in a Y-junction open channel

    Directory of Open Access Journals (Sweden)

    Jue Nee Tan

    2012-09-01

    Full Text Available In the laminar regimes typical of microfluidic systems’, mixing is governed by molecular diffusion; however this process is slow in nature. Consequently, passive or active methods are usually sought for effective mixing. In this work, open fluidic channels will be investigated; these channels are bounded on all but one face by an air/fluid interface. Firstly, it will be shown that flow in open channels can merge at a Y-junction in a stable manner; hence two fluids can be brought into contact with each other. Secondly, the mixing of these two fluids will be studied. At high flow rates (>300 μl/min mixing occurs at the junction without need for additional intervention, this mixing is far swifter than can be expected from molecular diffusion. At lower flow rates, intervention is required. A major motivation for open fluidic channels is the ability to interact with the surrounding air environment; this feature is used to effect the desired mixing. It is shown that by blowing an air jet across the junction, shear stresses at the air/fluid interface causes a flow profile within the fluid inductive to rapid mixing of the fluids.

  11. Air entrainment in open channel flows. Application to spillways

    Energy Technology Data Exchange (ETDEWEB)

    Chanson, H. (Queensland Univ., St. Lucia (Australia))

    1992-01-01

    In open channel flows an important design parameter is the amount of entrained air. The presence of air in high velocity flows or steep chutes increases the bulk of the flow and this is a design parameter that determines the height of chute sidewalls. Furthermore the presence of air within the boundary layer reduces the shear stress between flow layers and hence the shear forces. The resulting increase of fluid motion must be taken in account when designing ski jump and stilling basin downstream of a spillway. Besides the presence of air within high-velocity flows may prevent or reduce cavitation damage. Estimation of the quantity of air entrained along the spillway is required by the design engineer when sitting aerators to artificially introduce more air, or determining whether aerators are required. Recently air entrainment on chutes also been recognized for its contribution to air-water transfer of atmospheric gases such as oxygen and nitrogen. This article describes a general method to compute the flow characteristics of self-aerated flows. Firstly the uniform flow conditions are presented and comparisons will be made between model and prototype results. Then the basic equations for gradually varied aerated flows will be developed, and these results are discussed and compared with experimental data. 28 refs., 8 figs., 3 tabs.

  12. Uncoupling charge movement from channel opening in voltage-gated potassium channels by ruthenium complexes.

    Science.gov (United States)

    Jara-Oseguera, Andrés; Ishida, Itzel G; Rangel-Yescas, Gisela E; Espinosa-Jalapa, Noel; Pérez-Guzmán, José A; Elías-Viñas, David; Le Lagadec, Ronan; Rosenbaum, Tamara; Islas, León D

    2011-05-06

    The Kv2.1 channel generates a delayed-rectifier current in neurons and is responsible for modulation of neuronal spike frequency and membrane repolarization in pancreatic β-cells and cardiomyocytes. As with other tetrameric voltage-activated K(+)-channels, it has been proposed that each of the four Kv2.1 voltage-sensing domains activates independently upon depolarization, leading to a final concerted transition that causes channel opening. The mechanism by which voltage-sensor activation is coupled to the gating of the pore is still not understood. Here we show that the carbon-monoxide releasing molecule 2 (CORM-2) is an allosteric inhibitor of the Kv2.1 channel and that its inhibitory properties derive from the CORM-2 ability to largely reduce the voltage dependence of the opening transition, uncoupling voltage-sensor activation from the concerted opening transition. We additionally demonstrate that CORM-2 modulates Shaker K(+)-channels in a similar manner. Our data suggest that the mechanism of inhibition by CORM-2 may be common to voltage-activated channels and that this compound should be a useful tool for understanding the mechanisms of electromechanical coupling.

  13. Alpha Channeling in Open-System Magnetic Devices

    Energy Technology Data Exchange (ETDEWEB)

    Fisch, Nathaniel [Princeton Univ., NJ (United States)

    2016-06-19

    The Grant DE-SC0000736, Alpha Channeling in Open-System Magnetic Devices, is a continuation of the Grant DE-FG02-06ER54851, Alpha Channeling in Mirror Machines. In publications funded by DE-SC0000736, the grant DE-FG02-06ER54851 was actually credited. The key results obtained under Grant DE-SC0000736, Alpha Channeling in Open-System Magnetic Devices, appear in a series of publications. The earlier effort under DE-FG02- 06ER54851 was the subject of a previous Final Report. The theme of this later effort has been unusual confinement effects, or de-confinement effects, in open-field magnetic confinement devices. First, the possibilities in losing axisymmetry were explored. Then a number of issues in rotating plasma were addressed. Most importantly, a spinoff application to plasma separations was recognized, which also resulted in a provisional patent application. (That provisional patent application, however, was not pursued further.) Alpha channeling entails injecting waves into magnetically confined plasma to release energy from one particular ion while ejecting that ion. The ejection of the ion is actually a concomitant effect in releasing energy from the ion to the wave. In rotating plasma, there is the opportunity to store the energy in a radial electric field rather than in waves. In other words, the ejected alpha particle loses its energy to the radial potential, which in turn produces plasma rotation. This is a very useful effect, since producing radial electric fields by other means are technologically more difficult. In fact, one can heat ions, and then eject them, to produce the desired radial field. In each case, there is a separation effect of different ions, which generalizes the original alpha-channeling concept of separating alpha ash from hydrogen. In a further generalization of the separation concept, a double-well filter represents a new way to produce high-throughput separations of ions, potentially useful for nuclear waste remediation.

  14. Effect of flow field on open channel flow properties using numerical investigation and experimental comparison

    Energy Technology Data Exchange (ETDEWEB)

    Khazaee, I. [Department of Mechanical Engineering, Torbat-e-jam branch, Islamic Azad University, Torbat-e-jam (Iran, Islamic Republic of); Mohammadiun, M. [Department of Mechanical Engineering, Shahrood branch, Islamic Azad University, Shahrood (Iran, Islamic Republic of)

    2012-07-01

    In this paper a complete three-dimensional and two phase CFD model for flow distribution in an open channel investigated. The finite volume method (FVM) with a dynamic Sub grid-scale was carried out for seven cases of different aspect ratios, different inclination angles or slopes and convergence-divergence condition. The volume of fluid (VOF) method was used to allow the free-surface to deform freely with the underlying turbulence. The discharge through open channel flow is often evaluated by velocity-area integration method from the measurement of velocity at discrete locations in the measuring section. The variation of velocity along horizontal and vertical directions is thus very important to decide the location of the sensors. The aspect ratio of the channel, slope of the channel and divergence- convergence of the channel have investigated and the results show that the depth of water at the end of the channel is higher at AR=0.8 against the AR=0.4 and AR=1.2. Also it is clear that by increasing the inclination angle or slope of the channel in case1, case4 and case5 the depth of the water increases. Also it is clear that the outlet mass flow rate is at a minimum value at a range of inclination angle of the channel.

  15. The mechanical energy equation for total flow in open channels

    Institute of Scientific and Technical Information of China (English)

    刘士和; 范敏; 薛娇

    2014-01-01

    The mechanical energy equation is a fundamental equation of a 1-D mathematical model in Hydraulics and Engineering Fluid Mechanics. This equation for the total flow used to be deduced by extending the Bernoulli’s equation for the ideal fluid in the streamline to a stream tube, and then revised by considering the viscous effect and integrated on the cross section. This derivation is not rigorous and the effect of turbulence is not considered. In this paper, the energy equation for the total flow is derived by using the Navier-Stokes equations in Fluid Mechanics, the results are as follows:(1) A new energy equation for steady channel flows of in-compressible homogeneous liquid is obtained, which includes the variation of the turbulent kinetic energy along the channel, the for-mula for the mechanical energy loss of the total flow can be determined directly in the deduction process. (2) The theoretical solution of the velocity field for laminar flows in a rectangular open channel is obtained and the mechanical energy loss in the energy equa-tion is calculated. The variations of the coefficient of the mechanical energy loss against the Reynolds number and the width-depth ratio are obtained. (3) The turbulent flow in a rectangular open channel is simulated using 3-D Reynolds averaged equations closed by the Reynolds stress model (RSM), and the variations of the coefficient of the mechanical energy loss against the Reynolds number and the width-depth ratio are discussed.

  16. TRANSVERSE MIXING IN A TRAPEZOIDAL COMPOUND OPEN CHANNEL

    Institute of Scientific and Technical Information of China (English)

    ZENG Yu-hong; HUAI Wen-xin; GUYMER I

    2008-01-01

    Transverse mixing characteristics of solute in the open channel flow can provide useful information for river environmental management. The lateral mixing coefficient is a crucial parameter for reproducing the transverse mixing either by numerical simulation or by analytical prediction. Since the solute mixing can be greatly affected by the lateral variations in water depth, mixing coefficient should be determined in each sub-section (i.e., the main channel, side slope and flood plain) separately. In this article, the transverse mixing in a symmetric trapezoidal compound channel was studied based on laboratory measurement of longitudinal and transverse velocity components and lateral distribution of solute concentration. The lateral mixing coefficient was estimated by adopting different Schmidt numbers in different sub-sections divided according to the developing trend of the eddy viscosity, and finally a piecewise linear profile of mixing coefficient was adopted to analytically predict the transverse solute concentration. The comparison between the analytically predicted data and the measuring solute concentration proved that this is an effective way to estimate the lateral mixing in the open channel flow with lateral variations in water depth.

  17. Opening of K+ channels by capacitive stimulation from silicon chip

    Science.gov (United States)

    Ulbrich, M. H.; Fromherz, P.

    2005-10-01

    The development of stable neuroelectronic systems requires a stimulation of nerve cells from semiconductor devices without electrochemical effects at the electrolyte/solid interface and without damage of the cell membrane. The interaction must rely on a reversible opening of voltage-gated ion channels by capacitive coupling. In a proof-of-principle experiment, we demonstrate that Kv1.3 potassium channels expressed in HEK293 cells can be opened from an electrolyte/oxide/silicon (EOS) capacitor. A sufficient strength of electrical coupling is achieved by insulating silicon with a thin film of TiO2 to achieve a high capacitance and by removing NaCl from the electrolyte to enhance the resistance of the cell-chip contact. When a decaying voltage ramp is applied to the EOS capacitor, an outward current through the attached cell membrane is observed that is specific for Kv1.3 channels. An open probability up to fifty percent is estimated by comparison with a numerical simulation of the cell-chip contact.

  18. Basic hydraulic principles of open-channel flow

    Science.gov (United States)

    Jobson, Harvey E.; Froehlich, David C.

    1988-01-01

    The three basic principles of open-channel-flow analysis--the conservation of mass, energy, and momentum--are derived, explained, and applied to solve problems of open-channel flow. These principles are introduced at a level that can be comprehended by a person with an understanding of the principles of physics and mechanics equivalent to that presented in the first college level course of the subject. The reader is assumed to have a working knowledge of algebra and plane geometry as well as some knowledge of calculus. Once the principles have been derived, a number of example applications are presented that illustrate the computation of flow through culverts and bridges, and over structures, such as dams and weirs. Because resistance to flow is a major obstacle to the successful application of the energy principle to open-channel flow, procedures are outlined for the rational selection of flow resistance coefficients. The principle of specific energy is shown to be useful in the prediction of water-surface profiles both in the qualitative and quantitative sense. (USGS)

  19. From Pan-Reactive KV7 Channel Opener to Subtype Selective Opener/Inhibitor by Addition of a Methyl Group

    Science.gov (United States)

    Blom, Sigrid Marie; Rottländer, Mario; Kehler, Jan; Bundgaard, Christoffer; Schmitt, Nicole; Jensen, Henrik Sindal

    2014-01-01

    The voltage-gated potassium channels of the KV7 family (KV7.1–5) play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been to identify compounds capable of discriminating between the neuronally expressed subtypes (KV7.2–5), aiding the identification of the subunit composition of KV7 currents in various tissues, and possessing better therapeutic potential for particular indications. By taking advantage of the structure-activity relationship of acrylamide KV7 channel openers and the effects of these compounds on mutant KV7 channels, we have designed and synthesized a novel KV7 channel modulator with a unique profile. The compound, named SMB-1, is an inhibitor of KV7.2 and an activator of KV7.4. SMB-1 inhibits KV7.2 by reducing the current amplitude and increasing the time constant for the slow component of the activation kinetics. The activation of KV7.4 is seen as an increase in the current amplitude and a slowing of the deactivation kinetics. Experiments studying mutant channels with a compromised binding site for the KV7.2–5 opener retigabine indicate that SMB-1 binds within the same pocket as retigabine for both inhibition of KV7.2 and activation of KV7.4. SMB-1 may serve as a valuable tool for KV7 channel research and may be used as a template for further design of better subtype selective KV7 channel modulators. A compound with this profile could hold novel therapeutic potential such as the treatment of both positive and cognitive symptoms in schizophrenia. PMID:24956197

  20. From pan-reactive KV7 channel opener to subtype selective opener/inhibitor by addition of a methyl group.

    Directory of Open Access Journals (Sweden)

    Sigrid Marie Blom

    Full Text Available The voltage-gated potassium channels of the KV7 family (KV7.1-5 play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been to identify compounds capable of discriminating between the neuronally expressed subtypes (KV7.2-5, aiding the identification of the subunit composition of KV7 currents in various tissues, and possessing better therapeutic potential for particular indications. By taking advantage of the structure-activity relationship of acrylamide KV7 channel openers and the effects of these compounds on mutant KV7 channels, we have designed and synthesized a novel KV7 channel modulator with a unique profile. The compound, named SMB-1, is an inhibitor of KV7.2 and an activator of KV7.4. SMB-1 inhibits KV7.2 by reducing the current amplitude and increasing the time constant for the slow component of the activation kinetics. The activation of KV7.4 is seen as an increase in the current amplitude and a slowing of the deactivation kinetics. Experiments studying mutant channels with a compromised binding site for the KV7.2-5 opener retigabine indicate that SMB-1 binds within the same pocket as retigabine for both inhibition of KV7.2 and activation of KV7.4. SMB-1 may serve as a valuable tool for KV7 channel research and may be used as a template for further design of better subtype selective KV7 channel modulators. A compound with this profile could hold novel therapeutic potential such as the treatment of both positive and cognitive symptoms in schizophrenia.

  1. K sup + channel openers activate brain sulfonylurea-sensitive K sup + channels and block neurosecretion

    Energy Technology Data Exchange (ETDEWEB)

    Schmid-Antomarchi, H.; Amoroso, S.; Fosset, M.; Lazdunski, M. (Centre National de la Recherche Scientifique, Valbonne (France))

    1990-05-01

    Vascular K{sup +} channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate {sup 86}Rb{sup +} efflux from slices of substantia nigra. This {sup 86}Rb{sup +} efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K{sup +} channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K{sub 0.5}, the half-maximal effect of the enantiomer ({minus})-cromakalim, is as low as 10 nM, whereas K{sub 0.5} for nicorandil is 100 nM. These two compounds appear to have a much higher affinity for nerve cells than for smooth muscle cells. Openers of sulfonylurea-sensitive K{sup +} channels lead to inhibition of {gamma}-aminobutyric acid release. There is an excellent relationship between potency to activate {sup 86}Rb{sup +} efflux and potency to inhibit neurotransmitter release.

  2. CHARACTERISTICS OF FLOW RESISTANCE IN OPEN CHANNELS WITH NON-SUBMERGED RIGID VEGETATION

    Institute of Scientific and Technical Information of China (English)

    WU Fu-sheng

    2008-01-01

    The flow resistance factors of non-submerged rigid vegetation in open channels were analyzed. The formulas of drag coefficient CD and equivalent Manning's roughness coefficient nd were derived by analyzing the force of the flow of non-submerged rigid vegetation in open channel. The flow characteristics and mechanism of non-submerged rigid vegetation in open channel were studied through flume experiments.

  3. LONGITUDINAL DISPERSION IN SEDIMENT-LADEN OPEN CHANNEL FLOWS

    Institute of Scientific and Technical Information of China (English)

    Z.AHMAD; U.C.KOTHYARI; K.G.RANGA RAJU

    2004-01-01

    Laboratory experiments on longitudinal dispersion in clear-water and sediment-laden open channel flows are reported. Data from these experiments and those available from previous studies indicate that the suspended sediment present in the flow affects the longitudinal dispersion process. The observed velocity distributions over the depth of sediment-laden flows indicate that the velocity deviates from the mean velocity more in sediment-laden flows than in clear-water flows. The velocity distributions over the cross section and secondary flow in the channel are also expected to be altered due to the presence of suspended sediments in the flow. For these reasons, more dispersion is found in sediment-laden flows than in corresponding clear-water flows. A predictor for the dispersion coefficient in sediment-laden flows is proposed.

  4. A-jump in horizontal inverted semicircular open channels

    Directory of Open Access Journals (Sweden)

    I.M.H. Rashwan

    2013-12-01

    Full Text Available The hydraulic jump is a transitional state from supercritical to subcritical flow. The phenomenon of the hydraulic jump has been widely studied because of its frequent occurrence in nature and because of its uses in many practical applications. In the present study the momentum principle is used to derive an equation expressed the hydraulic jump (A-jump occurred in a short horizontal reach of an inverted semicircular open channel. The derived equation indicates that the initial water depth and the tail water depth (conjugate depths are functions of the critical water depth. Various elements of the hydraulic jump are expressed in dimensionless case. The procedure of dimensionless ratios described in the present paper can be used to determine various elements of A-jump in an inverted semicircular channel when either the discharge and the relative initial depth (or tail water depth is known or the discharge and the relative dissipated energy are known.

  5. Acetylcholine receptor: channel-opening kinetics evaluated by rapid chemical kinetic and single-channel current measurements.

    Science.gov (United States)

    Udgaonkar, J. B.; Hess, G. P.

    1987-01-01

    A combination of rapid chemical kinetic (quench-flow) and single-channel current measurements was used to evaluate kinetic parameters governing the opening of acetylcholine-receptor channels in the electric organ (electroplax) of Electrophorus electricus. Chemical kinetic measurements made on membrane vesicles, prepared from the E. electricus electroplax, using carbamoylcholine (200 microM-20 mM) at 12 degrees C, pH 7.0, and in the absence of a transmembrane voltage, yielded values for K1 (dissociation constant for receptor activation), phi (channel closing equilibrium constant), J (specific reaction rate for ion flux), and alpha max (maximum inactivation rate constant) of 1 mM, 3.4, 4 x 10(7) M-1 s-1, and 12 s-1, respectively. The single-channel current recordings were made with cells also from the E. electricus electroplax, at the same temperature and pH as the chemical kinetic measurements, using carbamoylcholine (50 microM-2 mM), acetylcholine (500 nM), or suberyldicholine (20 nM). Single-channel current measurements indicated the presence of a single, unique open-channel state of the E. electricus receptor, in concurrence with previous, less extensive measurements. The rate constant for channel closing (kc) obtained from the mean open time of the receptor channel is 1,100 s-1 for carbamoylcholine, 1,200 s-1 for acetylcholine, and 360 s-1 for suberyldicholine at zero membrane potential; and it decreases e-fold for an 80 mV decrease in transmembrane voltage in each case. The decrease in mean open times of the receptor channel that is associated with increasing the carbamoylcholine concentration is interpreted to be due to carbamoylcholine binding to the regulatory (inhibitory) site on the receptor. An analysis of data obtained with carbamoylcholine showed that the closed times within a burst of channel activity fit a two-exponential distribution, with a concentration-independent time constant considered to be the time constant for carbamoylcholine to dissociate

  6. Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

    Science.gov (United States)

    Bennion, David H.; Roseman, Edward F.; Holbrook, Christopher M.; Boase, James C.; Chiotti, Justin A.; Thomas, Michael V.; Wills, Todd C.; Drouin, Richard G.; Kessel, Steven T.; Krueger, Charles C.

    2017-01-01

    Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for

  7. A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME Study

    Directory of Open Access Journals (Sweden)

    Mitsunori Sugiyama

    2010-01-01

    Full Text Available Background: Morning blood pressure (BP surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS-restoring Ca-channel blocker (CCB azelnidipine (AZ on this age-related morning BP increase. Methods: We conducted a 16-week prospective study to clarify the effect of morning dosing of AZ on home BPs measured in the morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years; female, 53.6%. Results: At baseline, ME-Dif (morning systolic BP [SBP]–evening SBP increased with age, independently of ME-Ave (average of the morning and evening SBPs. This age-related increase of ME-Dif was exaggerated by regular alcohol drinking and beta-blocker use. After AZ treatment (14.3 ± 3.6 mg/day, ME-AV and ME-Dif were significantly reduced independently of each other, with reductions of –18.1 ± 15.6 and –2.5 ± 13.2 mmHg, respectively (both p < 0.001. AZ treatment decreased age-related increase in ME-Dif particularly in patients who were regular consumers of alcohol and in beta-blocker users. Conclusions: The new BRS-restoring CCB AZ significantly reduced age-related increase in morning BP and had some potential benefit on cardiovascular protection in hypertension, particularly in elderly patients and/or consumers of alcohol.

  8. Solute dispersion in open channel flow with bed absorption

    Science.gov (United States)

    Wang, Ping; Chen, G. Q.

    2016-12-01

    Reactive solute dispersion is of essential significance in various ecological and environmental applications. It is only qualitatively known that boundary absorption depletes pollutant around the boundary and reduces the concentration nearby. All the existing studies on this topic have been focused on the longitudinally distributed mean concentration, far from enough to fully characterize the transport process with tremendous cross-sectional concentration nonuniformity. This work presents an analytical study of the evolution of two-dimensional concentration distribution for solute dispersion in a laminar open channel flow with bed absorption. The fourth order Aris-Gill expansion proposed in our previous study (Wang and Chen, 2016b) is further extended for the case with bed absorption to cover the transitional effects of skewness and kurtosis. Results reveal the extremely nonuniform cross-sectional concentration distribution, and demonstrate that concentration at the bed instead of the mean should be used for reliable quantification of the absorption flux. The accurate two-dimensional concentration distribution presented in this study brings important environmental implications such as risk assessment associated with peak concentration position and duration of toxic pollutant cloud in open channel waters.

  9. Two dimensional velocity distribution in open channels using Renyi entropy

    Science.gov (United States)

    Kumbhakar, Manotosh; Ghoshal, Koeli

    2016-05-01

    In this study, the entropy concept is employed for describing the two-dimensional velocity distribution in an open channel. Using the principle of maximum entropy, the velocity distribution is derived by maximizing the Renyi entropy by assuming dimensionless velocity as a random variable. The derived velocity equation is capable of describing the variation of velocity along both the vertical and transverse directions with maximum velocity occurring on or below the water surface. The developed model of velocity distribution is tested with field and laboratory observations and is also compared with existing entropy-based velocity distributions. The present model has shown good agreement with the observed data and its prediction accuracy is comparable with the other existing models.

  10. Wall and Bed Shear Force in Rectangular Open Channels

    CERN Document Server

    Tavakkol, Sasan

    2016-01-01

    A method is introduced to determine the percentage of the total shear force acting on the walls and bed in rectangular open channels. The proposed method takes both the velocity gradients and secondary currents into account. In the current method the channel cross section is divided into subsections using the bisectors along which there are no secondary flow effects, and isovels orthogonal trajectories along which there is no shear stress. Based on these subsections and assuming the equilibrium between the shear force and gravitational force, the share of the bed and wall from the mean shear force of the flow are calculated. Calculated wall and bed shear forces are in very good agreement with experimental data with an average relative error less than 5%. It is also shown that neglecting the effect of secondary currents and only assuming zero-shear division lines does not yield to acceptable results. The method also provides a possible range for wall and bed shear forces which nicely covers the experimental da...

  11. STIM1 activates CRAC channels through rotation of the pore helix to open a hydrophobic gate

    Science.gov (United States)

    Yamashita, Megumi; Yeung, Priscilla S.-W.; Ing, Christopher E.; McNally, Beth A.; Pomès, Régis; Prakriya, Murali

    2017-02-01

    Store-operated Ca2+ release-activated Ca2+ (CRAC) channels constitute a major pathway for Ca2+ influx and mediate many essential signalling functions in animal cells, yet how they open remains elusive. Here, we investigate the gating mechanism of the human CRAC channel Orai1 by its activator, stromal interacting molecule 1 (STIM1). We find that two rings of pore-lining residues, V102 and F99, work together to form a hydrophobic gate. Mutations of these residues to polar amino acids produce channels with leaky gates that conduct ions in the resting state. STIM1-mediated channel activation occurs through rotation of the pore helix, which displaces the F99 residues away from the pore axis to increase pore hydration, allowing ions to flow through the V102-F99 hydrophobic band. Pore helix rotation by STIM1 also explains the dynamic coupling between CRAC channel gating and ion selectivity. This hydrophobic gating mechanism has implications for CRAC channel function, pharmacology and disease-causing mutations.

  12. Open-channel blockers of the NMDA receptor complex.

    Science.gov (United States)

    Albensi, Benedict C; Ilkanich, Erin

    2004-11-01

    A variety of compounds have been shown to limit or prevent excitotoxicity by blocking N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. However, many first-generation NMDA antagonists did not live up to clinical expectations in trials of acute brain injury because of the manifestation of multiple side effects. In spite of this, development of NMDA antagonists continues, where some of the newer agents block excitotoxicity through alternative mechanisms. For example, blockers selective to the NR2B subunit or agents that block metabotropic glutamate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are currently under investigation. Several years ago, the arylalkylamine spider toxins were demonstrated to function as open-channel blockers similar to memantine, which was very recently approved by the U.S. FDA for use in patients with Alzheimer's dementia. With this said, programs focusing on NMDA antagonism via alternative mechanisms may still hold promise for treating acute injury and even chronic forms of dementia.

  13. CURVED OPEN CHANNEL FLOW ON VEGETATION ROUGHENED INNER BANK

    Institute of Scientific and Technical Information of China (English)

    HUAI Wen-xin; LI Cheng-guang; ZENG Yu-hong; QIAN Zhong-dong; YANG Zhong-hua

    2012-01-01

    A RNG k-ε numerical model together with a laboratory measurement with Micro ADV are adopted to investigate the flow through a 180° curved open channel (a 4 m straight inflow section,a 180° curved section,and a 4m straight outflow section)partially covered with rigid vegetations on its inner bank.Under the combined action of the vegetation and the bend flow,the flow structure is complex.The stream-wise velocities in the vegetation region are much smaller than those in the non-vegetation region due to the retardation caused by the vegetation.For the same reason,no clear circulation is found in the vegetated region,while in the non-vegetation region,a slight counter-rotating circulation is found near the outer bank at both 90° and downstream curved cross-sections.A comparison between the numerical prediction and the laboratory measurement shows that the RNG k- model can well predict the flow structure of the bend flow with vegetation.Furthermore,the shear stress is analyzed based on the numerical prediction.The much smaller value in the inner vegetated region indicates that the vegetation can effectively protect the fiver bank from scouting and erosion,in other words,the sediment is more likely to be deposited in the vegetation region.

  14. Modeling algae growth in an open-channel raceway.

    Energy Technology Data Exchange (ETDEWEB)

    James, Scott Carlton

    2010-09-01

    Cost-effective implementation of microalgae as a solar-to-chemical energy conversion platform requires extensive system optimization; computer modeling can bring this to bear. This work uses modified versions of the U.S. Environmental Protection Agency's (EPA's) Environmental Fluid Dynamics Code (EFDC) in conjunction with the U.S. Army Corp of Engineers water-quality code (CE-QUAL) to simulate hydrodynamics coupled to growth kinetics of algae (Phaeodactylum tricornutum) in open-channel raceways. The model allows the flexibility to manipulate a host of variables associated with raceway-design, algal-growth, water-quality, hydrodynamic, and atmospheric conditions. The model provides realistic results wherein growth rates follow the diurnal fluctuation of solar irradiation and temperature. The greatest benefit that numerical simulation of the flow system offers is the ability to design the raceway before construction, saving considerable cost and time. Moreover, experiment operators can evaluate the impacts of various changes to system conditions (e.g., depth, temperature, flow speeds) without risking the algal biomass under study.

  15. Modeling algae growth in an open-channel raceway.

    Science.gov (United States)

    James, Scott C; Boriah, Varun

    2010-07-01

    Cost-effective implementation of microalgae as a solar-to-chemical energy conversion platform requires extensive system optimization; computer modeling can bring this to bear. This work uses modified versions of the U.S. Environmental Protection Agency's (EPA's) Environmental Fluid Dynamics Code (EFDC) in conjunction with the U.S. Army Corp of Engineers' water-quality code (CE-QUAL) to simulate hydrodynamics coupled to growth kinetics of algae (Phaeodactylum tricornutum) in open-channel raceways. The model allows the flexibility to manipulate a host of variables associated with raceway-design, algal-growth, water-quality, hydrodynamic, and atmospheric conditions. The model provides realistic results wherein growth rates follow the diurnal fluctuation of solar irradiation and temperature. The greatest benefit that numerical simulation of the flow system offers is the ability to design the raceway before construction, saving considerable cost and time. Moreover, experiment operators can evaluate the impacts of various changes to system conditions (e.g., depth, temperature, flow speeds) without risking the algal biomass under study.

  16. Langevin approach for stochastic Hodgkin-Huxley dynamics with discretization of channel open fraction

    Science.gov (United States)

    Huang, Yandong; Rüdiger, Sten; Shuai, Jianwei

    2013-12-01

    The random opening and closing of ion channels establishes channel noise, which can be approximated and included into stochastic differential equations (Langevin approach). The Langevin approach is often incorporated to model stochastic ion channel dynamics for systems with a large number of channels. Here, we introduce a discretization procedure of a channel-based Langevin approach to simulate the stochastic channel dynamics with small and intermediate numbers of channels. We show that our Langevin approach with discrete channel open fractions can give a good approximation of the original Markov dynamics even for only 10 K channels. We suggest that the better approximation by the discretized Langevin approach originates from the improved representation of events that trigger action potentials.

  17. Langevin approach for stochastic Hodgkin–Huxley dynamics with discretization of channel open fraction

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yandong [Department of Physics and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen 361005 (China); Rüdiger, Sten [Institute of Physics, Humboldt-Universität zu Berlin (Germany); Shuai, Jianwei, E-mail: jianweishuai@xmu.edu.cn [Department of Physics and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen 361005 (China)

    2013-12-13

    The random opening and closing of ion channels establishes channel noise, which can be approximated and included into stochastic differential equations (Langevin approach). The Langevin approach is often incorporated to model stochastic ion channel dynamics for systems with a large number of channels. Here, we introduce a discretization procedure of a channel-based Langevin approach to simulate the stochastic channel dynamics with small and intermediate numbers of channels. We show that our Langevin approach with discrete channel open fractions can give a good approximation of the original Markov dynamics even for only 10 K{sup +} channels. We suggest that the better approximation by the discretized Langevin approach originates from the improved representation of events that trigger action potentials.

  18. KR-31762, a novel KATP channel opener, exerts cardioprotective effects by opening SarcKATP channels in rat models of ischemia/reperfusion-induced heart injury.

    Science.gov (United States)

    Lee, Sung-Hun; Yang, Min-Kyu; Lim, Jong-Hyun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Won, Hyung-Sik; Lee, Chang-Soo; Choi, Wahn-Soo; Shin, Hwa-Sup

    2008-04-01

    The cardioprotective effects of KR-31762, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, KR-31762 (3 and 10 microM) significantly increased the left ventricular developed pressure (LVDP) and double product (heart rate x LVDP) after 30-min reperfusion in a concentration-dependent manner, while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31762 also significantly increased the time to contracture (TTC) during ischemic period (20.0, 22.4 and 26.4 min for control, 3 and 10 microM, respectively), while decreasing the release of lactate dehydrogenase (LDH) from the heart during 30 min reperfusion (30.4, 14.3 and 19.7 U/g heart weight, respectively). All these parameters except LDH release were reversed by glyburide (1 microM), a nonselective blocker of K+(ATP) channel, but not by 5-hydroxydecanoate, a selective blocker of mitoK+(ATP) channel. In anesthetized rats subjected to 45-min occlusion of left anterior descending coronary artery followed by 90-min reperfusion, KR-31762 significantly decreased the infarct size (60.8, 40.5 and 37.8% for control, 0.3 and 1.0 mg/kg, iv, respectively). KR-31762 slightly relaxed the isolated rat aorta precontracted with methoxamine (IC(50): 23.5 microM). These results suggest that KR-31762 exerts potent cardioprotective effects through the opening of sarcolemmal K(ATP) channel in rat hearts with the minimal vasorelaxant effects.

  19. Conformational change opening the CFTR chloride channel pore coupled to ATP-dependent gating.

    Science.gov (United States)

    Wang, Wuyang; Linsdell, Paul

    2012-03-01

    Opening and closing of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel are controlled by ATP binding and hydrolysis by its nucleotide binding domains (NBDs). This is presumed to control opening of a single "gate" within the permeation pathway, however, the location of such a gate has not been described. We used patch clamp recording to monitor access of cytosolic cysteine reactive reagents to cysteines introduced into different transmembrane (TM) regions in a cysteine-less form of CFTR. The rate of modification of Q98C (TM1) and I344C (TM6) by both [2-sulfonatoethyl] methanethiosulfonate (MTSES) and permeant Au(CN)(2)(-) ions was reduced when ATP concentration was reduced from 1mM to 10μM, and modification by MTSES was accelerated when 2mM pyrophosphate was applied to prevent channel closure. Modification of K95C (TM1) and V345C (TM6) was not affected by these manoeuvres. We also manipulated gating by introducing the mutations K464A (in NBD1) and E1371Q (in NBD2). The rate of modification of Q98C and I344C by both MTSES and Au(CN)(2)(-) was decreased by K464A and increased by E1371Q, whereas modification of K95C and V345C was not affected. These results suggest that access from the cytoplasm to K95 and V345 is similar in open and closed channels. In contrast, modifying ATP-dependent channel gating alters access to Q98 and I344, located further into the pore. We propose that ATP-dependent gating of CFTR is associated with the opening and closing of a gate within the permeation pathway at the level of these pore-lining amino acids.

  20. Phentolamine precludes inhibitory effect of the K+ channel opener pinacidil on insulin release

    NARCIS (Netherlands)

    Links, TP; Smitz, AJ; vanHaeften, TW

    1996-01-01

    The K+ channel opener pinacidil, in clinical use as an antihypertensive agent, acts by opening ATP-sensitive K+ channels in striated and smooth muscle cells. In vitro and in vivo studies have suggested that it also diminishes insulin secretion. Insulin secretion can be influenced directly - by actin

  1. Entanglement can increase asymptotic rates of zero-error classical communication over classical channels

    CERN Document Server

    Leung, Debbie; Matthews, William; Ozols, Maris; Roy, Aidan

    2010-01-01

    It is known that the number of different classical messages which can be communicated with a single use of a classical channel with zero probability of decoding error can sometimes be increased by using entanglement shared between sender and receiver. It has been an open question to determine whether entanglement can ever offer an advantage in terms of the zero-error communication rates achievable in the limit of many channel uses. In this paper we show, by explicit examples, that entanglement can indeed increase asymptotic zero-error capacity. Interestingly, in our examples the quantum protocols are based on the root systems of the exceptional Lie groups E7 and E8.

  2. Neuroprotective effects of a mitochondrial K+-ATP channel opener (diazoxide) are mediated by Bcl-2 expression upregulation

    Institute of Scientific and Technical Information of China (English)

    Majid Katebi; Mansooreh Soleimani; Mehdi Mehdizadeh

    2011-01-01

    Mitochondrial K+-ATP (mito-KATP) channels play an important role in cellular function and survival following ischemic stress. The present results revealed that intervention with diazoxide, a mito-KATP channel opener, led to an increase in Bcl-2 expression in the cerebral cortex of rats subjected to cerebral ischemia reperfusion injury. In addition, the intervention also led to clear improvements in neuronal mitochondrial morphology and consciousness post-injury. Glibenclamide, a mito-KATP channel blocker, exhibited the converse effects. Both diazoxide and glibenclamide exerted dose-dependent effects (in particular, at 18 mg/kg diazoxide and 25 mg/kg glibenclamide). These findings suggest that diazoxide exerts a neuroprotective effect on cerebral ischemia reperfusion injury by opening mito-KATP channels and upregulating Bcl-2 expression.

  3. Adaptation Independent Modulation of Auditory Hair Cell Mechanotransduction Channel Open Probability Implicates a Role for the Lipid Bilayer.

    Science.gov (United States)

    Peng, Anthony W; Gnanasambandam, Radhakrishnan; Sachs, Frederick; Ricci, Anthony J

    2016-03-09

    The auditory system is able to detect movement down to atomic dimensions. This sensitivity comes in part from mechanisms associated with gating of hair cell mechanoelectric transduction (MET) channels. MET channels, located at the tops of stereocilia, are poised to detect tension induced by hair bundle deflection. Hair bundle deflection generates a force by pulling on tip-link proteins connecting adjacent stereocilia. The resting open probability (P(open)) of MET channels determines the linearity and sensitivity to mechanical stimulation. Classically, P(open) is regulated by a calcium-sensitive adaptation mechanism in which lowering extracellular calcium or depolarization increases P(open). Recent data demonstrated that the fast component of adaptation is independent of both calcium and voltage, thus requiring an alternative explanation for the sensitivity of P(open) to calcium and voltage. Using rat auditory hair cells, we characterize a mechanism, separate from fast adaptation, whereby divalent ions interacting with the local lipid environment modulate resting P(open). The specificity of this effect for different divalent ions suggests binding sites that are not an EF-hand or calmodulin model. GsMTx4, a lipid-mediated modifier of cationic stretch-activated channels, eliminated the voltage and divalent sensitivity with minimal effects on adaptation. We hypothesize that the dual mechanisms (lipid modulation and adaptation) extend the dynamic range of the system while maintaining adaptation kinetics at their maximal rates.

  4. A model for open-close control of cation channels in the plasma membrane of retinal rod outer segments.

    Science.gov (United States)

    Ichikawa, K

    1989-06-01

    A model for open-close control of cation channels in the plasma membrane of retinal rod outer segments is presented. A channel is assumed to open when 3 cGMP molecules bind to it and close as soon as one of the 3 cGMP molecules is released from it. The calcium ion (divalent cation) is a modulator of the channel conductance. The channel conductance is low when Ca2+ binds to it, while it is high when it is free from Ca2+. From the above assumptions, the reaction scheme of channels with cGMP and Ca2+ is created and the fraction of channels in the open and closed states was calculated using equations for this scheme. The kinetic constants used in the model are estimated from the experimental results of many studies and from the theories. From this estimation, it was found that at the physiological concentrations of intracellular and extracellular Ca2+, almost all channels are bound with Ca2+ and are in the low conductance state. The present model accounts for the reported dose(cGMP)-response(membrane current or conductance) relationship, where the Hill coefficient decreases as the cGMP concentration increases. The dark-level cGMP concentration of 8.13 microM is estimated from the model. This is in good agreement with the reported values. Moreover, the model predicts the invariance of current noise at relatively low Ca2+ concentrations when the cGMP concentration is raised from the dark level to a saturation level. The dynamic properties (opening and closing actions) of the channels in the present model are also in good agreement with the reported observations. The burst mode opening and closing of a channel is predicted by the present model, and it was found that the number of openings in a burst is controlled by the forward and backward rate constants between a channel protein and cGMP molecules. The simulated waveform of a single channel is similar to the reported observations.

  5. Development of New Openers of ATP-Sensitive Potassium Channels of the Cell Membranes

    Directory of Open Access Journals (Sweden)

    Strutynskyi, R.B.

    2016-07-01

    Full Text Available Two innovative libraries (413 cyclosulfamides and 709 orthopyridine sulfamides of potential new openers of ATP-sensitive potassium channels of cell membranes were developed. It is shown experimentally that at least ten new original compounds have properties of pharmacological openers of the channels. Seven compounds, namely Z851154982, Z56762024, Z1269122570, Z31153162, Z45679561, Z756371174 and Z649723638, open channels of both types — sarcoplasmic as well as mitochondrial membranes: Simultaneously, Z734043408 compound is a potent activator of aforementioned channels of sarcolemmal membrane only. Z31197374 and Z666664306 compounds show the affinity onlyto КATP-channels of mitochondrial type. The results of the work can be used by pharmaceutical companies and scientific research institutes.

  6. Full Open Access Journals Have Increased Impact Factors

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2009-06-01

    Full Text Available We are pleased to report the increase of the impact factors of MDPI journals during 2007 and 2008. In 2005 and part of 2006, the use of a two tier publication system, whereby we offered full Open Access publication to those authors willing to contribute financially to support this option, while providing the alternative choice of free publication without Open Access for those authors who preferred not to pay, resulted in the obviously decreased impact factors seen in 2006 [...

  7. The coefficientof hydraulic friction of laminar open flows in smooth channels

    OpenAIRE

    Borovkov Valeriy Stepanovich; Medzveliya Manana Levanovna

    2015-01-01

    The article examines the dependence of the hydraulic friction coefficient of open laminar uniform streams on the relative width of channels with smooth bottom. The article presents the functional dependence that describes the hydraulic resistance in open channels with smooth bottoms.The experiments were carried out in a rectangular tray (6000×100×200). Aqueous solutions of glycerol were used as working fluids. The superficial tension and liquid density for the used liquids changed a little. T...

  8. Exclusive open-charm near-threshold cross sections in a coupled-channel approach

    CERN Document Server

    Uglov, T V; Nefediev, A V; Pakhlova, G V; Pakhlov, P N

    2016-01-01

    Data on open-charm channels collected by the Belle Collaboration are analysed simultaneously using a unitary approach based on a coupled-channel model in a wide energy range $\\sqrt{s}=3.7\\div 4.7$ GeV. The resulting fit provides a remarkably good overall description of the line shapes in all studied channels. Parameters of 5 vector charmonium resonances are extracted from the fit.

  9. Conformational changes opening and closing the CFTR chloride channel: insights from cysteine scanning mutagenesis.

    Science.gov (United States)

    El Hiani, Yassine; Linsdell, Paul

    2014-12-01

    Cystic fibrosis, the most common lethal genetic disease affecting young people in North America, is caused by failure of the chloride ion channel known as CFTR (cystic fibrosis transmembrane conductance regulator). CFTR belongs to the large family of ATP-binding cassette (ABC) membrane transporters. In CFTR, ATP-driven events at the nucleotide-binding domains (NBDs) open and close a gate that controls chloride permeation. However, the conformational changes concomitant with opening and closing of the CFTR gate are unknown. Diverse techniques including substituted cysteine accessibility method, disulfide cross-linking, and patch-clamp recording have been used to explore CFTR channel structure. Here, we consider the architecture of both the open and the closed CFTR channel. We review how CFTR channel structure changes between the closed and the open channel conformations and portray the relative function of both cytoplasmic and vestigial gates during the gating cycle. Understanding how the CFTR channel gates chloride permeation is central for understanding how CFTR defects lead to CF. Such knowledge opens the door for novel ways to maximize CFTR channel activity in a CF setting.

  10. FLOW STRUCTURE OF PARTLY VEGETATED OPEN-CHANNEL FLOWS WITH EELGRASS

    Institute of Scientific and Technical Information of China (English)

    WANG Chao; YU Ji-yu; WANG Pei-fang; GUO Peng-cheng

    2009-01-01

    Aquatic vegetation can influence the transport of sediment and contaminants by changing the mean velocity and turbulent flow structure in channels. It is important to understand the hydraulics of the flows over vegetation in order to manage fluvial processes. Experiments in an open-channel flume with natural vegetation were carried out to study the influence of vegetation on the flows. In a half channel with two different densities of vegetation, the flow velocity, Reynolds stresses, and turbulence intensities were measured using an Acoustic Doppler Velocimeter (ADV). We obtained velocity profiles in the lateral direction, Reynolds stresses in the vertical direction, and the flow transition between the vegetated and non-vegetated zones in different flow regimes. The results show that the streamwise velocity in the vegetated zone with higher density is almost entirely blocked. Reynolds stress distribution distinguishes with two different regions: inside and above the vegetation canopies. The turbulence intensities increase with increasing Reynolds number. The coherent vortices dominate the vertical transport of momentum and are advected clockwise between the vegetated zone and non-vegetated zone by secondary currents (a relatively minor flow superimposed on the primary flow, with significantly different speed and direction), generated by the anisotropy of the turbulence.

  11. Temperature and voltage coupling to channel opening in transient receptor potential melastatin 8 (TRPM8).

    Science.gov (United States)

    Raddatz, Natalia; Castillo, Juan P; Gonzalez, Carlos; Alvarez, Osvaldo; Latorre, Ramon

    2014-12-19

    Expressed in somatosensory neurons of the dorsal root and trigeminal ganglion, the transient receptor potential melastatin 8 (TRPM8) channel is a Ca(2+)-permeable cation channel activated by cold, voltage, phosphatidylinositol 4,5-bisphosphate, and menthol. Although TRPM8 channel gating has been characterized at the single channel and macroscopic current levels, there is currently no consensus regarding the extent to which temperature and voltage sensors couple to the conduction gate. In this study, we extended the range of voltages where TRPM8-induced ionic currents were measured and made careful measurements of the maximum open probability the channel can attain at different temperatures by means of fluctuation analysis. The first direct measurements of TRPM8 channel temperature-driven conformational rearrangements provided here suggest that temperature alone is able to open the channel and that the opening reaction is voltage-independent. Voltage is a partial activator of TRPM8 channels, because absolute open probability values measured with fully activated voltage sensors are less than 1, and they decrease as temperature rises. By unveiling the fast temperature-dependent deactivation process, we show that TRPM8 channel deactivation is well described by a double exponential time course. The fast and slow deactivation processes are temperature-dependent with enthalpy changes of 27.2 and 30.8 kcal mol(-1). The overall Q10 for the closing reaction is about 33. A three-tiered allosteric model containing four voltage sensors and four temperature sensors can account for the complex deactivation kinetics and coupling between voltage and temperature sensor activation and channel opening.

  12. Flow and bathymetry in sharp open-channel bends: Experiments and predictions

    NARCIS (Netherlands)

    Zeng, J.; Constantinescu, G.; Blanckaert, K.; Weber, L.

    2008-01-01

    This paper focuses on experiments and simulations conducted in very sharp open-channel bends with flat and equilibrium bathymetry, corresponding to the initial and final phases of the erosion and deposition processes, respectively. The study of flow in curved open bends is relevant for flow in natur

  13. Increased functional connectivity within mesocortical networks in open people.

    Science.gov (United States)

    Passamonti, L; Terracciano, A; Riccelli, R; Donzuso, G; Cerasa, A; Vaccaro, Mg; Novellino, F; Fera, F; Quattrone, A

    2015-01-01

    Openness is a personality trait reflecting absorption in sensory experience, preference for novelty, and creativity, and is thus considered a driving force of human evolution. At the brain level, a relation between openness and dopaminergic circuits has been proposed, although evidence to support this hypothesis is lacking. Recent behavioral research has also found that people with mania, a psychopathological condition linked to dopaminergic dysfunctions, may display high levels of openness. However, whether openness is related to dopaminergic circuits has not been determined thus far. We addressed this issue via three functional magnetic resonance imaging (fMRI) experiments in n=46 healthy volunteers. In the first experiment participants lied at rest in the scanner while in the other two experiments they performed active tasks that included the presentation of pleasant odors and pictures of food. Individual differences in openness and other personality traits were assessed via the NEO-PI-R questionnaire (NEO-Personality Inventory-Revised), a widely employed measure of the five-factor model personality traits. Correlation between fMRI and personality data was analyzed via state-of-art methods assessing resting-state and task-related functional connectivity within specific brain networks. Openness was positively associated with the functional connectivity between the right substantia nigra/ventral tegmental area, the major source of dopaminergic inputs in the brain, and the ipsilateral dorsolateral prefrontal cortex (DLPFC), a key region in encoding, maintaining, and updating information that is relevant for adaptive behaviors. Of note, the same connectivity pattern was consistently found across all of the three fMRI experiments. Given the critical role of dopaminergic signal in gating information in DLPFC, the increased functional connectivity within mesocortical networks in open people may explain why these individuals display a wide "mental permeability" to

  14. Lidocaine stabilizes the open state of CNS voltage-dependent sodium channels.

    Science.gov (United States)

    Castañeda-Castellanos, David R; Nikonorov, Igor; Kallen, Roland G; Recio-Pinto, E

    2002-03-28

    We have previously reported that the lidocaine action is different between CNS and muscle batrachotoxin-modified Na+ channels [Salazar et al., J. Gen. Physiol. 107 (1996) 743-754; Brain Res. 699 (1995) 305-314]. In this study we examined lidocaine action on CNS Na+ currents, to investigate the mechanism of lidocaine action on this channel isoform and to compare it with that proposed for muscle Na+ currents. Na+ currents were measured with the whole cell voltage clamp configuration in stably transfected cells expressing the brain alpha-subunit (type IIA) by itself (alpha-brain) or together with the brain beta(1)-subunit (alphabeta(1)-brain), or the cardiac alpha-subunit (hH1) (alpha-cardiac). Lidocaine (100 microM) produced comparable levels of Na+ current block at positive potentials and of hyperpolarizing shift of the steady-state inactivation curve in alpha-brain and alphabeta(1)-brain Na+ currents. Lidocaine accelerated the rates of activation and inactivation, produced an hyperpolarizing shift in the steady-state activation curve and increased the current magnitude at negative potentials in alpha-brain but not in alphabeta(1)-brain Na+ currents. The lidocaine action in alphabeta(1)-brain resembled that observed in alpha-cardiac Na+ currents. The lidocaine-induced increase in current magnitude at negative potentials and the hyperpolarizing shift in the steady-state activation curve of alpha-brain, are novel effects and suggest that lidocaine treatment does not always lead to current reduction/block when it interacts with Na+ channels. The data are explained by using a modified version of the model proposed by Vedantham and Cannon [J. Gen. Physiol., 113 (1999) 7-16] in which we postulate that the difference in lidocaine action between alpha-brain and alphabeta(1)-brain Na+ currents could be explained by differences in the lidocaine action on the open channel state.

  15. Increased migration of monocytes in essential hypertension is associated with increased transient receptor potential channel canonical type 3 channels

    DEFF Research Database (Denmark)

    Zhao, Zhigang; Ni, Yinxing; Chen, Jing

    2012-01-01

    Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performed...... of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246 ± 14% vs 151 ± 10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also significantly increased...... compared to normotensive control subjects (221 ± 20% vs 138 ± 18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from hypertensive patients...

  16. Neuroprotective effect of KR-31378 via KATP channel opening against ischemic insult.

    Science.gov (United States)

    Won, Ran; Lim, Jong-Yoon; Lee, Sang-Yeon; Park, Ji-Ho; Sohn, Nak-Won

    2004-08-01

    The opening of the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel has been proposed as a therapeutic approach for ischemia. Here we examined the opening effect of KR-31378 on the KATP channel using patch clamp recording in neuroblastoma 2a (N2a) cells and investigated the neuroprotective effect of KR-31378 in organotypic hippocampal slice cultures exposed to oxygen/glucose deprivation. The treatment with KR-31378 (10 microM) to N2a cells seemed to induce KATP channel opening in a dose dependent manner. The opening effect of KR-31378 was more significant than that of other known KATP channel openers. Pretreatment with KR-31378 (10 microM) showed a neuroprotective effect in both CA1 and CA3 regions and its effect was attenuated by glibenclamide in a dose dependent manner in both areas. This remarkable neuroprotective effect of KR-31378 seemed to be mediated by the opening of the KATP channel. These results suggest that KR-31378 could be a possible neuroprotective agent against cerebral ischemia.

  17. Open channel block of Kv3.1 currents by fluoxetine.

    Science.gov (United States)

    Sung, Min Ji; Ahn, Hye Sook; Hahn, Sang June; Choi, Bok Hee

    2008-01-01

    The action of fluoxetine, a serotonin reuptake inhibitor, on the cloned neuronal rat Kv3.1 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Fluoxetine reduced Kv3.1 whole-cell currents in a reversible, concentration-dependent manner, with an IC(50) value and a Hill coefficient of 13.4 muM and 1.4, respectively. Fluoxetine accelerated the decay rate of inactivation of Kv3.1 currents without modifying the kinetics of current activation. The inhibition increased steeply between 0 and +30 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +30 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.38. The binding (k(+1)) and dissociation (k(-1)) rate constants for fluoxetine-induced block of Kv3.1 were 5.7 microM(-1)s(-1) and 53.5 s(-1), respectively. The theoretical K(D) value derived by k(-1)/k(+1) yielded 9.3 microM. Fluoxetine did not affect the ion selectivity of Kv3.1. Fluoxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of fluoxetine, were superimposed. Inhibition of Kv3.1 by fluoxetine was use-dependent. The present results suggest that fluoxetine acts on Kv3.1 currents as an open-channel blocker.

  18. Measurement of turbulent flow in a narrow open channel

    Directory of Open Access Journals (Sweden)

    Sarkar Sankar

    2016-09-01

    Full Text Available The paper presents the experimental results of turbulent flow over hydraulically smooth and rough beds. Experiments were conducted in a rectangular flume under the aspect ratio b/h = 2 (b = width of the channel 0.5 m, and h = flow depth 0.25 m for both the bed conditions. For the hydraulically rough bed, the roughness was created by using 3/8″ commercially available angular crushed stone chips; whereas sand of a median diameter d50 = 1.9 mm was used as the bed material for hydraulically smooth bed. The three-dimensional velocity components were captured by using a Vectrino (an acoustic Doppler velocimeter. The study focuses mainly on the turbulent characteristics within the dip that were observed towards the sidewall (corner of the channel where the maximum velocity occurs below the free-surface. It was also observed that the nondimensional Reynolds shear stress changes its sign from positive to negative within the dip. The quadrant plots for the turbulent bursting shows that the signs of all the bursting events change within the dip. Below the dip, the probability of the occurrence of sweeps and ejections are more than that of inward and outward interactions. On the other hand, within the dip, the probability of the occurrence of the outward and inward interactions is more than that of sweeps and ejections.

  19. Roscovitine differentially affects CaV2 and Kv channels by binding to the open state.

    Science.gov (United States)

    Buraei, Zafir; Schofield, Geoffrey; Elmslie, Keith S

    2007-03-01

    Roscovitine potently inhibits cyclin-dependent kinases (CDK) and can independently slow the closing of neuronal (CaV2.2) calcium channels. We were interested if this drug could affect other ion channels similarly. Using whole cell recordings, we found that roscovitine specifically slows deactivation of all CaV2 channels (N, P/Q and R) by binding to the open state. This effect had a rapid onset and EC(50)=54, 120 and 54microM for N-, P/Q-, and R-type channels, respectively. Deactivation of other channel types was not slowed, including L-type calcium channels (CaV1.2, CaV1.3), potassium channels (native, Kv4.2, Kv2.1 and Kv1.3), and native sodium channels. However, most of the channels tested were inhibited by roscovitine. The inhibition was characterized by slow development and a lower affinity (EC(50)=100-300microM). Surprisingly, potassium channels were rapidly inhibited with an EC(50)=23microM, which is similar to the EC(50) for roscovitine block of cell division [Meijer, L., Borgne, A., Mulner, O., Chong, J., Blow, J., Inagaki, N., Inagaki, M., Delcros, J., Moulinoux, J., 1997. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem. 243, 527-536]. Potassium current inhibition seemed to result from open channel block. The high potency of these two rapid onset effects makes them complicating factors for ongoing clinical trials and research using roscovitine. Thus, the physiology and pharmacology of slow CaV2 deactivation and potassium channel block must be explored.

  20. Stability characteristics of the open channel flow above the asymmetrical irregular sand ripples

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Sandy bed cannot keep its original smoothness as the flows pass. With the increase of the flow intensity, the bed forms will appear as sand ripples and dune in turn. Among these morphologies, the sand ripple scale is the smallest, which is generally symmetrical when it just appears, but as time goes on, the asymmetrical form gradually develops. Just because of this sand ripples asymmetry, it manifests the influence of the flow on the bed morphology and also the impact on the laminar flow dynamical process, especially the stability characteristics. The stability features of laminar flow on open channels with the asymmetrical sand ripples are discussed, and also the results on the symmetrical sand ripples are compared in detail.

  1. Numerical simulation of turbulent flow in helically coiled open-channels with compound cross-sections

    Institute of Scientific and Technical Information of China (English)

    SHAO; Xuejun; WANG; Hong; CHEN; Zhi

    2004-01-01

    Turbulence structure in a helically coiled open channel flow is numerically simulated using three different turbulence models--the Launder and Ying model, the Naot and Rodi model, and the nonlinear k-ε Model (SY model). Simulation results were compared with observation of (i) turbulent flows in alternating point-bar type channel bends with rectangular sections, and (ii) straight open channel flows with compound cross-sections. Based on calculations of the impact of various channel curvatures on turbulence characteristics, accuracy of the three turbulence models was analyzed with observed data as a qualitative reference. It has been found out that the Launder and Ying model and the nonlinear k-ε Model are able to predict the same general trend as measured data, and the simulation of the effect of the centrifugal force on the formation of secondary currents produces a correct pattern.

  2. Solving non-Markovian open quantum systems with multi-channel reservoir coupling

    CERN Document Server

    Broadbent, Curtis J; Yu, Ting; Eberly, Joseph H

    2011-01-01

    We extend the non-Markovian quantum state diffusion (QSD) equation to open quantum systems which exhibit multi-channel coupling to a harmonic oscillator reservoir. Open quantum systems which have multi-channel reservoir coupling are those in which canonical transformation of reservoir modes cannot reduce the number of reservoir operators appearing in the interaction Hamiltonian to one. We show that the non-Markovian QSD equation for multi-channel reservoir coupling can, in some cases, lead to an exact master equation which we derive. We then derive the exact master equation for the three-level system in a vee-type configuration which has multi-channel reservoir coupling and give the analytical solution. Finally, we examine the evolution of the three-level vee-type system with generalized Ornstein-Uhlenbeck reservoir correlations numerically.

  3. Solving non-Markovian open quantum systems with multi-channel reservoir coupling

    Science.gov (United States)

    Broadbent, Curtis J.; Jing, Jun; Yu, Ting; Eberly, Joseph H.

    2012-08-01

    We extend the non-Markovian quantum state diffusion (QSD) equation to open quantum systems which exhibit multi-channel coupling to a harmonic oscillator reservoir. Open quantum systems which have multi-channel reservoir coupling are those in which canonical transformation of reservoir modes cannot reduce the number of reservoir operators appearing in the interaction Hamiltonian to one. We show that the non-Markovian QSD equation for multi-channel reservoir coupling can, in some cases, lead to an exact master equation which we derive. We then derive the exact master equation for the three-level system in a vee-type configuration which has multi-channel reservoir coupling and give the analytical solution. Finally, we examine the evolution of the three-level vee-type system with generalized Ornstein-Uhlenbeck reservoir correlations numerically.

  4. Nitric oxide suppresses stomatal opening by inhibiting inward-rectifying Kin channels in Arabidopsis guard cells

    Institute of Scientific and Technical Information of China (English)

    XUE ShaoWu; YANG Pin; HE YiKun

    2008-01-01

    We explore nitric oxide (NO) effect on K+in channels in Arabidopsis guard cells. We observed NO inhib-ited K+in currents when Ca2+ chelator EGTA (Ethylene glycol-bis(2-aminoethylether)-N,N,N',N'tetraacetic acid) was not added in the pipette solution; K+in currents were not sensitive to NO when cytosolic Ca2+ was chelated by EGTA. NO inhibited the Arabidopsis stomatal opening, but when EGTA was added in the bath solution, inhibition effect of NO on stomatal opening vanished. Thus, it implies that NO ele-vates cytosolic Ca2+ by activating plasma membrane Ca2+ channels firstly, then inactivates K+in chan-nels, resulting in stomatal opening suppressed subsequently.

  5. A MODIFIED SIMPLE ALGORITHM FOR 2-D FLOW IN OPEN CHANNEL

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    For two-dimensional water flow in open channel, by discritizing hydrodynamic differential equation of conservative form, the corresponding algebraic equations were derived which involve the relationship between velocity and depth. Based on the relationship, this paper deduced a modified formula of velocity correction for SIMPLE algorithm. As a test case, the flow in a prismatic channel with two different slopes was computed and a good result was obtained.

  6. Experimental studies of vertical mixing patterns in open channel flow generated by two delta wings side-by-side

    Science.gov (United States)

    Vaughan, Garrett

    Open channel raceway bioreactors are a low-cost system used to grow algae for biofuel production. Microalgae have many promises when it comes to renewable energy applications, but many economic hurdles must be overcome to achieve an economic fuel source that is competitive with petroleum-based fuels. One way to make algae more competitive is to improve vertical mixing in algae raceway bioreactors. Previous studies show that mixing may be increased by the addition of mechanisms such as airfoils. The circulation created helps move the algae from the bottom to top surface for necessary photosynthetic exchange. This improvement in light utilization allowed a certain study to achieve 2.2-2.4 times the amount of biomass relative to bioreactors without airfoils. This idea of increasing mixing in open channel raceways has been the focus of the Utah State University (USU) raceway hydraulics group. Computational Fluid Dynamics (CFD), Acoustic Doppler Velocimetry (ADV), and Particle Image Velocimetry (PIV) are all methods used at USU to computationally and experimentally quantify mixing in an open channel raceway. They have also been used to observe the effects of using delta wings (DW) in increasing vertical mixing in the raceway. These efforts showed great potential in the DW in increasing vertical mixing in the open channel bioreactor. However, this research begged the question, does the DW help increase algae growth? Three algae growth experiments comparing growth in a raceway with and without DW were completed. These experiments were successful, yielding an average 27.1% increase in the biomass. The DW appears to be a promising method of increasing algae biomass production. The next important step was to quantify vertical mixing and understand flow patterns due to two DWs side-by-side. Raceway channels are wider as they increase in size; and arrays of DWs will need to be installed to achieve quality mixing throughout the bioreactor. Quality mixing was attained for

  7. Double-Channel Stereoscopic Display Technology Based on OpenGL

    Directory of Open Access Journals (Sweden)

    Liu Shu

    2013-01-01

    Full Text Available The multi-channel stereoscopic display technology has become an attractive frontier research area in recent years, supporting users with correct spatial perception and large vision experience. This paper studies on the easiest case of double-channel. Focusing on the problem of complex network programming in traditional synchronous display method, a design plan of double-channel stereoscopic display system on one PC based on OpenGL is proposed, which reflects some innovation of the paper. A series of performance tests have been taken and the results agree well with the need for three-dimensional effect and synchronism.

  8. Catalyst-like modulation of transition states for CFTR channel opening and closing: new stimulation strategy exploits nonequilibrium gating.

    Science.gov (United States)

    Csanády, László; Töröcsik, Beáta

    2014-02-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is the chloride ion channel mutated in cystic fibrosis (CF) patients. It is an ATP-binding cassette protein, and its resulting cyclic nonequilibrium gating mechanism sets it apart from most other ion channels. The most common CF mutation (ΔF508) impairs folding of CFTR but also channel gating, reducing open probability (Po). This gating defect must be addressed to effectively treat CF. Combining single-channel and macroscopic current measurements in inside-out patches, we show here that the two effects of 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) on CFTR, pore block and gating stimulation, are independent, suggesting action at distinct sites. Furthermore, detailed kinetic analysis revealed that NPPB potently increases Po, also of ΔF508 CFTR, by affecting the stability of gating transition states. This finding is unexpected, because for most ion channels, which gate at equilibrium, altering transition-state stabilities has no effect on Po; rather, agonists usually stimulate by stabilizing open states. Our results highlight how for CFTR, because of its unique cyclic mechanism, gating transition states determine Po and offer strategic targets for potentiator compounds to achieve maximal efficacy.

