Sample records for increases channel open

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

    Directory of Open Access Journals (Sweden)

    Mauricio Antonio Retamal


    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.

  2. All channels open

    NARCIS (Netherlands)

    Frank Huysmans; Jos de Haan


    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

  3. Evaporative Lithography in Open Microfluidic Channel Networks

    KAUST Repository

    Lone, Saifullah


    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.

  4. Design of open rectangular and trapezoidal channels (United States)

    González, C. P.; Vera, P. E.; Carrillo, G.; García, S.


    In this work, the results of designing open channels in rectangular and trapezoidal form are presented. For the development of the same important aspects were taken as determination of flows by means of formula of the rational method, area of the surface for its implementation, optimal form of the flow to meet the needs of that environment. In the design the parameter of the hydraulic radius expressed in terms of the hydraulic area and wet perimeter was determined, considering that the surface on which the fluid flows is the product of the perimeter of the section and the length of the channel and where shear is generated by the condition of no slippage.

  5. Scour monitoring via turbulent open channel flow

    International Nuclear Information System (INIS)

    Fisher, M; Khan, A; Atamturktur, S


    Scour is the leading cause of bridge failure in the United States. It can result in the loss of lives and costs millions to repair the damage. A novel method is proposed for monitoring scour that exploits the turbulence in natural channels. The method utilizes the dynamic pressure associated with the turbulent velocity fluctuations in the flow to excite a flexible plate. A semi-empirical model is developed to describe the interaction of turbulent open channel flow with the plate. The model describes the variation of turbulent velocity fluctuations across the flow depth in an open channel resulting in a method for determining the average dynamic pressure on the flexible plate. The dynamic response of the plate is then modeled by superimposing the response of multiple modes of the disk to the random, turbulent dynamic pressure spectrum. The model is verified considering the pressure integration across the plate surface to ensure converged solutions. Due to the uncertainties in the material properties of the plate, the experimentally determined natural frequencies and vibration measurements are used to calibrate the model. The calibrated model predictions are then compared against an independent dataset for validation. In addition to describing the physical operation of the device, the semi-empirical model is also employed to optimize the field device. Measurements made using the field device also confirmed the model results, even in a non-design, misaligned flow condition. (paper)

  6. Mathematical modelling and its impact on open channel flow | Eyo ...

    African Journals Online (AJOL)

    Mathematical model for dredging (excavating) an open channel, namely, a river has been developed using the conditions for best hydraulic performances for the channel. Applying the model to a numerical example we determine new dimensions for the new open channel for two-channel sections, viz: the trapezoidal and ...

  7. Flow resistance in open channels with fixed movable bed (United States)

    Simoes, Francisco J.


    In spite of an increasingly large body of research by many investigators, accurate quantitative prediction of open channel flow resistance remains a challenge. In general, the relations between the elements influencing resistance (turbulence, boundary roughness, and channel shape features, such as discrete obstacles, bars, channel curvature, recirculation areas, secondary circulation, etc.) and mean flow variables are complex and poorly understood. This has resulted in numerous approaches to compute friction using many and diverse variables and equally diverse prescriptions for their use. In this paper, a new resistance law for surface (grain) resistance, the resistance due to the flow viscous effects on the channel boundary roughness elements, is presented for the cases of flow in the transition (5 friction losses in channels and natural rivers with plane beds, regardless of sediment transport conditions. This work is useful to hydraulic engineers involved with the derivation of depth-discharge relations in open channel flow and with the estimation of sediment transport rates for the case of bedload transport.

  8. TVD schemes for open channel flow (United States)

    Delis, A. I.; Skeels, C. P.


    The Saint Venant equations for modelling flow in open channels are solved in this paper, using a variety of total variation diminishing (TVD) schemes. The performance of second- and third-order-accurate TVD schemes is investigated for the computation of free-surface flows, in predicting dam-breaks and extreme flow conditions created by the river bed topography. Convergence of the schemes is quantified by comparing error norms between subsequent iterations. Automatically calculated time steps and entropy corrections allow high CFL numbers and smooth transition between different conditions. In order to compare different approaches with TVD schemes, the most accurate of each type was chosen. All four schemes chosen proved acceptably accurate. However, there are important differences between the schemes in the occurrence of clipping, overshooting and oscillating behaviour and in the highest CFL numbers allowed by a scheme. These variations in behaviour stem from the different orders and inherent properties of the four schemes.

  9. Reinvestigation on mixing length in an open channel turbulent flow (United States)

    Kundu, Snehasis; Kumbhakar, Manotosh; Ghoshal, Koeli


    The present study proposes a model on vertical distribution of streamwise velocity in an open channel turbulent flow through a newly proposed mixing length, which is derived for both clear water and sediment-laden turbulent flows. The analysis is based on a theoretical consideration which explores the effect of density stratification on the streamwise velocity profile. The derivation of mixing length makes use of the diffusion equation where both the sediment diffusivity and momentum diffusivity are taken as a function of height from the channel bed. The damping factor present in the mixing length of sediment-fluid mixture contains velocity and concentration gradients. This factor is capable of describing the dip-phenomenon of velocity distribution. From the existing experimental data of velocity, the mixing length data are calculated. The pattern shows that mixing length increases from bed to the dip-position, having a larger value at dip-position and then decreases up to the water surface with a zero value thereat. The present model agrees well with these data sets and this behavior cannot be described by any other existing model. Finally, the proposed mixing length model is applied to find the velocity distribution in wide and narrow open channels. The derived velocity distribution is compared with laboratory channel data of velocity, and the comparison shows good agreement.

  10. Turbulence characteristics in sharp open-channel bends

    NARCIS (Netherlands)

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


    In spite of its importance, little is known about the turbulence characteristics in open-channel bends. This paper reports on an experimental investigation of turbulence in one cross section of an open-channel bend. Typical flow features are a bicellular pattern of cross-stream circulation

  11. Frequency width of open channels in multiple scattering media

    NARCIS (Netherlands)

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


    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

  12. Drifting plasmons in open two-dimensional channels: modal analysis

    International Nuclear Information System (INIS)

    Sydoruk, O


    Understanding the properties of plasmons in two-dimensional channels is important for developing methods of terahertz generation. This paper presents a modal analysis of plasmonic reflection in open channels supporting dc currents. As it shows, the plasmons can be amplified upon reflection if a dc current flows away from a conducting boundary; de-amplification occurs for the opposite current direction. The problem is solved analytically, based on a perturbation calculation, and numerically, and agreement between the methods is demonstrated. The power radiated by a channel is found to be negligible, and plasmon reflection in open channels is shown to be similar to that in closed channels. Based on this similarity, the oscillator designs developed earlier for closed channels could be applicable also for open ones. The results develop the modal-decomposition technique further as an instrument for the design of terahertz plasmonic sources. (paper)

  13. Computation of gradually varied flow in compound open channel ...

    Indian Academy of Sciences (India)

    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 ...

  14. Computation of gradually varied flow in compound open channel ...

    Indian Academy of Sciences (India)

    1Department of Civil Engineering, Indian Institute of Technology Kharagpur, ... 2Department of Civil and Environmental Engineering, University of South Carolina, ... channels, interconnected storm water drainage systems and irrigation canals fed from different sources. The flow of water in an open channel can be treated as ...

  15. Computation of gradually varied flow in compound open channel ...

    Indian Academy of Sciences (India)

    Abstract. Although, natural channels are rarely rectangular or trapezoidal in cross section, these cross sections are assumed for the computation of steady, gradually var- ied flow in open channel networks. The accuracy of the computed results, therefore, becomes questionable due to differences in the hydraulic and ...

  16. Open-channel effects on heavy-quarkonium spectra: a phenomenological study within a one-open-channel approximation

    International Nuclear Information System (INIS)

    Matsuda, Y.; Kato, K.; Yabusaki, N.; Hirano, M.; Nakanishi, R.; Sakai, M.


    Open-channel effects on charmonium (S- and D-waves) and bottomonium (S-wave) J P = 1 - spectra are investigated within a one-open-channel approximation. Mass shifts and decay widths of these states just above the threshold are obtained by taking into account a coupling between confined quarkonium states and decaying states of the open channel. The final-state interaction (FSI) between the decaying meson and antimeson plays a very important role in producing a reasonable magnitude of coupling; the FSI provides the open-channel poles (R 1 , R 2 ) at the appropriate positions on the complex energy plane. The result is found to be independent of the detailed form of the transition potential and the final-state interaction. (author)

  17. universal specific energy curve for para- bolic open channels

    African Journals Online (AJOL)


    where A is the flow cross-sectional area, Q is the discharge and g is acceleration due to grav- ity. In parabolic open channels (illustrated in. Figure 1) by definition, the relationship be- tween flow depth y varies with the square of the water surface width b, i.e.. 2 cby. (1). (2) by. A. 3. 2. (compared to A =½by for a triangular open.

  18. Minoxidil opens mitochondrial KATP channels and confers cardioprotection (United States)

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


    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

  19. Secondary flow in sharp open-channel bends

    NARCIS (Netherlands)

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


    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

  20. Decelerating open-channel flow in a gradual expansion

    NARCIS (Netherlands)

    Hoan, N.T.; Booij, R.; Stive, M.J.F.; Verhagen, H.J.


    The velocity and turbulence distributions of decelerating open-channel flow in a gradual expansion were measured using LDV equipment. The results show that the logarithmic law can describe the mean velocity in the bottom region well while the Coles’ law can be applied to the outer region. The shear

  1. Transport of suspended particles in turbulent open channel flows

    NARCIS (Netherlands)

    Breugem, W.A.


    Two experiments are performed in order to investigate suspended sediment transport in a turbulent open channel flow. The first experiment used particle image velocimetry (PIV) to measure the fluid velocity with a high spatial resolution, while particle tracking velocimetry (PTV) was used to measure

  2. Port-Hamiltonian discretization for open channel flows

    NARCIS (Netherlands)

    Ramkrishna Pasumarthy, R.P.; Ambati, V.R.; van der Schaft, Arjan


    A finite-dimensional Port-Hamiltonian formulation for the dynamics of smooth open channel flows is presented. A numerical scheme based on this formulation is developed for both the linear and nonlinear shallow water equations. The scheme is verified against exact solutions and has the advantage of

  3. Microfluidic mixing in a Y-junction open channel

    Directory of Open Access Journals (Sweden)

    Jue Nee Tan


    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.

  4. LightNVM: The Linux Open-Channel SSD Subsystem

    DEFF Research Database (Denmark)

    Bjørling, Matias; Gonzalez, Javier; Bonnet, Philippe


    resource utilization. We propose that SSD management trade-offs should be handled through Open-Channel SSDs, a new class of SSDs, that give hosts control over their internals. We present our experience building LightNVM, the Linux Open-Channel SSD subsystem. We introduce a new Physical Page Ad- dress I....../O interface that exposes SSD parallelism and storage media characteristics. LightNVM integrates into traditional storage stacks, while also enabling storage engines to take advantage of the new I/O interface. Our experimental results demonstrate that LightNVM has modest host overhead, that it can be tuned...... to limit read latency variability and that it can be customized to achieve predictable I/O latencies....

  5. Mechanics of Bingham Flow in an Open Channel


    荻原, 能男; 宮沢, 直季; 三浦, 美香


    In this paper, the velocity distribution on turbulent Bingham flow in an open channel is derived theoretically and the fitness of this distribution is examined by comparing with results of experiment using the fluid of water and bentonite mixture which shows the behavior of Bingham flow. The results show that the theoretical turbulent velocity distribution obtained here conforms to results of experiment in the region of lower bentonite concentration. By experiment, the empirical fomulae to es...

  6. 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.

  7. Two open states of P2X receptor channels

    Directory of Open Access Journals (Sweden)

    Milos B. Rokic


    Full Text Available The occupancy of the ATP binding sites of P2X receptor (P2XR channels causes the rapid opening of a small cation-permeable pore, followed by a gradual dilation that renders the pore permeable to large organic cations. Electrophysiologically, this phenomenon was shown using whole-cell current recording on P2X2R-, P2X2/X5R-, P2X4R- and P2X7R-expressing cells that were bathed in N-methyl-D-glucamine-containing buffers in the presence and/or absence of small monovalent and divalent cations. The pore dilation of P2X4R and P2X7R caused a secondary current growth, whereas that of P2X2R showed a sustained kinetic coupling of dilation and desensitization, leading to receptor channel closure. The pore size of the P2X7R open and dilated states was estimated to be approximately 0.85 nm and greater than 1 nm, respectively. The P2XR pore dilation was also observed in intact cells by measurement of fluorescent dye uptake/release, application of polyethylene glycols of different sizes, and atomic force microscopy. However, pore dilation was not observed at the single channel level. Structural data describing the dilated state are not available, and the relevance of orthosteric and allosteric ligand interactions to pore dilation was not studied.

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

    Directory of Open Access Journals (Sweden)

    Darryl W Hondorp

    Full Text Available 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

  9. Modeling fluid flow in open channel with circular cross‐section ...

    African Journals Online (AJOL)

    Flow in a closed conduit is regarded as open channel flow, if it has a free surface. This study considers unsteady non]uniform open channel flow in a closed conduit with circular cross]section. We investigate the effects of the flow depth, the cross section area of flow, channel radius, slope of the channel, roughness coefficient ...

  10. Flow of two stratified fluids in an open channel with addition of fluids along the channel length

    International Nuclear Information System (INIS)

    Gardner, G.C.


    It is shown that two stably stratified fluids flowing in an open channel have two critical flow conditions. The one at higher flowrates is equivalent to the choked flow condition of a single fluid over a broad-crested weir, when the Froude number is unity. The lower critical condition imposes restrictions, which define the system if fluids are added progressively along the channel length and the flowrates increase from low to high values. However, if the flowrate does not become sufficiently large to pass through the lower critical condition, this condition will then define a form of choking, which again determines the system. It is shown that an important special case, with the proportional flowrates of the two fluids kept constant, has an analytical solution in which the relative depths of the fluids is a constant along the channel. Other systems must be solved numerically. (orig.)

  11. Facilitation by the beta2a subunit of pore openings in cardiac Ca2+ channels. (United States)

    Costantin, J; Noceti, F; Qin, N; Wei, X; Birnbaumer, L; Stefani, E


    1. Single channel recordings were performed on the cardiac calcium channel (alpha1C) in order to study the effect of coexpression of the accessory beta2a subunit. On-cell patch clamp recordings were performed after expression of these channels in Xenopus oocytes. 2. The alpha1C subunit, when expressed alone, had similar single channel properties to native cardiac channels. Slow transitions between low and high open probability (Po) gating modes were found as well as fast gating transitions between the open and closed states. 3. Coexpression of the beta2a subunit caused changes in the fast gating during high Po mode. In this mode, open time distributions reveal at least three open states and the beta2a subunit favours the occupancy of the longest, 10-15 ms open state. No effect of the beta2a subunit was found when the channel was gating in the low Po mode. 4. Slow gating transitions were also affected by the beta2a subunit. The high Po mode was maintained for the duration of the depolarizing pulse in the presence of the beta2a subunit; while the alpha1C channel when expressed alone, frequently switched into and out of the high Po mode during the course of a sweep. 5. The beta2a subunit also affected mode switching that occurred between sweeps. Runs analysis revealed that the alpha1C subunit has a tendency toward non-random mode switching. The beta2a subunit increased this tendency. A chi2 analysis of contingency tables indicated that the beta2a subunit caused the alpha1C channel to gain 'intrinsic memory', meaning that the mode of a given sweep can be non-independent of the mode of the previous sweep. 6. We conclude that the beta2a subunit causes changes to the alpha1C channel in both its fast and slow gating behaviour. The beta2a subunit alters fast gating by facilitating movement of the channel into an existing open state. Additionally, the beta2a subunit decreases the slow switching between low and high Po modes.

  12. Solute dispersion in open channel flow with bed absorption (United States)

    Wang, Ping; Chen, G. Q.


    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.

  13. Capillary Flows Along Open Channel Conduits: The Open-Star Section (United States)

    Weislogel, Mark; Geile, John; Chen, Yongkang; Nguyen, Thanh Tung; Callahan, Michael


    Capillary rise in tubes, channels, and grooves has received significant attention in the literature for over 100 years. In yet another incremental extension of such work, a transient capillary rise problem is solved for spontaneous flow along an interconnected array of open channels forming what is referred to as an 'open-star' section. This geometry possesses several attractive characteristics including passive phase separations and high diffusive gas transport. Despite the complex geometry, novel and convenient approximations for capillary pressure and viscous resistance enable closed form predictions of the flow. As part of the solution, a combined scaling approach is applied that identifies unsteady-inertial-capillary, convective-inertial-capillary, and visco-capillary transient regimes in a single parameter. Drop tower experiments are performed employing 3-D printed conduits to corroborate all findings.

  14. 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


    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.

  15. Rotenone induces KATP channel opening in PC12 cells in association with the expression of tyrosine hydroxylase. (United States)

    Bai, Qunhua; He, Junlin; Qiu, Jingfu; Wang, Yang; Wang, Shibo; Xiu, Yun; Yu, Chao


    The activation of ATP-sensitive potassium (KATP) channels in PC12 cells play a pivotal role in protection against the neurotoxic effect of rotenone. However, it remains unclear why rotenone seems to preferentially affect activation of KATP channels and if this could affect its physiological activity. In this study, we sought to determine how the different energy states caused by various doses of rotenone affect the KATP opening state and whether the KATP opening state influences the expression of tyrosine hydroxylase (TH) which is related with DA synthesis. With patch clamp technology, results showed that treatment of PC12 cells with rotenone (0.2-1 µg/ml) for 15 min can cause KATP channel opening with significantly increased intracellular ROS production. Treatment with rotenone (2-16 ng/ml) for 24 h also caused the channels to open with gently increased ROS. In order to study if the rather long-term action on KATP channel opening states could affect the specified function of PC12 cells, the KATP channel opener pinacidil and the inhibitor glibenclamide were used to treat cells for 24 h, and the expression of TH was detected. Our results showed that treatment of PC12 cells with glibenclamide for 24 h can notably promote TH expression and can also enhance the expression of TH which were reduced by rotenone. These data indicate that the energy states in PC12 induced by various doses of rotenone could significantly influence the opening states of KATP channels. However long-term energy stress may raise the opening rate and opening sensitivity of this channel. In addition, our results demonstrate for the first time that activation of plasma membrane KATP channels induced by rotenone inhibits TH expression which influences DA synthesis in PC12 cells.

  16. Increased Numbers of Ion Channels Promoted by an Intracellular Second Messenger (United States)

    Gunning, Richard


    The anomalous rectifier potassium current in Aplysia neurons was examined to determine the immediate cause of an increase in conductance induced by serotonin and mediated by adenosine 3' ,5' -monophosphate. Voltage-dependent cesium ion block and steady-state current power spectral density were measured under voltage clamp before and after application of serotonin. The amplitude of the anomalous rectifier conductance was increased by adding serotonin, but the shapes of the conductance-voltage curve and the power spectrum were not altered. Calculation of the number of functional channels and of the single-channel conductance from the power spectra indicates that the serotonin-induced increase in conductance resulted from an increase in the number of functional channels, while the single-channel conductance and the open-channel probability were unchanged.

  17. Predicting the impact of vegetations in open channels with different distributaries' operations on water surface profile using artificial neural networks

    International Nuclear Information System (INIS)

    Abdeen, Mostafa A. M.


    Most of the open water irrigation channels in Egypt suffer from the infestation of aquatic weeds, especially the submerged ones that cause numerous hydraulic problems for the open channels themselves and their water distributaries such as increasing water losses, obstructing water flow, and reducing channels' water distribution efficiencies. Accurate simulation and prediction of flow behavior in such channels is very essential for water distribution decision makers. Artificial neural networks (ANN) have proven to be very successful in the simulation of several physical phenomena, in general, and in the water research field in particular. Therefore, the current study aims towards introducing the utilization of ANN in simulating the impact of vegetation in main open channel, which supplies water to different distributaries, on the water surface profile in this main channel. Specifically, the study, presented in the current paper utilizes ANN technique for the development of various models to simulate the impact of different submerged weeds' densities, different flow discharges, and different distributaries operation scheduling on the water surface profile in an experimental main open channel that supplies water to different distributaries. In the investigated experiment, the submerged weeds were simulated as branched flexible elements. The investigated experiment was considered as an example for implementing the same methodology and technique in a real open channel system. The results showed that the ANN technique is very successful in simulating the flow behavior of the pre-mentioned open channel experiment with the existence of the submerged weeds. In addition, the developed ANN models were capable of predicting the open channel flow behavior in all the submerged weeds' cases that were considered in the ANN development process

  18. 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


    .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...

  19. Flow in a triangular open channel with hydraulic jump | Eyo | Journal ...

    African Journals Online (AJOL)

    Mathematical model for dredging a triangular open channel with hydraulic jump is developed using the method of successive approximation. Applying the model to a numerical example new parameters of the new (excavated) channel are determined and compared with those of the original channel. Another feature of the ...

  20. Before-after environmental impact assessment of an artificial channel opening on a south-western Atlantic choked lagoon system. (United States)

    Prestrelo, L; Monteiro-Neto, C


    This study aimed to evaluate the human induced impact of a channel opening in a choked lagoon and attempted to establish the cause-effect links for the observed changes. The same lagoon system was sampled before and after the channel opening event, and the differences in fish and crustacean assemblages and environmental variables between these periods analysed. The opening of the artificial channel resulted in salinity increases, leading to a shift in species composition, favouring marine species and reducing abundance and diversity of previously dominant freshwater species. Furthermore, saltwater entrance into the choked lagoon caused an unexpected decrease in species richness and biomass, plus deterioration of ecosystem processes, reducing fishing capacity. The effects of salinity on the ecosystem vary depending on the ecosystem's composition and capacity to overcome salinity changes, thus specific monitoring projects are important strategies for developing coastal lagoon conservation management. © 2016 The Fisheries Society of the British Isles.

  1. KCNQ2/3 openers show differential selectivity and site of action across multiple KCNQ channels. (United States)

    Zhang, Di; Thimmapaya, Rama; Zhang, Xu-Feng; Anderson, David J; Baranowski, John L; Scanio, Marc; Perez-Medrano, Arturo; Peddi, Sridhar; Wang, Zhi; Patel, Jyoti R; DeGoey, David A; Gopalakrishnan, Murali; Honore, Prisca; Yao, Betty B; Surowy, Carol S


    KCNQ2/3 voltage-gated potassium channels conduct low-threshold, slowly activating and non-inactivating currents to repolarize the neuronal resting membrane potential. The channels negatively regulate neuronal excitability and KCNQ2/3 openers are efficacious in hyperexcited states such as epilepsy and pain. We developed and utilized thallium influx assays to profile novel KCNQ2/3 channel openers with respect to selectivity across KCNQ subtypes and on requirement for tryptophan 236 of KCNQ2, a critical residue for activity of the KCNQ opener retigabine. Using distinct chemical series of openers, a quinazolinone series showed relatively poor selectivity across multiple KCNQ channels and lacked activity at the KCNQ2(W236L) mutant channel. In contrast, several novel benzimidazole openers showed selectivity for KCNQ2/3 and KCNQ2 and retain activity at KCNQ2(W236L). Profiling of several hundred KCNQ2/3 openers across multiple diverse chemical series revealed that openers show differential degrees of selectivity across subtypes, with selectivity most difficult to achieve against KCNQ2. In addition, we report the significant finding that KCNQ openers can pharmacologically differentiate between homomeric and heteromeric channels containing subtypes in common. Moreover, most openers assayed were dependent on the W236 for activity, whereas only a small number appear to use a distinct mechanism. Collectively, we provide novel insights into the molecular pharmacology of KCNQ channels by demonstrating differential selectivity and site of action for KCNQ2/3 openers. The high-throughput thallium influx assays should prove useful for rapid characterization of KCNQ openers and in guiding efforts to identify selective compounds for advancement towards the clinic. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Obtaining of Analytical Relations for Hydraulic Parameters of Channels With Two Phase Flow Using Open CFD Toolbox (United States)

    Varseev, E.


    The present work is dedicated to verification of numerical model in standard solver of open-source CFD code OpenFOAM for two-phase flow simulation and to determination of so-called “baseline” model parameters. Investigation of heterogeneous coolant flow parameters, which leads to abnormal friction increase of channel in two-phase adiabatic “water-gas” flows with low void fractions, presented.

  3. Constant fields and constant gradients in open ionic channels. (United States)

    Chen, D P; Barcilon, V; Eisenberg, R S


    Ions enter cells through pores in proteins that are holes in dielectrics. The energy of interaction between ion and charge induced on the dielectric is many kT, and so the dielectric properties of channel and pore are important. We describe ionic movement by (three-dimensional) Nemst-Planck equations (including flux and net charge). Potential is described by Poisson's equation in the pore and Laplace's equation in the channel wall, allowing induced but not permanent charge. Asymptotic expansions are constructed exploiting the long narrow shape of the pore and the relatively high dielectric constant of the pore's contents. The resulting one-dimensional equations can be integrated numerically; they can be analyzed when channels are short or long (compared with the Debye length). Traditional constant field equations are derived if the induced charge is small, e.g., if the channel is short or if the total concentration gradient is zero. A constant gradient of concentration is derived if the channel is long. Plots directly comparable to experiments are given of current vs voltage, reversal potential vs. concentration, and slope conductance vs. concentration. This dielectric theory can easily be tested: its parameters can be determined by traditional constant field measurements. The dielectric theory then predicts current-voltage relations quite different from constant field, usually more linear, when gradients of total concentration are imposed. Numerical analysis shows that the interaction of ion and channel can be described by a mean potential if, but only if, the induced charge is negligible, that is to say, the electric field is spatially constant.

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

    Directory of Open Access Journals (Sweden)

    Strutynskyi, R.B.


    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.

  5. Antagonism of Lidocaine Inhibition by Open-Channel Blockers That Generate Resurgent Na Current (United States)

    Bant, Jason S.; Aman, Teresa K.; Raman, Indira M.


    Na channels that generate resurgent current express an intracellular endogenous open-channel blocking protein, whose rapid binding upon depolarization and unbinding upon repolarization minimizes fast and slow inactivation. Na channels also bind exogenous compounds, such as lidocaine, which functionally stabilize inactivation. Like the endogenous blocking protein, these use-dependent inhibitors bind most effectively at depolarized potentials, raising the question of how lidocaine-like compounds affect neurons with resurgent Na current. We therefore recorded lidocaine inhibition of voltage-clamped, tetrodotoxin-sensitive Na currents in mouse Purkinje neurons, which express a native blocking protein, and in mouse hippocampal CA3 pyramidal neurons with and without a peptide from the cytoplasmic tail of NaVβ4 (the β4 peptide), which mimics endogenous open-channel block. To control channel states during drug exposure, lidocaine was applied with rapid-solution exchange techniques during steps to specific voltages. Inhibition of Na currents by lidocaine was diminished by either the β4 peptide or the native blocking protein. In peptide-free CA3 cells, prolonging channel opening with a site-3 toxin, anemone toxin II, reduced lidocaine inhibition; this effect was largely occluded by open-channel blockers, suggesting that lidocaine binding is favored by inactivation but prevented by open-channel block. In constant 100 μM lidocaine, current-clamped Purkinje cells continued to fire spontaneously. Similarly, the β4 peptide reduced lidocaine-dependent suppression of spiking in CA3 neurons in slices. Thus, the open-channel blocking protein responsible for resurgent current acts as a natural antagonist of lidocaine. Neurons with resurgent current may therefore be less susceptible to use-dependent Na channel inhibitors used as local anesthetic, antiarrhythmic, and anticonvulsant drugs. PMID:23486968

  6. Explicit solutions for critical and normal depths in trapezoidal and parabolic open channels


    Ali R. Vatankhah


    Normal and critical depths are important parameters in the design of open channels and analysis of gradually varied flow. In trapezoidal and parabolic channels, the governing equations are highly nonlinear in the normal and critical flow depths and thus solution of the implicit equations involves numerical methods (except for critical depth in parabolic channels). In current research explicit solutions have been obtained using the non-dimensional forms of the governing equations. For the trap...

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

    DEFF Research Database (Denmark)

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


    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...

  8. Distribution of Fecal Indicator Bacteria in Sediment of Local Open Channels Receiving Johkasou Effluent

    Directory of Open Access Journals (Sweden)

    Joni Aldilla Fajri


    Full Text Available Onsite wastewater treatment system named Johkasou has been widely applied in the Japanese rural areas, which the effluent is mainly discharged into stream channels. However, Johkasou effluent would potentially be a source of contamination that can deteriorate water and sediment quality of the receiving downstream network. In order to identify the effect of Johkasou effluent particularly in sediment, a study on the distribution of fecal indicators (F-RNA bacteriophages, total coliform (TC, and Escherichia coli [E. coli] in several sediment spots of local open channels receiving Johkasou effluent was conducted. The results showed that the contents of F-RNA bacteriophages, TC and E. coli in the sediment of open channels were detected in high levels while those contents in the sediment of Johkasou drainage channel were up to two orders magnitude higher than in the open channel. A high number of fecal bacteria in the receiving open channels was majorly influenced by the number of domestic households. Moderate correlations of fecal bacteria indicator with solid sediment and volatile sediment indicate that the sediment particles can be carriers of microbes to the downstream water networks. Therefore, water flushing and hydraulic events are suggested to reduce sediment depth that contained fecal bacteria indicator in the open channel.

  9. An experimental and analytical study of flow through a supersonic open channel with contoured floor (United States)

    Saheli, F. P.; Dunn, B.; Marrs, K.; Kumar, A.; Peery, K. M.


    A wind tunnel experiment was performed to study the characteristics of supersonic airflow (M(infinity) = 2.5-3.86) through an open channel with a contoured floor. The measured static pressures along the centerline of the channel floor exhibited an unexpected rise at the end of the channel. Complex three-dimensional interactions of compression and expansion waves within the channel coupled with external flow perturbations caused by model/tunnel wall interference were the suspected sources of this flow behavior. Three-dimensional inviscid flow analysis procedures were used to investigate and explain this phenomenon. The results of the computations and the experiment are presented and discussed.

  10. Influence of Chimney Flow Pattern on Natural Convection Heat Transfer of Open Channel Finned Plates

    International Nuclear Information System (INIS)

    Hong, Seung-Hyun; Chung, Bum-Jin


    The enhancement of the efficiency and effectiveness of the passive cooling system, have long been the topic of those studies. In this study, we investigated the heat transfer enhancement of finned plates, especially the chimney effect appeared in finned plates. The fin not only enlarges the heat transfer area but also draws fresh fluid from the open side of the channel composed of the base plate and fins, which further enhances the cooling capability of finned plate – a chimney flow pattern. This study aims at investigating the influence of the chimney flow pattern on the natural convection heat transfer of the finned plate. To analyze the phenomenological study, both experimental and numerical analyses were performed. Numerical analysis was performed for the natural convection heat transfer of a finned plate in an open channel. In order to investigate the influence of the chimney flow pattern the heat transfer, several fin height were simulated and compared. The temperature profiles varied drastically depending on the values of the Prandtl number. As the Prandtl number increases, the thermal boundary layer reduces

  11. Large-eddy simulation of open channel flow with surface cooling

    International Nuclear Information System (INIS)

    Walker, R.; Tejada-Martínez, A.E.; Martinat, G.; Grosch, C.E.


    Highlights: • Open channel flow comparable to a shallow tidal ocean flow is simulated using LES. • Unstable stratification is imposed by a constant surface cooling flux. • Full-depth, convection-driven, rotating supercells develop when cooling is applied. • Strengthening of cells occurs corresponding to an increasing of the Rayleigh number. - Abstract: Results are presented from large-eddy simulations of an unstably stratified open channel flow, driven by a uniform pressure gradient and with zero surface shear stress and a no-slip lower boundary. The unstable stratification is applied by a constant cooling flux at the surface and an adiabatic bottom wall, with a constant source term present to ensure the temperature reaches a statistically steady state. The structure of the turbulence and the turbulence statistics are analyzed with respect to the Rayleigh number (Ra τ ) representative of the surface buoyancy relative to shear. The impact of the surface cooling-induced buoyancy on mean and root mean square of velocity and temperature, budgets of turbulent kinetic energy (and components), Reynolds shear stress and vertical turbulent heat flux will be investigated. Additionally, colormaps of velocity fluctuations will aid the visualization of turbulent structures on both vertical and horizontal planes in the flow. Under neutrally stratified conditions the flow is characterized by weak, full-depth, streamwise cells similar to but less coherent than Couette cells in plane Couette flow. Increased Ra τ and thus increased buoyancy effects due to surface cooling lead to full-depth convection cells of significantly greater spanwise size and coherence, thus termed convective supercells. Full-depth convective cell structures of this magnitude are seen for the first time in this open channel domain, and may have important implications for turbulence analysis in a comparable tidally-driven ocean boundary layer. As such, these results motivate further study of the

  12. 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


    in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2-aminoethoxydiphenylborane (2-APB) and small interfering RNA knockdown...... 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...

  13. Development of Bed Ridges in Open Channels and their Effects on Secondary Currents and Wall Shear

    Directory of Open Access Journals (Sweden)

    Kamran Ansari


    Full Text Available A numerical analysis of the ridges on the bed of wide, open channels and their effects on the distribution of secondary currents and wall shear is undertaken using CFD (Computational Fluid Dynamics. The presence of the lines of boil, consisting of low speed streaks, periodically in the transverse direction, is reported in the literature due to the presence of the ridges. In the present work, simulations are run on channel sections with varying the number of ridges on the bed and the size of these ridges. The effect of these variations on the flow structures and shear stress distribution in wide open channels is reported. The results offer an interesting insight into the 3D (Three-Dimensional flow structures involved and the link between flow structures and bed morpho-dynamics in prismatic channels.



    Absi, Rafik


    International audience; In this study, we present analytical tools for velocity distribution in steady uniform open-channel flows. Simple dip-modified laws are presented. An ordinary differential equation based on an analysis of the Reynolds-averaged Navier-Stokes (RANS) equations is proposed. Comparisons of predicted velocity profiles with experimental data show good agreement. It is well known that dip-phenomenon depends on aspect ratio Ar (ratio of the channel width b to the water depth h)...

  15. Development of Bed Ridges in Open Channels and their Effects on Secondary Currents and Wall Shear


    Kamran Ansari; Ashfaque Ahmed Memon; Naeem Aziz Memon


    A numerical analysis of the ridges on the bed of wide, open channels and their effects on the distribution of secondary currents and wall shear is undertaken using CFD (Computational Fluid Dynamics). The presence of the lines of boil, consisting of low speed streaks, periodically in the transverse direction, is reported in the literature due to the presence of the ridges. In the present work, simulations are run on channel sections with varying the number of ridges on the bed and ...

  16. 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


    the threshold current to evoke action potentials in dorsal root ganglion neurons. The polyunsaturated fatty acids docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV 7.2/3 channel expressed in Xenopus oocytes......AIM: Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage-gated sodium and calcium channels. Effects on neuronal potassium channels are less explored and experimental data ambiguous. The aim of this study was to investigate...... anti-excitable effects of polyunsaturated fatty acids on the neuronal M-channel, important for setting the resting membrane potential in hippocampal and dorsal root ganglion neurons. METHODS: Effects of fatty acids and fatty-acid analogues on mouse dorsal root ganglion neurons and on the human KV 7...

  17. The marine algal toxin azaspiracid is an open state blocker of hERG potassium channels (United States)

    Twiner, Michael J.; Doucette, Gregory J.; Rasky, Andrew; Huang, Xi-Ping; Roth, Bryan L.; Sanguinetti, Michael C.


    Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in shellfish and represent an emerging human health risk. Although human exposure is primarily manifested by severe and protracted diarrhea, this toxin class has been shown to be highly cytotoxic, a teratogen to developing fish, and a possible carcinogen in mice. Until now, AZA's molecular target(s) has not yet been determined. Using three independent methods (voltage clamp, channel binding assay, and thallium flux assay), we have for the first time demonstrated that AZA1, AZA2, and AZA3 each bind to and block the hERG (human ether-à-go-go related gene) potassium channel heterologously expressed in HEK-293 mammalian cells. Inhibition of K+ current for each AZA analogue was concentration-dependent (IC50 value range: 0.64 - 0.84 μM). The mechanism of hERG channel inhibition by AZA1 was investigated further in Xenopus oocytes where it was shown to be an open state-dependent blocker and, using mutant channels, to interact with F656 but not with Y652 within the S6 transmembrane domain that forms the channel's central pore. AZA1, AZA2, and AZA3 were each shown to inhibit [3H]dofetilide binding to the hERG channel and thallium ion flux through the channel (IC50 value range: 2.1 – 6.6 μM). AZA1 did not block K+ current of the closely related EAG1 channel. Collectively, these data suggest that the AZAs physically block the K+ conductance pathway of hERG1 channels by occluding the cytoplasmic mouth of the open pore. Although the concentrations necessary to block hERG channels are relatively high, AZA-induced blockage may prove to contribute to the toxicological properties of the AZAs. PMID:22856456

  18. Marine algal toxin azaspiracid is an open-state blocker of hERG potassium channels. (United States)

    Twiner, Michael J; Doucette, Gregory J; Rasky, Andrew; Huang, Xi-Ping; Roth, Bryan L; Sanguinetti, Michael C


    Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in shellfish and represent an emerging human health risk. Although human exposure is primarily manifested by severe and protracted diarrhea, this toxin class has been shown to be highly cytotoxic, a teratogen to developing fish, and a possible carcinogen in mice. Until now, AZA's molecular target has not yet been determined. Using three independent methods (voltage clamp, channel binding assay, and thallium flux assay), we have for the first time demonstrated that AZA1, AZA2, and AZA3 each bind to and block the hERG (human ether-à-go-go related gene) potassium channel heterologously expressed in HEK-293 mammalian cells. Inhibition of K(+) current for each AZA analogue was concentration-dependent (IC(50) value range: 0.64-0.84 μM). The mechanism of hERG channel inhibition by AZA1 was investigated further in Xenopus oocytes where it was shown to be an open-state-dependent blocker and, using mutant channels, to interact with F656 but not with Y652 within the S6 transmembrane domain that forms the channel's central pore. AZA1, AZA2, and AZA3 were each shown to inhibit [(3)H]dofetilide binding to the hERG channel and thallium ion flux through the channel (IC(50) value range: 2.1-6.6 μM). AZA1 did not block the K(+) current of the closely related EAG1 channel. Collectively, these data suggest that the AZAs physically block the K(+) conductance pathway of hERG1 channels by occluding the cytoplasmic mouth of the open pore. Although the concentrations necessary to block hERG channels are relatively high, AZA-induced blockage may prove to contribute to the toxicological properties of the AZAs.

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

  20. Experimental Studies of Vertical Mixing Patterns in Open Channel Flow Generated by Two Delta Wings Side-by-Side


    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 airf...

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

    Directory of Open Access Journals (Sweden)

    Su Xue-Feng


    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.

  2. K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport (United States)


    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

  3. Interactions among DIV voltage-sensor movement, fast inactivation, and resurgent Na current induced by the NaVβ4 open-channel blocking peptide (United States)

    Lewis, Amanda H.


    Resurgent Na current flows as voltage-gated Na channels recover through open states from block by an endogenous open-channel blocking protein, such as the NaVβ4 subunit. The open-channel blocker and fast-inactivation gate apparently compete directly, as slowing the onset of fast inactivation increases resurgent currents by favoring binding of the blocker. Here, we tested whether open-channel block is also sensitive to deployment of the DIV voltage sensor, which facilitates fast inactivation. We expressed NaV1.4 channels in HEK293t cells and assessed block by a free peptide replicating the cytoplasmic tail of NaVβ4 (the “β4 peptide”). Macroscopic fast inactivation was disrupted by mutations of DIS6 (L443C/A444W; “CW” channels), which reduce fast-inactivation gate binding, and/or by the site-3 toxin ATX-II, which interferes with DIV movement. In wild-type channels, the β4 peptide competed poorly with fast inactivation, but block was enhanced by ATX. With the CW mutation, large peptide-induced resurgent currents were present even without ATX, consistent with increased open-channel block upon depolarization and slower deactivation after blocker unbinding upon repolarization. The addition of ATX greatly increased transient current amplitudes and further enlarged resurgent currents, suggesting that pore access by the blocker is actually decreased by full deployment of the DIV voltage sensor. ATX accelerated recovery from block at hyperpolarized potentials, however, suggesting that the peptide unbinds more readily when DIV voltage-sensor deployment is disrupted. These results are consistent with two open states in Na channels, dependent on the DIV voltage-sensor position, which differ in affinity for the blocking protein. PMID:23940261

  4. 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


    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.

  5. A DNS Investigation of Non-Newtonian Turbulent Open Channel Flow (United States)

    Guang, Raymond; Rudman, Murray; Chryss, Andrew; Slatter, Paul; Bhattacharya, Sati


    The flow of non-Newtonian fluids in open channels has great significance in many industrial settings from water treatment to mine waste disposal. The turbulent behaviour during transportation of these materials is of interest for many reasons, one of which is keeping settleable particles in suspension. The mechanism governing particle transport in turbulent flow has been studied in the past, but is not well understood. A better understanding of the mechanism operating in the turbulent flow of non-Newtonian suspensions in open channel would lead to improved design of many of the systems used in the mining and mineral processing industries. The objective of this paper is to introduce our work on the Direct Numerical Simulation of turbulent flow of non-Newtonian fluids in an open channel. The numerical method is based on spectral element/Fourier formulation. The flow simulation of a Herschel-Bulkley fluid agrees qualitatively with experimental results. The simulation results over-predict the flow velocity by approximately 15% for the cases considered, although the source of the discrepancy is difficult to ascertain. The effect of variation in yield stress and assumed flow depth are investigated and used to assess the sensitivity of the flow to these physical parameters. This methodology is seen to be useful in designing and optimising the transport of slurries in open channels.

  6. Modelling of supercritical turbulent flow over transversal ribs in an open channel

    Czech Academy of Sciences Publication Activity Database

    Příhoda, Jaromír; Šulc, J.; Sedlář, M.; Zubík, P.


    Roč. 16, č. 1 (2009), s. 65-74 ISSN 1802-1484 R&D Projects: GA ČR GA103/06/0461 Institutional research plan: CEZ:AV0Z20760514 Keywords : turbulent flow in open channels * flow over obstacles Subject RIV: BK - Fluid Dynamics

  7. Turbulence characteristics of flow in an open channel with temporally varying mobile bedforms

    Directory of Open Access Journals (Sweden)

    Hanmaiahgari Prashanth Reddy


    Full Text Available Turbulence of flow over mobile bedforms in natural open channels is not yet clearly understood. An attempt is made in this paper to determine the effect of naturally formed mobile bedforms on velocities, turbulent intensities and turbulent stresses. Instantaneous velocities are measured using a two-dimensional particle image velocimetry (PIV to evaluate the turbulence structure of free surface flow over a fixed (immobile bed, a weakly mobile bed and a temporally varying mobile bed with different stages of bedform development. This paper documents the vertical distribution of velocity, turbulence intensities, Reynolds shear stress and higher-order moments including skewness and turbulent diffusion factors. Analysis of the velocity distributions shows a substantial decrease of velocity near the bed with increasing bedform mobility due to increased friction. A modified logarithmic law with a reduced von Kármán constant and increased velocity shift is proposed for the case of the mobile bedforms. A significant increase in the Reynolds shear stress is observed in the mobile bedforms experiments accompanied by changes over the entire flow depth compared to an immobile bed. The skewness factor distribution was found to be different in the case of the flow over the mobile bedforms. All higher-order turbulence descriptors are found to be significantly affected by the formation of temporally varying and non-equilibrium mobile bedforms. Quadrant analysis indicates that sweep and outward events are found to be dominant in strongly mobile bedforms and govern the bedform mobility.

  8. In Vitro Contractile Response of Rabbit Myometrium to BKCa and KATP Potassium Channel Openers

    Directory of Open Access Journals (Sweden)

    Soňa Fraňová


    Full Text Available The aim of the study was to evaluate the participation of ligand-sensitive potassium large conductance calcium-activated channels (BKCa and ATP-sensitive potassium channels in uterine smooth muscle reactivity during different stages of the experimentally induced proliferatory and secretory phase in the sexual cycle in ovariectomised rabbits in vitro. The myometrial reactivity to oxytocin (10-6 mol l-1 was investigated by an in vitro method in female rabbits 14 days after ovariectomy treated with 17β-estradiol - 1 mg/kg/day i.m. for 7 days, or with a combination of progesterone 2 mg/kg/day s.c. for 7 days and 17β-estradiol - 0.2 mg/ kg/day (day 3–7. The strips of myometrial smooth muscle were incubated with a specific opener (NS 1619 and an antagonist (TEA of potassium large conductance calcium-activated channel, or with a specific opener (pinacidil and an antagonist (glybenclamide of ATP-sensitive potassium channels before the administration of oxytocin. NS1619 produced more potent inhibition of the oxytocin-induced contraction during the gestagen dominance (experimental secretory phase than the one observed during the oestrogen dominance (experimental proliferatory phase. TEA antagonized the NS1619 induced inhibition of the myometrial contraction. In the matter of KATP potassium channels, after the administration of pinacidil we observed a similar situation in the changes of myometrial contractility. Pinacidil produced more pronounced inhibition of oxytocin-induced contraction during the secretory phase, and its effect was abolished by the selective inhibitor glybenclamide. Our experimental results indicate that both potassium large conductance calcium-activated channels and ATP-sensitive potassium channels significantly participate in the regulation of myometrial oxytocin-induced contractions and the activity of these channels is probably influenced by the levels of oestrogens and gestagens.

  9. Morphology of the 1984 open-channel lava flow at Krafla volcano, northern Iceland (United States)

    Rossi, Matti J.


    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

  10. Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states. (United States)

    Bargiello, Thaddeus A; Oh, Seunghoon; Tang, Qingxiu; Bargiello, Nicholas K; Dowd, Terry L; Kwon, Taekyung


    Voltage is an important physiologic regulator of channels formed by the connexin gene family. Connexins are unique among ion channels in that both plasma membrane inserted hemichannels (undocked hemichannels) and intercellular channels (aggregates of which form gap junctions) have important physiological roles. The hemichannel is the fundamental unit of gap junction voltage-gating. Each hemichannel displays two distinct voltage-gating mechanisms that are primarily sensitive to a voltage gradient formed along the length of the channel pore (the transjunctional voltage) rather than sensitivity to the absolute membrane potential (V m or V i-o ). These transjunctional voltage dependent processes have been termed V j - or fast-gating and loop- or slow-gating. Understanding the mechanism of voltage-gating, defined as the sequence of voltage-driven transitions that connect open and closed states, first and foremost requires atomic resolution models of the end states. Although ion channels formed by connexins were among the first to be characterized structurally by electron microscopy and x-ray diffraction in the early 1980's, subsequent progress has been slow. Much of the current understanding of the structure-function relations of connexin channels is based on two crystal structures of Cx26 gap junction channels. Refinement of crystal structure by all-atom molecular dynamics and incorporation of charge changing protein modifications has resulted in an atomic model of the open state that arguably corresponds to the physiologic open state. Obtaining validated atomic models of voltage-dependent closed states is more challenging, as there are currently no methods to solve protein structure while a stable voltage gradient is applied across the length of an oriented channel. It is widely believed that the best approach to solve the atomic structure of a voltage-gated closed ion channel is to apply different but complementary experimental and computational methods and to use

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

    Directory of Open Access Journals (Sweden)

    Ting-Ting Zhang


    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.

  12. Permeation and dynamics of an open-activated TRPV1 channel. (United States)

    Darré, Leonardo; Furini, Simone; Domene, Carmen


    Transient receptor potential (TRP) ion channels constitute a large and diverse protein family, found in yeast and widespread in the animal kingdom. TRP channels work as sensors for a wide range of cellular and environmental signals. Understanding how these channels respond to physical and chemical stimuli has been hindered by the limited structural information available until now. The three-dimensional structure of the vanilloid receptor 1 (TRPV1) was recently determined by single particle electron cryo-microscopy, offering for the first time the opportunity to explore ionic conduction in TRP channels at atomic detail. In this study, we present molecular dynamics simulations of the open-activated pore domain of TRPV1 in the presence of three cationic species: Na(+), Ca(2+) and K(+). The dynamics of these ions while interacting with the channel pore allowed us to rationalize their permeation mechanism in terms of a pathway involving three binding sites at the intracellular cavity, as well as the extracellular and intracellular entrance of the selectivity filter. Furthermore, conformational analysis of the pore in the presence of these ions reveals specific ion-mediated structural changes in the selectivity filter, which influences the permeability properties of the TRPV1 channel. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Formulating the shear stress distribution in circular open channels based on the Renyi entropy (United States)

    Khozani, Zohreh Sheikh; Bonakdari, Hossein


    The principle of maximum entropy is employed to derive the shear stress distribution by maximizing the Renyi entropy subject to some constraints and by assuming that dimensionless shear stress is a random variable. A Renyi entropy-based equation can be used to model the shear stress distribution along the entire wetted perimeter of circular channels and circular channels with flat beds and deposited sediments. A wide range of experimental results for 12 hydraulic conditions with different Froude numbers (0.375 to 1.71) and flow depths (20.3 to 201.5 mm) were used to validate the derived shear stress distribution. For circular channels, model performance enhanced with increasing flow depth (mean relative error (RE) of 0.0414) and only deteriorated slightly at the greatest flow depth (RE of 0.0573). For circular channels with flat beds, the Renyi entropy model predicted the shear stress distribution well at lower sediment depth. The Renyi entropy model results were also compared with Shannon entropy model results. Both models performed well for circular channels, but for circular channels with flat beds the Renyi entropy model displayed superior performance in estimating the shear stress distribution. The Renyi entropy model was highly precise and predicted the shear stress distribution in a circular channel with RE of 0.0480 and in a circular channel with a flat bed with RE of 0.0488.

  14. Effects of potassium channel opener on the kinetics of thallium-201 in in-vitro and in-vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J.; Kim, E. J.; Ahn, B. C.; Chae, S. C.; Lee, K. B. [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of); Kim, C. K. [Mt. Sinai Medical School, New York (United States)


    Potassium channel opener (K-opener) opens membrane ATP-sensitive K{sup +}-channel and induces and increase in potassium efflux from cells. K-openers are powerful smooth muscle relaxants and currently used as antihypertensive, antianginal drugs or bronchodilators in clinic. Pharmacologic potency of newly synthesized K-opener is being evaluated with efflux capacity of preincubated Rb-83 from the isolated aortic vascular tissue preparation. Thallium has similar characteristics to those of rubidium and potassium in vivo. To evaluate the effect of pinacidil (a potent K-opener) on Tl-201 biokinetics, we have performed uptake/washout studies in cultured myocytes, and mice biodistribution study. Primary culture of spontaneous contracting myocytes was undertake from hearts of newborn Sprague-Dawley rat. Different concentration of pinacidil (100nM or 10uM) was co-incubated with Tl-201 in HBSS buffer to evaluate its effect on cellular uptake, or challenged to myocyte preparations pre-incubated with Tl-201 for washout study. Pinacidil was injected into mice simultaneous or 10-min after Tl-201 injection, and organ uptake and whole body retention ratio was measured using gamma counter or dose calibrator. Co-incubation of pinacidil with Tl-201 resulted in a decrease in Tl uptake into myocytes by 1.6 - 2.5 times, and an increase in washout by 1.6 - 3.1 times. Pinacidil injection resulted in mild decrease in blood, heart and liver uptake in mice, bur renal uptake was markedly decreased in a dose dependent manner. These results suggest that the pinacidil Tl-201 kinetics and may potentially affect the interpretation of Tl-201 myocardial imaging.

  15. Volumetric measurements by tomographic PIV of grid generated turbulence in an open channel flow


    Earl , Thomas; Thomas , Lionel; Cochard , Steve; Ben-Salah , Riadh; Tremblais , Benoit; David , Laurent


    International audience; This paper investigates the energy dissipation rate behind two combinations of trash racks (or meshes) in an open channel flow. Five trash rack assemblies divided the flume into four identical pools in the downstream direction. The global characteristics of the flow were compared with Tomo-PIV measurements that were taken in the water column of the flow. From the Tomo-PIV measurements, the instantaneous structures in the flow were visualised and the decay of turbulent ...

  16. A lattice Boltzmann model for solute transport in open channel flow (United States)

    Wang, Hongda; Cater, John; Liu, Haifei; Ding, Xiangyi; Huang, Wei


    A lattice Boltzmann model of advection-dispersion problems in one-dimensional (1D) open channel flows is developed for simulation of solute transport and pollutant concentration. The hydrodynamics are calculated based on a previous lattice Boltzmann approach to solving the 1D Saint-Venant equations (LABSVE). The advection-dispersion model is coupled with the LABSVE using the lattice Boltzmann method. Our research recovers the advection-dispersion equations through the Chapman-Enskog expansion of the lattice Boltzmann equation. The model differs from the existing schemes in two points: (1) the lattice Boltzmann numerical method is adopted to solve the advection-dispersion problem by meso-scopic particle distribution; (2) and the model describes the relation between discharge, cross section area and solute concentration, which increases the applicability of the water quality model in practical engineering. The model is verified using three benchmark tests: (1) instantaneous solute transport within a short distance; (2) 1D point source pollution with constant velocity; (3) 1D point source pollution in a dam break flow. The model is then applied to a 50-year flood point source pollution accident on the Yongding River, which showed good agreement with a MIKE 11 solution and gauging data.

  17. Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana. (United States)

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


    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.

  18. uFLIP-OC: Understanding Flash I/O Patterns on Open-Channel Solid State Drives

    DEFF Research Database (Denmark)

    Picoli, Ivan Luiz; Villegas Pasco, Carla Ysabela; Jónsson, Björn Thór


    Solid-State Drives (SSDs) have gained acceptance by providing the same block device abstraction as magnetic hard drives, at the cost of suboptimal resource utilisation and unpredictable performance. Recently, Open-Channel SSDs have emerged as a means to obtain predictably high performance, based...... suited for a given open-channel SSD. Our experiments on a DragonFire Card (DFC) SSD, equipped with the OX controller, illustrate the performance impact of media characteristics and parallelism. We discuss how uFLIP-OC can be used to guide the design of host-based data systems on open-channel SSDs....