  9. Solving non-Markovian open quantum systems with multi-channel reservoir coupling

    Energy Technology Data Exchange (ETDEWEB)

    Broadbent, Curtis J., E-mail: curtis.broadbent@rochester.edu [Rochester Theory Center, and Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States); Jing, Jun; Yu, Ting [Center for Controlled Quantum Systems, and the Department of Physics and Engineering Physics, Stevens Institute of Technology, Hoboken, NJ 07030 (United States); Eberly, Joseph H. [Rochester Theory Center, and Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States)

    2012-08-15

    We extend the non-Markovian quantum state diffusion (QSD) equation to open quantum systems which exhibit multi-channel coupling to a harmonic oscillator reservoir. Open quantum systems which have multi-channel reservoir coupling are those in which canonical transformation of reservoir modes cannot reduce the number of reservoir operators appearing in the interaction Hamiltonian to one. We show that the non-Markovian QSD equation for multi-channel reservoir coupling can, in some cases, lead to an exact master equation which we derive. We then derive the exact master equation for the three-level system in a vee-type configuration which has multi-channel reservoir coupling and give the analytical solution. Finally, we examine the evolution of the three-level vee-type system with generalized Ornstein-Uhlenbeck reservoir correlations numerically. - Highlights: Black-Right-Pointing-Pointer The concept of multi-channel vs. single-channel reservoir coupling is rigorously defined. Black-Right-Pointing-Pointer The non-Markovian quantum state diffusion equation for arbitrary multi-channel reservoir coupling is derived. Black-Right-Pointing-Pointer An exact time-local master equation is derived under certain conditions. Black-Right-Pointing-Pointer The analytical solution to the three-level system in a vee-type configuration is found. Black-Right-Pointing-Pointer The evolution of the three-level system under generalized Ornstein-Uhlenbeck noise is plotted for many parameter regimes.

  10. Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels

    DEFF Research Database (Denmark)

    Bang, Lone; Nielsen-Kudsk, J E; Gruhn, N

    1998-01-01

    The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed...... contractions induced by K+ (20 mM) compared with K+ (80 mM). In addition, concentration-relaxation curves for hydralazine (pD2 = 5.38 +/- 0.06; Emax = 85.9 +/- 3.6%) were shifted 10-fold to the right by the BK(Ca) blockers tetraethylammonium (1 mM) and iberiotoxin (0.1 microM). In contrast, nimodipine (a Ca2......+-entry blocker), relaxed contractions induced by K+ (20 mM) and K+ (80 mM) equally and nimodipine-induced relaxations were neither antagonized by tetraethylammonium nor by iberiotoxin. In isolated perfused rat hearts, hydralazine (1 microM) increased coronary flow by 28.8 +/- 2.7%. Iberiotoxin (0.1 micro...

  11. K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

    Science.gov (United States)

    2010-01-01

    Background Lung epithelial Na+ channels (ENaC) are regulated by cell Ca2+ signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K+ channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K+ channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport. Methods Verapamil-induced depression of heterologously expressed human αβγ ENaC in Xenopus oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and in vivo alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca2+ signal in H441 cells was analyzed using Fluo 4AM. Results The rate of in vivo AFC was reduced significantly (40.6 ± 6.3% of control, P minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca2+ signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2+ in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, KV (pyrithione-Na), K Ca3.1 (1-EBIO), and KATP (minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na+ and K+ transport pathways. Conclusions Our observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal. PMID:20507598

  12. K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

    Directory of Open Access Journals (Sweden)

    Su Xue-Feng

    2010-05-01

    Full Text Available Abstract Background Lung epithelial Na+ channels (ENaC are regulated by cell Ca2+ signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K+ channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K+ channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC by up-regulating both apical and basolateral ion transport. Methods Verapamil-induced depression of heterologously expressed human αβγ ENaC in Xenopus oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441, and in vivo alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca2+ signal in H441 cells was analyzed using Fluo 4AM. Results The rate of in vivo AFC was reduced significantly (40.6 ± 6.3% of control, P Ca3.1 (1-EBIO and KATP (minoxidil channel openers significantly recovered AFC. In addition to short-circuit current (Isc in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca2+ signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2+ in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, KV (pyrithione-Na, K Ca3.1 (1-EBIO, and KATP (minoxidil channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na+ and K+ transport pathways. Conclusions Our observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal.

  13. Tentative Study on Performance of Darriues-Type Hydroturbine Operated in Small Open Water Channel

    Science.gov (United States)

    Matsushita, D.; Moriyama, R.; Nakashima, K.; Watanabe, S.; Okuma, K.; Furukawa, A.

    2014-03-01

    The development of small hydropower is one of the realistic and preferable utilizations of renewable energy, but the extra-low head hydropower less than 2 m is almost undeveloped yet for some reasons. The authors have developed several types of Darrieus-type hydro-turbine system, and among them, the Darrieus-turbine with a wear and a nozzle installed upstream of turbine is so far in success to obtain more output power, i.e. more shaft torque, by gathering all water into the turbine. However, there can several cases exist, in which installing the wear covering all the flow channel width is unrealistic. Then, in the present study, the hydraulic performances of Darrieus-type hydro-turbine with the inlet nozzle is investigated, putting alone in a small open channel without upstream wear. In the experiment, the five-bladed Darrieus-type runner with the pitch-circle diameter of 300 mm and the blade span of 300 mm is vertically installed in the open channel with the width of 1,200 mm. The effectiveness of the shape of the inlet nozzle is also examined using two types of two-dimensional symmetric nozzle, the straight line nozzle (SL nozzle) with the converging angle of 45 degrees and the half diameter curved nozzle (HD nozzle) whose radius is a half diameter of runner pitch circle. Inlet and outlet nozzle widths are in common for the both nozzles, which are 540 mm and 240 mm respectively. All the experiments are carried out under the conditions with constant flow rate and downstream water level, and performances are evaluated by measured output torque and the measured head difference between the water levels upstream and downstream of the turbine. As a result, it is found that the output power is remarkably increased by installing the inlet nozzle, and the turbine with SL nozzle produces larger power than that with HD nozzle. However, the peak efficiency is deteriorated in both cases. The speed ratio defined by the rotor speed divided by the downstream water velocity at

  14. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

  15. The Effect of Confluence Angle on the Flow Pattern at a Rectangular Open-Channel

    Directory of Open Access Journals (Sweden)

    F. Rooniyan

    2014-02-01

    Full Text Available Flow connection in channels is a phenomenon which frequently happens in rivers, water and drainage channels and urban sewage systems. The phenomenon appears to be more complex in rivers than in channels, especially at the y-junction bed joint that causes erosion and sedimentation at some areas resulting to morphological changes. Flow behavior at the channel junction area depends on variables such as channel geometry, discharge ratio, tributary width and y-junction connection angle of the channel, bed level changes at the bed joint, flow characteristic at the bed joint upstream and flow Froude number in different sections. In this research, fluent numerical model and junction angles of 30o, 45o & 60o are used to analyze and evaluate the effect of channel junction geometry on the flow pattern and the flow separation zone dimensions in different ratios of flow discharge (upstream channel discharge to total discharge of the flow. Results for two ratios of flow discharge are represented. Results are in agreement with earlier studies and it is shown that the change of the channel crossing angle affects the flow pattern in the main channel and also that the dimensions of the created separation zone in the main channel become larger when the crossing angle increases. This phenomenon can also be observed when the flow discharge ratio is lower. Analysis showed that the least dimension of the separation zone will be at the crossing angle of 45o .

  16. Collecting a better water-quality sample: Reducing vertical stratification bias in open and closed channels

    Science.gov (United States)

    Selbig, William R.

    2017-01-01

    Collection of water-quality samples that accurately characterize average particle concentrations and distributions in channels can be complicated by large sources of variability. The U.S. Geological Survey (USGS) developed a fully automated Depth-Integrated Sample Arm (DISA) as a way to reduce bias and improve accuracy in water-quality concentration data. The DISA was designed to integrate with existing autosampler configurations commonly used for the collection of water-quality samples in vertical profile thereby providing a better representation of average suspended sediment and sediment-associated pollutant concentrations and distributions than traditional fixed-point samplers. In controlled laboratory experiments, known concentrations of suspended sediment ranging from 596 to 1,189 mg/L were injected into a 3 foot diameter closed channel (circular pipe) with regulated flows ranging from 1.4 to 27.8 ft3 /s. Median suspended sediment concentrations in water-quality samples collected using the DISA were within 7 percent of the known, injected value compared to 96 percent for traditional fixed-point samplers. Field evaluation of this technology in open channel fluvial systems showed median differences between paired DISA and fixed-point samples to be within 3 percent. The range of particle size measured in the open channel was generally that of clay and silt. Differences between the concentration and distribution measured between the two sampler configurations could potentially be much larger in open channels that transport larger particles, such as sand.

  17. A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Niciforovic, Ana P; Galpin, Jason D

    2013-01-01

    Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluor...... that the intrinsic open-state destabilization via aromatic repulsion represents a new mechanism by which ion channels, and likely other proteins, fine-tune conformational equilibria.......Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic...... fluorinated derivatives of aromatic residues previously implicated in the gating of Shaker potassium channels. Here we show that stepwise dispersion of the negative electrostatic surface potential of only one site, Phe481, stabilizes the channel open state. Furthermore, these data suggest that this apparent...

  18. Comparison сharacreristics of optrons with an open optical channel

    Directory of Open Access Journals (Sweden)

    Shvets O. H.

    2008-06-01

    Full Text Available In the present work characteristics of industrial optical sensors for objects positioning in space are considered. Comparison of their parameters with the parameters of the angular-linear displacement sensor designed has been made. Methods for optimization parameters of sensors with an open optical channel are proposed.

  19. Stationary bottom generated velocity fluctuations in one-dimensional open channel flow

    NARCIS (Netherlands)

    Jong, de Bartele

    1993-01-01

    Statistical characteristics are calculated for stationary velocity fluctuations in a one-dimensional open channel flow with a given vertical velocity profile and with one-dimensional irregular bottom waves, characterized by a spectral density function. The calculations are based on an approximate ca

  20. Large-eddy simulation of a curved open-channel flow over topography

    NARCIS (Netherlands)

    Van Balen, W.; Uijttewaal, W.S.J.; Blanckaert, K.

    2010-01-01

    Large-eddy simulation (LES) is performed of a curved open-channel flow over topography based on the laboratory experiment by Blanckaert [“Topographic steering, flow circulation, velocity redistribution and bed topography in sharp meander bends,” Water Resour. Res., doi:10.1029/2009WR008303 (in press

  1. Large-eddy simulation of a mildly curved open-channel flow

    NARCIS (Netherlands)

    Van Balen, W.; Uijttewaal, W.S.J.; Blanckaert, K.

    2009-01-01

    After validation with experimental data, large-eddy simulation (LES) is used to study in detail the open-channel flow through a curved flume. Based on the LES results, the present paper addresses four issues. Firstly, features of the complex bicellular pattern of the secondary flow, occurring in cur

  2. Large-eddy simulation of a curved open-channel flow over topography

    NARCIS (Netherlands)

    Van Balen, W.; Uijttewaal, W.S.J.; Blanckaert, K.

    2010-01-01

    Large-eddy simulation (LES) is performed of a curved open-channel flow over topography based on the laboratory experiment by Blanckaert [“Topographic steering, flow circulation, velocity redistribution and bed topography in sharp meander bends,” Water Resour. Res., doi:10.1029/2009WR008303 (in press

  3. Modes of Access: The Influence of Dissemination Channels on the Use of Open Access Monographs

    Science.gov (United States)

    Snijder, Ronald

    2014-01-01

    Introduction: This paper studies the effects of several dissemination channels in an open access environment by analysing the download data of the OAPEN Library. Method: Download data were obtained containing the number of downloads and the name of the Internet provider. Based on public information, each Internet provider was categorised. The…

  4. A Computer Method of Steady Non-Uniform Gradually Varied Flow in Open Channel & in River

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Most of water flow in open channel or in river belongs to steady non-uniform flow. The surface profiles are caused by changes of channel section. It is very important to analyze its computation. According to the regularity of its surface change, the suitable sectional dimensions of open channel or flood control work can be designed. Commonly, computation of non-uniform flow adopts the traditional methods by hand or by graphic method. The speed and precision of computation are restricted. In this paper, a software to calculate water surface profile is introduced. The software is put forward by using C++ .By means of interpolate method and dialogue between user and computer, we can calculate the water surface profile much more quickly and exactly.

  5. THRESHOLD CONDITION FOR CHOCKING IN OPEN CHANNELS AND EXCAVATION OF TAILRACE

    Institute of Scientific and Technical Information of China (English)

    NI Han-gen; LIU Ya-kun

    2005-01-01

    On the basis of energy and continuity equations a general threshold condition for chocking in open channels is obtained and a representation in terms of the Froude number at the upstream section and other parameters is given to predict whether the chocking phenomenon occurs or not at the downstream section.From the general threshold condition for chocking the limit contraction ratios of the channel width are introduced for both with and without the energy losses and a criterion for excavation of the tailrace to avoid chocking is derived.An example shows that using these criterion and the representation proposed for calculating flow depth it is very easy to determine the scheme of the excavation of the open channels.

  6. The coefficientof hydraulic friction of laminar open flows in smooth channels

    Directory of Open Access Journals (Sweden)

    Borovkov Valeriy Stepanovich

    2015-05-01

    Full Text Available The article examines the dependence of the hydraulic friction coefficient of open laminar uniform streams on the relative width of channels with smooth bottom. The article presents the functional dependence that describes the hydraulic resistance in open channels with smooth bottoms.The experiments were carried out in a rectangular tray (6000×100×200. Aqueous solutions of glycerol were used as working fluids. The superficial tension and liquid density for the used liquids changed a little. The article declares that the coefficient of hydraulic friction λ in the zone of the laminar flow depends on the relative width of the channels with smooth bottom. In the article it is also shown that the Charny formula satisfactorily agrees with the theoretical formula and with the experimental data.

  7. Velocity distribution measurements in a fishway like open channel by Laser Doppler Anemometry (LDA)

    Science.gov (United States)

    Sayeed-Bin-Asad, S. M.; Lundström, T. S.; Andersson, A. G.; Hellström, J. G. I.

    2016-03-01

    Experiments in an open channel flume with placing a vertical half cylinder barrier have been performed in order to investigate how the upstream velocity profiles are affected by a barrier. An experimental technique using Laser Doppler Velocimetry (LDV) was adopted to measure these velocity distributions in the channel for four different discharge rates. Velocity profiles were measured very close to wall and at 25, 50 and 100 mm upstream of the cylinder wall. For comparing these profiles with well-known logarithmic velocity profiles, velocity profiles were also measured in smooth open channel flow for all same four discharge rates. The results indicate that regaining the logarithmic velocity profiles upstream of the half cylindrical barrier occurs at 100 mm upstream of the cylinder wall.

  8. Velocity distribution measurements in a fishway like open channel by Laser Doppler Anemometry (LDA

    Directory of Open Access Journals (Sweden)

    Sayeed-Bin-Asad S.M.

    2016-01-01

    Full Text Available Experiments in an open channel flume with placing a vertical half cylinder barrier have been performed in order to investigate how the upstream velocity profiles are affected by a barrier. An experimental technique using Laser Doppler Velocimetry (LDV was adopted to measure these velocity distributions in the channel for four different discharge rates. Velocity profiles were measured very close to wall and at 25, 50 and 100 mm upstream of the cylinder wall. For comparing these profiles with well-known logarithmic velocity profiles, velocity profiles were also measured in smooth open channel flow for all same four discharge rates. The results indicate that regaining the logarithmic velocity profiles upstream of the half cylindrical barrier occurs at 100 mm upstream of the cylinder wall.

  9. Investigation of a corrugated channel flow with an open source PIV software

    Directory of Open Access Journals (Sweden)

    Sivas Deniz

    2016-01-01

    Full Text Available In this study, the corrugated channel flow was investigated by using an open-source particle image velocimetry (PIV software. The open-source software called OpenPIV was first verified by using images of an earlier experimental work of a vortex ring formation. The corrugated channel flow images were taken with 200 W power LED light source and a high speed camera and those images were analysed with these spatial and temporal tools of OpenPIV. Laminar, transient and turbulent flow regimes were identified when Reynolds number was below 1100, in between 1100 and 2000 and higher than 2000, respectively. The velocity vectors were found to be about 20% lower than the previous study results. The flow inside the grooves was also investigated with OpenPIV and flow characteristics at the grooves were captured when interrogation window size was lowered. The visualization of the flow was presented for different Reynolds numbers with the relative scale values. As a result of this study, OpenPIV software was determined as promising open source PIV analysis software.

  10. Morphology of the 1984 open-channel lava flow at Krafla volcano, northern Iceland

    Science.gov (United States)

    Rossi, Matti J.

    1997-09-01

    An open-channel lava flow of olivine tholeiite basalt, 9 km long and 1-2 km wide, formed in a volcanic eruption that took place in the Krafla volcano, Iceland, on the 4-18 September 1984. The eruption started with emplacement of a pahoehoe sheet which was fed by a 8.5-km-long fissure. After two days of eruption, lava effusion from the fissure ceased but one crater at the northern end of the fissure continued to release lava for another twelve days. That crater supplied an open-channel flow that moved toward the north along the rift valley. The lava was emplaced on a slope of 1°. The final lava flow is composed of five flow facies: (1) the initial pahoehoe sheet; (2) proximal slab pahoehoe and aa; (3) shelly-type overflows from the channel; (4) distal rubbly aa lava; and (5) secondary outbreaks of toothpaste lava and cauliflower aa. The main lava channel within the flow is 6.4 km long. The mean width of this channel is 189 m (103 m S.D.). An initial lava channel that forms in a Bingham plastic substance is fairly constant in width. This channel, however, varies in width especially in the proximal part indicating channel erosion. Large drifted blocks of channel walls are found throughout the flow front area and on the top of overflow levees. This suggests that the channel erosion was mainly mechanical. The lava flow has a mean height of 6 m above its surroundings, measured at the flow margins. However, a study of the pre-flow topography indicates that the lava filled a considerable topographic depression. Combined surface and pre-flow profiles give an average lava-flow thickness of 11 m; the thickness of the initial sheet-flow is estimated as 2 m. The volume of the lava flow calculated from these figures is 0.11 km 3. The mean effusion rate was 91 m 3/s. When lava flow models are used to deduce the rheological properties of this type of lava flow, the following points must be considered: (1) when a lava flow is emplaced along tectonic lineaments, its depth and

  11. Remote Sensing Open Access Journal: Increasing Impact through Quality Publications

    Directory of Open Access Journals (Sweden)

    Prasad S. Thenkabail

    2014-08-01

    Full Text Available Remote Sensing, an open access journal (http://www.mdpi.com/journal/remotesensing has grown at rapid pace since its first publication five years ago, and has acquired a strong reputation. It is a “pathfinder” being the first open access journal in remote sensing. For those academics who were used to waiting a year or two for their peer-reviewed scientific work to be reviewed, revised, edited, and published, Remote Sensing offers a publication time frame that is unheard of (in most cases, less than four months. However, we do this after multiple peer-reviews, multiple revisions, much editorial scrutiny and decision-making, and professional editing by an editorial office before a paper is published online in our tight time frame, bringing a paradigm shift in scientific publication. As a result, there has been a swift increase in submissions of higher and higher quality manuscripts from the best authors and institutes working on Remote Sensing, Geographic Information Systems (GIS, Global Navigation Satellite System (GNSS, GIScience, and all related geospatial science and technologies from around the world. The purpose of this editorial is to update everyone interested in Remote Sensing on the progress made over the last year, and provide an outline of our vision for the immediate future. [...

  12. Linear Modeling and Regulation Quality Analysis for Hydro-Turbine Governing System with an Open Tailrace Channel

    Directory of Open Access Journals (Sweden)

    Jiandong Yang

    2015-10-01

    Full Text Available On the basis of the state–space method (SSM, a novel linear mathematical model of the unsteady flow for the tailrace system with an open channel is proposed. This novel model is an elastic linearized model of water hammer. The validity of the model has been verified by several examples of numerical simulation, which are based on a finite difference technique. Then, the complete mathematical model for the hydro-turbine governing system of hydropower station with an open tailrace channel, which is used for simulating the transient process of the hydro-turbine governing system under load disturbance, is established by combining the models of hydro-turbine, generator, governor and open tailrace channel. Finally, according to the complete model, the regulation quality for hydro-turbine governing system with an open tailrace channel under load disturbance is studied, and the effects of open tailrace channel and tailrace surge tank on regulation quality are analyzed. The results indicate that: The open tailrace channel has a strong influence on the regulation quality by observing the water level fluctuations in tailrace surge tank. The surge shows a piecewise periodical change along with the variation in the length of an open channel. The open tailrace channel can be used to improve the regulation quality of hydro-turbine governing system.

  13. Numerical study on flow rate limitation of open capillary channel flow through a wedge

    Directory of Open Access Journals (Sweden)

    Ting-Ting Zhang

    2016-04-01

    Full Text Available The flow characteristics of slender-column flow in wedge-shaped channel under microgravity condition are investigated in this work. The one-dimensional theoretical model is applied to predict the critical flow rate and surface contour of stable flow. However, the one-dimensional model overestimates the critical flow rate for not considering the extra pressure loss. Then, we develop a three-dimensional simulation method with OpenFOAM, a computational fluid dynamics tool, to simulate various phenomena in wedge channels with different lengths. The numerical results are verified with the capillary channel flow experimental data on the International Space Station. We find that the three-dimensional simulation perfectly predicts the critical flow rates and surface contours under various flow conditions. Meanwhile, the general behaviors in subcritical, critical, and supercritical flow are studied in three-dimensional simulation considering variations of flow rate and open channel length. The numerical techniques for three-dimensional simulation is validated for a wide range of configurations and is hopeful to provide valuable guidance for capillary channel flow experiment and efficient liquid management in space.

  14. Performance Prediction of Darrieus-Type Hydroturbine with Inlet Nozzle Operated in Open Water Channels

    Science.gov (United States)

    Nakashima, K.; Watanabe, S.; Matsushita, D.; Tsuda, S.; Furukawa, A.

    2016-11-01

    Small hydropower is one of the renewable energies and is expected to be effectively used for local supply of electricity. We have developed Darrieus-type hydro-turbine systems, and among them, the Darrieus-turbine with a weir and a nozzle installed upstream of turbine is, so far, in success to obtain more output power by gathering all water into the turbine. However, there can several cases exist, in which installing the weir covering all the flow channel width is unrealistic, and in such cases, the turbine should be put alone in open channels without upstream weir. Since the output power is very small in such a utilization of small hydropower, it is important to derive more power for the cost reduction. In the present study, we parametrically investigate the preferable shape of the inlet nozzle for the Darrieus-type hydroturbine operated in an open flow channel. Experimental investigation is carried out in the open channel in our lab. Tested inlet nozzles are composed of two flat plates with the various nozzle converging angles and nozzle outlet (runner inlet) widths with the nozzle inlet width kept constant. As a result, the turbine with the nozzles having large converging angle and wide outlet width generates higher power. Two-dimensional unsteady numerical simulation is also carried out to qualitatively understand the flow mechanism leading to the better performance of turbine. Since the depth, the width and the flow rate in the real open flow channels are different from place to place and, in some cases from time to time, it is also important to predict the onsite performance of the hydroturbine from the lab experiment at planning stage. One-dimensional stream-tube model is developed for this purpose, in which the Darrieus-type hydroturbine with the inlet nozzle is considered as an actuator-disk modelled based on our experimental and numerical results.

  15. Position and motions of the S4 helix during opening of the Shaker potassium channel.

    Science.gov (United States)

    Phillips, L Revell; Swartz, Kenton J

    2010-12-01

    The four voltage sensors in voltage-gated potassium (Kv) channels activate upon membrane depolarization and open the pore. The location and motion of the voltage-sensing S4 helix during the early activation steps and the final opening transition are unresolved. We studied Zn(2+) bridges between two introduced His residues in Shaker Kv channels: one in the R1 position at the outer end of the S4 helix (R362H), and another in the S5 helix of the pore domain (A419H or F416H). Zn(2+) bridges readily form between R362H and A419H in open channels after the S4 helix has undergone its final motion. In contrast, a distinct bridge forms between R362H and F416H after early S4 activation, but before the final S4 motion. Both bridges form rapidly, providing constraints on the average position of S4 relative to the pore. These results demonstrate that the outer ends of S4 and S5 remain in close proximity during the final opening transition, with the S4 helix translating a significant distance normal to the membrane plane.

  16. Gradually-varied flow profiles in open channels analytical solutions by using Gaussian hypergeometric function

    CERN Document Server

    Jan, Chyan-Deng

    2014-01-01

    Gradually-varied flow (GVF) is a steady non-uniform flow in an open channel with gradual changes in its water surface elevation. The evaluation of GVF profiles under a specific flow discharge is very important in hydraulic engineering. This book proposes a novel approach to analytically solve the GVF profiles by using the direct integration and Gaussian hypergeometric function. Both normal-depth- and critical-depth-based dimensionless GVF profiles are presented. The novel approach has laid the foundation to compute at one sweep the GVF profiles in a series of sustaining and adverse channels, w

  17. Open channel flows of magnetic fluid induced by traveling magnetic field

    Science.gov (United States)

    Kuwahara, Takuya; Okubo, Masaaki; Yamane, Ryuichiro

    A theoretical analysis is made on laminar open channel flows of magnetic fluid induced by a non uniform traveling magnetic field which is applied with a stator of a single-sided linear induction motor. The induced flows are mainly in the direction opposite to the traveling direction of the magnetic field and in proportion to the phase velocity of the magnetic field. The velocity profiles are greatly affected by dimensionless wave number of the magnetic field. Near the bottom of the channel, the theoretical velocity distributions agree well with experimental ones which are measured with a laser optical fiber velocity sensor. However, the experimental velocity distributions become larger near the free surface.

  18. EXPERIMENTAL STUDY OF LANDSLIDE DAM-BREAK FLOOD OVER ERODIBLE BED IN OPEN CHANNELS

    Institute of Scientific and Technical Information of China (English)

    YAN Jun; CAO Zhi-xian; LIU Huai-han; CHEN Li

    2009-01-01

    Large-scale landslide dams may block the river flow and cause inundation upstream,and subsequently fail and result in severe flooding and damage in the downstream.The need for enhanced understanding of the inundation and flooding is evident.This article presents an experimental study of the inundation and landslide dam-break flooding over erodible bed in open channels.A set of automatic water-level probes is deployed to record the highly transient stage,and the post-flooding channel bed elevation is measured.New experimental data resources are provided for understanding the processes of landslide-induced flooding and for testing mathematical rivers models.

  19. SOME NEW DATA AND FORMULAS FOR RESISTANCE FLOW IN FLUVIAL OPEN CHANNELS

    Institute of Scientific and Technical Information of China (English)

    YANG Sheng-fa; HU Jiang; LI Dan-xun; WANG Xing-kui; GUO Yakun

    2011-01-01

    Flow resistance in fluvial open channels,especially in steep gravel-bed channels,still presents challenges to researchers and engineers.This article presents some new data from both the flume experiments and field measurements.Data analysis using the divided hydraulic radius approach shows that the relative roughness plays a significant role in the bed form resistance.A new set of formulas that incorporate the relative roughness are proposed.As compared with several existing formulas,the proposed formulas can be used to better estimate the bed form resistance.

  20. Methane emissions from sugarcane vinasse storage and transportation systems: Comparison between open channels and tanks

    Science.gov (United States)

    Oliveira, Bruna Gonçalves; Carvalho, João Luís Nunes; Chagas, Mateus Ferreira; Cerri, Carlos Eduardo Pellegrino; Cerri, Carlos Clemente; Feigl, Brigitte Josefine

    2017-06-01

    Over the last few years the brazilian sugarcane sector has produced an average of 23.5 million liters of ethanol annually. This scale of production generates large amounts of vinasse, which depending on the manner that is disposed, can result significant greenhouse gas emissions. This study aimed to quantify the methane (CH4) emissions associated with the two most widespread systems of vinasse storage and transportation used in Brazil; open channel and those comprising of tanks and pipes. Additionally, a laboratory incubation study was performed with the aim of isolating the effects of vinasse, sediment and the interaction between these factors on CH4 emissions. We observed significant differences in CH4 emissions between the sampling points along the channels during both years of evaluation (2012-2013). In the channel system, around 80% of CH4 emissions were recorded from uncoated sections. Overall, the average CH4 emission intensity was 1.36 kg CO2eq m-3 of vinasse transported in open channels, which was 620 times higher than vinasse transported through a system of tanks and closed pipes. The laboratory incubation corroborated field results, suggesting that vinasse alone does not contribute significant emissions of CH4. Higher CH4 emissions were observed when vinasse and sediment were incubated together. In summary, our findings demonstrate that CH4 emissions originate through the anaerobic decomposition of organic material deposited on the bottom of channels and tanks. The adoption of coated channels as a substitute to uncoated channels offers the potential for an effective and affordable means of reducing CH4 emissions. Ultimately, the modernization of vinasse storage and transportation systems through the adoption of tank and closed pipe systems will provide an effective strategy for mitigating CH4 emissions generated during the disposal phase of the sugarcane ethanol production process.

  1. PIP2 controls voltage-sensor movement and pore opening of Kv channels through the S4-S5 linker.

    Science.gov (United States)

    Rodriguez-Menchaca, Aldo A; Adney, Scott K; Tang, Qiong-Yao; Meng, Xuan-Yu; Rosenhouse-Dantsker, Avia; Cui, Meng; Logothetis, Diomedes E

    2012-09-04

    Voltage-gated K(+) (Kv) channels couple the movement of a voltage sensor to the channel gate(s) via a helical intracellular region, the S4-S5 linker. A number of studies link voltage sensitivity to interactions of S4 charges with membrane phospholipids in the outer leaflet of the bilayer. Although the phospholipid phosphatidylinositol-4,5-bisphosphate (PIP(2)) in the inner membrane leaflet has emerged as a universal activator of ion channels, no such role has been established for mammalian Kv channels. Here we show that PIP(2) depletion induced two kinetically distinct effects on Kv channels: an increase in voltage sensitivity and a concomitant decrease in current amplitude. These effects are reversible, exhibiting distinct molecular determinants and sensitivities to PIP(2). Gating current measurements revealed that PIP(2) constrains the movement of the sensor through interactions with the S4-S5 linker. Thus, PIP(2) controls both the movement of the voltage sensor and the stability of the open pore through interactions with the linker that connects them.

  2. Novel T-Violation observable open to any pair of decay channels at meson factories

    CERN Document Server

    Bernabeu, Jose; Nebot, Miguel

    2013-01-01

    Quantum Entanglement between the two neutral mesons produced in meson factories has allowed the first indisputable direct observation of Time Reversal Violation in the time evolution of the neutral meson between the two decays. The exceptional meson transitions are directly connected to semileptonic and CP-eigenstate decay channels. The possibility of extending the observable asymmetries to more decay channels confronts the problem of the "orthogonality condition", which can be stated with this tongue-twister: Given a decay channel $f$, Which is the decay channel $f'$ such that the meson state not decaying to $f'$ is orthogonal to the meson state not decaying to $f$? In this paper we propose an alternative $T$-Violation Asymmetry at meson factories which allows its opening to any pair of decay channels. Instead of searching which is the pair of decay channels associated to the $T$-reverse meson transition, we build an asymmetry which tags the initial states of both the Reference and the $T$-reverse meson tran...

  3. Novel T-Violation observable open to any pair of decay channels at meson factories

    Energy Technology Data Exchange (ETDEWEB)

    Bernabéu, José, E-mail: Jose.Bernabeu@uv.es; Botella, Francisco J., E-mail: Francisco.J.Botella@uv.es; Nebot, Miguel, E-mail: Miguel.Nebot@uv.es

    2014-01-20

    Quantum entanglement between the two neutral mesons produced in meson factories has allowed the first indisputable direct observation of Time Reversal Violation in the time evolution of the neutral meson between the two decays. The exceptional meson transitions are directly connected to semileptonic and CP eigenstate decay channels. The possibility of extending the observable asymmetries to more decay channels confronts the problem of the “orthogonality condition”, which can be stated with this tongue-twister: Given a decay channel f, which is the decay channel f{sup ′} such that the meson state not decaying to f{sup ′} is orthogonal to the meson state not decaying to f? In this Letter we propose an alternative T-Violation asymmetry at meson factories which allows its opening to any pair of decay channels. Instead of searching which is the pair of decay channels associated to the T-reverse meson transition, we build an asymmetry which tags the initial states of both the Reference and the T-reverse meson transitions. This observable filters the appropriate final states by means of two measurable survival probabilities. We discuss the methodology to be followed in the analysis of the new observable and the results expected in specific examples.

  4. Catalyst-like modulation of transition states for CFTR channel opening and closing: New stimulation strategy exploits nonequilibrium gating

    OpenAIRE

    Csanády, László; Töröcsik, Beáta

    2014-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is the chloride ion channel mutated in cystic fibrosis (CF) patients. It is an ATP-binding cassette protein, and its resulting cyclic nonequilibrium gating mechanism sets it apart from most other ion channels. The most common CF mutation (ΔF508) impairs folding of CFTR but also channel gating, reducing open probability (Po). This gating defect must be addressed to effectively treat CF. Combining single-channel and macroscopic current ...

  5. VELOCITY DISTRIBUTION IN TRAPEZOID-SECTION OPEN CHANNEL FLOW WITH A NEW REYNOLDS-STRESS EXPRESSION

    Institute of Scientific and Technical Information of China (English)

    Ma Zheng

    2003-01-01

    By considering that the coherent structure is the main cause of the Reynolds stress, a new Reynolds stress expression was given. On this basis the velocity distribution in the trapezoid-section open channel flow was worked out with the pseudo-spectral method. The results were compared with experimental data and the influence of the ratio of length to width of the cross-section and the lateral inclination on the velocity distribution was analyzed. This model can be used the large flux in rivers and open channes.

  6. Open Textbooks and Increased Student Access and Outcomes

    Science.gov (United States)

    Feldstein, Andrew; Martin, Mirta; Hudson, Amy; Warren, Kiara; Hilton, John, III; Wiley, David

    2012-01-01

    This study reports findings from a year-long pilot study during which 991 students in 9 core courses in the Virginia State University School of Business replaced traditional textbooks with openly licensed books and other digital content. The university made a deliberate decision to use open textbooks that were copyrighted under the Creative…

  7. Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Liin, Sara I; Karlsson, Urban; Bentzen, Bo Hjorth

    2016-01-01

    , by shifting the conductance-versus-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 μM). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel. CONCLUSIONS: These findings suggest that circulating...... acids reduce neuronal excitability. This article is protected by copyright. All rights reserved....

  8. ADVECTION AND DIFFUSION OF POISONOUS GAS CONTAMINANT RELEASED FROM BOTTOM SLUDGE IN OPEN CHANNEL

    Institute of Scientific and Technical Information of China (English)

    WU Zhou-hu

    2004-01-01

    In some cases, poisonous contaminants may be released from bottom sludge in open channels. The equation of advection and diffusion for the related problem was analyzed in this paper. The conditions for the definite solution to the equation were given. The analytic solution of poisonous gas concentration distribution was worked out. The reasonableness of this solution was discussed. The result is also of significance for other similar problems.

  9. The periplasmic loop provides stability to the open state of the CorA magnesium channel.

    Science.gov (United States)

    Palombo, Isolde; Daley, Daniel O; Rapp, Mikaela

    2012-08-10

    Crystal structures of the CorA Mg(2+) channel have suggested that metal binding in the cytoplasmic domain stabilizes the pentamer in a closed conformation. The open "metal free" state of the channel is, however, still structurally uncharacterized. Here, we have attempted to map conformational states of CorA from Thermotoga maritima by determining which residues support the pentameric structure in the presence or absence of Mg(2+). We find that when Mg(2+) is present, the pentamer is stabilized by the putative gating sites (M1/M2) in the cytoplasmic domain. Strikingly however, we find that the conserved and functionally important periplasmic loop is vital for the integrity of the pentamer when Mg(2+) is absent from the M1/M2 sites. Thus, although the periplasmic loops were largely disordered in the x-ray structures of the closed channel, our data suggests a prominent role for the loops in stabilizing the open conformation of the CorA channels.

  10. A specialized molecular motion opens the Hv1 voltage-gated proton channel.

    Science.gov (United States)

    Mony, Laetitia; Berger, Thomas K; Isacoff, Ehud Y

    2015-04-01

    The Hv1 proton channel is unique among voltage-gated channels for containing the pore and gate within its voltage-sensing domain. Pore opening has been proposed to include assembly of the selectivity filter between an arginine (R3) of segment S4 and an aspartate (D1) of segment S1. We determined whether gating involves motion of S1, using Ciona intestinalis Hv1. We found that channel opening is concomitant with solution access to the pore-lining face of S1, from the cytoplasm to deep inside the pore. Voltage- and patch-clamp fluorometry showed that this involves a motion of S1 relative to its surroundings. S1 motion and the S4 motion that precedes it are each influenced by residues on the other helix, thus suggesting a dynamic interaction between S1 and S4. Our findings suggest that the S1 of Hv1 has specialized to function as part of the channel's gate.

  11. Voltage dependence of cardiac excitation-contraction coupling: unitary Ca2+ current amplitude and open channel probability.

    Science.gov (United States)

    Altamirano, Julio; Bers, Donald M

    2007-09-14

    Excitation-contraction coupling in cardiac myocytes occurs by Ca2+-induced Ca2+ release, where L-type Ca2+ current evokes a larger sarcoplasmic reticulum (SR) Ca2+ release. The Ca2+-induced Ca2+ release amplification factor or gain (SR Ca2+ release/I(Ca)) is usually assessed by the V(m) dependence of current and Ca2+ transients. Gain rises at negative V(m), as does single channel I(Ca) (i(Ca)), which has led to the suggestion that the increases of i(Ca) amplitude enhances gain at more negative V(m). However, I(Ca) = NP(o) x i(Ca) (where NP(o) is the number of open channels), and NP(o) and i(Ca) both depend on V(m). To assess how i(Ca) and NP(o) separately influence Ca2+-induced Ca2+ release, we measured I(Ca) and junctional SR Ca2+ release in voltage-clamped rat ventricular myocytes using "Ca2+ spikes" (confocal microscopy). To vary i(Ca) alone, we changed [Ca2+](o) rapidly at constant test V(m) (0 mV) or abruptly repolarized from +120 mV to different V(m) (at constant [Ca2+](o)). To vary NP(o) alone, we altered Ca2+ channel availability by varying holding V(m) (at constant test V(m)). Reducing either i(Ca) or NP(o) alone increased excitation-contraction coupling gain. Thus, increasing i(Ca) does not increase gain at progressively negative test V(m). Such enhanced gain depends on lower NP(o) and reduced redundant Ca2+ channel openings (per junction) and a consequently smaller denominator in the gain equation. Furthermore, modest i(Ca) (at V(m) = 0 mV) may still effectively trigger SR Ca2+ release, whereas at positive V(m) (and smaller i(Ca)), high and well-synchronized channel openings are required for efficient excitation-contraction coupling. At very positive V(m), reduced i(Ca) must explain reduced SR Ca2+ release.

  12. Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

    Science.gov (United States)

    Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2015-01-01

    Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells.

  13. Diaphragm opening effects on shock wave formation and acceleration in a rectangular cross section channel

    Science.gov (United States)

    Pakdaman, S. A.; Garcia, M.; Teh, E.; Lincoln, D.; Trivedi, M.; Alves, M.; Johansen, C.

    2016-11-01

    Shock wave formation and acceleration in a high-aspect ratio cross section shock tube were studied experimentally and numerically. The relative importance of geometric effects and diaphragm opening time on shock formation are assessed. The diaphragm opening time was controlled through the use of slit-type (fast opening time) and petal-type (slow opening time) diaphragms. A novel method of fabricating the petal-type diaphragms, which results in a consistent burst pressure and symmetric opening without fragmentation, is presented. High-speed schlieren photography was used to visualize the unsteady propagation of the lead shock wave and trailing gas dynamic structures. Surface-mounted pressure sensors were used to capture the spatial and temporal development of the pressure field. Unsteady Reynolds-Averaged Navier-Stokes simulation predictions using the shear-stress-transport turbulence model are compared to the experimental data. Simulation results are used to explain the presence of high-frequency pressure oscillations observed experimentally in the driver section as well as the cause of the initial acceleration and subsequent rapid decay of shock velocity measured along the top and bottom channel surfaces. A one-dimensional theoretical model predicting the effect of the finite opening time of the diaphragm on the rate of driver depressurization and shock acceleration is proposed. The model removes the large amount of empiricism that accompanies existing models published in the literature. Model accuracy is assessed through comparisons with experiments and simulations. Limitations of and potential improvements in the model are discussed.

  14. Experimental and numerical investigation of the flow field in the gradual transition of rectangular to trapezoidal open channels

    Directory of Open Access Journals (Sweden)

    Adel Asnaashari

    2016-01-01

    Full Text Available Transitions are structures that can change geometry and flow velocity through varying the cross-sections of their channels. Under subcritical flow and steady flow conditions, it is necessary to reduce the flow velocity gradually due to increasing water pressure and adverse pressure gradients. Due to the separation of flow and subsequent eddy formation, a significant energy loss is incurred along the transition. This study presents the results of experimental investigations of the subcritical flow along the expansive transition of rectangular to trapezoidal channels. A numerical simulation was developed using a finite volume of fluid (VOF method with a Reynolds stress turbulence model. Water surface profiles and velocity distributions of flow through the transition were measured experimentally and compared with the numerical results. A good agreement between the experimental and numerical model results showed that the Reynolds model and VOF method are capable of simulating the hydraulic flow in open channel transitions. Also, the efficiency of the transition and coefficient of energy head loss were calculated. The results show that with an increasing upstream Froude number, the efficiency of the transition and coefficient of energy head loss decrease and increase, respectively. The results also show the ability of numerical simulation to simulate the flow separation zones and secondary current along the transition for different inlet discharges.

  15. The K+ channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Eva K Roth

    Full Text Available BACKGROUND: The identification of strategies to improve mutant CFTR function remains a key priority in the development of new treatments for cystic fibrosis (CF. Previous studies demonstrated that the K⁺ channel opener 1-ethyl-2-benzimidazolone (1-EBIO potentiates CFTR-mediated Cl⁻ secretion in cultured cells and mouse colon. However, the effects of 1-EBIO on wild-type and mutant CFTR function in native human colonic tissues remain unknown. METHODS: We studied the effects of 1-EBIO on CFTR-mediated Cl⁻ secretion in rectal biopsies from 47 CF patients carrying a wide spectrum of CFTR mutations and 57 age-matched controls. Rectal tissues were mounted in perfused micro-Ussing chambers and the effects of 1-EBIO were compared in control tissues, CF tissues expressing residual CFTR function and CF tissues with no detectable Cl⁻ secretion. RESULTS: Studies in control tissues demonstrate that 1-EBIO activated CFTR-mediated Cl⁻ secretion in the absence of cAMP-mediated stimulation and potentiated cAMP-induced Cl⁻ secretion by 39.2±6.7% (P<0.001 via activation of basolateral Ca²⁺-activated and clotrimazole-sensitive KCNN4 K⁺ channels. In CF specimens, 1-EBIO potentiated cAMP-induced Cl⁻ secretion in tissues with residual CFTR function by 44.4±11.5% (P<0.001, but had no effect on tissues lacking CFTR-mediated Cl⁻ conductance. CONCLUSIONS: We conclude that 1-EBIO potentiates Cl⁻secretion in native CF tissues expressing CFTR mutants with residual Cl⁻ channel function by activation of basolateral KCNN4 K⁺ channels that increase the driving force for luminal Cl⁻ exit. This mechanism may augment effects of CFTR correctors and potentiators that increase the number and/or activity of mutant CFTR channels at the cell surface and suggests KCNN4 as a therapeutic target for CF.

  16. The effect of potassium channel opener pinacidil on the non-pregnant rat uterus.

    Science.gov (United States)

    Novakovic, Radmila; Milovanovic, Slobodan; Protic, Dragana; Djokic, Jelena; Heinle, Helmut; Gojkovic-Bukarica, Ljiljana

    2007-09-01

    The effects of the K(+) channel opener, pinacidil on the spontaneous rhythmic contractions and contractions provoked by electrical field stimulation (50 Hz) or by oxytocin were investigated in the isolated uterus of the non-pregnant rat in oestrus. Pinacidil produced more potent inhibition of oxytocin-elicited contractions than of spontaneous rhythmic contractions or electrical field stimulation-induced contractions. Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K(+) (K(ATP)) channels, antagonized the pinacidil-induced inhibition of contractions elicited by oxytocin in a competitive manner. However, the pinacidil-induced inhibition of electrical field stimulation-elicited contractions and spontaneous rhythmic contractions was antagonized non-competitively by glibenclamide. In the uterine strips pre-contracted with 80 mM K(+), the pinacidil-induced maximal relaxation was not affected. The present data show that pinacidil exhibits potent relaxant properties in the rat non-pregnant uterus in oestrus and therefore should be taken into account as a possible agent for treatment of dysmenorrhoea. Based on glibenclamide affinity, it appears that the inhibitory response to pinacidil involves K(ATP )channels. We need further investigations to explain why the interaction between glibenclamide and pinacidil in this experimental model depends on the nature of contractions. The ability of pinacidil to completely relax the rat non-pregnant uterus pre-contracted with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) also play a part in its relaxant effect.

  17. Orbital Feshbach resonances with a small energy gap between open and closed channels

    Science.gov (United States)

    Cheng, Yanting; Zhang, Ren; Zhang, Peng

    2016-04-01

    Recently, a new type of Feshbach resonance, i.e., orbital Feshbach resonance (OFR), was proposed for the ultracold alkaline-earth-metal-like atoms and was experimentally observed in the ultracold gases of 173Yb atoms. Unlike most of the magnetic Feshbach resonances of ultracold alkali atoms, when the OFR of 173Yb atoms appears, the energy gap between the thresholds of the open channel (OC) and the closed channel (CC) is much smaller than the characteristic energy of the interatomic interaction, i.e., the van der Waals energy. In this paper we study the OFR in systems with a small CC-OC threshold gap. We show that in these systems the OFR can be induced by the coupling between the OC and either an isolated bound state of the CC or the scattering states of the CC. Moreover, we also show that in each case the two-channel Huang-Yang pesudopotential is always applicable for the approximate calculation of the low-energy scattering amplitude. Our results imply that in the two-channel theoretical calculations for these systems it is appropriate to take into account the contributions from the scattering states of the CC.

  18. Characterization of Unruh channel in the context of open quantum systems

    Science.gov (United States)

    Banerjee, Subhashish; Kumar Alok, Ashutosh; Omkar, S.; Srikanth, R.

    2017-02-01

    In this work, we study an important facet of field theories in curved space-time, viz. the Unruh effect, by making use of ideas of statistical mechanics and quantum foundations. Aspects of decoherence and dissipation, natural artifacts of open quantum systems, along with foundational issues such as the trade-off between coherence and mixing as well as various aspects of quantum correlations are investigated in detail for the Unruh effect. We show how the Unruh effect can be quantified mathematically by the Choi matrix approach. We study how environmentally induced decoherence modifies the effect of the Unruh channel. The differing effects of a dissipative or non-dissipative environment are noted. Further, useful parameters characterizing channel performance such as gate and channel fidelity are applied here to the Unruh channel, both with and without external influences. Squeezing, which is known to play an important role in the context of particle creation, is shown to be a useful resource in a number of scenarios.

  19. Experimental study of depth-limited open-channel flows over a gravel bed

    Institute of Scientific and Technical Information of China (English)

    Cheng Zeng; Chiwai Li; Hongwu Tang; Lingling Wang; Jingqiao Mao

    2015-01-01

    abstract Laboratory experiments of depth-limited open-channel flows over a gravel bed were conducted in the study. Two gravel patches with identical individual element size and different lengths (3.81 m and 7.5 m) were tested. The depth-limited uniform flow regime with relative submergence Sr ( ¼ D/ks) ranging from 2.68 to 5.94 was produced by adjusting the tailgate weir. The velocity profiles were measured by using both an ultra-sound velocity profiler (UVP) and an acoustic Doppler velocimeter (ADV). The conventional methods used to determine the zero-plane displacement and estimate the bed shear velocity were then reviewed and compared. The measured double-averaged (DA) velocity profiles were found to fit well with the log law and defect law with a non-universal Karman constantκ.κ-value remains nearly constant and in the range from 0.2 to 0.3 for the long patch (LP) cases andκ-values are scattered within a wider range from 0.3 to 0.5 for the short patch (SP) cases. While the Br-value in log law remains constant and equal to 8.5 for LP cases, the Br-value was found to decrease with the increase of the dimensionless roughness height ksþ for SP cases. The streamwise turbulence intensity distributions were found to be independent on the patch length and agree well with the available experimental data in the intermediate region and wall region. The Manning resistance coefficient and Darcy–Weisbach friction factor were analyzed. Theκ-value decreases to 0.22 for the fitting of the logarithmic flow resistance law under small relative submergence. The value of the integration constant Ar in the logarithmic law falls within the normal range between 3.25 and 6.25.

  20. Thermal stability of purified and reconstituted CFTR in a locked open channel conformation.

    Science.gov (United States)

    Aleksandrov, Luba A; Jensen, Timothy J; Cui, Liying; Kousouros, Joseph N; He, Lihua; Aleksandrov, Andrei A; Riordan, John R

    2015-12-01

    CFTR is unique among ABC transporters as the only one functioning as an ion channel and from a human health perspective because mutations in its gene cause cystic fibrosis. Although considerable advances have been made towards understanding CFTR's mechanism of action and the impact of mutations, the lack of a high-resolution 3D structure has hindered progress. The large multi-domain membrane glycoprotein is normally present at low copy number and when over expressed at high levels it aggregates strongly, limiting the production of stable mono-disperse preparations. While the reasons for the strong self-association are not fully understood, its relatively low thermal stability seems likely to be one. The major CF causing mutation, ΔF508, renders the protein very thermally unstable and therefore a great deal of attention has been paid to this property of CFTR. Multiple second site mutations of CFTR in NBD1 where F508 normally resides and small molecule binders of the domain increase the thermal stability of the mutant. These manipulations also stabilize the wild-type protein. Here we have applied ΔF508-stabilizing changes and other modifications to generate wild-type constructs that express at much higher levels in scaled-up suspension cultures of mammalian cells. After purification and reconstitution into liposomes these proteins are active in a locked-open conformation at temperatures as high as 50 °C and remain monodisperse at 4 °C in detergent or lipid for at least a week. The availability of adequate amounts of these and related stable active preparations of homogeneous CFTR will enable stalled structural and ligand binding studies to proceed.

  1. Turbulence of non-uniform open channel flows and mean velocity scaling

    Science.gov (United States)

    Stewart, R.; Fox, J.

    2014-12-01

    Turbulence and mean velocity distributions are well studied for uniform flows, however fully turbulent non-uniform open channel flows over rough gravel beds are an understudied class of realistic flows with significant geomorphologic importance. The two-fold objectives of this study are to investigate the effects of flow deceleration on multi-layer turbulence and determine velocity scales that produce self-similar profiles using turbulent boundary layer theory. Turbulence statistics were calculated from data collected using a three-dimensional acoustic Doppler velocimeter in backwater region produced by placing cylindrical obstruction downstream of measuring location. Results indicate inner turbulent processes are set according to shear velocity while outer layer of turbulence is not. Mean streamwise velocity profiles of 101 published datasets including 2211 data points from non-uniform decelerating rivers and laboratory flumes are scaled using inner, outer and 2 mixed methods. Theoretical arguments indicate the outer velocity scale determined from the AIP definition of equilibrium provides a more appropriate scaling for the velocity deficit of non-uniform open channel flows than inner scaling determined from Clauser equilibrium. Scaling results of mean profiles show outer scaling collapses data better than inner scaling. Mixed scaling approaches, which account for upstream conditions and the effect of bed roughness felt throughout the flow, provide a better scaling choice for this class of flows than either inner or outer scales alone. Results of this analysis provide insight on the behavior of turbulence in decelerating fully turbulent open channel flow over a rough gravel bed and provides a scaling useful for predicting velocity distributions.

  2. Analysis of radiometric signal in sedimentating suspension flow in open channel

    Directory of Open Access Journals (Sweden)

    Zych Marcin

    2015-01-01

    Full Text Available The article discusses issues related to the estimation of the sedimentating solid particles average flow velocity in an open channel using radiometric methods. Due to the composition of the compound, which formed water and diatomite, received data have a very weak signal to noise ratio. In the process analysis the known determining of the solid phase transportation time delay the classical cross-correlation function is the most reliable method. The use of advanced frequency analysis based on mutual spectral density function and wavelet transform of recorded signals allows a reduction of the noise contribution.

  3. Analysis of radiometric signal in sedimentating suspension flow in open channel

    Science.gov (United States)

    Zych, Marcin; Hanus, Robert; Petryka, Leszek; Świsulski, Dariusz; Doktor, Marek; Mastej, Wojciech

    2015-05-01

    The article discusses issues related to the estimation of the sedimentating solid particles average flow velocity in an open channel using radiometric methods. Due to the composition of the compound, which formed water and diatomite, received data have a very weak signal to noise ratio. In the process analysis the known determining of the solid phase transportation time delay the classical cross-correlation function is the most reliable method. The use of advanced frequency analysis based on mutual spectral density function and wavelet transform of recorded signals allows a reduction of the noise contribution.

  4. Numerical study of the effects of lamp configuration and reactor wall roughness in an open channel water disinfection UV reactor.

    Science.gov (United States)

    Sultan, Tipu

    2016-07-01

    This article describes the assessment of a numerical procedure used to determine the UV lamp configuration and surface roughness effects on an open channel water disinfection UV reactor. The performance of the open channel water disinfection UV reactor was numerically analyzed on the basis of the performance indictor reduction equivalent dose (RED). The RED values were calculated as a function of the Reynolds number to monitor the performance. The flow through the open channel UV reactor was modelled using a k-ε model with scalable wall function, a discrete ordinate (DO) model for fluence rate calculation, a volume of fluid (VOF) model to locate the unknown free surface, a discrete phase model (DPM) to track the pathogen transport, and a modified law of the wall to incorporate the reactor wall roughness effects. The performance analysis was carried out using commercial CFD software (ANSYS Fluent 15.0). Four case studies were analyzed based on open channel UV reactor type (horizontal and vertical) and lamp configuration (parallel and staggered). The results show that lamp configuration can play an important role in the performance of an open channel water disinfection UV reactor. The effects of the reactor wall roughness were Reynolds number dependent. The proposed methodology is useful for performance optimization of an open channel water disinfection UV reactor.

  5. 4D photogrammetric technique to study free surface water in open channels

    Science.gov (United States)

    Aubé, Damien; Berkaoui, Amine; Vinatier, Fabrice; Bailly, Jean-Stéphane; Belaud, Gilles

    2015-04-01

    Characteristics of three-dimensional surface water are considered as the most valuable information to understand hydrodynamic phenomena in open channel flow. An accurate and coherent description of the free water surface morphology improves the accuracy of hydraulic models which study river processes. However, amongst existing techniques to measure three-dimensional surface, stereo-photogrammetry is clearly the most effective technique to obtain an instantaneous and high accurate 3D free water surface and it's suitable to both flume and field condition. Our study aims at developing this technique in two controlled channels, one in interior with glass borders (length: 6 m, width: 0.3 m and depth: 0.5 m) and one outside with cement borders (length: 13 m, width: 0.7 m and depth: 0.4 m). A system consisting in three NIKON-D3200 cameras, mounted to an adjustable tripod head, which is fixed to an inverted aluminium T-bar with the center camera higher than the two side cameras. Each camera is fitted with a 28 mm lens and cameras are synchronized using a Phottix(R) system. The system was mounted at a downstream position from the channel with an oblique configuration. A series of pictures taken at a 3 s interval during the water weight bearing were reported and analyzed using the Photoscan Pro(R) software for image matching. Validation procedure of the technique was realized using an orthophotography of the lateral border of the interior channel to delimit the line of water surface, and using a video capture of a slide fixed inside the outside channel. A high resolution and dynamic elevation map of the surface water was constructed. Our study give encouraging results, with a good capture of water surface morphology and a limited occlusion issues. The confrontation of the results with the validation dataset highlight limitations that need to be discussed with the audience.

  6. Velocity profile of turbulent sediment-laden flows in open-channels

    Institute of Scientific and Technical Information of China (English)

    Deyu Zhong n; Lei Zhang; Baosheng Wu; Yongqiang Wang

    2015-01-01

    In this paper, a study was carried out on the velocity profile of sediment-laden flows in open channels using a two-phase mixture model for two-phase flows. The governing equations for water-sediment mixtures were derived based on the two-fluid equations for solid–liquid two-phase flows. The drift velocity, a key variable involved in the two-phase mixture equations, was derived from the equation of momentum conservation for the solid phase. The drift velocity shows that the inertia of flow, particle turbulence, and collisions effect contribute to the dispersion of the sediment particles in turbulent flows. Using the two-phase mixture equation, the vertical velocity profile of open channel flows was obtained. Further analysis indicated that the distribution of the velocity over depth of water-sediment mixtures, composed of two different phases, is significantly affected by the turbulence of water-sediment mixtures and the density stratification. However, the velocity distribution is also affected by other factors including collisions between particles and particle turbulence as a basic feature of two-phase flows where interphase interactions inevitably mark their influence on the velocity distribution. Comparisons of this approach with observations for a wide range of experimental conditions are presented in this paper, which show that this approach agrees well with the experiments.

  7. An effective Euler-Lagrange model for suspended sediment transport by open channel flows

    Institute of Scientific and Technical Information of China (English)

    Huabin Shi; Xiping Yu n

    2015-01-01

    An Euler–Lagrange two-phase flow model is developed to study suspended sediment transport by open-channel flows with an Eddy Interaction Model (EIM) applied to consider the effect of fluid turbulence on sediment diffusion. For the continuous phase, the mean fluid velocity, the turbulent kinetic energy and its dissipation rate are directly estimated by well-established empirical formulas. For the dispersed phase, sediment particles are tracked by solving the equation of motion. The EIM is applied to compute the particle fluctuation velocity. Neglecting the effect of particles on flow turbulence as usually suggested for dilute cases in the literature, the Euler–Lagrange model is applied to simulate suspended sediment transport in open channels. Although the numerical results agree well with those by the well-known random walk particle tracking model (RWM) and with the laboratory data for fine sediment cases, it is clearly shown that such an Euler–Lagrange model underestimates the sediment concentration for the medium-sized and coarse sediment cases. To improve the model, a formula is proposed to consider the local fluid turbulence enhancement around a particle due to vortex shedding in the wake. Numerical results of the modified model then agree very well with laboratory data for not only the fine but also the coarse sediment cases.

  8. A study on the stability of laminar open-channel flow over a sandy rippled bed

    Institute of Scientific and Technical Information of China (English)

    BAI; Yuchuan; XU; Haijue

    2005-01-01

    The bed of a river often features some kinds of bedform, such as sand ripples, dunes, and so on. Even if the bed is smooth initially, disturbances arising from the bed or other external sources will cause the laminar flow in an open channel to become unstable as soon as the flow develops, thereby leading to the formation of sand ripples on the bed. In return, the formation of the sand ripples will modify the instability path of the laminar flow passing over them. The wavy character of the bed will induce further instability of the flow, which is essentially different from that on a smooth bed: the neutral curve will move forward and the critical Reynolds number will decrease. The flow is unstable in response to a wider range of the disturbance wave number, or the laminar flow instability can happen more easily. The propagation speed of the sand ripples also affects the flow instability, since the stability of open channel flow over a movable bed is fundamentally different from that on a rigid bed. These instability effects are discussed in detail in this paper.

  9. Prediction of Velocity-Dip-Position at the Central Section of Open Channels using Entropy Theory

    Directory of Open Access Journals (Sweden)

    Snehasis Kundu

    2017-01-01

    Full Text Available An analytical model to predict the velocity-dip-position at the central section of open channels is presented in this study. Unlike the previous studies where empirical or semi-empirical models were suggested, in this study the model is derived by using entropy theory. Using the principle of maximum entropy, the model for dip-position is derived by maximizing the Shannon entropy function after assuming dimensionless dip-position at the central section as a random variable. No estimation of empirical parameter is required for calculating dip-position from the proposed model. The model is able to predict the location of maximum velocity at the central section of an open channel with any aspect ratio. The developed model of velocity-dip-position is tested with experimental data from twenty-two researchers reported in literature for a wide range of aspect ratio. The model is also compared with other existing empirical models. The present model shows good agreement with the observed data and provides least prediction error compared to other models.

  10. 3-D hybrid LES-RANS model for simulation of open-channel T-diversion flows

    Institute of Scientific and Technical Information of China (English)

    Jie ZHOU; Cheng ZENG

    2009-01-01

    The study of flow diversions in open channels plays an important practical role in the design and management of open-channel networks for irrigation or drainage.To accurately predict the mean flow and turbulence characteristics of open-channel dividing flows,a hybrid LES-RANS model,which combines the large eddy simulation (LES) model with the Reynolds-averaged Navier-Stokes (RANS) model,is proposed in the present study.The unsteady RANS model was used to simulate the upstream and downstream regions of a main channel,as well as the downstream region of a branch channel.The LES model was used to simulate the channel diversion region,where turbulent flow characteristics ate complicated.Isotropic velocity fluctuations were added at the inflow interface of the LES region to trigger the generation of resolved turbulence.A method based on the virtual body force is proposed to impose Reynolds-averaged velocity fields near the outlet of the LES region in order to take downstream flow effects computed by the RANS model into account and dissipate the excessive turbulent fluctuations.This hybrid approach saves computational effort and makes it easier to properly specify inlet and outlet boundary conditions.Comparison between computational results and experimental data indicates that this relatively new modeling approach can accurately predict open-channel T-diversion flows.

  11. Mathematical expression of discharge capacity of compound open channels using MARS technique

    Science.gov (United States)

    Parsaie, Abbas; Haghiabi, Amir Hamzeh

    2017-03-01

    In this paper, analytical methods, artificial neural network (ANN) and multivariate adaptive regression splines (MARS) techniques were utilised to estimate the discharge capacity of compound open channels (COC). To this end, related datasets were collected from literature. The results showed that the divided channel method with a coefficient of determination ( R 2) value of 0.76 and root mean square error (RMSE) value of 0.162 has the best performance, among the various analytical methods tested. The performance of applied soft computing models with R 2=0.97 and RMSE = 0.03 was found to be more accurate than analytical approaches. Comparison of MARS with the ANN model, in terms of developed discrepancy ratio (DDR) index, showed that the accuracy of MARS model was better than that of MLP model. Reviewing the structure of the derived MARS model showed that the longitudinal slope of the channel ( S), relative flow depth ( H r ) and relative area ( A r ) have a high impact on modelling and forecasting the discharge capacity of COCs.

  12. Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening.

    Science.gov (United States)

    Nakajo, Koichi; Kubo, Yoshihiro

    2014-06-12

    In voltage-gated K(+) channels, membrane depolarization induces an upward movement of the voltage-sensing domains (VSD) that triggers pore opening. KCNQ1 is a voltage-gated K(+) channel and its gating behaviour is substantially modulated by auxiliary subunit KCNE proteins. KCNE1, for example, markedly shifts the voltage dependence of KCNQ1 towards the positive direction and slows down the activation kinetics. Here we identify two phenylalanine residues on KCNQ1, Phe232 on S4 (VSD) and Phe279 on S5 (pore domain) to be responsible for the gating modulation by KCNE1. Phe232 collides with Phe279 during the course of the VSD movement and hinders KCNQ1 channel from opening in the presence of KCNE1. This steric hindrance caused by the bulky amino-acid residues destabilizes the open state and thus shifts the voltage dependence of KCNQ1/KCNE1 channel.

  13. KR-31761, a novel K+(ATP)-channel opener, exerts cardioprotective effects by opening both mitochondrial K+(ATP) and Sarcolemmal K+(ATP) channels in rat models of ischemia/reperfusion-induced heart injury.

    Science.gov (United States)

    Yang, Min-Kyu; Lee, Sung-Hun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Chung, Hun-Jong; Won, Hyung-Sik; Lee, Chang-Soo; Kwon, Suk-Hyung; Choi, Wahn-Soo; Shin, Hwa-Sup

    2009-02-01

    The cardioprotective effects of KR-31761, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia/30-min reperfusion, KR-31761 perfused prior to ischemia significantly increased both the left ventricular developed pressure (% of predrug LVDP: 17.8, 45.1, 54.2, and 62.6 for the control, 1 microM, 3 microM, and 10 microM, respectively) and double product (DP: heart rate x LVDP; % of predrug DP: 17.5, 44.9, 56.2, and 64.5 for the control, 1 microM, 3 microM, and 10 microM, respectively) at 30-min reperfusion while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31761 (10 microM) significantly increased the time to contracture during the ischemic period, whereas it concentration-dependently decreased the lactate dehydrogenase release during reperfusion. All these parameters were significantly reversed by 5-hydroxydecanoate (5-HD, 100 microM) and glyburide (1 microM), selective and nonselective blockers of the mitochondrial K+(ATP) (mitoK+(ATP)) channel and K+(ATP) channel, respectively. In anesthetized rats subjected to 30-min occlusion of left anterior descending coronary artery/2.5-h reperfusion, KR-31761 administered 15 min before the onset of ischemia significantly decreased the infarct size (72.2%, 55.1%, and 47.1% for the control, 0.3 mg/kg, i.v., and 1.0 mg/kg, i.v., respectively); and these effects were completely and almost completely abolished by 5-HD (10 mg/kg, i.v.) and HMR-1098, a selective blocker of sarcolemmal K+(ATP) (sarcK+(ATP)) channel (6 mg/kg, i.v.) administered 5 min prior to KR-31761 (72.3% and 67.9%, respectively). KR-31761 only slightly relaxed methoxamine-precontracted rat aorta (IC50: > 30.0 microM). These results suggest that KR-31761 exerts potent cardioprotective effects through the opening of both mitoK+(ATP) and sarcK+(ATP) channels in rat hearts with a minimal vasorelaxant effect.

  14. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR): CLOSED AND OPEN STATE CHANNEL MODELS.

    Science.gov (United States)

    Corradi, Valentina; Vergani, Paola; Tieleman, D Peter

    2015-09-18

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter superfamily. CFTR controls the flow of anions through the apical membrane of epithelia. Dysfunctional CFTR causes the common lethal genetic disease cystic fibrosis. Transitions between open and closed states of CFTR are regulated by ATP binding and hydrolysis on the cytosolic nucleotide binding domains, which are coupled with the transmembrane (TM) domains forming the pathway for anion permeation. Lack of structural data hampers a global understanding of CFTR and thus the development of "rational" approaches directly targeting defective CFTR. In this work, we explored possible conformational states of the CFTR gating cycle by means of homology modeling. As templates, we used structures of homologous ABC transporters, namely TM(287-288), ABC-B10, McjD, and Sav1866. In the light of published experimental results, structural analysis of the transmembrane cavity suggests that the TM(287-288)-based CFTR model could correspond to a commonly occupied closed state, whereas the McjD-based model could represent an open state. The models capture the important role played by Phe-337 as a filter/gating residue and provide structural information on the conformational transition from closed to open channel.

  15. Investigation on Twisting and Side Wall Opening Occurring in Curved Hat Channel Products Made of High Strength Steel Sheets

    Science.gov (United States)

    Takamura, Masato; Fukui, Ayako; Yano, Hiroshi; Hama, Takayuki; Sunaga, Hideyuki; Makinouchi, Akitake; Asakawa, Motoo

    2011-08-01

    High strength steel sheets are becoming increasingly important for the weight reduction of automotive bodies to meet the requirements for reduced environmental impact. However, dimensional defects resulting from springback are serious issues, and effective methods of predicting and reducing such defects are necessary. In this study, we numerically and experimentally analyzed the mechanisms of dimensional inaccuracies caused by springback occurring in curved hat channel deep drawing products. The analysis was based on the static explicit FEM software "TP-STRUCT" (the solver part is known as "STAMP3D"). The results of the experiments and simulations similarly show that the twist angle is positive (right-hand system) when the drawing height is relatively large. We calculated the twist torque around the longitudinal axis using the stress distributions obtained by FE analysis. Through the investigation of twist torque and its transition during the drawing and die removal processes, we found that the negative torque generated by side wall opening occurring in the die removal process is the dominant factor of the positive twist. Knowing such mechanisms of twist in cases with a relatively large drawing height, we attempted to explore methods of reducing side wall opening by giving the side wall a stepped shape with the eventual aim of reducing twist. Consequently, we concluded that the stepped shape on the side wall has marked effects of reducing side wall opening, mainly through the elimination of bending-unbending effects on die shoulders, which was verified by observing the stress distribution obtained by FE analysis.

  16. Mouth breathing increases the pentylenetetrazole-induced seizure threshold in mice: a role for ATP-sensitive potassium channels.

    Science.gov (United States)

    Niaki, Seyed Esfandiar Akhavan; Shafaroodi, Hamed; Ghasemi, Mehdi; Shakiba, Bijan; Fakhimi, Ali; Dehpour, Ahamd Reza

    2008-08-01

    Nasal obstruction and consequent mouth breathing have been shown to change the acid-base balance, producing respiratory acidosis. Additionally, there exists a large body of evidence maintaining that acidosis affects the activity of ATP-sensitive potassium (K(ATP)) channels, which play a crucial role in the function of the central nervous system (CNS), for example, in modulating seizure threshold. Thus, in the study described here, we examined whether mouth breathing, induced by surgical ligation of nostrils, could affect the seizure threshold induced by pentylenetetrazole in male NMRI mice. Using the selective K(ATP) channel opener (diazoxide) and blocker (glibenclamide), we also evaluated the possible role of K(ATP) channels in this process. Our data revealed that seizure threshold was increased 6 to 72 hours after nasal obstruction, reaching a peak 48 hours afterward, compared with either control or sham-operated mice (Pmouth breathing, which could result in respiratory acidosis, increases seizure threshold in mice and K(ATP) channels may play a role in this effect.

  17. A rigorous proof of MIMO channel capacity's increase with antenna number

    Institute of Scientific and Technical Information of China (English)

    GONG Jian-min; M.R. Soleymani; J.F.Hayes

    2008-01-01

    It is well known that adding more antennas at the transmitter or at the receiver may offer larger channel capacity, in the multiple-input multiple-output(MIMO) communication systems. In this letter, a simple proof is presented for the fact that the channel capacity increases with an increase in the number of receiving antennas. The proof is based on the famous capacity formula of Foschini and Gans with matrix theory.

  18. The relation of turbulence to diffusion in open-channel flows

    Science.gov (United States)

    Keefer, Thomas N.

    1971-01-01

    This investigation examines the interrelation between turbulent diffusion, dispersion, and the statistical properties of turbulence in an open-channel flow. The experiments were conducted in a 3. 87- foot wide flume over four boundary roughnesses. The results are from studies made of: (1) the influence of turbulence on the vertical and lateral diffusion of plumes of heated water and a neutrally-buoyant salt solution from a point source at the mid-depth of flow; (2) the velocity concentration covariance along the axis of a salt solution plume using a single-electrode conductivity probe and hot-film sensor; (3) lateral and longitudinal surface diffusion measured by dropping polyethylene particles on the water surface; and (4) longitudinal space-time velocity correlation measurements.

  19. EXPERIMENTAL INVESTIGATION ON SOUND SPEED PROPAGATING THROUGH HIGH SPEED AERATED FLOW IN OPEN CHANNEL

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    An experiment concerning the sound propaga-tion in aerated open channel flow was designed and conductedin a variable slope chute. The acquisition of sound data wasdone by the hydro-phones installed into the bottom wall of thechute. The data were analyzed and processed by the tape re-corder and a 3562A analyzer. The primary experimetal resultsindicated that the sound speed in aerated flow is varied with the air concentration and highly lower than each of the soundspeed in pure water or air. As released by the derived theoryformula, the minimum sound of 24m/s in aerated flow hap-pened when the air concentration achieved to 50%. This resultshows that the compressibility of high speed aerated flowshould be considered when the air concentration is near to50%. A criterion of compressibility of high speed aerated flowwas also giv. En in this paper.

  20. Sprinting performance of two Iberian fish: Luciobarbus bocagei and Pseudochondrostoma duriense in an open channel flume

    Science.gov (United States)

    Sanz-Ronda, Francisco Javier; Ruiz-Legazpi, Jorge; Bravo-Cordoba, Francisco Javier; Makrakis, Sergio; Castro-Santos, Theodore R.

    2015-01-01

    This paper presents sprinting data from Iberian barbel (Luciobarbus bocagei) and northern straight-mouth nase (Pseudochondrostoma duriense), volitionally swimming against high velocity flows (1.5, 2.5 and 3 m s−1) in an open channel flume. Swimming endurance and speed greatly exceeded previously published observations with both species attaining swim speeds >20 body lengths s−1. Flow velocity was the primary variable limiting the distance both species were able to traverse. Barbel swam greater distances than nase at higher flow velocities, with longer individuals attaining greater distances than smaller ones. The results challenge established fish passage guidelines, suggesting that in some cases these species are capable of passing much higher velocities than was previously believed.

  1. Control of Energy Density inside a Disordered Medium by Coupling to Open or Closed Channels

    Science.gov (United States)

    Sarma, Raktim; Yamilov, Alexey G.; Petrenko, Sasha; Bromberg, Yaron; Cao, Hui

    2016-08-01

    We demonstrate experimentally the efficient control of light intensity distribution inside a random scattering system. The adaptive wave front shaping technique is applied to a silicon waveguide containing scattering nanostructures, and the on-chip coupling scheme enables access to all input spatial modes. By selectively coupling the incident light to the open or closed channels of the disordered system, we not only vary the total energy stored inside the system by a factor of 7.4, but also change the energy density distribution from an exponential decay to a linear decay and to a profile peaked near the center. This work provides an on-chip platform for controlling light-matter interactions in turbid media.

  2. EXPERIMENTAL STUDY OF 3-D TURBULENT BEND FLOWS IN OPEN CHANNEL

    Institute of Scientific and Technical Information of China (English)

    LIU Yue-qin; ZHENG Shao-wen; WU Qiang

    2005-01-01

    A generalized bend flow model, treating a 90° single bend and 60° continuous bends, was designed to quantitatively describe 3-D turbulence mechanism of circulating not-fully-developed flow in open channels with bends.The 3-D fluctuating velocities of turbulent flow were measured and analyzed with a 3-D acoustic-Doppler velocimeter.Formula for 3-D turbulent intensity was derived using the dimension analysis approach.Expressions of vertical turbulent-intensity distributions were obtained with the multivariant-regression theory, which agree with experiment data.Distributions of turbulent intensity and turbulent stress were characterized, and their relationships were concluded.In the bend-turbulent-flow core region, longitudinal and lateral turbulent-intensity distributions are coincident with linear distribution, but in near-wall region are coincident with the Gamma distribution.Vertical turbulent intensity distributions are coincident with the Rayleigh distribution.Herein, it is concluded that the bend turbulence is anisotropic.

  3. A lanthanum chelate possessing an open-channel framework with water nanotubes: properties and desalination.

    Science.gov (United States)

    Chen, Mao-Long; Guo, Yi-Chao; Yang, Fang; Liang, Jin-Xia; Cao, Ze-Xing; Zhou, Zhao-Hui

    2014-04-28

    A new type of thermally stable chelate {La(H2O)4[La(1,3-pdta)(H2O)]3}n · 12nH2O (1) [1,3-H4pdtaCH2[CH2N(CH2CO2H)2]2] with an open-channel shows significant and unusual solvent transport properties and demonstrates a use for low-pressure desalination, which is constructed by cheap and available lanthanum salt and 1,3-propanediaminetetraacetate. The chelate could be converted reversibly to its trihydrate {La(H2O)4[La(1,3-pdta)(H2O)]3}n · 3nH2O (1a), dehydrated product {La(H2O)4[La(1,3-pdta)(H2O)]3}n (1b) and ethanol adduct {La(H2O)4[La(1,3-pdta)(H2O)]3}n · 3nH2O · 3nEtOH (1c). The latter nano-confined ethanol shows a remarkable downfield shift (Δδ = 6.0 ppm) for the methylene group in the solid 13C NMR spectrum compared with that of the free EtOH. Crystal 1 with a regular hexagonal appearance can be used directly for saline water desalination on a small-scale at an ambient temperature, demonstrating a low energy consumption and environmentally friendly method. This is attributed to the 10.0 Å hydrophobic open-channel containing water nanotubes (WNTs, Φ = 4.2 Å). The nano-confined WNTs can be removed at a low temperature (45 °C).

  4. Role of protein sulfation in vasodilation induced by minoxidil sulfate, a K+ channel opener

    Energy Technology Data Exchange (ETDEWEB)

    Meisheri, K.D.; Oleynek, J.J.; Puddington, L. (Cardiovascular Diseases Research, Upjohn Laboratories, Upjohn Company, Kalamazoo, MI (United States))

    1991-09-01

    Evidence from contractile, radioisotope ion flux and electrophysiological studies suggest that minoxidil sulfate (MNXS) acts as a K+ channel opener in vascular smooth muscle. This study was designed to examine possible biochemical mechanisms by which MNXS exerts such an effect. Experiments performed in the isolated rabbit mesenteric artery (RMA) showed that MNXS, 5 microM, but not the parent compound minoxidil, was a potent vasodilator. Whereas the relaxant effects of an another K+ channel opener vasodilator, BRL-34915 (cromakalim), were removed by washing with physiological saline solution, the effects of MNXS persisted after repeated washout attempts. Furthermore, after an initial exposure of segments of intact RMA to (35S) MNXS, greater than 30% of the radiolabel was retained 2 hr after removal of the drug. In contrast, retention of radiolabel was not detected with either (3H)MNXS (label on the piperidine ring of MNXS) or (3H)minoxidil (each less than 3% after a 2-hr washout). These data suggested that the sulfate moiety from MNXS was closely associated with the vascular tissue. To determine if proteins were the acceptors of sulfate from MNXS, intact RMAs were incubated with (35S)MNXS, and then 35S-labeled proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by fluorography. Preferential labeling of a 116 kD protein was detected by 2 and 5 min of treatment. A 43 kD protein (resembling actin) also showed significant labeling. A similar profile of 35S-labeled proteins was observed in (35S) MNXS-treated A7r5 rat aortic smooth muscle cells, suggesting that the majority of proteins labeled by (35S)MNXS in intact RMA were components of smooth muscle cells.

  5. Outer region scaling using the freestream velocity for nonuniform open channel flow over gravel

    Science.gov (United States)

    Stewart, Robert L.; Fox, James F.

    2017-06-01

    The theoretical basis for outer region scaling using the freestream velocity for nonuniform open channel flows over gravel is derived and tested for the first time. Owing to the gradual expansion of the flow within the nonuniform case presented, it is hypothesized that the flow can be defined as an equilibrium turbulent boundary layer using the asymptotic invariance principle. The hypothesis is supported using similarity analysis to derive a solution, followed by further testing with experimental datasets. For the latter, 38 newly collected experimental velocity profiles across three nonuniform flows over gravel in a hydraulic flume are tested as are 43 velocity profiles previously published in seven peer-reviewed journal papers that focused on fluid mechanics of nonuniform open channel over gravel. The findings support the nonuniform flows as equilibrium defined by the asymptotic invariance principle, which is reflective of the consistency of the turbulent structure's form and function within the expanding flow. However, roughness impacts the flow structure when comparing across the published experimental datasets. As a secondary objective, we show how previously published mixed scales can be used to assist with freestream velocity scaling of the velocity deficit and thus empirically account for the roughness effects that extend into the outer region of the flow. One broader finding of this study is providing the theoretical context to relax the use of the elusive friction velocity when scaling nonuniform flows in gravel bed rivers; and instead to apply the freestream velocity. A second broader finding highlighted by our results is that scaling of nonuniform flow in gravel bed rivers is still not fully resolved theoretically since mixed scaling relies to some degree on empiricism. As researchers resolve the form and function of macroturbulence in the outer region, we hope to see the closing of this research gap.

  6. Badges to Acknowledge Open Practices: A Simple, Low-Cost, Effective Method for Increasing Transparency.

    Science.gov (United States)

    Kidwell, Mallory C; Lazarević, Ljiljana B; Baranski, Erica; Hardwicke, Tom E; Piechowski, Sarah; Falkenberg, Lina-Sophia; Kennett, Curtis; Slowik, Agnieszka; Sonnleitner, Carina; Hess-Holden, Chelsey; Errington, Timothy M; Fiedler, Susann; Nosek, Brian A

    2016-05-01

    Beginning January 2014, Psychological Science gave authors the opportunity to signal open data and materials if they qualified for badges that accompanied published articles. Before badges, less than 3% of Psychological Science articles reported open data. After badges, 23% reported open data, with an accelerating trend; 39% reported open data in the first half of 2015, an increase of more than an order of magnitude from baseline. There was no change over time in the low rates of data sharing among comparison journals. Moreover, reporting openness does not guarantee openness. When badges were earned, reportedly available data were more likely to be actually available, correct, usable, and complete than when badges were not earned. Open materials also increased to a weaker degree, and there was more variability among comparison journals. Badges are simple, effective signals to promote open practices and improve preservation of data and materials by using independent repositories.

  7. Plasmodesmata without callose and calreticulin in higher plants - open channels for fast symplastic transport?

    Directory of Open Access Journals (Sweden)

    Kirill N. Demchenko

    2014-03-01

    Full Text Available Plasmodesmata (PD represent membrane-lined channels that link adjacent plant cells across the cell wall. PD of higher plants contain a central tube of endoplasmic reticulum called desmotubule. Membrane and lumen proteins seem to be able to move through the desmotubule, but most transport processes through PD occur through the cytoplasmic annulus (Brunkard et al., 2013. Calreticulin (CRT, a highly conserved Ca2+-binding protein found in all multi-cellular eukaryotes, predominantly located in the ER, was shown to localize to PD, though not all PD accumulate CRT. In nitrogen fixing actinorhizal root nodules of the Australian tree Casuarina glauca, the primary walls of infected cells containing the microsymbiont become lignified upon infection. TEM analysis of these nodules showed that during the differentiation of infected cells, PD connecting infected cells, and connecting infected and adjacent uninfected cells, were reduced in number as well as diameter (Schubert et al., 2013. In contrast with PD connecting young infected cells, and most PD connecting mature infected and adjacent uninfected cells, PD connecting mature infected cells did not accumulate CRT. Furthermore, as shown here, these PD were not associated with callose, and based on their diameter, they probably had lost their desmotubules. We speculate that either this is a slow path to PD degradation, or that the loss of callose accumulation and presumably also desmotubules leads to the PD becoming open channels and improves metabolite exchange between cells.

  8. Open Tubular Microreactor with Enzyme Functionalized Micro- fluidic Channel for Amperometric Detection of Glucose

    Institute of Scientific and Technical Information of China (English)

    张蕾; 曲平; 盛金; 雷建平; 鞠烷先

    2012-01-01

    A simple and efficient method using enzyme immobilized microfluidic channel as open tubular microreactor was designed for amperometric detection of glucose. The microreactor was composed of a polydimethylsilicone/ glass hybrid device with three reservoirs, a cooling cave and a 6 cm capillary with a sampling fracture as micro-channel. The microchannel was further modified by thermal polymerization, followed by covalently attaching with glucose oxidase. Through fracture sampling and electrochromatography separation, the production via enzymatic reaction was determinated by Pt electrode at the end of capillary. The linear range for the detection of glucose was 0.05--7.5 mmol·L-1 with detection limit of 23μmol.L-1 The inter-and intra-chip reproducibilities for determination of 2.5 mmol-L-1 glucose were 98.5% (n=5) and 96.0% (n=5), respectively. With the advantage of flexible assembly, rapid efficiency, good stability and low-cost, this microreactor provided a potential platform for estab- lishing a portable enzyme-based chemical detection system in practical application.

  9. Mathematical expression of discharge capacity of compound open channels using MARS technique

    Indian Academy of Sciences (India)

    Abbas Parsaie; Amir Hamzeh Haghiabi

    2017-03-01

    In this paper, analytical methods, artificial neural network (ANN) and multivariate adaptive regression splines (MARS) techniques were utilised to estimate the discharge capacity of compound open channels (COC). To this end, related datasets were collected from literature. The results showed that the dividedchannel method with a coefficient of determination (R2) value of 0.76 and root mean square error (RMSE) value of 0.162 has the best performance, among the various analytical methods tested. The performance of applied soft computing models with R2 = 0.97 and RMSE = 0.03 was found to be more accurate than analytical approaches. Comparison of MARS with the ANN model, in terms of developed discrepancy ratio (DDR) index, showed that the accuracy of MARS model was better than that of MLP model. Reviewing the structure of the derived MARS model showed that the longitudinal slope of the channel (S), relative flow depth (Hr) and relative area (Ar) have a high impact on modelling and forecasting the discharge capacity of COCs.

  10. Resveratrol enhances airway surface liquid depth in sinonasal epithelium by increasing cystic fibrosis transmembrane conductance regulator open probability.

    Directory of Open Access Journals (Sweden)

    Shaoyan Zhang

    Full Text Available BACKGROUND: Chronic rhinosinusitis engenders enormous morbidity in the general population, and is often refractory to medical intervention. Compounds that augment mucociliary clearance in airway epithelia represent a novel treatment strategy for diseases of mucus stasis. A dominant fluid and electrolyte secretory pathway in the nasal airways is governed by the cystic fibrosis transmembrane conductance regulator (CFTR. The objectives of the present study were to test resveratrol, a strong potentiator of CFTR channel open probability, in preparation for a clinical trial of mucociliary activators in human sinus disease. METHODS: Primary sinonasal epithelial cells, immortalized bronchoepithelial cells (wild type and F508del CFTR, and HEK293 cells expressing exogenous human CFTR were investigated by Ussing chamber as well as patch clamp technique under non-phosphorylating conditions. Effects on airway surface liquid depth were measured using confocal laser scanning microscopy. Impact on CFTR gene expression was measured by quantitative reverse transcriptase polymerase chain reaction. RESULTS: Resveratrol is a robust CFTR channel potentiator in numerous mammalian species. The compound also activated temperature corrected F508del CFTR and enhanced CFTR-dependent chloride secretion in human sinus epithelium ex vivo to an extent comparable to the recently approved CFTR potentiator, ivacaftor. Using inside out patches from apical membranes of murine cells, resveratrol stimulated an ~8 picosiemens chloride channel consistent with CFTR. This observation was confirmed in HEK293 cells expressing exogenous CFTR. Treatment of sinonasal epithelium resulted in a significant increase in airway surface liquid depth (in µm: 8.08+/-1.68 vs. 6.11+/-0.47,control,p<0.05. There was no increase CFTR mRNA. CONCLUSION: Resveratrol is a potent chloride secretagogue from the mucosal surface of sinonasal epithelium, and hydrates airway surface liquid by increasing CFTR

  11. THREE-DIMENSIONAL LARGE EDDY SIMULATION OF FREE SURFACE TURBULENT FLOW IN OPEN CHANNEL WITHIN SUBMERGED VEGETATION DOMAIN

    Institute of Scientific and Technical Information of China (English)

    Su Xiao-hui; Li C. W.; Chen Bi-hong

    2003-01-01

    A three-dimensional Large Eddy Simulation (LES) has been performed of hydrodynamic behavior of turbulent flow in open channel that the lower part of the domain is occupied by a drag force layer to represent vegetation.One equation model is used to closing the resolvable scale equations.The turbulent characteristic length is parameterized by a k-l model.A phenomenal model is employed to express the performance of vegetation in the open channel.The result reveals that the present model has the capacity of describing three-dimensional structure of large eddy appearing in turbulent flow in open channel with vegetation region and has the capacity of tracing the development of large eddies.

  12. Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel.

    Science.gov (United States)

    Hilf, Ricarda J C; Dutzler, Raimund

    2009-01-01

    The X-ray structure of a pentameric ligand-gated ion channel from Erwinia chrysanthemi (ELIC) has recently provided structural insight into this family of ion channels at high resolution. The structure shows a homo-pentameric protein with a barrel-stave architecture that defines an ion-conduction pore located on the fivefold axis of symmetry. In this structure, the wide aqueous vestibule that is encircled by the extracellular ligand-binding domains of the five subunits narrows to a discontinuous pore that spans the lipid bilayer. The pore is constricted by bulky hydrophobic residues towards the extracellular side, which probably serve as barriers that prevent the diffusion of ions. This interrupted pore architecture in ELIC thus depicts a non-conducting conformation of a pentameric ligand-gated ion channel, the thermodynamically stable state in the absence of bound ligand. As ligand binding promotes pore opening in these ion channels and the specific ligand for ELIC has not yet been identified, we have turned our attention towards a homologous protein from the cyanobacterium Gloebacter violaceus (GLIC). GLIC was shown to form proton-gated channels that are activated by a pH decrease on the extracellular side and that do not desensitize after activation. Both prokaryotic proteins, ELIC and GLIC form ion channels that are selective for cations over anions with poor discrimination among monovalent cations, characteristics that resemble the conduction properties of the cation-selective branch of the family that includes acetylcholine and serotonin receptors. Here we present the X-ray structure of GLIC at 3.1 A resolution. The structure reveals a conformation of the channel that is distinct from ELIC and that probably resembles the open state. In combination, both structures suggest a novel gating mechanism for pentameric ligand-gated ion channels where channel opening proceeds by a change in the tilt of the pore-forming helices.

  13. Large Eddy Simulation of Dilute Sediment Suspension in an Open Channel Flow

    Science.gov (United States)

    Agegnehu, Getnet; Smith, Heather D.

    2012-11-01

    Flow and suspended sediment transport in fully developed turbulent open channel flow has been investigated using Large Eddy Simulation. We used a three-dimensional, non-hydrostatic model, OpenFOAM for this study. Pre-evaluation of three existing turbulence closure schemes is performed by comparing the mean flow and turbulent quantities with the direct numerical simulation results of Moser et al. (1999). It is found that the Dynamic Mixed Smagorinsky model underestimates the wall shear stress compared to the Dynamic Smagorinsky and one equation Eddy Viscosity schemes. Moreover, the Dynamic Smagorinsky scheme gives relatively better results in both the mean and turbulent quantities. The advection-diffusion equation is solved for suspended sediment transport and the effect of sediment roughness is included in the momentum equation based on the rough wall formulation proposed by Cebeci and Bradshaw (1977). A pick up function based on van Rijn (1984) is used to determine the sediment erosion. The settling process is taken into account with a settling velocity appearing in the concentration equation. Sediment and flow quantities are validated by comparing with the experimental data of Lyn (1988). The coupled hydrodynamics results are in good agreement with the experimental data.

  14. Improved Interference-Free Channel Allocation in Coordinated Multiuser Multi-Antenna Open-Access Small Cells

    KAUST Repository

    Radaydeh, Redha

    2016-02-16

    This paper investigates low-complexity joint interference avoidance and desired link improvement for single channel allocation in multiuser multi-antenna access points (APs) for open-access small cells. It is considered that an active user is equipped with an atenna array that can be used to suppress interference sources but not to provide spatial diversity. On the other hand, the operation of APs can be coordinated to meet design requirements, and each of which can unconditionally utilize assigned physical channels. Moreover, each AP is equipped with uncorrelated antennas that can be reused simultaneously to serve many active users. The analysis provides new approaches to exploit physical channels, transmit antennas, and APs to mitigate interference, while providing the best possible link gain to an active user through the most suitable interference-free channel. The event of concurrent service requests placed by active users on a specific interference-free channel is discussed for either interference avoidance through identifying unshared channels or desired link improvement via multiuser scheduling. The applicability of the approaches to balance downlink loads is explained, and practical scenarios due to imperfect identification of interference-free channels and/or scheduled user are thoroughly investigated. The developed results are applicable for any statistical and geometric models of the allocated channel to an active user as well as channel conditions of interference users. They can be used to study various performance measures. Numerical and simulation results are presented to explain some outcomes of this work.

  15. Mechanoprotection by Polycystins against Apoptosis Is Mediated through the Opening of Stretch-Activated K2P Channels

    Directory of Open Access Journals (Sweden)

    Rémi Peyronnet

    2012-03-01

    Full Text Available How renal epithelial cells respond to increased pressure and the link with kidney disease states remain poorly understood. Pkd1 knockout or expression of a PC2 pathogenic mutant, mimicking the autosomal dominant polycystic kidney disease, dramatically enhances mechanical stress-induced tubular apoptotic cell death. We show the presence of a stretch-activated K+ channel dependent on the TREK-2 K2P subunit in proximal convoluted tubule epithelial cells. Our findings further demonstrate that polycystins protect renal epithelial cells against apoptosis in response to mechanical stress, and this function is mediated through the opening of stretch-activated K2P channels. Thus, to our knowledge, we establish for the first time, both in vitro and in vivo, a functional relationship between mechanotransduction and mechanoprotection. We propose that this mechanism is at play in other important pathologies associated with apoptosis and in which pressure or flow stimulation is altered, including heart failure or atherosclerosis.

  16. From pan-reactive KV7 channel opener to subtype selective opener/inhibitor by addition of a methyl group

    DEFF Research Database (Denmark)

    Blom, Sigrid Marie; Rottländer, Mario; Kehler, Jan;

    2014-01-01

    The voltage-gated potassium channels of the KV7 family (KV7.1-5) play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been to....... A compound with this profile could hold novel therapeutic potential such as the treatment of both positive and cognitive symptoms in schizophrenia.......The voltage-gated potassium channels of the KV7 family (KV7.1-5) play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been...

  17. Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression

    Science.gov (United States)

    Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

    2013-01-01

    Human ether-a-go-go-related gene (HERG) K+ channel underlies the rapidly activating delayed rectifier K+ conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels. PMID:23793622

  18. Increasing Access to Higher Education through Open and Distance Learning: Empirical Findings from Mzuzu University, Malawi

    Science.gov (United States)

    Chawinga, Winner Dominic; Zozie, Paxton Andrew

    2016-01-01

    Slowly but surely, open and distance learning (ODL) programmes are being regarded as one of the most practical ways that universities across the world are increasingly adopting in order to increase access to university education. Likewise, Mzuzu University (MZUNI) set up the Centre for Open and Distance Learning (CODL) to oversee the running of…

  19. Engineering of an E. coli outer membrane protein FhuA with increased channel diameter

    Directory of Open Access Journals (Sweden)

    Dworeck Tamara

    2011-08-01

    Full Text Available Abstract Background Channel proteins like FhuA can be an alternative to artificial chemically synthesized nanopores. To reach such goals, channel proteins must be flexible enough to be modified in their geometry, i.e. length and diameter. As continuation of a previous study in which we addressed the lengthening of the channel, here we report the increasing of the channel diameter by genetic engineering. Results The FhuA Δ1-159 diameter increase has been obtained by doubling the amino acid sequence of the first two N-terminal β-strands, resulting in variant FhuA Δ1-159 Exp. The total number of β-strands increased from 22 to 24 and the channel surface area is expected to increase by ~16%. The secondary structure analysis by circular dichroism (CD spectroscopy shows a high β-sheet content, suggesting the correct folding of FhuA Δ1-159 Exp. To further prove the FhuA Δ1-159 Exp channel functionality, kinetic measurement using the HRP-TMB assay (HRP = Horse Radish Peroxidase, TMB = 3,3',5,5'-tetramethylbenzidine were conducted. The results indicated a 17% faster diffusion kinetic for FhuA Δ1-159 Exp as compared to FhuA Δ1-159, well correlated to the expected channel surface area increase of ~16%. Conclusion In this study using a simple "semi rational" approach the FhuA Δ1-159 diameter was enlarged. By combining the actual results with the previous ones on the FhuA Δ1-159 lengthening a new set of synthetic nanochannels with desired lengths and diameters can be produced, broadening the FhuA Δ1-159 applications. As large scale protein production is possible our approach can give a contribution to nanochannel industrial applications.

  20. Hydrodynamic behavior in the outer shear layer of partly obstructed open channels

    Science.gov (United States)

    Ben Meftah, Mouldi; De Serio, Francesca; Mossa, Michele

    2014-06-01

    Despite the many studies on flow in partly obstructed open channels, this issue remains of fundamental importance in order to better understand the interaction between flow behavior and the canopy structure. In the first part of this study we suggest a new theoretical approach able to model the flow pattern within the shear layer in the unobstructed domain, adjacent to the canopy area. Differently from previous studies, the new analytical solution of flow momentum equations takes into account the transversal velocity component of the flow, which is modelled as a linear function of the streamwise velocity. The proposed theoretical model is validated by different experiments carried out on a physical model of a very large rectangular channel by the research group of the Department of Civil, Environmental, Building Engineering and Chemistry of the Technical University of Bari. An array of vertical, rigid, and circular steel cylinders was partially mounted on the bottom in the central part of the flume, leaving two lateral areas of free flow circulation near the walls. The three-dimensional flow velocity components were measured using a 3D Acoustic Doppler Velocimeter. A comparison of the measured and predicted data of the present study with those obtained in other previous studies, carried out with different canopy density, show a non-dependence of this analytical solution on the array density and the Reynolds number. In the second part of the paper, detailed observations of turbulent intensities and spanwise Reynolds stresses in the unobstructed flow are analyzed and discussed. Differently from some earlier studies, it was observed that the peak of the turbulence intensity and that of the spanwise Reynolds stress are significantly shifted toward the center of the shear layer.

  1. Effects of KRN4884, a novel K+ channel opener, on ionic currents in rabbit femoral arterial myocytes.

    Science.gov (United States)

    Muraki, Katsuhiko; Sasaoka, Akiko; Ohya, Susumu; Watanabe, Minoru; Imaizumi, Yuji

    2003-11-01

    Effects of KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine), a novel K(+) channel opener, on ionic currents were examined in rabbit femoral arterial myocytes (RFAMs). Under whole-cell clamp conditions where cells were superfused with 5.9 mM K(+) bathing solution, KRN4884 elicited an outward current at -30 mV. KRN4884-induced current had a reversal potential of -78 mV and was abolished by application of glibenclamide (glib). KRN4884 was approximately 43 times more potent than levcromakalim in activating an ATP-sensitive K(+) current (I(K-ATP)). On the other hand, KRN4884 affected neither voltage-dependent Ca(2+) nor delayed rectifier K(+) channel currents. In the inside-out patch clamp configuration where cells were superfused with the symmetrical 140 mM K(+) solution, KRN4884 activated 47 pS K(+) channels in the presence of adenosine diphosphate. Similar 47 pS K(+) channels, which were reversibly inhibited by glib, were recorded under outside-out patch conditions. Using RT-PCR analysis, we found that inward rectifier K channel 6.1 (Kir6.1) and sulfonylurea 2B (SUR2B) transcripts were predominantly expressed in rabbit femoral artery. These results indicate that KRN4884 potently activates I(K-ATP) in RFAMs. The KRN4884-sensitive 47 pS K(+) channel activity underlying I(K-ATP) is a vascular type K(ATP) channel consisting of Kir6.1 and SUR2B and has similar characteristics to those of ATP-sensitive K(+) channels activated by K(+) channel openers in other types of smooth muscles.

  2. A specific two-pore domain potassium channel blocker defines the structure of the TASK-1 open pore.

    Science.gov (United States)

    Streit, Anne K; Netter, Michael F; Kempf, Franca; Walecki, Magdalena; Rinné, Susanne; Bollepalli, Murali K; Preisig-Müller, Regina; Renigunta, Vijay; Daut, Jürgen; Baukrowitz, Thomas; Sansom, Mark S P; Stansfeld, Phillip J; Decher, Niels

    2011-04-22

    Two-pore domain potassium (K(2P)) channels play a key role in setting the membrane potential of excitable cells. Despite their role as putative targets for drugs and general anesthetics, little is known about the structure and the drug binding site of K(2P) channels. We describe A1899 as a potent and highly selective blocker of the K(2P) channel TASK-1. As A1899 acts as an open-channel blocker and binds to residues forming the wall of the central cavity, the drug was used to further our understanding of the channel pore. Using alanine mutagenesis screens, we have identified residues in both pore loops, the M2 and M4 segments, and the halothane response element to form the drug binding site of TASK-1. Our experimental data were used to validate a K(2P) open-pore homology model of TASK-1, providing structural insights for future rational design of drugs targeting K(2P) channels.

  3. A Specific Two-pore Domain Potassium Channel Blocker Defines the Structure of the TASK-1 Open Pore*

    Science.gov (United States)

    Streit, Anne K.; Netter, Michael F.; Kempf, Franca; Walecki, Magdalena; Rinné, Susanne; Bollepalli, Murali K.; Preisig-Müller, Regina; Renigunta, Vijay; Daut, Jürgen; Baukrowitz, Thomas; Sansom, Mark S. P.; Stansfeld, Phillip J.; Decher, Niels

    2011-01-01

    Two-pore domain potassium (K2P) channels play a key role in setting the membrane potential of excitable cells. Despite their role as putative targets for drugs and general anesthetics, little is known about the structure and the drug binding site of K2P channels. We describe A1899 as a potent and highly selective blocker of the K2P channel TASK-1. As A1899 acts as an open-channel blocker and binds to residues forming the wall of the central cavity, the drug was used to further our understanding of the channel pore. Using alanine mutagenesis screens, we have identified residues in both pore loops, the M2 and M4 segments, and the halothane response element to form the drug binding site of TASK-1. Our experimental data were used to validate a K2P open-pore homology model of TASK-1, providing structural insights for future rational design of drugs targeting K2P channels. PMID:21362619

  4. Effectiveness Using Circular Fibre Steel Flap Gate As a Control Structure Towards the Hydraulic Characteristics in Open Channel

    Science.gov (United States)

    Adib, M. R. M.; Amirza, A. R. M.; Wardah, T.; Junaidah, A.

    2016-07-01

    Hydraulic control gate structure plays an important role in regulating the flow of water in river, canal or water reservoir. One of the most appropriate structures in term of resolving the problem of flood occured is the construction of circular fibre steel flap gate. Therefore, an experiment has been conducted by using an open channel model at laboratory. In this case, hydraulic jump and backwater were the method to determined the hydraulic characteristics of circular fibre steel flap gate in an open channel model. From the experiment, the opening angle of flap gate can receive discharges with the highest flow rate of 0.035 m3/s with opening angle was 47°. The type of jump that occurs at the slope of 1/200 for a distance of 5.0 m is a standing jump or undulating wave. The height of the backwater can be identified based on the differences of specific force which is specific force before jump, F1 and specific force after jump, F2 from the formation of backwater. Based on the research conducted, the tendency of incident backwater wave occurred was high in every distance of water control location from water inlet is flap slope and the slope of 1/300 which is 0.84 m/s and 0.75 m/s of celerity in open channel model.

  5. Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure

    Institute of Scientific and Technical Information of China (English)

    Li-hong FAN; Hong-yan TIAN; Ai-qun MA; Zhi HU; Jian-hua HUO; Yong-xiao CAO

    2008-01-01

    Aim:To determine whether ATP-sensitive potassium channels are altered in VSMC from arotas and mesenteric arteries of obese rat,and their association with obesity-triggered increase in blood pressure.Methods:Obesity was induced by 24 weeks of high-fat diet feeding in male Sprague-Dawley rats.Control rats were fed with standard laboratory rat chow.Blood pressure and body weight of these rats were measured every 4 weeks.At the end of 24 weeks,KATP channel-mediated relaxation responses in the aortas and mesenteric arteries,KATP channel current,and gene expression were examined,respectively.Results:Blood pres-sure and body weight were increased in rats fed with high-fat diet.KATP channel-mediated relaxation responses,currents,and KATP expression in VSMC of both aortas and mesenteric arteries were inhibited in these rats.Conclusion:Altered ATP-sensitive potassium channels in obese rats may underscore obesity-triggered increase in blood pressure.

  6. A Numerical Study of Non-hydrostatic Shallow Flows in Open Channels

    Science.gov (United States)

    Zerihun, Yebegaeshet T.

    2017-06-01

    The flow field of many practical open channel flow problems, e.g. flow over natural bed forms or hydraulic structures, is characterised by curved streamlines that result in a non-hydrostatic pressure distribution. The essential vertical details of such a flow field need to be accounted for, so as to be able to treat the complex transition between hydrostatic and non-hydrostatic flow regimes. Apparently, the shallow-water equations, which assume a mild longitudinal slope and negligible vertical acceleration, are inappropriate to analyse these types of problems. Besides, most of the current Boussinesq-type models do not consider the effects of turbulence. A novel approach, stemming from the vertical integration of the Reynolds-averaged Navier-Stokes equations, is applied herein to develop a non-hydrostatic model which includes terms accounting for the effective stresses arising from the turbulent characteristics of the flow. The feasibility of the proposed model is examined by simulating flow situations that involve non-hydrostatic pressure and/or nonuniform velocity distributions. The computational results for free-surface and bed pressure profiles exhibit good correlations with experimental data, demonstrating that the present model is capable of simulating the salient features of free-surface flows over sharply-curved overflow structures and rigid-bed dunes.

  7. Experimental investigation of internal structure of open-channel flow with intense transport of sediment

    Directory of Open Access Journals (Sweden)

    Matoušek Václav

    2015-12-01

    Full Text Available Gravity-driven open-channel flows carrying coarse sediment over an erodible granular deposit are studied. Results of laboratory experiments with artificial sediments in a rectangular tilting flume are described and analyzed. Besides integral quantities such as flow rate of mixture, transport concentration of sediment and hydraulic gradient, the experiments include measurements of the one-dimensional velocity distribution across the flow. A vertical profile of the longitudinal component of local velocity is measured across the vertical axis of symmetry of a flume cross section using three independent measuring methods. Due to strong flow stratification, the velocity profile covers regions of very different local concentrations of sediment from virtually zero concentration to the maximum concentration of bed packing. The layered character of the flow results in a velocity distribution which tends to be different in the transport layer above the bed and in the sediment-free region between the top of the transport layer and the water surface. Velocity profiles and integral flow quantities are analyzed with the aim of evaluating the layered structure of the flow and identifying interfaces in the flow with a developed transport layer above the upper plane bed.

  8. Simulation and analysis of ice processes in an artificial open channel

    Institute of Scientific and Technical Information of China (English)

    GUO Xin-lei; YANG Kai-lin; FU Hui; WANG Tao; GUO Yong-xin

    2013-01-01

    The Middle Route Project for South-to-North Water Transfer,which consists of a long artificial open channel and various hydraulic constructions,is a big water conveyance system.A numerical modeling of water conveyance in the ice period for such large-scale and long distance water transfer project is developed based on the integration of a river ice model and an unsteady flow model with complex inner boundaries.A simplified method to obtain the same flow discharge in the upstream and downstream of the structure by neglecting the storage effect is proposed for dealing with the inner boundaries.According to the measured and design data in winter-spring period,the whole ice process,which includes the formation of the ice cover,its development,the melting and the breaking up as well as the ice-water dynamic response during the gate operation for the middle route,is simulated.The ice characteristics and the water conveyance capacity are both analyzed and thus the hydraulic control conditions for a safety regulation are obtained.At last,the uncertainties of some parameters related to the ice model are discussed.

  9. One-dimensional velocity profiles in open-channel flow with intense transport of coarse sediment

    Directory of Open Access Journals (Sweden)

    Zrostlík Štěpán

    2015-01-01

    Full Text Available The paper deals with laboratory experiments in open-channel flows with intense transport of model sediment (coarse plastic particles in our new tilting flume. The major objectives of the paper are: 1. to discuss applied measuring methods, 2. to analyze measured velocity profiles. Ad 1. A profile of the longitudinal component of local velocity was measured across the vertical axis of symmetry of a flume cross section using three independent measuring methods (Prandtl tube, Ultrasonic Velocity Profiler, Acoustic Doppler Velocity Profiler. Due to strong stratification of the flow in the flume, parts of the profile are measured in regions of very different local concentrations of sediment (from virtually zero concentration to the maximum concentration of bed packing. This makes measurements complicated, particularly for ultrasonic measuring techniques. Profiles measured using the different techniques are evaluated and mutually compared. Ad 2. The layered character of the flow causes that shapes of velocity profiles tend to be different in the transport layer (rich on transported particles above the bed and in the solids-free region between the top of the transport layer and the water surface. Shapes of the profiles are analyzed. Particular attention is paid to the logarithmic profile in the solids-free region of the flow cross section. The profile can be handled using the law of the hydraulically-rough wall. In the law, the eroded top of the bed with the transport layer is supposed to be the rough boundary and appropriate values are sought for its variables.

  10. Quantification of the bed load effects on turbulent open-channel flows

    Science.gov (United States)

    Liu, Detian; Liu, Xiaofeng; Fu, Xudong; Wang, Guangqian

    2016-04-01

    With a computational model combining large eddy simulation and a discrete element model, detailed quantification of the bed load effects on turbulent open-channel flows is presented. The objective is the revelation of bed load particle impact on the mean flow properties and coherent structures. Two comparative numerical experiments with mobile and immobile beds are conducted. Mean properties (e.g., velocity and Reynolds stress profiles) show good agreement with experimental data. Comparing the mobile and immobile cases, the effective bed position is nearly the same, whereas the equivalent sand roughness is changed. The flow experiences higher bottom shear stress over immobile bed. To quantify impact on turbulent structures, a revised quadrant analysis is performed to calculate four key parameters of ejection and sweep events (duration, maximum shear stress, transported momentum, and period). Results show that the ejection and sweep events have comparable importance in the outer region. However, sweep becomes dominant in the near-wall region. The motion of particles enhances the sweep dominance by breaking up the ejection structures and decreasing their occurrence ratio. The results also suggest that the ejection events are easier to be influenced by the particle motions because they originate from the near-wall region. The duration, maximum shear stress, and transported momentum decrease close to the bed. The period remains relatively constant in the outer region but decreases near the bed. Visualization of the coherent structure reveals that the instantaneous particle motion has strong correlation with the bursting cycle events.

  11. Antispasmodic activity of Symplocos paniculata is mediated through opening of ATP-dependent K+ channel

    Directory of Open Access Journals (Sweden)

    Khalid Hussain Janbaz

    2016-06-01

    Full Text Available Symplocos paniculata is a medicinal plant used by native healers to manage gastrointestinal ailments. The crude methanolic extract of S. paniculata was screened pharmacologically both in vitro and in vivo for the validation of its therapeutic potential. It suppressed the spontaneous activity of isolated rabbit jejunum preparations and also caused inhibition of the low K+ (20 mM- induced spastic contractions in isolated rabbit jejunum preparations in a manner comparable to cromakalim. The relaxant effect was found to be blocked following glibenclamide exposure of the isolated tissue preparations similar to cromakalim, suggesting that observed response was likely to be mediated through opening of ATP dependent K+ channels. Following oral administration to mice provided protection against castor oil-induced diarrhea in a manner similar to loperamide. The plant material was found safe in toxicity study up to oral dose of 8 g/kg in mice. Hence, present study provides a scientific basis for the vernacular use of S. paniculata in gastro-intestinal system.

  12. DNS-DEM of Suspended Sediment Particles in an Open Channel Flow

    Science.gov (United States)

    Pakseresht, Pedram; Apte, Sourabh; Finn, Justin

    2016-11-01

    DNS with point-particle based discrete element model (DEM) is used to study particle-turbulence interactions in an open channel flow at Reτ of 710, corresponding to the experimental observations of Righetti & Romano. Large particles of diameter 200 microns (10 in wall units) with volume loading on the order of 10-3 are simulated using four-way coupling with closure models for drag, added mass, lift, pressure, and inter-particle collision forces. The point-particle model is able to accurately capture the effect of particles on the fluid flow in the outer layer. However, the particle is significantly larger than the wall-normal grid in the near-wall region, but slightly smaller than the axial and longitudinal grid resolutions. The point-particle model fails to capture the interactions in the near-wall region. In order to improve the near-wall predictions, particles are represented by Lagrangian material points which are used to perform interpolations from the grid to the Lagrangian points and to distribute the two-way coupling force to the Eulerian grid. Predictions using this approach is compared with the experimental data to evaluate its effectiveness. NSF project #1133363, Sediment-Bed-Turbulence Coupling in Oscillatory Flows.

  13. POINTWISE AND UPWIND DISCRETIZATIONS OF SOURCE TERMS IN OPEN-CHANNEL FLOOD ROUTING

    Institute of Scientific and Technical Information of China (English)

    MENG Jian; CAO Zhi-xian; CARLING Paul A.

    2006-01-01

    Upwind algorithms are becoming progressively popular for river flood routing due to their capability of resolving trans-critical flow regimes. For consistency, these algorithms suggest natural upwind discretization of the source term, which may be essential for natural channels with irregular geometry. Yet applications of these upwind algorithms to natural river flows are rare, and in such applications the traditional and simpler pointwise, rather than upwind discretization of the source term is used. Within the framework of a first-order upwind algorithm, this paper presents a comparison of upwind and pointwise discretizations of the source term. Numerical simulations were carried out for a selected irregular channel comprising a pool-riffle sequence in the River Lune, England with observed data. It is shown that the impact of pointwise discretization, compared to the upwind, is appreciable mainly in flow zones with the Froude number closer to or larger than unity. The discrepancy due to pointwise and upwind discretizations of the source term is negligible in flow depth and hence in water surface elevation, but well manifested in mean velocity and derived flow quantities. Also the occurrence of flow reversal and equalisation over the pool-riffle sequence in response to increasing discharges is demonstrated.

  14. IgG from Amyotrophic Lateral Sclerosis Patients Increases Current Through P-Type Calcium Channels in Mammalian Cerebellar Purkinje Cells and in Isolated Channel Protein in Lipid Bilayer

    Science.gov (United States)

    Llinas, R.; Sugimori, M.; Cherksey, B. D.; Smith, R. Glenn; Delbono, O.; Stefani, E.; Appel, S.

    1993-12-01

    The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltage-dependent barium currents (IBa) in mammalian dissociated Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of IBa without modifying their voltage kinetics. This increased IBa could be blocked by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider toxin) and by a peptide toxin from the same spider venom, ω-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBa open time without affecting slope conductance. The results described above were not seen with normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances inward current through P-type calcium channels. Since P-type Ca2+ channels are present in motoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.

  15. Insulin Increases Expression of TRPC6 Channels in Podocytes by a Calcineurin-Dependent Pathway

    DEFF Research Database (Denmark)

    Xia, Shengqiang; Liu, Ying; Li, Xinming

    2016-01-01

    BACKGROUND/AIMS: Insulin signaling to podocytes is relevant for the function of the glomerulus. Now, we tested the hypothesis that insulin increases the surface expression of canonical transient receptor potential canonical type 6 (TRPC6) channels in podocytes by a calcineurin-dependent pathway. ...

  16. Loop diuretics are open-channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics

    Science.gov (United States)

    Ju, Min; Scott-Ward, Toby S; Liu, Jia; Khuituan, Pissared; Li, Hongyu; Cai, Zhiwei; Husbands, Stephen M; Sheppard, David N

    2014-01-01

    BACKGROUND AND PURPOSE Loop diuretics are widely used to inhibit the Na+, K+, 2Cl− co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade. EXPERIMENTAL APPROACH Using the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR. KEY RESULTS When added to the intracellular solution, loop diuretics inhibited CFTR Cl− currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to loop diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl− channels with ‘very fast’ speed and drug-induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with ‘intermediate’ speed and drug-induced blocking events were distinct from channel closures. CONCLUSIONS AND IMPLICATIONS Structure–activity analysis of the loop diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking loop diuretics within the intracellular vestibule of the CFTR pore. We conclude that loop diuretics are open-channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity. PMID:24117047

  17. Increasing lifetime of the plasma channel formed in air using picosecond and nanosecond laser pulses

    Science.gov (United States)

    Narayanan, V.; Singh, V.; Pandey, Pramod K.; Shukla, Neeraj; Thareja, R. K.

    2007-04-01

    We report experiments on a pump-probe configuration to elucidate the formation of a plasma channel by the hydrodynamic evolution of air breakdown in laser focus. A stable air breakdown was produced by focusing a picosecond laser pulse to create a shock driven plasma channel in the laser focus for propagating a nanosecond pulse. A four fold increase in the lifetime of the channel estimated by monitoring the temporal evolution of the fluorescence of a spectral line at 504.5nm of N+ transition 3pS3-3sP03 is reported. Assuming plasma in local thermal equilibrium plasma temperature of ˜8.2eV and an electron density of ˜1.4×1018cm-3 were determined using a Stark broadening of 649.2nm line of NII transition 3dD03-4pD3 in the channel. An enhancement in the electron density of the plasma channel was observed at the 7ns delay of the nanosecond laser pulse relative to the picosecond laser pulse.

  18. Surface velocity divergence model of air/water interfacial gas transfer in open-channel flows

    Science.gov (United States)

    Sanjou, M.; Nezu, I.; Okamoto, T.

    2017-04-01

    Air/water interfacial gas transfer through a free surface plays a significant role in preserving and restoring water quality in creeks and rivers. However, direct measurements of the gas transfer velocity and reaeration coefficient are still difficult, and therefore a reliable prediction model needs to be developed. Varying systematically the bulk-mean velocity and water depth, laboratory flume experiments were conducted and we measured surface velocities and dissolved oxygen (DO) concentrations in open-channel flows to reveal the relationship between DO transfer velocity and surface divergence (SD). Horizontal particle image velocimetry measurements provide the time-variations of surface velocity divergence. Positive and negative regions of surface velocity divergence are transferred downstream in time, as occurs in boil phenomenon on natural river free-surfaces. The result implies that interfacial gas transfer is related to bottom-situated turbulence motion and vertical mass transfer. The original SD model focuses mainly on small-scale viscous motion, and this model strongly depends on the water depth. Therefore, we modify the SD model theoretically to accommodate the effects of the water depth on gas transfer, introducing a non-dimensional parameter that includes contributions of depth-scale large-vortex motion, such as secondary currents, to surface renewal events related to DO transport. The modified SD model proved effective and reasonable without any dependence on the bulk mean velocity and water depth, and has a larger coefficient of determination than the original SD model. Furthermore, modeling of friction velocity with the Reynolds number improves the practicality of a new formula that is expected to be used in studies of natural rivers.

  19. Relationship between ecosystem respiration and aeration constant in open channel dissolved oxygen analysis

    Science.gov (United States)

    Parker, S. J.; Butler, A. P.; Heppell, C. M.

    2015-12-01

    Using the open channel diel method of Odum (1956) and the night-time regression method (Hornberger and Kelly, 1985), we analysed a time series of dissolved oxygen (DO) in two slow flowing streams for a two month period in summer 2014 and obtained values for ecosystem respiration and the aeration constant for each day in the period. We then used the standard dissolved oxygen lumped model to generate a DO time series behaviour for one of those rivers selecting respiration and aeration parameters by randomly sampling from the values obtained from the data. Two synthetic time series were created, one where respiration and aeration were independent of temperature and a second where respiration and aeration were affected by temperature according to the modified Arrhenius relationship. With these two synthetic time series, we again recovered the respiration and aeration input parameters using the night- time regression method and compared those recovered parameters with the input parameters. Because the simulations were conducted with parameters that were known, the values recovered using the night-time regression method (i.e post-simulation) could be compared with parameters driving the simulation (i.e. pre-simulation input values). For values based on data, we found a strong correlation between the aeration constant and respiration for both rivers. For the synthetic time series, no such correlation was found, either with the temperature independent or temperature dependent time series. The night-time regression method also recovered perfectly the input parameters, so the correlation was not brought about as a result of implementing the method itself. We are currently investigating the cause of the correlation.

  20. Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine.

    Science.gov (United States)

    Kim, Sung Eun; Ahn, Hye Sook; Choi, Bok Hee; Jang, Hyun-Jong; Kim, Myung-Jun; Rhie, Duck-Joo; Yoon, Shin-Hee; Jo, Yang-Hyeok; Kim, Myung-Suk; Sung, Ki-Wug; Hahn, Sang June

    2007-05-01

    The effects of sibutramine on voltage-gated K+ channel (Kv)4.3, Kv1.3, and Kv3.1, stably expressed in Chinese hamster ovary cells, were investigated using the whole-cell patch-clamp technique. Sibutramine did not significantly decrease the peak Kv4.3 currents, but it accelerated the rate of decay of current inactivation in a concentration-dependent manner. This phenomenon was effectively characterized by integrating the total current over the duration of a depolarizing pulse to +40 mV. The IC50 value for the sibutramine block of Kv4.3 was 17.3 microM. Under control conditions, the inactivation of Kv4.3 currents could be fit to a biexponential function, and the time constants for the fast and slow components were significantly decreased after the application of sibutramine. The association (k+1) and dissociation (k-1) rate constants for the sibutramine block of Kv 4.3 were 1.51 microM-1s-1 and 27.35 s-1, respectively. The theoretical KD value, derived from k-1/k+1, yielded a value of 18.11 microM. The block of Kv4.3 by sibutramine displayed a weak voltage dependence, increasing at more positive potentials, and it was use-dependent at 2 Hz. Sibutramine did not affect the time course for the deactivating tail currents. Neither steady-state activation and inactivation nor the recovery from inactivation was affected by sibutramine. Sibutramine caused the concentration-dependent block of the Kv1.3 and Kv3.1 currents with an IC50 value of 3.7 and 32.7 microM, respectively. In addition, sibutramine reduced the tail current amplitude and slowed the deactivation of the tail currents of Kv1.3 and Kv3.1, resulting in a crossover phenomenon. These results indicate that sibutramine acts on Kv4.3, Kv1.3, and Kv3.1 as an open channel blocker.

  1. Mouth-opening increases upper-airway collapsibility without changing resistance during midazolam sedation.

    Science.gov (United States)

    Ayuse, T; Inazawa, T; Kurata, S; Okayasu, I; Sakamoto, E; Oi, K; Schneider, H; Schwartz, A R

    2004-09-01

    Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to -3.6 +/- 2.9 cm H2O compared with -8.7 +/- 2.8 (p = 0.002) for closed mouths and -7.2 +/- 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 +/- 6.6 vs. 17.7 +/- 7.6 vs. 21.5 +/- 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 +/- 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

  2. Hair cell BK channels interact with RACK1, and PKC increases its expression on the cell surface by indirect phosphorylation

    OpenAIRE

    Surguchev, Alexei; Bai, Jun-Ping; Joshi, Powrnima; Navaratnam, Dhasakumar

    2012-01-01

    Large conductance (BK) calcium activated potassium channels (Slo) are ubiquitous and implicated in a number of human diseases including hypertension and epilepsy. BK channels consist of a pore forming α-subunit (Slo) and a number of accessory subunits. In hair cells of nonmammalian vertebrates these channels play a critical role in electrical resonance, a mechanism of frequency selectivity. Hair cell BK channel clusters on the surface and currents increase along the tonotopic axis and contrib...

  3. Error control and channel access technique of the computer-based truck dispatching system in the open-pit mine

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, G.; Wang, Y.; Huang, Z. [China University of Mining and Technology (China)

    1994-06-01

    The disposition of hardware and software of a computer-based truck dispatching system for open-pit mine are described in the paper. The advantages of random channel access technique of the CSMA/CA/CD of the SWARQ error control and of encoding of constant proportion code were proved by theoretical analysis. The block diagram of the main communication software is given. 3 refs., 4 figs.

  4. Crystal Structure of Inhibitor-Bound P450BM-3 Reveals Open Conformation of Substrate Access Channel

    Energy Technology Data Exchange (ETDEWEB)

    Haines, Donovan C.; Chen, Baozhi; Tomchick, Diana R.; Bondlela, Muralidhar; Hegde, Amita; Machius, Mischa; Peterson, Julian A. (Texas); (UTSMC)

    2008-08-19

    P450BM-3 is an extensively studied P450 cytochrome that is naturally fused to a cytochrome P450 reductase domain. Crystal structures of the heme domain of this enzyme have previously generated many insights into features of P450 structure, substrate binding specificity, and conformational changes that occur on substrate binding. Although many P450s are inhibited by imidazole, this compound does not effectively inhibit P450BM-3. {omega}-Imidazolyl fatty acids have previously been found to be weak inhibitors of the enzyme and show some unusual cooperativity with the substrate lauric acid. We set out to improve the properties of these inhibitors by attaching the {omega}-imidazolyl fatty acid to the nitrogen of an amino acid group, a tactic that we used previously to increase the potency of substrates. The resulting inhibitors were significantly more potent than their parent compounds lacking the amino acid group. A crystal structure of one of the new inhibitors bound to the heme domain of P450BM-3 reveals that the mode of interaction of the amino acid group with the enzyme is different from that previously observed for acyl amino acid substrates. Further, required movements of residues in the active site to accommodate the imidazole group provide an explanation for the low affinity of imidazole itself. Finally, the previously observed cooperativity with lauric acid is explained by a surprisingly open substrate-access channel lined with hydrophobic residues that could potentially accommodate lauric acid in addition to the inhibitor itself.

  5. Hypoxic pulmonary hypertension and novel ATP-sensitive potassium channel opener: the new hope on the horizon

    Institute of Scientific and Technical Information of China (English)

    Yu JIN; Wei-ping XIE; Hong WANG

    2012-01-01

    Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries.The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance,reverse pulmonary vascular remodeling,and thereby improving right ventricular function.Iptakalim,a lipophilic para-amino compound with a low molecular weight,has been demonstrated to be a new selective ATP-sensitive potassium (KATP) channel opener via pharmacological,electrophysiological,biochemical studies,and receptor binding tests.In hypoxia-induced animal models,iptakalim decreases the elevated mean pressure in pulmonary arteries,and attenuates remodeling in the right ventricle,pulmonary arteries and airways.Furthermore,iptakalim has selective antihypertensive effects,selective vasorelaxation effects on smaller arteries,and protective effects on endothelial cells,but no effects on the central nervous,respiratory,digestive or endocrine systems at therapeutic dose.Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1,reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells.Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials,it can be a potential candidate of HPH in the future.

  6. On the exact analytical solution for the spatial moments of the cross-sectional average concentration in open channel flows

    Science.gov (United States)

    Pannone, Marilena

    2012-08-01

    This paper shows how an exact analytical solution for the transient-state spatial moments of the cross-sectional average tracer concentration in large open channel flows can be derived from the depth-averaged advection-diffusion equation resorting to the method of Green's functions, without any simplifying assumption about the regularity of the actual concentration field, the smallness of the fluctuations, or the large space-time scale of variation of the average concentration gradient (justifying the a priori localization of the problem), which were the basis of the classic Taylor dispersion theory. The results reveal that in agreement with the findings by Aris (1956) and later by others for flows within a conduit, there are an initial centroid displacement and a variance deficit dependent on the specific position and dimension of the initial injection. The second central moment asymptotically tends to the linearly increasing function predictable on the basis of Taylor's classic theory, and the skewness, which is constantly zero for the cross-sectionally uniform injection, in the case of nonuniform initial distributions tends to slowly vanish after having reached a maximum. Thus, the persistent asymmetry exhibited by the field concentration data, as well as the retardations and the accelerations in the peak trajectory, can be justified without making any a priori assumption about the physical mechanism underlying their appearance, like transient storage phenomena, just by rigorously solving the governing equation for the cross-sectional average concentration in the presence of nonuniform, asymmetrically located solute injections.

  7. Groundwater flow into underground openings in fractured crystalline rocks: an interpretation based on long channels

    Science.gov (United States)

    Black, John H.; Woodman, Nicholas D.; Barker, John A.

    2016-12-01

    Rethinking an old tracer experiment in fractured crystalline rock suggests a concept of groundwater flow in sparse networks of long channels that is supported by results from an innovative lattice network model. The model, HyperConv, can vary the mean length of `strings' of connected bonds, and the gaps between them, using two independent probability functions. It is found that networks of long channels are able to percolate at lower values of (bond) density than networks of short channels. A general relationship between mean channel length, mean gap length and probability of percolation has been developed which incorporates the well-established result for `classical' lattice network models as a special case. Using parameters appropriate to a 4-m diameter drift located 360 m below surface at Stripa Mine Underground Research Laboratory in Sweden, HyperConv is able to reproduce values of apparent positive skin, as observed in the so-called Macropermeability Experiment, but only when mean channel length exceeds 10 m. This implies that such channel systems must cross many fracture intersections without bifurcating. A general relationship in terms of flow dimension is suggested. Some initial investigations using HyperConv show that the commonly observed feature, `compartmentalization', only occurs when channel density is just above the percolation threshold. Such compartments have been observed at Kamaishi Experimental Mine (Japan) implying a sparse flow network. It is suggested that compartments and skin are observable in the field, indicate sparse channel systems, and could form part of site characterization for deep nuclear waste repositories.