  19. 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


    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.

  20. 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.

  1. Transient mixed convection in a channel with an open cavity filled with porous media

    International Nuclear Information System (INIS)

    Buonomo, B; Cresci, G; Manca, O; Mesolella, P; Nardini, S


    In this work transient mixed convection in a porous medium in a horizontal channel with a open cavity below is studied numerically. The cavity presents a heated wall at uniform heat flux and the other walls of the cavity and the channel are assumed adiabatic. Air flows through the horizontal channel. The heated wall of the cavity experiences a uniform heat flux in such a way that the forced flow is perpendicular to the motion due to natural convection. The study is carried out employing Brinkman-Forchheimer-extended Darcy model and two energy equations due to the local thermal non-equilibrium assumption. The flow in the channel is assumed to be two-dimensional, laminar, incompressible. Boussinesq approximation is considered. The thermophysical properties of the fluid are evaluated at the ambient temperature. The results for stream function and temperature distribution given at different times are obtained. Wall temperature value are given and also, the velocity and temperature profiles in several sections of the cavity are presented. In addition, the Nusselt number, both local and average, is presented along with the temporal variations of the average Nusselt number.

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

    Directory of Open Access Journals (Sweden)

    Prasad S. Thenkabail


    Full Text Available Remote Sensing, an open access journal ( 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. [...

  3. On the Modeling of an Open Channel MEMS Based Capacitive Flow Sensor

    Directory of Open Access Journals (Sweden)

    Vafaghi Maryam


    Full Text Available In this paper an open channel MEMS capacitive flow sensor has been designed based on a microplate deflection measuring. Proposed flow sensor consists with two separate units, one for sensing the static fluid pressure and the other for sensing the fluid static and dynamic pressure. The governing equation whose solution holds the answer to all our questions about the sensor’s characteristics is a nonlinear elasto-electrostatic equation. Sensor’s static response and mechanical behavior of the sensing elements in a channel have been simulated numerically by using of Step by Step Linearization Method. The sensor stability has been examined and the stable region of the sensor has been studied. The effect of fluid velocity and static pressure on stability limit of the sensor has been investigated and the effect of bias voltage on sensor sensitivity has been studied.

  4. Volumetric Measurements by Tomographic PIV of an Open Channel Flow Behind a Turbulent Grid


    Earl , Thomas; Ben-Salah , Riadh; Thomas , Lionel; Tremblais , Benoit; Cochard , Steve; David , Laurent


    National audience; This paper investigates the energy dissipation rate behind two combinations of trash racks (or meshes) in an open channel flow from tomo-PIV measurements. Five trash rack assemblies divided the flume into four identical pools. Each trash rack assembly is composed of a fine wire mesh and two regular square grids, characterised by their mesh size M. The Reynolds numbers with respect to M were 4300 and 9600 corresponding to a mean velocity ¯U through each pool between 0.35 and...

  5. Two-phase modeling of turbulence in dilute sediment-laden, open-channel flows


    Jha, Sanjeev K.; Bombardelli, Fabián A.


    In this paper, we focus on assessing the performance of diverse turbulence closures in the simulation of dilute sediment-laden, open-channel flows. To that end, we base our analysis on a framework developed in a companion paper of this special issue, which puts forward a standard sediment transport model (SSTM), a partial two-fluid model (PTFM) and a complete two-fluid model (CTFM), in three- and one-dimensional (3D and 1D) versions. First, we propose in this paper extensions of the transport...

  6. Intsy: a low-cost, open-source, wireless multi-channel bioamplifier system. (United States)

    Erickson, Jonathan C; Hayes, James A; Bustamante, Mauricio; Joshi, Rajwol; Rwagaju, Alfred; Paskaranandavadivel, Niranchan; Angeli, Timothy R


    Multi-channel electrical recordings of physiologically generated signals are common to a wide range of biomedical fields. The aim of this work was to develop, validate, and demonstrate the practical utility of a high-quality, low-cost 32/64-channel bioamplifier system with real-time wireless data streaming capability. The new "Intsy" system integrates 3 main off-the-shelf hardware components: 1) Intan RHD2132 bioamplifier; 2) Teensy 3.2 microcontroller; and 3) RN-42 Bluetooth 2.1 module with a custom LabView interface for real-time data streaming and visualization. Practical utility was validated by measuring serosal gastric slow waves and surface EMG on the forearm with various contraction force levels. Quantitative comparisons were made to a gold-standard commercial system (Biosemi ActiveTwo). Intsy signal quality was quantitatively comparable to that of the ActiveTwo. Recorded slow wave signals had high SNR (24 ± 2.7 dB) and wavefront propagation was accurately mapped. Surface EMG spike bursts were characterized by high SNR (≥10 dB) and activation timing was readily identified. Stable data streaming rates achieved were 3.5 kS/s for wireless and 64 kS/s for USB-wired transmission. Intsy has the highest channel count of any existing open-source, wireless-enabled module. The flexibility, portability and low cost ($1300 for the 32-channel version, or $2500 for 64 channels) of this new hardware module reduce the entry barrier for a range of electrophysiological experiments, as are typical in the gastrointestinal (EGG), cardiac (ECG), neural (EEG), and neuromuscular (EMG) domains. © 2018 Institute of Physics and Engineering in Medicine.

  7. 4D photogrammetric technique to study free surface water in open channels (United States)

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


    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.

  8. Numerical study of the effects of lamp configuration and reactor wall roughness in an open channel water disinfection UV reactor. (United States)

    Sultan, Tipu


    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Tilisolol hydrochloride dilates coronary arteries through an ATP-sensitive K(+)-channel opening mechanism in dogs. (United States)

    Liu, Q; Nakae, I; Takahashi, M; Takaoka, A; Kinoshita, M


    Tilisolol is a beta-blocking agent with vasodilatory properties that was recently shown to possess a potassium (K+) channel opening activity. We investigated whether tilisolol has vasodilatory effects on coronary circulation in dogs. Mongrel dogs were chronically instrumented for measurements of circumflex coronary artery diameter (CoD) and coronary blood flow (CBF). We compared the effects of tilisolol on dog coronary arteries with those of two beta-blockers, propranolol and arotinolol. Both propranolol (1 mg/kg, intravenously, i.v.) and arotinolol (0.25 mg/kg, i.v.) decreased CoD and increased coronary vascular resistance (CVR). Tilisolol (2 mg/kg, i.v.) decreased CVR but had no significant effect on CoD. To investigate the mechanism of the coronary action of tilisolol, we examined differences in the response to tilisolol in the absence and presence of glibenclamide, an ATP-sensitive K+ channel blocker. Tilisolol (1,2,4, and 8 mg/kg, i.v.) produced a dose-dependent decrease in CVR without glibenclamide, whereas pretreatment with glibenclamide significantly suppressed this effect. Without glibenclamide, tilisolol had no significant effect on CoD at doses of 1-4 mg/kg (i.v.). However, at the higher dose of 8 mg/kg (i.v.), tilisolol significantly increased CoD (1.00 +/- 0.15%, p < 0.01). After pretreatment with glibenclamide, tilisolol (1-8 mg/kg, i.v.) produced a significant decrease in CoD. Therefore, we concluded that tilisolol exerts its vasodilatory effect on the coronary circulation through an ATP-sensitive K+ channel opening mechanism, and that its vasodilatory action is more prominent in coronary resistance vessels than in large coronary arteries.

  10. Explicit solutions for critical and normal depths in trapezoidal and parabolic open channels

    Directory of Open Access Journals (Sweden)

    Ali R. Vatankhah


    Full Text Available Normal and critical depths are important parameters in the design of open channels and analysis of gradually varied flow. In trapezoidal and parabolic channels, the governing equations are highly nonlinear in the normal and critical flow depths and thus solution of the implicit equations involves numerical methods (except for critical depth in parabolic channels. In current research explicit solutions have been obtained using the non-dimensional forms of the governing equations. For the trapezoidal cross section, the maximum error of critical flow depth is less than 6 × 10−6% (near exact solution and the maximum error of normal depth is less than 0.25% (very accurate solution. The maximum error of normal flow depth for parabolic cross section is also less than 8 × 10−3% (near exact solution. Proposed explicit equations have definite physical concept, high accuracy, easy calculation, and wide application range compared with the existing direct equations.

  11. Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening. (United States)

    Nakajo, Koichi; Kubo, Yoshihiro


    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.

  12. Fluctuations of nuclear cross sections in the region of strong overlapping resonances and at large number of open channels

    International Nuclear Information System (INIS)

    Kun, S.Yu.


    On the basis of the symmetrized Simonius representation of the S matrix statistical properties of its fluctuating component in the presence of direct reactions are investigated. The case is considered where the resonance levels are strongly overlapping and there is a lot of open channels, assuming that compound-nucleus cross sections which couple different channels are equal. It is shown that using the averaged unitarity condition on the real energy axis one can eliminate both resonance-resonance and channel-channel correlations from partial r transition amplitudes. As a result, we derive the basic points of the Epicson fluctuation theory of nuclear cross sections, independently of the relation between the resonance overlapping and the number of open channels, and the validity of the Hauser-Feshbach model is established. If the number of open channels is large, the time of uniform population of compound-nucleus configurations, for an open excited nuclear system, is much smaller than the Poincare time. The life time of compound nucleus is discussed


    Dinh Thanh, Mung; Kimura, Ichiro; Shimizu, Yasuyuki

    Open-channel confluence flows are common in natural river systems as well as in environmental and hydraulic engineering, such as in river engineering. Often, these flows are three-dimensional and complex,while numerical studies fully describing confluence flow are still few. This paper presents the results of investigation of confluence flow using a three-dimensional numerical model with the linear and nonlinear k-ε models. To treat the dynamic boundary condition at the free surface, non-hydrostatic pressure is included in the present model. The model is validated using the experimental data available. Adequacy of the present model with two turbulence models above is indicated based on the result analysis. The nonlinear model is indicated as the more advantageous one than the linear one.

  14. Wastewater diffusive dilution and sedimentation of the fine contaminated particles for nonuniform flow in open channels

    Directory of Open Access Journals (Sweden)

    Lyapin Anton


    Full Text Available The influence of non-uniformity on mass transfer processes in open channels have been investigated under the action of urbanization factors. The study is related to the urgent problem of environmental degradation of water objects in urbanized areas. It is known that the water quality in the water objects depends on the manner in which the contaminants spread how they mix with the river water and diluted by it. The main results of the study consist of recommendations to incorporate non-uniformity factor to the calculation of diffusion dilution of wastewater and prediction of river processes. So the effect of the flow non-uniformity on the diffusion model of pollutants dilution and diffusion coefficient have been investigated. Formulas for the concentration profiles calculating and the average concentration of fine particulate matter in nonuniform gradually varied flow were presented. The deposition length of suspended contaminants were received, based on the hydraulic resistance laws of nonuniform gradually varied flow.

  15. QD-2: a novel open-framework aluminoborate with intersecting three-dimensional helical channels. (United States)

    Wang, Guo-Ming; Li, Jin-Hua; Huang, Hai-Lan; Li, Hui; Zhang, Jing


    A novel open-framework aluminoborate, [CH3NH2(CH2)3NH ]-[AlB5O10] (QD-2), has been synthesized under hydrothermal conditions and characterized by IR, elemental analysis, thermogravimetric analysis, and powder and single-crystal X-ray diffractions. The compound crystallizes in the orthorhombic system, space group P2(1)2(1)2(1) (No. 19), a = 9.4352(4) A, b = 10.2972(2) A, c = 13.7511(5) A, V = 1336.0(8) A3, and Z = 4. Its structure consists of AlO4 tetrahedra and B5O10 clusters, which are interconnected to form the first example of a three-dimensional aluminoborate with intersecting helical channels.

  16. Molecular Dynamics of Channelrhodopsin at the Early Stages of Channel Opening. (United States)

    Takemoto, Mizuki; Kato, Hideaki E; Koyama, Michio; Ito, Jumpei; Kamiya, Motoshi; Hayashi, Shigehiko; Maturana, Andrés D; Deisseroth, Karl; Ishitani, Ryuichiro; Nureki, Osamu


    Channelrhodopsin (ChR) is a light-gated cation channel that responds to blue light. Since ChR can be readily expressed in specific neurons to precisely control their activities by light, it has become a powerful tool in neuroscience. Although the recently solved crystal structure of a chimeric ChR, C1C2, provided the structural basis for ChR, our understanding of the molecular mechanism of ChR still remains limited. Here we performed electrophysiological analyses and all-atom molecular dynamics (MD) simulations, to investigate the importance of the intracellular and central constrictions of the ion conducting pore observed in the crystal structure of C1C2. Our electrophysiological analysis revealed that two glutamate residues, Glu122 and Glu129, in the intracellular and central constrictions, respectively, should be deprotonated in the photocycle. The simulation results suggested that the deprotonation of Glu129 in the central constriction leads to ion leakage in the ground state, and implied that the protonation of Glu129 is important for preventing ion leakage in the ground state. Moreover, we modeled the 13-cis retinal bound; i.e., activated C1C2, and performed MD simulations to investigate the conformational changes in the early stage of the photocycle. Our simulations suggested that retinal photoisomerization induces the conformational change toward channel opening, including the movements of TM6, TM7 and TM2. These insights into the dynamics of the ground states and the early photocycle stages enhance our understanding of the channel function of ChR.

  17. Molecular Dynamics of Channelrhodopsin at the Early Stages of Channel Opening.

    Directory of Open Access Journals (Sweden)

    Mizuki Takemoto

    Full Text Available Channelrhodopsin (ChR is a light-gated cation channel that responds to blue light. Since ChR can be readily expressed in specific neurons to precisely control their activities by light, it has become a powerful tool in neuroscience. Although the recently solved crystal structure of a chimeric ChR, C1C2, provided the structural basis for ChR, our understanding of the molecular mechanism of ChR still remains limited. Here we performed electrophysiological analyses and all-atom molecular dynamics (MD simulations, to investigate the importance of the intracellular and central constrictions of the ion conducting pore observed in the crystal structure of C1C2. Our electrophysiological analysis revealed that two glutamate residues, Glu122 and Glu129, in the intracellular and central constrictions, respectively, should be deprotonated in the photocycle. The simulation results suggested that the deprotonation of Glu129 in the central constriction leads to ion leakage in the ground state, and implied that the protonation of Glu129 is important for preventing ion leakage in the ground state. Moreover, we modeled the 13-cis retinal bound; i.e., activated C1C2, and performed MD simulations to investigate the conformational changes in the early stage of the photocycle. Our simulations suggested that retinal photoisomerization induces the conformational change toward channel opening, including the movements of TM6, TM7 and TM2. These insights into the dynamics of the ground states and the early photocycle stages enhance our understanding of the channel function of ChR.

  18. Non-Fickian dispersion in open-channel flow over a porous bed (United States)

    Bottacin-Busolin, Andrea


    Solute transport in rivers has been traditionally represented using one-dimensional models assuming advection and Fickian dispersion along the main flow direction and transient storage in surface and subsurface dead zones. Experimental evidence from several stream tracer studies has shown that the longitudinal scaling of the moments of the breakthrough curves (BTCs) is inconsistent with classic 1-D solute transport models. In this work, simulations of advection and diffusion in a 2-D and 3-D channel flow over a porous bed are presented assuming an exponentially attenuated profile of the transverse mixing coefficient in the porous medium, as suggested by recent experimental and numerical studies. It is shown that the longitudinal transport in the channel is superdiffusive, and the skewness of the concentration distributions can be almost constant over a broad temporal range, with no sign of approaching zero at large times. A sensitivity analysis shows that, at large times, longitudinal dispersion is controlled by the cross-sectional profile of the in-bed transverse mixing coefficient, and by the difference between the average velocity in the channel and in the porous bed. The normalized concentration distributions can be approximated by beta-distributions with time-dependent parameters, and relationships are derived between the scaling of the parameters under power-law approximation and the scaling of the spatial and temporal moments. The results provide new insights into the physical mechanisms that control the anomalous scaling of the moments observed in field tracer studies and opens new possibilities for predictive and inverse modeling of transport processes in rivers and their catchments.

  19. A Computer Model for the Hydraulic Analysis of Open Channel Cross Sections

    Directory of Open Access Journals (Sweden)

    W. H. Shayya


    Full Text Available Irrigation and hydraulic engineers are often faced with the difficulty of tedious trial solutions of the Manning equation to determine the various geometric elements of open channels. This paper addresses the development of a computer model for the design of the most commonly used channel-sections. The developed model is intended as an educational tool. It may be applied to the hydraulic design of trapezoidal , rectangular, triangular, parabolic, round-concered rectangular, and circular cross sections. Two procedures were utilized for the solution of the encountered implicit equations; the Newton-Raphson and the Regula-Falsi methods.  In order to initiate the solution process , these methods require one and two initial guesses, respectively. Tge result revealed that the Regula-Flasi method required more iterations to coverage to the solution compared to the Newton-Raphson method, irrespective of the nearness of the initial guess to the actual solution. The average number of iterations for the Regula-Falsi method was approximately three times that of the Newton-Raphson method.

  20. 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))


    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.

  1. Outer region scaling using the freestream velocity for nonuniform open channel flow over gravel (United States)

    Stewart, Robert L.; Fox, James F.


    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.

  2. Hydrodynamic characterization and evaluation of an open channel reactor for the degradation of paracetamol

    International Nuclear Information System (INIS)

    Abreu Zamora, Maria A.; Gonzalez Lopez, Dagoberto E.; Robaina Leon, Yalaina; Dominguez Catasus, Judith; Borroto Portela, Jorge I.; Jauregui Haza, Ulises J.


    The conventional wastewater treatment plants do not guarantee the degradation of Persistent Organic Pollutants (POPs). Advanced oxidation processes, like photodegradation that use artificial ultraviolet and solar radiation, are proposed as an alternative for the treatment of contaminated water with POPs. In the present work, the hydrodynamic characterization and evaluation of an open channel reactor for the degradation of paracetamol are presented. The hydrodynamic characterization was performed through the analysis of the residence time distribution using a radioisotope 99m Tc. This process was done in two steps. First, the open channel reactor was evaluated in continuous mode operation. To study the influence of the fluid volume in the reactor and the diameter of the flow distributor's orifices on the flow pattern, an experimental 3 2 design with two replicas in the center was used. The dependent variables were the number of perfectly mixed tanks (J), the mean residence time of the model (τ) and the experimental mean residence time (Trm). The model of perfectly mixed tanks in series exchanging with stagnant zones was assumed as the best model. In a second moment, the mixing time of the system operating in close loop mode was determined. Finally, the degradation of paracetamol in aqueous dissolution trough photolysis, photolysis intensified with H 2 O 2 , photo-Fenton with artificial ultraviolet radiation and photo-Fenton with solar radiation was evaluated. The results show that the photo-Fenton processes employing artificial ultraviolet and solar radiation warranty the total degradation of the pharmaceutical after 15 minutes of reaction. (Author)

  3. SPH modelling of depth‐limited turbulent open channel flows over rough boundaries (United States)

    Kazemi, Ehsan; Nichols, Andrew; Tait, Simon


    Summary A numerical model based on the smoothed particle hydrodynamics method is developed to simulate depth‐limited turbulent open channel flows over hydraulically rough beds. The 2D Lagrangian form of the Navier–Stokes equations is solved, in which a drag‐based formulation is used based on an effective roughness zone near the bed to account for the roughness effect of bed spheres and an improved sub‐particle‐scale model is applied to account for the effect of turbulence. The sub‐particle‐scale model is constructed based on the mixing‐length assumption rather than the standard Smagorinsky approach to compute the eddy‐viscosity. A robust in/out‐flow boundary technique is also proposed to achieve stable uniform flow conditions at the inlet and outlet boundaries where the flow characteristics are unknown. The model is applied to simulate uniform open channel flows over a rough bed composed of regular spheres and validated by experimental velocity data. To investigate the influence of the bed roughness on different flow conditions, data from 12 experimental tests with different bed slopes and uniform water depths are simulated, and a good agreement has been observed between the model and experimental results of the streamwise velocity and turbulent shear stress. This shows that both the roughness effect and flow turbulence should be addressed in order to simulate the correct mechanisms of turbulent flow over a rough bed boundary and that the presented smoothed particle hydrodynamics model accomplishes this successfully. © 2016 The Authors International Journal for Numerical Methods in Fluids Published by John Wiley & Sons Ltd PMID:28066121

  4. Design and production of stopper made of concrete foam composite used for open channel conduit cover and parking bumper (United States)

    Syam, Bustami; Sebayang, Alexander; Sebayang, Septian; Muttaqin, Maraghi; Darmadi, Harry; Basuki, WS; Sabri, M.; Abda, S.


    Open channel conduit is designed and produced with the aims to reduce excess water, whether from rain, seepage, or excess irrigation water in an area. It is also included in one of the important components of urban infrastructure in tackling the problem of flooding and waterlogging. On the roadway, e.g. housing complex the open channel conduits should function the same, however conduit covers are needed. The covers should be also designed to function as parking bumper. This paper discusses the design and production of the stoppers using our newly invented materials; the stoppers are structurally tested under static, dynamic, and bump test. Response of the conduit cover are found from structural analysis using finite element software ANSYS MECHANICAL version 17.5. Two types of stoppers are introduced: flat and curvy configuration. It was obtained that both types are suitable for open channel conduit cover and parking bumper.

  5. 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


    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...... stabilization is the consequence of the amelioration of an inherently repulsive open-state interaction between the partial negative charge on the face of Phe481 and a highly co-evolved acidic side chain, Glu395, and this interaction is potentially modulated through the Tyr485 hydroxyl. We propose...... 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....

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

    KAUST Repository

    Radaydeh, Redha


    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.

  7. Influence of increased static pressure in MHD-channel of hypervelocity wind tunnel on its characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Alfyorov, V.I.; Rudakova, A.P.; Rukavets, V.P.; Shcherbakov, G.I. [Central Aerohydrodynamic Institute (TsAGI), Zhukovsky (Russian Federation)


    One of the main weaknesses of available MHD gas acceleration wind tunnels which restricts their application for simulating vehicle re-entry flights and reproducing scramjet combustion chamber conditions is a relatively low static pressure in the channel (P{approximately}0.1 to 0.2 Atm). The possibility of increasing this pressure and the influence of the increased pressure on the MHD-accelerator characteristics are the subject of the present paper. It is shown that the main challenge is the necessity of increasing the total Lorentz force proportionally to the channel gas density at electrode current density not resulting in heat and electrical breakdown and the development of the side walls and interelectrode insulators designed for higher heat fluxes, q {approximately} 5 to 10 kw/cm{sup 2}. Some possible wall design versions are suggested. The influence of increased pressure is investigated using the Faraday - type MED channel at static pressures in the MHD channel from 0.2 to 1.0 Atm and total accelerating current I = 300 to 1,100 Amps when B=2.5T. Forty five electrodes are used in the MHD channel at maximum current density of 50 A/cm{sup 2}. The channel flow is calculated by applying the model of a gas in thermodynamic equilibrium. The influence of the increased pressure on electrodynamic (accelerator electrode voltages and currents, Hall voltage and current) and gasdynamic (distributions of static pressure, temperature, velocity, Mach numbers, etc., along the channel length) characteristics is evaluated. Some recommendations on the development of MHD channels for hypersonic wind tunnels designed for high pressure are suggested.

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

    Directory of Open Access Journals (Sweden)

    Dworeck Tamara


    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.

  9. Increasing Flight Software Reuse with OpenSatKit (United States)

    McComas, David C.


    In January 2015 the NASA Goddard Space Flight Center (GSFC) released the Core Flight System (cFS) as open source under the NASA Open Source Agreement (NOSA) license. The cFS is based on flight software (FSW) developed for 12 spacecraft spanning nearly two decades of effort and it can provide about a third of the FSW functionality for a low-earth orbiting scientific spacecraft. The cFS is a FSW framework that is portable, configurable, and extendable using a product line deployment model. However, the components are maintained separately so the user must configure, integrate, and deploy them as a cohesive functional system. This can be very challenging especially for organizations such as universities building cubesats that have minimal experience developing FSW. Supporting universities was one of the primary motivators for releasing the cFS under NOSA. This paper describes the OpenSatKit that was developed to address the cFS deployment challenges and to serve as a cFS training platform for new users. It provides a fully functional out-of-the box software system that includes NASA's cFS, Ball Aerospace's command and control system COSMOS, and a NASA dynamic simulator called 42. The kit is freely available since all of the components have been released as open source. The kit runs on a Linux platform, includes 8 cFS applications, several kit-specific applications, and built in demos illustrating how to use key application features. It also includes the software necessary to port the cFS to a Raspberry Pi and instructions for configuring COSMOS to communicate with the target. All of the demos and test scripts can be rerun unchanged with the cFS running on the Raspberry Pi. The cFS uses a 3-tiered layered architecture including a platform abstraction layer, a Core Flight Executive (cFE) middle layer, and an application layer. Similar to smart phones, the cFS application layer is the key architectural feature for users to extend the FSW functionality to meet their

  10. Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells. (United States)

    DeHart, David N; Fang, Diana; Heslop, Kareem; Li, Li; Lemasters, John J; Maldonado, Eduardo N


    Enhancement of aerobic glycolysis and suppression of mitochondrial metabolism characterize the pro-proliferative Warburg phenotype of cancer cells. High free tubulin in cancer cells closes voltage dependent anion channels (VDAC) to decrease mitochondrial membrane potential (ΔΨ), an effect antagonized by erastin, the canonical promotor of ferroptosis. Previously, we identified six compounds (X1-X6) that also block tubulin-dependent mitochondrial depolarization. Here, we hypothesized that VDAC opening after erastin and X1-X6 increases mitochondrial metabolism and reactive oxygen species (ROS) formation, leading to ROS-dependent mitochondrial dysfunction, bioenergetic failure and cell death. Accordingly, we characterized erastin and the two most potent structurally unrelated lead compounds, X1 and X4, on ROS formation, mitochondrial function and cell viability. Erastin, X1 and X4 increased ΔΨ followed closely by an increase in mitochondrial ROS generation within 30-60 min. Subsequently, mitochondria began to depolarize after an hour or longer indicative of mitochondrial dysfunction. N-acetylcysteine (NAC, glutathione precursor and ROS scavenger) and MitoQ (mitochondrially targeted antioxidant) blocked increased ROS formation after X1 and prevented mitochondrial dysfunction. Erastin, X1 and X4 selectively promoted cell killing in HepG2 and Huh7 human hepatocarcinoma cells compared to primary rat hepatocytes. X1 and X4-dependent cell death was blocked by NAC. These results suggest that ferroptosis induced by erastin and our erastin-like lead compounds was caused by VDAC opening, leading to increased ΔΨ, mitochondrial ROS generation and oxidative stress-induced cell death. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Experimental and numerical modelling of turbulent flow over an inclined backward-facing step in an open channel

    Czech Academy of Sciences Publication Activity Database

    Příhoda, Jaromír; Zubík, P.; Šulc, J.; Sedlář, M.