  8. Assessing the performance of multi-purpose channel management measures at increasing scales

    Science.gov (United States)

    Wilkinson, Mark; Addy, Steve

    2016-04-01

    In addition to hydroclimatic drivers, sediment deposition from high energy river systems can reduce channel conveyance capacity and lead to significant increases in flood risk. There is an increasing recognition that we need to work with the interplay of natural hydrological and morphological processes in order to attenuate flood flows and manage sediment (both coarse and fine). This typically includes both catchment (e.g. woodland planting, wetlands) and river (e.g. wood placement, floodplain reconnection) restoration approaches. The aim of this work was to assess at which scales channel management measures (notably wood placement and flood embankment removal) are most appropriate for flood and sediment management in high energy upland river systems. We present research findings from two densely instrumented research sites in Scotland which regularly experience flood events and have associated coarse sediment problems. We assessed the performance of a range of novel trial measures for three different scales: wooded flow restrictors and gully tree planting at the small scale (engineered log jams at the intermediate scale (5-60 km2), and flood embankment lowering at the large scale (350 km2). Our results suggest that at the smallest scale, care is needed in the installation of flow restrictors. It was found for some restrictors that vertical erosion can occur if the tributary channel bed is disturbed. Preliminary model evidence suggested they have a very limited impact on channel discharge and flood peak delay owing to the small storage areas behind the structures. At intermediate scales, the ability to trap sediment by engineered log jams was limited. Of the 45 engineered log jams installed, around half created a small geomorphic response and only 5 captured a significant amount of coarse material (during one large flood event). As scale increases, the chance of damage or loss of wood placement is greatest. Monitoring highlights the importance of structure design

  9. Offset-Free Model Predictive Control of Open Water Channel Based on Moving Horizon Estimation

    Science.gov (United States)

    Ekin Aydin, Boran; Rutten, Martine

    2016-04-01

    Model predictive control (MPC) is a powerful control option which is increasingly used by operational water managers for managing water systems. The explicit consideration of constraints and multi-objective management are important features of MPC. However, due to the water loss in open water systems by seepage, leakage and evaporation a mismatch between the model and the real system will be created. These mismatch affects the performance of MPC and creates an offset from the reference set point of the water level. We present model predictive control based on moving horizon estimation (MHE-MPC) to achieve offset free control of water level for open water canals. MHE-MPC uses the past predictions of the model and the past measurements of the system to estimate unknown disturbances and the offset in the controlled water level is systematically removed. We numerically tested MHE-MPC on an accurate hydro-dynamic model of the laboratory canal UPC-PAC located in Barcelona. In addition, we also used well known disturbance modeling offset free control scheme for the same test case. Simulation experiments on a single canal reach show that MHE-MPC outperforms disturbance modeling offset free control scheme.

  10. Assessing and Testing Hydrokinetic Turbine Performance and Effects on Open Channel Hydrodynamics: An Irrigation Canal Case Study.

    Energy Technology Data Exchange (ETDEWEB)

    Gunawan, Budi [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Neary, Vincent Sinclair [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mortensen, Josh [United States Bureau of Reclamation, Denver, CO (United States); Roberts, Jesse D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-05-01

    Hydrokinetic energy from flowing water in open channels has the potential to support local electricity needs with lower regulatory or capital investment than impounding water with more conventional means. MOU agencies involved in federal hydropower development have identified the need to better understand the opportunities for hydrokinetic (HK) energy development within existing canal systems that may already have integrated hydropower plants. This document provides an overview of the main considerations, tools, and assessment methods, for implementing field tests in an open-channel water system to characterize current energy converter (CEC) device performance and hydrodynamic effects. It describes open channel processes relevant to their HK site and perform pertinent analyses to guide siting and CEC layout design, with the goal of streamlining the evaluation process and reducing the risk of interfering with existing uses of the site. This document outlines key site parameters of interest and effective tools and methods for measurement and analysis with examples drawn from the Roza Main Canal, in Yakima, WA to illustrate a site application.

  11. Hydraulics of combining flow in a right-angled compound open channel junction

    Indian Academy of Sciences (India)

    Sushant K Biswal; Pranab Mohapatra; K Muralidhar

    2016-01-01

    Although combining flows are common in natural streams, no comprehensive experimental data has been compiled to characterize the three-dimensional flow field within the compound channel confluence. The present study examines the time-averaged flow structure at confluence over a rigid bed. Current knowledge of channel confluence, based on laboratory observation indicates that cross flow interactions exert a significant influence on confluence events. Secondary current and turbulent stresses are reproduced well by the hydraulic model and found greater in the interface region as relative flow ratio decreases. Velocity fields in combining flow region arising from varying discharge ratios are presented. A zone of depression in surface elevation in compound channel junction is observed as well. The flow field in compound channel is seen to be moderately different from that of simple channel junction. This study contributes to a better knowledge of hydraulic key processes into fundamental aspect of combining flow dynamics.

  12. THE USE OF NEW DISTRIBUTION CHANNELS TO INCREASE THE EFFICIENCY OF INSURANCE COMPANIES

    Directory of Open Access Journals (Sweden)

    Olga N. Kozlova

    2017-09-01

    Full Text Available The article deals with the issues of increasing the efficiency of insurance companies on the basis of using new non-traditional distribution channels. The relevance of the topic is justified by the automation of management processes, a new generation of consumers focused on new technologies, the use of the Internet, growing and selling functional mobile gadgets. The insurance companies use new distribution channels via the Internet network along with the traditional means for the expansion of the insurance portfolio and attracting active and passive consumers. The calculations carried out on the basis of the data of the Bank of Russia show that the share of such sales is growing, but not leading. The use of the Internet depends on many factors, but primarily on the types of insurance. The authors carry out calculations on the use of distribution channels in various types of insurance. The complexity and variety of products on life insurance requires qualified intermediaries, therefore, the use of new distribution channels here is not widespread in contrast to classical accident insurance or compulsory insurance, where sales are more efficient when organizing through the Internet. Selling through Internet has a number of advantages that reduce the cost of doing business, reduce the agency network, the cost of print advertising to attract passive and strengthen the relationship with active consumers. The authors also conduct analysis of the advantages and disadvantages of using mobile gadgets to work with potential customers, quantitative and qualitative benefits of implementing mobile apps in the work of insurance companies. The conclusions are made about the complexity of calculation of economic efficiency of implementing mobile applications. The possible directions of increasing the efficiency of using new distribution channels by insurance companies are defined.

  13. Rapid antidepressants stimulate the decoupling of GABAB receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η

    OpenAIRE

    Workman, E R; Haddick, P C G; Bush, K.; Dilly, G A; Niere, F; Zemelman, B V; Raab-Graham, K F

    2015-01-01

    A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces a rapid antidepressant response. Lasting changes in the synapse structure and composition underlie the effectiveness of these drugs. We recently discovered that rapid antidepressants cause a shift in the γ-aminobutyric acid receptor (GABABR) signaling pathway, such that GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal and mamma...

  14. Fine sediment dynamics in unsteady open-channel flow studied with acoustic and optical systems

    Science.gov (United States)

    Bagherimiyab, Fereshteh; Lemmin, Ulrich

    2012-09-01

    In order to simulate fine sediment dynamics over an armored bed in a tidal river, unsteady accelerating, then steady open-channel flow over a movable (but not moving) coarse gravel bed (D50=5.5 mm) was studied. A layer of fine sediment (D50=120 μm) was placed on the coarse gravel bed. The thickness of the fine sediment layer on the gravel bed was varied between 4 and 6 mm, but it was found that the thickness of the layer had no effect on the results. Quasi-instantaneous profiles of velocity and sediment concentration were taken simultaneously and co-located. An Acoustic Doppler Velocity Profiler (ADVP) was combined with Particle Tracking Velocimetry (PTV) for suspended sediment particle tracking. Measurements resolved turbulence scales. During the final phase of the accelerating flow range, fine sediment suspension from the bed started in packets and rapidly created a ripple pattern that remained nearly stationary. Thereafter, vortex shedding produced most of the sediment suspension into the water column in the form of events or packets, making suspension intermittent. Simultaneously, sediment particles rolled along the bed following the ripple structure, thus slowly advancing the ripple pattern in the direction of the flow without altering ripple geometry. Fine sediment particles and hydrogen bubbles were used individually or combined as flow tracers in the acoustic measurements. When used individually, hydrogen bubbles provided full depth flow and backscattering information, whereas sediment particles traced only the lower layers of the flow, indicating sediment suspension. When both tracers were combined, hydrogen bubbles could only be distinguished from sediment particles when results at two different acoustic carrier frequencies were compared. The intermittency was observed in the backscattering of the acoustic system. The event structure in fine sediment suspension is seen by the PTV method. PTV velocity vectors varied in speed and orientation, were

  15. A sodium channel gene SCN9A polymorphism that increases nociceptor excitability.

    Science.gov (United States)

    Estacion, Mark; Harty, T Patrick; Choi, Jin-Sung; Tyrrell, Lynda; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2009-12-01

    Sodium channel Na(V)1.7, encoded by the SCN9A gene, is preferentially expressed in nociceptive primary sensory neurons, where it amplifies small depolarizations. In studies on a family with inherited erythromelalgia associated with Na(V)1.7 gain-of-function mutation A863P, we identified a nonsynonymous single-nucleotide polymorphism within SCN9A in the affected proband and several unaffected family members; this polymorphism (c. 3448C&T, Single Nucleotide Polymorphisms database rs6746030, which produces the amino acid substitution R1150W in human Na(V)1.7 [hNa(V)1.7]) is present in 1.1 to 12.7% of control chromosomes, depending on ethnicity. In this study, we examined the effect of the R1150W substitution on function of the hNa(V)1.7 channel, and on the firing of dorsal root ganglion (DRG) neurons in which this channel is normally expressed. We show that this polymorphism depolarizes activation (7.9-11mV in different assays). Current-clamp analysis shows that the 1150W allele depolarizes (6mV) resting membrane potential and increases ( approximately 2-fold) the firing frequency in response to depolarization in DRG neurons in which it is present. Our results suggest that polymorphisms in the Na(V)1.7 channel may influence susceptibility to pain.

  16. Erythropoietin Increases Expression and Function of Transient Receptor Potential Canonical 5 Channels

    DEFF Research Database (Denmark)

    Liu, Ying; Xu, Yunfei; Thilo, Florian;

    2011-01-01

    Hypertension is a common complication in hemodialysis patients during erythropoietin (EPO) treatment. The underlying mechanisms of EPO-induced hypertension still remain to be determined. Increased transient receptor potential canonical (TRPC) channels have been associated with hypertension. Now......, TRPC gene expression was investigated using quantitative real-time RT-PCR and immunoblotting in cultured human endothelial cells and in monocytes from hemodialysis patients. EPO dose-dependently increased TRPC5 mRNA in endothelial cells. EPO increased TRPC5 mRNA stability, that is, EPO prolonged...

  17. Probing kinetic drug binding mechanism in voltage-gated sodium ion channel: open state versus inactive state blockers.

    Science.gov (United States)

    Pal, Krishnendu; Gangopadhyay, Gautam

    2015-01-01

    The kinetics and nonequilibrium thermodynamics of open state and inactive state drug binding mechanisms have been studied here using different voltage protocols in sodium ion channel. We have found that for constant voltage protocol, open state block is more efficient in blocking ionic current than inactive state block. Kinetic effect comes through peak current for mexiletine as an open state blocker and in the tail part for lidocaine as an inactive state blocker. Although the inactivation of sodium channel is a free energy driven process, however, the two different kinds of drug affect the inactivation process in a different way as seen from thermodynamic analysis. In presence of open state drug block, the process initially for a long time remains entropy driven and then becomes free energy driven. However in presence of inactive state block, the process remains entirely entropy driven until the equilibrium is attained. For oscillating voltage protocol, the inactive state blocking is more efficient in damping the oscillation of ionic current. From the pulse train analysis it is found that inactive state blocking is less effective in restoring normal repolarisation and blocks peak ionic current. Pulse train protocol also shows that all the inactive states behave differently as one inactive state responds instantly to the test pulse in an opposite manner from the other two states.

  18. Fluorescence-tracking of activation gating in human ERG channels reveals rapid S4 movement and slow pore opening.

    Directory of Open Access Journals (Sweden)

    Zeineb Es-Salah-Lamoureux

    Full Text Available BACKGROUND: hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening. METHODS AND FINDINGS: Tetramethylrhodamine-5-maleimide (TMRM fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449 in the S1-S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the V((1/2 of activation to -27.5+/-2.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1-S2 linker cysteines with valines allowed unobstructed recording of S3-S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-V(ON, with V((1/2 (,1 = -37.8+/-1.7 mV, and V((1/2 (,2 = 43.5+/-7.9 mV. The first phase, V((1/2 (,1, was approximately 20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-V((1/2 = -18.3+/-1.2 mV, and relatively unchanged in a non-inactivating E519C:S620T mutant (V((1/2 = -34.4+/-1.5 mV, suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarization (V((1/2 = -20.6+/-1.2, k = 11.4 mV and L520C quenching during depolarization (V((1/2 = -26.8+/-1.0, k = 13.3 mV matched the respective voltage dependencies of hERG ionic tails, and deactivation time constants from -40 to -110 mV, suggesting they detected pore-S4 rearrangements related to ionic current flow during pore opening and closing. CONCLUSION: THE DATA INDICATE: 1

  19. Gradually varied flow in compound open channels; Flujo gradualmente variado en canales de seccion compuesta

    Energy Technology Data Exchange (ETDEWEB)

    Sotela Avila, Gilberto [Universidad Nacional Autonoma de Mexico (Mexico)

    2001-03-01

    The author shows that the computation of gradually-varied-flow profiles in prismatic compound channels involves the solution of the dynamic equation, but using the compound channel Froude number defined by Blalock and Sturm. The same equation is used for non-prismatic channels by dividing the channel into short reaches and carrying the computation step by step through an iterative process. [Spanish] El autor demuestra que los perfiles del flujo gradualmente variado en canales prismaticos de seccion compuesta se pueden determinar mediante la integracion de la llamada ecuacion dinamica, pero usando el numero de Froude definido por Blalock y Sturm para este tipo de canales. Cuando no son prismaticos, tambien se aplica la ecuacion de la energia por tramos y el calculo sigue un proceso iterativo una vez definidos los tirantes criticos multiples y la zona en que se desarrolla el perfil.

  20. Effects of the shape of the hydrograph and unsteadiness on flow properties and hysteresis in open channel flow

    Science.gov (United States)

    Bagherimiyab, F.; Roy, A.; Lemmin, U.

    2013-12-01

    Flows in rivers and open channels become unsteady during flood events. This study examines experimentally the relationships between the shape of the hydrographs and the characteristics of the accelerating, stabilizing and decelerating phases and the hysteretic trajectories. Seven symmetrical hydrographs with different unsteadiness (20 s, 30 s, 45 s, 60 s, 90 s, 150 s and 210 s accelerating and decelerating phases) and 90 s peak steady range were investigated in open-channel flow over a loose gravel bed. Detailed, quasi-instantaneous velocity profiles were measured using a 3D Acoustic Doppler Velocity Profiler (ADVP). Even though discharge was varied linearly at a constant rate over the rising and falling limb of each hydrograph, the change in relative submergence was not linear during parts of these periods. Important variations were observed between the two limbs of the hydrographs, but also among the different unsteadiness conditions, resulting in considerable differences in the flow dynamics. The discrepancy between the variation of the discharge and the observed water level over time indicates that flow adjustment over the rough bed takes place along the channel. This adjustment differs for the accelerating and the decelerating phases. Different hysteretic loops are formed for each hydrograph. In each loop, water depth for the accelerating range is different from that of the decelerating range for the same discharge. The transition from the accelerating range to the peak flow range is gradual. It is particularly marked for the 20 s hydrograph, where steady state peak flow is only attained at the very end of the peak flow range. The hydrograph with the lowest unsteadiness (210 s) remains in steady state during the whole peak steady flow range. Compared to the other hydrographs, it is characterized by a higher water depth for the same discharge and at the end it reaches a lower water depth for the same discharge. During the accelerating range, both mean velocity

  1. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production.

  2. Osteoblasts detect pericellular calcium concentration increase via neomycin-sensitive voltage gated calcium channels.

    Science.gov (United States)

    Sun, Xuanhao; Kishore, Vipuil; Fites, Kateri; Akkus, Ozan

    2012-11-01

    The mechanisms underlying the detection of critically loaded or micro-damaged regions of bone by bone cells are still a matter of debate. Our previous studies showed that calcium efflux originates from pre-failure regions of bone matrix and MC3T3-E1 osteoblasts respond to such efflux by an increase in the intracellular calcium concentration. The mechanisms by which the intracellular calcium concentration increases in response to an increase in the pericellular calcium concentration are unknown. Elevation of the intracellular calcium may occur via release from the internal calcium stores of the cell and/or via the membrane bound channels. The current study applied a wide range of pharmaceutical inhibitors to identify the calcium entry pathways involved in the process: internal calcium release from endoplasmic reticulum (ER, inhibited by thapsigargin and TMB-8), calcium receptor (CaSR, inhibited by calhex), stretch-activated calcium channel (SACC, inhibited by gadolinium), voltage-gated calcium channels (VGCC, inhibited by nifedipine, verapamil, neomycin, and ω-conotoxin), and calcium-induced-calcium-release channel (CICRC, inhibited by ryanodine and dantrolene). These inhibitors were screened for their effectiveness to block intracellular calcium increase by using a concentration gradient induced calcium efflux model which mimics calcium diffusion from the basal aspect of cells. The inhibitor(s) which reduced the intracellular calcium response was further tested on osteoblasts seeded on mechanically loaded notched cortical bone wafers undergoing damage. The results showed that only neomycin reduced the intracellular calcium response in osteoblasts, by 27%, upon extracellular calcium stimulus induced by concentration gradient. The inhibitory effect of neomycin was more pronounced (75% reduction in maximum fluorescence) for osteoblasts seeded on notched cortical bone wafers loaded mechanically to damaging load levels. These results imply that the increase in

  3. Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels.

    Science.gov (United States)

    Espinosa, F; Marks, G; Heintz, N; Joho, R H

    2004-04-01

    The voltage-gated potassium channels Kv3.1 and Kv3.3 are widely expressed in the brain, including areas implicated in the control of motor activity and in areas thought to regulate arousal states. Although Kv3.1 and Kv3.3-single mutants show some physiological changes, previous studies revealed relatively subtle behavioral alterations suggesting that Kv3.1 and Kv3.3 channel subunits may be encoded by a pair of redundant genes. In agreement with this hypothesis, Kv3.1/Kv3.3-deficient mice display a 'strong' mutant phenotype that includes motor dysfunction (ataxia, myoclonus, tremor) and hyperactivity when exposed to a novel environment. In this paper we report that Kv3.1/Kv3.3-deficient mice are also constitutively hyperactive. Compared to wildtype mice, double mutants display 'restlessness' that is particularly prominent during the light period, when mice are normally at rest, characterized by more than a doubling of ambulatory and stereotypic activity, and accompanied by a 40% sleep reduction. When we reinvestigated both single mutants, we observed constitutive increases of ambulatory and stereotypic activity in conjunction with sleep loss in Kv3.1-single mutants but not in Kv3.3-single mutants. These findings indicate that the absence of Kv3.1-channel subunits is primarily responsible for the increased motor drive and the reduction in sleep time.

  4. Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance.

    Science.gov (United States)

    Contreras, E; Tamayo, L; Amigo, M

    1988-04-13

    The influence of calcium channel blockers on morphine-induced analgesia and on tolerance to the chronic administration of the opiate was investigated in mice. The effects of a test dose of morphine were significantly increased by the administration of diltiazem, flunarizine, nicardipine and verapamil. In contrast, nifedipine induced an antagonistic effect. The calcium channel antagonists did not change the reaction time to thermal stimulation in mice (hot plate test). The administration of nifedipine, flunarizine and verapamil reduced the intensity of the tolerance induced by a single dose of morphine administered in a slow release preparation. Diltiazem induced a non-significant decrease of the process. The present results are in accordance with the known interaction of acute and chronic morphine administration with the intracellular calcium concentration in neurones of the central nervous system.

  5. Increased HCN channel driven inward rectification in benign cramp fasciculation syndrome.

    Science.gov (United States)

    Czesnik, Dirk; Howells, James; Negro, Francesco; Wagenknecht, Melanie; Hanner, Susanne; Farina, Dario; Burke, David; Paulus, Walter

    2015-11-01

    Muscle cramps are a common complaint associated with sudden painful involuntary contractions of a muscle. The mechanisms responsible for muscle cramps are still not clear. Axonal excitability and multi-unit electromyography studies were performed in 20 patients suffering from benign cramp fasciculation syndrome, not currently on medication. The measures of axonal excitability suggested greater inward rectification, indicative of an increase in Ih. Mathematical modelling suggested that the data were best explained by depolarization of the voltage dependence of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Parameters associated with polarization of resting membrane potential were not changed. These findings suggest that a role for HCN channels may become apparent during the rhythmic discharge associated with a voluntary contraction. Consistent with this view, patients had higher motor unit discharge rates than healthy controls during maximal voluntary effort.

  6. Increasing energy efficiency by geometric modification of hoe-type furrow opener

    Directory of Open Access Journals (Sweden)

    R Rahimzadeh

    2016-09-01

    grain and biological yield was measured. ANOVA test, uniformity test and mean comparison were conducted by using Genstat software. Results and Discussion The soil bin test results showed that opener design and forward speed both have significant influences on the horizontal force (p<0.01. Horizontal force was increased with increasing of forward speeds. The same result was reported by Wheeler and Godwin, 1996 and Astafford, 1979. The lowest horizontal force (average 1.66 kN occurred at 1 m.s-1 and the highest (average 1.94 kN occurred at 2 m.s-1 forward speeds. Horizontal force increased in O2 (2.8% and decreased in O1 (3.4% compared with the control (average 1.77 kN. Moreover, openers had significant influence on the vertical force (p<0.01. Vertical force values were negative in O1 (average -0.05 kN and O2 (average -0.07 kN in comparison with positive value in the control (average +0.01 kN. The effect of forward speed on vertical force was not statistically significant. The field results showed that there were significant differences among the openers in the numbers of seedling, grain and biological yield (p<0.01. The O2 opener (with the average of 48 seedlings per one meter row had 33% and 24% more seedlings in comparison with O1 and check furrow openers, respectively. Probably, using dick bald in O2 design leads to increased seed germination. Increasing of seed germination by using disk furrow opener as an advantage is reported by Kushwaha and Foster, 1993. The O2 furrow opener would also increase grain yield about 36% compared with both O1 and check furrow openers. Conclusions It can be concluded that the newly designed furrow opener (O2 could improve the energy efficiency with increasing crop yield. Hence, O2 furrow opener could be recommended for direct planting in rain-fed farming.

  7. Increasing energy efficiency by geometric modification of hoe-type furrow opener

    Directory of Open Access Journals (Sweden)

    R Rahimzadeh

    2016-09-01

    grain and biological yield was measured. ANOVA test, uniformity test and mean comparison were conducted by using Genstat software. Results and Discussion The soil bin test results showed that opener design and forward speed both have significant influences on the horizontal force (p<0.01. Horizontal force was increased with increasing of forward speeds. The same result was reported by Wheeler and Godwin, 1996 and Astafford, 1979. The lowest horizontal force (average 1.66 kN occurred at 1 m.s-1 and the highest (average 1.94 kN occurred at 2 m.s-1 forward speeds. Horizontal force increased in O2 (2.8% and decreased in O1 (3.4% compared with the control (average 1.77 kN. Moreover, openers had significant influence on the vertical force (p<0.01. Vertical force values were negative in O1 (average -0.05 kN and O2 (average -0.07 kN in comparison with positive value in the control (average +0.01 kN. The effect of forward speed on vertical force was not statistically significant. The field results showed that there were significant differences among the openers in the numbers of seedling, grain and biological yield (p<0.01. The O2 opener (with the average of 48 seedlings per one meter row had 33% and 24% more seedlings in comparison with O1 and check furrow openers, respectively. Probably, using dick bald in O2 design leads to increased seed germination. Increasing of seed germination by using disk furrow opener as an advantage is reported by Kushwaha and Foster, 1993. The O2 furrow opener would also increase grain yield about 36% compared with both O1 and check furrow openers. Conclusions It can be concluded that the newly designed furrow opener (O2 could improve the energy efficiency with increasing crop yield. Hence, O2 furrow opener could be recommended for direct planting in rain-fed farming.

  8. Developing a 2D vertical flow and sediment transport model for open channels using the Youngs-VOF method

    Science.gov (United States)

    Zhao, Dongmiao; Tang, Jun; Wu, Xiuguang; Lin, Changning; Liu, Lijun; Chen, Jian

    2016-05-01

    A 2D vertical (2DV) numerical model, without σ-coordinate transformation in the vertical direction, is developed for the simulation of fl ow and sediment transport in open channels. In the model, time-averaged Reynolds equations are closed by the k-ɛ nonlinear turbulence model. The modifi ed Youngs-VOF method is introduced to capture free surface dynamics, and the free surface slope is simulated using the ELVIRA method. Based on the power-law scheme, the k-ɛ model and the suspended-load transport model are solved numerically with an implicit scheme applied in the vertical plane and an explicit scheme applied in the horizontal plane. Bedload transport is modeled using the Euler-WENO scheme, and the grid-closing skill is adopted to deal with the moving channel bed boundary. Verifi cation of the model using laboratory data shows that the model is able to adequately simulate fl ow and sediment transport in open channels, and is a good starting point for the study of sediment transport dynamics in strong nonlinear fl ow scenarios.

  9. The effect of number and configuration of sediment microbial fuel cells on their performance in an open channel architecture

    Science.gov (United States)

    Abazarian, Elham; Gheshlaghi, Reza; Mahdavi, Mahmood A.

    2016-09-01

    The aim of this study is to investigate the effect of the number of sediment microbial fuel cells (SMFCs) with different configurations on the electricity generation in open channels. For this purpose, two open channels, one with three and another with four SMFCs, were operated over a long period of time and their performances were analyzed. Individual SMFCs followed an almost similar trend for electricity generation during the operation time. In addition, it was found that three-SMFC stacking in series mode produced a relatively higher maximum power density (18 mW m-2) than four-SMFC stacking (16 mW m-2). However, in parallel mode, four-SMFC stacking had a higher maximum power density of 90 mW m-2 compared to three-SMFC stacking with maximum power density of 78 mW m-2. These findings indicate that different numbers of cells significantly affect electricity generation depending on the type of SMFC configuration in the channel. The results would be helpful for application of SMFCs in large-scale.

  10. Automatic tracking of red blood cells in micro channels using OpenCV

    Science.gov (United States)

    Rodrigues, Vânia; Rodrigues, Pedro J.; Pereira, Ana I.; Lima, Rui

    2013-10-01

    The present study aims to developan automatic method able to track red blood cells (RBCs) trajectories flowing through a microchannel using the Open Source Computer Vision (OpenCV). The developed method is based on optical flux calculation assisted by the maximization of the template-matching product. The experimental results show a good functional performance of this method.

  11. D-branes as coherent states in the open string channel

    CERN Document Server

    Cantcheff, Marcelo Botta

    2007-01-01

    We show that bosonic D-brane states may be represented as coherent states in an open string representation. By using the Thermo Field Dynamics (TFD) formalism, we may construct a condensed state of open string modes which encodes the information on the D-brane configuration. We also introduce a construction alternative to TFD, which does not require to assume thermal equilibrium. It is shown that the dynamics of the system, combined with geometric properties of the duplication rules of TFD, is sufficient to obtain the thermal states and their analytic continuations in a geometric fashion. We adopt this approach to show that bosonic D-brane states in the open string sector may also be built as boundary states in a special sense. Some implications of this study on the interpretation of the open/closed duality and on the kinematical/algebraic structure of an open string field theory are also commented.

  12. Comparison of the effects of the K(+)-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle.

    Science.gov (United States)

    Wickenden, A. D.; Grimwood, S.; Grant, T. L.; Todd, M. H.

    1991-01-01

    1 The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca(2+)-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non-competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed. PMID:1878752

  13. In-channel printing-device opening assay for micropatterning multiple cells and gene analysis.

    Science.gov (United States)

    Zhou, Hao; Zhao, Liang; Zhang, Xueji

    2015-02-17

    Herein we report an easy but versatile method for patterning different cells on a single substrate by using a microfluidic approach that allows not only spatial and temporal control of multiple microenvironments but also retrieval of specific treated cells to profile their expressed genetic information at around 10-cell resolution. By taking advantages of increased surface area of gold nanoparticles on a poly(dimethylsiloxane) (PDMS) coated substrate, cell adhesive-promotive protein, human fibronectin (hFN) can be significantly accumulated on designed regions where cells can recognize the protein and spread out. Moreover, the whole device can be easily opened by hand without any loss of patterned cells which could be retrieved by mouth-pipet. Consequently, we demonstrate the possibility of analyzing the difference of gene expression patterns between wild type MCF-7 cell and MCF/Adr (drug-resistant cell line) from less than 400 cells in total for a single comprehensive assay, including parallel experiments, controls, and multiple dose treatments. Certain genes, especially the P-glycoprotein coding gene (ABCB1), show high expression level in resistant cells compared with the wild type, suggesting a possible pathway that may contribute to the antidrug mechanism.

  14. Hydrogen Sulfide Regulates Inward-Rectifying K+ Channels in Conjunction with Stomatal Closure1[OPEN

    Science.gov (United States)

    Papanatsiou, Maria; Scuffi, Denisse; Blatt, Michael R.; García-Mata, Carlos

    2015-01-01

    Hydrogen sulfide (H2S) is the third biological gasotransmitter, and in animals, it affects many physiological processes by modulating ion channels. H2S has been reported to protect plants from oxidative stress in diverse physiological responses. H2S closes stomata, but the underlying mechanism remains elusive. Here, we report the selective inactivation of current carried by inward-rectifying K+ channels of tobacco (Nicotiana tabacum) guard cells and show its close parallel with stomatal closure evoked by submicromolar concentrations of H2S. Experiments to scavenge H2S suggested an effect that is separable from that of abscisic acid, which is associated with water stress. Thus, H2S seems to define a unique and unresolved signaling pathway that selectively targets inward-rectifying K+ channels. PMID:25770153

  15. Increasing Public Access to University Qualifications: Evolution of The University of the West Indies Open Campus

    Science.gov (United States)

    Thomas, Michael L.; Soares, Judith

    2009-01-01

    This paper traces the evolution of The University of the West Indies' Open Campus (UWIOC), which is expected to expand service and increase access to the underserved communities of the Eastern Caribbean. At present, UWI, which caters to the needs of the 16 far flung countries of the Commonwealth Caribbean, has not been able to fully serve these…

  16. The Molecular Mechanism by which PIP2 Opens the Intracellular G-Loop Gate of a Kir3.1 Channel

    OpenAIRE

    Meng, Xuan-Yu; Zhang, Hong-Xing; Logothetis, Diomedes E.; Cui, Meng

    2012-01-01

    Inwardly rectifying potassium (Kir) channels are characterized by a long pore comprised of continuous transmembrane and cytosolic portions. A high-resolution structure of a Kir3.1 chimera revealed the presence of the cytosolic (G-loop) gate captured in the closed or open conformations. Here, we conducted molecular-dynamics simulations of these two channel states in the presence and absence of phosphatidylinositol bisphosphate (PIP2), a phospholipid that is known to gate Kir channels. Simulati...

  17. Normal insulin release during sustained hyperglycaemia in hypokalaemic periodic paralysis : Role of the potassium channel opener pinacidil in impaired muscle strength

    NARCIS (Netherlands)

    Ligtenberg, JJM; VanHaeften, TW; VanderKolk, LE; Smit, AJ; Sluiter, WJ; Links, TP

    1996-01-01

    1. Hypokalaemic periodic paralysis is characterized by attacks of muscle weakness, Glucose, insulin and an abnormal regulation of ATP-sensitive potassium channels may be involved in these attacks, We studied the effect of hyperglycaemia and of the potassium channel opener pinacidil on insulin releas

  18. Fiber-distributed multi-channel open-path H2S sensor based on tunable diode laser absorption spectroscopy

    Institute of Scientific and Technical Information of China (English)

    Dong Chen; Wenqing Liu; Yujun Zhang; Jianguo Liu; Ruifeng Kan; Min Wang; Xi Fang; Yiben Cui

    2007-01-01

    Tunable diode laser based gas detectors are now being used in a wide variety of applications for safety and environmental interest. A fiber-distributed multi-channel open-path H2S sensor based on tunable diode laser absorption spectroscopy (TDLAS) is developed, the laser used is a telecommunication near infrared distributed feed-back (DFB) tunable diode laser, combining with wavelength modulation specby combining optical fiber technique. An on-board reference cell provides on-line sensor calibration and almost maintenance-free operation. The sensor is suitable for large area field H2S monitoring application.

  19. Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments ligand affinity.

    Science.gov (United States)

    M'Barek, Sarrah; Chagot, Benjamin; Andreotti, Nicolas; Visan, Violeta; Mansuelle, Pascal; Grissmer, Stephan; Marrakchi, Mohamed; El Ayeb, Mohamed; Sampieri, François; Darbon, Hervé; Fajloun, Ziad; De Waard, Michel; Sabatier, Jean-Marc

    2005-08-15

    Scorpion toxins interact with their target ion channels through multiple molecular contacts. Because a "gain of function" approach has never been described to evaluate the importance of the molecular contacts in defining toxin affinity, we experimentally examined whether increasing the molecular contacts between a toxin and an ion channel directly impacts toxin affinity. For this purpose, we focused on two scorpion peptides, the well-characterized maurotoxin with its variant Pi1-like disulfide bridging (MTX(Pi1)), used as a molecular template, and butantoxin (BuTX), used as an N-terminal domain provider. BuTX is found to be 60-fold less potent than MTX(Pi1) in blocking Kv1.2 (IC(50) values of 165 nM for BuTX versus 2.8 nM for MTX(Pi1)). Removal of its N-terminal domain (nine residues) further decreases BuTX affinity for Kv1.2 by 5.6-fold, which is in agreement with docking simulation data showing the importance of this domain in BuTX-Kv1.2 interaction. Transfer of the BuTX N-terminal domain to MTX(Pi1) results in a chimera with five disulfide bridges (BuTX-MTX(Pi1)) that exhibits 22-fold greater affinity for Kv1.2 than MTX(Pi1) itself, in spite of the lower affinity of BuTX as compared to MTX(Pi1). Docking experiments performed with the 3-D structure of BuTX-MTX(Pi1) in solution, as solved by (1)H-NMR, reveal that the N-terminal domain of BuTX participates in the increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicate that acting on molecular contacts between a toxin and a channel is an efficient strategy to modulate toxin affinity. (c) 2005 Wiley-Liss, Inc.

  20. Adenosine triphosphate-sensitive potassium channel opener protects PC12 cells against hypoxia-induced apoptosis through PI3K/Akt and Bcl-2 signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang; Chunhong Jia; Danyang Zhao; Yang Lu; Runling Wang; Jia Li

    2010-01-01

    Although previous studies have shown the neuroprotective effects of the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener against ischemic neuronal damage, little is known about the mechanisms involved. Phosphatidylinositol-3 kinase (PI3K)/v-akt murine thy-moma viral oncogene homolog (Akt) and Bcl-2 are thought to be important factors that mediate neuroprotection. The present study investigated the effects of KATP openers on hypoxia-induced PC12 cell apoptosis, as well as mRNA and protein expression of Akt and Bcl-2. Results demon-strated that pretreatment of PC12 cells with pinacidil, a KATP opener, resulted in decreased PC12 cell apoptosis following hypoxia, as detected by Annexin-V fluorescein isothiocyanate/ propidium iodide double staining flow cytometry. In addition, mRNA and protein expression of phosphorylated Akt (p-Akt) and Bcl-2 increased, as detected by immunofluorescence, Western blot analysis, and reverse-transcription polymerase chain reaction. The protective effect of this preconditioning was attenuated by glipizide, a selective KATP blocker. These results demonstrate for the first time that the protective mechanisms of KATP openers on PC12 cell apoptosis following hypoxia could result from activation of the PI3K/Akt signaling pathway, which further activates expression of the downstream Bcl-2 gene.

  1. Characterization of Unruh Channel in the context of Open Quantum Systems

    CERN Document Server

    Banerjee, Subhashish; Omkar, S; Srikanth, R

    2016-01-01

    We show through the Choi matrix approach that the effect of Unruh acceleration on a qubit is similar to the interaction of the qubit with a vacuum bath, despite the finiteness of the Unruh temperature. Thus, rather counterintuitvely, from the perspective of decoherence in this framework, the particle experiences a vacuum bath with a temperature-modified interaction strength, rather than a thermal bath. We investigate how this "relativistic decoherence" is modified by the presence of environmentally induced decoherence, by studying the degradation of quantum information, as quantified by parameters such as nonlocality, teleportation fidelity, entanglement, coherence and quantum measurement-induced disturbance (a discord-like measure). Also studied are the performance parameters such as gate and channel fidelity. We highlight the distinction between dephasing and dissipative environmental interactions, by considering the actions of quantum non-demolition and squeezed generalized amplitude damping channels, resp...

  2. Photo-switchable tweezers illuminate pore-opening motions of an ATP-gated P2X ion channel.

    Science.gov (United States)

    Habermacher, Chloé; Martz, Adeline; Calimet, Nicolas; Lemoine, Damien; Peverini, Laurie; Specht, Alexandre; Cecchini, Marco; Grutter, Thomas

    2016-01-25

    P2X receptors function by opening a transmembrane pore in response to extracellular ATP. Recent crystal structures solved in apo and ATP-bound states revealed molecular motions of the extracellular domain following agonist binding. However, the mechanism of pore opening still remains controversial. Here we use photo-switchable cross-linkers as 'molecular tweezers' to monitor a series of inter-residue distances in the transmembrane domain of the P2X2 receptor during activation. These experimentally based structural constraints combined with computational studies provide high-resolution models of the channel in the open and closed states. We show that the extent of the outer pore expansion is significantly reduced compared to the ATP-bound structure. Our data further reveal that the inner and outer ends of adjacent pore-lining helices come closer during opening, likely through a hinge-bending motion. These results provide new insight into the gating mechanism of P2X receptors and establish a versatile strategy applicable to other membrane proteins.

  3. High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes

    DEFF Research Database (Denmark)

    Thilo, Florian; Lee, Marlene; Xia, Shengqiang

    2014-01-01

    Transient receptor potential canonical (TRPC) channels type 6 play an important role in the function of human podocytes. Diabetic nephropathy is characterized by altered TRPC6 expression and functions of podocytes. Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxid...

  4. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    Directory of Open Access Journals (Sweden)

    Nagendra Sanyasihally Ningaraj

    2013-05-01

    Full Text Available Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB. Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells. In this study, we validated the non-invasive and clinically relevant Dynamic Contrast Enhancing-Magnetic Resonance Imaging (DCE-MRI method with invasive, clinically irrelevant but highly accurate Quantitative Autoradiography (QAR method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa channel activator NS-1619. Our results show that human gliomas and brain tumor endothelial cells that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents’ delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.

  5. Online distribution channel increases article usage on Mendeley: a randomized controlled trial.

    Science.gov (United States)

    Kudlow, Paul; Cockerill, Matthew; Toccalino, Danielle; Dziadyk, Devin Bissky; Rutledge, Alan; Shachak, Aviv; McIntyre, Roger S; Ravindran, Arun; Eysenbach, Gunther

    2017-01-01

    Prior research shows that article reader counts (i.e. saves) on the online reference manager, Mendeley, correlate to future citations. There are currently no evidenced-based distribution strategies that have been shown to increase article saves on Mendeley. We conducted a 4-week randomized controlled trial to examine how promotion of article links in a novel online cross-publisher distribution channel (TrendMD) affect article saves on Mendeley. Four hundred articles published in the Journal of Medical Internet Research were randomized to either the TrendMD arm (n = 200) or the control arm (n = 200) of the study. Our primary outcome compares the 4-week mean Mendeley saves of articles randomized to TrendMD versus control. Articles randomized to TrendMD showed a 77% increase in article saves on Mendeley relative to control. The difference in mean Mendeley saves for TrendMD articles versus control was 2.7, 95% CI (2.63, 2.77), and statistically significant (p Mendeley (Spearman's rho r = 0.60). This is the first randomized controlled trial to show how an online cross-publisher distribution channel (TrendMD) enhances article saves on Mendeley. While replication and further study are needed, these data suggest that cross-publisher article recommendations via TrendMD may enhance citations of scholarly articles.

  6. On the turbulent flow around water turbines placed in an open channel: an experimental study

    Science.gov (United States)

    Sotiropoulos, F.; Chamorro, L. P.; Arndt, R.

    2010-12-01

    A growing interest in water turbines (using tidal, river, marine currents) has been observed during the last few years. Fundamental understanding of the turbulent flow around the water turbines is crucial to predict the potential effects of these structures on the local morphology, water flow and power available in the current, among others. In this study, a series of model water turbines (single and an aligned array) of 50 cm rotor diameter were placed in the main channel of the Saint Anthony Falls Laboratory at the University of Minnesota. The main channel is approx 2.5 m wide, 1.8 m height and 85 m long. Flow around the water turbines were analyzed under subcritical conditions. Turbine hub heights coincided with the channel mid height. A series of acoustic Doppler anemometers (ADV) were used to obtain 3 velocity components of the flow at a rate of 200 Hz. Selected streamwise and spanwise vertical planes were measured to describe the kinematics around the water turbines. Potential interactions with the lateral walls were also addressed. High order statistics (mean velocity, turbulence intensities and Reynolds stresses) as well as two point correlations and spectra were computed to infer fundamental differences and similitude with their counterparts, the wind turbines.

  7. THE LOSS OF STABILITY OF LAMINAR FLOW IN OPEN CHANNEL AND THE MECHANISM OF SAND RIPPLE FORMATION

    Institute of Scientific and Technical Information of China (English)

    白玉川; 罗纪生

    2002-01-01

    In the flow on a mobile bed in an open channel, sand ripple often appears after the sediment begins to move. Different scholars have different views on the formation of sand ripples. This paper holds that as the ripple in general is very small, its formation is due to the instability of the laminar flow or the evolution of the small-scale coherent structures in the sublayer adjacent to the wall of the open channel. When the shear stresses caused by the disturbing waves or the coherent structure near the bed surface boundary and the water flow itself are greater than the shields stresses, responses on the bed surface appear and the sand ripple forms. If the frequency of the shear stress caused by the disturbance is close to the natural frequency of the sand grains that produced resonance,such a phenomenon is called the "detection property" of the sediment. It is at this point that the maximum resonance appears and the sand ripple develops rapidly.

  8. Dual state-parameter optimal estimation of one-dimensional open channel model using ensemble Kalman filter

    Institute of Scientific and Technical Information of China (English)

    LAI Rui-xun; FANG Hong-wei; HE Guo-jian; YU Xin; YANG Ming; WANG Ming

    2013-01-01

    In this paper,both state variables and parameters of one-dimensional open channel model are estimated using a framework of the Ensemble Kalman Filter (EnKF).Compared with observation,the predicted accuracy of water level and discharge are improved while the parameters of the model are identified simultaneously.With the principles of the EnKF,a state-space description of the Saint-Venant equation is constructed by perturbing the measurements with Gaussian error distribution.At the same time,the roughness,one of the key parameters in one-dimensional open channel,is also considered as a state variable to identify its value dynamically.The updated state variables and the parameters are then used as the initial values of the next time step to continue the assimilation process.The usefulness and the capability of the dual EnKF are demonstrated in the lower Yellow River during the water-sediment regulation in 2009.In the optimization process,the errors between the prediction and the observation are analyzed,and the rationale of inverse roughness is discussed.It is believed that (1) the flexible approach of the dual EnKF can improve the accuracy of predicting water level and discharge,(2) it provides a probabilistic way to identify the model error which is feasible to implement but hard to handle in other filter systems,and (3) it is practicable for river engineering and management.

  9. Effectiveness comparison of channel-assisted mini-incision and open Achilles shortening for treatment of healed Achilles tendon rupture

    Directory of Open Access Journals (Sweden)

    Hong-zhe QI

    2017-08-01

    Full Text Available Objective To compare the clinical effectiveness between the channel-assisted mini-invasion and open Achilles shortening for treatment of the elongated Achilles tendon following previous rupture. Methods The clinical data of 19 patients admitted from Dec. 2013 to Dec. 2015 and met the inclusion criteria were analyzed retrospectively. Eight patients were treated with shortening operation by channel-assisted minimally invasive repair system, while 11 patients received dissection of Krackow Achilles tendon shortening. There was no significant difference between the two groups in gender, age, injury to operation time, preoperative calf circumference and preoperative AOFAS (American Orthopaedic Foot & Ankle Society score (P>0.05. Results The operation time, incision length and postoperative hospital days were significantly less in min-invasion group than in incision group (P0.05. Conclusion Channel-assisted minimally invasive Achilles tendon shortening operation has not only similar effectiveness to the incision shorting operation for the treatment of elongated Achilles tendon following previous rupture, but also has the advantages of shortening operation time and stay in hospital and avoidance of sural nerve injury. DOI: 10.11855/j.issn.0577-7402.2017.07.12

  10. Effect of a Weir-Type Obstruction with Different Geometric and Hydraulic Conditions on Flow Structure in an Open Channel

    Directory of Open Access Journals (Sweden)

    Shahid Ali

    2014-07-01

    Full Text Available This paper presents results from an experimental study which was conducted at Technical University Delft, Netherland. The research was made on obstructions resembling weirs in an open channel. This weir-type obstruction was a representative of groyne/dike in a natural channel. The experimentation was performed in the laboratory for different values of inflow (25 l/sec and 40 l/sec, weir with and without vegetation and with different leeward slopes of the weir (1:4 and 1:7. The results were obtained for Reynolds normal stresses, longitudinal and vertical velocities. A comparison was made between the results of 1:4 and 1:7 leeward slope ratios. The data was collected with a LDA (Laser Doppler Anemometer. The vegetation was modeled with vertical circular rods placed over the crest of the weir. The blockage area due to this vegetation was 25% of the total area. The velocity data was gathered at around ten locations both at upstream and downstream the weir to get an insight into the flow structure. The results have been presented in the shape of vertical profiles both for velocities as well as Reynolds stresses at different locations of the channel.

  11. Closure of mitochondrial potassium channels favors opening of the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.

    Science.gov (United States)

    Korotkov, Sergey M; Brailovskaya, Irina V; Shumakov, Anton R; Emelyanova, Larisa V

    2015-06-01

    It is known that a closure of ATP sensitive (mitoKATP) or BK-type Ca(2+) activated (mitoKCa) potassium channels triggers opening of the mitochondrial permeability transition pore (MPTP) in cells and isolated mitochondria. We found earlier that the Tl(+)-induced MPTP opening in Ca(2+)-loaded rat liver mitochondria was accompanied by a decrease of 2,4-dinitrophenol-uncoupled respiration and increase of mitochondrial swelling and ΔΨmito dissipation in the medium containing TlNO3 and KNO3. On the other hand, our study showed that the mitoKATP inhibitor, 5-hydroxydecanoate favored the Tl(+)-induced MPTP opening in the inner membrane of Ca(2+)-loaded rat heart mitochondria (Korotkov et al. 2013). Here we showed that 5-hydroxydecanoate increased the Tl(+)-induced MPTP opening in the membrane of rat liver mitochondria regardless of the presence of mitoKATP modulators (diazoxide and pinacidil). This manifested in more pronounced decrease in the uncoupled respiration and acceleration of both the swelling and the ΔΨmito dissipation in isolated rat liver mitochondria, incubated in the medium containing TlNO3, KNO3, and Ca(2+). A slight delay in Ca(2+)-induced swelling of the mitochondria exposed to diazoxide could be result of an inhibition of succinate oxidation by the mitoKATP modulator. Mitochondrial calcium retention capacity (CRC) was markedly decreased in the presence of the mitoKATP inhibitor (5-hydroxydecanoate) or the mitoKCa inhibitor (paxilline). We suggest that the closure of mitoKATP or mitoKCa in calcium loaded mitochondria favors opening of the Tl(+)-induced MPTP in the inner mitochondrial membrane.

  12. Characteristics of geometric distortion correction with increasing field-of-view in open-configuration MRI.

    Science.gov (United States)

    Hong, Cheolpyo; Lee, Dong-Hoon; Han, Bong Soo

    2014-07-01

    Open-configuration magnetic resonance imaging (MRI) systems are becoming increasingly desirable for musculoskeletal imaging and image-guided radiotherapy because of their non-claustrophobic configuration. However, geometric image distortion in large fields-of-view (FOV) due to field inhomogeneity and gradient nonlinearity hinders the practical applications of open-type MRI. We demonstrated the use of geometric distortion correction for increasing FOV in open MRI. Geometric distortion was modeled and corrected as a global polynomial function. The appropriate polynomial order was identified as the minimum difference between the coordinates of control points in the distorted MR image space and those predicted by polynomial modeling. The sixth order polynomial function was found to give the optimal value for geometric distortion correction. The area of maximum distortion was<1 pixel with an FOV of 285mm. The correction performance error was increased at most 1.2% and 2.9% for FOVs of 340mm and~400mm compared with the FOV of 285mm. In particular, unresolved distortion was generated by local deformation near the gradient coil center. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Open b and $b\\bar{b}$ cross section using inclusive and exclusive channels at ATLAS

    CERN Document Server

    Christidi, I A

    2011-01-01

    The production of b-quarks in proton-proton collisions at the LHC provides an important test of perturbative QCD. The cross-section can either be measured inclusively, using all tagged b-jets, or exclusively, exploiting specific B-hadron decay final states. This note describes the measurements of the inclusive b-jet and bb(bar) production cross sections, the inclusive B → J/ΨX cross-section and the observation of the exclusive channels B± → J/ΨK ± , Bd → J/ΨK 0∗ and Bs → J/Ψφ performed with the ATLAS detector at the LHC.

  14. Silent S-Type Anion Channel Subunit SLAH1 Gates SLAH3 Open for Chloride Root-to-Shoot Translocation.

    Science.gov (United States)

    Cubero-Font, Paloma; Maierhofer, Tobias; Jaslan, Justyna; Rosales, Miguel A; Espartero, Joaquín; Díaz-Rueda, Pablo; Müller, Heike M; Hürter, Anna-Lena; Al-Rasheid, Khaled A S; Marten, Irene; Hedrich, Rainer; Colmenero-Flores, José M; Geiger, Dietmar

    2016-08-22

    Higher plants take up nutrients via the roots and load them into xylem vessels for translocation to the shoot. After uptake, anions have to be channeled toward the root xylem vessels. Thereby, xylem parenchyma and pericycle cells control the anion composition of the root-shoot xylem sap [1-6]. The fact that salt-tolerant genotypes possess lower xylem-sap Cl(-) contents compared to salt-sensitive genotypes [7-10] indicates that membrane transport proteins at the sites of xylem loading contribute to plant salinity tolerance via selective chloride exclusion. However, the molecular mechanism of xylem loading that lies behind the balance between NO3(-) and Cl(-) loading remains largely unknown. Here we identify two root anion channels in Arabidopsis, SLAH1 and SLAH3, that control the shoot NO3(-)/Cl(-) ratio. The AtSLAH1 gene is expressed in the root xylem-pole pericycle, where it co-localizes with AtSLAH3. Under high soil salinity, AtSLAH1 expression markedly declined and the chloride content of the xylem sap in AtSLAH1 loss-of-function mutants was half of the wild-type level only. SLAH3 anion channels are not active per se but require extracellular nitrate and phosphorylation by calcium-dependent kinases (CPKs) [11-13]. When co-expressed in Xenopus oocytes, however, the electrically silent SLAH1 subunit gates SLAH3 open even in the absence of nitrate- and calcium-dependent kinases. Apparently, SLAH1/SLAH3 heteromerization facilitates SLAH3-mediated chloride efflux from pericycle cells into the root xylem vessels. Our results indicate that under salt stress, plants adjust the distribution of NO3(-) and Cl(-) between root and shoot via differential expression and assembly of SLAH1/SLAH3 anion channel subunits.

  15. Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness.

    Science.gov (United States)

    MacLean, Katherine A; Johnson, Matthew W; Griffiths, Roland R

    2011-11-01

    A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

  16. Hydrodynamics of concordant and discordant fixed bed open-channel confluences

    Science.gov (United States)

    Birjukova Canelas, Olga; Lage Ferreira, Rui Miguel; Heleno Cardoso, António

    2017-04-01

    The detailed characterization of the flow field in river confluences constitutes a relevant step towards the understanding of the hydro-morpho-dynamics of these key zones of the fluvial system. With a few exceptions, existing works on this topic covered concordant bed scenarios, meaning that both confluent channels had the same elevation. This laboratory study aims to contribute to a detailed three-dimensional characterization of the flow field at a fixed bed confluence, as well as to shed light on how bed elevation discordance modifies the flow patterns of the converging flows. While the junction angle and the discharge ratio were kept fixed, two scenarios were studied on the basis of detailed water level and 3D ADV measurements at the denser mesh ever. The internal flow structure of the concordant bed scenario mostly complied with the classical conceptual models. A relevant difference concerns the size of the stagnation zone, much smaller close to the bed of the discordant bed confluence. A more significant difference is a horizontal flow structure, not previously identified in the literature, characterized by strong streamwise mean vorticity and strong secondary motion. It is observed for the discordant bed case, occurring along the inner wall of the main channel and downstream the junction corner. This structure is spatially well-correlated to a pronounced imbalance of cross-stream and vertical normal Reynolds stresses. This highlights the role of Reynolds stress anisotropy (RSA) that is generated in the shear layers than accompany the entrance of the tributary flow. Since this structure is not present in the concordant case, where RSA is also evident, it is argued that convective effects should also play a role in its formation, presumably due to deflection of the flow in the main channel by the tributary. The newly identified secondary motion should, thus, be a combination of Prandtĺs second kind and Prandtĺs first kind of secondary flow. The relative

  17. Increased expression of HERG K(+) channels contributes to myelodysplastic syndrome progression and displays correlation with prognosis stratification.

    Science.gov (United States)

    Lu, Li; Du, Wen; Liu, Wei; Guo, Dongmei; He, Xiaoqi; Li, Huiyu

    2016-12-01

    Human ether-a-go-go-related gene (HERG) K(+) channels are shown to be aberrantly expressed in a variety of cancer cells where they play roles in contributing to cancer progression. Myelodysplastic syndromes (MDS) are a group of clinical heterogeneous disorders characterized by bone marrow failure and dysplasia of blood cells. However, the involvement of HERG K(+) channels in MDS development is poorly understood. The expression of HERG K(+) channels in untreated MDS, acute myeloid leukemia (AML) patients and the control group was detected by flow cytometry. The roles of HERG K(+) channels in regulation of SKM-1 cell proliferation, apoptosis, and cell cycle were determined by CCK-8 assay and flow cytometry, respectively. We found that expression of HERG K(+) channels in MDS patients was significantly higher than controls and was lower than AML. Percentage of HERG K(+) channels on CD34+CD38- cells gradually increased from controls to high-grade MDS subtypes. And HERG K(+) channel levels showed an ascending tendency from low-risk to high-risk MDS group. In addition, the CCK-8 assay, apoptosis and cell cycle analysis were performed and showed that blockage of HERG K(+) channels decreased the proliferation of MDS cells but rarely had effects on cell apoptosis and cell cycle distribution. Our study demonstrated that HERG K(+) channels might be a potential tumor marker of MDS. These channels were likely to contribute to MDS progression and were helpful for predicting prognosis of MDS. Inhibition of HERG K(+) channels might be a novel therapeutic measure for MDS.

  18. Functional Contributions of Positive Charges in the Pore-Lining Helix 3 of the Bordetella pertussis CyaA-Hemolysin to Hemolytic Activity and Ion-Channel Opening

    Directory of Open Access Journals (Sweden)

    Chattip Kurehong

    2017-03-01

    Full Text Available The Bordetella pertussis CyaA-hemolysin (CyaA-Hly domain was previously demonstrated to be an important determinant for hemolysis against target erythrocytes and ion-channel formation in planar lipid bilayers (PLBs. Here, net-charge variations in the pore-lining helix of thirteen related RTX cytolysins including CyaA-Hly were revealed by amino acid sequence alignments, reflecting their different degrees of hemolytic activity. To analyze possible functional effects of net-charge alterations on hemolytic activity and channel formation of CyaA-Hly, specific mutations were made at Gln574 or Glu581 in its pore-lining α3 of which both residues are highly conserved Lys in the three highly active RTX cytolysins (i.e., Escherichia coli α-hemolysin, Actinobacillus pleuropneumoniae toxin, and Aggregatibacter actinomycetemcomitans leukotoxin. All six constructed CyaA-Hly mutants that were over-expressed in E. coli as 126 kDa His-tagged soluble proteins were successfully purified via immobilized Ni2+-affinity chromatography. Both positive-charge substitutions (Q574K, Q574R, E581K, E581R and negative-charge elimination (E581Q appeared to increase the kinetics of toxin-induced hemolysis while the substitution with a negatively-charged side-chain (Q574E completely abolished its hemolytic activity. When incorporated into PLBs under symmetrical conditions (1.0 M KCl, pH 7.4, all five mutant toxins with the increased hemolytic activity produced clearly-resolved single channels with higher open probability and longer lifetime than the wild-type toxin, albeit with a half decrease in their maximum conductance. Molecular dynamics simulations for 50 ns of a trimeric CyaA-Hly pore model comprising three α2-loop-α3 transmembrane hairpins revealed a significant role of the positive charge at both target positions in the structural stability and enlarged diameter of the simulated pore. Altogether, our present data have disclosed functional contributions of positively

  19. Behavior of near-field dilution of thermal buoyant jet discharged horizontally in compound open-channel

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The RNG к-ε model considering the buoyancy effect,which is solved by the hybrid finite analytic method,is used to simulate the mixture of the horizontal round thermal buoyant jet in compound open channel flow.The mixing features near the spout and flowing characteristic of the secondary currents are studied by numerical simulation.Meanwhile,(1) the distribution of the measured isovels for stream-wise velocity,(2) secondary currents,(3) the distribution of the measured isovels for temperature of typical cross-section near the spout,were obtained by the three-dimensional Micro ADV and the Temperature measuring device.Compared with experimental data,the RNG к-εmodel based on buoyancy effect can preferably simulate the jet which performs the bifurcation phenomenon,jet reattachment (Conada effect) and beach secondary currents phenomenon with the effect of ambient flow,buoyancy,and secondary currents of compound section and so on.

  20. Numerical and Experimental Investigation of Natural Convection in Open-Ended Channels with Application to Building Integrated Photovoltaic (BIPV Systems

    Directory of Open Access Journals (Sweden)

    Timchenko V.

    2015-01-01

    Full Text Available Numerical and experimental investigations of the flow and heat transfer in open-ended channel formed by the double skin façade have been undertaken in order to improve understanding of the phenomena and to apply it to passive cooling of building integrated photovoltaic systems. Both uniform heating and non-uniform heating configurations in which heat sources alternated with unheated zones on both skins were studied. Different periodic and asymmetric heating modes have been considered for the same aspect ratio 1/15 of wall distance to wall height and for periodicity 1/15 and 4/15 of heated/unheated zones and heat input, 220 W/m2. In computational study three dimensional transient LES simulation was carried out. It is shown that in comparison to uniformly heating configuration, non-uniformly heating configuration enhances both convective heat transfer and chimney effect.

  1. A LINEAR THEORY FOR DISTURBANCE OF COHERENT STRUCTURE AND MECHANISM OF SAND WAVES IN OPEN-CHANNEL FLOW

    Institute of Scientific and Technical Information of China (English)

    Yuchuan BAI; Andreas MALCHEREK; Changbo JIANG

    2001-01-01

    The formation of sand wave is such a process in which the roughness and discontinuity of the original bed surface cause the disturbance of the bottom laminar flow in an open channel,and the development of the disturbance in turn leads to instability of the flow and the appearance of the coherent structure. The evolution and development of the coherent structure further promote the undulations of bed surface and sand waves rise finally. The sand wave is explained as a result of action that the bed sediment particles are disturbed by the coherent structure. This study shows that the sand wave formation is the result of disturbance action of neutral coherent structure, and the sand wave shape obtained in computations is identical to the practical one.

  2. EVALUATION OF THE SHADING METHOD FOR REDUCING IMAGE BLOOMING IN THE PIV MEASUREMENT OF OPEN CHANNEL FLOWS

    Institute of Scientific and Technical Information of China (English)

    ZHONG Qiang; LI Dan-xun; CHEN Qi-gang; WANG Xing-kui

    2012-01-01

    The shading method is a simple but effective way of reducing image blooming in the measurement of open channel flows with the Particle Image Veloeimetry (PIV).The current paper proposes a simplified analytical model for light attenuation using this method.The model is verified against experimental data,and the influence of several parameters is illustrated numerically.The possible adverse effect due to the light attenuation is shown to be limited when the parameters in the shading method are in an adequate range,as shown by processing standard images of Case B in PIV Challenge 03.A simple criterion for setting the shade in experiment is given for controlling the errors caused by the shading technique within an acceptable range.

  3. Sediment, water column, and open-channel denitrification in rivers measured using membrane-inlet mass spectrometry

    Science.gov (United States)

    Reisinger, Alexander J.; Tank, Jennifer L.; Hoellein, Timothy J.; Hall, Robert O.

    2016-05-01

    Riverine biogeochemical processes are understudied relative to headwaters, and reach-scale processes in rivers reflect both the water column and sediment. Denitrification in streams is difficult to measure, and is often assumed to occur only in sediment, but the water column is potentially important in rivers. Dissolved nitrogen (N) gas flux (as dinitrogen (N2)) and open-channel N2 exchange methods avoid many of the artificial conditions and expenses of common denitrification methods like acetylene block and 15N-tracer techniques. We used membrane-inlet mass spectrometry and microcosm incubations to quantify net N2 and oxygen flux from the sediment and water column of five Midwestern rivers spanning a land use gradient. Sediment and water column denitrification ranged from below detection to 1.8 mg N m-2 h-1 and from below detection to 4.9 mg N m-2 h-1, respectively. Water column activity was variable across rivers, accounting for 0-85% of combined microcosm denitrification and 39-85% of combined microcosm respiration. Finally, we estimated reach-scale denitrification at one Midwestern river using a diel, open-channel N2 exchange approach based on reach-scale metabolism methods, providing an integrative estimate of riverine denitrification. Reach-scale denitrification was 8.8 mg N m-2 h-1 (95% credible interval: 7.8-9.7 mg N m-2 h-1), higher than combined sediment and water column microcosm estimates from the same river (4.3 mg N m-2 h-1) and other estimates of reach-scale denitrification from streams. Our denitrification estimates, which span habitats and spatial scales, suggest that rivers can remove N via denitrification at equivalent or higher rates than headwater streams.