    Roč. 14, 4a (2012), s. 6-12 ISSN 1335-4205 R&D Projects: GA ČR GA103/09/0977 Institutional support: RVO:61388998 Keywords : open channel flow * inclined backward-facing step Subject RIV: BK - Fluid Dynamics

  12. DNS-DEM of Suspended Sediment Particles in an Open Channel Flow (United States)

    Pakseresht, Pedram; Apte, Sourabh; Finn, Justin


    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. Estimation of two-dimensional velocity distribution profile using General Index Entropy in open channels (United States)

    Shojaeezadeh, Shahab Aldin; Amiri, Seyyed Mehrab


    Estimation of velocity distribution profile is a challenging subject of open channel hydraulics. In this study, an entropy-based method is used to derive two-dimensional velocity distribution profile. The General Index Entropy (GIE) can be considered as the generalized form of Shannon entropy which is suitable to combine with the different form of Cumulative Distribution Function (CDF). Using the principle of maximum entropy (POME), the velocity distribution is defined by maximizing the GIE by treating the velocity as a random variable. The combination of GIE and a CDF proposed by Marini et al. (2011) was utilized to introduce an efficient entropy model whose results are comparable with several well-known experimental and field data. Consequently, in spite of less sensitivity of the related parameters of the model to flow conditions and less complexity in application of the model compared with other entropy-based methods, more accuracy is obtained in estimating velocity distribution profile either near the boundaries or the free surface of the flow.

  14. Entropy-Based Modeling of Velocity Lag in Sediment-Laden Open Channel Turbulent Flow

    Directory of Open Access Journals (Sweden)

    Manotosh Kumbhakar


    Full Text Available In the last few decades, a wide variety of instruments with laser-based techniques have been developed that enable experimentally measuring particle velocity and fluid velocity separately in particle-laden flow. Experiments have revealed that stream-wise particle velocity is different from fluid velocity, and this velocity difference is commonly known as “velocity lag” in the literature. A number of experimental, as well as theoretical investigations have been carried out to formulate deterministic mathematical models of velocity lag, based on several turbulent features. However, a probabilistic study of velocity lag does not seem to have been reported, to the best of our knowledge. The present study therefore focuses on the modeling of velocity lag in open channel turbulent flow laden with sediment using the entropy theory along with a hypothesis on the cumulative distribution function. This function contains a parameter η, which is shown to be a function of specific gravity, particle diameter and shear velocity. The velocity lag model is tested using a wide range of twenty-two experimental runs collected from the literature and is also compared with other models of velocity lag. Then, an error analysis is performed to further evaluate the prediction accuracy of the proposed model, especially in comparison to other models. The model is also able to explain the physical characteristics of velocity lag caused by the interaction between the particles and the fluid.

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

    Directory of Open Access Journals (Sweden)

    Khalid Hussain Janbaz


    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.

  16. Performance of the analytical solutions for Taylor dispersion process in open channel flow (United States)

    Zeng, L.; Wu, Zi; Fu, Xudong; Wang, Guangqian


    The present paper provides a systematical analysis for concentration distribution of Taylor dispersion in laminar open channel flow, seeking fundamental understandings for the physical process of solute transport that generally applies to natural rivers. As a continuation and a direct numerical verification of the previous theoretical work (Wu, Z., Chen, G.Q., 2014. Journal of Hydrology, 519: 1974-1984.), in this paper we attempt to understand that to what extent the obtained analytical solutions are valid for the multi-dimensional concentration distribution, which is vital for the key conclusion of the so-called slow-decaying transient effect. It is shown that as a first estimation, even asymptotically, the longitudinal skewness of the concentration distribution should be incorporated to predict the vertical concentration correctly. Thus the traditional truncation of the concentration expansion is considered to be insufficient for the first estimation. The analytical solution by the two-scale perturbation analysis with modifications up to the second order is shown to be a most economical solution to give a reasonably good prediction.

  17. Channel response to increased and decreased bedload supply from land use change: contrasts between two catchments (United States)

    Kondolf, G. M.; Piégay, H.; Landon, N.


    The catchments of Pine Creek, Idaho, USA (200 km 2), and the Drôme River in the Drôme Department, France (1640 km 2), illustrate contrasting changes in land use, bedload sediment production, and channel response. Hard-rock mining began in the catchment of Pine Creek near the end of the 19th century and, together with road construction, timber harvest, and historically heavy grazing of uplands, resulted in increased tributary bedload yield. Increased bedload migrating to the channel, combined with removal of large cedar trees on the floodplain, resulted in channel instability, which propagated downstream over a period of decades. On many reaches of Pine Creek, active channel width has increased by over 50% since 1933. Over roughly the same time period, the Drôme River catchment was extensively reforested (after at least one century of denudation and heavy grazing) and numerous check dams were constructed on torrents to reduce erosion. As a result, the Drôme River has experienced a reduction in bedload sediment supply since the late 19th century. In addition, gravel has been extracted from some reaches. Consequently, the channel has degraded and gravel bars have been colonized with woody riparian vegetation. Channel widths in wide, braided reaches decreased from 1947 to 1970 by 60%. On Pine Creek, channel instability has resulted in bank erosion (exposing contaminated mine tailings) and increased flood hazard. On the Drôme River, degradation has undermined bridges and embankments, and lowered the water table in areas dependent on groundwater for irrigation, resulting in loss of 6 million m 3 of groundwater storage since 1960. Though they differ in drainage area by nearly an order of magnitude, Pine Creek and the Drôme River provide an excellent contrast in that they represent two sides of an epicycle of alluvial sedimentation set off in each case by land disturbance. In both cases, the most recent channel changes, though in opposite directions, were viewed as

  18. 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 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.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.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.Resveratrol is a potent chloride secretagogue from the mucosal surface of sinonasal epithelium, and hydrates airway surface liquid by increasing CFTR channel open probability. The foundation for a

  19. Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats

    DEFF Research Database (Denmark)

    Liu, Daoyan; Yang, Dachun; He, Hongbo


    We tested the hypothesis that transient receptor potential canonical type 3 (TRPC3) channels are increased in vascular smooth muscle cells and aortic tissue from spontaneously hypertensive rats (SHR) compared with normotensive Wistar Kyoto rats. Expression of TRPC3 was analyzed by immunohistochem...

  20. ATP-sensitive potassium (KATP channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Uttio Roy Chowdhury

    Full Text Available Elevated intraocular pressure is the most prevalent and only treatable risk factor for glaucoma, a degenerative disease of the optic nerve. While treatment options to slow disease progression are available, all current therapeutic and surgical treatments have unwanted side effects or limited efficacy, resulting in the need to identify new options. Previous reports from our laboratory have established a novel ocular hypotensive effect of ATP-sensitive potassium channel (KATP openers including diazoxide (DZ and nicorandil (NCD. In the current study, we evaluated the role of Erk1/2 signaling pathway in KATP channel opener mediated reduction of intraocular pressure (IOP. Western blot analysis of DZ and NCD treated primary normal trabecular meshwork (NTM cells, human TM (isolated from perfusion cultures of human anterior segments and mouse eyes showed increased phosphorylation of Erk1/2 when compared to vehicle treated controls. DZ and NCD mediated pressure reduction (p0.1. Histologic evaluation of transmission electron micrographs from DZ + U0126 and NCD + U0126 treated eyes revealed no observable morphological changes in the ultrastructure of the conventional outflow pathway. Taken together, the results indicate that the Erk1/2 pathway is necessary for IOP reduction by KATP channel openers DZ and NCD.

  1. Low pressure drop filtration of airborne molecular organic contaminants using open-channel networks (United States)

    Dallas, Andrew J.; Joriman, Jon; Ding, Lefei; Weineck, Gerald; Seguin, Kevin


    Airborne molecular contamination (AMC) continues to play a very decisive role in the performance of many microelectronic devices and manufacturing processes. Besides airborne acids and bases, airborne organic contaminants such as 1-methyl-2-pyrrolidinone (NMP), hexamethyldisiloxane (HMDSO), trimethylsilanol (TMS), perfluoroalkylamines and condensables are of primary concern in these applications. Currently, the state of the filtration industry is such that optimum filter life and removal efficiency for organics is offered by granular carbon filter beds. However, the attributes that make packed beds of activated carbon extremely efficient also impart issues related to elevated filter weight and pressure drop. Most of the lower pressure drop AMC filters currently offered are quite expensive and are simply pleated combinations of various adsorptive and reactive media. On the other hand, low pressure drop filters, such as those designed as open-channel networks (OCN's), offer good filter life and removal efficiency with the additional benefits of significant reductions in overall filter weight and pressure drop. Equally important for many applications, the OCN filters can reconstruct the airflow so as to enhance the operation of a tool or process. For tool mount assemblies and fan filter units (FFUs) this can result in reduced fan and blower speeds, which subsequently can provide reduced vibration and energy costs. Additionally, these low pressure drop designs can provide a cost effective way of effectively removing AMC in full fab (or HVAC) filtration applications without significantly affecting air-handling requirements. Herein, we will present a new generation of low pressure drop OCN filters designed for the removal of airborne organics in a wide range of applications.

  2. Velocity-based analysis of sediment incipient deposition in rigid boundary open channels. (United States)

    Aksoy, Hafzullah; Safari, Mir Jafar Sadegh; Unal, Necati Erdem; Mohammadi, Mirali


    Drainage systems must be designed in a way to minimize undesired problems such as decrease in hydraulic capacity of the channel, blockage and transport of pollutants due to deposition of sediment. Channel design considering self-cleansing criteria are used to solve the sedimentation problem. Incipient deposition is one of the non-deposition self-cleansing design criteria that can be used as a conservative method for channel design. Experimental studies have been carried out in five different cross-section channels, namely trapezoidal, rectangular, circular, U-shape and V-bottom. Experiments were performed in a tilting flume using four different sizes of sands as sediment in nine different channel bed slopes. Two well-known methods, namely the Novak & Nalluri and Yang methods are considered for the analysis of sediment motion. Equations developed using experimental data are found to be in agreement with the literature. It is concluded that the design velocity depends on the shape of the channel cross-section. Rectangular and V-bottom channels need lower and higher incipient deposition velocities, respectively, in comparison with other channels.

  3. Effects of free-surface on design charts for open channels

    African Journals Online (AJOL)


    Dec 14, 2011 ... Normal depth is an important parameter for the design of channels and canals. For rectangular, trapezoidal, and circular channel sections it is possible to express normal depth by a trial-and-error procedure or analytically. However, the effects of free-surface on the design charts for determination of the ...

  4. Groundwater flow into underground openings in fractured crystalline rocks: an interpretation based on long channels (United States)

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


    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.

  5. First experiences with an on-axis LDV-system in special application to open-channel flow

    International Nuclear Information System (INIS)

    Arnold, U.; Stein, U.; Pasche, E.


    Non-intrusive simultaneous measurement of the main and transverse velocity component in compound open-channel flow requires the application of two-component on-axis LDV technique. In this paper a modified TSI single color, two-frequency on-axis LDV equipment is described and several alternatives of signal processing are discussed. For a comparative investigation of signal quality power spectra of single Doppler bursts were determined in order to measure mean signal-to-noise ratios at the exit of the system specific signal separation devices. The major objective of these experiment was to examine the LDV-system's applicability to counter-type signal processing with respect to reliable measurement of turbulent quantities. Finally some preliminary experiments are described concerning the application of the on-axis LDV equipment to high and low turbulent open-channel flow

  6. Hall effect mobility for SiC MOSFETs with increasing dose of nitrogen implantation into channel region (United States)

    Noguchi, Munetaka; Iwamatsu, Toshiaki; Amishiro, Hiroyuki; Watanabe, Hiroshi; Kita, Koji; Yamakawa, Satoshi


    The Hall effect mobility (μHall) of the Si-face 4H-SiC metal–oxide–semiconductor field effect transistor (MOSFET) with a nitrogen (N)-implanted channel region was investigated by increasing the N dose. The μHall in the channel region was systematically examined regarding channel structures, that is, the surface and buried channels. It was experimentally demonstrated that increasing the N dose results in an improvement in μHall in the channel region due to the formation of the buried channel. However, further increase in N dose was found to decrease the μHall in the channel region, owing to the decrease in the electron mobility in the N-implanted bulk region.

  7. Modification of single Na+ channels by batrachotoxin. (United States)

    Quandt, F N; Narahashi, T


    The modifications in the properties of voltage-gated Na+ channels caused by batrachotoxin were studied by using the patch clamp method for measuring single channel currents from excised membranes of N1E-115 neuroblastoma cells. The toxin-modified open state of the Na+ channel has a decreased conductance in comparison to that of normal Na+ channels. The lifetime of the modified open state is drastically prolonged, and channels now continue to open during a maintained depolarization so that the probability of a channel being open becomes constant. Modified and normal open states of Na+ channels coexist in batrachotoxin-exposed membrane patches. Unlike the normal condition, Na+ channels exposed to batrachotoxin open spontaneously at large negative potentials. These spontaneous openings apparently cause the toxin-induced increase in Na+ permeability which, in turn, causes membrane depolarization.

  8. 2-Dimensional Numerical Analysis of Flow and Bed Evolution in Open-Channel Bends with Cylindrical Roughness


    冨永, 晃宏; 青木, 健太郎


    Vegetation in a river has a similar effect as permeable super dikes. Such an effect can be substituted by a group of cylindrical roughness. In this study, 3-dimensional flow structures and bed evolution were measured in a curved open channel with cylindrical roughness located along the outer bank. A series of cylinder decreased the scour at the outer bank. Especially submerged cylindrical roughness can reduce the bed evolution much more. Flow structures over the submerged cylindrical roughnes...

  9. 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)


    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.


    Directory of Open Access Journals (Sweden)

    Olga N. Kozlova


    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.

  11. 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)


    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.

  12. ANN Model for Predicting the Impact of Submerged Aquatic Weeds Existence on the Hydraulic Performance of Branched Open Channel System Accompanied by Water Structures

    International Nuclear Information System (INIS)

    Abdeen, Mostafa A. M.; Abdin, Alla E.


    The existence of hydraulic structures in a branched open channel system urges the need for considering the gradually varied flow criterion in evaluating the different hydraulic characteristics in this type of open channel system. Computations of hydraulic characteristics such as flow rates and water surface profiles in branched open channel system with hydraulic structures require tremendous numerical effort especially when the flow cannot be assumed uniform. In addition, the existence of submerged aquatic weeds in this branched open channel system adds to the complexity of the evaluation of the different hydraulic characteristics for this system. However, this existence of aquatic weeds can not be neglected since it is very common in Egyptian open channel systems. Artificial Neural Network (ANN) has been widely utilized in the past decade in civil engineering applications for the simulation and prediction of the different physical phenomena and has proven its capabilities in the different fields. The present study aims towards introducing the use of ANN technique to model and predict the impact of submerged aquatic weeds existence on the hydraulic performance of branched open channel system. Specifically the current paper investigates a branched open channel system that consists of main channel supplies water to two branch channels that are infested by submerged aquatic weeds and have water structures such as clear over fall weirs and sluice gates. The results of this study showed that ANN technique was capable, with small computational effort and high accuracy, of predicting the impact of different infestation percentage for submerged aquatic weeds on the hydraulic performance of branched open channel system with two different hydraulic structures

  13. 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)


    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.

  14. 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 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.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.THE DATA INDICATE: 1 that rapid environmental changes occur at the

  15. Open Channel Natural Convection Heat Transfer on a Vertical Finned Plate

    International Nuclear Information System (INIS)

    Park, Joo Hyun; Heo, Jeong Hwan; Chung, Bum Jin


    The natural convection heat transfer of vertical plate fin was investigated experimentally. Heat transfer systems were replaced by mass-transfer systems, based on the analogy concept. The experimental results lie within the predictions of the existing heat transfer correlations of plate-fin for the natural convections. An overlapped thermal boundary layers caused increasing heat transfer, and an overlapped momentum boundary layers caused decreasing heat transfer. As the fin height increases, heat transfer was enhanced due to increased inflow from the open side of the fin spacing. When fin spacing and fin height are large, heat transfer was unaffected by the fin spacing and fin height. Passive cooling by natural convection becomes more and more important for the nuclear systems as the station black out really happened at the Fukushima NPPs. In the RCCS (Reactor Cavity Cooling System) of a VHTR (Very High Temperature Reactor), natural convection cooling through duct system is adopted. In response to the stack failure event, extra cooling capacity adopting the fin array has to be investigated. The finned plate increases the surface area and the heat transfer increases. However, the plate of fin arrays may increase the pressure drop and the heat transfer decreases. Therefore, in order to enhance the passive cooling with fin arrays, the parameters for the fin arrays should be optimized. According to Welling and Wooldridge, a natural convection on vertical plate fin is function of Gr, Pr, L, t, S, and H. The present work investigated the natural convection heat transfer of a vertical finned plate with varying the fin height and the fin spacing. In order achieve high Rayleigh numbers, an electroplating system was employed and the mass transfer rates were measured using a copper sulfate electroplating system based on the analogy concept

  16. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels. (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin


    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

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


    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

  18. Structural models of the transmembrane region of voltage-gated and other K+ channels in open, closed, and inactivated conformations. (United States)

    Durell, S R; Hao, Y; Guy, H R


    A large collaborative, multidisciplinary effort involving many research laboratories continues which uses indirect methods of molecular biology and membrane biophysics to analyze the three-dimensional structures and functional mechanisms of K+ channels. This work also extends to the distant relatives of these channels, including the voltage-gated Na+ and Ca2+ channels. The role that our group plays in this process is to combine the information gained from experimental studies with molecular modeling techniques to generate atomic-scale structural models of these proteins. The modeling process involves three stages which are summarized as: (I) prediction of the channel sequence transmembrane topology, including the functionality and secondary structure of the segments; (II) prediction of the relative positions of the transmembrane segments, and (III) filling in all atoms of the amino acid residues, with conformations for energetically stabilized interactions. Both physiochemical and evolutionary principles (including sequence homology analysis) are used to guide the development. In addition to testing the steric and energetic feasibilities of different structural hypotheses, the models provide guidance for the design of new experiments. Structural modeling also serves to "fill in the gaps" of experimental data, such as predicting additional residue interactions and conformational changes responsible for functional processes. The modeling process is currently at the stage that experimental studies have definitely confirmed most of our earlier predictions about the transmembrane topology and functionality of different segments. Additionally, this report describes the detailed, three-dimensional models we have developed for the entire transmembrane region and important functional sites of the voltage-gated Shaker K+ channel in the open, closed, and inactivated conformations (including the ion-selective pore and voltage-sensor regions). As part of this effort, we also

  19. Large Eddy Simulation of the flow in 90r angled open-channel confluences with discordant beds (United States)

    Ramos, Pedro; Schindfessel, Laurent; De Mulder, Tom


    The aim of the present contribution is to investigate the effect of difference in bed elevations of the tributary and main channel in a 90˚ angled open-channel confluence onto the hydrodynamics. Large Eddy Simulations (LES) are used to investigate the three-dimensional complex flow patterns for four different discordance ratios (ΔzT/hd = 0, 0.1, 0.25 and 0.4), with geometries previously studied by other authors, whose data will be used for comparison purposes. The values of the ratio between the upstream main channel discharge and the total combined discharge varies between 0.083 and 0.917. With LES, it is possible to resolve a portion of the turbulent motions, which is beneficial to the accuracy of the simulations. This contribution develops further analysis on some findings of the aforementioned studies, mostly regarding the role of the bed discordance on the recirculation zone dimensions and on the influence of the tributary flow on the main stream. Points of interest are the orientation of the tributary's inflow angle and the dimensions of the separation zone. These parameters are important for the longitudinal momentum balance, which determines the head losses occurring at the confluence. Additionally, the distribution of Turbulent Kinetic Energy (TKE) and bed shear stresses are studied. Previous studied indicated that the presence of a bed discordance has a pronounced effect on these points of interest. The present contribution elaborates these findings and adds knowledge from time-resolved simulations. Since in a LES the flow and turbulence are for the most part resolved, it enables a thorough study of the hydrodynamics in an open-channel confluence, of which the understanding of the physical phenomena occurring in natural confluences will benefit.

  20. Pentobarbital inhibition of human recombinant α1A P/Q-type voltage-gated calcium channels involves slow, open channel block (United States)

    Schober, A; Sokolova, E; Gingrich, KJ


    BACKGROUND AND PURPOSE Pre-synaptic neurotransmitter release is largely dependent on Ca2+ entry through P/Q-type (CaV2.1) voltage-gated Ca2+ channels (PQCCs) at most mammalian, central, fast synapses. Barbiturates are clinical depressants and inhibit pre-synaptic Ca2+ entry. PQCC barbiturate pharmacology is generally unclear, specifically in man. The pharmacology of the barbiturate pentobarbital (PB) in human recombinant α1A PQCCs has been characterized. EXPERIMENTAL APPROACH PB effects on macroscopic Ca2+(ICa) and Ba2+(IBa) currents were studied using whole-cell patch clamp recording in HEK-293 cells heterologously expressing (α1A)human(β2aα2δ-1)rabbit PQCCs. KEY RESULTS PB reversibly depressed peak current (Ipeak) and enhanced apparent inactivation (fractional current at 800 ms, r800) in a concentration-dependent fashion irrespective of charge carrier (50% inhibitory concentration: Ipeak, 656 µM; r800, 104 µM). Rate of mono-exponential IBa decay was linearly dependent on PB concentration. PB reduced channel availability by deepening non-steady-state inactivation curves without altering voltage dependence, slowed recovery from activity-induced unavailable states and produced use-dependent block. PB (100 µM) induced use-dependent block during physiological, high frequency pulse trains and overall depressed PQCC activity by two-fold. CONCLUSION AND IMPLICATIONS The results support a PB pharmacological mechanism involving a modulated receptor with preferential slow, bimolecular, open channel block (Kd = 15 µM). Clinical PB concentrations (<200 µM) inhibit PQCC during high frequency activation that reduces computed neurotransmitter release by 16-fold and is comparable to the magnitude of Ca2+-dependent facilitation, G-protein modulation and intrinsic inactivation that play critical roles in PQCC modulation underlying synaptic plasticity. The results are consistent with the hypothesis that PB inhibition of PQCCs contributes to central nervous system

  1. Opening of calcium-activated potassium channels improves long-term left-ventricular function after coronary artery occlusion in mice

    NARCIS (Netherlands)

    Behmenburg, Friederike; Hölscher, Nina; Flögel, Ulrich; Hollmann, Markus W.; Heinen, André; Huhn, Ragnar


    Background: Opening of mitochondrial calcium-activated potassium channels (BKCa) reduces infarct size after myocardial ischemia/reperfusion injury (I/R). It is unknown if targeting BKCa-channels improves cardiac performance in the long-term after I/R. Methods: Experiments were conducted in

  2. Increasing Brand Awareness Trough Utilization Of Social Media And Expansion Of Relevant Market Channels


    Nummelin, Aura


    The purpose of this thesis is to suggest ways to increase and develop the brand image of A. Ahlström Real Estate Ltd. The plan involves more effort put on B2B events, adding new service concepts, highlighting social media as a marketing tool and creating a new sales strategy for foreign customers. The goal is not to create a brand, but rather enhance and develop the already existing one. By implementing a variety of social media channels into their marketing strategy A. Ahlström Real...

  3. Radiation heat transfer within an open-cycle MHD generator channel (United States)

    Delil, A. A. M.


    Radiation heat transfer in an MHD generator was modeled using the Sparrow and Cess model for radiation in an emitting, absorbing and scattering medium. The resulting general equations can be considerably reduced by introducing simplifying approximations for the channel and MHD gas properties. The simplifications lead to an engineering model, which is very useful for one-dimensional channel flow approximation. The model can estimate thermo-optical MHD gas properties, which can be substituted in the energy equation. The model considers the contribution of solid particles in the MHD gas to radiation heat transfer, considerable in coal-fired closed cycle MHD generators. The modeling is applicable also for other types of flow at elevated temperatures, where radiation heat transfer is an important quantity.

  4. Three dimensional flow field at confluent fixed-bed open channels


    Schleiss, Anton; De Cesare, Giovanni; Franca, Mário J.; Pfister, Michael; Birjukova, Olga; Guillén Ludeña, Sebastián; Alegria, Francisco; Cardoso, Antonio H.


    River confluences are known for their marked 3D patterns and, due to the complexity of local flow features and bed morphology, they require particular consideration. Although there are studies on the flow structure in junctions of two streams, amore detailed description of the flow patterns is still required. The objective of this work is to contribute to such description at river confluence for concordant bed, where both main and tributary channel beds have the same elevation. For that purpo...

  5. The marine algal toxin azaspiracid is an open state blocker of hERG potassium channels


    Twiner, Michael J.; Doucette, Gregory J.; Rasky, Andrew; Huang, Xi-Ping; Roth, Bryan L.; Sanguinetti, Michael C.


    Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in shellfish and represent an emerging human health risk. Although human exposure is primarily manifested by severe and protracted diarrhea, this toxin class has been shown to be highly cytotoxic, a teratogen to developing fish, and a possible carcinogen in mice. Until now, AZA's molecular target(s) has not yet been determined. Using three independent methods (voltage clamp, channel binding assay, and thallium flux ...

  6. Construction of robust open metal-organic frameworks with chiral channels and permanent porosity. (United States)

    Sun, Daofeng; Ke, Yanxiong; Collins, David J; Lorigan, Gary A; Zhou, Hong-Cai


    Four new metal-organic frameworks (MOFs) containing chiral channels have been synthesized using an achiral, triazine-based trigonal-planar ligand, 4,4',4' '-s-triazine-2,4,6-triyltribenzoate (TATB), and an hourglass secondary building unit (SBU): Zn3(TATB)2(H2O)2.4DMF.6H2O (1); Cd3(TATB)2(H2O)2.7DMA.10H2O (2); [H2N(CH3)2][Zn3(TATB)2(HCOO)].HN(CH3)2.3DMF.3H2O (3); [H2N(CH3)2][Cd3(TATB)2(CH3COO)].HN(CH3)2.3DMA.4H2O (4). MOFs 1 and 2 are isostructural and possess (10,3)-a nets containing large chiral channels of 20.93 and 21.23 A, respectively, but are thermally unstable due to the easy removal of coordinated water molecules on the SBU. Replacement of these water molecules by formate or acetate generated in situ leads to 3 and 4, respectively. Formate or acetate links SBUs to form infinite helical chains bridged by TATB to create three-dimensional anionic networks, in which one of the two oxygen atoms of the formate or acetate is uncoordinated and points into the void of the channels. This novel SBU-stabilization and channel-functionalization strategy may have general implications in the preparation of new MOFs. Thermogravimetric analysis (TGA) shows that solvent-free 3' is thermally stable to 410 degrees C, while TGA studies on samples vapor-diffused with water, methanol, and chloroform show reversible adsorption. MOF 3 also has permanent porosity with a large Langmuir surface area of 1558 m2/g. All complexes exhibit similar strong luminescence with a lambdamax of approximately 423 nm upon excitation at 268.5 nm.