  4. Large-conductance K+ channel openers NS1619 and NS004 as inhibitors of mitochondrial function in glioma cells.

    Science.gov (United States)

    Debska, Grazyna; Kicinska, Anna; Dobrucki, Jerzy; Dworakowska, Beata; Nurowska, Ewa; Skalska, Jolanta; Dolowy, Krzysztof; Szewczyk, Adam

    2003-06-01

    Recently, it has been reported that large-conductance Ca(2+)-activated potassium channels, also known as BK(Ca)-type potassium channels, are present in the inner mitochondrial membrane of the human glioma LN229 cell line. Hence, in the present study, we have investigated whether BK(Ca)-channel openers (BK(Ca)COs), such as the benzimidazolone derivatives NS004 (5-trifluoromethyl-1-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-2H-benzimidazole-2-one) and NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one), affect the functioning of LN229 glioma cell mitochondria in situ. We examined the effect of BK(Ca)COs on mitochondrial membrane potential, mitochondrial respiration and plasma membrane potassium current in human glioma cell line LN229. We found that BK(Ca)COs decrease the mitochondrial membrane potential with an EC(50) value of 3.6+/-0.4 microM for NS1619 and 5.4+/-0.8 microM for NS004. This mitochondrial depolarization was accompanied by an inhibition of the mitochondrial respiratory chain. Both BK(Ca)COs induced whole-cell potassium current blocked by charybdotoxin, as measured by the patch-clamp technique. The BK(Ca)COs had no effect on membrane bilayer conductance. Moreover, the inhibition of mitochondrial function by NS004 and NS1619 was without effect on cell survival, as measured by lactate dehydrogenase release from the cells.

  5. Gradually-varied open-channel flow profiles normalized by critical depth and analytically solved by using Gaussian hypergeometric functions

    Directory of Open Access Journals (Sweden)

    C. D. Jan

    2012-10-01

    Full Text Available The equation of one-dimensional gradually-varied flow (GVF in sustaining and non-sustaining open channels is normalized using the critical depth, hc, and then analytically solved by the direct integration method with the use of the Gaussian hypergeometric function (GHF. The GHF-based solution so obtained from the hc-based dimensionless GVF equation is more useful and versatile than its counterpart from the GVF equation normalized by the normal depth, hn, because the GHF-based solutions of the hc-based dimensionless GVF equation for the mild (M and adverse (A profiles can asymptotically reduce to the hc-based dimensionless horizontal (H profiles as hc/hn → 0. An in-depth analysis of the hc-based dimensionless profiles expressed in terms of the GHF for GVF in sustaining and adverse wide channels has been conducted to discuss the effects of hc/hn and the hydraulic exponent N on the profiles This paper has laid the foundation to compute at one sweep the hc-based dimensionless GVF profiles in a series of sustaining and adverse channels, which have horizontal slopes sandwiched in between them, by using the GHF-based solutions.

  6. Hyporheic flow and dissolved oxygen distribution in fish nests: The effects of open channel velocity, permeability patterns, and groundwater upwelling

    Science.gov (United States)

    Cardenas, M. Bayani; Ford, Aimee E.; Kaufman, Matthew H.; Kessler, Adam J.; Cook, Perran L. M.

    2016-12-01

    Many fish lay their eggs in nests, or redds, which they construct in sediment. The viability of eggs depends on many factors, particularly their oxygenation. Because dissolved oxygen is typically saturated within the stream channel, the dissolved oxygen distribution within the redd depends on whether or not hyporheic flow and transport occur within the sediment. We conducted a series of flume and numerical flow and age transport modeling experiments with the aim of understanding the effects of salmonid redds on the hyporheic transport of young oxygenated water. Hyporheic flow was visualized directly through dye injections. Dissolved oxygen throughout the fish nest was measured using a planar optode. Experiments were conducted at various open channel flow velocities in order to understand their effect on dissolved oxygen, and computational simulations considered various sediment textures and ambient groundwater upwelling rates to add process-level insight. We found that, as also shown by previous studies, the redd topography induces multiscale hyporheic flow that effectively flushes the egg pocket location with younger presumably oxygenated water; older water upwells and forms anoxic zones. This pattern persists even at the lowest channel flow rates and at small upwelling velocities of older ambient groundwater which splits the multiscale hyporheic flow cells into isolated pockets. Large groundwater upwelling rates can shut down all the hyporheic flushing. The relatively coarse texture of the redd further promotes hyporheic flushing of the redd sediment with oxygenated water. Thus, redd morphology and sediment texture optimally combine to induce hyporheic exchange flow that delivers young oxygenated water to the egg pocket.

  7. Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization

    Science.gov (United States)

    Degani-Katzav, Nurit; Klein, Moshe; Har-Even, Moran; Gortler, Revital; Tobi, Ruthi; Paas, Yoav

    2017-01-01

    Ivermectin (IVM) is a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. By activating invertebrate pentameric glutamate-gated chloride channels (GluCl receptors; GluClRs), IVM induces sustained chloride influx and long-lasting membrane hyperpolarization that inhibit neural excitation in nematodes. Although IVM activates the C. elegans heteromeric GluClα/β receptor, it cannot activate a homomeric receptor composed of the C. elegans GluClβ subunits. To understand this incapability, we generated a homopentameric α7-GluClβ chimeric receptor that consists of an extracellular ligand-binding domain of an α7 nicotinic acetylcholine receptor known to be potentiated by IVM, and a chloride-selective channel domain assembled from GluClβ subunits. Application of IVM prior to acetylcholine inhibited the responses of the chimeric α7-GluClβR. Adding IVM to activated α7-GluClβRs, considerably accelerated the decline of ACh-elicited currents and stabilized the receptors in a non-conducting state. Determination of IVM association and dissociation rate constants and recovery experiments suggest that, following initial IVM binding to open α7-GluClβRs, the drug induces a conformational change and locks the ion channel in a closed state for a long duration. We further found that IVM also inhibits the activation by glutamate of a homomeric receptor assembled from the C. elegans full-length GluClβ subunits. PMID:28218274

  8. Sudden acceleration of flames in open channels driven by hydraulic resistance

    CERN Document Server

    Yanez, J; Bykov, V

    2012-01-01

    Hydrogen-air deflagrations with venting at the end of obstructed tubes are studied experimentally and numerically. A shockless transition to the so-called chocked regime of the flame propagation is reported. Mixtures with 13% vol. of hydrogen were ignited from the open end of the tube at the interface between fuel and the ambient air. Three venting ratios were selected, closed, 40% and 100%. In all cases the flame initially propagates without acceleration at a velocity close to the laminar flame speed. The flame configuration excludes most of conventionally acknowledged phenomena of the DDT, namely, volumetric explosions, igniting shock and shock waves interactions. However, after an induction period, of the order of 1 sec, the flame accelerates more than 100 times, within a period of 3-30 ms, until the steady-state choked regime is established. The mechanism of such rapid acceleration is investigated both numerically and analytically. A one dimensional reduced description was suggested and analyzed to model ...

  9. Two-dimensional crystals of mesoporous silica SBA-15 nanosheets with perpendicular and open channels

    Directory of Open Access Journals (Sweden)

    Yi-Qi Yeh

    2014-11-01

    Full Text Available A preparation of mesoporous silica SBA-15 thin sheets with perpendicular nanochannels (SBA(⊥ and open ends is reported here. At a synthesis condition of pH = 2 where the silica condensation is extremely slow, micron-sized single-crystal-like hexagonally faceted nanosheets (SBA(⊥-pH2 with aspect ratio of 10–50 were formed. The nanosheets can attach to each other in sideway to extend the thin sheet. At pH = 5, multi-domain SBA(⊥-pH5 nanosheets are formed, and stacking attachment of sheets is preferred. Vivid Moiré patterns are observed in large areas of stacked silica sheets, indicating excellent structure order.

  10. Hair cell BK channels interact with RACK1, and PKC increases its expression on the cell surface by indirect phosphorylation.

    Science.gov (United States)

    Surguchev, Alexei; Bai, Jun-Ping; Joshi, Powrnima; Navaratnam, Dhasakumar

    2012-07-15

    Large conductance (BK) calcium activated potassium channels (Slo) are ubiquitous and implicated in a number of human diseases including hypertension and epilepsy. BK channels consist of a pore forming α-subunit (Slo) and a number of accessory subunits. In hair cells of nonmammalian vertebrates these channels play a critical role in electrical resonance, a mechanism of frequency selectivity. Hair cell BK channel clusters on the surface and currents increase along the tonotopic axis and contribute significantly to the responsiveness of these hair cells to sounds of high frequency. In contrast, messenger RNA levels encoding the Slo gene show an opposite decrease in high frequency hair cells. To understand the molecular events underlying this paradox, we used a yeast two-hybrid screen to isolate binding partners of Slo. We identified Rack1 as a Slo binding partner and demonstrate that PKC activation increases Slo surface expression. We also establish that increased Slo recycling of endocytosed Slo is at least partially responsible for the increased surface expression of Slo. Moreover, analysis of several PKC phosphorylation site mutants confirms that the effects of PKC on Slo surface expression are likely indirect. Finally, we show that Slo clusters on the surface of hair cells are also increased by increased PKC activity and may contribute to the increasing amounts of channel clusters on the surface of high-frequency hair cells.

  11. High glucose-induced oxidative stress increases transient receptor potential channel expression in human monocytes

    DEFF Research Database (Denmark)

    Wuensch, Tilo; Thilo, Florian; Krueger, Katharina;

    2010-01-01

    Transient receptor potential (TRP) channel-induced cation influx activates human monocytes, which play an important role in the pathogenesis of atherosclerosis. In the present study, we investigated the effects of high glucose-induced oxidative stress on TRP channel expression in human monocytes....

  12. EEG channels reduction using PCA to increase XGBoost's accuracy for stroke detection

    Science.gov (United States)

    Fitriah, N.; Wijaya, S. K.; Fanany, M. I.; Badri, C.; Rezal, M.

    2017-07-01

    In Indonesia, based on the result of Basic Health Research 2013, the number of stroke patients had increased from 8.3 ‰ (2007) to 12.1 ‰ (2013). These days, some researchers are using electroencephalography (EEG) result as another option to detect the stroke disease besides CT Scan image as the gold standard. A previous study on the data of stroke and healthy patients in National Brain Center Hospital (RS PON) used Brain Symmetry Index (BSI), Delta-Alpha Ratio (DAR), and Delta-Theta-Alpha-Beta Ratio (DTABR) as the features for classification by an Extreme Learning Machine (ELM). The study got 85% accuracy with sensitivity above 86 % for acute ischemic stroke detection. Using EEG data means dealing with many data dimensions, and it can reduce the accuracy of classifier (the curse of dimensionality). Principal Component Analysis (PCA) could reduce dimensionality and computation cost without decreasing classification accuracy. XGBoost, as the scalable tree boosting classifier, can solve real-world scale problems (Higgs Boson and Allstate dataset) with using a minimal amount of resources. This paper reuses the same data from RS PON and features from previous research, preprocessed with PCA and classified with XGBoost, to increase the accuracy with fewer electrodes. The specific fewer electrodes improved the accuracy of stroke detection. Our future work will examine the other algorithm besides PCA to get higher accuracy with less number of channels.

  13. Computational analysis of the effects of the hERG channel opener NS1643 in a human ventricular cell model

    DEFF Research Database (Denmark)

    Peitersen, Torben; Grunnet, Morten; Benson, Alan P

    2008-01-01

    BACKGROUND: Dysfunction or pharmacologic inhibition of repolarizing cardiac ionic currents can lead to fatal arrhythmias. The hERG potassium channel underlies the repolarizing current I(Kr), and mutations therein can produce both long and short QT syndromes (LQT2 and SQT1). We previously reported...... on the diphenylurea compound NS1643, which acts on hERG channels in two distinct ways: by increasing overall conductance and by shifting the inactivation curve in the depolarized direction. OBJECTIVE: The purpose of this study was to determine which of the two components contributes more to the antiarrhythmic effects...... of NS1643 under normokalemic and hypokalemic conditions. METHODS: The study consisted of mathematical simulation of action potentials in a human ventricular ionic cell model in single cell and string of 100 cells. RESULTS: Regardless of external potassium concentration or diastolic interval used, NS1643...

  14. Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames.

    Science.gov (United States)

    Liang, Xue-Hai; Shen, Wen; Sun, Hong; Migawa, Michael T; Vickers, Timothy A; Crooke, Stanley T

    2016-08-01

    Increasing the levels of therapeutic proteins in vivo remains challenging. Antisense oligonucleotides (ASOs) are often used to downregulate gene expression or to modify RNA splicing, but antisense technology has not previously been used to directly increase the production of selected proteins. Here we used a class of modified ASOs that bind to mRNA sequences in upstream open reading frames (uORFs) to specifically increase the amounts of protein translated from a downstream primary ORF (pORF). Using ASO treatment, we increased the amount of proteins expressed from four genes by 30-150% in a dose-dependent manner in both human and mouse cells. Notably, systemic treatment of mice with ASO resulted in an ∼80% protein increase of LRPPRC. The ASO-mediated increase in protein expression was sequence-specific, occurred at the level of translation and was dependent on helicase activity. We also found that the type of RNA modification and the position of modified nucleotides in ASOs affected translation of a pORF. ASOs are a useful class of therapeutic agents with broad utility.

  15. A Comparison of Critical Regimes in Collapsible Tube, Pipe, Open Channel and Gas-Dynamic Flows

    Science.gov (United States)

    Arun, C. P.

    2003-11-01

    Though of considerable interest to clinical scientists, collapsible tubes are only recently receiving due interest by fluid physicists. The subject of critical phenomena in collapsible tube flow appears not to have been examined critically. For example, it has been proposed in the past that shock waves in physiological tubes are abnormal. We propose a classification of flow through collapsible tubes recognising that compressibility in gas-dynamic and pipe flow (cf.waterhammer) corresponds to distensibility in collapsible tube flow. Thus, opening and closing waves of collapsible tube flow (predistension regime) is subcritical flow and the post-distension regime, supercritical. Physiological tubes are often hyperelastic and contractile and often, when distension is very significant, a hypercritical regime corresponding to hypersonic gas-dynamic flow is admissible. Such a hypercritical regime would allow storage of energy and muscle contraction in the wall of the tube and hence continuance of propulsion in the essentially intermittent flow that is seen in collapsible tubes. Such a mechanism appears to be in operation in the human aorta, bowel and urethra. The present work offers a comparison of critical regimes in various fluid flow situations including collapsible tubes, that is in harmony with known phenomena seen in nature.

  16. Fast-onset lidocaine block of rat NaV1.4 channels suggests involvement of a second high-affinity open state.

    Science.gov (United States)

    Gingrich, Kevin J; Wagner, Larry E

    2016-06-01

    Local anesthetics (LAs) block resting, open, and inactivated states of voltage-gated Na(+) channels where inactivated states are thought to bind with highest affinity. However, reports of fast-onset block occurring over milliseconds hint at high-affinity block of open channels. Movement of voltage-sensor domain IV-segment 4 (DIVS4) has been associated with high affinity LA block termed voltage-sensor block (VSB) that also leads to a second open state. These observations point to a second high-affinity open state that may underlie fast-onset block. To test for this state, we analyzed the modulation of Na(+) currents by lidocaine and its quaternary derivative (QX222) from heterologously expressed (Xenopus laevis oocytes) rat skeletal muscle μ1 NaV1.4 (rSkM1) with β1 (WT-β1), and a mutant form (IFM-QQQ mutation in the III-IV interdomain, QQQ) lacking fast inactivation, in combination with Markov kinetic gating models. 100 μM lidocaine induced fast-onset (τonset≈2 ms), long-lived (τrecovery≈120 ms) block of WT-β1 macroscopic currents. Lidocaine blocked single-channel and macroscopic QQQ currents in agreement with our previously described mechanism of dual, open-channel block (DOB mechanism). A DOB kinetic model reproduced lidocaine effects on QQQ currents. The DOB model was extended to include trapping fast-inactivation and activation gates, and a second open state (OS2); the latter arising from DIVS4 translocation that precedes inactivation and exhibits high-affinity, lidocaine binding (apparent Kd=25 μM) that accords with VSB (DOB-S2VSB mechanism). The DOB-S2VSB kinetic model predicted fast-onset block of WT-β1. The findings support the involvement of a second, high-affinity, open state in lidocaine modulation of Na(+) channels.

  17. Increase of ATP-sensitive potassium (KATP channels in the heart of type-1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Chen Zhih-Cherng

    2012-01-01

    Full Text Available Abstract Background An impairment of cardiovascular function in streptozotocin (STZ-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (KATP channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac KATP channels in diabetic disorders. Methods Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr were used to examine the effect of hyperglycemia on cardiac function and the expression of KATP channels. KATP channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of KATP channels by Western blot and Northern blot analysis. Results The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of KATP channel. Two subunits of cardiac KATP channel (SUR2A and kir 6.2 were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac KATP in these diabetic rats. Conclusions Both mRNA and protein expression of cardiac KATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some KATP channel drugs.

  18. A Monotonically Increasing Lower Bound on the Capacity of the Fiber-Optical Channel

    CERN Document Server

    Keykhosravi, Kamran; Durisi, Giuseppe

    2015-01-01

    An achievable rate is derived for the fiber-optical channel, described by the nonlinear Schr\\"odinger equation and discretized in time and space. The model takes into account the effects of nonlinearity, dispersion, and noise. The obtained achievable rate goes to infinity with a pre-log factor of one half as the power grows large. Since any achievable rate is a lower bound on the capacity of the same channel, the result proves that the capacity of the discretized fiber-optical channel grows unboundedly.

  19. K(ATP channel opener diazoxide prevents neurodegeneration: a new mechanism of action via antioxidative pathway activation.

    Directory of Open Access Journals (Sweden)

    Noemí Virgili

    Full Text Available Pharmacological modulation of ATP-sensitive potassium channels has become a promising new therapeutic approach for the treatment of neurodegenerative diseases due to their role in mitochondrial and cellular protection. For instance, diazoxide, a well-known ATP-sensitive potassium channel activator with high affinity for mitochondrial component of the channel has been proved to be effective in animal models for different diseases such as Alzheimer's disease, stroke or multiple sclerosis. Here, we analyzed the ability of diazoxide for protecting neurons front different neurotoxic insults in vitro and ex vivo. Results showed that diazoxide effectively protects NSC-34 motoneurons from glutamatergic, oxidative and inflammatory damage. Moreover, diazoxide decreased neuronal death in organotypic hippocampal slice cultures after exicitotoxicity and preserved myelin sheath in organotypic cerebellar cultures exposed to pro-inflammatory demyelinating damage. In addition, we demonstrated that one of the mechanisms of actions implied in the neuroprotective role of diazoxide is mediated by the activation of Nrf2 expression and nuclear translocation. Nrf2 expression was increased in NSC-34 neurons in vitro as well as in the spinal cord of experimental autoimmune encephalomyelitis animals orally administered with diazoxide. Thus, diazoxide is a neuroprotective agent against oxidative stress-induced damage and cellular dysfunction that can be beneficial for diseases such as multiple sclerosis.

  20. Increasing Public Access to University Qualifications: Evolution of The University of the West Indies Open Campus

    Directory of Open Access Journals (Sweden)

    Michael L. Thomas

    2009-02-01

    Full Text Available This paper traces the evolution of The University of the West Indies’ Open Campus (UWIOC, which is expected to expand service and increase access to the underserved communities of the Eastern Caribbean. At present, UWI, which caters to the needs of the 16 far flung countries of the Commonwealth Caribbean, has not been able to fully serve these countries, the UWI-12, in a way that is commensurate with their developmental needs. Historically, the institution has been dominated by campus-based education, and its three campuses have been poles of attraction for scholars and scholarship to the significant advantage of the countries in which they are located: Jamaica, Trinidad and Tobago, and Barbados. The University’s creation of an open campus, a fourth campus, enables it to expand its scope, enhance its appeal, and improve the efficiency of its services to individuals, communities, and countries. This new campus, a merger of UWI’s Outreach sector, which comprises the School of Continuing Studies, the Tertiary Level Institute Unit, and The UWI Distance Education Centre, will have a physical presence in each contributing country and will function as a network of real and virtual modes to deliver education and training to anyone with access to Internet facilities.

  1. Real-time Control of Combined Water Quantity & Quality in Open Channels

    NARCIS (Netherlands)

    Xu, M.

    2013-01-01

    Fresh water supply and flood protection are two central issues in water management. Society needs more and more fresh water and a safe water system to guarantee a better life. A more severe climate will result in more droughts and extreme storms. As a consequence, salt water intrusion will increase.

  2. Real-time Control of Combined Water Quantity & Quality in Open Channels

    NARCIS (Netherlands)

    Xu, M.

    2013-01-01

    Fresh water supply and flood protection are two central issues in water management. Society needs more and more fresh water and a safe water system to guarantee a better life. A more severe climate will result in more droughts and extreme storms. As a consequence, salt water intrusion will increase.

  3. An increase in [Ca2+]i activates basolateral chloride channels and inhibits apical sodium channels in frog skin epithelium

    DEFF Research Database (Denmark)

    Brodin, Birger; Rytved, K A; Nielsen, R

    1996-01-01

    The aim of this study was to investigate the mechanisms by which increases in free cytosolic calcium ([Ca2+]i) cause a decrease in macroscopic sodium absorption across principal cells of the frog skin epithelium. [Ca2+]i was measured with fura-2 in an epifluorescence microscope set-up, sodium...... absorption was measured by the voltage-clamp technique and cellular potential was measured using microelectrodes. The endoplasmic reticulum calcium-ATPase inhibitor thapsigargin (0.4 microM) increased [Ca2+]i from 66 +/- 9 to 137 +/- 19 nM (n = 13, P = 0.002). Thapsigargin caused the amiloride-sensitive...

  4. Performance of an open limestone channel for treating a stream affected by acid rock drainage (León, Spain).

    Science.gov (United States)

    Santofimia, Esther; López-Pamo, Enrique

    2016-07-01

    The generation of acid rock drainage (ARD) was observed after the oxidation dissolution of pyrite-rich black shales, which were excavated during the construction of a highway in León (Spain). ARDs are characterized by the presence of high concentrations of sulfate and metals (Al, Fe, Mn, Zn, Cu, Co, Ni, Th, and U) that affect the La Silva stream. Dissolved element concentrations showed values between one and four orders of magnitude higher than those of natural waters of this area. A passive treatment system was constructed; the aim of which was to improve the quality of the water of the stream. This work provides a hydrochemical characterization of the La Silva stream after its transit through the different elements that constitute the passive treatment system (open limestone channel (OLC), small ponds, and a wetland), during its first year of operation. The passive treatment system has two sections separated by a tunnel 230 m long. The first section, which stretches between the highway and the tunnel entrance, is an OLC 350 m long with a slope of 16 %. The second section, which stretches from the tunnel exit to the end wetland, has a length of 700 m and a slope of 6 %; it is in this section where six small ponds are located. In the first section of this passive treatment system, the OLC was effectively increasing the pH from 3 to 4-4.5 and eliminating all of the dissolved Fe and the partially dissolved Al. These elements, after hydrolysis at a pH 3-3.5 and 4-4.5, respectively, had precipitated as schwertmannite and hydrobasaluminite, while other dissolved metals were removed totally or partially for adsorption by the precipitates and/or by coprecipitation. The second section receives different inputs of water such as ARDs and natural waters. After exiting the treatment system, the stream is buffered by Al at a pH of 4-4.3, showing high Al concentrations (19-101 mg/L) but with a complete removal of dissolved Fe. Unfortunately, the outflow shows similar or

  5. Calcium and Vitamin D increase mRNA levels for the growth control hIK1 channel in human epidermal keratinocytes but functional channels are not observed

    Directory of Open Access Journals (Sweden)

    Rossie Sandra

    2004-06-01

    Full Text Available Abstract Background Intermediate-conductance, calcium-activated potassium channels (IKs modulate proliferation and differentiation in mesodermal cells by enhancing calcium influx, and they contribute to the physiology of fluid movement in certain epithelia. Previous reports suggest that IK channels stimulate proliferative growth in a keratinocyte cell line; however, because these channels indirectly promote calcium influx, a critically unique component of the keratinocyte differentiation program, an alternative hypothesis is that they would be anti-proliferative and pro-differentiating. This study addresses these hypotheses. Methods Real-time PCR, patch clamp electrophysiology, and proliferation assays were used to determine if human IK1 (hIK1 expression and function are correlated with either proliferation or differentiation in cultured human skin epidermal keratinocytes, and skin biopsies grown in explant culture. Results hIK1 mRNA expression in human keratinocytes and skin was increased in response to anti-proliferative/pro-differentiating stimuli (elevated calcium and Vitamin D. Correspondingly, the hIK1 agonist 1-EBIO inhibited keratinocyte proliferation suggesting that the channel could be anti-proliferative and pro-differentiating. However, this proliferative inhibition by 1-EBIO was not reversed by a panel of hIK1 blockers, calling into question the mechanism of 1-EBIO action. Subsequent patch clamp electrophysiological analysis failed to detect hIK1 channel currents in keratinocytes, even those expressing substantial hIK1 mRNA in response to calcium and Vitamin D induced differentiation. Identical electrophysiological recording conditions were then used to observe robust IK1 currents in fibroblasts which express IK1 mRNA levels comparable to those of keratinocytes. Thus, the absence of observable hIK1 currents in keratinocytes was not a function of the electrophysiological techniques. Conclusion Human keratinocyte differentiation is

  6. Turbulence characteristics of open channel flow over non-equilibrium 3-D mobile dunes

    Indian Academy of Sciences (India)

    PRASHANTH REDDY HANMAIAHGARI; RAM BALACHANDAR

    2016-09-01

    This paper reports velocity measurements over mobile dunes using an acoustic Doppler velocimetry (ADV). Experiments were conducted with two different flow conditions resulting in the formation of two different size mobile dunes. Dunes height, wavelength and velocity of dunes found to be increasing with increase in average flow velocity for a constant flow depth. The quasi-stationary bed condition was assumed while measuring the velocity distribution along the depth. The effect of the non-equilibrium mobile dunes on the flow characteristics and turbulence is examined by computing turbulent intensities, turbulent kinetic energy and Reynolds shear stresses using time averaged and time–space averaged velocity measurements. The magnitudes of transverse velocities are approximately 1/10 of streamwise velocities and vertical velocities are approximately half of the transverse velocities. The considerable magnitudes of transverse velocities over mobile bedforms necessitate measurement of 3-D velocity components to analyze the flow field. Computed turbulence intensities are found to be maximum in the region consisting of the trough and the reattachment point of the dunes. It is observed that streamwise turbulence intensities near the bed are twice the transverse turbulence intensities, and transverse turbulence intensities are twice the vertical turbulence intensities. Reynolds stresses (transverse fluxes of streamwise and vertical momentum) are observed to be high on mobile bedforms which shows mobile dunes reinforce the secondary currents. Peak values of turbulent kinetic energy (TKE) and Reynolds stresses are also found in the region consisting of the trough and the reattachment point. It is visually observed in the present experiments that maximum erosion takes place at the reattachment point and eroded sediment is carried as totalload and dropped on the lee slope of the subsequent downstream dune. This phenomenon is caused by flow expansion in the separation zone

  7. Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    ZENG QingHua; LI XingTing; ZHONG GuoGan; ZHANG WenJie; SUN ChengWen

    2009-01-01

    Using fura-2-acetoxymethyl eater (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]1) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats.The effect of ET-1 on [Ca2+]1 elevation was abolished in the presence of the ETA receptor blocker BQ123,but was not affected by the ETa receptor blocker BQ788. ET-1-induced an increase in [Ca2+]1, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibltors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an Increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETa receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.

  8. Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.

  9. Molecular mechanisms underlying the effect of the novel BK channel opener GoSlo: involvement of the S4/S5 linker and the S6 segment.

    Science.gov (United States)

    Webb, Timothy I; Kshatri, Aravind Singh; Large, Roddy J; Akande, Adebola Morayo; Roy, Subhrangsu; Sergeant, Gerard P; McHale, Noel G; Thornbury, Keith D; Hollywood, Mark A

    2015-02-17

    GoSlo-SR-5-6 is a novel large-conductance Ca(2+)-activated K(+) (BK) channel agonist that shifts the activation V1/2 of these channels in excess of -100 mV when applied at a concentration of 10 μM. Although the structure-activity relationship of this family of molecules has been established, little is known about how they open BK channels. To help address this, we used a combination of electrophysiology, mutagenesis, and mathematical modeling to investigate the molecular mechanisms underlying the effect of GoSlo-SR-5-6. Our data demonstrate that the effects of this agonist are practically abolished when three point mutations are made: L227A in the S4/S5 linker in combination with S317R and I326A in the S6C region. Our data suggest that GoSlo-SR-5-6 interacts with the transmembrane domain of the channel to enhance pore opening. The Horrigan-Aldrich model suggests that GoSlo-SR-5-6 works by stabilizing the open conformation of the channel and the activated state of the voltage sensors, yet decouples the voltage sensors from the pore gate.

  10. Ocular Hypotensive Effects of the ATP-Sensitive Potassium Channel Opener Cromakalim in Human and Murine Experimental Model Systems.

    Directory of Open Access Journals (Sweden)

    Uttio Roy Chowdhury

    Full Text Available Elevated intraocular pressure (IOP is the most prevalent and only treatable risk factor for glaucoma, a leading cause of irreversible blindness worldwide. Unfortunately, all current therapeutics used to treat elevated IOP and glaucoma have significant and sometimes irreversible side effects necessitating the development of novel compounds. We evaluated the IOP lowering ability of the broad spectrum KATP channel opener cromakalim. Cultured human anterior segments when treated with 2 μM cromakalim showed a decrease in pressure (19.33 ± 2.78 mmHg at 0 hours to 13.22 ± 2.64 mmHg at 24 hours; p<0.001 when compared to vehicle treated controls (15.89 ± 5.33 mmHg at 0 h to 15.56 ± 4.88 mmHg at 24 hours; p = 0.89. In wild-type C57BL/6 mice, cromakalim reduced IOP by 18.75 ± 2.22% compared to vehicle treated contralateral eyes (17.01 ± 0.32 mmHg at 0 hours to 13.82 ± 0.37 mmHg at 24 hours; n = 10, p = 0.002. Cromakalim demonstrated an additive effect when used in conjunction with latanoprost free acid, a common ocular hypotensive drug prescribed to patients with elevated IOP. To examine KATP channel subunit specificity, Kir6.2(-/- mice were treated with cromakalim, but unlike wild-type animals, no change in IOP was noted. Histologic analysis of treated and control eyes in cultured human anterior segments and in mice showed similar cell numbers and extracellular matrix integrity within the trabecular meshwork, with no disruptions in the inner and outer walls of Schlemm's canal. Together, these studies suggest that cromakalim is a potent ocular hypotensive agent that lowers IOP via activation of Kir6.2 containing KATP channels, its effect is additive when used in combination with the commonly used glaucoma drug latanoprost, and is not toxic to cells and tissues of the aqueous humor outflow pathway, making it a candidate for future therapeutic development.

  11. Did Open Solar Magnetic Field Increase during the Last 100 Years: A Reanalysis of Geomagnetic Activity

    CERN Document Server

    Mursula, K; Karinen, A

    2004-01-01

    Long-term geomagnetic activity presented by the aa index has been used to show that the heliospheric magnetic field has more than doubled during the last 100 years. However, serious concern has been raised on the long-term consistency of the aa index and on the centennial rise of the solar magnetic field. Here we reanalyze geomagnetic activity during the last 100 years by calculating the recently suggested IHV (Inter-Hour Variability) index as a measure of local geomagnetic activity for seven stations. We find that local geomagnetic activity at all stations follows the same qualitative long-term pattern: an increase from early 1900s to 1960, a dramatic dropout in 1960s and a (mostly weaker) increase thereafter. Moreover, at all stations, the activity at the end of the 20th century has a higher average level than at the beginning of the century. This agrees with the result based on the aa index that global geomagnetic activity, and thereby, the open solar magnetic field has indeed increased during the last 100...

  12. Assessing cumulative watershed stressors: Using LIDAR to assess the amount of open lands and young forest associated with in-channel erosion for North Shore tributaries

    Science.gov (United States)

    Hydrologists with the US Forest Service have demonstrated the cumulative impacts of land use change, particularly additional open lands and young forest (< 15 yrs) on bank full flows and in-channel erosion. Mapping these impacts has been difficult due to challenges associated ...

  13. Redistribution of velocity and bed-shear stress in straight and curved open channels by means of a bubble screen: laboratory experiments

    NARCIS (Netherlands)

    Blanckaert, K.; Buschman, F.A.; Schielen, R.; Wijbenga, J.H.A.

    2008-01-01

    Open-channel beds show variations in the transverse direction due to the interaction between downstream flow, cross-stream flow, and bed topography, which may reduce the navigable width or endanger the foundations of structures. The reported preliminary laboratory study shows that a bubble screen ca

  14. Size effects on the open probability of two-state ion channel system in cell membranes using microcanonical formalism based on gamma function

    Science.gov (United States)

    Erdem, Riza; Aydiner, Ekrem

    2016-08-01

    Ion channel systems are a class of proteins that reside in the membranes of all biological cells and forms conduction pores that regulate the transport of ions into and out of cells. They can be investigated theoretically in the microcanonical formalism since the number of accessible states can be easily evaluated by using the Stirling approximation to deal with factorials. In this work, we have used gamma function (Γ (n)) to solve the two-state or open-close channel model without any approximation. New values are calculated for the open probability (p0) and the relative error between our numerical results and the approximate one using Stirling formula is presented. This error (p0 app — p0)/p0 is significant for small channel systems.

  15. Conditional knockout of Fgf13 in murine hearts increases arrhythmia susceptibility and reveals novel ion channel modulatory roles.

    Science.gov (United States)

    Wang, Xiangchong; Tang, He; Wei, Eric Q; Wang, Zhihua; Yang, Jing; Yang, Rong; Wang, Sheng; Zhang, Yongjian; Pitt, Geoffrey S; Zhang, Hailin; Wang, Chuan

    2017-03-01

    The intracellular fibroblast growth factors (iFGF/FHFs) bind directly to cardiac voltage gated Na(+) channels, and modulate their function. Mutations that affect iFGF/FHF-Na(+) channel interaction are associated with arrhythmia syndromes. Although suspected to modulate other ionic currents, such as Ca(2+) channels based on acute knockdown experiments in isolated cardiomyocytes, the in vivo consequences of iFGF/FHF gene ablation on cardiac electrical activity are still unknown. We generated inducible, cardiomyocyte-restricted Fgf13 knockout mice to determine the resultant effects of Fgf13 gene ablation. Patch clamp recordings from ventricular myocytes isolated from Fgf13 knockout mice showed a ~25% reduction in peak Na(+) channel current density and a hyperpolarizing shift in steady-state inactivation. Electrocardiograms on Fgf13 knockout mice showed a prolonged QRS duration. The Na(+) channel blocker flecainide further prolonged QRS duration and triggered ventricular tachyarrhythmias only in Fgf13 knockout mice, suggesting that arrhythmia vulnerability resulted, at least in part, from a loss of functioning Na(+) channels. Consistent with these effects on Na(+) channels, action potentials in Fgf13 knockout mice, compared to Cre control mice, exhibited slower upstrokes and reduced amplitude, but unexpectedly had longer durations. We investigated candidate sources of the prolonged action potential durations in myocytes from Fgf13 knockout mice and found a reduction of the transient outward K(+) current (Ito). Fgf13 knockout did not alter whole-cell protein levels of Kv4.2 and Kv4.3, the Ito pore-forming subunits, but did decrease Kv4.2 and Kv4.3 at the sarcolemma. No changes were seen in the sustained outward K(+) current or voltage-gated Ca(2+) current, other candidate contributors to the increased action potential duration. These results implicate that FGF13 is a critical cardiac Na(+) channel modulator and Fgf13 knockout mice have increased arrhythmia

  16. Inlet effects on roll-wave development in shallow turbulent open-channel flows

    Directory of Open Access Journals (Sweden)

    Campomaggiore Francesca

    2016-03-01

    Full Text Available The present work investigates the effect of the flow profile induced by an inlet condition on the roll-wave evolution in turbulent clear-water flows. The study employs theoretical and numerical analyses. Firstly, the influence of the inlet condition on the spatial evolution of a single perturbation in a hypercritical flow is examined through the expansion near a wavefront analysis. The results show that an accelerated unperturbed profile reduces the disturbance spatial growth. A decelerated profile causes an increase. The effect of the flow profile on the spatial evolution of roll-wave trains is then numerically investigated solving the Saint Venant equations with a second-order Runge-Kutta Total Variation Diminishing (TVD Finite Volume scheme. The numerical simulations comply with the analytical results for the initial and transition phases of the roll-wave development. The unperturbed profile influences even the roll-waves statistical characteristics in the final stage, with a more evident effect in case of accelerated profiles. The influence of the flow profile should be therefore accounted for in the formulation of predictive criteria for roll-waves appearance based on the estimation of the disturbance spatial growth rate.

  17. Basal interstitial water pressure in laboratory debris flows over a rigid bed in an open channel

    Directory of Open Access Journals (Sweden)

    N. Hotta

    2012-08-01

    Full Text Available Measuring the interstitial water pressure of debris flows under various conditions gives essential information on the flow stress structure. This study measured the basal interstitial water pressure during debris flow routing experiments in a laboratory flume. Because a sensitive pressure gauge is required to measure the interstitial water pressure in shallow laboratory debris flows, a differential gas pressure gauge with an attached diaphragm was used. Although this system required calibration before and after each experiment, it showed a linear behavior and a sufficiently high temporal resolution for measuring the interstitial water pressure of debris flows. The values of the interstitial water pressure were low. However, an excess of pressure beyond the hydrostatic pressure was observed with increasing sediment particle size. The measured excess pressure corresponded to the theoretical excess interstitial water pressure, derived as a Reynolds stress in the interstitial water of boulder debris flows. Turbulence was thought to induce a strong shear in the interstitial space of sediment particles. The interstitial water pressure in boulder debris flows should be affected by the fine sediment concentration and the phase transition from laminar to turbulent debris flow; this should be the subject of future studies.

  18. Grain-size distribution in suspension over a sand-gravel bed in open channel flow

    Institute of Scientific and Technical Information of China (English)

    Koeli GHOSHAL; Debasish PAL

    2014-01-01

    Grain-size distributions of suspended load over a sand-gravel bed at two different flow velocities were studied in a laboratory flume. The experiments had been performed to study the influence of flow velocity and suspension height on grain-size distribution in suspension over a sand-gravel bed. The experimental findings show that with an increase of flow velocity, the grain-size distribution of suspended load changed from a skewed form to a bimodal one at higher suspension heights. This study focuses on the determination of the parameter βn which is the ratio of the sediment diffusion coefficient to the momentum diffusion coefficient of n th grain-size. A new relationship has been proposed involvingβn , the normalizing settling velocity of sediment particles and suspension height, which is applicable for widest range of normalizing settling velocity available in literature so far. A similar parameter β for calculating total suspension concentration is also developed. The classical Rouse equation is modified with βn and β and used to compute grain-size distribution and total concentration in suspension, respectively. The computed values have shown good agreement with the measured values of experimental data.

  19. Increased anion channel activity is an unavoidable event in ozone-induced programmed cell death.

    Directory of Open Access Journals (Sweden)

    Takashi Kadono

    Full Text Available BACKGROUND: Ozone is a major secondary air pollutant often reaching high concentrations in urban areas under strong daylight, high temperature and stagnant high-pressure systems. Ozone in the troposphere is a pollutant that is harmful to the plant. PRINCIPAL FINDINGS: By exposing cells to a strong pulse of ozonized air, an acute cell death was observed in suspension cells of Arabidopsis thaliana used as a model. We demonstrated that O(3 treatment induced the activation of a plasma membrane anion channel that is an early prerequisite of O(3-induced cell death in A. thaliana. Our data further suggest interplay of anion channel activation with well known plant responses to O(3, Ca(2+ influx and NADPH-oxidase generated reactive oxygen species (ROS in mediating the oxidative cell death. This interplay might be fuelled by several mechanisms in addition to the direct ROS generation by O(3; namely, H(2O(2 generation by salicylic and abscisic acids. Anion channel activation was also shown to promote the accumulation of transcripts encoding vacuolar processing enzymes, a family of proteases previously reported to contribute to the disruption of vacuole integrity observed during programmed cell death. SIGNIFICANCE: Collectively, our data indicate that anion efflux is an early key component of morphological and biochemical events leading to O(3-induced programmed cell death. Because ion channels and more specifically anion channels assume a crucial position in cells, an understanding about the underlying role(s for ion channels in the signalling pathway leading to programmed cell death is a subject that warrants future investigation.

  20. Capture of DNA in microfluidic channel using magnetic beads: increasing capture efficiency with integrated microfluidic mixer

    DEFF Research Database (Denmark)

    Lund-Olesen, Torsten; Dufva, Hans Martin; Hansen, Mikkel Fougt

    2007-01-01

    We have studied the hybridization of target DNA in solution with probe DNA on magnetic beads immobilized on the channel sidewalls in a magnetic bead separator. The hybridization is carried out under a liquid flow and is diffusion limited. Two systems are compared: one with a straight microfluidic...... channel and one with an integrated staggered herringbone mixer. Fluorescence microscopy studies show that the hybridization is much more efficient in the system with the integrated mixer. The results, which are discussed in terms of a simple model, are relevant for any diffusion-limited reaction taking...... place on the surface in a microfluidic system....

  1. DNS of horizontal open channel flow with finite-size, heavy particles at low solid volume fraction

    CERN Document Server

    Kidanemariam, Aman G; Doychev, Todor; Uhlmann, Markus

    2013-01-01

    We have performed direct numerical simulation of turbulent open channel flow over a smooth horizontal wall in the presence of finite-size, heavy particles. The spherical particles have a diameter of approximately 7 wall units, a density of 1.7 times the fluid density and a solid volume fraction of 0.0005. The value of the Galileo number is set to 16.5, while the Shields parameter measures approximately 0.2. Under these conditions, the particles are predominantly located in the vicinity of the bottom wall, where they exhibit strong preferential concentration which we quantify by means of Voronoi analysis and by computing the particle-conditioned concentration field. As observed in previous studies with similar parameter values, the mean streamwise particle velocity is smaller than that of the fluid. We propose a new definition of the fluid velocity "seen" by finite-size particles based on an average over a spherical surface segment, from which we deduce in the present case that the particles are instantaneousl...

  2. Coastline changes and sedimentation related with the opening of an artificial channel: the Valo Grande Delta, SE Brazil.

    Science.gov (United States)

    De Mahiques, Michel M; Figueira, Rubens C L; Alves, Daniel P V; Italiani, Diana M; Martins, Cristina C; Dias, João M A

    2014-12-01

    The role played by human activity in coastline changes indicates a general tendency of retreating coasts, especially deltaic environments, as a result of the recent trend of sea level rise as well as the blockage of the transfer of sediments towards the coast, especially due to the construction of dams. This is particularly important in deltaic environments which have been suffering a dramatic loss of area in the last decades. In contrast, in this paper, we report the origin and evolution of an anthropogenic delta, the Valo Grande delta, on the south-eastern Brazilian coast, whose origin is related to the opening of an artificial channel and the diversion of the main flow of the Ribeira de Iguape River. The methodology included the analysis of coastline changes, bathymetry and coring, which were used to determine the sedimentation rates and grain-size changes over time. The results allowed us to recognize the different facies of the anthropogenic delta and establish its lateral and vertical depositional trends. Despite not being very frequent, anthropogenic deltas represent a favorable environment for the record of natural and anthropogenic changes in historical times and, thus, deserve more attention from researchers of different subjects.

  3. KR-31378, a potassium-channel opener, induces the protection of retinal ganglion cells in rat retinal ischemic models.

    Science.gov (United States)

    Choi, Anho; Choi, Jun-Sub; Yoon, Yone-Jung; Kim, Kyung-A; Joo, Choun-Ki

    2009-04-01

    KR-31378 is a newly developed K(ATP)-channel opener. To investigate the ability of KR-31378 to protect retinal ganglion cells (RGC), experiments were conducted using two retinal ischemia models. Retinal ischemia was induced by transient high intraocular pressure (IOP) for acute ischemia and by three episcleral vein occlusion for chronic retinal ischemia. KR-31378 was injected intraperitoneally and administered orally in the acute and chronic ischemia models, respectively. Under the condition of chronic ischemia, RGC density in the KR-31378-treated group was statistically higher than that in the non-treated group, and IOP was reduced. In the acute retinal ischemia model, 90% of RGC were degenerated after one week in non-treated retina, but, RGC in KR-31378-treated retina were protected from ischemic damage in a dose-dependent manner and showed inhibited glial fibrillary acidic protein (GFAP) expression. Furthermore, the KR-31378 protective effect was inhibited by glibenclamide treatment in acute ischemia. These findings indicate that systemic KR-31378 treatment may protect against ischemic injury-induced ganglion cell loss in glaucoma.

  4. Increased Expression of the Calcium-Activated Chloride Channel in Hclca1 in Airways of Patients with Obstructive Chronic Bronchitis

    Directory of Open Access Journals (Sweden)

    Hans-Peter Hauber

    2005-01-01

    Full Text Available BACKGROUND: Interleukin (IL-9 and its effect on enhancing the human calcium-activated chloride channel 1 (hCLCA1 expression have been shown to induce mucin production. Increased expression of hCLCA1 may, in turn, contribute to mucus overproduction in chronic obstructive pulmonary disease (COPD with a chronic bronchitis (CB phenotype.

  5. Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity.

    Science.gov (United States)

    Cipolla, Marilyn J; Sweet, Julie; Chan, Siu-Lung; Tavares, Matthew J; Gokina, Natalia; Brayden, Joseph E

    2014-07-01

    Brain parenchymal arterioles (PAs) are high-resistance vessels that branch off pial arteries and perfuse the brain parenchyma. PAs are the target of cerebral small vessel disease and have been shown to have greater pressure-induced tone at lower pressures than pial arteries. We investigated mechanisms by which brain PAs have increased myogenic tone compared with middle cerebral arteries (MCAs), focusing on differences in vascular smooth muscle (VSM) calcium and ion channel function. The amount of myogenic tone and VSM calcium was measured using Fura 2 in isolated and pressurized PAs and MCAs. Increases in intraluminal pressure caused larger increases in tone and cytosolic calcium in PAs compared with MCAs. At 50 mmHg, myogenic tone was 37 ± 5% for PAs vs. 6.5 ± 4% for MCAs (P channel (VDCC) inhibitor nifedipine than MCAs (EC50 for PAs was 3.5 ± 0.4 vs. 82.1 ± 2.1 nmol/l for MCAs;P channel inhibitor iberiotoxin, whereas MCAs constricted ∼15%. Thus increased myogenic tone in PAs appears related to differences in ion channel activity that promotes VSM membrane depolarization but not to a direct sensitization of the contractile apparatus to calcium.

  6. Increased Throughput in Ion Channel Drug Development and Exploration by Automation of Electrophysiology

    DEFF Research Database (Denmark)

    Willumsen, N. J.

    2006-01-01

    Ion channels constitute macromolecular communication gates that are present in the membranes of all living cells. They are crucial for practically any physiological process, either as chemical or electrical signal transducers or as transmembrane routes for the bulk transport of salts. Not surpris...

  7. Channel-opening kinetic mechanism for human wild-type GluK2 and the M867I mutant kainate receptor.

    Science.gov (United States)

    Han, Yan; Wang, Congzhou; Park, Jae Seon; Niu, Li

    2010-11-02

    GluK2 is a kainate receptor subunit that is alternatively spliced at the C-terminus. Previous studies implicated GluK2 in autism. In particular, the methionine-to-isoleucine replacement at amino acid residue 867 (M867I) that can only occur in the longest isoform of the human GluK2 (hGluK2), as the disease (autism) mutation, is thought to cause gain-of-function. However, the kinetic properties of the wild-type hGluK2 and the functional consequence of this gain-of-function mutation at the molecular level are not well understood. To investigate whether the M867I mutation affects the channel properties of the human GluK2 kainate receptor, we have systematically characterized the rate and the equilibrium constants pertinent to channel opening and channel desensitization for this mutant and the wild-type hGluK2 receptor, along with the wild-type rat GluK2 kainate receptor (rGluK2) as the control. Our results show that the M867I mutation does not affect either the rate or the equilibrium constants of the channel opening but does slow down the channel desensitization rate by ~1.6-fold at saturating glutamate concentrations. It is possible that a consequence of this mutation on the desensitization rate is linked to facilitating the receptor trafficking and membrane expression, given the close proximity of M867 to the forward trafficking motif in the C-terminal sequence. By comparing the kinetic data of the wild-type human and rat GluK2 receptors, we also find that the human GluK2 has a ~3-fold smaller channel-opening rate constant but an identical channel-closing rate constant and thus a channel-opening probability of 0.85 vs 0.96 for rGluK2. Furthermore, the intrinsic equilibrium dissociation constant K(1) for hGluK2, like the EC(50) value, is ~2-fold lower than rGluK2. Our results therefore suggest that the human GluK2 is relatively a slowly activating channel but more sensitive to glutamate, as compared to the rat ortholog, despite the fact that the human and rat forms

  8. MHD mixed convection analysis in an open channel by obstructed Poiseuille flow of non-Newtonian power law fluid

    Science.gov (United States)

    Rabbi, Khan Md.; Rakib, Tawfiqur; Das, Sourav; Mojumder, Satyajit; Saha, Sourav

    2016-07-01

    This paper demonstrates magneto-hydrodynamic (MHD) mixed convection flow through a channel with a rectangular obstacle at the entrance region using non-Newtonian power law fluid. The obstacle is kept at uniformly high temperature whereas the inlet and top wall of the channel are maintained at a temperature lower than obstacle temperature. Poiseuille flow is implemented as the inlet velocity boundary condition. Grid independency test and code validation are performed to justify the computational accuracy before solving the present problem. Galerkin weighted residual method has been appointed to solve the continuity, momentum and energy equations. The problem has been solved for wide range of pertinent parameters like Richardson number (Ri = 0.1 - 10) at a constant Reynolds number (Re = 100), Hartmann number (Ha = 0 - 100), power index (n = 0.6 - 1.6). The flow and thermal field have been thoroughly discussed through streamline and isothermal lines respectively. The heat transfer performance of the given study has been illustrated by average Nusselt number plots. It is observed that increment of Hartmann number (Ha) tends to decrease the heat transfer rate up to a critical value (Ha = 20) and then let increase the heat transfer performance. Thus maximum heat transfer rate has been recorded for higher Hartmann number and Rayleigh number in case of pseudo-plastic (n = 0.6) non-Newtonian fluid flow.

  9. [Does open access publishing increase the impact of scientific articles? An empirical study in the field of intensive care medicine].

    Science.gov (United States)

    Riera, M; Aibar, E

    2013-05-01

    Some studies suggest that open access articles are more often cited than non-open access articles. However, the relationship between open access and citations count in a discipline such as intensive care medicine has not been studied to date. The present article analyzes the effect of open access publishing of scientific articles in intensive care medicine journals in terms of citations count. We evaluated a total of 161 articles (76% being non-open access articles) published in Intensive Care Medicine in the year 2008. Citation data were compared between the two groups up until April 30, 2011. Potentially confounding variables for citation counts were adjusted for in a linear multiple regression model. The median number (interquartile range) of citations of non-open access articles was 8 (4-12) versus 9 (6-18) in the case of open access articles (p=0.084). In the highest citation range (>8), the citation count was 13 (10-16) and 18 (13-21) (p=0.008), respectively. The mean follow-up was 37.5 ± 3 months in both groups. In the 30-35 months after publication, the average number (mean ± standard deviation) of citations per article per month of non-open access articles was 0.28 ± 0.6 versus 0.38 ± 0.7 in the case of open access articles (p=0.043). Independent factors for citation advantage were the Hirsch index of the first signing author (β=0.207; p=0.015) and open access status (β=3.618; p=0.006). Open access publishing and the Hirsch index of the first signing author increase the impact of scientific articles. The open access advantage is greater for the more highly cited articles, and appears in the 30-35 months after publication. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  10. Oral administration of the KATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Mahy Nicole

    2011-11-01

    Full Text Available Abstract Background Multiple Sclerosis (MS is an acquired inflammatory demyelinating disorder of the central nervous system (CNS and is the leading cause of nontraumatic disability among young adults. Activated microglial cells are important effectors of demyelination and neurodegeneration, by secreting cytokines and others neurotoxic agents. Previous studies have demonstrated that microglia expresses ATP-sensitive potassium (KATP channels and its pharmacological activation can provide neuroprotective and anti-inflammatory effects. In this study, we have examined the effect of oral administration of KATP channel opener diazoxide on induced experimental autoimmune encephalomyelitis (EAE, a mouse model of MS. Methods Anti-inflammatory effects of diazoxide were studied on lipopolysaccharide (LPS and interferon gamma (IFNγ-activated microglial cells. EAE was induced in C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Mice were orally treated daily with diazoxide or vehicle for 15 days from the day of EAE symptom onset. Treatment starting at the same time as immunization was also assayed. Clinical signs of EAE were monitored and histological studies were performed to analyze tissue damage, demyelination, glial reactivity, axonal loss, neuronal preservation and lymphocyte infiltration. Results Diazoxide inhibited in vitro nitric oxide (NO, tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6 production and inducible nitric oxide synthase (iNOS expression by activated microglia without affecting cyclooxygenase-2 (COX-2 expression and phagocytosis. Oral treatment of mice with diazoxide ameliorated EAE clinical signs but did not prevent disease. Histological analysis demonstrated that diazoxide elicited a significant reduction in myelin and axonal loss accompanied by a decrease in glial activation and neuronal damage. Diazoxide did not affect the number of infiltrating lymphocytes positive for CD3 and CD20

  11. On the Effect of Aspect Ratio of Open Heated Channel Including an Active Obstacle upon the Turbulent Characteristics of a Thermal Plume: Experimental Analysis

    Directory of Open Access Journals (Sweden)

    Taoufik Naffouti

    2016-01-01

    Full Text Available This paper reports an experimental investigation of aspect ratio effect of open vertical channel on turbulent characteristics of a thermal plume. The physical configuration is constituted essentially by a prallelepipedic channel and an obstacle of a rectangular section. The thermal plume is generated by a rectangular obstacle heated uniformly at the upper surface. This active source is placed at the entry of a vertical channel open at the ends. The symmetrical heating of channel walls by joule effect and by thermal radiation emitted by the plume, causes the appearance of a thermosiphon flow which interacts with this one. To investigate the flow fluctuations, an anemometer at constant current (CCA is used. The results carried out with air (Pr = 0.71 are performed for Rayleigh number equal to 0.63 107 over a wide range of aspect ratio 1.25 ≤ A ≤ 30. Effects of this pertinent parameter are displayed upon thermal and dynamic turbulent fields. Using Taylor hypothesis, time and length scales of turbulent thermal field are studied. It is found that the turbulent characteristics of the flow are significantly influenced by the variation of aspect ratio. An optimum aspect ratio of channel characterized by a strong homogenization of turbulence of the flow is observed. The fine analysis of temperature fluctuations spectra shows the evolution of the vortices in energy cascade owing to the strong effect of thermosiphon flow which favours the vortex stretching.

  12. 3D Lagrangian Model of Particle Saltation in an Open Channel Flow with Emphasis on Particle-Particle Collisions

    Science.gov (United States)

    Moreno, P. A.; Bombardelli, F. A.

    2012-12-01

    Particles laying motionless at the bed of rivers, lakes and estuaries can be put into motion when the shear stress exerted by the flow on the particles exceeds the critical shear stress. When these particles start their motion they can either remain suspended by long periods of time (suspended load) or move close to the bed (bed load). Particles are transported as bed load in three different modes: Sliding, rolling and saltation. Saltation is usually described as the bouncing motion of sediment particles in a layer a few particle diameters thick. The amount of particles and the bed-load mode in which they move depend on the particle size and density, and the flow intensity, usually quantified by the shear velocity. The bottom shear stress in natural streams will most likely be large enough to set saltation as the most important bed-load transport mechanism among all three modes. Thus, studying the saltation process is crucial for the overall understanding of bed-load transport. Particularly, numerical simulations of this process have been providing important insight regarding the relative importance of the physical mechanisms involved in it. Several processes occur when particles are saltating near the bed: i) Particles collide with the bed, ii) they "fly" between collisions with the bed, as a result of their interaction with the fluid flow, iii) and they collide among themselves. These processes can be simulated using a three-dimensional Eulerian-Lagrangian model. In order to mimic these processes we have experimented with an averaged turbulent flow field represented by the logarithmic law of the wall, and with a more involved approach in which a computed turbulent velocity field for a flat plate was used as a surrogate of the three-dimensional turbulent conditions present close to stream beds. Since flat-plate and open-channel boundary layers are essentially different, a dynamic similarity analysis was performed showing that the highly-resolved three

  13. Toosendanin increases free-Ca2+ concentration in NG108-15 cells via L-type Ca2+ channels

    Institute of Scientific and Technical Information of China (English)

    Tong-hui XU; Jun DING; Yu-liang SHI

    2004-01-01

    AIM: To examine if toosendanin (TSN) affects intracellular free-Ca2+ concentration ([Ca2+]i) in neuroblastomaxglioma hybrid cells (NG108-15 cells). METHODS: The [Ca2+]i was determined by laser-scanning confocal microscopic imaging technique in which Fluo-3 was used as Ca2+ indicator. RESULTS: TSN induced an increase in resting [Ca2+]i and in high K+-evoked Ca2+ transient in differentiated NG108-15 cells. The TSN-induced increase in [Ca2+]i was dose-dependent and disappeared in CdCl2-, nifedipine-containing or Ca2+-free solution, and appeared after washing out the Ca2+ channel blockers or adding Ca2+. CONCLUSION: TSN increased [Ca2+]i in differentiated NG108-15 cells. The [Ca2+]i enhancement was due to the influx of extracellular Ca2+ and related to L-type Ca2+ channels.

  14. Throughput increase of the covert communication channel organized by the stable steganography algorithm using spatial domain of the image

    Directory of Open Access Journals (Sweden)

    O.V. Kostyrka

    2016-09-01

    Full Text Available At the organization of a covert communication channel a number of requirements are imposed on used steganography algorithms among which one of the main are: resistance to attacks against the built-in message, reliability of perception of formed steganography message, significant throughput of a steganography communication channel. Aim: The aim of this research is to modify the steganography method, developed by the author earlier, which will allow to increase the throughput of the corresponding covert communication channel when saving resistance to attacks against the built-in message and perception reliability of the created steganography message, inherent to developed method. Materials and Methods: Modifications of a steganography method that is steady against attacks against the built-in message which is carrying out the inclusion and decoding of the sent (additional information in spatial domain of the image allowing to increase the throughput of the organized communication channel are offered. Use of spatial domain of the image allows to avoid accumulation of an additional computational error during the inclusion/decoding of additional information due to “transitions” from spatial domain of the image to the area of conversion and back that positively affects the efficiency of decoding. Such methods are considered as attacks against the built-in message: imposing of different noise on a steganography message, filtering, lossy compression of a ste-ganography message where the JPEG and JPEG2000 formats with different quality coefficients for saving of a steganography message are used. Results: It is shown that algorithmic implementations of the offered methods modifications remain steady against the perturbing influences, including considerable, provide reliability of perception of the created steganography message, increase the throughput of the created steganography communication channel in comparison with the algorithm implementing

  15. Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries.

    Science.gov (United States)

    Pereira, Camila A; Ferreira, Nathanne S; Mestriner, Fabiola L; Antunes-Rodrigues, José; Evora, Paulo R B; Resstel, Leonardo B M; Carneiro, Fernando S; Tostes, Rita C

    2015-10-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10 mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment.

  16. Increased intracellular magnesium attenuates β-adrenergic stimulation of the cardiac Ca(V)1.2 channel.

    Science.gov (United States)

    Brunet, Sylvain; Scheuer, Todd; Catterall, William A

    2013-01-01

    Increases in intracellular Mg(2+) (Mg(2+)(i)), as observed in transient cardiac ischemia, decrease L-type Ca(2+) current of mammalian ventricular myocytes (VMs). However, cardiac ischemia is associated with an increase in sympathetic tone, which could stimulate L-type Ca(2+) current. Therefore, the effect of Mg(2+)(i) on L-type Ca(2+) current in the context of increased sympathetic tone was unclear. We tested the impact of increased Mg(2+)(i) on the β-adrenergic stimulation of L-type Ca(2+) current. Exposure of acutely dissociated adult VMs to higher Mg(2+)(i) concentrations decreased isoproterenol stimulation of the L-type Ca(2+) current from 75 ± 13% with 0.8 mM Mg(2+)(i) to 20 ± 8% with 2.4 mM Mg(2+)(i). We activated this signaling cascade at different steps to determine the site or sites of Mg(2+)(i) action. Exposure of VMs to increased Mg(2+)(i) attenuated the stimulation of L-type Ca(2+) current induced by activation of adenylyl cyclase with forskolin, inhibition of cyclic nucleotide phosphodiesterases with isobutylmethylxanthine, and inhibition of phosphoprotein phosphatases I and IIA with calyculin A. These experiments ruled out significant effects of Mg(2+)(i) on these upstream steps in the signaling cascade and suggested that Mg(2+)(i) acts directly on Ca(V)1.2 channels. One possible site of action is the EF-hand in the proximal C-terminal domain, just downstream in the signaling cascade from the site of regulation of Ca(V)1.2 channels by protein phosphorylation on the C terminus. Consistent with this hypothesis, Mg(2+)(i) had no effect on enhancement of Ca(V)1.2 channel activity by the dihydropyridine agonist (S)-BayK8644, which activates Ca(V)1.2 channels by binding to a site formed by the transmembrane domains of the channel. Collectively, our results suggest that, in transient ischemia, increased Mg(2+)(i) reduces stimulation of L-type Ca(2+) current by the β-adrenergic receptor by directly acting on Ca(V)1.2 channels in a cell-autonomous manner

  17. Increasing Open Source Software Integration on the Department of Defense Unclassified Desktop

    Science.gov (United States)

    2008-06-01

    simplest remedy to the OSS-Exchange barrier is the use of the Evolution e-mail client, with Outlook Web Access ( OWA ) enabled on the Exchange server... OWA need not be permitted to communicate outside the intranet (something that is often blocked due to security concerns); it simply serves as the...communications channel for internal Evolution clients. When operated in “Exchange mode” (using OWA ), the Evolution client provides both a look-and

  18. The 3.5 ångström X-ray structure of the human connexin26 gap junction channel is unlikely that of a fully open channel.

    Science.gov (United States)

    Zonta, Francesco; Polles, Guido; Sanasi, Maria Federica; Bortolozzi, Mario; Mammano, Fabio

    2013-02-27

    The permeability of gap junction channels to metabolites, and not simply to small inorganic ions, is likely to play an important role in development, physiology as well as in etiology of several diseases. Here, we combined dual patch clamp and fluorescence imaging techniques with molecular dynamics (MD) simulations to investigate the permeation of calcein, a relatively large fluorescent tracer (MW 622 Da) through homomeric gap junction channels formed by wild type human connexin26 (hCx26wt) protomers. Our experimental data indicate that the unitary flux of calcein driven by a 125 μM concentration difference is Jpore = 226 molecule/s per channel. In the light of Eyring transition state theory adapted for the liquid phase, this value corresponds to an energy barrier of ~20 kBT (where kB is the Boltzmann constant and T is absolute temperature). The barrier predicted by our MD simulations, based on the 3.5 Å X-ray structural model of the hCx26wt gap junction channel, is ~45 kBT. The main contributions to the energetics of calcein permeation originated from the interaction between the permeating molecule and the charged aminoacids lining the channel pore. Assigning a fake zero total charge to the calcein molecule yielded a value for the barrier height compatible with the experimental data. These results can be accounted for by two different (although not mutually exclusive) hypotheses: (1) the X-ray model of the hCx26wt gap junction channel is not representative of a fully open state; (2) post translational modifications affecting the hCx26wt protein in our expression system differed from the modifications undergone by the proteins in the conditions used to obtain the crystal structure. Hypothesis (1) is compatible with data indicating that, only 10% or less of the channels forming a gap junction plaque are in the open state, and therefore the averaging procedure intrinsic in the generation of the crystal structure data more closely reflects that of a closed

  19. Metamizol acts as an ATP sensitive potassium channel opener to inhibit the contracting response induced by angiotensin II but not to norepinephrine in rat thoracic aorta smooth muscle.

    Science.gov (United States)

    Valenzuela, Fermín; García-Saisó, Sebastián; Lemini, Cristina; Ramírez-Solares, Rafael; Vidrio, Horacio; Mendoza-Fernández, Víctor

    2005-08-01

    Clinically metamizol (MZ) has been related to alteration on haemodynamic parameters and modifications on blood pressure in humans when administered intravenously. These effects have been observed at MZ therapeutic doses. Experimentally, MZ is able to induce relaxation on several types of vascular smooth muscles and modulates the contraction induced by phenylephrine. However, the mechanism underlying the MZ effects on vascular reactivity is not clear. Potassium channels (K) present on vascular smooth muscle cells closely regulate the vascular reactivity and membrane potential. There are four described types of K in vascular tissue: K voltage sensitive (K(V)), K calcium sensitive (K(Ca)2+), K ATP sensitive (K(ATP) and K inward rectification (K(IR), voltage sensitive). The aim of this work was to investigate MZ effects on angiotensin II (AT II) and noradrenaline (NA) induced contraction and to evaluate the K participation on MZ modulating effect on vascular smooth muscle contraction, using isometric and patch clamp techniques. MZ induces relaxation in a concentration dependent manner. Furthermore, MZ strongly inhibits in a concentration dependent fashion the contraction induced by AT II. However, MZ inhibition on NA induced contraction was moderated compared with that observed on AT II. MZ effects on AT II induced contraction was blocked by glybenclamide (a specific K(ATP) blocker, 3 microM, *p < 0.01). In patch clamp experiments, MZ (3 mM) induces an increase on potassium current (K+) mediated by K(ATP) in similar way as diazoxide (a specific K(ATP) opener, 3 microM). Our results suggest that MZ induces relaxation and inhibits contraction induced by AT II acting as a K(ATP) opener.

  20. A mechanism for the auto-inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel opening and its relief by cAMP.

    Science.gov (United States)

    Akimoto, Madoka; Zhang, Zaiyong; Boulton, Stephen; Selvaratnam, Rajeevan; VanSchouwen, Bryan; Gloyd, Melanie; Accili, Eric A; Lange, Oliver F; Melacini, Giuseppe

    2014-08-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels control neuronal and cardiac electrical rhythmicity. There are four homologous isoforms (HCN1-4) sharing a common multidomain architecture that includes an N-terminal transmembrane tetrameric ion channel followed by a cytoplasmic "C-linker," which connects a more distal cAMP-binding domain (CBD) to the inner pore. Channel opening is primarily stimulated by transmembrane elements that sense membrane hyperpolarization, although cAMP reduces the voltage required for HCN activation by promoting tetramerization of the intracellular C-linker, which in turn relieves auto-inhibition of the inner pore gate. Although binding of cAMP has been proposed to relieve auto-inhibition by affecting the structure of the C-linker and CBD, the nature and extent of these cAMP-dependent changes remain limitedly explored. Here, we used NMR to probe the changes caused by the binding of cAMP and of cCMP, a partial agonist, to the apo-CBD of HCN4. Our data indicate that the CBD exists in a dynamic two-state equilibrium, whose position as gauged by NMR chemical shifts correlates with the V½ voltage measured through electrophysiology. In the absence of cAMP, the most populated CBD state leads to steric clashes with the activated or "tetrameric" C-linker, which becomes energetically unfavored. The steric clashes of the apo tetramer are eliminated either by cAMP binding, which selects for a CBD state devoid of steric clashes with the tetrameric C-linker and facilitates channel opening, or by a transition of apo-HCN to monomers or dimer of dimers, in which the C-linker becomes less structured, and channel opening is not facilitated.

  1. Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement

    DEFF Research Database (Denmark)

    Almgren, Malin; Persson, Ann-Sophie; Fenghua, Chen

    2007-01-01

    The megencephaly mice show dramatic progressive increase in brain size and seizures. The overgrowth affects primarily the hippocampus and ventral cortex. The phenotype originates from a mutation in the Shaker-like voltage-gated potassium channel Kv1.1 brain, which results in a malfunctioning......), and these new mceph/mceph neurons showed increased migration and had a 6-week survival rate as the new neurons in wild type DG. Also when seizures were frequent in mceph/mceph (9 weeks old), the proliferation rate was three-fold higher than in wild type. The number of TUNEL-positive cells in hippocampus...... was lower in mceph/mceph supporting additional overgrowth mechanism than induced by seizures. In conclusion, lack of a functional Kv1.1 ion channel subunit in the mceph/mceph mice causes a unique neuronal hyperplasia in distinct hippocampal regions and consequently hippocampal enlargement from 2 to 3 weeks...

  2. Rapid antidepressants stimulate the decoupling of GABA(B) receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η.

    Science.gov (United States)

    Workman, E R; Haddick, P C G; Bush, K; Dilly, G A; Niere, F; Zemelman, B V; Raab-Graham, K F

    2015-03-01

    A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces a rapid antidepressant response. Lasting changes in the synapse structure and composition underlie the effectiveness of these drugs. We recently discovered that rapid antidepressants cause a shift in the γ-aminobutyric acid receptor (GABABR) signaling pathway, such that GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal and mammalian Target of Rapamycin activity. However, little is known about the molecular and biochemical mechanisms that initiate this shift. Herein, we show that GABABR signaling to Kir3 (GIRK) channels decreases with NMDAR blockade. Blocking NMDAR signaling stabilizes the adaptor protein 14-3-3η, which decouples GABABR signaling from Kir3 and is required for the rapid antidepressant efficacy. Consistent with these results, we find that key proteins involved in GABABR signaling bidirectionally change in a depression model and with rapid antidepressants. In socially defeated rodents, a model for depression, GABABR and 14-3-3η levels decrease in the hippocampus. The NMDAR antagonists AP5 and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3-3η expression and decrease Kir3.2. Taken together, these data suggest that the shift in GABABR function requires a loss of GABABR-Kir3 channel activity mediated by 14-3-3η. Our findings support a central role for 14-3-3η in the efficacy of rapid antidepressants and define a critical molecular mechanism for activity-dependent alterations in GABABR signaling.

  3. Rapid antidepressants stimulate the decoupling of GABAB receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η

    Science.gov (United States)

    Workman, E R; Haddick, P C G; Bush, K; Dilly, G A; Niere, F; Zemelman, B V; Raab-Graham, K F

    2015-01-01

    A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces a rapid antidepressant response. Lasting changes in the synapse structure and composition underlie the effectiveness of these drugs. We recently discovered that rapid antidepressants cause a shift in the γ-aminobutyric acid receptor (GABABR) signaling pathway, such that GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal and mammalian Target of Rapamycin activity. However, little is known about the molecular and biochemical mechanisms that initiate this shift. Herein, we show that GABABR signaling to Kir3 (GIRK) channels decreases with NMDAR blockade. Blocking NMDAR signaling stabilizes the adaptor protein 14-3-3η, which decouples GABABR signaling from Kir3 and is required for the rapid antidepressant efficacy. Consistent with these results, we find that key proteins involved in GABABR signaling bidirectionally change in a depression model and with rapid antidepressants. In socially defeated rodents, a model for depression, GABABR and 14-3-3η levels decrease in the hippocampus. The NMDAR antagonists AP5 and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3-3η expression and decrease Kir3.2. Taken together, these data suggest that the shift in GABABR function requires a loss of GABABR-Kir3 channel activity mediated by 14-3-3η. Our findings support a central role for 14-3-3η in the efficacy of rapid antidepressants and define a critical molecular mechanism for activity-dependent alterations in GABABR signaling. PMID:25560757

  4. Substitutions at the opening of the Rubisco central solvent channel affect holoenzyme stability and CO2/O 2 specificity but not activation by Rubisco activase.

    Science.gov (United States)

    Esquivel, M Gloria; Genkov, Todor; Nogueira, Ana S; Salvucci, Michael E; Spreitzer, Robert J

    2013-12-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the initial step of carbon metabolism in photosynthesis. The holoenzyme comprises eight large subunits, arranged as a tetramer of dimers around a central solvent channel that defines a fourfold axis of symmetry, and eight small subunits, arranged as two tetramers at the poles of the axis. The phylogenetically divergent small-subunit loops between β-strands A and B form the entrance to the solvent channel. In the green alga Chlamydomonas reinhardtii, Ile-58 from each of the four small-subunit βA-βB loops defines the minimal diameter of the channel opening. To understand the role of the central solvent channel in Rubisco function, directed mutagenesis and transformation of Chlamydomonas were employed to replace Ile-58 with Ala, Lys, Glu, Trp, or three Trp residues (I58W3) to close the entrance to the channel. The I58E, I58K, and I58W substitutions caused only small decreases in photosynthetic growth at 25 and 35 °C, whereas I58W3 had a substantial effect at both temperatures. The mutant enzymes had decreased carboxylation rates, but the I58W3 enzyme had decreases in both carboxylation and CO2/O2 specificity. The I58E, I58W, and I58W3 enzymes were inactivated at lower temperatures than wild-type Rubisco, and were degraded at slower rates under oxidative stress. However, these mutant enzymes were activated by Rubisco activase at normal rates, indicating that the structural transition required for carboxylation is not affected by altering the solvent channel opening. Structural dynamics alone may not be responsible for these distant effects on the Rubisco active site.

  5. Statistical analysis of turbulent super-streamwise vortices based on observations of streaky structures near the free surface in the smooth open channel flow

    Science.gov (United States)

    Zhong, Qiang; Chen, Qigang; Wang, Hao; Li, Danxun; Wang, Xingkui

    2016-05-01

    Long streamwise-elongated high- and low-speed streaks are repeatedly observed near the free surface in open channel flows in natural rivers and lab experiments. Super-streamwise vortex model has been proposed to explain this widespread phenomenon for quite some time. However, statistical evidence of the existence of the super-streamwise vortices as one type of coherent structures is still insufficient. Correlation and proper orthogonal decomposition (POD) analysis based on PIV experimental data in the streamwise-spanwise plane near the free surface in a smooth open channel flow are employed to investigate this topic. Correlation analysis revealed that the streaky structures appear frequently near the free surface and their occurrence probability at any spanwise position is equal. The spanwise velocity fluctuation usually flows from low-speed streaks toward high-speed streaks. The average spanwise width and spacing between neighboring low (or high) speed streaks are approximately h and 2h respectively. POD analysis reveals that there are streaks with different spanwise width in the instantaneous flow fields. Typical streamwise rotational movement can be sketched out directly based on the results from statistical analyses. Point-by-point analysis indicates that this pattern is consistent everywhere in the measurement window and is without any inhomogeneity in the spanwise direction, which reveals the essential difference between coherent structures and secondary flow cells. The pattern found by statistical analysis is consistent with the notion that the super-streamwise vortices exist universally as one type of coherent structure in open channel flows.

  6. Native pyroglutamation of huwentoxin-IV: a post-translational modification that increases the trapping ability to the sodium channel.

    Directory of Open Access Journals (Sweden)

    Mingqiang Rong

    Full Text Available Huwentoxin-IV (HWTX-IV, a tetrodotoxin-sensitive (TTX-s sodium channel antagonist, is found in the venom of the Chinese spider Ornithoctonus huwena. A naturally modified HWTX-IV (mHWTX-IV, having a molecular mass 18 Da lower than HWTX-IV, has also been isolated from the venom of the same spider. By a combination of enzymatic fragmentation and MS/MS de novo sequencing, mHWTX-IV has been shown to have the same amino acid sequence as that of HWTX-IV, except that the N-terminal glutamic acid replaced by pyroglutamic acid. mHWTX-IV inhibited tetrodotoxin-sensitive voltage-gated sodium channels of dorsal root ganglion neurons with an IC50 nearly equal to native HWTX-IV. mHWTX-IV showed the same activation and inactivation kinetics seen for native HWTX-IV. In contrast with HWTX-IV, which dissociates at moderate voltage depolarization voltages (+50 mV, 180000 ms, mHWTX-IV inhibition of TTX-sensitive sodium channels is not reversed by strong depolarization voltages (+200 mV, 500 ms. Recovery of Nav1.7current was voltage-dependent and was induced by extreme depolarization in the presence of HWTX-IV, but no obvious current was elicited after application of mHWTX-IV. Our data indicate that the N-terminal modification of HWTX-IV gives the peptide toxin a greater ability to trap the voltage sensor in the sodium channel. Loss of a negative charge, caused by cyclization at the N-terminus, is a possible reason why the modified toxin binds much stronger. To our knowledge, this is the first report of a pyroglutamic acid residue in a spider toxin; this modification seems to increase the trapping ability of the voltage sensor in the sodium channel.

  7. An increased expression of Ca(2+) channel alpha(1A) subunit immunoreactivity in deep cerebellar neurons of rolling mouse Nagoya.

    Science.gov (United States)

    Sawada, K; Sakata-Haga, H; Ando, M; Takeda, N; Fukui, Y

    2001-12-01

    Rolling mouse Nagoya (RMN) is an ataxic mutant and carries a mutation in the gene coding for the alpha(1A) subunit of the P/Q-type Ca(2+) channel. We examined the immunohistochemical expression of the alpha(1A) subunit in deep cerebellar nuclei of RMN. The antibody used recognized residues 865-883 of the mouse alpha(1A) subunit not overlapping the altered sequences in RMN. In RMN, many neurons exhibited definite alpha(1A) subunit-staining in the medial nucleus, interposed nucleus, and lateral nucleus of deep cerebellar nuclei. The number of positive neurons in these nuclei was significantly higher in RMN than in controls. Increased expression of the alpha(1A) subunit in deep cerebellar neurons might compensate for the altered function of the P/Q-type Ca(2+) channel of RMN.

  8. Increasing the object recognition distance of compact open air on board vision system

    Science.gov (United States)

    Kirillov, Sergey; Kostkin, Ivan; Strotov, Valery; Dmitriev, Vladimir; Berdnikov, Vadim; Akopov, Eduard; Elyutin, Aleksey

    2016-10-01

    The aim of this work was developing an algorithm eliminating the atmospheric distortion and improves image quality. The proposed algorithm is entirely software without using additional hardware photographic equipment. . This algorithm does not required preliminary calibration. It can work equally effectively with the images obtained at a distances from 1 to 500 meters. An algorithm for the open air images improve designed for Raspberry Pi model B on-board vision systems is proposed. The results of experimental examination are given.

  9. Marked increases in mucociliary clearance produced by synergistic secretory agonists or inhibition of the epithelial sodium channel

    Science.gov (United States)

    Joo, Nam Soo; Jeong, Jin Hyeok; Cho, Hyung-Ju; Wine, Jeffrey J.

    2016-01-01

    Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca2+-activated chloride channels mediate anion/fluid secretion. MCCV was increased by the cAMP-elevating agonists, forskolin or isoproterenol (10 μM) and by the Ca2+-elevating agonist, carbachol (0.3 μM). The CFTR-selective inhibitor, CFTRinh-172, modestly reduced MCCV-increases induced by forskolin or isoproterenol but not increases induced by carbachol. The ENaC inhibitor benzamil increased basal MCCV as well as MCCV increases produced by forskolin or carbachol. MCC velocity was most dramatically accelerated by the synergistic combination of forskolin and carbachol, which produced near-maximal clearance rates regardless of prior treatment with CFTR or ENaC inhibitors. In CF airways, where CFTR-mediated secretion (and possibly synergistic MCC) is lost, ENaC inhibition via exogenous agents may provide therapeutic benefit, as has long been proposed. PMID:27830759

  10. Technology Alliance Portfolios and Financial Performance : Value-Enhancing and Cost-Increasing Effects of Open Innovation

    NARCIS (Netherlands)

    Faems, Dries; de Visser, Matthias; Andries, Petra; Van Looy, Bart

    2010-01-01

    Firms increasingly adopt an open innovation model in which they rely on technology alliances to complement and supplement their internal innovation efforts. Although previous studies provide in-depth insight into the impact of technology alliances on the innovation performance, they remain relativel

  11. Technology alliance portfolios and financial performance: value-enhancing and cost-increasing effects of open innovation

    NARCIS (Netherlands)

    Faems, Dries; Visser, de Matthias; Andries, Petra; Looy, van Bart

    2012-01-01

    Firms increasingly adopt an open innovation model in which they rely on technology alliances to complement and supplement their internal innovation efforts. Although previous studies provide in-depth insight into the impact of technology alliances on the innovation performance, they remain relativel

  12. Formaldehyde increases intracellular calcium concentration in primary cultured hippocampal neurons partly through NMDA receptors and T-type calcium channels

    Institute of Scientific and Technical Information of China (English)

    Ye-Nan Chi; Xu Zhang; Jie Cai; Feng-Yu Liu; Guo-Gang Xing; You Wan

    2012-01-01

    Objective Formaldehyde at high concentrations is a contributor to air pollution.It is also an endogenous metabolic product in cells,and when beyond physiological concentrations,has pathological effects on neurons.Formaldehyde induces mis-folding and aggregation of neuronal tau protein,hippocampal neuronal apoptosis,cognitive impairment and loss of memory functions,as well as excitation of peripheral nociceptive neurons in cancer pain models.Intracellular calcium ([Ca2+]i) is an important intracellular messenger,and plays a key role in many pathological processes.The present study aimed to investigate the effect of formaldehyde on [Ca2+]i and the possible involvement of N-methyl-D-aspartate receptors (NMDARs) and T-type Ca2+ channels on the cell membrane.Methods Using primary cultured hippocampal neurons as a model,changes of [Ca2+]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy.Results Formaldehyde at 1 mmol/L approximately doubled [Ca2+]i.(2R)-amino-5-phosphonopentanoate (AP5,25 μtmol/L,an NMDAR antagonist) and mibefradil (MIB,1 μtmol/L,a T-type Ca2+ channel blocker),given 5 min after formaldehyde perfusion,each partly inhibited the formaldehyde-induced increase of [Ca2+]i,and this inhibitory effect was reinforced by combined application of AP5 and MIB.When applied 3 min before formaldehyde perfusion,AP5 (even at 50 μmol/L) did not inhibit the formaldehyde-induced increase of [Ca2+]i,but MIB (1 μmol/L) significantly inhibited this increase by 70%.Conclusion These results suggest that formaldehyde at a low concentration increases [Ca2+]i in cultured hippocampal neurons; NMDARs and T-type Ca2+ channels may be involved in this process.

  13. Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

    Science.gov (United States)

    Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

    2015-09-01

    Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Increasing the efficiency of a portable PEM fuel cell by altering the cathode channel geometry: A numerical and experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Henriques, T.; Cesar, B.; Branco, P.J. Costa [Instituto Superior Tecnico (IST), Center for Innovation in Electrical and Energy Engineering, CIE3, Av. Rovisco Pais, 1049-001, Lisboa (Portugal)

    2010-04-15

    Portable fuel cells are receiving great attention today mainly because their energy density is higher than any portable battery solution. Among other types, portable polymer electrolyte membrane (PEM) fuel cells are an established technology where research on increasing their efficiency is leading product development and manufacturing. The objective of this work was to study and evaluate the redesign of a commercial portable fuel cell, improving its efficiency. A three-dimensional model of the original PEM fuel cell with parallel plus a transversal flow channel design was developed using Comsol Multiphysics, including the effects of liquid water formation and electric current production. Using this model, the effects of different channel geometries and respective cathode flow rates on the cell's performance, including the local transport characteristics, were studied. Laboratory tests with various fuel cell stacks using the new channels structure were effectuated for an evaluation of the fuel cell's performance, showing improvements in its efficiency of up to 26.4%. (author)

  15. Whether trade openness has increased all the components of Portuguese public expenditure

    Directory of Open Access Journals (Sweden)

    Paulo Reis Mourao

    2007-09-01

    Full Text Available This work aims at identifying the public outlays that has been influenced by the growth of Portuguese trade openness since the end of World War II. For the Portuguese reality, it is one of the first attempts to discuss a large set of simultaneously tested control variables. For this purpose, the methodology started from a model that tries to the public expenditures to a system of simultaneous macroeconomic forces and, for testing, it followed the steps associated with cointegration analysis. Using the most convenient techniques, a restrictive set of four expenditures (subsidies, interest payments, other current expenditures, and total public expenditures as a proportion of GDP was found among the wider set suggested by the Literature. The nature of these expenditures supports the claim that, for the Portuguese case, a particular validity of the compensation hypothesis has been observed. The achieved evidence promotes an important rule: in addition to there being a long-term relation between (some public expenditures and trade openness, short-term relations may also appear.

  16. Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner.

    Science.gov (United States)

    Eckford, Paul D W; Li, Canhui; Ramjeesingh, Mohabir; Bear, Christine E

    2012-10-26

    The cystic fibrosis transmembrane conductance regulator (CFTR) acts as a channel on the apical membrane of epithelia. Disease-causing mutations in the cystic fibrosis gene can lead to CFTR protein misfolding as in the case of the F508del mutation and/or channel dysfunction. Recently, a small molecule, VX-770 (ivacaftor), has shown efficacy in restoring lung function in patients bearing the G551D mutation, and this has been linked to repair of its channel gating defect. However, these studies did not reveal the mechanism of action of VX-770 in detail. Normally, CFTR channel activity is regulated by phosphorylation, ATP binding, and hydrolysis. Hence, it has been hypothesized that VX-770 modifies one or more of these metabolic events. In this study, we examined VX-770 activity using a reconstitution system for purified CFTR protein, a system that enables control of known regulatory factors. We studied the consequences of VX-770 interaction with CFTR incorporated in planar lipid bilayers and in proteoliposomes, using a novel flux-based assay. We found that purified and phosphorylated CFTR was potentiated in the presence of Mg-ATP, suggesting that VX-770 bound directly to the CFTR protein, rather than associated kinases or phosphatases. Interestingly, we also found that VX-770 enhanced the channel activity of purified and mutant CFTR in the nominal absence of Mg-ATP. These findings suggest that VX-770 can cause CFTR channel opening through a nonconventional ATP-independent mechanism. This work sets the stage for future studies of the structural properties that mediate CFTR gating using VX-770 as a probe.

  17. Take time to make time : What to consider when managing multi-channel sales systems with the objective to increase sales efficiency

    OpenAIRE

    Alm, Ragnar; KYRÖNLAHTI, RUDY

    2016-01-01

    Traditional sales systems have been disrupted by technological developments. In order to  adapt, companies are changing the way they interact with their customers in business-to-business markets. In the last three decades, multi-channel strategies have spurred the proliferation of different sales channels and new ways of managing sales systems. The purpose of this research was to investigate what should be considered when managing multi-channel sales systems with the objective of increasing s...

  18. Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels

    DEFF Research Database (Denmark)

    Chen, Xiaoping; Yang, Dachun; Ma, Shuangtao

    2010-01-01

    Vasomotion describes oscillations of arterial vascular tone due to synchronized changes of intracellular calcium concentrations. Since increased calcium influx into vascular smooth muscle cells from spontaneously hypertensive rats (SHR) has been associated with variances of transient receptor...

  19. Realizing the increased potential of an open-system high-definition digital projector design

    Science.gov (United States)

    Daniels, Reginald

    1999-05-01

    Modern video projectors are becoming more compact and capable. Various display technologies are very competitive and are delivering higher performance and more compact projectors to market at an ever quickening pace. However the end users are often left with the daunting task of integrating the 'off the self projectors' into a previously existing system. As the projectors become more digitally enhanced, there will be a series of designs, and the digital projector technology matures. The design solutions will be restricted by the state of the art at the time of manufacturing. In order to allow the most growth and performance for a given price, many design decisions will be made and revisited over a period of years or decades. A modular open digital system design concept is indeed a major challenge of the future high definition digital displays for al applications.

  20. Theoretical analysis and numerical simulation of mechanical energy loss and wall resistance of steady open channel flow

    Institute of Scientific and Technical Information of China (English)

    刘士和; 薛娇

    2016-01-01

    The mechanical energy loss and the wall resistance are very important in practical engineering. These problems are investigated through theoretical analysis and numerical simulation in this paper. The results are as follows. (1) A new mechanical energy equation for the total flow is obtained, and a general formula for the calculation of the mechanical energy loss is proposed. (2) The general relationship between the wall resistance and the mechanical energy loss for the steady channel flow is obtained, the simplified form of which for the steady uniform channel flow is in consistent with the formula used in Hydraulics deduced byπ theorem and dimensional analysis. (3) The steady channel flow over a backward facing step with a small expansion ratio is numerica- lly simulated, and the mechanical energy loss, the wall resistance as well as the relationship between the wall resistance and the mechanical energy loss are calculated and analyzed.

  1. Upregulated TRPC3 and downregulated TRPC1 channel expression during hypertension is associated with increased vascular contractility in rat

    Directory of Open Access Journals (Sweden)

    Muzamil M Noorani

    2011-07-01

    Full Text Available Transient receptor potential C1 and C3 (TRPC1 and TRPC3 are expressed in vascular smooth muscle cells and are thought to be involved in vascular contractility. In the present study, we determined the effect of systemic hypertension on TRPC1/TRPC3 channel expression and vascular contractility in rat carotid artery (CA. CA were studied from male spontaneously hypertensive (SHR, Wistar Kyoto (WKY and Long-Evans (LE rats. TRPC1/3 expression was determined by RT-PCR and Western blot. TRP channel function was evaluated by whole cell patch clamp, using UTP (60 µM to stimulate TRPC1/3 channels. Contractions of endothelium-denuded CA segments to UTP (1 – 300 µM and phenylephrine (Phe; 0.1 nM-10 µM were measured in an isometric tension bath. TRPC1 and TRPC3 mRNA was present in CA of both WKY and SHR. Western blot demonstrated 3.1 ± 1.2 times greater TRPC3 expression and 0.5 ± 0.2 times TRPC1 in SHR versus WKY CA. Isolated CA showed potentiated contraction to UTP in the SHR versus WKY. Activation of voltage-dependent Ca2+ channels (VDCC in UTP-mediated constriction only occurred in SHR CA. Contraction to Phe was unaltered between WKY and SHR CA and involved equal significant VDCC activation in both groups. Patch clamp demonstrated that the UTP-stimulated current (Iutp was greater in SHR compared to the normotensive WKY and LE rats with peak Iutp (at -110 mV of -63 ± 24 pA compared to -25 ± 4 pA, respectively. We demonstrate that UTP-mediated but not Phe-mediated constrictions are potentiated in the CA during hypertension. Expression of TRPC1 is decreased whereas TRPC3 is increased in SHR CA. Interestingly, VDCC activation only contributes to UTP-mediated contraction of SHR CAs whereas it contributes substantially and equally in Phe-mediated contraction. We speculate that the alteration of TRPC channel expression in hypertension leads to greater smooth muscle depolarization, VDCC activation, and vascular contractility in the UTP (but not Phe

  2. Multi-Channel Retail Supply Chain Management: Fulfillment systems in Multi-Channel Retailing - Customer Expectations and Economic Performance

    OpenAIRE

    Lang, Gerald

    2010-01-01

    International audience; Increasingly, store-based retailers are opening an additional online sales channel and becoming multi-channel retailers. The integration of these different channels raises the question how to redefine the strategic marketing elements and the operations, as the two channels have different constraints and require different competences. This multi-channel retailing has major impacts on the operations and the supply-chain management. Order fulfillment for the customers usi...

  3. The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Nardi, Antonio; Calloe, Kirstine

    2007-01-01

    -channel analysis revealed that NS11021 increased the open probability of the channel by altering gating kinetics without affecting the single-channel conductance. NS11021 (10 microM) influenced neither a number of cloned Kv channels nor endogenous Na(+) and Ca(2+) channels (L- and T-type) in guinea pig cardiac...

  4. SUMOylation of the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Increases Surface Expression and the Maximal Conductance of the Hyperpolarization-Activated Current

    Science.gov (United States)

    Parker, Anna R.; Welch, Meghyn A.; Forster, Lori A.; Tasneem, Sarah M.; Dubhashi, Janhavi A.; Baro, Deborah J.

    2017-01-01

    Small Ubiquitin-like Modifier (SUMO) is a ∼10 kDa peptide that can be post-translationally added to a lysine (K) on a target protein to facilitate protein–protein interactions. Recent studies have found that SUMOylation can be regulated in an activity-dependent manner and that ion channel SUMOylation can alter the biophysical properties and surface expression of the channel. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel surface expression can be regulated in an activity-dependent manner through unknown processes. We hypothesized that SUMOylation might influence the surface expression of HCN2 channels. In this manuscript, we show that HCN2 channels are SUMOylated in the mouse brain. Baseline levels of SUMOylation were also observed for a GFP-tagged HCN2 channel stably expressed in Human embryonic kidney (Hek) cells. Elevating GFP-HCN2 channel SUMOylation above baseline in Hek cells led to an increase in surface expression that augmented the hyperpolarization-activated current (Ih) mediated by these channels. Increased SUMOylation did not alter Ih voltage-dependence or kinetics of activation. There are five predicted intracellular SUMOylation sites on HCN2. Site-directed mutagenesis indicated that more than one K on the GFP-HCN2 channel was SUMOylated. Enhancing SUMOylation at one of the five predicted sites, K669, led to the increase in surface expression and Ih Gmax. The role of SUMOylation at additional sites is currently unknown. The SUMOylation site at K669 is also conserved in HCN1 channels. Aberrant SUMOylation has been linked to neurological diseases that also display alterations in HCN1 and HCN2 channel expression, such as seizures and Parkinson’s disease. This work is the first report that HCN channels can be SUMOylated and that this can regulate surface expression and Ih. PMID:28127275

  5. Three-Dimensional Simulation of High Reynolds Turbulent Flows in a Rectangular Open Channel with the Presence of a Disruptive Element (Obstacles Transversely

    Directory of Open Access Journals (Sweden)

    Boudiaf H’ssine

    2015-03-01

    Full Text Available This study aims at describing a three-dimensional simulation of a turbulent flow with a high Reynolds number in a rectangular open channel with the presence of a disruptive element (obstacles transversely. The numerical study is based on measuring the flow velocity in two directions, i.e., horizontal and vertical, in four planes located near the obstacle built across a simulated channel. For the modeling of the free surface, a Volume Of Fluid (VOF multiphase flow model is used. In the present case, namely a study of turbulence, three numerical models are compared, a k-ε standard, a k-w standard and a Reynolds Stress Model (RSM. The verification of the simulation results has allowed us to show the advantages of the Reynolds stress model. This model is more representative of the phenomena of an intense vortex flow in the presence of obstacles, especially in drainage systems.

  6. Range extension and channel capacity increase in impulse-radio ultra-wideband communications

    DEFF Research Database (Denmark)

    Rodes Lopez, Roberto; Yu, Xianbin; Caballero Jambrina, Antonio

    2010-01-01

    and its performance is compared. By utilizing optimum UWB pulse design and employing a digital signal processing (DSP) receiver, a bit-error-rate above the forward error correction (FEC) limit for 8 meters of wireless emission is obtained in our photonic generation UWB system. A noticeable increase...

  7. Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets

    DEFF Research Database (Denmark)

    Maedler, Kathrin; Størling, Joachim; Sturis, Jeppe

    2004-01-01

    -regulated kinase (ERK) 1/2, an effect that was abrogated by 3 micromol/l NN414. Similarly, 1 micromol/l of the mitogen-activated protein kinase/ERK kinase 1/2 inhibitor PD098059 or 1 micromol/l of the l-type Ca(2+) channel blocker nimodipine prevented glucose- and IL-1beta-induced ERK activation, beta......Increasing evidence indicates that a progressive decrease in the functional beta-cell mass is the hallmark of both type 1 and type 2 diabetes. The underlying causes, beta-cell apoptosis and impaired secretory function, seem to be partly mediated by macrophage production of interleukin (IL)-1beta...... and/or high-glucose-induced beta-cell production of IL-1beta. Treatment of type 1 and type 2 diabetic patients with the potassium channel opener diazoxide partially restores insulin secretion. Therefore, we studied the effect of diazoxide and of the novel potassium channel opener NN414, selective...

  8. Alterations in expression of Cat-315 epitope of perineuronal nets during normal ageing, and its modulation by an open-channel NMDA receptor blocker, memantine.

    Science.gov (United States)

    Yamada, Jun; Ohgomori, Tomohiro; Jinno, Shozo

    2017-03-08

    The perineuronal net (PNN), a specialized aggregate of the extracellular matrix, is involved in neuroprotection against oxidative stress, which is now recognized as a major contributor to age-related decline in brain functions. In this study, we investigated the age-related molecular changes of PNNs using monoclonal antibody Cat-315, which recognizes human natural killer-1 (HNK-1) glycan on aggrecan-based PNNs. Western blot analysis showed that the expression levels of Cat-315 epitope in the hippocampus were higher in middle-aged (MA, 12-month-old) mice than in young adult (YA, 2-month-old) mice. Although there were no differences in the expression levels of Cat-315 epitope between old age (OA, 20-month-old) and MA mice, Cat-315 immunoreactivity was also detected in astrocytes of OA mice. To focus on Cat-315 epitope in PNNs, we used YA and MA mice in the following experiments. Optical disector analysis showed that there were no differences in the numbers of Cat-315-positive (Cat-315(+) ) PNNs between YA and MA mice. Fluorescence intensity analysis indicated that Cat-315 immunoreactivity in PNNs increased with age in the dorsal hippocampus, which is mainly involved in cognitive functions. Administration of an open-channel blocker of NMDA receptor, memantine, reduced the expression levels of Cat-315 epitope in the hippocampus. Furthermore, the numbers of glutamatergic and GABAergic terminals colocalized with Cat-315 epitope around parvalbumin-positive neurons were decreased by memantine. These findings provide novel insight into the involvement of PNNs in normal brain ageing, and suggest that memantine may counteract the age-related alterations in expression levels of Cat-315 epitope via regulation of its subcellular localization. This article is protected by copyright. All rights reserved.

  9. Predictability of tracer dilution in large open channel flows: Analytical solution for the coefficient of variation of the depth-averaged concentration

    Science.gov (United States)

    Pannone, Marilena

    2014-03-01

    A large-time analytical solution is proposed for the spatial variance and coefficient of variation of the depth-averaged concentration due to instantaneous, cross sectionally uniform solute sources in pseudorectangular open channel flows. The mathematical approach is based on the use of the Green functions and on the Fourier decomposition of the depth-averaged velocities, coupled with the method of the images. The variance spatial trend is characterized by a minimum at the center of the mass and two mobile, decaying symmetrical peaks which, at very large times, are located at the inflexion points of the average Gaussian distribution. The coefficient of variation, which provides an estimate of the expected percentage deviation of the depth-averaged point concentrations about the section-average, exhibits a minimum at the center which decays like t-1 and only depends on the river diffusive time scale. The defect of cross-sectional mixing quickly increases with the distance from the center, and almost linearly at large times. Accurate numerical Lagrangian simulations were performed to validate the analytical results in preasymptotic and asymptotic conditions, referring to a particularly representative sample case for which cross-sectional depth and velocity measurements were known from a field survey. In addition, in order to discuss the practical usefulness of computing large-time concentration spatial moments in river flows, and resorting to directly measured input data, the order of magnitude of section-averaged concentrations and corresponding coefficients of variation was estimated in field conditions and for hypothetical contamination scenarios, considering a unit normalized mass impulsively injected across the transverse section of 81 U.S. rivers.

  10. Design of Mine-used Ultrasonic Open-channel Flowmeter%矿用超声波明渠流量计的设计

    Institute of Scientific and Technical Information of China (English)

    徐乐年; 刘伟光; 王全

    2011-01-01

    针对矿井水中含有的煤粉、泥沙等杂质淤积在明渠流量计探头表面而使其无法正常工作的问题,设计了一种基于M-Bus的矿用超声波明渠流量计.该流量计由量水堰槽、智能超声波流量传感器组成,选定量水堰槽可确定实时流量与实测水头高度的关系式,通过智能超声波流量传感器测出水头高度即可计算出明渠的实时流量.实际应用表明,该流量计具有测量准确、可靠性高、操作简单等优点.%In view of problem that open-channel flowmeter can't work normally because mine water contains impurities of coal powder and sediment which deposit on surface of probe of open-channel flowmeter, a mine-used ultrasonic open-channel flowmeter based on M-Bus was designed.The flowmeter is composed of water-level weir slot and intelligent ultrasonic flow sensor, which can get formula between real-time flow and measured height of water head by water-level weir slot and calculate real-time flow by intelligent ultrasonic flow sensor to measure height of water head.The actual application showed that the flowmeter has advantages of accurate measurement, high reliability and simple operation.

  11. External bioenergy-induced increases in intracellular free calcium concentrations are mediated by Na+/Ca2+ exchanger and L-type calcium channel.

    Science.gov (United States)

    Kiang, Juliann G; Ives, John A; Jonas, Wayne B

    2005-03-01

    External bioenergy (EBE, energy emitted from a human body) has been shown to increase intracellular calcium concentration ([Ca2+]i, an important factor in signal transduction) and regulate the cellular response to heat stress in cultured human lymphoid Jurkat T cells. In this study, we wanted to elucidate the underlying mechanisms. A bioenergy specialist emitted bioenergy sequentially toward tubes of cultured Jurkat T cells for one 15-minute period in buffers containing different ion compositions or different concentrations of inhibitors. [Ca2+], was measured spectrofluorometrically using the fluorescent probe fura-2. The resting [Ca2+]i in Jurkat T cells was 70 +/- 3 nM (n = 130) in the normal buffer. Removal of external calcium decreased the resting [Ca2+]i to 52 +/- 2 nM (n = 23), indicating that Ca2+ entry from the external source is important for maintaining the basal level of [Ca2+]i. Treatment of Jurkat T cells with EBE for 15 min increased [Ca2+]i by 30 +/- 5% (P EBE did not attenuate [Ca2+]i responsiveness to EBE. Removal of external Ca2+ or Na+, but not Mg2+, inhibited the EBE-induced increase in [Ca2+]i. Dichlorobenzamil, an inhibitor of Na+/Ca2+ exchangers, also inhibited the EBE-induced increase in [Ca2+]i in a concentration-dependent manner with an IC50 of 0.11 +/- 0.02 nM. When external [K+] was increased from 4.5 mM to 25 mM, EBE decreased [Ca2+]i. The EBE-induced increase was also blocked by verapamil, an L-type voltage-gated Ca2+ channel blocker. These results suggest that the EBE-induced [Ca2+]i increase may serve as an objective means for assessing and validating bioenergy effects and those specialists claiming bioenergy capability. The increase in [Ca2+]i is mediated by activation of Na+/Ca2+ exchangers and opening of L-type voltage-gated Ca2+ channels.

  12. Single-channel kinetics of BK (Slo1 channels

    Directory of Open Access Journals (Sweden)

    Yanyan eGeng

    2015-01-01

    Full Text Available Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1 channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD attached to four surrounding transmembrane voltage sensing domains (VSD and a large intracellular cytosolic domain (CTD, also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.

  13. Increasing the acquisition speed of a multi-channel guided wave system via simultaneous coded excitations

    Science.gov (United States)

    Hua, Jiadong; Michaels, Jennifer E.; Chen, Xin; Lin, Jing

    2017-02-01

    Many guided wave systems that are being evaluated for nondestructive evaluation or structural health monitoring utilize multiple transducers. Data are typically acquired by exciting each transducer in turn and recording received signals on the remaining transducers either simultaneously or separately. For either case, it can be very slow to acquire data because of the multiple transmission cycles combined with a slow repetition rate and extensive signal averaging. This long acquisition time brings another disadvantage by increasing the risk of environmental changes occurring during the complete acquisition process. For example, applied loads and temperature could change over the several seconds that are frequently required to acquire data. To increase the acquisition speed, it is proposed here to simultaneously trigger multiple transmitters, and each transmitter is driven with a unique, coded excitation. The simultaneously transmitted waves are captured by one or more receivers, and their responses are processed by dispersive matched filtering to separately extract the contribution from each transmitter. Results are shown for signals obtained from a spatially distribution array mounted on an aluminum plate.

  14. Self-selected or mandated, open access increases citation impact for higher quality research.

    Directory of Open Access Journals (Sweden)

    Yassine Gargouri

    Full Text Available BACKGROUND: Articles whose authors have supplemented subscription-based access to the publisher's version by self-archiving their own final draft to make it accessible free for all on the web ("Open Access", OA are cited significantly more than articles in the same journal and year that have not been made OA. Some have suggested that this "OA Advantage" may not be causal but just a self-selection bias, because authors preferentially make higher-quality articles OA. To test this we compared self-selective self-archiving with mandatory self-archiving for a sample of 27,197 articles published 2002-2006 in 1,984 journals. METHDOLOGY/PRINCIPAL FINDINGS: The OA Advantage proved just as high for both. Logistic regression analysis showed that the advantage is independent of other correlates of citations (article age; journal impact factor; number of co-authors, references or pages; field; article type; or country and highest for the most highly cited articles. The OA Advantage is real, independent and causal, but skewed. Its size is indeed correlated with quality, just as citations themselves are (the top 20% of articles receive about 80% of all citations. CONCLUSIONS/SIGNIFICANCE: The OA advantage is greater for the more citable articles, not because of a quality bias from authors self-selecting what to make OA, but because of a quality advantage, from users self-selecting what to use and cite, freed by OA from the constraints of selective accessibility to subscribers only. It is hoped that these findings will help motivate the adoption of OA self-archiving mandates by universities, research institutions and research funders.

  15. Getting physicians to open the survey: little evidence that an envelope teaser increases response rates

    Directory of Open Access Journals (Sweden)

    Ziegenfuss Jeanette Y

    2012-03-01

    Full Text Available Abstract Background Physician surveys are an important tool to assess attitudes, beliefs and self-reported behaviors of this policy relevant group. In order for a physician to respond to a mailed survey, they must first open the envelope. While there is some evidence that package elements can impact physician response rates, the impact of an envelope teaser is unknown. Here we assess this by testing the impact of adding a brightly colored "$25 incentive" sticker to the outside of an envelope on response rates and nonresponse bias in a survey of physicians. Methods In the second mailing of a survey assessing physicians' moral beliefs and views on controversial health care topics, initial nonrespondents were randomly assigned to receive a survey in an envelope with a colored "$25 incentive" sticker (teaser group or an envelope without a sticker (control group. Response rates were compared between the teaser and control groups overall and by age, gender, region of the United States, specialty and years in practice. Nonresponse bias was assessed by comparing the demographic composition of the respondents to the nonrespondents in the experimental and control condition. Results No significant differences in response rates were observed between the experimental and control conditions overall (p = 0.38 or after stratifying by age, gender, region, or practice type. Within the teaser condition, there was some variation in response rate by years since graduation. There was no independent effect of the teaser on response when simultaneously controlling for demographic characteristics (OR = 0.875, p = 0.4112. Conclusions Neither response rates nor nonresponse bias were impacted by the use of an envelope teaser in a survey of physicians in the United States.

  16. Ways of increasing excavator fleet productivity in Russian coal open pits (Kuzbass case study

    Directory of Open Access Journals (Sweden)

    Drygin Michael

    2017-01-01

    Full Text Available A steady increase in coal extraction in Russian Federation and worldwide results from objective causes of natural resources availability and development of advanced coal processing technologies. In the context of the long-standing economic crisis, considerable investments in coal in-dustry are not to be expected. Consequently, the reserve for extraction growth lies in increasing productivity of the key equipment applied in Kuzbass coal pits. The production data analysis revealed that the presented excavators working capacity does not depend on the bucket volume and the cycle time. It is hereby specified that working capacity is primarily de-pendent on the actual operation cycle time. As it is demonstrated, the key reserve for increasing the working capacity consists in elevating efficiency of actual performance time use.

  17. Finding differentially expressed genes in two-channel DNA microarray datasets: how to increase reliability of data preprocessing.

    Science.gov (United States)

    Rotter, Ana; Hren, Matjaz; Baebler, Spela; Blejec, Andrej; Gruden, Kristina

    2008-09-01

    Due to the great variety of preprocessing tools in two-channel expression microarray data analysis it is difficult to choose the most appropriate one for a given experimental setup. In our study, two independent two-channel inhouse microarray experiments as well as a publicly available dataset were used to investigate the influence of the selection of preprocessing methods (background correction, normalization, and duplicate spots correlation calculation) on the discovery of differentially expressed genes. Here we are showing that both the list of differentially expressed genes and the expression values of selected genes depend significantly on the preprocessing approach applied. The choice of normalization method to be used had the highest impact on the results. We propose a simple but efficient approach to increase the reliability of obtained results, where two normalization methods which are theoretically distinct from one another are used on the same dataset. Then the intersection of results, that is, the lists of differentially expressed genes, is used in order to get a more accurate estimation of the genes that were de facto differentially expressed.

  18. Water quality model parameter identification of an open channel in a long distance water transfer project based on finite difference, difference evolution and Monte Carlo.

    Science.gov (United States)

    Shao, Dongguo; Yang, Haidong; Xiao, Yi; Liu, Biyu

    2014-01-01

    A new method is proposed based on the finite difference method (FDM), differential evolution algorithm and Markov Chain Monte Carlo (MCMC) simulation to identify water quality model parameters of an open channel in a long distance water transfer project. Firstly, this parameter identification problem is considered as a Bayesian estimation problem and the forward numerical model is solved by FDM, and the posterior probability density function of the parameters is deduced. Then these parameters are estimated using a sampling method with differential evolution algorithm and MCMC simulation. Finally this proposed method is compared with FDM-MCMC by a twin experiment. The results show that the proposed method can be used to identify water quality model parameters of an open channel in a long distance water transfer project under different scenarios better with fewer iterations, higher reliability and anti-noise capability compared with FDM-MCMC. Therefore, it provides a new idea and method to solve the traceability problem in sudden water pollution accidents.

  19. Role of TRPV1 channels of the dorsal periaqueductal gray in the modulation of nociception and open elevated plus maze-induced antinociception in mice.

    Science.gov (United States)

    Mascarenhas, Diego Cardozo; Gomes, Karina Santos; Nunes-de-Souza, Ricardo Luiz

    2015-10-01

    Recent findings have identified the presence of transient receptor potential vanilloid-1 (TRPV1) channels within the dorsal portion of the periaqueductal gray (dPAG), suggesting their involvement in the control of pain and environmentally-induced antinociception. Environmentally, antinociception may be achieved through the use of an open elevated plus maze (oEPM, an EPM with 4 open arms), a highly aversive environmental situation. Here, we investigated the role of these TRPV1 channels within the dPAG in the modulation of a tonic pain and in the oEPM-induced antinociception. Male Swiss mice, under the nociceptive effect of 2.5% formalin injected into the right hind paw, received intra-dPAG injections of the TRPV1 agonist (capsaicin: 0, 0.01, 0.1 or 1.0 nmol/0.2 μL; Experiment 1) or antagonist (capsazepine: 0, 10 or 30 nmol/0.2 μL; Experiment 2) or combined injections of capsazepine (30 nmol) and capsaicin (1.0 nmol) (Experiment 3) and the time spent licking the formalin-injected paw was recorded. In Experiment 4, mice received intra-dPAG capsazepine (0 or 30 nmol) and were exposed to the oEPM or to a control situation, an enclosed EPM (eEPM; an EPM with 4 enclosed arms). Results showed that while capsaicin (1 nmol) decreased the time spent licking the formalin-injected paw, capsazepine did not change nociceptive response. Capsazepine (30 nmol) blocked pain inhibition induced by capsaicin and mildly attenuated the oEPM-induced antinociception. Our results revealed an important role of TRPV1 channels within the dPAG in the modulation of pain and in the phenomenon known as fear-induced antinociception in mice.

  20. H-ras transformation sensitizes volume-activated anion channels and increases migratory activity of NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Klausen, Thomas K; Stock, Christian;

    2008-01-01

    The expression of the H-ras oncogene increases the migratory activity of many cell types and thereby contributes to the metastatic behavior of tumor cells. Other studies point to an involvement of volume-activated anion channels (VRAC) in (tumor) cell migration. In this paper, we tested whether...... VRACs are required for the stimulation of cell migration upon expression of the H-ras oncogene. We compared VRAC activation and migration of wild-type and H-ras-transformed NIH3T3 fibroblasts by means of patch-clamp techniques and time-lapse video microscopy. Both cell types achieve the same degree...... of VRAC activation upon maximal stimulation, induced by reducing extracellular osmolarity from 300 to 190 mOsm/l. However, upon physiologically relevant reductions in extracellular osmolarity (275 mOsm/l), the level of VRAC activation is almost three times higher in H-ras-transformed compared to wild...

  1. Chronic inflammatory injury results in increased coupling of delta opioid receptors to voltage-gated Ca2+ channels.

    Science.gov (United States)

    Pradhan, Amynah; Smith, Monique; McGuire, Brenna; Evans, Christopher; Walwyn, Wendy

    2013-03-04

    Opioid receptors regulate a diverse array of physiological functions. Mu opioid receptor agonists are well-known analgesics for treating acute pain. In contrast, animal models suggest that chronic pain is more effectively relieved by delta opioid receptor agonists. A number of studies have shown that chronic pain results in increased function of delta opioid receptors. This is proposed to result from enhanced trafficking of the delta opioid receptor to the cell membrane induced by persistent tissue injury. However, recent studies have questioned this mechanism, which has resulted in some uncertainty as to whether delta opioid receptors are indeed upregulated in chronic pain states. To clarify this question, we have examined the effect of chronic inflammatory pain over time using both an ex vivo measure of delta function: receptor-Ca2+ channel coupling, and an in vivo measure; the relief of chronic pain by a delta opioid receptor agonist. In addition, as beta-arrestin 2 can regulate delta opioid receptor trafficking and signaling, we have further examined whether deleting this scaffolding and signal transduction molecule alters delta opioid receptor function. We used the Complete Freund's Adjuvant model of inflammatory pain, and examined the effectiveness of the delta agonist, SNC80, to both inhibit Ca2+ channels in primary afferent neurons and to attenuate mechanical allodynia. In naïve beta-arrestin 2 wildtype and knockout mice, SNC80 neither significantly inhibited voltage-dependent Ca2+ currents nor produced antinociception. However, following inflammatory pain, both measures showed a significant and long-lasting enhancement of delta opioid receptor function that persisted for up to 14 days post-injury regardless of genotype. Furthermore, although this pain model did not alter Ca2+ current density, the contribution of N-type Ca2+ channels to the total current appeared to be regulated by the presence of beta-arrestin 2. Our results indicate that there is an

  2. The opening of maitotoxin-sensitive calcium channels induces the acrosome reaction in human spermatozoa: differences from the zona pellucida

    Institute of Scientific and Technical Information of China (English)

    Julio C Chávez; Claudia L Trevi(n)o; Gerardo A de Blas; José L de la Vega-Beltrán; Takuya Nishigaki; Mayel Chirinos; María Elena González-González; Fernando Larrea; Alejandra Solís; Alberto Darszon

    2011-01-01

    The acrosome reaction(AR),an absolute requirement for spermatozoa and egg fusion,requires the influx of Ca2+into the spermatozoa through voltage-dependent Ca2+channels and store-operated channels.Maitotoxin(MTx),a Ca2+-mobilizing agent,has been shown to be a potent inducer of the mouse sperm AR,with a pharmacology similar to that of the zona pellucida(ZP),possibly suggesting a common pathway for both inducers.Using recombinant human ZP3(rhZP3),mouse ZP and two MTx channel blockers(U73122 and U73343),we investigated and compared the MTx-and ZP-induced ARs in human and mouse spermatozoa.Herein,we report that MTx induced AR and elevated intracellular Ca2+([Ca2+]1)in human spermatozoa,both of which were blocked by U73122 and U73343.These two compounds also inhibited the MTx-induced AR in mouse spermatozoa.In disagreement with our previous proposal,the AR triggered by rhZP3 or mouse ZP was not blocked by U73343,indicating that in human and mouse spermatozoa,the AR induction by the physiologicalligands or by MTx occurred through distinct pathways.U73122,but not U73343(inactive analogue),can block phospholipase C(PLC).Another PLC inhibitor,edelfosine,also blocked the rhZP3-and ZP-induced ARs.These findings confirmed the participation of a PLC-dependent signalling pathway in human and mouse zona protein-induced AR.Notably,edelfosine also inhibited the MTx-induced mouse sperm AR but not that of the human,suggesting that toxin-induced AR is PLC-dependent in mice and PLC-independent in humans.

  3. Opening the Black Box: Strategies for Increased User Involvement in Existing Algorithm Implementations.

    Science.gov (United States)

    Mühlbacher, Thomas; Piringer, Harald; Gratzl, Samuel; Sedlmair, Michael; Streit, Marc

    2014-12-01

    An increasing number of interactive visualization tools stress the integration with computational software like MATLAB and R to access a variety of proven algorithms. In many cases, however, the algorithms are used as black boxes that run to completion in isolation which contradicts the needs of interactive data exploration. This paper structures, formalizes, and discusses possibilities to enable user involvement in ongoing computations. Based on a structured characterization of needs regarding intermediate feedback and control, the main contribution is a formalization and comparison of strategies for achieving user involvement for algorithms with different characteristics. In the context of integration, we describe considerations for implementing these strategies either as part of the visualization tool or as part of the algorithm, and we identify requirements and guidelines for the design of algorithmic APIs. To assess the practical applicability, we provide a survey of frequently used algorithm implementations within R regarding the fulfillment of these guidelines. While echoing previous calls for analysis modules which support data exploration more directly, we conclude that a range of pragmatic options for enabling user involvement in ongoing computations exists on both the visualization and algorithm side and should be used.

  4. Enhanced Sucrose Loading Improves Rice Yield by Increasing Grain Size1[OPEN

    Science.gov (United States)

    Wang, Liang; Lu, Qingtao

    2015-01-01

    Yield in cereals is a function of grain number and size. Sucrose (Suc), the main carbohydrate product of photosynthesis in higher plants, is transported long distances from source leaves to sink organs such as seeds and roots. Here, we report that transgenic rice plants (Oryza sativa) expressing the Arabidopsis (Arabidopsis thaliana) phloem-specific Suc transporter (AtSUC2), which loads Suc into the phloem under control of the phloem protein2 promoter (pPP2), showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. Compared with wild-type plants, pPP2::AtSUC2 plants had larger spikelet hulls and larger and heavier grains. Grain filling was accelerated in the transgenic plants, and more photoassimilate was transported from the leaves to the grain. In addition, microarray analyses revealed that carbohydrate, amino acid, and lipid metabolism was enhanced in the leaves and grain of pPP2::AtSUC2 plants. Thus, enhancing Suc loading represents a promising strategy to improve rice yield to feed the global population. PMID:26504138

  5. BER Analysis to Increase Capacity of A Cellular System Using SDMA Over a Multipath Rayleigh Fading Channel

    Directory of Open Access Journals (Sweden)

    M. Gangadharappa

    2010-07-01

    Full Text Available In this paper, we have presented how the capacity of cellular system can be enhanced by using Space Division Multiple Access (SDMA with directive antenna in mobile communication systems. One of the biggest draw back of wireless environment is the limited bandwidth. However,the users sharing this limited bandwidth have been increased considerably. SDMA is a technology by which the capacity of the existing mobile communication system can economically be increased. Adaptive Antenna provides a spot beam for each users in the cells as it moves. This paper analysis the comparison of average Bit Error Rate (BER of SDMA and Code Division Multiple Access (CDMAtechnique and the way in which SDMA can be introduced to increase the capacity of a cellular system in Frequency Selective Multipath Rayleigh Fading Channel. The BER is found for a standard omni directional base station antenna, and the another set of curve is found for flat top beam having a directivity of 8 dB. We see that SDMA offers improved capacity in wireless communication system.

  6. AB095. Increased expression of TMEM16A/Ano1 chloride channel associated with diabetic erectile dysfunction

    Science.gov (United States)

    Ruan, Yajun; Chen, Yingwei; Li, Mingchao; Wang, Tao; Yang, Jun; Rao, Ke; Wang, Shaogang; Yang, Weimin; Liu, Jihong; Ye, Zhangqun

    2016-01-01

    Objective To investigate the presence, location and functional role of TMEM16A/anotamin-1 (Ano1) calcium-activated chloride channel (CaCC) in the penile of rats with diabetic erectile dysfunction. Methods Eight-week-old male Sprague-Dawley (SD) rats were administrated streptozotocin (diabetic) or citrate buffer (control) randomly. Erectile function was measured by cavernous nerve electrostimulation at 12th week after diabetes was induced. The effect of Ano1 specific inhibitor—T16Ainh-A01 on intracavernous pressure (ICP) was evaluated. Then the penile tissues were harvested for molecular exploration. Real-time PCR and Western Blotting were used to assess the expression of Ano1 in penile tissues. Immunofluorescent labelling of penile tissue allowed localization of Ano1. Cavernous smooth muscle cell (CSMC) was cultured in high glucose medium. The change of Ano1 was measured using Western Blotting. The proliferation of CSMC was evaluated by cell counting kit-8 (CCK-8). Results Erectile function was impaired in diabetic rats. The expression of Ano1 was increased in rats with diabetic erectile dysfunction at mRNA and protein levels. Immunofluorescent labelling revealed the presence of Ano1 mainly in cavernous smooth muscle cells. The inhibition of Ano1 increased the ICP of DED rats. High glucose in vitro enhanced the proliferation of CSMC and the expression level of Ano1. Conclusions Ano1 is expressed in rat penile tissue and is increased with diabetes mellitus. The inhibition of Ano1 increased the ICP of DED rats. The alerted Ano1 may be associated with diabetic erectile dysfunction. It is a potential therapy target for ED in the future.

  7. Multi-walled carbon nanotubes increase anxiety levels in rats and reduce exploratory activity in the open field test.

    Science.gov (United States)

    Sayapina, N V; Batalova, T A; Chaika, V V; Kuznetsov, V L; Sergievich, A A; Kolosov, V P; Perel'man, Yu M; Golokhvast, K S

    2015-01-01

    The results of the first study on the effects of multi-walled carbon nanotubes (MWNTs) on the exploratory activity and the emotional state in laboratory rats assessed by the open field test are reported. During three or ten days, rats received 8-10 nm MWNTs added to their food at a dose of 500 mg/kg. It was demonstrated that, in the group of rats which were fed with MWNTs, the integrated anxiety level index began to increase as early as the third day of the experiment; on the tenth day, it appeared to be twice increased. It was also demonstrated that MWNTs decreased the integrated exploratory activity index nearly twofold on the third day and nearly fourfold on the tenth day.

  8. An open source workbook in Excel for viewing and analyzing demagnetization data from paleomagnetic discrete samples and u-channels

    Science.gov (United States)

    Sagnotti, L.

    2012-12-01

    Modern rock magnetometers and stepwise demagnetization procedures result in the production of large datasets, which need a versatile and fast software for their display and analysis. Various software packages for paleomagnetic analyses have been recently developed to overcome the problems linked to the limited capability and the loss of operability of early codes written in obsolete computer languages and/or platforms, not compatible with modern 64 bit processors. Here I present a new software for viewing and analyzing demagnetization data from paleomagnetic discrete samples and u-channels, which consists of a workbook for Microsoft Excel. The widespread diffusion of Excel ensures multiplatform operability and offers guarantees for long term operability, independently form the development of new processors and operating systems. In order to reduce the problems linked to the rapid evolution of the programming environments, the workbook makes use of a few macros, written in Visual Basic and necessary only to automatically save the output data. The workbook is designed for an interactive operability and all the commands and choices can be entered by sliding menus associated to single cells. All the standard demagnetization diagrams (Zijderveld orthogonal projection diagrams, stereographic projection of unit vectors, decay of the remanence intensity) are featured and both the user-driven and the automatic computation of the remanence characteristic components by principal component analysis are allowed. In addition, various other common demagnetization parameters (MDF, deltaGRM) are computed. The whole workbook is free for use and modification. The program has the following features which may be valuable for various users: - Operability in nearly all the computers and platforms; - Easy inputs of demagnetization data by "copy and paste" from ASCII files. The required data consist of only 9 columns: (1) sample code, (2) demagnetization steps, (3-5) raw measurements from

  9. Orientations and proximities of the extracellular ends of transmembrane helices S0 and S4 in open and closed BK potassium channels.

    Directory of Open Access Journals (Sweden)

    Xiaowei Niu

    Full Text Available The large-conductance potassium channel (BK α subunit contains a transmembrane (TM helix S0 preceding the canonical TM helices S1 through S6. S0 lies between S4 and the TM2 helix of the regulatory β1 subunit. Pairs of Cys were substituted in the first helical turns in the membrane of BK α S0 and S4 and in β1 TM2. One such pair, W22C in S0 and W203C in S4, was 95% crosslinked endogenously. Under voltage-clamp conditions in outside-out patches, this crosslink was reduced by DTT and reoxidized by a membrane-impermeant bis-quaternary ammonium derivative of diamide. The rate constants for this reoxidation were not significantly different in the open and closed states of the channel. Thus, these two residues are approximately equally close in the two states. In addition, 90% crosslinking of a second pair, R20C in S0 and W203C in S4, had no effect on the V50 for opening. Taken together, these findings indicate that separation between residues at the extracellular ends of S0 and S4 is not required for voltage-sensor activation. On the contrary, even though W22C and W203C were equally likely to form a disulfide in the activated and deactivated states, relative immobilization by crosslinking of these two residues favored the activated state. Furthermore, the efficiency of recrosslinking of W22C and W203C on the cell surface was greater in the presence of the β1 subunit than in its absence, consistent with β1 acting through S0 to stabilize its immobilization relative to α S4.

  10. An integrated model coupling open-channel flow, turbidity current and flow exchanges between main river and tributaries in Xiaolangdi Reservoir, China

    Science.gov (United States)

    Wang, Zenghui; Xia, Junqiang; Li, Tao; Deng, Shanshan; Zhang, Junhua

    2016-12-01

    The ever growing importance of sustainable management of reservoir sedimentation has promoted the development and applications of turbidity current models. However, there are few effective and practical models in literature for turbidity currents in a reservoir where the impounded area involves both the main river and its many tributaries. An integrated numerical model coupling open-channel flow, turbidity current and flow exchanges between main river and tributaries is proposed, which can simulate the complex flow and sediment transport in a reservoir where these three physical processes coexist. The model consists of two sets of governing equations for the open-channel flow and turbidity current, which are based on the modified St. Venant equations by taking into account the effect of lateral flow exchanges. These two sets of equations are solved in the finite volume method framework and the solutions are executed in an alternating calculation mode. Different methods are respectively proposed to calculate the discharge of flow exchange caused by free surface gradient and turbidity current intrusion. For the surface-gradient driven flow exchange, a storage cell method, which re-defines the relationship between water level and representative cross-sectional area, is used to update the water level at confluence. For the turbidity current intrusion, a discharge formula is proposed based on the analysis of the energy and momentum transformation in the intruding turbid water body. This formula differs from previous ones in that the effect of tributary bed slope is considered. Two events of water-sediment regulation conducted in the Xiaolangdi Reservoir in 2004 and 2006 were simulated to test the ability of this model. The predicted reservoir drawdown process, the turbidity current evolution and the sediment venting efficiency were in close agreement with the measurements. The necessity to couple the flow exchanges was demonstrated by comparing the performance of the

  11. A competing hydrophobic tug on L596 to the membrane core unlatches S4-S5 linker elbow from TRP helix and allows TRPV4 channel to open.

    Science.gov (United States)

    Teng, Jinfeng; Loukin, Stephen H; Anishkin, Andriy; Kung, Ching

    2016-10-18

    We have some generalized physical understanding of how ion channels interact with surrounding lipids but few detailed descriptions on how interactions of particular amino acids with contacting lipids may regulate gating. Here we discovered a structure-specific interaction between an amino acid and inner-leaflet lipid that governs the gating transformations of TRPV4 (transient receptor potential vanilloid type 4). Many cation channels use a S4-S5 linker to transmit stimuli to the gate. At the start of TRPV4's linker helix is leucine 596. A hydrogen bond between the indole of W733 of the TRP helix and the backbone oxygen of L596 secures the helix/linker contact, which acts as a latch maintaining channel closure. The modeled side chain of L596 interacts with the inner lipid leaflet near the polar-nonpolar interface in our model-an interaction that we explored by mutagenesis. We examined the outward currents of TRPV4-expressing Xenopus oocyte upon depolarizations as well as phenotypes of expressing yeast cells. Making this residue less hydrophobic (L596A/G/W/Q/K) reduces open probability [Po; loss-of-function (LOF)], likely due to altered interactions at the polar-nonpolar interface. L596I raises Po [gain-of-function (GOF)], apparently by placing its methyl group further inward and receiving stronger water repulsion. Molecular dynamics simulations showed that the distance between the levels of α-carbons of H-bonded residues L596 and W733 is shortened in the LOFs and lengthened in the GOFs, strengthening or weakening the linker/TRP helix latch, respectively. These results highlight that L596 lipid attraction counteracts the latch bond in a tug-of-war to tune the Po of TRPV4.