  7. 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


    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, yc, 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 yc-based dimensionless GVF equation is more useful and versatile than its counterpart from the GVF equation normalized by the normal depth, yn, because the GHF-based solutions of the yc-based dimensionless GVF equation for the mild (M and adverse (A profiles can asymptotically reduce to the yc-based dimensionless horizontal (H profiles as yc/yn → 0. An in-depth analysis of the yc-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 yc/yn and the hydraulic exponent N on the profiles. This paper has laid the foundation to compute at one sweep the yc-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.

  8. 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


    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.

  9. PyFLOWGO: An open-source platform for simulation of channelized lava thermo-rheological properties (United States)

    Chevrel, Magdalena Oryaëlle; Labroquère, Jérémie; Harris, Andrew J. L.; Rowland, Scott K.


    Lava flow advance can be modeled through tracking the evolution of the thermo-rheological properties of a control volume of lava as it cools and crystallizes. An example of such a model was conceived by Harris and Rowland (2001) who developed a 1-D model, FLOWGO, in which the velocity of a control volume flowing down a channel depends on rheological properties computed following the thermal path estimated via a heat balance box model. We provide here an updated version of FLOWGO written in Python that is an open-source, modern and flexible language. Our software, named PyFLOWGO, allows selection of heat fluxes and rheological models of the user's choice to simulate the thermo-rheological evolution of the lava control volume. We describe its architecture which offers more flexibility while reducing the risk of making error when changing models in comparison to the previous FLOWGO version. Three cases are tested using actual data from channel-fed lava flow systems and results are discussed in terms of model validation and convergence. PyFLOWGO is open-source and packaged in a Python library to be imported and reused in any Python program (

  10. Increased extracellular pressure stimulates tumor proliferation by a mechanosensitive calcium channel and PKC-β. (United States)

    Basson, Marc D; Zeng, Bixi; Downey, Christina; Sirivelu, Madhu P; Tepe, Jetze J


    Large tumors exhibit high interstitial pressure heightened by growth against the constraining stroma. Such pressures could stimulate tumor proliferation via a mechanosensitive ion channel. We studied the effects of 0-80 mmHg increased extracellular pressure for 24 h on proliferation of SW620, Caco-2, and CT-26 colon; MCF-7 breast; and MLL and PC3 prostate cancer cells, and delineated its mechanism in SW620 cells with specific inhibitors and siRNA. Finally, we compared NF-kB, phospho-IkB and cyclin D1 immunoreactivity in the high pressure centers and low pressure peripheries of human tumors. Pressure-stimulated proliferation in all cells. Pressure-driven SW620 proliferation required calcium influx via the T-type Ca(2+) channel Cav3.3, which stimulated PKC-β to invoke the IKK-IkB-NF-kB pathway to increase proliferation and S-phase fraction. The mitotic index and immunoreactivity of NF-kB, phospho-IkB, and cyclin D1 in the center of 28 large human colon, lung, and head and neck tumors exceeded that in tumor peripheries. Extracellular pressure increases [Ca(2+)]i via Cav3.3, driving a PKC-β- IKK- IkB-NF-kB pathway that stimulates cancer cell proliferation. Rapid proliferation in large stiff tumors may increase intratumoral pressure, activating this pathway to stimulate further proliferation in a feedback cycle that potentiates tumor growth. Targeting this pathway may inhibit proliferation in large unresectable tumors. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. The effect of bed roughness on the free surface of an open channel flow and implications for remotely monitoring river discharge (United States)

    Johnson, Erika; Cowen, Edwin


    The effect of increased bed roughness on the free surface turbulence signature of an open channel flow is investigated with the goal of incorporating the findings into a methodology to remotely monitor volumetric flow rates. Half of a wide (B = 2 m) open channel bed is covered with a 3 cm thick layer of loose gravel (D50 = 0.6 cm). Surface PIV (particle image velocimetry) experiments are conducted for a range of flow depths (B/H = 10-30) and Reynolds numbers (ReH = 10,000-60,000). It is well established that bed roughness in wall-bounded flows enhances the vertical velocity fluctuations (e.g. Krogstad et al. 1992). When the vertical velocity fluctuations approach the free surface they are redistributed (e.g. Cowen et al. 1995) to the surface parallel component directions. It is anticipated and confirmed that the interaction of these two phenomena result in enhanced turbulence at the free surface. The effect of the rough bed on the integral length scales and the second order velocity structure functions calculated at the free surface are investigated. These findings have important implications for developing new technologies in stream gaging.

  12. A new 3-D open-framework cadmium borovanadate with plane-shaped channels and high catalytic activity for the oxidation of cyclohexanol. (United States)

    Feng, Yuquan; Qiu, Dongfang; Fan, Huitao; Li, Min; Huang, Qunzeng; Shi, Hengzhen


    A new 3-D open-framework cadmium borovanadate with 6-connected topology was hydrothermally obtained and structurally characterized. It not only features new cadmium(II) borovanadate which possesses an open-framework structure with unique plane-shaped channels, but also exhibits interesting absorption properties and high catalytic activities for the oxidation of cyclohexanol.

  13. Increased HCN channel driven inward rectification in benign cramp fasciculation syndrome. (United States)

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


    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. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:

  14. Integration of biological kinetics and computational fluid dynamics to model the growth of Nannochloropsis salina in an open channel raceway. (United States)

    Park, Stephen; Li, Yebo


    Microalgal growth and systemic productivity is not only affected by environmental conditions such as temperature, irradiance, and nutrient concentrations, but also by physical processes such as fluid flow and particulate sedimentation. Modeling and simulating the system is a cost-effective way to predict the growth behavior under various environmental and physical conditions while determining effective engineering approaches to maximize productivity. Many mathematical models have been proposed to describe microalgal growth, while computational fluid dynamics (CFD) have been used to model the behavior of many fluid systems. Integrating the growth kinetics into a CFD model can help researchers understand the impact of a variety of parameters and determine what measures can be taken to overcome some obstacles in the aquaculture industry--self-shading, biomass sedimentation, and contamination--which prevent the production of high biomass yields. The aim of this study was to integrate physical and environmental effects to predict space- and time-dependent algal growth in industrial scale raceways. A commercial CFD software, ANSYS-Fluent 14.5, was used to solve the proposed models in regards to fluid flow, heat transfer, and nutrient balance. User-defined functions written in C language were used to incorporate the kinetic equations into a three-dimensional standard k-ε turbulence model of an open channel raceway system driven by a single paddlewheel. Simulated results were compared with light intensity, temperature, nutrient concentration, and algal biomass data acquired for 56 day from an industrial scale raceway pond constructed for the growth of Nannochloropsis salina and were observed to be in good agreement with one another. There was up to a 17.6% increase in simulated productivity when the incoming CO2 concentration was increased from 0.0006 to 0.150 g L(-1), while the effect of paddlewheel velocity was not significant. Sensitivity analysis showed that the model

  15. 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


    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...... decreases action potential duration and triangulation. For single cells, NS1643 increases the postrepolarization refractory time but shortens the absolute refractory period. In one dimensional simulations, NS1643 increases the vulnerable window for unidirectional block but suppresses the emergence...

  16. The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

    Directory of Open Access Journals (Sweden)

    Weijie Liang


    Full Text Available Background/Aims: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS, toll-like receptor 4 (TLR4, receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis, which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP channel opening against high glucose-induced cardiac injury and inflammation. Methods: H9c2 cardiac cells were treated with 35 mM glucose (HG to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP and secretion of inflammatory cytokines were measured as injury indexes. Results: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis or TAK-242 (an inhibitor of TLR4 co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener or pinacidil (Pin, a non-selective KATP channel opener or N-acetyl-L-cysteine (NAC, a ROS scavenger pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker or glibenclamide (Gli, a non-selective KATP channel blocker pre-treatment did not aggravate HG-induced injury and inflammation. Conclusion: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.

  17. Hydrodynamics of concordant and discordant fixed bed open-channel confluences (United States)

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


    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

  18. Online distribution channel increases article usage on Mendeley: a randomized controlled trial. (United States)

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


    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  < 0.01). There was a positive correlation between pageviews driven by TrendMD and article saves on 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.

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

    Directory of Open Access Journals (Sweden)

    R Rahimzadeh


    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.

  20. In Search for the Open Educator: Proposal of a Definition and a Framework to Increase Openness Adoption Among University Educators


    Nascimbeni, Fabio (UNIR); Burgos, Daniel (UNIR)


    The paper explores the change process that university teachers need to go through in order to become fluent with Open Education approaches. Based on a literature review and a set of interviews with a number of leading experts in the field of Open Educational Resources and Open Education, the paper puts forward an original definition of Open Educator which takes into account all the components of teachers' work: learning design, teaching resources, pedagogical approaches and assessment methods...

  1. In Search for the Open Educator: Proposal of a Definition and a Framework to Increase Openness Adoption among University Educators (United States)

    Nascimbeni, Fabio; Burgos, Daniel


    The paper explores the change process that university teachers need to go through in order to become fluent with Open Education approaches. Based on a literature review and a set of interviews with a number of leading experts in the field of Open Educational Resources and Open Education, the paper puts forward an original definition of Open…

  2. 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.


    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.

  3. Hydrodynamic and Sediment Responses of Open Channels to Exposed Pipe Encasements.

    Directory of Open Access Journals (Sweden)

    J Q Mao

    Full Text Available The effects of exposed pipe encasements on the local variation of hydrodynamic and sediment conditions in a river channel are examined. Laboratory experiments are performed to assess the response of water level, flow regime and bed deformation to several representative types of concrete encasements. The experimental conditions considered are: three types of exposed pipe encasements exposed on the bed, including trapezoidal shape, circular-arc shape and polygonal shape, and three sets of discharges, including annual discharge, once-in-3-year flood, and once-in-50-year flood. Our experiments show that: (1 the amount of backwater definitely depends on the encasement geometric shape and the background discharge; (2 smaller discharges generally tend to induce local scour of river bed downstream of the encasement, and the order of sensitivity of bed deformation to the encasement geometric shape is trapezoidal > circular-arc > polygonal; (3 comparatively speaking, the polygonal encasement may be considered as a suitable protective structure for pipelines across alluvial rivers, with relatively modest effects on the local hydrodynamic conditions and bed stabilization.

  4. Hydrodynamic and Sediment Responses of Open Channels to Exposed Pipe Encasements. (United States)

    Mao, J Q; Zhang, H Q; Dai, H C; Yuan, B H; Hu, T F


    The effects of exposed pipe encasements on the local variation of hydrodynamic and sediment conditions in a river channel are examined. Laboratory experiments are performed to assess the response of water level, flow regime and bed deformation to several representative types of concrete encasements. The experimental conditions considered are: three types of exposed pipe encasements exposed on the bed, including trapezoidal shape, circular-arc shape and polygonal shape, and three sets of discharges, including annual discharge, once-in-3-year flood, and once-in-50-year flood. Our experiments show that: (1) the amount of backwater definitely depends on the encasement geometric shape and the background discharge; (2) smaller discharges generally tend to induce local scour of river bed downstream of the encasement, and the order of sensitivity of bed deformation to the encasement geometric shape is trapezoidal > circular-arc > polygonal; (3) comparatively speaking, the polygonal encasement may be considered as a suitable protective structure for pipelines across alluvial rivers, with relatively modest effects on the local hydrodynamic conditions and bed stabilization.

  5. Revelation of the interactions between bedload and turbulent flow in open channels using a LES-DEM coupled model (United States)

    Liu, X.; Liu, D.; Fu, X.


    Bedload transport is an important transport mode for sediment, which has great influence on the erosion and deposition near channel bed. To fully understand the mechanism of bedload transport, it is critical to know the motion characteristics and the interaction between bedload particles and turbulent structures. However, the motion of bedload particles can rarely be measured accurately because of experimental difficulties. In this work, a model of bedload transport in open channel flows is built by combining large eddy simulation (LES) with discrete element model (DEM) using a momentum coupling method. For the particles, a four-way coupling approach is utilized. Numerical experiments are conducted and post processed by statistic and quadrant threshold analysis. The characteristics of the kinematics and dynamics of the bedload particles are of particular interest during the analysis. The particle trajectory, velocity distribution and force condition are processed for further analysis. The model is validated by flow field and bedload transport rate data. The model produces an exponential form of the velocity statistics, which have been confirmed by experiments in the literature. The quadrant analysis also reveals rich information about the interaction between the particle and the flow. Among many things, it is found that the ejection events are influenced more than the sweep event. It is because the sweep event is more controlled by the outer flow. The size of the near wall coherent structure is smaller and their occurrence is less frequent when the particles are in motion.

  6. Direct numerical simulation of open channel flow over smooth-to-rough and rough-to-smooth step changes (United States)

    Rouhi, Amirreza; Chung, Daniel; Hutchins, Nicholas


    Direct numerical simulations (DNSs) are reported for open channel flow over streamwise-alternating patches of smooth and fully rough walls. Owing to the streamwise periodicity, the flow configuration is composed of a step change from smooth to rough, and a step change from rough to smooth. The friction Reynolds number varies from 443 over the smooth patch to 715 over the rough patch. The flow is thoroughly studied by mean and fluctuation profiles, and spectrograms. The detailed flow from DNS reveals discrepancies of up to 50% among the various definitions of the internal-layer thickness, with apparent power-law exponents differing by up to 60%. The definition based on the logarithmic slope of the velocity profile, as proposed by Chamorro et al. (Boundary-Layer Meteorol., vol. 130, 2009, pp. 29-41), is most consistent with the physical notion of the internal layer; this is supported by the defect similarity based on this internal-layer thickness, and the streamwise homogeneity of the dissipation length-scale within this internal layer. The statistics inside this internal-layer, and the growth of the internal layer itself, are minimally affected by the streamwise periodicity when the patch length is at least six times the channel height.

  7. Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. (United States)

    Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick


    A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of "openness" occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures. Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found. These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.

  8. EEG channels reduction using PCA to increase XGBoost's accuracy for stroke detection (United States)

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


    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.

  9. Flexion-Type Supracondylar Humeral Fractures: Ulnar Nerve Injury Increases Risk of Open Reduction. (United States)

    Flynn, Kelly; Shah, Apurva S; Brusalis, Christopher M; Leddy, Kelly; Flynn, John M


    .4-fold increase in the odds of open reduction. The presence of an ulnar nerve injury at presentation resulted in an additional 6.7-fold higher risk of open reduction among flexion-type supracondylar humeral fractures. Patients and families should be counseled regarding the high rate of open reduction for flexion-type supracondylar humeral fractures, particularly those with an associated ulnar nerve injury. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

  10. Soft Sensing of Non-Newtonian Fluid Flow in Open Venturi Channel Using an Array of Ultrasonic Level Sensors-AI Models and Their Validations. (United States)

    Chhantyal, Khim; Viumdal, Håkon; Mylvaganam, Saba


    In oil and gas and geothermal installations, open channels followed by sieves for removal of drill cuttings, are used to monitor the quality and quantity of the drilling fluids. Drilling fluid flow rate is difficult to measure due to the varying flow conditions (e.g., wavy, turbulent and irregular) and the presence of drilling cuttings and gas bubbles. Inclusion of a Venturi section in the open channel and an array of ultrasonic level sensors above it at locations in the vicinity of and above the Venturi constriction gives the varying levels of the drilling fluid in the channel. The time series of the levels from this array of ultrasonic level sensors are used to estimate the drilling fluid flow rate, which is compared with Coriolis meter measurements. Fuzzy logic, neural networks and support vector regression algorithms applied to the data from temporal and spatial ultrasonic level measurements of the drilling fluid in the open channel give estimates of its flow rate with sufficient reliability, repeatability and uncertainty, providing a novel soft sensing of an important process variable. Simulations, cross-validations and experimental results show that feedforward neural networks with the Bayesian regularization learning algorithm provide the best flow rate estimates. Finally, the benefits of using this soft sensing technique combined with Venturi constriction in open channels are discussed.

  11. Soft Sensing of Non-Newtonian Fluid Flow in Open Venturi Channel Using an Array of Ultrasonic Level Sensors—AI Models and Their Validations

    Directory of Open Access Journals (Sweden)

    Khim Chhantyal


    Full Text Available In oil and gas and geothermal installations, open channels followed by sieves for removal of drill cuttings, are used to monitor the quality and quantity of the drilling fluids. Drilling fluid flow rate is difficult to measure due to the varying flow conditions (e.g., wavy, turbulent and irregular and the presence of drilling cuttings and gas bubbles. Inclusion of a Venturi section in the open channel and an array of ultrasonic level sensors above it at locations in the vicinity of and above the Venturi constriction gives the varying levels of the drilling fluid in the channel. The time series of the levels from this array of ultrasonic level sensors are used to estimate the drilling fluid flow rate, which is compared with Coriolis meter measurements. Fuzzy logic, neural networks and support vector regression algorithms applied to the data from temporal and spatial ultrasonic level measurements of the drilling fluid in the open channel give estimates of its flow rate with sufficient reliability, repeatability and uncertainty, providing a novel soft sensing of an important process variable. Simulations, cross-validations and experimental results show that feedforward neural networks with the Bayesian regularization learning algorithm provide the best flow rate estimates. Finally, the benefits of using this soft sensing technique combined with Venturi constriction in open channels are discussed.

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

    Directory of Open Access Journals (Sweden)

    Chen Zhih-Cherng


    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.

  13. 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


    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...

  14. Dynamic Lift on an Artificial Static Armor Layer During Highly Unsteady Open Channel Flow

    Directory of Open Access Journals (Sweden)

    Stephan Mark Spiller


    Full Text Available The dynamic lift acting on a 100 mm × 100 mm section of a static armor layer during unsteady flow is directly measured in a series of physical experiments. The static armor layer is represented by an artificial streambed mold, made from an actual gravel bed. Data from a total of 190 experiments are presented, undertaken in identical conditions. Results show that during rapid discharge increases, the dynamic lift on the streambed repeatedly exhibits three clear peaks. The magnitude of the observed lift depends on the following hydrograph characteristics: (1 the initial flow depth; (2 the ramping duration and therefore the ramping rate; and (3 the total discharge increase. An adjusted unsteadiness parameter combines those three hydrograph characteristics for rapid discharge increases. Direct correlations between the unsteadiness parameter and the measured dynamic lift during unsteady flow are presented. In addition, the armor layer porosity showed a major impact on the observed effects. It is shown that increasing bed porosity leads to decreasing dynamic lift.

  15. The cholinomimetic morantel as an open channel blocker of the Ascaris suum ACR-16 nAChR. (United States)

    Abongwa, Melanie; Baber, Katherine E; Martin, Richard J; Robertson, Alan P


    Nematode parasite infections pose a significant threat in human and veterinary medicine. At least a third of the world's population is at risk from nematode parasite infections. These infections not only cause health problems, but also cause loss of livestock production and hence, economic losses. Anthelmintic drugs are the mainstay by which control of nematode parasite infections is achieved. Many of the currently available anthelmintics act on nicotinic acetylcholine receptors (nAChRs). However, the detailed mode of action (MOA) of these anthelmintics is not clearly understood. Elucidation of the MOA of anthelmintics is highly desirable; an in-depth knowledge of the MOA will better inform on mechanisms of resistance development and on ways to slow down or overcome resistance. The cholinomimetic anthelmintic, morantel, has a complex MOA involving the activation and block of levamisole-sensitive single nAChR channels (L-type nAChR or L-nAChR). More recently, morantel has been demonstrated to activate Haemonchus contortus and Parascaris equorum ACR-26/ACR-27 nAChRs expressed in Xenopus laevis oocytes. Previous studies in our laboratory, however, have shown morantel does not activate the nicotine-sensitive nAChR (N-type nAChR or N-nAChR), Ascaris suum ACR-16 (Asu-ACR-16). In this study, we used two-electrode voltage-clamp (TEVC) electrophysiology to investigate the inhibitory effects of morantel, on expressed Asu-ACR-16 nAChRs in X. laevis oocytes. Our results show that morantel acts as a non-competitive antagonist on Asu-ACR-16. This non-competitive antagonism by morantel was further demonstrated to be voltage-sensitive. We conclude based on our findings that morantel is a non-competitive voltage-sensitive open channel blocker of Asu-ACR-16.

  16. Effect of KC399, a newly synthesized K+ channel opener, on acetylcholine-induced electrical and mechanical activities in rabbit tracheal smooth muscle. (United States)

    Kamei, K.; Nabata, H.; Kuriyama, H.; Watanabe, Y.; Itoh, T.


    1. Effects of KC399, an opener of ATP-sensitive K+ channels were investigated on membrane potential, isometric force and intracellular Ca2+ ([Ca2+]i) mobilization induced by acetylcholine (ACh) in smooth muscle from the rabbit trachea. 2. In these smooth muscle cells, ACh (0.1 and 1 microM) depolarized the membrane in a concentration-dependent manner, KC399 (1-100 nM) hyperpolarized the membrane whether in the presence or absence of ACh. When the concentration of ACh was increased, the absolute values of the membrane potential induced by the maximum concentration of KC399 were less negative. 3. ACh (0.1 to 10 microM) concentration-dependently produced a phasic, followed by a tonic increase in both [Ca2+]i and force. KC399 (above 3 nM) lowered the resting [Ca2+]i and attenuated the ACh-induced phasic and tonic increases in [Ca2+]i and force, in a concentration-dependent manner. The magnitude of the inhibition was greater for the ACh-induced tonic responses than for the phasic ones. Nicardipine (0.3 microM), a blocker of the L-type Ca2+ channel, attenuated the ACh-induced tonic, but not phasic, increases in [Ca2+]i and force. KC399 further attenuated the ACh-induced tonic responses in the presence of nicardipine. 4. In beta-escin-skinned strips, Ca2+ (0.3-10 microM) produced a contraction in a concentration-dependent manner. KC399 (0.1 microM) had no effect on the Ca(2+)-force relationship in the presence or absence of ATP with GTP. However, at a very high concentration (1 microM), this agent slightly shifted the relationship to the right and attenuated the maximum Ca(2+)-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8564210

  17. Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy


    Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick


    A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of ?openness? occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of c...

  18. Poly(ethylene glycol as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor.

    Directory of Open Access Journals (Sweden)

    Wan-Chen Lin

    Full Text Available High-affinity blockers for an ion channel often have complex molecular structures that are synthetically challenging and/or laborious. Here we show that high-affinity blockers for the mouse nicotinic acetylcholine receptor (AChR can be prepared from a structurally simple material, poly(ethylene glycol (PEG. The PEG-based blockers (PQ1-5, comprised of a flexible octa(ethylene glycol scaffold and two terminal quaternary ammonium groups, exert low- to sub-micromolar affinities for the open AChR pore (measured via single-channel analysis of AChRs expressed in human embryonic kidney cells. PQ1-5 are comparable in pore-binding affinity to the strongest AChR open-channel blockers previously reported, which have complex molecular structures. These results suggest a general approach for designing potent open-channel blockers from a structurally flexible polymer. This design strategy involves simple synthetic procedures and does not require detailed information about the structure of an ion-channel pore.

  19. 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.


    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

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

    Directory of Open Access Journals (Sweden)

    Campomaggiore Francesca


    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.

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

    Directory of Open Access Journals (Sweden)

    N. Hotta


    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.

  2. Ghrelin inhibits proliferation and increases T-type Ca2+ channel expression in PC-3 human prostate carcinoma cells

    International Nuclear Information System (INIS)

    Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana; Sandoval, Alejandro; Monroy, Alma; Felix, Ricardo; Monjaraz, Eduardo


    Research highlights: → Ghrelin decreases prostate carcinoma PC-3 cells proliferation. → Ghrelin favors apoptosis in PC-3 cells. → Ghrelin increase in intracellular free Ca 2+ levels in PC-3 cells. → Grelin up-regulates expression of T-type Ca 2+ channels in PC-3 cells. → PC-3 cells express T-channels of the Ca V 3.1 and Ca 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 2+ levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca 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 2+ channel expression.

  3. 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.

  4. Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver ischemia/reperfusion injury. (United States)

    Nogueira, Mateus Antunes; Coelho, Ana Maria Mendonça; Sampietre, Sandra Nassa; Patzina, Rosely Antunes; Pinheiro da Silva, Fabiano; D'Albuquerque, Luiz Augusto Carneiro; Machado, Marcel Cerqueira Cesar


    control group did not present alterations when compared to the diazoxide and saline groups. Diazoxide maintains liver mitochondrial function, increases liver tolerance to ischemia/reperfusion injury, and reduces the systemic inflammatory response. These effects require further evaluation for using in a clinical setting.

  5. Bed particle entrainment and motion in turbulent open-channel flows: a high-resolution experimental study (United States)

    Nikora, Vladimir; Cameron, Stuart; Amir, Mohammad; Stewart, Mark; Witz, Matthew


    In spite of significant efforts of geoscientists and engineers, the exact mechanics of sediment entrainment and transport by turbulent flows remains unclear and continues to be the focus of many research groups worldwide. The talk outlines current developments in this direction at the University of Aberdeen, where an extensive experimental programme has recently been completed. The experiments were conducted in the Aberdeen Open Channel Facility (AOCF, 20 m long, 1.18 m wide) over wide ranges of flow submergence (1.9-8.0), bulk Reynolds number (4400-83000), and channel aspect ratio (9-39). The flume bed was covered by hexagonally-packed glass beads 16 mm in diameter. For entrainment experiments, selected glass particles were replaced with lighter particles (nylon and delrin). Instantaneous velocity fields before, during, and after entrainment were measured with an advanced multi-mode Particle Image Velocimetry (PIV) system developed by S. Cameron. This system was also used for 3D particle tracking in the entrainment experiments. The main types of experiments included: (1) multi-mode turbulence measurements with fixed-bed conditions to assess the background flow structure (10 min to 120 min duration of velocity records); (2) simultaneous measurements of fluctuating differential pressure acting on 23 fixed particles with in-built pressure sensors, synchronously with PIV; (3) measurements of waiting times for particle entrainment, employing a specially designed system (SMC-1) for automatic placement of the particles on the bed and subsequent measurement of the time before entrainment; (4) long-term direct measurements of the instantaneous drag force acting on a single particle (attached to the bed) at different protrusions, synchronously with PIV; and (5) synchronous measurements of the flow field around a particle before, at, and during entrainment, supplemented with 3D particle tracking. The key results include: (1) the refined turbulence structure of a rough

  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


    We theoretically analyze the channel capacity of a 5th-order Gaussian pulse-based ultra-wideband (UWB) system and experimentally demonstrate 2 Gbit/s UWB-over-fiber transmission systems incorporating wireless transmission. Both electrical and photonic UWB pulse generation methods are employed...

  7. 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


    antibodies plus their respective antigenic peptide or in the presence of anti-β-actin antibodies or random immunoglobulins not related to TRPC channels showed no inhibitory effects of norepinephrine-induced vasomotion and calcium influx. Administration of candesartan or telmisartan, but not amlodipine to SHR...

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

    DEFF Research Database (Denmark)

    Willumsen, N. J.


    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...