  12. Selective gas adsorption and unique structural topology of a highly stable guest-free zeolite-type MOF material with N-rich chiral open channels.

    Science.gov (United States)

    Li, Jian-Rong; Tao, Ying; Yu, Qun; Bu, Xian-He; Sakamoto, Hirotoshi; Kitagawa, Susumu

    2008-01-01

    A new multifunctional di-topic tetrazolate-based ligand, 2,3-di-1H-tetrazol-5-ylpyrazine (H(2)dtp) has been designed and synthesized. The solvothermal reaction of this ligand with ZnCl(2) gave a robust guest-free three-dimensional zeolite-like chiral metal-organic framework (MOF) complex, [Zn(dtp)], which crystallized in chiral space group P6(1) and possessed chiral open channels with nitrogen-rich walls and the diameter of approximately 4.1 A. This framework presents a unique uniform etd (8,3) topology, is the first example of its type in MOFs, and exhibits high thermal stability with the decomposition temperature above 380 degrees C and permanent porosity. It is interesting that this material is able to selectively adsorb O(2) and CO(2) over N(2) gas, being a rare example in MOFs. In addition, C(2)H(2) and MeOH adsorption results show that although the framework channel holds nitrogen-rich walls that may provide H-bonding sites, no NH H-bond effect between the guest molecules and microporous surface was observed.

  13. Rates of cortisol increase and decrease in channel catfish and sunshine bass exposed to an acute confinement stressor.

    Science.gov (United States)

    Davis, Kenneth B; Small, Brian C

    2006-05-01

    Channel catfish and sunshine bass were exposed to a low-water stress event and allowed to recover in fresh water or a solution of metomidate (dl-1-(1-phenylethyl)-5-(metoxycarbonyl) imidazole hydrochloride), which inhibits the synthesis of cortisol. Change in time of plasma cortisol was used as an index of cortisol secretion and clearance. Plasma cortisol and glucose increased during the exposure to low-water stress in both fish, but the changes of both plasma components were more dramatic in sunshine bass. Exposure to metomidate during recovery resulted in a short-term increase in plasma glucose but differences between controls and metomidate-exposed fish were relatively minor thereafter. Cortisol began to decrease in catfish immediately after the removal of the stress but continued to increase for 15 min in sunshine bass recovering in fresh water and for 5 min in bass recovering in metomidate. Catfish recovering in fresh water had a cortisol elimination rate of -1.28 ng/mL/min compared with -2.45 ng/mL/min for fish recovering in metomidate (P>0.05) while sunshine bass recovering in fresh water had an elimination rate of -6.96 ng/mL/min compared with -4.50 ng/mL/min for fish recovering in metomidate (P>0.05). These data indicate that the rapid decrease of plasma cortisol after removal of the stressor is due to an almost immediate decrease of secretion, tissue uptake and a rapid renal loss due to the absence of a plasma binding protein.

  14. Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

    Science.gov (United States)

    Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

    2016-02-01

    Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.

  15. Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes.

    Science.gov (United States)

    Devi, Sulochana; Markandeya, Yogananda; Maddodi, Nityanand; Dhingra, Anuradha; Vardi, Noga; Balijepalli, Ravi C; Setaluri, Vijayasaradhi

    2013-05-01

    Mutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss of responsiveness of TRPM1 to mGluR6 signaling. Here, we show that human melanocytes express mGluR6, and treatment of melanocytes with L-AP4, a type III mGluR-selective agonist, enhances Ca(2+) uptake. Knockdown of TRPM1 or mGluR6 by shRNA abolished L-AP4-induced Ca(2+) influx and TRPM1 currents, showing that TRPM1 activity in melanocytes is positively coupled to mGluR6 signaling. Gαo protein is absent in melanocytes. However, forced expression of Gαo restored negative coupling of TRPM1 to mGluR6 signaling, but treatment with pertussis toxin, an inhibitor of Gi /Go proteins, did not affect basal or mGluR6-induced Ca(2+) uptake. Additionally, chronic stimulation of mGluR6 altered melanocyte morphology and increased melanin content. These data suggest differences in coupling of TRPM1 function to mGluR6 signaling explain different cellular responses to glutamate in the retina and the skin.

  16. Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel.

    Science.gov (United States)

    Amodeo, Giuseppe Federico; Scorciapino, Mariano Andrea; Messina, Angela; De Pinto, Vito; Ceccarelli, Matteo

    2014-01-01

    Voltage Dependent Anion-selective Channels (VDACs) are pore-forming proteins located in the outer mitochondrial membrane. They are responsible for the access of ions and energetic metabolites into the inner membrane transport systems. Three VDAC isoforms exist in mammalian, but their specific role is unknown. In this work we have performed extensive (overall ∼5 µs) Molecular Dynamics (MD) simulations of the human VDAC isoforms to detect structural and conformational variations among them, possibly related to specific functional roles of these proteins. Secondary structure analysis of the N-terminal domain shows a high similarity among the three human isoforms of VDAC but with a different plasticity. In particular, the N-terminal domain of the hVDAC1 is characterized by a higher plasticity, with a ∼20% occurrence for the 'unstructured' conformation throughout the folded segment, while hVDAC2, containing a peculiar extension of 11 amino acids at the N-terminal end, presents an additional 310-helical folded portion comprising residues 10' to 3, adhering to the barrel wall. The N-terminal sequences of hVDAC isoforms are predicted to have a low flexibility, with possible consequences in the dynamics of the human VDACs. Clear differences were found between hVDAC1 and hVDAC3 against hVDAC2: a significantly modified dynamics with possible important consequence on the voltage-gating mechanism. Charge distribution inside and at the mouth of the pore is responsible for a different preferential localization of ions with opposite charge and provide a valuable rationale for hVDAC1 and hVDAC3 having a Cl-/K+ selectivity ratio of 1.8, whereas hVDAC2 of 1.4. Our conclusion is that hVDAC isoforms, despite sharing a similar scaffold, have modified working features and a biological work is now requested to give evidence to the described dissimilarities.

  17. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Science.gov (United States)

    Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

    2016-01-01

    The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

  18. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Directory of Open Access Journals (Sweden)

    Yukiko Ihara

    Full Text Available The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG, a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB, which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+ bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg were recorded using a video-electroencephalography (EEG monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

  19. Contemporary open partial nephrectomy is associated with diminished procedure-specific morbidity despite increasing technical challenges: a single institutional experience.

    Science.gov (United States)

    Kava, Bruce R; De Los Santos, Rosely; Ayyathurai, Rajinikanth; Shirodkar, Samir; Manoharan, Murugesan; Leveillee, Raymond; Bird, Vincent; Ciancio, Gaetano; Soloway, Mark S

    2010-08-01

    To review trends in open partial nephrectomy (OPN) at our center, concentrating on patient selection, technique and perioperative complications. A comprehensive database was developed by chart review of consecutive patients undergoing OPN for renal masses at our center. Patient selection, technical modifications, perioperative morbidity, and histopathology were compared in patients undergoing OPN between 1992-1999, 2000-2003, and 2004-2008. Complications were divided into procedure-specific (PSCs) and nonspecific medical complications (NMCs). They were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. One hundred and sixty-three OPNs were performed. Temporal trends identified include: an increase in the mean patient BMI (p = 0.04), an increase in the percentage of patients with central tumors (p analysis [odds ratio 1.067, CI 95% (1.002-1.136); p = 0.031]. Increasingly, OPN is being utilized for a cohort of challenging patients who are overweight and have centrally located tumors. Despite this, the risk of PSCs is low. Patients who are overweight are at increased risk for perioperative NMCs.

  20. Improved ramped bunch train to increase the transformer ratio of a two-channel multimode dielectric wakefield accelerator

    Directory of Open Access Journals (Sweden)

    G. V. Sotnikov

    2011-03-01

    Full Text Available Here we show a possibility of applying the ramped drive bunch train (RBT technique to a two-channel coaxial dielectric wakefield accelerator (CDWA. For numerical research we study a 28 GHz structure with two nested alumina cylindrical shells having these diameters: outer shell, OD=28.1  mm, ID=27  mm; inner shell, OD=6.35  mm, ID=4.0  mm. The structure is to be excited by a train of four annular bunches having energy 14 MeV and axial rms length 1 mm; the total charge of bunches is 200 nC. In the case of equally charged drive bunches, spaced apart by the principal wakefield wavelength 10.67 mm, we obtained transformer ratio T=3.4. If the bunch charge is increasing as the ratio 1∶3∶5∶7 and the bunches are spaced by one and one-half wavelengths, we obtained T=3.8. We found that if the charge ratios are 1.0∶2.4∶3.5∶5.0 and the spaces between the bunches are 2.5, 2.5, and 4.5 wakefield periods, then T increases strongly, T∼20. The RBT also can be used successfully in a high gradient THz CDWA structure. A particle-in-cell simulation shows that the four drive bunches can move without appreciable distortion.

  1. Anion-Channel Blockers Inhibit S-Type Anion Channels and Abscisic Acid Responses in Guard Cells.

    Science.gov (United States)

    Schwartz, A.; Ilan, N.; Schwarz, M.; Scheaffer, J.; Assmann, S. M.; Schroeder, J. I.

    1995-10-01

    The effects of anion-channel blockers on light-mediated stomatal opening, on the potassium dependence of stomatal opening, on stomatal responses to abscisic acid (ABA), and on current through slow anion channels in the plasma membrane of guard cells were investigated. The anion-channel blockers anthracene-9-carboxylic acid (9-AC) and niflumic acid blocked current through slow anion channels of Vicia faba L. guard cells. Both 9-AC and niflumic acid reversed ABA inhibition of stomatal opening in V. faba L. and Commelina communis L. The anion-channel blocker probenecid also abolished ABA inhibition of stomatal opening in both species. Additional tests of 9-AC effects on stomatal aperture in Commelina revealed that application of this anion-channel blocker allowed wide stomatal opening under low (1 mM) KCI conditions and increased the rate of stomatal opening under both low and high (100 mM) KCI conditions. These results indicate that anion channels can function as a negative regulator of stomatal opening, presumably by allowing anion efflux and depolarization, which prohibits ion up-take in guard cells. Furthermore, 9-AC prevented ABA induction of stomatal closure. A model in which ABA activation of anion channels contributes a rate-limiting mechanism during ABA-induced stomatal closure and inhibition of stomatal opening is discussed.

  2. Open public spaces and street furniture: the potential for increased use of photovoltaics in the built environment

    Energy Technology Data Exchange (ETDEWEB)

    Abbate-Gardner, C. [Officine di Architettura, Rome (Italy)

    1996-07-01

    The trend toward industrializing architectural components, the increasing complexity and multifunctional purpose of buildings and the concern for the CO{sub 2} emissions common to our cities is pushing design research to experiment with new environmentally friendly construction technology. Current experiments in integrating photovoltaic (PV) systems in buildings and the built environment have already been proven to offer numerous advantages. This article focuses on the notable flexibility and adaptability of PV integration in urban structures due to the features of its industrial components. To illustrate this point, I should like to offer a brief overview of some selected examples of the use of PV in public open spaces to demonstrate that it is possible to achieve a positive integration with its environmental context, while enhancing the architectural quality of the PV material and respecting its technological efficiency. (author)

  3. "Eyes Open - Eyes Closed" EEG/fMRI data set including dedicated "Carbon Wire Loop" motion detection channels.

    Science.gov (United States)

    van der Meer, Johan; Pampel, André; van Someren, Eus; Ramautar, Jennifer; van der Werf, Ysbrand; Gomez-Herrero, German; Lepsien, Jöran; Hellrung, Lydia; Hinrichs, Hermann; Möller, Harald; Walter, Martin

    2016-06-01

    This data set contains electroencephalography (EEG) data as well as simultaneous EEG with functional magnetic resonance imaging (EEG/fMRI) data. During EEG/fMRI, the EEG cap was outfitted with a hardware-based add-on consisting of carbon-wire loops (CWL). These yielded six extra׳CWL׳ signals related to Faraday induction of these loops in the main magnetic field "Measurement and reduction of motion and ballistocardiogram artefacts from simultaneous EEG and fMRI recordings" (Masterton et al., 2007) [1]. In this data set, the CWL data make it possible to do a direct regression approach to deal with the BCG and specifically He artifact. The CWL-EEG/fMRI data in this paper has been recorded on two MRI scanners with different Helium pump systems (4 subjects on a 3 T TIM Trio and 4 subjects on a 3T VERIO). Separate EEG/fMRI data sets have been recorded for the helium pump ON as well as the helium pump OFF conditions. The EEG-only data (same subjects) has been recorded for a motion artifact-free reference EEG signal outside of the scanner. This paper also links to an EEGlab "EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis" (Delorme and Makeig, 2004) [2] plugin to perform a CWL regression approach to deal with the He pump artifact, as published in the main paper "Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections-A validation of a real-time simultaneous EEG/fMRI correction method" (van der Meer et al., 2016) [3].

  4. Boiling Heat Transfer on Porous Surfaces with Vapor Channels

    Institute of Scientific and Technical Information of China (English)

    吴伟; 杜建华; 王补宣

    2002-01-01

    Boiling heat transfer on porous coated surfaces with vapor channels was investigated experimentally to determine the effects of the size and density of the vapor channels on the boiling heat transfer. Observations showed that bubbles escaping from the channels enhanced the heat transfer. Three regimes were identified: liquid flooding, bubbles in the channel and the bottom drying out region. The maximum heat transfer occurred for an optimum vapor channel density and the boiling heat transfer performance was increased if the channels were open to the bottom of the porous coating.

  5. Modulation of BK channels contributes to activity-dependent increase of excitability through MTORC1 activity in CA1 pyramidal cells of mouse hippocampus

    Directory of Open Access Journals (Sweden)

    Steven eSpringer

    2015-01-01

    Full Text Available Memory acquisition and synaptic plasticity are accompanied by changes in the intrinsic excitability of CA1 pyramidal neurons. These activity-dependent changes in excitability are mediated by modulation of intrinsic currents which alters the responsiveness of the cell to synaptic inputs. The afterhyperpolarization, a major contributor to the regulation of neuronal excitability, is reduced in animals that have acquired several types of hippocampus-dependent memory tasks and also following synaptic potentiation by high frequency stimulation. BK channels underlie the fast afterhyperpolarization and contribute to spike repolarization, and this afterhyperpolarization is reduced in animals that successfully acquired trace-eyeblink conditioning. This suggests that BK channel function is activity-dependent, but the mechanisms are unknown. In this study, we found that blockade of BK channels with paxilline (10µM increased spike half-width and instantaneous frequency in response to a +100pA depolarization. In addition, induction of LTP by theta burst stimulation (TBS in CA1 pyramidal neurons reduced BK channel’s contribution to spike repolarization and instantaneous frequency. This result indicates that BK channel activity is decreased following synaptic potentiation. Interestingly, blockade of mammalian target of rapamycin (MTORC1 with rapamycin (400 nM following synaptic potentiation restored BK channel function, suggesting a role for protein translation in signaling events which decreased postsynaptic BK channel activity following synaptic potentiation.

  6. Mechanoprotection by polycystins against apoptosis is mediated through the opening of stretch-activated K(2P) channels

    NARCIS (Netherlands)

    Peyronnet, Rémi; Sharif-Naeini, Reza; Folgering, Joost H A; Arhatte, Malika; Jodar, Martine; El Boustany, Charbel; Gallian, Claire; Tauc, Michel; Duranton, Christophe; Rubera, Isabelle; Lesage, Florian; Pei, York; Peters, Dorien J M; Somlo, Stefan; Sachs, Frederick; Patel, Amanda; Honoré, Eric; Duprat, Fabrice

    2012-01-01

    How renal epithelial cells respond to increased pressure and the link with kidney disease states remain poorly understood. Pkd1 knockout or expression of a PC2 pathogenic mutant, mimicking the autosomal dominant polycystic kidney disease, dramatically enhances mechanical stress-induced tubular apopt

  7. [Potential-dependent Cation Selective Ion Channels Formed by Peroxiredoxin 6 in the Lipid Bilayer].

    Science.gov (United States)

    Grigoriev, P A; Sharapov, M G; Novoselov, V I

    2015-01-01

    The antioxidant enzyme peroxiredoxin 6 forms cation selective ion cluster-type channels in the lipid bilayer. Channel clustering as oligomeric structure consists of three or more subunits--channels with conductance of about 350 pS in the 200 mM KCl. Mean dwell time of the channel's open states decreases with increasing membrane voltage. A possible molecular mechanism of the observed potential-dependent inactivation of the channel cluster is discussed.

  8. Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana [Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla (Mexico); Sandoval, Alejandro [School of Medicine FES Iztacala, National Autonomous University of Mexico (UNAM), Tlalnepantla (Mexico); Monroy, Alma; Felix, Ricardo [Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City (Mexico); Monjaraz, Eduardo, E-mail: emguzman@siu.buap.mx [Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla (Mexico)

    2010-12-03

    Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating the cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.

  9. Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts

    Science.gov (United States)

    Fedorov, Vadim V.; Glukhov, Alexey V.; Ambrosi, Christina M.; Kostecki, Geran; Chang, Roger; Janks, Deborah; Schuessler, Richard B.; Moazami, Nader; Nichols, Colin G.; Efimov, Igor R.

    2011-01-01

    INTRODUCTION This study compared the effects of ATP-regulated potassium channel (KATP) openers, diazoxide and pinacidil, on diseased and normal human atria and ventricles. METHODS We optically mapped the endocardium of coronary-perfused right (n=11) or left (n=2) posterior atrial-ventricular free wall preparations from human hearts with congestive heart failure (CHF, n=8) and non-failing human hearts without (NF, n=3) or with (INF, n=2) infarction. We also analyzed the mRNA expression of the KATP targets Kir6.1, Kir6.2, SUR1, and SUR2 in the left atria and ventricles of NF (n=8) and CHF (n=4) hearts. RESULTS In both CHF and INF hearts, diazoxide significantly decreased action potential durations (APDs) in atria (by −21±3% and −27±13%, p<0.01) and ventricles (by −28±7% and −28±4%, p<0.01). Diazoxide did not change APD (0±5%) in NF atria. Pinacidil significantly decreased APDs in both atria (−46 to - 80%, p<0.01) and ventricles (−65 to −93%, p<0.01) in all hearts studied. The effect of pinacidil on APD was significantly higher than that of diazoxide in both atria and ventricles of all groups (p<0.05). During pinacidil perfusion, burst pacing induced flutter/fibrillation in all atrial and ventricular preparations with dominant frequencies of 14.4±6.1 Hz and 17.5 ±5.1 Hz, respectively. Glibenclamide (10 μM) terminated these arrhythmias and restored APDs to control values. Relative mRNA expression levels of KATP targets were correlated to functional observations. CONCLUSION Remodeling in response to CHF and/or previous infarct potentiated diazoxide-induced APD shortening. The activation of atrial and ventricular KATP channels enhances arrhythmogenicity, suggesting that such activation may contribute to reentrant arrhythmias in ischemic hearts. PMID:21586291

  10. Cellular Entry of the Diphtheria Toxin Does Not Require the Formation of the Open-Channel State by Its Translocation Domain

    Directory of Open Access Journals (Sweden)

    Alexey S. Ladokhin

    2017-09-01

    Full Text Available Cellular entry of diphtheria toxin is a multistage process involving receptor targeting, endocytosis, and translocation of the catalytic domain across the endosomal membrane into the cytosol. The latter is ensured by the translocation (T domain of the toxin, capable of undergoing conformational refolding and membrane insertion in response to the acidification of the endosomal environment. While numerous now classical studies have demonstrated the formation of an ion-conducting conformation—the Open-Channel State (OCS—as the final step of the refolding pathway, it remains unclear whether this channel constitutes an in vivo translocation pathway or is a byproduct of the translocation. To address this question, we measure functional activity of known OCS-blocking mutants with H-to-Q replacements of C-terminal histidines of the T-domain. We also test the ability of these mutants to translocate their own N-terminus across lipid bilayers of model vesicles. The results of both experiments indicate that translocation activity does not correlate with previously published OCS activity. Finally, we determined the topology of TH5 helix in membrane-inserted T-domain using W281 fluorescence and its depth-dependent quenching by brominated lipids. Our results indicate that while TH5 becomes a transbilayer helix in a wild-type protein, it fails to insert in the case of the OCS-blocking mutant H322Q. We conclude that the formation of the OCS is not necessary for the functional translocation by the T-domain, at least in the histidine-replacement mutants, suggesting that the OCS is unlikely to constitute a translocation pathway for the cellular entry of diphtheria toxin in vivo.

  11. Demagnetization Analysis in Excel (DAIE) - An open source workbook in Excel for viewing and analyzing demagnetization data from paleomagnetic discrete samples and u-channels

    Science.gov (United States)

    Sagnotti, Leonardo

    2013-04-01

    Modern rock magnetometers and stepwise demagnetization procedures result in the production of large datasets, which need a versatile and fast software for their display and analysis. Various software packages for paleomagnetic analyses have been recently developed to overcome the problems linked to the limited capability and the loss of operability of early codes written in obsolete computer languages and/or platforms, not compatible with modern 64 bit processors. The Demagnetization Analysis in Excel (DAIE) workbook is a new software that has been designed to make the analysis of demagnetization data easy and accessible on an application (Microsoft Excel) widely diffused and available on both the Microsoft Windows and Mac OS X operating systems. The widespread diffusion of Excel should guarantee a long term working life, since compatibility and functionality of current Excel files should be most likely maintained during the development of new processors and operating systems. DAIE is designed for viewing and analyzing stepwise demagnetization data of both discrete and u-channel samples. DAIE consists of a single file and has an open modular structure organized in 10 distinct worksheets. The standard demagnetization diagrams and various parameters of common use are shown on the same worksheet including selectable parameters and user's choices. The remanence characteristic components may be computed by principal component analysis (PCA) on a selected interval of demagnetization steps. Saving of the PCA data can be done both sample by sample, or in automatic by applying the selected choices to all the samples included in the file. The DAIE open structure allows easy personalization, development and improvement. The workbook has the following features which may be valuable for various users: - Operability in nearly all the computers and platforms; - Easy inputs of demagnetization data by "copy and paste" from ASCII files; - Easy export of computed parameters and

  12. Voltage-gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity and Invasion Via Persistent MAPK Signaling

    Science.gov (United States)

    House, Carrie D.; Wang, Bi-Dar; Ceniccola, Kristin; Williams, Russell; Simaan, May; Olender, Jacqueline; Patel, Vyomesh; Baptista-Hon, Daniel T.; Annunziata, Christina M.; Silvio Gutkind, J.; Hales, Tim G.; Lee, Norman H.

    2015-06-01

    Functional expression of voltage-gated Na+ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using pharmacological inhibitors/activators and siRNA-mediated gene knockdowns, we correlated channel activity with Rap1-dependent persistent MAPK activation in the SW620 human colon cancer cell line. We further demonstrated that VGSC activity induces downstream changes in invasion-related gene expression via a PKA/ERK/c-JUN/ELK-1/ETS-1 transcriptional pathway. This is the first study illustrating a molecular mechanism linking functional activity of VGSCs to transcriptional activation of invasion-related genes.

  13. The novel ATP-sensitive potassium channel opener iptakalim prevents insulin resistance associated with hypertension via restoring endothelial function

    Institute of Scientific and Technical Information of China (English)

    Yu WANG; Fu-hu ZENG; Chao-liang LONG; Zhi-yuan PAN; Wen-yu CUI; Ru-huan WANG; Guo-shu LIU; Hai WANG

    2011-01-01

    To investigate the effects of iptakalim on endothelial dysfunction induced by insulin resistance (IR) and to determine whether iptakalim improved IR associated with hypertension in fructose-fed rats (FFRs) and spontaneously hypertensive rats (SHRs).Methods:Human umbilical vein endothelial cells (HUVECs) were used for in vitro study.The levels of endothelial vasoactive mediators and eNOS protein expression were determined using radioimmunoassays,ELISAs,colorimetric assays or Western blotting.Sprague-Dawley rats were fed with a high-fructose diet.In both FFRs and SHRs,tail-cuff method was used to measure systolic blood pressure (SBP),and hyperinsulinemic-euglycemic clamp was used to evaluate IR states.Results:(1) Cultured HUVECs incubated with the PI3-kinase inhibitor wortmannin (50 nmol/L) and insulin (100 nmol/L) induced endothelial dysfunction characterized by significantly reduced release of NO and expression of eNOS protein,and significantly increased production of ET-1.Pretreatment with iptakalim (0.1-10 μmol/L) could prevent the endothelial dysfunction.(2) In FFRs,the levels of SBP,fasting plasma glucose and insulin were significantly elevated,whereas the glucose infusion rate (GIR) and insulin sensitive index (ISI) were significantly decreased,and the endothelium-dependent vascular relaxation response to ACh was impaired.These changes could be prevented by oral administration of iptakalim (1,3,or 9 mg-kg-1-d-1,for 4 weeks).The imbalance between serum NO and ET-1 was also ameliorated by iptakalim.(3) In 2-4 month-old SHRs (IR was established at the age of 4 months),oral administration of iptakalim (1,3,or 9 mg.kg-1.d-1,for 8 weeks) significantly ameliorated hypertension and increased the GIR to the normal level.Conclusion:These results demonstrate that iptakalim could protect against IR-induced endothelial dysfunction,and ameliorate IR associated with hypertension,possibly via restoring the balance between NO and ET-1 signaling.

  14. [Biochemical mechanisms of the cardioprotective effect of the K(ATP) channels opener flocalin (medicinal form) in ischemia-reperfusion of myocardium].

    Science.gov (United States)

    Strutyns'kyĭ, R B; Kotsiuruba, A V; Rovenets', R A; Strutyns'ka, N A; Iagupols'kyĭ, Iu L; Sagach, V F; Moĭbenko, O O

    2013-01-01

    In experiments on the anaesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min) of myocardium it was investigated changes of biochemical processes in arterial blood at intragastric introduction of medicinal form (tablets) of flocalin (the fluorine-containing opener of ATP-sensitive potassium channels) in a dose 2,2 mg/kg. The data analysis allowed to define a few possible mechanisms of cardioprotective action offlocalin, which prevented the opening of a mitochondrial permeability transition pore (MPTP) and inhibition of apoptosis induced by it. They consist, from one side, in activating of the constitutive de novo biosynthesis of nitric oxide by cNOS, from other side, in suppression of inducible nitric oxide de novo synthesis by iNOS in such way to prevent the formation of toxic peroxynitrite by co-operation of surplus nitric oxide with superoxide anion, thereby limits the generation of toxic active forms of nitrogen (*NO2) and oxygen (*OH). The first effect of flocalin takes place due to limitation the degradation of L-arginine by arginase which keeps substrat for cNOS, second--due to the inhibition of superoxide generation, in particular, by xanthine oxidase (marker uric acid), lipoxigenase (marker LTC4) and cyclooxygenase (marker TxB2). Because LTC4 have coronaroconstrictory, arrhythmogenic and chemoattractory properties in the conditions of myocardial ischemia, inhibition of its production both with superoxide generation (markers H2O2 and diene conjugates) may be the another mechanisms of flocalin's cardioprotection. Powerful antiischemic action of flocalin (marker nitrite anion) as the mechanisms of cardioprotection is possible as well as inhibition of ATP and GTP degradation (marker hypoxanthine+xanthine+inosine levels in the blood) and, possibly, stimulation ofhaem degradation by haem oxygenase (markers total bilirubin and Fe in the blood). Diminishing content of free arachidonic acid in arterial blood can testify

  15. Incorporating a trend analysis of large flow perturbations into stochastic modeling of particle transport in open channel flow

    Science.gov (United States)

    Tsai, Christina W.; Lin, Emily Y.; Hung, Serena Y.

    2016-10-01

    In extreme flow conditions, both the flow carrying capacity and movement of particles may abruptly change from those associated with regular flows. This study investigates movement of sediment particles in response to extreme flow events using a Lagrangian stochastic jump diffusion particle tracking model (SJD-PTM). The study attempts to investigate the frequency change of extreme flow event occurrences and its impact on suspended sediment particle movement. Using the concept of logistic regression, the trend magnitude of extreme flow events can be used as an input of the proposed stochastic jump diffusion particle tracking model with Logistic regression (SJ-PTM_LR) to account for the potential effects of environmental change. The predicted frequency change of extreme flows from available data in the Chijiawan region in central Taiwan is illustrated in this study. Both ensemble mean and variance of particle trajectory can be quantified under such predicted frequency trend change of extreme flow occurrences via simulations of SJ-PTM_LR. Results show that particle movement uncertainty may undergo a significant increase by taking the effect of the predicted flow frequency trend into consideration. Such probabilistic outcome provides a valuable means for assessing the probability of failure (i.e., risk) resulting from sedimentation processes.

  16. Evaluation of Gas Retention in Waste Simulants: Intermediate-Scale Column and Open-Channel-Depth Tests

    Energy Technology Data Exchange (ETDEWEB)

    Powell, Michael R.; Gauglitz, Phillip A.; Denslow, Kayte M.; Fischer, Christopher M.; Heldebrant, David J.; Prowant, Matthew S.; Sande, Susan; Davis, James M.; Telander, Monty R.

    2014-02-14

    Gas generation in Hanford’s radioactive waste storage tanks can lead to gas accumulation within the layer of settled solids (sludge) at the tank bottom. The gas, which may be hazardous and/or flammable, is formed principally by radiation-driven chemical reactions. Accumulation of these gases within the sludge increases the sludge-layer volume, which decreases the available tank volume for waste storage. Further, accumulation of large amounts of gas in the sludge can potentially result in a relatively rapid release of the accumulated gas if the sludge-layer density is reduced to less than that of the overlying sludge or that of the supernatant liquid. The potential for rapid release of large amounts of hazardous and/or flammable gases is a safety hazard that needs to be managed. Accordingly, a thorough understanding is needed of the circumstances that can lead to problematic gas accumulation in sludge layers. The Deep-Sludge Gas Release Event Project (DSGREP) is tasked with developing an improved understanding of these gas release events.

  17. Angiotensin II increases nerve-evoked contractions in mouse tail artery by a T-type Ca(2+) channel-dependent mechanism.

    Science.gov (United States)

    Reardon, Trent F; Callaghan, Brid P; Brock, James A

    2015-08-15

    Angiotensin II (Ang II) increases sympathetic nerve-evoked contractions of arterial vessels. Here the mechanisms underlying this effect were investigated in mouse tail artery. Isometrically mounted segments of mouse distal tail artery were used to investigate the effects of endothelium denudation, blocking Ca(2+) channels and inhibiting superoxide signalling on Ang II-induced facilitation of nerve-evoked contractions. In addition, in situ amperometry was used to assess effects of Ang II on noradrenaline release. Ang II (0.1-1nM) increased nerve-evoked contractions but did not change noradrenaline release. Losartan (Ang II type 1 receptor antagonist), but not PD 123319 (Ang II type 2 receptor antagonist), blocked the facilitatory effect of Ang II on nerve-evoked contractions. Ang II increased vascular muscle reactivity to phenylephrine and UK-14304 (α1- and α2-adrenoceptor agonists, respectively). Endothelial denudation increased nerve-evoked contractions and reduced the facilitatory effect of Ang II on these responses. Efonidipine (L- and T-type Ca(2+) channel blocker) and NNC 55-0396 (T-type Ca(2+) channel blocker) also attenuated this effect of Ang II, while nifedipine (L-type Ca(2+) channel blocker) did not. Blockers of superoxide generation/signalling did not change the facilitatory effect of Ang II on nerve-evoked contractions. The findings indicate that Ang II increases the contribution of T-type Ca(2+) channels to neural activation of the vascular muscle. In addition, Ang II appears to reduce the inhibitory influence of the endothelium on nerve-evoked contractions.

  18. Petrological evidence for non-linear increase of magmatic intrusion rates before eruption at open vent mafic volcanoe

    Science.gov (United States)

    Ruth, D. C. S.; Costa Rodriguez, F.

    2015-12-01

    The most active volcanoes on earth erupt in a yearly to decadal time scales, typically erupt mafic magmas and are open-vent systems with prominent degassing plumes (e.g. Mayon, Arenal, Llaima, Etna). Here we investigate the plumbing systems, dynamics, and processes that drive eruptions at these systems. These are key questions for improving hazard evaluation, and better understanding the unrest associated with these types of volcanoes. The petrology and geochemistry from six historical eruptions (1947-2006) of Mayon volcano (Philippines) shows that all lavas are basaltic andesite with phenocrysts of plagioclase + orthopyroxene (Opx) + clinopyroxene. Opx crystals show a variety of compositions and zoning patterns (reverse, normal or complex) with Mg# (= 100 *Mg/[Mg+Fe]) varying from 67 to 81. The simplest interpretation is that the low Mg# parts of the crystals resided on an upper crustal and crystal rich reservoir that was intruded by more primitive magmas from which the high Mg# parts of the crystals grew. Modelling Mg-Fe diffusion in Opx shows that times since magma injection and eruption range from a few days up to 3.5 years in all of the investigated eruptions. The longest diffusion times are shorter than the repose times between the eruptions, which implies that crystal recycling between eruptive events is negligible. This is a surprising result that shows that for each eruption a different part of the evolved crystal-rich plumbing system is activated. This can be due to random intrusion location or an irreversibility of the plumbing system that prevents multiple eruptions from the same crystal-rich part. Moreover, we find that the number of intrusions markedly increases before each eruption in a non-linear manner. Such an increased rate of intrusions with time might reflect non-linear rheological properties of the crystal-rich system, of the enclosing rocks, or the non-linear evolution of crystal-melt reaction-dissolution fronts during magma intrusions.

  19. Increased tolerance to stress in cardiac expressed gain-of-function of adenosine triphosphate-sensitive potassium channel subunit Kir6.1.

    Science.gov (United States)

    Henn, Matthew C; Janjua, M Burhan; Zhang, Haixia; Kanter, Evelyn M; Makepeace, Carol M; Schuessler, Richard B; Nichols, Colin G; Lawton, Jennifer S

    2016-12-01

    The adenosine triphosphate-sensitive potassium (KATP) channel opener diazoxide (DZX) prevents myocyte volume derangement and reduced contractility secondary to stress. KATP channels are composed of pore-forming (Kir6.1 or Kir6.2) and regulatory (sulfonylurea receptor, SUR1 or SUR2) subunits. Gain of function (GOF) of Kir6.1 subunits has been implicated in cardiac pathology in Cantu syndrome in humans (cardiomegaly, lymphedema, and pericardial effusions). We hypothesized that GOF of Kir6.1 subunits would result in altered myocyte response to stress. Isolated cardiac myocytes from wild type (WT) and transgenic Kir6.1GOF mice were exposed to Tyrode's physiologic solution for 20 min, test solution (Tyrode's or stress [hyperkalemic cardioplegia {CPG, known myocyte stress}] +/- KATP channel opener DZX), followed by Tyrode's for 20 min. Myocyte volume and contractility were measured and compared. WT myocytes demonstrated significant swelling in response to stress, but significantly less swelling was seen in Kir6.1GOF myocytes. DZX prevented swelling secondary to CPG in WT but resulted in a nonsignificant reduction in swelling in Kir6.1GOF myocytes. Both WT and Kir6.1GOF myocytes demonstrated a reduction in contractility during stress, although this was only significant in Kir6.1GOF myocytes. DZX was not associated with an improvement in contractility in Kir6.1GOF myocytes following stress. Similar to previous results in Kir6.1(-/-) myocytes, Kir6.1GOF myocytes demonstrate resistance (less volume derangement) to stress of cardioplegia. Understanding the role of Kir6.1 in myocyte response to stress may aid in the treatment of patients with Cantu syndrome and warrants further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The Five 'R's' for Developing Trusted Software Frameworks to increase confidence in, and maximise reuse of, Open Source Software.

    Science.gov (United States)

    Fraser, Ryan; Gross, Lutz; Wyborn, Lesley; Evans, Ben; Klump, Jens

    2015-04-01

    Recent investments in HPC, cloud and Petascale data stores, have dramatically increased the scale and resolution that earth science challenges can now be tackled. These new infrastructures are highly parallelised and to fully utilise them and access the large volumes of earth science data now available, a new approach to software stack engineering needs to be developed. The size, complexity and cost of the new infrastructures mean any software deployed has to be reliable, trusted and reusable. Increasingly software is available via open source repositories, but these usually only enable code to be discovered and downloaded. As a user it is hard for a scientist to judge the suitability and quality of individual codes: rarely is there information on how and where codes can be run, what the critical dependencies are, and in particular, on the version requirements and licensing of the underlying software stack. A trusted software framework is proposed to enable reliable software to be discovered, accessed and then deployed on multiple hardware environments. More specifically, this framework will enable those who generate the software, and those who fund the development of software, to gain credit for the effort, IP, time and dollars spent, and facilitate quantification of the impact of individual codes. For scientific users, the framework delivers reviewed and benchmarked scientific software with mechanisms to reproduce results. The trusted framework will have five separate, but connected components: Register, Review, Reference, Run, and Repeat. 1) The Register component will facilitate discovery of relevant software from multiple open source code repositories. The registration process of the code should include information about licensing, hardware environments it can be run on, define appropriate validation (testing) procedures and list the critical dependencies. 2) The Review component is targeting on the verification of the software typically against a set of

  1. Epilepsy-Related Slack Channel Mutants Lead to Channel Over-Activity by Two Different Mechanisms

    Directory of Open Access Journals (Sweden)

    Qiong-Yao Tang

    2016-01-01

    Full Text Available Twelve sodium-activated potassium channel (KCNT1, Slack genetic mutants have been identified from severe early-onset epilepsy patients. The changes in biophysical properties of these mutants and the underlying mechanisms causing disease remain elusive. Here, we report that seven of the 12 mutations increase, whereas one mutation decreases, the channel’s sodium sensitivity. Two of the mutants exhibit channel over-activity only when the intracellular Na+ ([Na+]i concentration is ∼80 mM. In contrast, single-channel data reveal that all 12 mutants increase the maximal open probability (Po. We conclude that these mutant channels lead to channel over-activity predominantly by increasing the ability of sodium binding to activate the channel, which is indicated by its maximal Po. The sodium sensitivity of these epilepsy causing mutants probably determines the [Na+]i concentration at which these mutants exert their pathological effects.

  2. GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease.

    Directory of Open Access Journals (Sweden)

    Yutao Liu

    Full Text Available DNA copy number variants (CNVs have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC. This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1. (p = 0.017, fisher's exact test. It was validated with array comparative genomic hybridization (arrayCGH and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio = 3.5, 95% CI -1.1-12.0. Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4. Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.

  3. A Methodology for Measuring Voice Quality Using PESQ and Interactive Voice Response in the GSM Channel Designed by OpenBTS

    Directory of Open Access Journals (Sweden)

    Pavol Partila

    2013-01-01

    Full Text Available This article discusses a methodology for rating the quality of mobile calls. Majority telecommunications service from the perspective of the whole world is using mobile telephony networks. One of the problems affecting this service and its quality are landscape barriers, which prevent the spread signal. Price and complex construction of classic BTS does not allow their dense distribution. In such cases, one solution is to use OpenBTS technology. Design of OpenBTS is more available, so it can be applied to much more places and more complex points. Purpose of this measurement is a model for effective stations deployment, due to shape and distribution of local barriers that reduce signal power, and thus the quality of speech. GSM access point for our mobile terminals is OpenBTS USRP N210 station. The PESQ method for evaluating of speech quality is compared with the subjective evaluation, which provides Asterisk PBX with IVR call back. Measurement method was taken into account the call quality depending on terminal position. The measured results and its processing bring knowledge to use this technology for more complicated locations with degraded signal level and increases the quality of voice services in telecommunications.

  4. The amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) opens large-conductance Ca2+-activated K+ channels and relaxes vascular smooth muscle.

    Science.gov (United States)

    Gessner, Guido; Heller, Regine; Hoshi, Toshinori; Heinemann, Stefan H

    2007-01-26

    2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) has been developed to retain the antiarrhythmic properties of the parent molecule amiodarone but to eliminate its undesired side effects. In patch-clamp experiments, KB130015 activated large-conductance, Ca2+-activated BK(Ca) channels formed by hSlo1 (alpha) subunits in HEK 293 cells. Channels were reversibly activated by shifting the open-probability/voltage (P(o)/V) relationship by about -60 mV in 3 muM intracellular free Ca2+ ([Ca2+]in). No effect on the single-channel conductance was observed. KB130015-mediated activation of BK(Ca) channels was half-maximal at 20 microM with a Hill coefficient of 2.8. BK(Ca) activation by KB130015 did not require the presence of Ca2+ and still occurred with saturating (100 microM) [Ca2+]in. Effects of the prototypic BK(Ca) activator NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one) and those of KB130015 were not additive suggesting that both activators may at least partially share a common mechanism of action. KB130015-mediated activation was observed also for BK(Ca) channels from insects and for human BK(Ca) channels with already profoundly left-shifted voltage-dependence. In contrast, human intermediate conductance Ca2+-activated channels were inhibited by KB130015. Using segments of porcine pulmonary arteries, KB130015 induced endothelium-independent vasorelaxation, half-maximal at 43 microM KB130015. Relaxation was inhibited by 1 mM tetraethylammonium, suggesting that KB130015 can activate vascular smooth muscle type BK(Ca) channels under physiological conditions. Interestingly, the shift in the P(o)/V relationship was considerably stronger (-90 mV in 3 microM [Ca2+]in) for BK(Ca) channels containing Slo-beta1 subunits. Thus, KB130015 belongs to a novel class of BK(Ca) channel openers that exert an effect depending on the subunit composition of the channel complex.

  5. Full Equations (FEQ) model for the solution of the full, dynamic equations of motion for one-dimensional unsteady flow in open channels and through control structures

    Science.gov (United States)

    Franz, Delbert D.; Melching, Charles S.

    1997-01-01

    The Full EQuations (FEQ) model is a computer program for solution of the full, dynamic equations of motion for one-dimensional unsteady flow in open channels and through control structures. A stream system that is simulated by application of FEQ is subdivided into stream reaches (branches), parts of the stream system for which complete information on flow and depth are not required (dummy branches), and level-pool reservoirs. These components are connected by special features; that is, hydraulic control structures, including junctions, bridges, culverts, dams, waterfalls, spillways, weirs, side weirs, and pumps. The principles of conservation of mass and conservation of momentum are used to calculate the flow and depth throughout the stream system resulting from known initial and boundary conditions by means of an implicit finite-difference approximation at fixed points (computational nodes). The hydraulic characteristics of (1) branches including top width, area, first moment of area with respect to the water surface, conveyance, and flux coefficients and (2) special features (relations between flow and headwater and (or) tail-water elevations, including the operation of variable-geometry structures) are stored in function tables calculated in the companion program, Full EQuations UTiLities (FEQUTL). Function tables containing other information used in unsteady-flow simulation (boundary conditions, tributary inflows or outflows, gate settings, correction factors, characteristics of dummy branches and level-pool reservoirs, and wind speed and direction) are prepared by the user as detailed in this report. In the iterative solution scheme for flow and depth throughout the stream system, an interpolation of the function tables corresponding to the computational nodes throughout the stream system is done in the model. FEQ can be applied in the simulation of a wide range of stream configurations (including loops), lateral-inflow conditions, and special features. The

  6. Evaporation from open microchannel grooves.

    Science.gov (United States)

    Kachel, Sibylle; Zhou, Ying; Scharfer, Philip; Vrančić, Christian; Petrich, Wolfgang; Schabel, Wilhelm

    2014-02-21

    The evaporation of water from open u-shaped microchannel grooves was investigated with particular emphasis on the roles of channel width and air flow conditions. Given the small dimensions of the microchannels, all measurements were conducted in a range where convection and diffusion are of equal importance and known correlations for the calculation of mass transfer coefficients cannot be applied. The evaporation rates were measured using a new optical method and a gravimetric method. Both measurement methods yielded mass transfer coefficients that are in agreement with each other. The observed relation between mass transfer coefficient, air velocity and channel width vastly differs from the predictions obtained from macroscopic structures. With respect to diagnostic devices we conclude that analyte concentration in an open microchannel groove strongly increases even within short times due to the evaporation process and we show that wider channels are more favourable in terms of minimizing the relative evaporation rate.

  7. Maximum opening of the mouth by mouth prop during dental procedures increases the risk of upper airway constriction

    Directory of Open Access Journals (Sweden)

    Hiroshi Ito

    2010-05-01

    Full Text Available Hiroshi Ito1, Hiroyoshi Kawaai1, Shinya Yamazaki1, Yosuke Suzuki21Division of Systemic Management, Department of Oral Function, 2Division of Radiology and Diagnosis, Department of Medical Sciences, Ohu University, Post Graduate School of Dentistry, Koriyama City, Fukushima Prefecture, JapanAbstract: From a retrospective evaluation of data on accidents and deaths during dental procedures, it has been shown that several patients who refused dental treatment died of asphyxia during dental procedures. We speculated that forcible maximum opening of the mouth by using a mouth prop triggers this asphyxia by affecting the upper airway. Therefore, we assessed the morphological changes of the upper airway following maximal opening of the mouth. In 13 healthy adult volunteers, the sagittal diameter of the upper airway on lateral cephalogram was measured between the two conditions; closed mouth and maximally open mouth. The dyspnea in each state was evaluated by a visual analog scale. In one subject, a computed tomograph (CT was taken to assess the three-dimensional changes in the upper airway. A significant difference was detected in the mean sagittal diameter of the upper airway following use of the prop (closed mouth: 18.5 ± 3.8 mm, maximally open mouth: 10.4 ± 3.0 mm. All subjects indicated upper airway constriction and significant dyspnea when their mouth was maximally open. Although a CT scan indicated upper airway constriction when the mouth was maximally open, muscular compensation was admitted. Our results further indicate that the maximal opening of the mouth narrows the upper airway diameter and leads to dyspnea. The use of a prop for the patient who has communication problems or poor neuromuscular function can lead to asphyxia. When the prop is used for patient refusal in dentistry, the respiratory condition should be monitored strictly, and it should be kept in mind that the “sniffing position” is effective for avoiding upper airway

  8. The analgesic effect of dipyrone in peripheral tissue involves two different mechanisms: neuronal K(ATP) channel opening and CB(1) receptor activation.

    Science.gov (United States)

    dos Santos, Gilson Gonçalves; Dias, Elayne Vieira; Teixeira, Juliana Maia; Athie, Maria Carolina Pedro; Bonet, Ivan José Magayewski; Tambeli, Cláudia Herrera; Parada, Carlos Amilcar

    2014-10-15

    Dipyrone (metamizole) is an analgesic pro-drug used to control moderate pain. It is metabolized in two major bioactive metabolites: 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The aim of this study was to investigate the participation of peripheral CB1 and CB2 cannabinoid receptors activation in the anti-hyperalgesic effect of dipyrone, 4-MAA or 4-AA. PGE2 (100ng/50µL/paw) was locally administered in the hindpaw of male Wistar rats, and the mechanical nociceptive threshold was quantified by electronic von Frey test, before and 3h after its injection. Dipyrone, 4-MAA or 4-AA was administered 30min before the von Frey test. The selective CB1 receptor antagonist AM251, CB2 receptor antagonist AM630, cGMP inhibitor ODQ or KATP channel blocker glibenclamide were administered 30min before dipyrone, 4-MAA or 4-AA. The antisense-ODN against CB1 receptor expression was intrathecally administered once a day during four consecutive days. PGE2-induced mechanical hyperalgesia was inhibited by dipyrone, 4-MAA, and 4-AA in a dose-response manner. AM251 or ODN anti-sense against neuronal CB1 receptor, but not AM630, reversed the anti-hyperalgesic effect mediated by 4-AA, but not by dipyrone or 4-MAA. On the other hand, the anti-hyperalgesic effect of dipyrone or 4-MAA was reversed by glibenclamide or ODQ. These results suggest that the activation of neuronal CB1, but not CB2 receptor, in peripheral tissue is involved in the anti-hyperalgesic effect of 4-aminoantipyrine. In addition, 4-methylaminoantipyrine mediates the anti-hyperalgesic effect by cGMP activation and KATP opening. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Experimental investigations and numerical simulations for an open channel flow of a weak elastic polymer solution around a T-profile

    Energy Technology Data Exchange (ETDEWEB)

    Balan, C.; Neagoe, A.; Nistoran, D. [Hydraulics and Hydraulic Machinery Department - REOROM Group, University ' ' Politehnica' ' of Bucharest, Splaiul Independentei 313, 79590, Bucharest (Romania); Legat, V. [University of Louvain-la-Neuve - Center for Systems Engineering Applied Mechanics (CESAME), Batiment Euler, Av. Georges Lemaitre 4, 1348, Louvain-la-Neuve (Belgium)

    2004-03-01

    The present paper is concerned with experimental and numerical investigations of planar complex flows of ''weak'' elastic polymer solutions (whose concentration are below the critical overlap concentration), characterised by small relaxation times ({lambda}<0.1 s) and almost constant shear viscosities for small and medium shear rates. The main aim of the study is to detect to what extent a very small amount of elasticity present in a viscous fluid can influence its behaviour in complex flows, without introducing major modifications of classical rheological tests. The samples are polymer solutions of low PIB molecular weight dissolved in highly viscous Newtonian mineral oil. The analysed motion is steady, and takes place in an open channel around a ''T'' profile. Maximum values of the characteristic parameters for the experiments, the Reynolds and Weissenberg numbers, were 45 and 0.1, respectively. The experiments show a decrease of the wake length downstream the profile for weak elastic solutions in comparison to the Newtonian solvent. Actually, the same wake length as in the Newtonian case was obtained for tested polymer solutions, but at higher Re numbers. Numerical simulations using the Giesekus model predict the same behaviour and are consistent with experiments from both qualitative and quantitative point of views. The results of research conclude that, even in small amounts, the presence of elasticity in pure viscous liquids induces quantitative changes from Newtonian flow in complex dominant elongational flows, at elongational rates for which the sudden thickening of extensional viscosity is remarkable. The study is important, since it should enable better understanding and modelling of viscoelastic flows that involve dilute polymer solutions, or fluids with similar rheology; biofluid mechanics being one area of application of this research. Corroboration of experimental flow visualization with numerical simulation is

  10. Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

    Directory of Open Access Journals (Sweden)

    Jonathan Maiangwa

    2017-05-01

    Full Text Available The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent

  11. Shaker-type Kv1 channel blockers increase the peristaltic activity of guinea-pig ileum by stimulating acetylcholine and tachykinins release by the enteric nervous system.

    Science.gov (United States)

    Vianna-Jorge, Rosane; Oliveira, Cyntia F; Garcia, Maria L; Kaczorowski, Gregory J; Suarez-Kurtz, Guilherme

    2003-01-01

    1 A constant intraluminal pressure system was used to evaluate the effects of Kv1 channel blockers on the peristaltic activity of guinea-pig ileum. 2 The nortriterpene correolide, a non-selective inhibitor of all Kv1 sub-types, causes progressive and sustained reduction of the pressure threshold for eliciting peristaltic contractions. 3 Margatoxin (MgTX), alpha-dendrotoxin (alpha-DTX) and dendrotoxin-K (DTX-K), highly selective peptidyl inhibitors of certain Kv1 sub-types, cause immediate reduction of the pressure threshold. This effect subsides with time, irrespective of the peptides' concentration in the bath. In preparations pretreated with saturating concentrations of MgTX, correolide further stimulates the peristaltic activity. 4 Iberiotoxin (IbTX), a selective inhibitor of the high-conductance Ca(2+)-activated K(+) (BK) channels, and charybdotoxin (ChTX), which inhibits Kv1.2 and Kv1.3 as well as BK channels, fail to stimulate the peristaltic activity. 5 Blockade of muscarinic receptors by atropine reduces, and occasionally suppresses the peristaltic activity of guinea-pig ileum. In atropine-treated preparations, correolide and MgTX retain their abilities to reduce the pressure threshold and are able to restore the peristaltic reflex in the preparations where this reflex was suppressed by atropine. 6 The stimulatory effect of correolide and MgTX in atropine-treated preparations is abolished by subsequent addition of selective antagonists of both NK1 and NK2 receptors. 7 In conclusion, blockade of Kv1, particularly Kv1.1 channels, increases the peristaltic activity of guinea-pig ileum by enhancing the release of neurotransmitters at the enteric nervous system. In contrast, stimulation of the myogenic motility by blockade of BK channels does not affect the threshold for the peristaltic reflex.

  12. Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins.

    Science.gov (United States)

    Lau, D; Vega-Saenz de Miera, E C; Contreras, D; Ozaita, A; Harvey, M; Chow, A; Noebels, J L; Paylor, R; Morgan, J I; Leonard, C S; Rudy, B

    2000-12-15

    Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 -/- mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

  13. Impact of organic nutrient load on biomass accumulation, feed channel pressure drop increase and permeate flux decline in membrane systems

    KAUST Repository

    Bucs, Szilard

    2014-12-01

    The influence of organic nutrient load on biomass accumulation (biofouling) and pressure drop development in membrane filtration systems was investigated. Nutrient load is the product of nutrient concentration and linear flow velocity. Biofouling - excessive growth of microbial biomass in membrane systems - hampers membrane performance. The influence of biodegradable organic nutrient load on biofouling was investigated at varying (i) crossflow velocity, (ii) nutrient concentration, (iii) shear, and (iv) feed spacer thickness. Experimental studies were performed with membrane fouling simulators (MFSs) containing a reverse osmosis (RO) membrane and a 31 mil thick feed spacer, commonly applied in practice in RO and nanofiltration (NF) spiral-wound membrane modules. Numerical modeling studies were done with identical feed spacer geometry differing in thickness (28, 31 and 34 mil). Additionally, experiments were done applying a forward osmosis (FO) membrane with varying spacer thickness (28, 31 and 34 mil), addressing the permeate flux decline and biofilm development. Assessed were the development of feed channel pressure drop (MFS studies), permeate flux (FO studies) and accumulated biomass amount measured by adenosine triphosphate (ATP) and total organic carbon (TOC).Our studies showed that the organic nutrient load determined the accumulated amount of biomass. The same amount of accumulated biomass was found at constant nutrient load irrespective of linear flow velocity, shear, and/or feed spacer thickness. The impact of the same amount of accumulated biomass on feed channel pressure drop and permeate flux was influenced by membrane process design and operational conditions. Reducing the nutrient load by pretreatment slowed-down the biofilm formation. The impact of accumulated biomass on membrane performance was reduced by applying a lower crossflow velocity and/or a thicker and/or a modified geometry feed spacer. The results indicate that cleanings can be delayed

  14. Impact of organic nutrient load on biomass accumulation, feed channel pressure drop increase and permeate flux decline in membrane systems.

    Science.gov (United States)

    Bucs, Sz S; Valladares Linares, R; van Loosdrecht, M C M; Kruithof, J C; Vrouwenvelder, J S

    2014-12-15

    The influence of organic nutrient load on biomass accumulation (biofouling) and pressure drop development in membrane filtration systems was investigated. Nutrient load is the product of nutrient concentration and linear flow velocity. Biofouling - excessive growth of microbial biomass in membrane systems - hampers membrane performance. The influence of biodegradable organic nutrient load on biofouling was investigated at varying (i) crossflow velocity, (ii) nutrient concentration, (iii) shear, and (iv) feed spacer thickness. Experimental studies were performed with membrane fouling simulators (MFSs) containing a reverse osmosis (RO) membrane and a 31 mil thick feed spacer, commonly applied in practice in RO and nanofiltration (NF) spiral-wound membrane modules. Numerical modeling studies were done with identical feed spacer geometry differing in thickness (28, 31 and 34 mil). Additionally, experiments were done applying a forward osmosis (FO) membrane with varying spacer thickness (28, 31 and 34 mil), addressing the permeate flux decline and biofilm development. Assessed were the development of feed channel pressure drop (MFS studies), permeate flux (FO studies) and accumulated biomass amount measured by adenosine triphosphate (ATP) and total organic carbon (TOC). Our studies showed that the organic nutrient load determined the accumulated amount of biomass. The same amount of accumulated biomass was found at constant nutrient load irrespective of linear flow velocity, shear, and/or feed spacer thickness. The impact of the same amount of accumulated biomass on feed channel pressure drop and permeate flux was influenced by membrane process design and operational conditions. Reducing the nutrient load by pretreatment slowed-down the biofilm formation. The impact of accumulated biomass on membrane performance was reduced by applying a lower crossflow velocity and/or a thicker and/or a modified geometry feed spacer. The results indicate that cleanings can be delayed

  15. The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model.

    Science.gov (United States)

    Guo, Feng; Xu, Xiaoxue; Cai, Jiqun; Hu, Huiyuan; Sun, Wei; He, Guilin; Shao, Dongxue; Wang, Lei; Chen, Tianbao; Shaw, Chris; Zhu, Tong; Hao, Liying

    2013-02-01

    Voltage-gated sodium channels (VGSC) have been linked to inherited forms of epilepsy. The expression and biophysical properties of VGSC in the hippocampal neuronal culture model have not been clarified. In order to evaluate mechanisms of epileptogenesis that are related to VGSC, we examined the expression and function of VGSC in the hippocampal neuronal culture model in vitro and spontaneously epileptic rats (SER) in vivo. Our data showed that the peak amplitude of transient, rapidly-inactivating Na(+) current (I(Na,T)) in model neurons was significantly increased compared with control neurons, and the activation curve was shifted to the negative potentials in model neurons in whole cell recording by patch-clamp. In addition, channel activity of persistent, non-inactivating Na(+) current (I(Na,P)) was obviously increased in the hippocampal neuronal culture model as judged by single-channel patch-clamp recording. Furthermore, VGSC subtypes Na(V)1.1, Na(V)1.2 and Na(V)1.3 were up-regulated at the protein expression level in model neurons and SER as assessed by Western blotting. Four subtypes of VGSC proteins in SER were clearly present throughout the hippocampus, including CA1, CA3 and dentate gyrus regions, and neurons expressing VGSC immunoreactivity were also detected in hippocampal neuronal culture model by immunofluorescence. These findings suggested that the up-regulation of voltage-gated sodium channels subtypes in neurons coincided with an increased sodium current in the hippocampal neuronal culture model, providing a possible explanation for the observed seizure discharge and enhanced excitability in epilepsy.

  16. PA1b, a plant peptide, induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel and triggers secretion in pancreatic β cells

    Institute of Scientific and Technical Information of China (English)

    HU ZhiTao; DUN XinPeng; ZHANG Ming; ZHU HongLiang; XIE Li; WU ZhengXing; CHEN ZhengWang; XU Tao

    2007-01-01

    Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2+]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2+]i elevation was abolished in the absence of extracellular Ca2+ or in the presence of L-type Ca2+ channel blocker, nimodipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2+ channels and influx of extracellular Ca2+, and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell.

  17. 明渠网络中基于带权Lyapunov函数的边界反馈控制稳定性%Stability of Boundary Feedback Control Based on Weighted Lyapunov Function in Networks of Open Channels

    Institute of Scientific and Technical Information of China (English)

    岑丽辉; 席裕庚

    2009-01-01

    A Lyapunov function is constructed based on the weighted sum of entropies for the case of two open channels in cascade, which is described by the Saint-Venant equations. A class of boundary feedback controllers is presented to guaran-tee the local closed-loop asymptotic stability in a neighborhood of the equilibrium point by means of the Lyapunov design ap-proach.

  18. Kv3.1/Kv3.2 channel positive modulators enable faster activating kinetics and increase firing frequency in fast-spiking GABAergic interneurons.

    Science.gov (United States)

    Boddum, Kim; Hougaard, Charlotte; Xiao-Ying Lin, Julie; von Schoubye, Nadia Lybøl; Jensen, Henrik Sindal; Grunnet, Morten; Jespersen, Thomas

    2017-02-24

    Due to their fast kinetic properties, Kv3.1 voltage gated potassium channels are important in setting and controlling firing frequency in neurons and pivotal in generating high frequency firing of interneurons. Pharmacological activation of Kv3.1 channels may possess therapeutic potential for treatment of epilepsy, hearing disorders, schizophrenia and cognitive impairments. Here we thoroughly investigate the selectivity and positive modulation of the two small molecules, EX15 and RE01, on Kv3 channels. Selectivity studies, conducted in Xenopus laevis oocytes confirmed a positive modulatory effect of the two compounds on Kv3.1 and to a minor extent on Kv3.2 channels. RE01 had no effect on the Kv3.3 and Kv3.4 channels, whereas EX15 had an inhibitory impact on the Kv3.4 mediated current. Voltage-clamp experiments in monoclonal hKv3.1b/HEK293 cells (34 °C) revealed that the two compounds indeed induced larger currents and faster activation kinetics. They also decrease the speed of deactivation and shifted the voltage dependence of activation, to a more negative activation threshold. Application of action potential clamping and repetitive stimulation protocols of hKv3.1b expressing HEK293 cells revealed that EX15 and RE01 significantly increased peak amplitude, half width and decay time of Kv3.1 mediated currents, even during high-frequency action potential clamping (250 Hz). In rat hippocampal slices, EX15 and RE01 increased neuronal excitability in fast-spiking interneurons in dentate gyrus. Action potential frequency was prominently increased at minor depolarizing steps, whereas more marginal effects of EX15 and RE01 were observed after stronger depolarizations. In conclusion, our results suggest that EX15 and RE01 positive modulation of Kv3.1 and Kv3.2 currents facilitate increased firing frequency in fast-spiking GABAergic interneurons.

  19. Increased gamma- and decreased delta-oscillations in a mouse deficient for a potassium channel expressed in fast-spiking interneurons.

    Science.gov (United States)

    Joho, R H; Ho, C S; Marks, G A

    1999-10-01

    Kv3.1 is a voltage-gated, fast activating/deactivating potassium (K(+)) channel with a high-threshold of activation and a large unit conductance. Kv3.1 K(+) channels are expressed in fast-spiking, parvalbumin-containing interneurons in cortex, hippocampus, striatum, the thalamic reticular nucleus (TRN), and in several nuclei of the brain stem. A high density of Kv3.1 channels contributes to short-duration action potentials, fast afterhyperpolarizations, and brief refractory periods enhancing the capability in these neurons for high-frequency firing. Kv3.1 K(+) channel expression in the TRN and cortex also suggests a role in thalamocortical and cortical function. Here we show that fast gamma and slow delta oscillations recorded from the somatomotor cortex are altered in the freely behaving Kv3.1 mutant mouse. Electroencephalographic (EEG) recordings from homozygous Kv3.1(-/-) mice show a three- to fourfold increase in both absolute and relative spectral power in the gamma frequency range (20-60 Hz). In contrast, Kv3.1-deficient mice have a 20-50% reduction of power in the slow delta range (2-3 Hz). The increase in gamma power is most prominent during waking in the 40- to 55-Hz range, whereas the decrease in delta power occurs equally across all states of arousal. Our findings suggest that Kv3. 1-expressing neurons are involved in the generation and maintenance of cortical fast gamma and slow delta oscillations. Hence the Kv3. 1-mutant mouse could serve as a model to study the generation and maintenance of fast gamma and slow delta rhythms and their involvement in behavior and cognition.

  20. Alterations in plasma membrane promote overexpression and increase of sodium influx through epithelial sodium channel in hypertensive platelets.