  9. Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase


    Liu, Chung-Hung; Chang, Hsueh-Kai; Lee, Sue-Ping; Shieh, Ru-Chi


    Inward rectifier K+ channels are important for maintaining normal electrical function in many cell types. The proper function of these channels requires the presence of membrane phosphoinositide 4,5-bisphosphate (PIP2). Stimulation of the Ca2+-sensing receptor CaR, a pleiotropic G protein-coupled receptor, activates both Gq/11, which decreases PIP2, and phosphatidylinositol 4-kinase (PI-4-K), which, conversely, increases PIP2. How membrane PIP2 levels are regulated by CaR activation and wheth...

  10. The increased activity of TRPV4 channel in the astrocytes of the adult rat hippocampus after cerebral hypoxia/ischemia.

    Directory of Open Access Journals (Sweden)

    Olena Butenko

    Full Text Available The polymodal transient receptor potential vanilloid 4 (TRPV4 channel, a member of the TRP channel family, is a calcium-permeable cationic channel that is gated by various stimuli such as cell swelling, low pH and high temperature. Therefore, TRPV4-mediated calcium entry may be involved in neuronal and glia pathophysiology associated with various disorders of the central nervous system, such as ischemia. The TRPV4 channel has been recently found in adult rat cortical and hippocampal astrocytes; however, its role in astrocyte pathophysiology is still not defined. In the present study, we examined the impact of cerebral hypoxia/ischemia (H/I on the functional expression of astrocytic TRPV4 channels in the adult rat hippocampal CA1 region employing immunohistochemical analyses, the patch-clamp technique and microfluorimetric intracellular calcium imaging on astrocytes in slices as well as on those isolated from sham-operated or ischemic hippocampi. Hypoxia/ischemia was induced by a bilateral 15-minute occlusion of the common carotids combined with hypoxic conditions. Our immunohistochemical analyses revealed that 7 days after H/I, the expression of TRPV4 is markedly enhanced in hippocampal astrocytes of the CA1 region and that the increasing TRPV4 expression coincides with the development of astrogliosis. Additionally, adult hippocampal astrocytes in slices or cultured hippocampal astrocytes respond to the TRPV4 activator 4-alpha-phorbol-12,-13-didecanoate (4αPDD by an increase in intracellular calcium and the activation of a cationic current, both of which are abolished by the removal of extracellular calcium or exposure to TRP antagonists, such as Ruthenium Red or RN1734. Following hypoxic/ischemic injury, the responses of astrocytes to 4αPDD are significantly augmented. Collectively, we show that TRPV4 channels are involved in ischemia-induced calcium entry in reactive astrocytes and thus, might participate in the pathogenic mechanisms of

  11. The Anatomy of the Blue Dragon: Changes in Lava Flow Morphology and Physical Properties Observed in an Open Channel Lava Flow as a Planetary Analogue (United States)

    Sehlke, A.; Kobs-Nawotniak, S. E.; Hughes, S. S.; Sears, D. W. G.; Downs, M.; Whittington, A. G.; Lim, D. S. S.; Heldmann, J. L.


    microcrystals, strongly increasing the viscosity of the lava several orders of magnitude. The results of this study allows us to correlate T, X, η, φc, φb, and ρ to the lava flow morphology expressed as surface roughness, which can then be used as a tool to infer these physical properties of the rocks for open channel lava flows on other airless bodies, such as the Moon and Mercury, based on DTMs.

  12. The lack of a role for potassium channel opening in the action of relaxin in the rat isolated uterus; a comparison with levcromakalim and salbutamol. (United States)

    Hughes, S J; Hollingsworth, M


    1. The effects of relaxin in vitro in the isolated uterus from the non-pregnant rat were compared with those of levcromakalim and salbutamol in tissue bath, 42K+ -efflux and electrophysiological studies, to determine whether relaxin exhibits the characteristics of an opener of KATP-channels. 2. In uterus exposed to oxytocin (0.2 nM), tetraethylammonium (TEA, 10 mM) and glibenclamide (10 microM) produced large rightward shifts of the log10 concentration-effect curve to levcromakalim (125 fold and 118 fold, respectively). TEA (10 mM) caused only small rightward shifts of the log10 concentration-effect curves to salbutamol and relaxin (5.2 fold and 7.5 fold respectively). Glibenclamide did not antagonize salbutamol or relaxin. 3. Levromakalim (0.2 and 2 microM) suppressed the spasm evoked by low ( 40 mM) concentrations of KCl. Salbutamol (1.5 nM) inhibited the spasm evoked by low concentrations of KCl ( Salbutamol (15 nM) and relaxin (3 and 30 nM) inhibited the spasm evoked by low and high concentrations of KCl (10-80 mM). 4. Relaxin (0.12 microM) did not produce an increase in 42K+-efflux from longitudinal segments of rat myometrium. Exposure of tissues to relaxin (0.12 microM), in the presence of diltiazem (1 microM) plus KCl (20 mM), resulted in a small increase in 42K+-efflux of short duration. 5. Electrophysiological recording showed that the phasic spasms of the uterus exposed to oxytocin (0.2 nM) were accompanied by bursts of spiking activity superimposed upon a plateau potential. Inhibition of the mechanical activity of the uterus by levcromakalim (2 and 10 microM), salbutamol (30 nM) or relaxin (0.18 microM) was accompanied by a reduction in the duration of the plateau potential and the number of spikes without membrane hyperpolarization. 6. Unlike levcromakalim, relaxin did not selectively inhibit the spasm evoked by low concentrations of KCl and was not markedly antagonized by TEA or glibenclamide. Under conditions where a cromakalim-induced increase of the

  13. Numerical Modeling of CO2 and Brine Leakage through Open Fracture in a Fault Zone: Open Channel Flow or Darcy Flow

    Directory of Open Access Journals (Sweden)

    Ning Liu


    Full Text Available Understanding fluids migration and leakage risk along the fault zone is necessary to guarantee the safety of CO2 geological storage. The validity of Darcy’s law gets challenged in dealing with the flow in open fractures since the occurring of turbulence flow. In this study, we develop a 2D model with usage of T2Well, an integrated wellbore-reservoir simulator, to investigate the leakage problem along open fractures which are embedded in a fault zone from the deep injection reservoir to shallow aquifers. The results record a positive feedback of gas expansion and pressure response in fracture, which causes a quick downward propagation of highly gas saturated zone from the top of fracture and an easy gas breakthrough in the shallower aquifers. The decreasing of aperture size of fracture significantly enhances the leakage rates in fracture, but with less influences as aperture increases. In comparison, the Equivalent Porous Media models show a good approximation with the momentum model of large apertures but poor for the small one. Nevertheless, the differences are small in terms of final CO2 distribution among various aquifers, suggesting that Darcy’s law may be still “effective” in solving flow problem along fractures in a constant injection system at a large time scale.

  14. Ensemble modeling of stochastic unsteady open-channel flow in terms of its time-space evolutionary probability distribution - Part 2: numerical application (United States)

    Dib, Alain; Kavvas, M. Levent


    The characteristic form of the Saint-Venant equations is solved in a stochastic setting by using a newly proposed Fokker-Planck Equation (FPE) methodology. This methodology computes the ensemble behavior and variability of the unsteady flow in open channels by directly solving for the flow variables' time-space evolutionary probability distribution. The new methodology is tested on a stochastic unsteady open-channel flow problem, with an uncertainty arising from the channel's roughness coefficient. The computed statistical descriptions of the flow variables are compared to the results obtained through Monte Carlo (MC) simulations in order to evaluate the performance of the FPE methodology. The comparisons show that the proposed methodology can adequately predict the results of the considered stochastic flow problem, including the ensemble averages, variances, and probability density functions in time and space. Unlike the large number of simulations performed by the MC approach, only one simulation is required by the FPE methodology. Moreover, the total computational time of the FPE methodology is smaller than that of the MC approach, which could prove to be a particularly crucial advantage in systems with a large number of uncertain parameters. As such, the results obtained in this study indicate that the proposed FPE methodology is a powerful and time-efficient approach for predicting the ensemble average and variance behavior, in both space and time, for an open-channel flow process under an uncertain roughness coefficient.

  15. 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


    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

  16. A novel role of the antitumor agent tricyclodecan-9-yl-xanthogenate as an open channel blocker of KCNQ1/KCNE1. (United States)

    Wu, Meikui; Takemoto, Makoto; Luo, Huan; Xu, Jian-Jun; Lu, Mei-Hong; Kameyama, Masaki; Takumi, Toru; Song, Wen-Jie


    Tricyclodecan-9-yl-xanthogenate (D609) is widely known for its antitumor and antiviral properties via the inhibition of phosphatidylcholine-specific phospholipase C and sphingomyelin synthase. Previously, we found that chronic application of D609 suppressed the K + channel, KCNQ1/KCNE1, more drastically than expected from its actions on the enzymes, suggesting a direct action of D609 on the channel. Here, we aimed to test this possibility by studying the affinity, specificity, and mechanisms of D609 on KCNQ1/KCNE1. The effect of D609 on KCNQ1/KCNE1 was studied using an in vitro expression system and in native cells, using electrophysiological techniques. We found that D609 rapidly and reversibly inhibited KCNQ1/KCNE1 channels expressed in human embryonic kidney 293 T (HEK293T) cells, in a concentration-dependent manner with a high affinity. D609 neither suppressed endogenous K + currents in HEK293T cells, nor inhibited the sustained and transient K + currents of mouse neostriatal neurons, but blocked a KCNQ1/KCNE1-like current in neostriatal neurons. D609 potently blocked I Ks , the cardiac KCNQ1/KCNE1 channel, in guinea pig cardiac muscle cells. The action of D609 on KCNQ1/KCNE1 depended on the usage of the channel, suggesting that D609 binds to the channel in the open state. We identified D609 as a potent and specific open channel blocker of KCNQ1/KCNE1. Because KCNQ1/KCNE1 is highly expressed in the heart, the inner ear and the pancreas, D609, when used as an antitumor or antiviral drug, may affect the function of a number of organs in vivo even when used at low concentrations. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. 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


    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

  18. 3D Lagrangian Model of Particle Saltation in an Open Channel Flow with Emphasis on Particle-Particle Collisions (United States)

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


    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

  19. Effect of buried plates on scour profiles downstream of hydraulic jump in open channels with horizontal and reverse bed slopes

    Directory of Open Access Journals (Sweden)

    Akram Abbaspour


    Full Text Available Local scour downstream of sluice gates in erosive beds is one of the main concerns of hydraulic engineers because it can cause considerable damage to structures. Many researchers have conducted various studies to predict the maximum depth and length of scour holes and to develop new methods to control this phenomenon. In the methods that have recently been examined, embedded buried plates are used to control the scour in the erosive beds. In this study, using a physical model, the effect of buried plates in erosive beds on the depth of scour downstream of a hydraulic jump was studied. Several experiments were performed in which plates were buried at 50° and 90° angles at different distances from the apron in open channels with horizontal and reverse bed slopes. The results of experiments in which the scour profiles were drawn in dimensionless forms show that the angle and position of the plates are important to controlling and reducing scour depth. In fact, by reducing the angle of buried plates, the maximum depth of scour is also reduced. Also, comparison of the results of a single buried plate and double buried plates shows that using two buried plates at the distances of 30 and 45 cm from the non-erodible bed is more effective in reducing the scour depth. The best distances of the buried plates with angles of 90° and 50° from the non-erodible bed are 45 cm and 30 cm, respectively, in the condition with a single buried plate.

  20. Opening communication channels with people living with HIV using mobile phone text messaging: insights from the CAMPS trial. (United States)

    Mbuagbaw, Lawrence; Thabane, Lehana; Ongolo-Zogo, Pierre


    Using two-way mobile phone text messages to improve adherence to antiretroviral medication enhances communication between patients and health workers. We describe the implications of participants' responses to text messages in the Cameroon Mobile Phone SMS (CAMPS) trial. This is a cross-sectional analysis of data from the intervention arm of the CAMPS trial. CAMPS was a randomized controlled trial of motivational text messaging versus usual care to improve adherence to antiretroviral medication among people living with HIV in Yaounde, Cameroon (n = 200) over a 6 month period. Participants in the intervention arm (n = 101) were given a contact phone number, but were not required to respond to their reminder messages. If they did, their responses were noted and reported as counts and percentages. We received 99 phone calls and 55 text messages (154 responses) from 48 participants during the study period. The median number of responses was 1 (first quartile [Q1]: 1; third quartile [Q3]: 3). Half (n = 79, 51.1%) of them were expressions of gratitude. The rest included requests for logistical (n = 21, 13.6%), medical (n = 20, 12.9%) and financial (n = 11, 7.1%) support. Initiating two-way mobile communication opens more channels for people living with HIV to express unmet needs. Researchers, policy makers and clinicians should be ready to respond to the needs expressed by patients who respond to text messages. Pan-African Clinical Trials Registry: PACTR201011000261458;

  1. Increased transient receptor potential vanilloid type 1 (TRPV1) channel expression in hypertrophic heart

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Schulz, Nico


    The aim of this study was to compare the expression of transient receptor potential vanilloid type 1 (TRPV1) channels in hypertrophic hearts from transgenic mice showing overexpression of the catalytic subunit alpha of protein phosphatase 2A alpha (PP2Ac alpha) with wild-type mice and with TRPV1-...... alpha transgenic mice compared to wild-type mice and TRPV1-/- mice (8.6±1.3mg/g; 5.4±0.3mg/g; and 5.4±0.4mg/g; respectively; p...

  2. 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


    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.

  3. Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase. (United States)

    Liu, Chung-Hung; Chang, Hsueh-Kai; Lee, Sue-Ping; Shieh, Ru-Chi


    Inward rectifier K + channels are important for maintaining normal electrical function in many cell types. The proper function of these channels requires the presence of membrane phosphoinositide 4,5-bisphosphate (PIP 2 ). Stimulation of the Ca 2+ -sensing receptor CaR, a pleiotropic G protein-coupled receptor, activates both G q/11 , which decreases PIP 2 , and phosphatidylinositol 4-kinase (PI-4-K), which, conversely, increases PIP 2 . How membrane PIP 2 levels are regulated by CaR activation and whether these changes modulate inward rectifier K + are unknown. In this study, we found that activation of CaR by the allosteric agonist, NPSR568, increased inward rectifier K + current (I K1 ) in guinea pig ventricular myocytes and currents mediated by Kir2.1 channels exogenously expressed in HEK293T cells with a similar sensitivity. Moreover, using the fluorescent PIP 2 reporter tubby-R332H-cYFP to monitor PIP 2 levels, we found that CaR activation in HEK293T cells increased membrane PIP 2 concentrations. Pharmacological studies showed that both phospholipase C (PLC) and PI-4-K are activated by CaR stimulation with the latter played a dominant role in regulating membrane PIP 2 and, thus, Kir currents. These results provide the first direct evidence that CaR activation upregulates currents through inward rectifier K + channels by accelerating PIP 2 synthesis. The regulation of I K1 plays a critical role in the stability of the electrical properties of many excitable cells, including cardiac myocytes and neurons. Further, synthetic allosteric modulators that increase CaR activity have been used to treat hyperparathyroidism, and negative CaR modulators are of potential importance in the treatment of osteoporosis. Thus, our results provide further insight into the roles played by CaR in the cardiovascular system and are potentially valuable for heart disease treatment and drug safety.

  4. 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. (United States)

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


    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.

  5. Two-Dimensional Simulation of Flows in an Open Channel with Groin-Like Structures by iRIC Nays2DH

    Directory of Open Access Journals (Sweden)

    Md. Shahjahan Ali


    Full Text Available This study presents the results obtained from the numerical simulation on turbulent flows around a single groin for different orientations. Here iRIC Nays2DH, which is based on 2D model, is used to simulate the flows in a straight open channel with groin of 45°, 90°, and 135° angled with the approaching flow. A depth-averaged k-ε model is used as turbulence closure model with finite differential advections as upwind scheme. The numerical results of velocity and bed shear stress profiles are compared with the available experimental data. Good agreements are found between experimental and calculated results. From the simulation, it is observed that the peak of velocity and bed shear stress is maximum at the position of head of groin when lateral distance y/l=1, where l is the groin length. The position of maximum velocity and bed shear stress is found to be shifted towards downstream with increasing y/l. The maximum velocity and bed shear stress for 135° groin are found lower than the other two cases for all the sections of y/l.

  6. Mitochondrial dynamics and respiration within cells with increased open pore cytoskeletal meshes

    Directory of Open Access Journals (Sweden)

    David H. Jang


    Full Text Available The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and fusion in healthy and diseased cells, and differences in mitochondria locomotion in more open networks either in response to cytoskeletal destabilizers or by cell line. We found that mitochondria within fibrosarcoma cells and within fibroblast cells treated with an actin-destabilizing toxin resulted in increased net travel, increased average velocity, and increased diffusion of mitochondria when compared to control fibroblasts. Although the mitochondria within the fibrosarcoma travel further than mitochondria within their healthy counterparts, fibroblasts, the dependence on mitochondria for respiration is much lower with higher rates ofhydrogen peroxide production and was confirmed using the OROBOROS O2K. We also found that rates of fission and fusion of the mitochondria equilibrate despite significant alteration of the cytoskeleton. Rates ranged from 15% to 25%, where the highest rates were observed within the fibrosarcoma cell line. This result is interesting because the fibrosarcoma cell line does not have increased respiration metrics including when compared to fibroblast. Mitochondria travel further, faster, and have an increase in percent mitochondria splitting or joining while not dependent on the mitochondria for a

  7. Hydraulic characteristics of flood waves passing compound channels


    冨永, 晃宏; 長尾, 正志; 三尾, 憲史; 劉, 建


    Hydraulic characteristics of unsteady flows were investigated experimentally when flood waves were passing through compound open channels. Some noticeable features of unsteady flow structure in compound channels were revealed which were significantly different from those in single rectangular channels. The unsteadiness of velocity appears very large in main channels and the peak of velocity appears very earlier than in rectangular channels. Lateral shear stress increases in a rising stage at ...

  8. Persistent human cardiac Na+ currents in stably transfected mammalian cells: Robust expression and distinct open-channel selectivity among Class 1 antiarrhythmics. (United States)

    Wang, Ging Kuo; Russell, Gabriella; Wang, Sho-Ya


    Miniature persistent late Na(+) currents in cardiomyocytes have been linked to arrhythmias and sudden death. The goals of this study are to establish a stable cell line expressing robust persistent cardiac Na(+) currents and to test Class 1 antiarrhythmic drugs for selective action against resting and open states. After transient transfection of an inactivation-deficient human cardiac Na(+) channel clone (hNav1.5-CW with L409C/A410W double mutations), transfected mammalian HEK293 cells were treated with 1 mg/ml G-418. Individual G-418-resistant colonies were isolated using glass cylinders. One colony with high expression of persistent Na(+) currents was subjected to a second colony selection. Cells from this colony remained stable in expressing robust peak Na(+) currents of 996 ± 173 pA/pF at +50 mV (n = 20). Persistent late Na(+) currents in these cells were clearly visible during a 4-second depolarizing pulse albeit decayed slowly. This slow decay is likely due to slow inactivation of Na(+) channels and could be largely eliminated by 5 μM batrachotoxin. Peak cardiac hNav1.5-CW Na(+) currents were blocked by tetrodotoxin with an IC(50) value of 2.27 ± 0.08 μM (n = 6). At clinic relevant concentrations, Class 1 antiarrhythmics are much more selective in blocking persistent late Na(+) currents than their peak counterparts, with a selectivity ratio ranging from 80.6 (flecainide) to 3 (disopyramide). We conclude that (1) Class 1 antiarrhythmics differ widely in their resting- vs. open-channel selectivity, and (2) stably transfected HEK293 cells expressing large persistent hNav1.5-CW Na(+) currents are suitable for studying as well as screening potent open-channel blockers.

  9. Opening

    International Nuclear Information System (INIS)

    Grimstad, Erlend


    The views of the Norwegian Government on oil and gas issues are presented. Today Norwegian deliveries of natural gas account for a substantial and growing part of the supplies of gas to Europe. The Government has always tried to implement rules and regulations, which encourage the efficient exploitation of the petroleum resources. The two pillars of the gas marketing system are negotiation of non-field specific gas supply contracts and government allocation of these contracts to individual fields. The Gas Supply Committee is established to make recommendations on allocation issues. Many gas fields on the Continental Shelf have large portions of oil and condensate attached to the gas production. These fields can be produced more efficiently. In Norway, natural gas is gradually becoming a more important part of the Norwegian petroleum activities, and the potential gas resources are expected to be of the same order as the expected potential oil resources. In the present situation, injection gas is needed to optimize the oil production and this imposes constraints on new exports of natural gas. The overall goals of the petroleum industry were reported to the parliament in 1998. In 1999 a supplementary report was presented that covers (1) The oil market and Norwegian policy, (2) The competitiveness of the Norwegian Shelf, (3) The Investment Panel's report which analyzes cost overruns for recent petroleum development projects, and (4) A specific report on cost increases in the Aasgard project. These items are discussed in some detail

  10. Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

    International Nuclear Information System (INIS)

    Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.; Nicholson, Graham M.


    The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na v ) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na v channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons, P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na v currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na v channel gating, observed clinically in response to ciguatera poisoning

  11. Single-channel kinetics of BK (Slo1 channels

    Directory of Open Access Journals (Sweden)

    Yanyan eGeng


    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.

  12. Take time to make time : What to consider when managing multi-channel sales systems with the objective to increase sales efficiency




    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...

  13. Can an old dog learn (and want to experience) new tricks? Cognitive training increases openness to experience in older adults. (United States)

    Jackson, Joshua J; Hill, Patrick L; Payne, Brennan R; Roberts, Brent W; Stine-Morrow, Elizabeth A L


    The present study investigated whether an intervention aimed to increase cognitive ability in older adults also changes the personality trait of openness to experience. Older adults completed a 16-week program in inductive reasoning training supplemented by weekly crossword and Sudoku puzzles. Changes in openness to experience were modeled across four assessments over 30 weeks using latent growth curve models. Results indicate that participants in the intervention condition increased in the trait of openness compared with a waitlist control group. The study is one of the first to demonstrate that personality traits can change through nonpsychopharmocological interventions. PsycINFO Database Record (c) 2012 APA, all rights reserved

  14. [Does open access publishing increase the impact of scientific articles? An empirical study in the field of intensive care medicine]. (United States)

    Riera, M; Aibar, E


    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.

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

    DEFF Research Database (Denmark)

    Xia, Shengqiang; Liu, Ying; Li, Xinming


    of NOX4, another target gene of the calcineurin-NFAT pathway, were affected in a similar way. Immunoblotting showed that the administration of 100 nmol/L insulin increased TRPC6-proteins 2-fold within 48 hours. Insulin increased the activity of NFATc1 in nuclear extracts (p

  16. Ensemble modeling of stochastic unsteady open-channel flow in terms of its time-space evolutionary probability distribution - Part 1: theoretical development (United States)

    Dib, Alain; Kavvas, M. Levent


    The Saint-Venant equations are commonly used as the governing equations to solve for modeling the spatially varied unsteady flow in open channels. The presence of uncertainties in the channel or flow parameters renders these equations stochastic, thus requiring their solution in a stochastic framework in order to quantify the ensemble behavior and the variability of the process. While the Monte Carlo approach can be used for such a solution, its computational expense and its large number of simulations act to its disadvantage. This study proposes, explains, and derives a new methodology for solving the stochastic Saint-Venant equations in only one shot, without the need for a large number of simulations. The proposed methodology is derived by developing the nonlocal Lagrangian-Eulerian Fokker-Planck equation of the characteristic form of the stochastic Saint-Venant equations for an open-channel flow process, with an uncertain roughness coefficient. A numerical method for its solution is subsequently devised. The application and validation of this methodology are provided in a companion paper, in which the statistical results computed by the proposed methodology are compared against the results obtained by the Monte Carlo approach.

  17. 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


    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...... 35%. Consistent with higher VRAC activity in H-ras than in wild-type fibroblasts, more VRAC blocker is needed to achieve a comparable degree of inhibition of migration. We suggest that H-ras modulates the volume set point of VRAC and thus facilitates transient changes of cell volume required...

  18. Effects of increased occlusal vertical dimension on the jaw-opening reflex in adult rats. (United States)

    Makiguchi, Mio; Funaki, Yukiha; Kato, Chiho; Okihara, Hidemasa; Ishida, Takayoshi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi


    Malocclusion with deep overbite and facial esthetics improve when facial height is intentionally increased during orthodontic extrusion of the posterior teeth. Thus, a better understanding of post-treatment stability of increased occlusal vertical dimension (iOVD) in adult patients is important. We focused on the jaw-opening reflex (JOR), which plays an important role in the control of jaw movements during mastication, and investigated the effects of iOVD on the JOR in rats with an electrophysiological technique. One hundred and twenty 13-week-old male Wistar rats were randomly divided into control and experimental groups. Rats in the experimental group received a 2-mm buildup of composite resin on the maxillary molars at 13 weeks of age. The JOR was induced by low-intensity electrical stimulation of the left inferior alveolar nerve. The electromyographic responses were recorded from the digastric muscle at 13, 14, 15, 17, 19, and 23 weeks of age. JOR properties including latency, duration, and peak-to-peak amplitude were measured and compared between the groups. The latency of the JOR was significantly longer and the peak-to-peak amplitude was significantly smaller in the experimental group than in the control group from 14 to 19 weeks of age, while the reflex duration was not significantly different. Intra-group comparisons of the latency and peak-to-peak amplitudes among rats 14-19 weeks of age were significantly different between the experimental group and the control group. iOVD affected the latency and amplitude of the JOR but not the duration. The JOR adapted after 10 weeks of iOVD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Open design eight-channel transmit/receive coil for high-resolution and real-time ankle imaging at 7 T. (United States)

    Orzada, Stephan; Bitz, Andreas K; Schäfer, Lena C; Ladd, Susanne C; Ladd, Mark E; Maderwald, Stefan


    At 1.5 T, real-time MRI of joint movement has been shown to be feasible. However, 7 T, provides higher SNR and thus an improved potential for parallel imaging acceleration. The purpose of this work was to build an open, U-shaped eight-channel transmit/receive microstrip coil for 7 T MRI to enable high-resolution and real-time imaging of the moving ankle joint. A U-shaped eight-channel transmit/receive array for the human ankle was built. S-parameters and g-factor were measured. SAR calculations of different ankle postures were performed to ensure patient safety. Inhomogeneities in the transmit field consequent to the open design were compensated for by the use of static RF shimming. High-resolution and real-time imaging was performed in human volunteers. The presented array showed good performance with regard to patient comfort and image quality. High acceleration factors of up to 4 are feasible without visible acceleration artifacts. Reasonable image homogeneity was achieved with RF shimming. Open, noncylindrical designs for transmit/receive coils are practical at 7 T and real-time imaging of the moving joint is feasible with the presented coil design.

  20. Moessbauer effect: on the application of digital synthesis in order tosynchronize the frequency of the function generator of the transducer with the frequency of the channel opening commands, in 'multiscale' operation

    International Nuclear Information System (INIS)

    Carrilho, R.J.; Marins, J.E.R.


    A new instrument for the channel opening command, synchronized to the movement, is designed, developed and produced, together with a new and complete amplifier for the transducer activation. (L.C.) [pt

  1. The Effect of Discharge Ratio and Confluence Angle on Local Scouring at 60 Degree Erodible Open Channel with SSIIM1 Model

    Directory of Open Access Journals (Sweden)

    R. Ghobadian


    Full Text Available Introduction: Flow and sediment transport has an important role in entrance deformation of open channel junctions. As water moved through a drainage network, it forced to converge at confluence. Due to increasing of water discharge and collision of converging flows, a complex three-dimensional and most highly turbulent location were occurred in the vicinity of the junction. Therefore a deep scour hole and point bar has developed in this area that caused the change in rivers morphology. Despite the large amount of research carried out on flow patterns in river confluences, only a few researches have focused on sediment transport. Materials and methods: In this research three dimensional model (SSIIM1 was used to study of flow pattern and sediment and erosion pattern at 60 degree Junction .the Navier-Stockes equation of turbulent flow in a general three-dimensional geometry are solved to obtain the water velocity: , (1 Where U is average velocity, ρ is density of water, is pressure, the Kronecker delta, which is 1 if i is equal to j and 0 otherwise and general space dimension. The last term is Reynolds stress, often modeled with the following equation: (2 Where and k are eddy viscosity and turbulent kinetic energy respectively. Van Rijn's relations were used to calculate sediment suspended and bed load transport. Dirichlet and zero gradients boundary conditions were used at inflow and outflow boundary respectively. fixed-lid approach was used to computed free surface by using zero gradient for all variables. The wall law for rough boundaries was also used as a boundary condition for bed and wall. In equilibrium situation, The sediment concentration for the cell closet to the bed was specified as the bed boundary condition. Specified value was used for sediment concentration of other boundary conditions at upstream boundary and zero gradients for the water surface, outlet, and the sides. the only simulation of local scouring and sedimentation at

  2. RIM1/2-Mediated Facilitation of Cav1.4 Channel Opening Is Required for Ca2+-Stimulated Release in Mouse Rod Photoreceptors. (United States)

    Grabner, Chad P; Gandini, Maria A; Rehak, Renata; Le, Yun; Zamponi, Gerald W; Schmitz, Frank


    in a normal fashion. Our findings strongly argue that RIM1/2 facilitate Ca(2+) entry and in turn Ca(2+) evoked release by modulating Cav1.4 channel openings; however, RIM1/2 are not needed for the retention of Cav1.4 at the synapse. In summary, a key function of RIM1/2 at rod ribbons is to enhance Cav1.4 channel activity, possibly through direct or indirect modulation of the channel. Copyright © 2015 the authors 0270-6474/15/3513133-15$15.00/0.

  3. Ligand induced change of β2 adrenergic receptor from active to inactive conformation and its implication for the closed/open state of the water channel: insight from molecular dynamics simulation, free energy calculation and Markov state model analysis. (United States)

    Bai, Qifeng; Pérez-Sánchez, Horacio; Zhang, Yang; Shao, Yonghua; Shi, Danfeng; Liu, Huanxiang; Yao, Xiaojun


    The reported crystal structures of β2 adrenergic receptor (β2AR) reveal that the open and closed states of the water channel are correlated with the inactive and active conformations of β2AR. However, more details about the process by which the water channel states are affected by the active to inactive conformational change of β2AR remain illusive. In this work, molecular dynamics simulations are performed to study the dynamical inactive and active conformational change of β2AR induced by inverse agonist ICI 118,551. Markov state model analysis and free energy calculation are employed to explore the open and close states of the water channel. The simulation results show that inverse agonist ICI 118,551 can induce water channel opening during the conformational transition of β2AR. Markov state model (MSM) analysis proves that the energy contour can be divided into seven states. States S1, S2 and S5, which represent the active conformation of β2AR, show that the water channel is in the closed state, while states S4 and S6, which correspond to the intermediate state conformation of β2AR, indicate the water channel opens gradually. State S7, which represents the inactive structure of β2AR, corresponds to the full open state of the water channel. The opening mechanism of the water channel is involved in the ligand-induced conformational change of β2AR. These results can provide useful information for understanding the opening mechanism of the water channel and will be useful for the rational design of potent inverse agonists of β2AR.

  4. Alterations in expression of Cat-315 epitope of perineuronal nets during normal ageing, and its modulation by an open-channel NMDA receptor blocker, memantine. (United States)

    Yamada, Jun; Ohgomori, Tomohiro; Jinno, Shozo


    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. © 2017 Wiley Periodicals, Inc.

  5. Increasing the value of geospatial informatics with open approaches for Big Data (United States)

    Percivall, G.; Bermudez, L. E.


    Open approaches to big data provide geoscientists with new capabilities to address problems of unmatched size and complexity. Consensus approaches for Big Geo Data have been addressed in multiple international workshops and testbeds organized by the Open Geospatial Consortium (OGC) in the past year. Participants came from government (NASA, ESA, USGS, NOAA, DOE); research (ORNL, NCSA, IU, JPL, CRIM, RENCI); industry (ESRI, Digital Globe, IBM, rasdaman); standards (JTC 1/NIST); and open source software communities. Results from the workshops and testbeds are documented in Testbed reports and a White Paper published by the OGC. The White Paper identifies the following set of use cases: Collection and Ingest: Remote sensed data processing; Data stream processing Prepare and Structure: SQL and NoSQL databases; Data linking; Feature identification Analytics and Visualization: Spatial-temporal analytics; Machine Learning; Data Exploration Modeling and Prediction: Integrated environmental models; Urban 4D models. Open implementations were developed in the Arctic Spatial Data Pilot using Discrete Global Grid Systems (DGGS) and in Testbeds using WPS and ESGF to publish climate predictions. Further development activities to advance open implementations of Big Geo Data include the following: Open Cloud Computing: Avoid vendor lock-in through API interoperability and Application portability. Open Source Extensions: Implement geospatial data representations in projects from Apache, Location Tech, and OSGeo. Investigate parallelization strategies for N-Dimensional spatial data. Geospatial Data Representations: Schemas to improve processing and analysis using geospatial concepts: Features, Coverages, DGGS. Use geospatial encodings like NetCDF and GeoPackge. Big Linked Geodata: Use linked data methods scaled to big geodata. Analysis Ready Data: Support "Download as last resort" and "Analytics as a service". Promote elements common to "datacubes."

  6. Two-Dimensional Simulation of Flows in an Open Channel with Groin-Like Structures by iRIC Nays2DH


    Md. Shahjahan Ali; Md. Milon Hasan; Masuma Haque


    This study presents the results obtained from the numerical simulation on turbulent flows around a single groin for different orientations. Here iRIC Nays2DH, which is based on 2D model, is used to simulate the flows in a straight open channel with groin of 45°, 90°, and 135° angled with the approaching flow. A depth-averaged k-ε model is used as turbulence closure model with finite differential advections as upwind scheme. The numerical results of velocity and bed shear stress profiles are c...

  7. Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy (United States)

    Ismail, M; Bokaee, S; Davies, J; Harrington, K J; Pandha, H


    Aquaporins (AQPs) are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. In this study, we investigate the role of inhibiting AQPs in sensitising prostate cancer cells to cryotherapy. PC-3 and DU145 prostate cancer cells were cooled to 0, −5 and −10°C. The expression of AQP3 in response to freezing was determined using real-time quantitative polymerase chain reaction (RT–qPCR) and western blot analysis. Aquaporins were inhibited using mercuric chloride (HgCl2) and small interfering RNA (siRNA) duplex, and cell survival was assessed using a colorimetric assay. There was a significant increase in AQP3 expression in response to freezing. Cells treated with AQP3 siRNA were more sensitive to cryoinjury compared with control cells (Pcryotherapy. PMID:19513079

  8. Direct effect of chronic hypoxia in suppressing large conductance Ca(2+)-activated K(+) channel activity in ovine uterine arteries via increasing oxidative stress. (United States)

    Hu, Xiang-Qun; Huang, Xiaohui; Xiao, Daliao; Zhang, Lubo


    Chronic hypoxia has a direct effect in down-regulating the BKCa channel β1 subunit and inhibiting the BKCa channel activity in uterine arteries of pregnant sheep. Oxidative stress plays a causal role in hypoxia-mediated suppression of BKCa channel function. The steroid hormone-induced effect on BKCa channels is a target of hypoxia-mediated oxidative stress. Inhibition of oxidative stress ameliorates the adverse effect of hypoxia both ex vivo and in vivo in pregnant sheep exposed to long-term high-altitude hypoxia. Our findings provide novel evidence of a causative role of oxidative stress in hypoxia-mediated inhibition of the BKCa channel activity in uterine arteries and new insights in understanding and alleviating pregnancy complications associated with gestational hypoxia such as pre-eclampsia and fetal growth restriction. Uterine arteries of pregnant sheep acclimatized to long-term high-altitude hypoxia were associated with a decrease in large-conductance Ca(2+)-activated K(+) (BKCa) channel activity. The present study tested the hypothesis that prolonged hypoxia has a direct effect in suppressing BKCa channel activity by increasing oxidative stress. Uterine arteries were isolated from non-pregnant and near-term (∼142 days) pregnant sheep, and were treated ex vivo with 21.0 or 10.5% O2 for 48 h. The hypoxia treatment significantly increased the production of reactive oxygen species in uterine arteries, which was blocked by N-acetylcysteine. In uterine arteries of pregnant sheep, hypoxia significantly inhibited BKCa channel current density, decreased NS1619-induced relaxations and increased pressure-dependent tone, which were annulled by N-acetylcysteine. In accordance, hypoxia resulted in down-regulation of BKCa channel β1 subunit, which was restored in the presence of N-acetylcysteine. In addition, the N-acetylcysteine treatment significantly increased BKCa channel β1 subunit abundance and BKCa channel current density in uterine arteries from pregnant

  9. A 1D-2D coupled SPH-SWE model applied to open channel flow simulations in complicated geometries (United States)

    Chang, Kao-Hua; Sheu, Tony Wen-Hann; Chang, Tsang-Jung


    In this study, a one- and two-dimensional (1D-2D) coupled model is developed to solve the shallow water equations (SWEs). The solutions are obtained using a Lagrangian meshless method called smoothed particle hydrodynamics (SPH) to simulate shallow water flows in converging, diverging and curved channels. A buffer zone is introduced to exchange information between the 1D and 2D SPH-SWE models. Interpolated water discharge values and water surface levels at the internal boundaries are prescribed as the inflow/outflow boundary conditions in the two SPH-SWE models. In addition, instead of using the SPH summation operator, we directly solve the continuity equation by introducing a diffusive term to suppress oscillations in the predicted water depth. The performance of the two approaches in calculating the water depth is comprehensively compared through a case study of a straight channel. Additionally, three benchmark cases involving converging, diverging and curved channels are adopted to demonstrate the ability of the proposed 1D and 2D coupled SPH-SWE model through comparisons with measured data and predicted mesh-based numerical results. The proposed model provides satisfactory accuracy and guaranteed convergence.

  10. Effects of Potassium-Channel Opener on Thallium-201 Kinetics: In-vitro Study in Rat Myocyte Preparations and In-vivo Mice Biodistribution Study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Tae; Kim, Eun Ji; Ahn, Byeong Cheol; Son, Kang Kyun; Lee, Kyu Bo [Kyungpook National University School of Medicine, Taegu (Korea, Republic of); Ha, Jeoung Hee [Youngnam University Medical School, Taegu (Korea, Republic of); Kim, Chun Ki [Mt. Sinai School of Medicine, New York (United States)


    Potassium channel opener (K-opener) opens ATP-sensitive K{sup +}-channel located at membrane and induces potassium efflux from cytosol, resulting in intracellular hyperpolarization. Newly synthesized K-opener is currently examined for pharmacologic potency by means of rubidium release test from smooth muscle strip preincubated with Rb-86. Since in-vive behavior of thallium is similar to that of rubidium, we hypothesized that K-opener can alter T1-201 kinetics in vivo. This study was prepared to investigate the effects of pinacidil (one of potent K-openers) on the T1-201 uptake and clearance in cultured myocyte, and in-vivo biodistribution in mice. Spontaneous contracting myocytes were prepared to imitate in-vivo condition from 20 hearts of 3-5 days old Sprague-Dawley rat and cultured for 3-5 days before use (5 X 105 cells/ml). Pinacidil was dissolved in 10% DMSO solution at a final concentration of 100nM or 10uM and was co-incubated with T1-201 in HBSS buffer for 20-min to evaluate its effect on cellular T1-uptake, or challenged to cell preparation pre-incubated with T1-201 for washout study. Two, 40 or 100 mg of pinacidil was injected intravenously into ICR mice at 10 min after 5 muCi T1-201 injection, and organ uptake and whole body retention rate were measured at different time points. Co-incubation of pinacidil with T1-201 resulted in a decrease in T1-201 uptake into cultured myocyte by 1.6 to 2.5 times, depending on pinacidil concentration and activity of T1-201 used. Pinacidil enhanced T1-201 washout by 1.6-3.1 times from myocyte preparations pre-incubated with T1-201. Pinacidil treatment appears to be resulted in mild decreases in blood and liver activity in normal mice, in contrast, renal and cardiac uptake were mildly decreased in a dose dependent manner. Whole body retention ratios of T1-201 were lower at 24 hour after injection with 100 mg of pinacidil than control. These results suggest that treatment with K-opener may affect the interpretation of T1

  11. Single Na+ channels activated by veratridine and batrachotoxin (United States)


    Voltage-sensitive Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers in the presence of either of the alkaloid toxins veratridine (VT) or batrachotoxin (BTX). Both of these toxins are known to cause persistent activation of Na+ channels. With BTX as the channel activator, single channels remain open nearly all the time. Channels activated with VT open and close on a time scale of 1-10 s. Increasing the VT concentration enhances the probability of channel opening, primarily by increasing the rate constant of opening. The kinetics and voltage dependence of channel block by 21-sulfo-11-alpha-hydroxysaxitoxin are identical for VT and BTX, as is the ionic selectivity sequence determined by bi-ionic reversal potential (Na+ approximately Li+ greater than K+ greater than Rb+ greater than Cs+). However, there are striking quantitative differences in open channel conduction for channels in the presence of the two activators. Under symmetrical solution conditions, the single channel conductance for Na+ is about twice as high with BTX as with VT. Furthermore, the symmetrical solution single channel conductances show a different selectivity for BTX (Na+ greater than Li+ greater than K+) than for VT (Na+ greater than K+ greater than Li+). Open channel current-voltage curves in symmetrical Na+ and Li+ are roughly linear, while those in symmetrical K+ are inwardly rectifying. Na+ currents are blocked asymmetrically by K+ with both BTX and VT, but the voltage dependence of K+ block is stronger with BTX than with VT. The results show that the alkaloid neurotoxins not only alter the gating process of the Na+ channel, but also affect the structure of the open channel. We further conclude that the rate-determining step for conduction by Na+ does not occur at the channel's "selectivity filter," where poorly permeating ions like K+ are excluded. PMID:2435846

  12. Sodium channel activators: model of binding inside the pore and a possible mechanism of action. (United States)

    Tikhonov, Denis B; Zhorov, Boris S


    Sodium channel activators, batrachotoxin and veratridine, cause sodium channels to activate easier and stay open longer than normal channels. Traditionally, this was explained by an allosteric mechanism. However, increasing evidence suggests that activators can bind inside the pore. Here, we model the open sodium channel with activators and propose a novel mechanism of their action. The activator-bound channel retains a hydrophilic pathway for ions between the ligand and conserved asparagine in segment S6 of repeat II. One end of the activator approaches the selectivity filter, decreasing the channel conductance and selectivity. The opposite end reaches the gate stabilizing it in the open state.

  13. Implementation of vibration correction schemes to the evaluation of a turbulent flow in an open channel by tomographic particle image velocimetry

    International Nuclear Information System (INIS)

    Earl, T A; Thomas, L; David, L; Cochard, S; Tremblais, B


    The aim of this paper is to investigate and quantify the effect of vibration on experimental tomographic particle image velocimetry (TPIV) measurements. The experiment consisted of turbulence measurements in an open channel flow. Specifically, five trash rack assemblies, composed of regular grids, divided a 5 m long flume into four sequential, identical pools. This set-up established a globally stationary flow, with each pool generating a controlled amount of turbulence that is reset at every trash rack. TPIV measurements were taken in the central pool. To eliminate the vibration from the measurements, three vibration correction regimes are proposed and compared to a global volume self-calibration (Wieneke 2008 Exp. Fluids 45 549–56), a now standard calibration procedure in TPIV. As the amplitude of the vibrations was small, it was possible to extract acceptable reconstruction re-projection qualities (Q I  > 75%) and velocity fields from the standard treatment. This paper investigates the effect of vibration on the cross-correlation signal and turbulence statistics, and shows the improvement to velocity field data by several correction schemes. A synthetic model was tested that simulated camera vibration to demonstrate its effects on key velocity parameters and to observe the effects on reconstruction and cross-correlation metrics. This work has implications for experimental measurements where vibrations are unavoidable and seemingly undetectable such as those in large open channel flows. (paper)

  14. 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. (United States)

    Shao, Dongguo; Yang, Haidong; Xiao, Yi; Liu, Biyu


    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.

  15. Extracellular calcium-sensing-receptor (CaR)-mediated opening of an outward K(+) channel in murine MC3T3-E1 osteoblastic cells: evidence for expression of a functional CaR (United States)

    Ye, C. P.; Yamaguchi, T.; Chattopadhyay, N.; Sanders, J. L.; Vassilev, P. M.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)


    The existence in osteoblasts of the G-protein-coupled extracellular calcium (Ca(o)(2+))-sensing receptor (CaR) that was originally cloned from parathyroid and kidney remains controversial. In our recent studies, we utilized multiple detection methods to demonstrate the expression of CaR transcripts and protein in several osteoblastic cell lines, including murine MC3T3-E1 cells. Although we and others have shown that high Ca(o)(2+) and other polycationic CaR agonists modulate the function of MC3T3-E1 cells, none of these actions has been unequivocally shown to be mediated by the CaR. Previous investigations using neurons and lens epithelial cells have shown that activation of the CaR stimulates Ca(2+)-activated K(+) channels. Because osteoblastic cells express a similar type of channel, we have examined the effects of specific "calcimimetic" CaR activators on the activity of a Ca(2+)-activated K(+) channel in MC3T3-E1 cells as a way of showing that the CaR is not only expressed in those cells but is functionally active. Patch-clamp analysis in the cell-attached mode showed that raising Ca(o)(2+) from 0.75 to 2.75 mmol/L elicited about a fourfold increase in the open state probability (P(o)) of an outward K(+) channel with a conductance of approximately 92 pS. The selective calcimimetic CaR activator, NPS R-467 (0.5 micromol/L), evoked a similar activation of the channel, while its less active stereoisomer, NPSS-467 (0.5 micromol/L), did not. Thus, the CaR is not only expressed in MC3T3-E1 cells, but is also functionally coupled to the activity of a Ca(2+)-activated K(+) channel. This receptor, therefore, could transduce local or systemic changes in Ca(o)(2+) into changes in the activity of this ion channel and related physiological processes in these and perhaps other osteoblastic cells.

  16. Experimental study of the possibility of reducing the resistance and unevenness of output field of velocities in flat diffuser channels with large opening angles (United States)

    Dmitriev, S. S.; Vasil'ev, K. E.; Mokhamed, S. M. S. O.; Gusev, A. A.; Barbashin, A. V.


    In modern combined cycle gas turbines (CCGT), when designing the reducers from the output diffuser of a gas turbine to a boiler-utilizer, wide-angle diffusers are used, in which practically from the input a flow separation and transition to jet stream regime occurs. In such channels, the energy loss in the field of velocities sharply rise and the field of velocities in the output from them is characterized by considerable unevenness that worsens the heat transfer process in the first by motion tube bundles of the boiler-utilizer. The results of experimental research of the method for reducing the energy loss and alignment of the field of velocities at the output from a flat asymmetrical diffuser channel with one deflecting wall with the opening angle of 40° by means of placing inside the channel the flat plate parallel to the deflecting wall are presented in the paper. It is revealed that, at this placement of the plate in the channel, it has a chance to reduce the energy loss by 20%, considerably align the output field of velocities, and decrease the dynamic loads on the walls in the output cross-section. The studied method of resistance reduction and alignment of the fields of velocities in the flat diffuser channels was used for optimization of the reducer from the output diffuser of the gas turbine to the boiler-utilizer of CCGT of PGU-450T type of Kaliningrad Thermal Power Plant-2. The obtained results are evidence that the configuration of the reducer installed in the PGU-450T of Kaliningrad Thermal Power Plant-2 is not optimal. It follows also from the obtained data that working-off the reducer should be necessarily conducted by the test results of the channel consisting of the model of reducer with the model of boiler-utilizer installed behind it. Application of the method of alignment of output field of velocities and reducing the resistance in the wide-angle diffusers investigated in the work made it possible—when using the known model of diffusion

  17. Evaluation of effect of low opening operation on increasing wear of bearing bushings of guide vanes used in hydropower plants

    International Nuclear Information System (INIS)

    Kim, Jong Sung; Kim, Se Na


    A guide vane plays a key role in controlling the flow rate of water supplied to the turbine of a hydropower plant. It has been reported that guide vane bearing bushings are subjected to considerable wear, which requires them to be maintained. An ancillary service such as frequency control and black start causes cyclic low opening operation of the guide vanes. It is empirically well known that such operation increases the wear rate of the guide vane bearing bushing. In this study, the effect of low opening operation on the increasing wear of the guide vane bearing bushing is quantitatively assessed via finite element flow analysis, finite element stress analysis, and relative wear evaluation. As a result of the assessment, it is identified that the pressure applied on the guide vane surface increases and the contact length between the outer surface of the guide vane stem and the inner surface of the bearing bushing decreases with a decrease in the opening of the guide vane. In addition, low opening of the guide vanes results in an increase in the relative wear owing to the generation of high contact pressure on the bearing bushing surfaces

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

    NARCIS (Netherlands)

    Faems, D.L.M.; de Visser, Matthias; Andries, Petra; van Looy, Bart; van Looy, Bart


    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

  19. 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


    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

  20. Opening the Door to the American Dream: Increasing Higher Education Access and Success for Immigrants. New York Fact Sheet (United States)

    Erisman, Wendy; Looney, Shannon


    This fact sheet presents a snapshot of important facts that are specific to the state of New York from the "Opening the Door to the American Dream: Increasing Higher Education Access and Success for Immigrants" report, which exposes systemic barriers that prevent immigrants from entering college and/or completing bachelor's degrees…

  1. Frog ANP increases the amiloride-sensitive Na(+) channel activity in urinary bladder cells of Japanese tree frog, Hyla japonica. (United States)

    Yamada, Toshiki; Matsuda, Kouhei; Uchiyama, Minoru


    We examined the mechanism of amiloride-sensitive Na(+) channels (ENaC) activated by fANP in epithelial cells of frog urinary bladder by using a cell-attached patch-clamp technique. ENaC activities in the epithelial cells were significantly increased following administration of both 10(-9)M fANP and 10(-5)M 8-Br-cGMP. Both fANP and 8-Br-cGMP, however, failed to activate the ENaC in the presence of 10(-6)M amiloride. In addition, 8-Br-cGMP failed to activate the ENaC in the presence of a PKA inhibitor, KT-5720. In the next experiment, we measured both cGMP and cAMP production levels after treatment of fANP on the frog urinary bladder cells. Frog ANP significantly increased cGMP production, but not the cAMP production. Taken together, these results suggest that fANP activates ENaC through increases in cGMP production and activation of PKA.

  2. Whether trade openness has increased all the components of Portuguese public expenditure

    Directory of Open Access Journals (Sweden)

    Paulo Reis Mourao


    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.

  3. Non stochastic distribution of single channels in planar lipid bilayers. (United States)

    Krasilnikov, O V; Merzliak, P G; Yuldasheva, L N; Nogueira, R A; Rodrigues, C G


    The selectivity of the planar lipid bilayers modified by two channel-forming proteins (alpha-toxin S. aureus and colicin Ia) was examined. It was established that in all cases the value of zero current potential depended on the amount of open ion channels and increased with the number of channels (from one to about 5-7). These facts point out both the interactions among ion channels and their non stochastic distribution on the membrane surface.

  4. Safety of wet welding with increased open circuit voltages up to 150 V d.c

    International Nuclear Information System (INIS)

    Schmidt, K.; Kozig, G.; Ross, J.A.S.; Green, H.L.


    An experimental test programme was performed to demonstrate that wet welding with open circuit voltages up to 150 V d.c. would not result in dangerous situations for the diver induced by electric shock. Sea water, fresh water, different types of diving suits and some worst case situations, resulting from a disregard of good working practice were considered to be test parameters. In sea water a diver will not be endangered by corresponding electric potentials if good working practice is adopted. This was demonstrated even for worst case conditions, e.g. water leakage into the dry suit, accidental positioning to the diver between torch and work piece (stretched arm) and partial removal of coating from the welding rod. The fresh water tests demonstrated higher voltages on the diver but well below accepted threshold limit values. The term 'fresh water' should be critically considered, however, the test results relate only to the water conductivity studied. (orig.) With 30 figs [de

  5. An open source workbook in Excel for viewing and analyzing demagnetization data from paleomagnetic discrete samples and u-channels (United States)

    Sagnotti, L.


    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

  6. KCa3.1 channel inhibition leads to an ICAM-1 dependent increase of cell-cell adhesion between A549 lung cancer and HMEC-1 endothelial cells (United States)

    Bulk, Etmar; Kramko, Nadzeya; Liashkovich, Ivan; Glaser, Felix; Schillers, Hermann; Schnittler, Hans-Joachim; Oberleithner, Hans; Schwab, Albrecht


    Early metastasis leads to poor prognosis of lung cancer patients, whose 5-year survival rate is only 15%. We could recently show that the Ca2+ sensitive K+ channel KCa3.1 promotes aggressive behavior of non-small cell lung cancer (NSCLC) cells and that it can serve as a prognostic marker in NSCLC. Since NSCLC patients die of metastases, we investigated whether KCa3.1 channels contribute to poor patient prognosis by regulating distinct steps of the metastatic cascade. We investigated the extravasation of NSCLC cells and focused on their adhesion to endothelial cells and on transendothelial migration. We quantified the adhesion forces between NSCLC cells and endothelial cells by applying single cell force spectroscopy, and we monitored transendothelial migration using live-cell imaging. Inhibition of KCa3.1 channels with senicapoc or KCa3.1 silencing increases the adhesion force of A549 lung cancer cells to human microvascular endothelial cells (HMEC-1). Western blotting, immunofluorescence staining and biotinylation assays indicate that the elevated adhesion force is due to increased expression of ICAM-1 in both cell lines when KCa3.1 channels are downregulated. Consistent with this interpretation, an anti-ICAM-1 blocking antibody abolishes the KCa3.1-dependent increase in adhesion. Senicapoc inhibits transendothelial migration of A549 cells by 50%. Selectively silencing KCa3.1 channels in either NSCLC or endothelial cells reveals that transendothelial migration depends predominantly on endothelial KCa3.1 channels. In conclusion, our findings disclose a novel function of KCa3.1 channels in cancer. KCa3.1 channels regulate ICAM-1 dependent cell-cell adhesion between endothelial and cancer cells that affects the transmigration step of the metastatic cascade. PMID:29348824

  7. To Investigate the Flow Structure of Discontinuous Vegetation Patches of Two Vertically Different Layers in an Open Channel

    Directory of Open Access Journals (Sweden)

    Naveed Anjum


    Full Text Available In the present study, the flow structure of discontinuous double-layered vegetation patches was investigated using a 3D Reynolds stress turbulence model (RSM. The channel domain was built using GAMBIT (Geometry and Mesh Building Intelligent Toolkit. For the simulation and postprocessing, FLUENT (ANSYS was used to analyze the distribution of the mean velocity, Reynolds stresses, and other flow properties against two different flow conditions. The results captured by the turbulence model at specific locations and the cross section are presented in the form of various velocity profiles and contour plots. In the gap portion, the velocity was visibly lower than that in the vegetation areas, while the influence of patch distribution was not visible in the overlying flow layer. The velocity profiles at critical locations were categorized by numerous modulation points and velocity projections close to the bed, principally for positions straight after the vegetation structures. A distinction in the velocity at the topmost of the smaller vegetation structure was prominent. Reynolds stresses, turbulent kinetic energy, and turbulence intensity exhibited large fluctuations inside the vegetation regions and just behind the vegetation structures compared with in the gap regions.