    Science.gov (United States)

    Cerecedo, D; Martínez-Vieyra, Ivette; Sosa-Peinado, Alejandro; Cornejo-Garrido, Jorge; Ordaz-Pichardo, Cynthia; Benítez-Cardoza, Claudia

    2016-08-01

    Platelets are small, anucleated cell fragments that activate in response to a wide variety of stimuli, triggering a complex series of intracellular pathways leading to a hemostatic thrombus formation at vascular injury sites. However, in essential hypertension, platelet activation contributes to causing myocardial infarction and ischemic stroke. Reported abnormalities in platelet functions, such as platelet hyperactivity and hyperaggregability to several agonists, contribute to the pathogenesis and complications of thrombotic events associated with hypertension. Platelet membrane lipid composition and fluidity are determining for protein site accessibility, structural arrangement of platelet surface, and response to appropriate stimuli. The present study aimed to demonstrate whether structural and biochemical abnormalities in lipid membrane composition and fluidity characteristic of platelets from hypertensive patients influence the expression of the Epithelial Sodium Channel (ENaC), fundamental for sodium influx during collagen activation. Wb, cytometry and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) assays demonstrated ENaC overexpression in platelets from hypertensive subjects and in relation to control subjects. Additionally, our results strongly suggest a key role of β-dystroglycan as a scaffold for the organization of ENaC and associated proteins. Understanding of the mechanisms of platelet alterations in hypertension should provide valuable information for the pathophysiology of hypertension.

  1. Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels

    Directory of Open Access Journals (Sweden)

    Stephan eKratzer

    2013-07-01

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS and field excitatory postsynaptic potentials (fEPSP were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean  Standard error of the mean; 231.8  31.2% of control; n=10 while neither affecting fEPSPs (104.3 ± 4.2%; n=10 nor long-term potentiation (LTP. However, when Schaffer-collaterals were excited via action potentials (APs generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n=8 and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1 expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.

  2. Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels

    Directory of Open Access Journals (Sweden)

    Graffe Carolina C

    2010-10-01

    Full Text Available Abstract Background Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. Methods The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2, the beta-fraction of the epithelial sodium channel (u-ENaCbeta, cyclic-AMP (u-cAMP, prostaglandin E2 (u-PGE2. Free water clearance (CH2O, fractional excretion of sodium (FENa, and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. Results Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. Conclusion During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system Trial Registration Clinical Trials Identifier: NCT00281762

  3. A CACNA1C variant associated with reduced voltage-dependent inactivation, increased CaV1.2 channel window current, and arrhythmogenesis.

    Directory of Open Access Journals (Sweden)

    Jessica A Hennessey

    Full Text Available Mutations in CACNA1C that increase current through the CaV1.2 L-type Ca2+ channel underlie rare forms of long QT syndrome (LQTS, and Timothy syndrome (TS. We identified a variant in CACNA1C in a male child of Filipino descent with arrhythmias and extracardiac features by candidate gene sequencing and performed functional expression studies to electrophysiologically characterize the effects of the variant on CaV1.2 channels. As a baby, the subject developed seizures and displayed developmental delays at 30 months of age. At age 5 years, he displayed a QTc of 520 ms and experienced recurrent VT. Physical exam at 17 years of age was notable for microcephaly, short stature, lower extremity weakness and atrophy with hyperreflexia, spastic diplegia, multiple dental caries and episodes of rhabdomyolysis. Candidate gene sequencing identified a G>C transversion at position 5731 of CACNA1C (rs374528680 predicting a glycine>arginine substitution at residue 1911 (p.G1911R of CaV1.2. The allele frequency of this variant is 0.01 in Malays, but absent in 984 Caucasian alleles and in the 1000 genomes project. In electrophysiological analyses, the variant decreased voltage-dependent inactivation, thus causing a gain of function of CaV1.2. We also observed a negative shift of V1/2 of activation and positive shift of V1/2 of channel inactivation, resulting in an increase of the window current. Together, these suggest a gain-of-function effect on CaV1.2 and suggest increased susceptibility for arrhythmias in certain clinical settings. The p.G1911R variant was also identified in a case of sudden unexplained infant death (SUID, for which an increasing number of clinical observations have demonstrated can be associated with arrhythmogenic mutations in cardiac ion channels. In summary, the combined effects of the CACNA1C variant to diminish voltage-dependent inactivation of CaV1.2 and increase window current expand our appreciation of mechanisms by which a gain of

  4. Mechanosensitive Channels

    Science.gov (United States)

    Martinac, Boris

    Living cells are exposed to a variety of mechanical stimuli acting throughout the biosphere. The range of the stimuli extends from thermal molecular agitation to potentially destructive cell swelling caused by osmotic pressure gradients. Cellular membranes present a major target for these stimuli. To detect mechanical forces acting upon them cell membranes are equipped with mechanosensitive (MS) ion channels. Functioning as molecular mechanoelectrical transducers of mechanical forces into electrical and/or chemical intracellular signals these channels play a critical role in the physiology of mechanotransduction. Studies of prokaryotic MS channels and recent work on MS channels of eukaryotes have significantly increased our understanding of their gating mechanism, physiological functions, and evolutionary origins as well as their role in the pathology of disease.

  5. Targeting at SUR2B/Kir6.1 subtype of ATP-sensitive potassium channel opener natakalim improves pressure overload-induced heart failure

    Institute of Scientific and Technical Information of China (English)

    TANG Yuan; LONG Chao-liang; WANG Hai

    2008-01-01

    Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure. Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding (AAB) .The effects of natakalim (1,3, 9 mg·kg-1·d-1, 10 weeks) were assessed on myocardial hypertrophy and heart failure, cardiac histology, vasoactive compounds, and gene expression. Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels. Results Ten weeks after the onset of pressure overload, natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure. Natakalim inhibited the changes of left ventricular haemodynamic parameters, reversed the increase of heart mass index, left ventricular weight index and lung weight index remarkably. Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim. Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats. The content of serum NO and plasma PGI2 was increased, while that of plasma ET-1 and cardiac tissue hydroxyproline, ANP and BNP mRNA was down-regulated in natakalim-treated rats. Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats; however, natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE. Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.

  6. GABAA increases calcium in subventricular zone astrocyte-like cells through L- and T-type voltage-gated calcium channels

    Directory of Open Access Journals (Sweden)

    Stephanie Z Young

    2010-04-01

    Full Text Available In the adult neurogenic subventricular zone (SVZ, the behavior of astrocyte-like cells and some of their functions depend on changes in intracellular Ca2+ levels and tonic GABAA receptor activation. However, it is unknown whether, and if so how, GABAA receptor activity regulates intracellular Ca2+ dynamics in SVZ astrocytes. To monitor Ca2+ activity selectively in astrocyte-like cells, we used two lines of transgenic mice expressing either GFP fused to a Gq-coupled receptor or DsRed under the human glial fibrillary acidic protein (hGFAP promoter. GABAA receptor activation induced Ca2+ increases in 40-50% of SVZ astrocytes. GABAA-induced Ca2+ increases were prevented with nifedipine and mibefradil, blockers of L- and T-type voltage-gated calcium channels (VGCC. The L-type Ca2+ channel activator BayK 8644 increased the percentage of GABAA-responding astrocyte-like cells to 75%, suggesting that the majority of SVZ astrocytes express functional VGCCs. SVZ astrocytes also displayed spontaneous Ca2+ activity, the frequency of which was regulated by tonic GABAA receptor activation. These data support a role for ambient GABA in tonically regulating intracellular Ca2+ dynamics through GABAA receptors and VGCC in a subpopulation of astrocyte-like cells in the postnatal SVZ.

  7. 四川南向开放与国际通道建设院一个研究综述%Southward Opening-up and International Channel Construction of Sichuan:A Literature Review

    Institute of Scientific and Technical Information of China (English)

    周俊

    2014-01-01

    The pattern of opening-up in China is shown as an echelon manner from the south to the north China, from the east to the west and from the coastal region to the inland. Based on the changes of situation both home and abroad, the strategy of opening-up in China turns from the eastern coastal regions, key development regions before, to Westward and Southward Opening-up and Coast and Inland Advancing Abreast. The opening-up of Sichuan started rather late in the national strategic plan. Scholars have made certain researches on the strategic status and significance of Sichuan in the opening-up pattern of China, but their studies laid emphasis on different aspects and started from different perspectives. The research on the southward opening-up of Sichuan focuses on the economic and trade relationship between Sichuan and the Associate of South East Asia Countries and the South Asia. However, the study of the international Channel construction, which is the bottleneck of the southward opening-up of Sichuan, needs more work and efforts. As a significant supporting condition of southward opening-up of Sichuan, it is of great strategy to deepen the research. The research on southward opening-up and international channel construction of Sichuan must be strengthened in the future, including tight correlation analysis of southward opening-up and international channel construction of Sichuan, the breakthrough direction, basic framework and tactics of southward opening-up of Sichuan after the international financial crisis as well as the routes and strategies of the international channel construction.%中国对外开放格局是沿着由南向北、由东西向、由沿海沿边向内地逐步梯次展开的。根据国内外形势的变化,中国的对外开放战略由东部沿海为重点逐步转向“西进南下”和“海陆并进”。四川的对外开放在国家战略层面上起步较晚。学者们对四川在中国对外开放中的战略地位和意义有所研

  8. Involvement of Residents Does Not Increase Postoperative Complications After Open Reduction Internal Fixation of Ankle Fractures: An Analysis of 3251 Cases.

    Science.gov (United States)

    Louie, Philip K; Schairer, William W; Haughom, Bryan D; Bell, Joshua A; Campbell, Kevin J; Levine, Brett R

    Ankle fractures are common injuries frequently treated by foot and ankle surgeons. Therefore, it has become a core competency for orthopedic residency training. Surgical educators must balance the task of training residents with optimizing patient outcomes and minimizing morbidity and mortality. The present study aimed to determine the effect of resident involvement on the 30-day postoperative complication rates after open reduction and internal fixation of ankle fractures. A second objective of the present study was to determine the independent risk factors for complications after this procedure. We identified patients in the American College of Surgeons National Surgical Quality Improvement Program database who had undergone open reduction internal fixation for ankle fractures from 2005 to 2012. Propensity score matching was used to help account for a potential selection bias. We performed univariate and multivariate analyses to identify the independent risk factors associated with short-term postoperative complications. A total of 3251 open reduction internal fixation procedures for ankle fractures were identified, of which 959 (29.4%) had resident involvement. Univariate (2.82% versus 4.54%; p = .024) and multivariate (odds ratio 0.71; p = .75) analyses demonstrated that resident involvement did not increase short-term complication rates. The independent risk factors for complications after open reduction internal fixation of ankle fractures included insulin-dependent diabetes, increasing age, higher American Society of Anesthesiologists score, and longer operative times. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Flow Resistance in Open Channels and Limits of Applicability of Manning's Formula; Resistencia al flujo en canales y limites de aplicabilidad de la formula de manning

    Energy Technology Data Exchange (ETDEWEB)

    Aldama, Alvaro A; R Ocon, Afredo [Instituto Mexicano de Tecnologia del Agua, Jiutepec, Morelos (Mexico)

    2002-03-01

    The concepts involved in the estimation of flow resistance in open channels are reviewed. In particular, of expressions for the friction factor that allow the derivation of expressions for the friction factor that appears in Darcy-Weisbach's formula for circular channels flowing full or at a depth equal half the diameter, and for wide channels, conveying hydraulically rough, fully turbulent flow. The results of such analyses show that it is possible to avoid adjustments to the numerical values that appear in Colebrook's formula, in order to reproduce experimental data. They also make it possible to explain the empirical dispersion observed in the values of the parameters of an expression used to estimate the Darcy-Weisbach friction coefficient for wide channels. On the basis of these results, the range of validity for Manning's formula is determined. Finally, additional evidence is provided in the estimation of flow resistance in open channels, being well represented by the hydraulic radius alone. This observation allows to foresees the possibility of developing a universally valid formula for the Darcy-Weisbach friction factor, applicable to flow in open channels. [Spanish] Se revisan los conceptos involucrados en la estimacion de la resistencia al flujo en canales. En particular, se senalan los inconvenientes de la popular formula de Manning. Tambien se presentan analisis teoricos que permiten determinar expresiones para el factor de friccion de la formula de Darcy-Weisbach para canales circulares trabajando llenos a la mitad, y para canales anchos conduciendo flujo hidraulicamente rugoso con turbulencia desarrollada. Se demuestra que los resultados de dichos analisis permiten evitar hacer ajustes en los valores numericos que aparecen en la formula de Colebrook, a fin de reproducir observaciones experimentales. Asimismo, hacen posible explicar la dispersion experimental en los valores de los parametros que aparecen en una expresion para el calculo

  10. Zn(2+) induces hyperpolarization by activation of a K(+) channel and increases intracellular Ca(2+) and pH in sea urchin spermatozoa.

    Science.gov (United States)

    Beltrán, Carmen; Rodríguez-Miranda, Esmeralda; Granados-González, Gisela; García de De la Torre, Lucia; Nishigaki, Takuya; Darszon, Alberto

    2014-10-01

    Zinc (Zn(2+)) has been recently recognized as a crucial element for male gamete function in many species although its detailed mechanism of action is poorly understood. In sea urchin spermatozoa, Zn(2+) was reported as an essential trace ion for efficient sperm motility initiation and the acrosome reaction by modulating intracellular pH (pHi). In this study we found that submicromolar concentrations of free Zn(2+) change membrane potential (Em) and increase the concentration of intracellular Ca(2+) ([Ca(2+)]i) and cAMP in Lytechinus pictus sperm. Our results indicate that the Zn(2+) response in sperm of this species mainly involves an Em hyperpolarization caused by K(+) channel activation. The pharmacological profile of the Zn(2+)-induced hyperpolarization indicates that the cGMP-gated K(+) selective channel (tetraKCNG/CNGK), which is crucial for speract signaling, is likely a main target for Zn(2+). Considering that Zn(2+) also induces [Ca(2+)]i fluctuations, our observations suggest that Zn(2+) activates the signaling cascade of speract, except for an increase in cGMP, and facilitates sperm motility initiation upon spawning. These findings provide new insights about the role of Zn(2+) in male gamete function.

  11. ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs

    DEFF Research Database (Denmark)

    Xing, Dezhi; Kjølbye, Anne Louise; Nielsen, Morten S

    2003-01-01

    INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments...

  12. Restoration of the response of the middle cerebral artery of the rat to acidosis in hyposmotic hyponatremia by the opener of large-conductance calcium sensitive potassium channels (BKCa).

    Science.gov (United States)

    Aleksandrowicz, Marta; Dworakowska, Beata; Dolowy, Krzysztof; Kozniewska, Ewa

    2017-09-01

    Hyposmotic hyponatremia (the decrease of extracellular concentration of sodium ions from 145 to 121 mM and the decrease of hyposmolality from 300 to 250 mOsm/kg H2O) impairs response of the middle cerebral artery (MCA) to acetylcholine and NO donor (S-nitroso-N-acetyl-DL-penicillamine). Since acidosis activates a similar intracellular signaling pathway, the present study was designed to verify the hypothesis that the response of the MCA to acidosis is impaired during acute hyposmotic hyponatremia due to abnormal NO-related signal transduction in vascular smooth muscle cells. Studies performed on isolated, cannulated, and pressurized rat MCA revealed that hyposmotic hyponatremia impaired the response of the MCA to acidosis and this was associated with hyposmolality rather than with decreased sodium ion concentration. Response to acidosis was restored by the BKCa but not by the KATP channel activator. Patch-clamp electrophysiology performed on myocytes freshly isolated from MCAs, demonstrated that hyposmotic hyponatremia does not affect BKCa currents but decreases the voltage-dependency of the activation of the BKCa channels in the presence of a specific opener of these channels. Our study suggests that reduced sensitivity of BKCa channels in the MCA to agonists results in the lack of response of this artery to acidosis during acute hyposmotic hyponatremia.

  13. Quantum Interference and Selectivity through Biological Ion Channels

    Science.gov (United States)

    Salari, Vahid; Naeij, Hamidreza; Shafiee, Afshin

    2017-01-01

    The mechanism of selectivity in ion channels is still an open question in biology for more than half a century. Here, we suggest that quantum interference can be a solution to explain the selectivity mechanism in ion channels since interference happens between similar ions through the same size of ion channels. In this paper, we simulate two neighboring ion channels on a cell membrane with the famous double-slit experiment in physics to investigate whether there is any possibility of matter-wave interference of ions via movement through ion channels. Our obtained decoherence timescales indicate that the quantum states of ions can only survive for short times, i.e. ≈100 picoseconds in each channel and ≈17–53 picoseconds outside the channels, giving the result that the quantum interference of ions seems unlikely due to environmental decoherence. However, we discuss our results and raise few points, which increase the possibility of interference. PMID:28134331

  14. Increased leaf photosynthesis caused by elevated stomatal conductance in a rice mutant deficient in SLAC1, a guard cell anion channel protein.

    Science.gov (United States)

    Kusumi, Kensuke; Hirotsuka, Shoko; Kumamaru, Toshiharu; Iba, Koh

    2012-09-01

    In rice (Oryza sativa L.), leaf photosynthesis is known to be highly correlated with stomatal conductance; however, it remains unclear whether stomatal conductance dominantly limits the photosynthetic rate. SLAC1 is a stomatal anion channel protein controlling stomatal closure in response to environmental [CO(2)]. In order to examine stomatal limitations to photosynthesis, a SLAC1-deficient mutant of rice was isolated and characterized. A TILLING screen of N-methyl-N-nitrosourea-derived mutant lines was conducted for the rice SLAC1 orthologue gene Os04g0674700, and four mutant lines containing mutations within the open reading frame were obtained. A second screen using an infrared thermography camera revealed that one of the mutants, named slac1, had a constitutive low leaf temperature phenotype. Measurement of leaf gas exchange showed that slac1 plants grown in the greenhouse had significantly higher stomatal conductance (g (s)), rates of photosynthesis (A), and ratios of internal [CO(2)] to ambient [CO(2)] (C (i)/C (a)) compared with wild-type plants, whereas there was no significant difference in the response of photosynthesis to internal [CO(2)] (A/C (i) curves). These observations demonstrate that in well-watered conditions, stomatal conductance is a major determinant of photosynthetic rate in rice.

  15. Kinematic characteristics of horseshoe vortex upstream of circular cylinders in open channel flow%明渠柱体上游马蹄涡的运动学特征研究

    Institute of Scientific and Technical Information of China (English)

    陈启刚; 齐梅兰; 李金钊

    2016-01-01

    To investigate the kinematic characteristics of horseshoe vortex upstream of cylinders, the swirl⁃ing strength method is introduced to identify horseshoe vortices, and a method of fitting the local velocity field with an elliptic vortex are proposed to characterize these vortices. The elliptic vortex is constructed by overlapping the Oseen vortex with an inclined unidirectional shear flow. The proposed methods were used to investigate the time-averaged horseshoe vortex upstream of a circular cylinder in open channel flow. The time averaged horseshoe vortex is captured by averaging instantaneous velocity fields measured with PIV. The results show that, in flows with cylinder Reynolds number larger than 104, the position of horseshoe vortex is unchanged while the upstream separation point moves downstream slowly. The distances from the vortex center to the cylinder axis and the bed are 0.67D and 0.06D, respectively, with D being the cylin⁃der diameter. Comparing with those in open channel flows,the horseshoe vortex and separation point in tur⁃bulent boundary layers are further upstream. With the increasing of cylinder Reynolds number, the horse⁃shoe vortex strengthens itself but keeps the size unchanged, results in increasing shear stress on the bed. The dependence of vortex-induced shear stress with the flow strength indicates that it is physically reason⁃able to formulate equations for local scour based on the kinematic characteristics of horseshoe vortex.%马蹄涡是水下柱体结构周围床面冲刷的主要动力。为掌握马蹄涡的运动学特征,引入了基于旋转强度的马蹄涡识别方法,提出了基于椭圆涡拟合的马蹄涡特征提取方法,其中,椭圆涡由Oseen涡和倾斜单向剪切流叠加而成。基于上述方法,通过开展明渠圆柱绕流PIV实验,对柱体上游对称面时均流场中马蹄涡的运动学特征进行了研究。结果表明,在柱体雷诺数大于104的紊流柱体绕流中,

  16. In-vivo administration of CLC-K kidney chloride channels inhibitors increases water diuresis in rats: a new drug target for hypertension?

    Science.gov (United States)

    Liantonio, Antonella; Gramegna, Gianluca; Camerino, Giulia M; Dinardo, Maria M; Scaramuzzi, Antonia; Potenza, Maria A; Montagnani, Monica; Procino, Giuseppe; Lasorsa, Domenica R; Mastrofrancesco, Lisa; Laghezza, Antonio; Fracchiolla, Giuseppe; Loiodice, Fulvio; Perrone, Maria G; Lopedota, Angela; Conte, Salvatore; Penza, Rosa; Valenti, Giovanna; Svelto, Maria; Camerino, Diana Conte

    2012-01-01

    The human kidney-specific chloride channels ClC-Ka (rodent ClC-K1) and ClC-Kb (rodent ClC-K2) are important determinants of renal function, participating to urine concentration and blood pressure regulation mechanisms. Here we tested the hypothesis that these chloride channels could represent new drug targets for inducing diuretic and antihypertensive effects. To this purpose, the CLC-K blockers benzofuran derivatives MT-189 and RT-93 (10, 50, 100 mg/kg), were acutely administered by gavage in Wistar rats, and pharmacodynamic and pharmacokinetic parameters determined by functional, bioanalytical, biochemical and molecular biology assays. Plasma concentration values for MT-189 and RT-93 were indicative of good bioavailability. Both MT-189 and RT-93 dose-dependently increased urine volume without affecting electrolyte balance. A comparable reduction of SBP was observed in rats after MT-189, RT-93 or furosemide administration. Benzofuran derivatives treatment did not affect kidney CLC-K mRNA level or inner medulla osmolality, whereas a significant vasopressin-independent down-regulation of aquaporin water channel type 2 was observed at protein and transcriptional levels. In rats treated with benzofuran derivatives, the observed polyuria was mainly water diuresis; this finding indirectly supports a cross-talk between chloride and water transport in nephron. Moreover, preliminary in-vitro evaluation of the drugs capability to cross the blood-inner ear barrier suggests that these compounds have a limited ability to induce potential auditory side effects. CLC-K blockers may represent a new class of drugs for the treatment of conditions associated with expanded extracellular volume, with a hopeful high therapeutic potential for hypertensive patients carrying ClC-K gain-of-function polymorphisms.

  17. Rattlesnake Phospholipase A2 Increases CFTR-Chloride Channel Current and Corrects ∆F508CFTR Dysfunction: Impact in Cystic Fibrosis.

    Science.gov (United States)

    Faure, Grazyna; Bakouh, Naziha; Lourdel, Stéphane; Odolczyk, Norbert; Premchandar, Aiswarya; Servel, Nathalie; Hatton, Aurélie; Ostrowski, Maciej K; Xu, Haijin; Saul, Frederick A; Moquereau, Christelle; Bitam, Sara; Pranke, Iwona; Planelles, Gabrielle; Teulon, Jacques; Herrmann, Harald; Roldan, Ariel; Zielenkiewicz, Piotr; Dadlez, Michal; Lukacs, Gergely L; Sermet-Gaudelus, Isabelle; Ollero, Mario; Corringer, Pierre-Jean; Edelman, Aleksander

    2016-07-17

    Deletion of Phe508 in the nucleotide binding domain (∆F508-NBD1) of the cystic fibrosis transmembrane regulator (CFTR; a cyclic AMP-regulated chloride channel) is the most frequent mutation associated with cystic fibrosis. This mutation affects the maturation and gating of CFTR protein. The search for new high-affinity ligands of CFTR acting as dual modulators (correctors/activators) presents a major challenge in the pharmacology of cystic fibrosis. Snake venoms are a rich source of natural multifunctional proteins, potential binders of ion channels. In this study, we identified the CB subunit of crotoxin from Crotalus durissus terrificus as a new ligand and allosteric modulator of CFTR. We showed that CB interacts with NBD1 of both wild type and ∆F508CFTR and increases their chloride channel currents. The potentiating effect of CB on CFTR activity was demonstrated using electrophysiological techniques in Xenopus laevis oocytes, in CFTR-HeLa cells, and ex vivo in mouse colon tissue. The correcting effect of CB was shown by functional rescue of CFTR activity after 24-h ΔF508CFTR treatments with CB. Moreover, the presence of fully glycosylated CFTR was observed. Molecular docking allowed us to propose a model of the complex involving of the ABCβ and F1-like ATP-binding subdomains of ΔF508-NBD1. Hydrogen-deuterium exchange analysis confirmed stabilization in these regions, also showing allosteric stabilization in two other distal regions. Surface plasmon resonance competition studies showed that CB disrupts the ∆F508CFTR-cytokeratin 8 complex, allowing for the escape of ∆F508CFTR from degradation. Therefore CB, as a dual modulator of ΔF508CFTR, constitutes a template for the development of new anti-CF agents.

  18. K(v)7 channels: function, pharmacology and channel modulators.

    Science.gov (United States)

    Dalby-Brown, William; Hansen, Henrik H; Korsgaard, Mads P G; Mirza, Naheed; Olesen, Søren-P

    2006-01-01

    K(v)7 channels are unique among K(+) channels, since four out of the five channel subtypes have well-documented roles in the development of human diseases. They have distinct physiological functions in the heart and in the nervous system, which can be ascribed to their voltage-gating properties. The K(v)7 channels also lend themselves to pharmacological modulation, and synthetic openers as well as blockers of the channels, regulating neuronal excitability, have existed even before the K(v)7 channels were identified by cloning. In the present review we give an account on the focused efforts to develop selective modulators, openers as well as blockers, of the K(v)7 channel subtypes, which have been undertaken during recent years, along with a discussion of the K(v)7 ion channel physiology and therapeutic indications for modulators of the neuronal K(v)7 channels.

  19. Calculation of the critical velocity and the critical slope of trailing hydro-transport in open channels%尾矿流槽临界流速和临界坡度计算

    Institute of Scientific and Technical Information of China (English)

    胡去劣; 熊梦婕

    2011-01-01

    The minimun flow rate which can keep the open channel without siltation is called “the critical velocity”. It is significant to the design of trailing hydro-transport. According to the assumption of the minimum energy loss of the muddy water under the critical condition, a formula is obtained by using the differential method in maths. Based on both theory and experiments, the derivation process of this formula is clear and correct. Many factors such as the characteristic parameters of the open channel and the two-phase-flow have been considered,which makes the formula more comprehensive. Meanwhile, it is also in good agreement with the experiment outcome that 94% of the test records are close to the calculation results. So this formula can be applied to multifarious working conditions in trailing hydro-transport projects. In general, this research has solved a special engineering problem successfully and it will be useful to the design of the critical velocity and critical slope of the trailing hydro-transport in open channels.%尾矿流槽保持不淤的最小流速称为临界流速,该流速对流槽设计有着重要意义.在浑水流动能量损失方程基础上,根据浑水流动临界流速的理念,采用求极值的方法,推得临界流速公式.该式综合了流槽与二相流的特性,考虑的因素较全面.并将计算结果与试验数据相比较,对比147个试验数据,其中计算相对误差小于10%的约占94%,说明该式的计算精度较高.

  20. The modeling of the channel deformations in the rivers flowing into permafrost with an increase in ambient temperature

    Science.gov (United States)

    Debolskaya, E. I.; Zamjatina, E. V.; Gritsuk, I. I.; Maslikova, O. Ja.

    2012-04-01

    Global climate changes in recent decades inevitably lead to more frequent catastrophic events. Their negative effects on rivers flowing into the permafrost zone, may be exacerbated by significant changes in bed deformations caused not only the influence of water flow, but significant changes of the bed due to the influence of increasing water and air temperatures on the structure of its constituent materials. The coastal slopes composed of permafrost will be subject to thermal abrasion. The purpose of this paper is to investigate the influence of river flow during the increase of water temperature on the deformation of the coastal slopes, composed of permafrost rocks with the addition of ice layers. The method of investigation is laboratory and mathematical modeling. The basis of the three-dimensional mathematical model of the coastal slopes thermoerosion of the rivers flowing in permafrost regions, and its verification is the results of the laboratory experiments conducted in the hydraulic tray. When the water temperature in the main stream rises the ice plate begins to melt forming the cavity where small streams are formed. The soil layers lose hard icy base and begin to sag under gravity. In the mathematical model law of the phase transition movement (Stefan condition) is determined from the heat balance equation. To determine the longitudinal velocity and the turbulent exchange coefficient we use the approach of "shallow water". The value of the transverse velocity is calculated from the equation of continuity. Coastal slope deformation during thawing is determined primarily by deposition of rock under the influence of gravity. An erosion due to water current in the mainstream and in the cavities may play a role under sufficient looseness of the rocks. The parameterization of the rocks deposition is almost impossible without knowing the composition of the soil, its porosity, ice content, moisture content. The determination of the rate and amount of slipping is

  1. Controlled Conjugated Backbone Twisting for an Increased Open-Circuit Voltage while Having a High Short-Circuit Current in Poly(hexylthiophene) Derivatives

    KAUST Repository

    Ko, Sangwon

    2012-03-21

    Conjugated polymers with nearly planar backbones have been the most commonly investigated materials for organic-based electronic devices. More twisted polymer backbones have been shown to achieve larger open-circuit voltages in solar cells, though with decreased short-circuit current densities. We systematically impose twists within a family of poly(hexylthiophene)s and examine their influence on the performance of polymer:fullerene bulk heterojunction (BHJ) solar cells. A simple chemical modification concerning the number and placement of alkyl side chains along the conjugated backbone is used to control the degree of backbone twisting. Density functional theory calculations were carried out on a series of oligothiophene structures to provide insights on how the sterically induced twisting influences the geometric, electronic, and optical properties. Grazing incidence X-ray scattering measurements were performed to investigate how the thin-film packing structure was affected. The open-circuit voltage and charge-transfer state energy of the polymer:fullerene BHJ solar cells increased substantially with the degree of twist induced within the conjugated backbone-due to an increase in the polymer ionization potential-while the short-circuit current decreased as a result of a larger optical gap and lower hole mobility. A controlled, moderate degree of twist along the poly(3,4-dihexyl-2,2′:5′,2′′- terthiophene) (PDHTT) conjugated backbone led to a 19% enhancement in the open-circuit voltage (0.735 V) vs poly(3-hexylthiophene)-based devices, while similar short-circuit current densities, fill factors, and hole-carrier mobilities were maintained. These factors resulted in a power conversion efficiency of 4.2% for a PDHTT:[6,6]-phenyl-C 71-butyric acid methyl ester (PC 71BM) blend solar cell without thermal annealing. This simple approach reveals a molecular design avenue to increase open-circuit voltage while retaining the short-circuit current. © 2012 American

  2. 旋转式明渠流综合实验平台研制与应用%Development and application of comprehensive experiment platform for rotatable open channel flow

    Institute of Scientific and Technical Information of China (English)

    戎贵文; 袁岳; 肖柏青; 许光泉

    2015-01-01

    In order to cultivate the innovative ability of college students and overcome the disadvantages in the experiment device of single open channel flow,such as simple experiment content,occupation of large area,and high cost,a comprehensive experi-ment platform for rotatable open channel flow was developed based on the conventional hydraulic experiment apparatus and bas-ic principle of fluid flow.The experiment platform used the rotatable method to integrate different open channel flow experi-ments,which can meet the demand of conducting various conventional open channel flow experiments in the same platform,and the demand of modern teaching including the comprehensive,designed,and innovative training plans.The platform has the ad-vantages of perfect design,complete function,and convenient reestablishment,which is of important significance for the cultiva-tion of innovative talents with water conservancy major.%为了培养大学生创新能力和克服单个明渠流实验装置测试内容单一、占地大、成本高等缺陷,在研究传统水力学实验装置和流体运动基本原理的基础上,自主研制开发了一套旋转式明渠流综合实验平台。该实验平台采用旋转方式创造性地将多种明渠水流实验集为一身,能够满足学生在同一实验平台上进行多种常规明渠流实验的需求,从而满足高校综合性、设计性、创新创业训练计划等现代教学的要求。实践表明,该实验平台具有设计巧妙、功能齐全、改造方便等优点,对水利类专业构建创新型人才培养模式有重要意义。

  3. Test of the Bank Lending Channel: The Case of Poland

    Directory of Open Access Journals (Sweden)

    Yu HSING

    2013-11-01

    Full Text Available This paper tests the bank lending channel for Poland based on a simultaneousequation model consisting of demand for and supply of bank loans. The three-stage least squares method is employed in empirical work. This paper finds support for a bank lending channel for Poland. Expansionary monetary policy through a lower money market rate or open market purchase of government bonds to increase bank reserves/deposits would increase bank loan supply.

  4. New distribution channels for advertising through computer games and mobile devices.

    OpenAIRE

    Sivagnanasuntharam, Sivasathees

    2008-01-01

    The development in advertising industry has lately gone from open advertising through few, major distribution channels to a hidden and targeting advertising integrated into everyday life. Advertisers grow increasingly unhappy with the value delivered by the traditional mediums. They turn to alternative distribution channels in order to increase the success rate of advertising campaigns. Channels seen as unattractively with little purchasing power previously are attracting advertisers attenti...

  5. Interaction of hydrogen sulfide with ion channels.

    Science.gov (United States)

    Tang, Guanghua; Wu, Lingyun; Wang, Rui

    2010-07-01

    1. Hydrogen sulfide (H(2)S) is a signalling gasotransmitter. It targets different ion channels and receptors, and fulfils its various roles in modulating the functions of different systems. However, the interaction of H(2)S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically. 2. H(2)S is the first identified endogenous gaseous opener of ATP-sensitive K(+) channels in vascular smooth muscle cells. Through the activation of ATP-sensitive K(+) channels, H(2)S lowers blood pressure, protects the heart from ischemia and reperfusion injury, inhibits insulin secretion in pancreatic beta cells, and exerts anti-inflammatory, anti-nociceptive and anti-apoptotic effects. 3. H(2)S inhibited L-type Ca(2+) channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca(2+) levels. H(2)S activated small and medium conductance K(Ca) channels but its effect on BK(Ca) channels has not been consistent. 4. H(2)S-induced hyperalgesia and pro-nociception seems to be related to the sensitization of both T-type Ca(2+) channels and TRPV(1) channels. The activation of TRPV(1) and TRPA(1) by H(2)S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl(-) secretion. 5. The activation of Cl(-) channel by H(2)S has been shown as a protective mechanism for neurons from oxytosis. H(2)S also potentiates N-methyl-d-aspartic acid receptor-mediated currents that are involved in regulating synaptic plasticity for learning and memory. 6. Given the important modulatory effects of H(2)S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re-evaluated.

  6. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Hiroyuki [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Nemoto, Eiji, E-mail: e-nemoto@umin.ac.jp [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Kanaya, Sousuke; Hamaji, Nozomu; Sato, Hisae; Shimauchi, Hidetoshi [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)

    2010-04-16

    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca{sup 2+}Ca{sub o}{sup 2+} has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca{sub o}{sup 2+} signaling in odontogenesis remains unclear. We found that elevated Ca{sub o}{sup 2+} increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca{sup 2+} increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca{sup 2+} channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca{sup 2+}, suggesting that the Ca{sup 2+} influx from Ca{sup 2+} channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca{sup 2+}-sensing receptors (CaSR) and only respond slightly to other cations such as Sr{sup 2+} and spermine, suggesting that dental pulp cells respond to Ca{sub o}{sup 2+} to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca{sub o}{sup 2+} among cations.

  7. Transpiration increases during the dry season: patterns of tree water use in eucalypt open-forests of northern Australia.

    Science.gov (United States)

    O'Grady, A. P.; Eamus, D.; Hutley, L. B.

    1999-07-01

    Australian savannas exhibit marked seasonality in precipitation, with more than 90% of the annual total falling between October and May. The dry season is characterized by declining soil water availability and high vapor pressure deficits (up to 2.5 kPa). We used heat pulse technology to measure whole-tree transpiration rates on a daily and seasonal basis for the two dominant eucalypts at a site near Darwin, Australia. Contrary to expectations, transpiration rates were higher during the dry season than during the wet season, largely because of increased evaporative demand and the exploitation of groundwater reserves by the trees. Transpiration rates exhibited a marked hysteresis in relation to vapor pressure deficit, which was more marked in the dry season than in the wet season. This result may be attributable to low soil hydraulic conductivity, or the use of stored stem water, or both. Tree water use was strongly correlated with leaf area and diameter at breast height and there were no differences in transpiration between the species studied. These results are discussed in relation to scaling tree water use to stand water use.

  8. The Role of Potassium Channels in the Temperature Control of Stomatal Aperture.

    Science.gov (United States)

    Ilan, N.; Moran, N.; Schwartz, A.

    1995-07-01

    We used the patch-clamp technique to examine the effect of temperature (13-36[deg]C) on the depolarization-activated K channels (KD channels) and on the hyperpolarization-activated channels (KH channels) in the plasma membrane of Vicia faba guard-cell protoplasts. The steady-state whole-cell conductance of both K channel types increased with temperature up to 20[deg]C. However, whereas the whole-cell conductance of the KH channels increased further and saturated at 28[deg]C, that of KD channels decreased at higher temperatures. The unitary conductance of both channel types increased with temperature like the rate of diffusion in water (temperature quotient of approximately 1.5), constituting the major contribution to the conductance increase in the whole cells. The mean number of available KH channels was not affected significantly by temperature, but the mean number of available KD channels increased significantly between 13 and 20[deg]C and declined drastically above 20[deg]C. This decrease and the reduced steady-state voltage-dependent probability of opening of the KD channels above 28[deg]C (because of a shift of voltage dependence by +21 mV) account for the depression of the whole-cell KD conductance at the higher temperatures. This may be a basic mechanism by which leaves of well-watered plants keep their stomata open during heat stress to promote cooling by transpiration.

  9. State-dependent blocker interactions with the CFTR chloride channel: implications for gating the pore.

    Science.gov (United States)

    Linsdell, Paul

    2014-12-01

    Chloride permeation through the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is subject to voltage-dependent open-channel block by a diverse range of cytoplasmic anions. However, in most cases the ability of these blocking substances to influence the pore opening and closing process has not been reported. In the present work, patch clamp recording was used to investigate the state-dependent block of CFTR by cytoplasmic Pt(NO2)4(2-) ions. Two major effects of Pt(NO2)4(2-) were identified. First, this anion caused fast, voltage-dependent block of open channels, leading to an apparent decrease in single-channel current amplitude. Secondly, Pt(NO2)4(2-) also decreased channel open probability due to an increase in interburst closed times. Interestingly, mutations in the pore that weakened (K95Q) or strengthened (I344K, V345K) interactions with Pt(NO2)4(2-) altered blocker effects both on Cl(-) permeation and on channel gating, suggesting that both these effects are a consequence of Pt(NO2)4(2-) interaction with a single site within the pore. Experiments at reduced extracellular Cl(-) concentration hinted that Pt(NO2)4(2-) may have a third effect, possibly increasing channel activity by interfering with channel closure. These results suggest that Pt(NO2)4(2-) can enter from the cytoplasm into the pore inner vestibule of both open and closed CFTR channels, and that Pt(NO2)4(2-) bound in the inner vestibule blocks Cl(-) permeation as well as interfering with channel opening and, perhaps, channel closure. Implications for the location of the channel gate in the pore, and the operation of this gate, are discussed.

  10. p53 increases intra-cellular calcium release by transcriptional regulation of calcium channel TRPC6 in GaQ3-treated cancer cells.

    Directory of Open Access Journals (Sweden)

    Esha Madan

    Full Text Available p53 and calcium signaling are inter-dependent and are known to show both synergistic and antagonistic effects on each other in the cellular environment. However, no molecular mechanism or cellular pathway is known which shows direct regulation between these important cellular signaling molecules. Here we have shown that in cancer cells treated with anti-neoplastic drug GaQ3, p53, there is an increase in intracellular calcium levels by transcriptional regulation of a novel calcium channel gene TRPC6. p53 directly binds to a 22 bp response element in the TRPC6 gene promoter and increase its mRNA and protein expression. Over-expression of TRPC6 results in calcium-dependent apoptotic death and activation of apoptotic genes in a variety of cancer cells. This research work shows that p53 and its transcriptional activity is critical in regulation of calcium signaling and an increase in the intracellular calcium level might be one of the anti-cancer strategies to induce apoptosis in cancer cells.

  11. Effects of antigliomatin from the scorpion venom of Buthus martensii Karsch on chloride channels on C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Zan Wang; Mingxian Li; Hongmei Meng; Min Huang; Weihong Lin; Li Cui; Shao Wang

    2011-01-01

    Using whole-cell patch-clamp recordings, the effects of antigliomatin were observed on chloride channels on C6 glioma cells cultured in vitro. Antigliomatin was extracted from the venom of the scorpion Buthus martensii Karsch. Chloride channels are closed under normal osmotic pressure. When osmotic pressure was reduced to 120, 110 and 100 mV, the cell volume enlarged, chloride channels opened, and the chloride channel current increased. Three minutes after antigliomatin treatment, the chloride channel current decreased in a dose-dependent manner. These results show that antigliomatin extracted from the venom of the scorpion Buthus martensii Karsch diminishes chloride channel currents on C6 glioma cells.

  12. A Leucine Zipper Motif Essential for Gating of Hyperpolarization-activated Channels*

    Science.gov (United States)

    Wemhöner, Konstantin; Silbernagel, Nicole; Marzian, Stefanie; Netter, Michael F.; Rinné, Susanne; Stansfeld, Phillip J.; Decher, Niels

    2012-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pacemakers in cardiac myocytes and neurons. Although their membrane topology closely resembles that of voltage-gated K+ channels, the mechanism of their unique gating behavior in response to hyperpolarization is still poorly understood. We have identified a highly conserved leucine zipper motif in the S5 segment of HCN family members. In order to study the role of this motif for channel function, the leucine residues of the zipper were individually mutated to alanine, arginine, or glutamine residues. Leucine zipper mutants traffic to the plasma membrane, but the channels lose their sensitivity to open upon hyperpolarization. Thus, our data indicate that the leucine zipper is an important molecular determinant for hyperpolarization-activated channel gating. Residues of the leucine zipper interact with the adjacent S6 segment of the channel. This interaction is essential for voltage-dependent gating of the channel. The lower part of the leucine zipper, at the intracellular mouth of the channel, is important for stabilizing the closed state. Mutations at these sites increase current amplitudes or result in channels with deficient closing and increased min-Po. Our data are further supported by homology models of the open and closed state of the HCN2 channel pore. Thus, we conclude that the leucine zipper of HCN channels is a major determinant for hyperpolarization-activated channel gating. PMID:23048023

  13. Effect of Flow Channel Shape on Performance in Reverse Electrodialysis

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Kilsung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Deok Han; Kim, Daejoong [Sogang Univ., Seoul (Korea, Republic of)

    2017-05-15

    Reverse electrodialysis (RED), which generates electrical energy from the difference in concentration of two solutions, has been actively studied owing to its high potential and the increased interest in renewable energy resulting from the Paris Agreement on climate change. For RED commercialization, its power density needs to be maximized, and therefore various methods have been discussed. In this paper, the power density was measured using various flow shapes based on the aspect ratio, opening ratio, and number of distribution channels. We found that the power density is enhanced with a decrease in the aspect ratio and an increase in the opening ratio and number of distribution channels.

  14. Intra-operative tissue oxygen tension is increased by local insufflation of humidified-warm CO2 during open abdominal surgery in a rat model.

    Directory of Open Access Journals (Sweden)

    Jean K Marshall

    Full Text Available Maintenance of high tissue oxygenation (PtO2 is recommended during surgery because PtO2 is highly predictive of surgical site infection and colonic anastomotic leakage. However, surgical site perfusion is often sub-optimal, creating an obstructive hurdle for traditional, systemically applied therapies to maintain or increase surgical site PtO2. This research tested the hypothesis that insufflation of humidified-warm CO2 into the abdominal cavity would increase sub-peritoneal PtO2 during open abdominal surgery.15 Wistar rats underwent laparotomy under general anesthesia. Three sets of randomized cross-over experiments were conducted in which the abdominal cavity was subjected to alternating exposure to 1 humidified-warm CO2 & ambient air; 2 humidified-warm CO2 & dry-cold CO2; and 3 dry-cold CO2 & ambient air. Sub-peritoneal PtO2 and tissue temperature were measured with a polarographic oxygen probe.Upon insufflation of humidified-warm CO2, PtO2 increased by 29.8 mmHg (SD 13.3; p<0.001, or 96.6% (SD 51.9, and tissue temperature by 3.0°C (SD 1.7 p<0.001, in comparison with exposure to ambient air. Smaller, but significant, increases in PtO2 were seen in experiments 2 and 3. Tissue temperature decreased upon exposure to dry-cold CO2 compared with ambient air (-1.4°C, SD 0.5, p = 0.001.In a rat model, insufflation of humidified-warm CO2 into the abdominal cavity during open abdominal surgery causes an immediate and potentially clinically significant increase in PtO2. The effect is an additive result of the delivery of CO2 and avoidance of evaporative cooling via the delivery of the CO2 gas humidified at body temperature.

  15. Increased expression of T-cell KV1.3 and KCa3.1 channels in the inflamed intestinal wall from patients with active ulcerative colitis

    DEFF Research Database (Denmark)

    Hansen, Lars Koch; Larsen, Dorte; Sadda, Veeranjaneyulu;

    INTRODUCTION: T-cell KV1.3 and KCa3.1 channels have been proposed to be important effector proteins during T-cell activation and also in autoimmune disease by controlling T-cell motility, cytokine production, and proliferation. The role of KV1.3 channels in ulcerative colitis (UC) has not been...

  16. Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-Ylyase expression and activating KATp channels

    Institute of Scientific and Technical Information of China (English)

    Hong-yan LING; Guang WANG; Wei ZHANG; Xing LI; Shou-hong ZHOU; Bi HU

    2012-01-01

    Aim:To investigate the effect of arecoline,a major component of betel nut,on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect.Methods:Male Wistar rats were fed a high-fructose or control diet for 16 weeks.At the beginning of week 13,the rats were injected ip with low (0.5 mg·kg 1·d-1),medi u m (1.0 mg·kg1·d-1) or high (5.0 mg·kg 1·d 1) doses of arecoline for 4 weeks.At the termination of the treatments,blood was collected,fasting blood glucose (FBG) and serum insulin (FSI) levels were measured,and insulin sensitivity index (ISI) was calculated.The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR).The mRNA and protein expression of cystathionine-y-lyase (CSE) in the thoracic aortas was analyzed using RTPCR and Western blot analysis,respectively.Results:In high fructose-fed rats,the levels of FBG and FSI were remarkably increased,whereas the ISI and the mRNA and protein expression of CSE were significantly decreased.ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced.These changes were reversed by treatment with high dose arecoline.Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) orthe ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline.On the contrary,treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats,and pretreatment with propargylglycine or glibenclamide did not cause further changes.Conclusion:Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats,and the potential mechanism of action might be associated with increase of CSE expression and activation of KATP channels by arecoline.

  17. Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating KATP channels

    Science.gov (United States)

    Ling, Hong-yan; Wang, Guang; Zhang, Wei; Li, Xing; Zhou, Shou-hong; Hu, Bi

    2012-01-01

    Aim: To investigate the effect of arecoline, a major component of betel nut, on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect. Methods: Male Wistar rats were fed a high-fructose or control diet for 16 weeks. At the beginning of week 13, the rats were injected ip with low (0.5 mg·kg−1·d−1), medium (1.0 mg·kg−1·d−1) or high (5.0 mg·kg−1·d−1) doses of arecoline for 4 weeks. At the termination of the treatments, blood was collected, fasting blood glucose (FBG) and serum insulin (FSI) levels were measured, and insulin sensitivity index (ISI) was calculated. The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR). The mRNA and protein expression of cystathionine-γ-lyase (CSE) in the thoracic aortas was analyzed using RT-PCR and Western blot analysis, respectively. Results: In high fructose-fed rats, the levels of FBG and FSI were remarkably increased, whereas the ISI and the mRNA and protein expression of CSE were significantly decreased. ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced. These changes were reversed by treatment with high dose arecoline. Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) or the ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibenclamide did not cause further changes. Conclusion: Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats, and the potential mechanism of action might be associated with increase of CSE expression and activation of KATP channels by arecoline. PMID:22820911

  18. Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating K(ATP) channels.

    Science.gov (United States)

    Ling, Hong-yan; Wang, Guang; Zhang, Wei; Li, Xing; Zhou, Shou-hong; Hu, Bi

    2012-08-01

    To investigate the effect of arecoline, a major component of betel nut, on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect. Male Wistar rats were fed a high-fructose or control diet for 16 weeks. At the beginning of week 13, the rats were injected ip with low (0.5 mg·kg(-1)·d(-1)), medium (1.0 mg·kg(-1)·d(-1)) or high (5.0 mg·kg(-1)·d(-1)) doses of arecoline for 4 weeks. At the termination of the treatments, blood was collected, fasting blood glucose (FBG) and serum insulin (FSI) levels were measured, and insulin sensitivity index (ISI) was calculated. The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR). The mRNA and protein expression of cystathionine-γ-lyase (CSE) in the thoracic aortas was analyzed using RT-PCR and Western blot analysis, respectively. In high fructose-fed rats, the levels of FBG and FSI were remarkably increased, whereas the ISI and the mRNA and protein expression of CSE were significantly decreased. ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced. These changes were reversed by treatment with high dose arecoline. Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) or the ATP-sensitive potassium (K(ATP)) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibenclamide did not cause further changes. Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats, and the potential mechanism of action might be associated with increase of CSE expression and activation of K(ATP) channels by arecoline.

  19. BK channel modulators: a comprehensive overview

    DEFF Research Database (Denmark)

    Nardi, Antonio; Olesen, Søren-Peter

    2008-01-01

    and blockers 4) Marketed and/or investigational drugs with BK-modulating side properties and structural analogues 5) Naturally-occurring BK channel openers and structural analogues 6) Synthetic BK channel openers. This review is intended to provide readers with current opinion on the BK channel as a drug...

  20. A model to investigate the influence of suspended sediment on the mass transport of a pollutant in open channel flow. M.S. Thesis - Old Dominion Univ.

    Science.gov (United States)

    Chapman, R. S.

    1977-01-01

    An explicit two-dimensional finite difference model, designed to investigate the influence of suspended sediment on the pollutant transport process, is presented. Specific attention is directed toward examining the role of suspended sediment in: (1) the turbulent vertical transport mechanism in a stratified flow, and (2) pollutant uptake due to sorption. Results presented indicate that suspended sediment plays a major role in the pollutant transport process, and subsequently, any meaningful attempt to model the fate of a pollutant in an alluvial channel must account for the presence of a suspended sediment concentration profile. Similarly, the vertical and longitudinal pollutant concentration distributions provided by the model may be utilized to improve upon the predictive capacities of existing water quality models.

  1. Niflumic acid hyperpolarizes the smooth muscle cells by opening BK(Ca) channels through ryanodine-sensitive Ca(2+) release in spiral modiolar artery.

    Science.gov (United States)

    Li, Li; Ma, Ke-Tao; Zhao, Lei; Si, Jun-Qiang

    2008-12-25

    The mechanism by which niflumic acid (NFA), a Cl(-) channel antagonist, hyperpolarizes the smooth muscle cells (SMCs) of cochlear spiral modiolar artery (SMA) was explored. Guinea pigs were used as subjects and perforated patch clamp and intracellular recording technique were used to observe NFA-induced response of SMC in the acutely isolated SMA preparation. The results showed that bath application of NFA, indanyloxyacetic acid 94 (IAA-94) and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) caused hyperpolarization and evoked outward currents in all cells at low resting potential (RP), but had no effects in cells at high RP. In the low RP SMCs, the average RP was about (-42.47+/-1.38) mV (n=24). Application of NFA (100 mumol/L), IAA-94 (10 mumol/L) and DIDS (200 mumol/L) shifted the RP to (13.7+/-4.3) mV (n=9, P<0.01), (11.4+/-4.2) mV (n=7, P<0.01) and (12.3+/-3.7) mV (n=8, P<0.01), respectively. These drug-induced responses were in a concentration-dependent manner. NFA-induced hyperpolarization and outward current were almost blocked by charybdotoxin (100 nmol/L), iberiotoxin (100 nmol/L), tetraethylammonium (10 mmol/L), BAPTA-AM (50 mumol/L), ryanodine (10 mumol/L) and caffeine (0.1-10 mmol/L), respectively, but not by nifedipine (100 mumol/L), CdCl2 (100 mumol/L) and Ca(2+)-free medium. It is concluded that NFA induces a release of intracellular calcium from the Ca(2+) stores and the released intracellular calcium in turn causes concentration-dependent and reversible hyperpolarization and evokes outward currents in the SMCs of the cochlear SMA via activation of the Ca(2+)-activated potassium channels.

  2. “Eyes Open – Eyes Closed” EEG/fMRI data set including dedicated “Carbon Wire Loop” motion detection channels

    Directory of Open Access Journals (Sweden)

    Johan van der Meer

    2016-06-01

    This paper also links to an EEGlab “EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis” (Delorme and Makeig, 2004 [2] plugin to perform a CWL regression approach to deal with the He pump artifact, as published in the main paper “Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections-A validation of a real-time simultaneous EEG/fMRI correction method” (van der Meer et al., 2016 [3].

  3. A high proportion of blue light increases the photosynthesis capacity and leaf formation rate of Rosa × hybrida but does not affect time to flower opening.

    Science.gov (United States)

    Terfa, Meseret Tesema; Solhaug, Knut Asbjørn; Gislerød, Hans Ragnar; Olsen, Jorunn Elisabeth; Torre, Sissel

    2013-05-01

    Alterations in light quality affect plant morphogenesis and photosynthetic responses but the effects vary significantly between species. Roses exhibit an irradiance-dependent flowering control but knowledge on light quality responses is scarce. In this study we analyzed, the responses in morphology, photosynthesis and flowering of Rosa × hybrida to different blue (B) light proportions provided by light-emitting diodes (LED, high B 20%) and high pressure sodium (HPS, low B 5%) lamps. There was a strong morphological and growth effect of the light sources but no significant difference in total dry matter production and flowering. HPS-grown plants had significantly higher leaf area and plant height, yet a higher dry weight proportion was allocated to leaves than stems under LED. LED plants showed 20% higher photosynthetic capacity (Amax ) and higher levels of soluble carbohydrates. The increase in Amax correlated with an increase in leaf mass per unit leaf area, higher stomata conductance and CO2 exchange, total chlorophyll (Chl) content per area and Chl a/b ratio. LED-grown leaves also displayed a more sun-type leaf anatomy with more and longer palisade cells and a higher stomata frequency. Although floral initiation occurred at a higher leaf number in LED, the time to open flowers was the same under both light conditions. Thereby the study shows that a higher portion of B light is efficient in increasing photosynthesis performance per unit leaf area, enhancing growth and morphological changes in roses but does not affect the total Dry Matter (DM) production or time to open flower.

  4. Transmission from theory to practice: Experiences using open-source code development and a virtual short course to increase the adoption of new theoretical approaches

    Science.gov (United States)

    Harman, C. J.

    2015-12-01

    Even amongst the academic community, new theoretical tools can remain underutilized due to the investment of time and resources required to understand and implement them. This surely limits the frequency that new theory is rigorously tested against data by scientists outside the group that developed it, and limits the impact that new tools could have on the advancement of science. Reducing the barriers to adoption through online education and open-source code can bridge the gap between theory and data, forging new collaborations, and advancing science. A pilot venture aimed at increasing the adoption of a new theory of time-variable transit time distributions was begun in July 2015 as a collaboration between Johns Hopkins University and The Consortium of Universities for the Advancement of Hydrologic Science (CUAHSI). There were four main components to the venture: a public online seminar covering the theory, an open source code repository, a virtual short course designed to help participants apply the theory to their data, and an online forum to maintain discussion and build a community of users. 18 participants were selected for the non-public components based on their responses in an application, and were asked to fill out a course evaluation at the end of the short course, and again several months later. These evaluations, along with participation in the forum and on-going contact with the organizer suggest strengths and weaknesses in this combination of components to assist participants in adopting new tools.

  5. Increase of financing channels for house-purchasers with rigid demand%增加刚性需求购房者融资渠道分析

    Institute of Scientific and Technical Information of China (English)

    王盟; 刘艳娟

    2012-01-01

    针对建筑企业管理中房价上涨过快的问题,采用融资租赁经营的房地产开发经营新模式,通过对融资租赁各方的利益分析,指出采取增加社会筹资渠道解决问题的办法,特别是从刚性需求购房者、政府层面、房地产开发商、银行四个方面进行了分析。研究结果对于解决人民的生活条件,促进经济发展有促进作用。%Financing leasing is a new mode in real estate development and management to deal with fast-growing housing prices in construction enterprise management.Increase of social financing channels was pointed out as a solution based on the analysis of financing leasing parties' benefit.Particular analysis was made of house-purchasers with rigid demand,government,real estate developers and banks.These measures will greatly improve people’s living standard and promote economic development.

  6. Le Chatelier's principle with multiple relaxation channels

    Science.gov (United States)

    Gilmore, R.; Levine, R. D.

    1986-05-01

    Le Chatelier's principle is discussed within the constrained variational approach to thermodynamics. The formulation is general enough to encompass systems not in thermal (or chemical) equilibrium. Particular attention is given to systems with multiple constraints which can be relaxed. The moderation of the initial perturbation increases as additional constraints are removed. This result is studied in particular when the (coupled) relaxation channels have widely different time scales. A series of inequalities is derived which describes the successive moderation as each successive relaxation channel opens up. These inequalities are interpreted within the metric-geometry representation of thermodynamics.

  7. Effects of fractal gating of potassium channels on neuronal behaviours

    Science.gov (United States)

    Zhao, De-Jiang; Zeng, Shang-You; Zhang, Zheng-Zhen

    2010-10-01

    The classical model of voltage-gated ion channels assumes that according to a Markov process ion channels switch among a small number of states without memory, but a bunch of experimental papers show that some ion channels exhibit significant memory effects, and this memory effects can take the form of kinetic rate constant that is fractal. Obviously the gating character of ion channels will affect generation and propagation of action potentials, furthermore, affect generation, coding and propagation of neural information. However, there is little previous research on this series of interesting issues. This paper investigates effects of fractal gating of potassium channel subunits switching from closed state to open state on neuronal behaviours. The obtained results show that fractal gating of potassium channel subunits switching from closed state to open state has important effects on neuronal behaviours, increases excitability, rest potential and spiking frequency of the neuronal membrane, and decreases threshold voltage and threshold injected current of the neuronal membrane. So fractal gating of potassium channel subunits switching from closed state to open state can improve the sensitivity of the neuronal membrane, and enlarge the encoded strength of neural information.

  8. Cardiac ion channels in health and disease.

    Science.gov (United States)

    Amin, Ahmad S; Tan, Hanno L; Wilde, Arthur A M

    2010-01-01

    Cardiac electrical activity depends on the coordinated propagation of excitatory stimuli through the heart and, as a consequence, the generation of action potentials in individual cardiomyocytes. Action potential formation results from the opening and closing (gating) of ion channels that are expressed within the sarcolemma of cardiomyocytes. Ion channels possess distinct genetic, molecular, pharmacologic, and gating properties and exhibit dissimilar expression levels within different cardiac regions. By gating, ion channels permit ion currents across the sarcolemma, thereby creating the different phases of the action potential (e.g., resting phase, depolarization, repolarization). The importance of ion channels in maintaining normal heart rhythm is reflected by the increased incidence of arrhythmias in inherited diseases that are linked to mutations in genes encoding ion channels or their accessory proteins and in acquired diseases that are associated with changes in ion channel expression levels or gating properties. This review discusses ion channels that contribute to action potential formation in healthy hearts and their role in inherited and acquired diseases.

  9. Effect of N-bromoacetamide on single sodium channel currents in excised membrane patches.

    Science.gov (United States)

    Patlak, J; Horn, R

    1982-03-01

    We have studied the effect of N-bromoacetamide (NBA) on the behavior of single sodium channel currents in excised patches of rat myotube membrane at 10 degree C. Inward sodium currents were activated by voltage steps from holding potentials of about -100 mV to test potentials of -40 mV. The cytoplasmic-face solution was isotonic CsF. Application of NBA or pronase to the cytoplasmic face of the membrane irreversibly removed sodium channel inactivation, as determined by averaged single-channel records. Teh lifetime of the open channel at -40 mV was increased about 10-fold by NBA treatment without affecting the amplitude of single-channel currents. A binomial analysis was used both before and after treatment to determine the number of channels within the excised patch. NBA was shown to have little effect on activation kinetics, as determined by an examination of both the rising phase of averaged currents and measurements f the delay between the start of the pulse and the first channel opening. Our data support a kinetic model of sodium channel activation in which the rate constant leading back from the open state to the last closed state is slower than expected from a strict Hodgkin-Huxley model. The data also suggest that the normal open-channel lifetime is primarily determined by the inactivation process in the voltage range we have examined.

  10. RESEARCH AND APPLICATIONS OF REAL -TIME MONITORING TECHNOLOGY FOR WATER LEVEL AND DISCHARGE OF OPEN CHANNEL IN IRRIGATION DISTRICT%灌区明渠水位流量实时监测技术研究与应用

    Institute of Scientific and Technical Information of China (English)

    马腾远; 张庆; 宋玉娟; 王贵田; 马树升

    2011-01-01

    Real-time monitoring water level and discharge of open channel in irrigation district is critical to improve water saving and crop water productivity with quantitative irrigation. In this paper, the necessary components in the monitoring system: water level sensor, ultrasonic flowmeter, data acquisition and flow calculation software and data communication system are described in detail.%灌区明渠水位流量监测对于计量灌溉促进灌区节水和提高作物水分生产率意义重大.本文就监测系统中必备的水位传感器、明渠超声波流量计、数据采集及流量积算软件及数据通信系统等进行了详细阐述.

  11. Study on influence of intake open channel arrangement form on temperature rise of cooling water%电厂取水明渠布置形式对取水温升的影响研究

    Institute of Scientific and Technical Information of China (English)

    刘海成; 陈汉宝

    2011-01-01

    文章以印尼某燃煤电厂工程为背景,研究了取排水明渠的不同布置形式对温排水扩散趋势和取水口温升的影响.并对原设计方案进行优化,在取水温升满足设计要求的条件下使工程更为经济合理.可为类似工程提供参考.%Based on the background of a coal-fired power plant project in Indonesia, the influence of intake open channel arrangement form on the temperature rise of cooling water was studied.Then the original design scheme was optimized in a more economical and rational way .That provides a reference for similar projects.

  12. Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins

    OpenAIRE

    Lau, David; Vega-Saenz de Miera, Eleazar; Contreras, Diego; Ozaita Mintegui, Andrés, 1969-; Harvey, Michael; Chow, Alan; Noebels, Jeffrey L; Paylor, Richard; Morgan, James I.; Leonard, Christopher S.; Rudy, Bernardo

    2000-01-01

    Voltage-gated K+ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to −10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidenc...

  13. ACL injury while jumping rope in a patient with an unintended increase in the tibial slope after an opening wedge high tibial osteotomy.

    Science.gov (United States)

    Jung, Kwang Am; Lee, Su Chan; Hwang, Seung Hyun; Song, Moon Bok

    2009-08-01

    High tibial osteotomy (HTO) is an accepted surgical technique for the treatment of medial compartmental arthrosis of the knee in younger patients. Compared to total knee arthroplasty, HTO may be a good choice in patients who wish to continue with heavy labor and/or impact sports. Based on the rehabilitation protocol after HTO, impact sports, such as running, jumping rope, and full sports activities, are generally permitted 6 months postoperatively. Jumping rope is an excellent form of aerobic exercise, and when done properly, jumping rope can lead to a dramatic improvement in rehabilitation and full sports activities. However, an adequate evaluation should be performed prior to initiating impact sports. We present the case of a ruptured anterior cruciate ligament that occurred in a patient with an unintended increase in the tibial slope after an opening wedge HTO who was jumping rope.

  14. Openness, Web 2.0 Technology, and Open Science

    Science.gov (United States)

    Peters, Michael A.

    2010-01-01

    Open science is a term that is being used in the literature to designate a form of science based on open source models or that utilizes principles of open access, open archiving and open publishing to promote scientific communication. Open science increasingly also refers to open governance and more democratized engagement and control of science…

  15. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

    Science.gov (United States)

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

    2016-02-01

    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the