  8. An integrated model coupling open-channel flow, turbidity current and flow exchanges between main river and tributaries in Xiaolangdi Reservoir, China (United States)

    Wang, Zenghui; Xia, Junqiang; Li, Tao; Deng, Shanshan; Zhang, Junhua


    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

  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. Electroconvulsive stimulations prevent chronic stress-induced increases in L-type calcium channel mRNAs in the hippocampus and basolateral amygdala

    DEFF Research Database (Denmark)

    Maigaard, Katrine; Pedersen, Ida Hageman; Jørgensen, Anders


    in the brain. We find that stress tended to upregulate Ca(v)1.2 and Ca(v)1.3 channels in a brain region specific manner, while ECS tended to normalise this effect. This was more pronounced for Ca(v)1.2 channels, where stress clearly increased expression in both the basolateral amygdala, dentate gyrus and CA3......, while stress only upregulated Ca(v)1.3 channel expression significantly in the dentate gyrus. ECS effects on Ca(v)1.2 channel expression were generally specific to stressed animals. Our findings are consistent with and extent previous studies on the involvement of intracellular calcium ion dysfunction...

  11. Defensin-like ZmES4 mediates pollen tube burst in maize via opening of the potassium channel KZM1.

    Directory of Open Access Journals (Sweden)

    Suseno Amien


    Full Text Available In contrast to animals and lower plant species, sperm cells of flowering plants are non-motile and are transported to the female gametes via the pollen tube, i.e. the male gametophyte. Upon arrival at the female gametophyte two sperm cells are discharged into the receptive synergid cell to execute double fertilization. The first players involved in inter-gametophyte signaling to attract pollen tubes and to arrest their growth have been recently identified. In contrast the physiological mechanisms leading to pollen tube burst and thus sperm discharge remained elusive. Here, we describe the role of polymorphic defensin-like cysteine-rich proteins ZmES1-4 (Zea mays embryo sac from maize, leading to pollen tube growth arrest, burst, and explosive sperm release. ZmES1-4 genes are exclusively expressed in the cells of the female gametophyte. ZmES4-GFP fusion proteins accumulate in vesicles at the secretory zone of mature synergid cells and are released during the fertilization process. Using RNAi knock-down and synthetic ZmES4 proteins, we found that ZmES4 induces pollen tube burst in a species-preferential manner. Pollen tube plasma membrane depolarization, which occurs immediately after ZmES4 application, as well as channel blocker experiments point to a role of K(+-influx in the pollen tube rupture mechanism. Finally, we discovered the intrinsic rectifying K(+ channel KZM1 as a direct target of ZmES4. Following ZmES4 application, KZM1 opens at physiological membrane potentials and closes after wash-out. In conclusion, we suggest that vesicles containing ZmES4 are released from the synergid cells upon male-female gametophyte signaling. Subsequent interaction between ZmES4 and KZM1 results in channel opening and K(+ influx. We further suggest that K(+ influx leads to water uptake and culminates in osmotic tube burst. The species-preferential activity of polymorphic ZmES4 indicates that the mechanism described represents a pre-zygotic hybridization

  12. Defensin-Like ZmES4 Mediates Pollen Tube Burst in Maize via Opening of the Potassium Channel KZM1 (United States)

    Márton, Mihaela L.; Debener, Thomas; Geiger, Dietmar; Becker, Dirk; Dresselhaus, Thomas


    In contrast to animals and lower plant species, sperm cells of flowering plants are non-motile and are transported to the female gametes via the pollen tube, i.e. the male gametophyte. Upon arrival at the female gametophyte two sperm cells are discharged into the receptive synergid cell to execute double fertilization. The first players involved in inter-gametophyte signaling to attract pollen tubes and to arrest their growth have been recently identified. In contrast the physiological mechanisms leading to pollen tube burst and thus sperm discharge remained elusive. Here, we describe the role of polymorphic defensin-like cysteine-rich proteins ZmES1-4 (Zea mays embryo sac) from maize, leading to pollen tube growth arrest, burst, and explosive sperm release. ZmES1-4 genes are exclusively expressed in the cells of the female gametophyte. ZmES4-GFP fusion proteins accumulate in vesicles at the secretory zone of mature synergid cells and are released during the fertilization process. Using RNAi knock-down and synthetic ZmES4 proteins, we found that ZmES4 induces pollen tube burst in a species-preferential manner. Pollen tube plasma membrane depolarization, which occurs immediately after ZmES4 application, as well as channel blocker experiments point to a role of K+-influx in the pollen tube rupture mechanism. Finally, we discovered the intrinsic rectifying K+ channel KZM1 as a direct target of ZmES4. Following ZmES4 application, KZM1 opens at physiological membrane potentials and closes after wash-out. In conclusion, we suggest that vesicles containing ZmES4 are released from the synergid cells upon male-female gametophyte signaling. Subsequent interaction between ZmES4 and KZM1 results in channel opening and K+ influx. We further suggest that K+ influx leads to water uptake and culminates in osmotic tube burst. The species-preferential activity of polymorphic ZmES4 indicates that the mechanism described represents a pre-zygotic hybridization barrier and may be a

  13. 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.

  14. Panel on increasing the visibility and publicity for data activities and assuring the open exchange of data

    International Nuclear Information System (INIS)

    Schultz, D.R.


    This panel was charged with leading and stimulating discussion regarding two principal issues: (1) the need to increase the visibility of atomic data production and collection activities in recognition of their role as vitally important resources for diverse applications, and (2) the need to assure the open exchange of this data. Comments by the panelists, supplemented by interaction with the audience, are summarized here along with the principal conclusions

  15. Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model. (United States)

    Morse, Alyson; McDonald, Michelle M; Schindeler, Aaron; Peacock, Lauren; Mikulec, Kathy; Cheng, Tegan L; Liu, Min; Ke, Hua Zhu; Little, David G


    Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength. The application of these antibodies to improve orthopedic repair has shown varied results, and may be dependent on the location and severity of the bony injury. We examined Scl-Ab treatment within an established rat osteotomy model with periosteal stripping analogous to open fracture repair. In one study, Scl-Ab was given 25 mg/kg bi-weekly, either from the time of fracture or from 3 weeks post-fracture up to an end-point of 12 weeks. A second study treated only delayed union open fractures that did not show radiographic union by week 6 post-fracture. Outcome measures included radiographic union, microCT analysis of bone volume and architecture, and histology. In the first study, Scl-Ab given from either 0 or 3 weeks significantly improved callus bone volume (+52%, p union rate was not changed. In the second study treating only established delayed fractures, bony callus volume was similarly increased by Scl-Ab treatment; however, this did not translate to increased biomechanical strength or union improvement. Sclerostin antibody treatment has limited effects on the healing of challenging open fractures with periosteal stripping, but shows the greatest benefits on callus size and strength with earlier intervention.

  16. Lignin Modification Leads to Increased Nodule Numbers in Alfalfa1[C][W][OPEN (United States)

    Gallego-Giraldo, Lina; Bhattarai, Kishor; Pislariu, Catalina I.; Nakashima, Jin; Jikumaru, Yusuke; Kamiya, Yuji; Udvardi, Michael K.; Monteros, Maria J.; Dixon, Richard A.


    Reduction of lignin levels in the forage legume alfalfa (Medicago sativa) by down-regulation of the monolignol biosynthetic enzyme hydroxycinnamoyl coenzyme A:shikimate hydroxycinnamoyl transferase (HCT) results in strongly increased digestibility and processing ability of lignocellulose. However, these modifications are often also associated with dwarfing and other changes in plant growth. Given the importance of nitrogen fixation for legume growth, we evaluated the impact of constitutively targeted lignin modification on the belowground organs (roots and nodules) of alfalfa plants. HCT down-regulated alfalfa plants exhibit a striking reduction in root growth accompanied by an unexpected increase in nodule numbers when grown in the greenhouse or in the field. This phenotype is associated with increased levels of gibberellins and certain flavonoid compounds in roots. Although HCT down-regulation reduced biomass yields in both the greenhouse and field experiments, the impact on the allocation of nitrogen to shoots or roots was minimal. It is unlikely, therefore, that the altered growth phenotype of reduced-lignin alfalfa is a direct result of changes in nodulation or nitrogen fixation efficiency. Furthermore, HCT down-regulation has no measurable effect on carbon allocation to roots in either greenhouse or 3-year field trials. PMID:24406794

  17. 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: [Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla (Mexico)


    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.

  18. Opening the Black Box: Strategies for Increased User Involvement in Existing Algorithm Implementations. (United States)

    Mühlbacher, Thomas; Piringer, Harald; Gratzl, Samuel; Sedlmair, Michael; Streit, Marc


    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.

  19. 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


    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.

  20. Polyunsaturated fatty acids modify the gating of Kv channels

    Directory of Open Access Journals (Sweden)

    Cristina eMoreno


    Full Text Available Polyunsaturated fatty acids (PUFAs have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will focus on the role of PUFAs on the gating of two Kv channels, Kv1.5 and Kv11.1. Kv1.5 channels are blocked by n-3 PUFAs of marine (docosahexaenoic and eicosapentaenoic acid, DHA and EPA and plant origin (alpha-linolenic acid, ALA at physiological concentrations. The blockade of Kv1.5 channels by PUFAs steeply increased in the range of membrane potentials coinciding with those of Kv1.5 channel activation, suggesting that PUFAs-channel binding may derive a significant fraction of its voltage sensitivity through the coupling to channel gating. A similar shift in the activation voltage was noted for the effects of arachidonic acid (AA and DHA on Kv1.1, Kv1.2, and Kv11.1 channels. PUFAs-Kv1.5 channel interaction is time-dependent, producing a fast decay of the current upon depolarization. Thus, Kv1.5 channel opening is a prerequisite for the PUFA-channel interaction. Similar to the Kv1.5 channels, the blockade of Kv11.1 channels by AA and DHA steeply increased in the range of membrane potentials that coincided with the range of Kv11.1 channel activation, suggesting that the PUFAs-Kv channel interactions are also coupled to channel gating. Furthermore, AA regulates the inactivation process in other Kv channels, introducing a fast voltage-dependent inactivation in non-inactivating Kv channels. These results have been explained within the framework that AA closes voltage-dependent potassium channels by inducing conformational changes in the selectivity filter, suggesting that Kv channel gating is lipid dependent.

  1. Analysis of liquid relief valves opening demand during pressure increase abnormal scenarios at Embalse nuclear power plant

    International Nuclear Information System (INIS)

    Bedrossian, Gustavo C.; Gersberg, Sara


    Two hypothetical scenarios have been analyzed where, after an initiating event, Embalse nuclear power plant primary heat transport system could undergo a pressure increase. These abnormal events are a loss of feedwater to the steam generators and a loss of Class IV power supply with Class III restoration. This analysis focuses on primary system liquid relief valves action, specially on their opening demand. Calculation results show that even when these valves are expected to open during the transient, primary system maximum allowable pressure would not be exceeded if they failed to open. System response was also studied in case that one of these relief valves did not close once primary system pressure decreases. For the scenario of loss of feedwater to steam generators, if the degasser-condenser could not be bottled-up, Emergency Cooling Injection conditions would be reached due to a continuos loss of coolant. In case of loss of Class IV -and assuming degasser-condenser bottling-up as service water would not be available- it was observed that primary system should remain pressurized, and with core cooled by thermo siphoning mechanism. (author)

  2. Demagnetization Analysis in Excel (DAIE) - An open source workbook in Excel for viewing and analyzing demagnetization data from paleomagnetic discrete samples and u-channels (United States)

    Sagnotti, Leonardo


    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

  3. 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.


    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.

  4. An open 8-channel parallel transmission coil for static and dynamic 7T MRI of the knee and ankle joints at multiple postures. (United States)

    Jin, Jin; Weber, Ewald; Destruel, Aurelien; O'Brien, Kieran; Henin, Bassem; Engstrom, Craig; Crozier, Stuart


    We present the initial in vivo imaging results of an open architecture eight-channel parallel transmission (pTx) transceive radiofrequency (RF) coil array that was designed and constructed for static and dynamic 7T MRI of the knee and ankle joints. The pTx coil has a U-shaped dual-row configuration (200 mm overall length longitudinally) that allows static and dynamic imaging of the knee and ankle joints at various postures and during active movements. This coil structure, in combination with B 1 shimming, allows flexible configuration of B 1 transmit profiles, with good homogeneity over 120-mm regions of interest. This coil enabled high-resolution gradient echo (e.g., 3D dual-echo steady state [DESS] and 3D multiecho data image combination [MEDIC]) and turbo spin echo (TSE) imaging (e.g., with proton density weighting [PDw], PDw with fat saturation, and T 1 and T 2 weightings) with local RF energy absorption rates well below regulatory limits. High-resolution 2D and 3D image series (e.g., 0.3 mm in-plane resolution for TSE, 0.47 mm isotropic for DESS and MEDIC) were obtained from the knee and ankle joints with excellent tissue contrast. Dynamic imaging during continuous knee and ankle flexion-extension cycles were successfully acquired. The new open pTx coil array provides versatility for high-quality static and dynamic MRI of the knee and ankle joints at 7T. Magn Reson Med 79:1804-1816, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  5. Leptin increases L-type Ca2+ channel expression and GnRH-stimulated LH release in LβT2 gonadotropes (United States)

    Avelino-Cruz, José E.; Flores, Amira; Cebada, Jorge; Mellon, Pamela L.; Felix, Ricardo; Monjaraz, Eduardo


    Leptin, a mediator of long-term regulation of energy balance, has been implicated in the release of adenohypophyseal gonadotropins by regulating gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. However, a direct effect of leptin on hormone release from gonadotropes remains virtually unexplored. In the current report, we assessed the long-term (48 h) actions of leptin on voltage-gated channel activity and luteinizing hormone (LH) production in mouse pituitary gonadotrope LβT2 cells. Electrophysiological recordings showed that leptin treatment significantly increased whole-cell patch clamp Ba2+ current through L-type Ca2+ channels. Quantitative RT-PCR analysis revealed increased levels of L-type (α1D) Ca2+ channel mRNA. Likewise, radioimmunoassays using specific antibodies provided evidence that leptin alone had no effect on LH release but did enhance GnRH-induced secretion of the hormone. Leptin had no apparent effects on LH gene transcription in absence of GnRH, as measured by transient transfection assays using a LH promoter-reporter gene and real time RT-PCR. These observations suggest that leptin might affect LH release by acting directly on the gonadotropes, favoring hormone production by enhancing responsiveness to GnRH as a result of increased Ca2+ channel expression. PMID:18834922

  6. Increased tolerance to stress in cardiac expressed gain-of-function of adenosine triphosphate-sensitive potassium channel subunit Kir6.1. (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


    The adenosine triphosphate-sensitive potassium (K ATP ) channel opener diazoxide (DZX) prevents myocyte volume derangement and reduced contractility secondary to stress. K ATP 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}] +/- K ATP 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.

  7. Soothing music can increase oxytocin levels during bed rest after open-heart surgery: a randomised control trial. (United States)

    Nilsson, Ulrica


    To evaluate the effect of bed rest with music on relaxation for patients who have undergone heart surgery on postoperative day one. Music intervention has been evaluated as an appropriate nursing intervention to reduce patients 'pain, stress and anxiety levels in several clinical settings, but its effectiveness in increasing patients' subjective and objective relaxation levels has not been examined. A randomised controlled trial. Forty patients undergoing open coronary artery bypass grafting and/or aortic valve replacement surgery were randomly allocated to either music listening during bed rest (n = 20) or bed rest only (n = 20). Relaxation was assessed during bed rest the day after surgery by determining the plasma oxytocin, heart rate, mean arterial blood pressure, PaO2 SaO2 and subjective relaxation levels. In the music group, levels of oxytocin increased significantly in contrast to the control group for which the trend over time was negative i.e., decreasing values. Subjective relaxation levels increased significantly more and there were also a significant higher levels of PaO2 in the music group compared to the control group. There was no difference in mean arterial blood pressure, heart rate and SaO2 between the groups. Listening to music during bed rest after open-heart surgery has some effects on the relaxation system as regards s-oxytocin and subjective relaxations levels. This effect seems to have a causal relation from the psychological (music makes patients relaxed) to the physical (oxytocin release). Music intervention should be offered as an integral part of the multimodal regime administered to the patients that have undergone cardiovascular surgery. It is a supportive source that increases relaxation.

  8. Anti-KCNQ1 K⁺ channel autoantibodies increase IKs current and are associated with QT interval shortening in dilated cardiomyopathy. (United States)

    Li, Jin; Seyler, Claudia; Wiedmann, Felix; Schmidt, Constanze; Schweizer, Patrick A; Becker, Rüdiger; Katus, Hugo A; Thomas, Dierk


    Autoimmune-associated proarrhythmia in dilated cardiomyopathy (DCM) is poorly understood. Given the significance of KCNQ1 potassium channels in heart rhythm disorders, we hypothesized that circulating anti-KCNQ1 autoantibodies directly modulate cardiac electrophysiology in DCM patients. The purpose of this pilot study was to characterize ion channel autoantibodies in DCM targeting the cardiac repolarizing K(+) current, IKs, and the underlying KCNQ1 potassium channel. One hundred and fifty DCM patients were screened for anti-KCNQ1 autoantibodies using an enzyme-linked immunosorbent assay. Autoantibodies targeting the extracellular pore domain of the KCNQ1 channel were detected in 6% of study patients. Seropositive individuals exhibited significantly shorter corrected QT intervals when compared with seronegative patients (371 ± 39.9 ms vs. 408 ± 47.9 ms; P = 0.036). There was no difference in clinical severity of heart failure between groups. The functional significance of anti-KCNQ1 antibodies was determined in human embryonic kidney 293 cells expressing KCNQ1/KCNE1 using the whole-cell patch clamp technique. IKs recordings demonstrated a 2.7-fold increase in mean current density on exposure to patients' sera containing anti-KCNQ1 antibodies in contrast to seronegative controls (8.74 ± 1.44 pA/pF vs. 3.26 ± 0.36 pA/pF; P = 0.003). IKs enhancement was not associated with increased KCNQ1 protein levels or altered cell surface expression of the channel. Anti-KCNQ1 autoantibodies found in a subgroup of DCM patients are associated with QT interval shortening and increased IKs current.

  9. Resveratrol attenuates cortical neuron activity: roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels. (United States)

    Wang, Ya-Jean; Chan, Ming-Huan; Chen, Linyi; Wu, Sheng-Nan; Chen, Hwei-Hisen


    Resveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities. However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. The large-conductance calcium-activated potassium channels (BKCa) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. The present study aimed to determine the effects of resveratrol on BKCa currents and voltage-gated sodium currents in cortical neurons. Resveratrol concentration-dependently increased the current amplitude and the opening activity of BKCa channels, but suppressed the amplitude of voltage-gated sodium currents. Similar to the BKCa channel opener NS1619, resveratrol decreased the firing rate of action potentials. In addition, the enhancing effects of BKCa channel blockers tetraethylammonium (TEA) and paxilline on action potential firing were sensitive to resveratrol. Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BKCa channels and closing the voltage-gated sodium channels. As BKCa channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol.

  10. Novel eclipsed 2D cadmium(II) coordination polymers with open-channel structure constructed from terephthalate and 3-(2-pyridyl)pyrazole: crystal structures, emission properties, and inclusion of guest molecules. (United States)

    Zou, Ru-Qiang; Bu, Xian-He; Zhang, Ruo-Hua


    Five new eclipsed two-dimensional (2D) coordination polymers, [[Cd(2)(TPT)(2)L(2)](GM(1))(3/2)(H(2)O)](infinity) (1) (TPT = terephthalate, L = 3-(2-pyridyl)pyrazole, GM(1) = terephthalic acid), [[Cd(TPT)L](GM(2))(H(2)O)(2)]( infinity) (2) (GM(2) = L = 3-(2-pyridyl)pyrazole), [[Cd(TPT)L](GM(3))(1/2)(H(2)O)](infinity) (3) (GM(3) = mesitylene), [[Cd(4)(TPT)(4)L(4)](GM(4))(7/2)](infinity) (4) (GM(4) = tetramethylbenzene), and [[Cd(TPT)L](GM(5))(1/2)](infinity) (5) (GM(5) = naphthalene), have been synthesized and characterized by X-ray diffraction. All the five complexes take the similar eclipsed 2D open-channel framework with different guest molecules included in the cavities of their channels. TGA analysis indicates that the eclipsed open-channel frameworks are thermally stable up to 300 degrees C. The porous property of the 2D framework of 5 was also investigated by the XRPD technique, which indicated that the guest molecules included in the open-channel frameworks are removable and the framework is maintained after the removal of the guest molecules. Moreover, complexes 1-5 also display strong blue emission in the solid state.

  11. The Increased Activity of TRPV4 Channel in the Astrocytes of the Adult Rat Hippocampus after Cerebral Hypoxia/Ischemia

    Czech Academy of Sciences Publication Activity Database

    Butenko, Olena; Džamba, Dávid; Benešová, Jana; Honsa, Pavel; Benfenati, V.; Rusňáková, Vendula; Ferroni, S.; Anděrová, Miroslava


    Roč. 7, č. 6 (2012), e39959 E-ISSN 1932-6203 R&D Projects: GA ČR GAP303/10/1338; GA MŠk(CZ) LC554 Grant - others:GA ČR(CZ) GD309/08/H079 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50520701 Keywords : ischemia * astrocytes * transient receptor channel Subject RIV: FH - Neurology; FH - Neurology (BTO-N) Impact factor: 3.730, year: 2012

  12. Increased expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in reactive astrocytes following ischemia

    Czech Academy of Sciences Publication Activity Database

    Honsa, Pavel; Pivoňková, Helena; Harantová, Lenka; Butenko, Olena; Kriška, Ján; Džamba, Dávid; Rusňáková, Vendula; Valihrach, Lukáš; Kubista, Mikael; Anděrová, Miroslava


    Roč. 62, č. 12 (2014), s. 2004-2021 ISSN 0894-1491 R&D Projects: GA ČR GA13-02154S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:GA MŠk(CZ) CZ.1.07/2.3.00/30.0045 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : Astrocytes * focal and global cerebral ischemia * HCN channels Subject RIV: FH - Neurology Impact factor: 6.031, year: 2014

  13. 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


    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.

  14. Impact of organic nutrient load on biomass accumulation, feed channel pressure drop increase and permeate flux decline in membrane systems

    KAUST Repository

    Bucs, Szilard


    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. Open-source electronic data capture system offered increased accuracy and cost-effectiveness compared with paper methods in Africa. (United States)

    Dillon, David G; Pirie, Fraser; Rice, Stephen; Pomilla, Cristina; Sandhu, Manjinder S; Motala, Ayesha A; Young, Elizabeth H


    Existing electronic data capture options are often financially unfeasible in resource-poor settings or difficult to support technically in the field. To help facilitate large-scale multicenter studies in sub-Saharan Africa, the African Partnership for Chronic Disease Research (APCDR) has developed an open-source electronic questionnaire (EQ). To assess its relative validity, we compared the EQ against traditional pen-and-paper methods using 200 randomized interviews conducted in an ongoing type 2 diabetes case-control study in South Africa. During its 3-month validation, the EQ had a lower frequency of errors (EQ, 0.17 errors per 100 questions; paper, 0.73 errors per 100 questions; P-value ≤0.001), and a lower monetary cost per correctly entered question, compared with the pen-and-paper method. We found no marked difference in the average duration of the interview between methods (EQ, 5.4 minutes; paper, 5.6 minutes). This validation study suggests that the EQ may offer increased accuracy, similar interview duration, and increased cost-effectiveness compared with paper-based data collection methods. The APCDR EQ software is freely available ( Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Modification of single Na+ channels by batrachotoxin.


    Quandt, F N; Narahashi, T


    The modifications in the properties of voltage-gated Na+ channels caused by batrachotoxin were studied by using the patch clamp method for measuring single channel currents from excised membranes of N1E-115 neuroblastoma cells. The toxin-modified open state of the Na+ channel has a decreased conductance in comparison to that of normal Na+ channels. The lifetime of the modified open state is drastically prolonged, and channels now continue to open during a maintained depolarization so that the...

  17. PA-6 inhibits inward rectifier currents carried by V93I and D172N gain-of-function KIR2.1 channels, but increases channel protein expression. (United States)

    Ji, Yuan; Veldhuis, Marlieke G; Zandvoort, Jantien; Romunde, Fee L; Houtman, Marien J C; Duran, Karen; van Haaften, Gijs; Zangerl-Plessl, Eva-Maria; Takanari, Hiroki; Stary-Weinzinger, Anna; van der Heyden, Marcel A G


    The inward rectifier potassium current I K1 contributes to a stable resting membrane potential and phase 3 repolarization of the cardiac action potential. KCNJ2 gain-of-function mutations V93I and D172N associate with increased I K1 , short QT syndrome type 3 and congenital atrial fibrillation. Pentamidine-Analogue 6 (PA-6) is an efficient (IC 50  = 14 nM with inside-out patch clamp methodology) and specific I K1 inhibitor that interacts with the cytoplasmic pore region of the K IR 2.1 ion channel, encoded by KCNJ2. At 10 μM, PA-6 increases wild-type (WT) K IR 2.1 expression in HEK293T cells upon chronic treatment. We hypothesized that PA-6 will interact with and inhibit V93I and D172N K IR 2.1 channels, whereas impact on channel expression at the plasma membrane requires higher concentrations. Molecular modelling was performed with the human K IR 2.1 closed state homology model using FlexX. WT and mutant K IR 2.1 channels were expressed in HEK293 cells. Patch-clamp single cell electrophysiology measurements were performed in the whole cell and inside-out mode of the patch clamp method. K IR 2.1 expression level and localization were determined by western blot analysis and immunofluorescence microscopy, respectively. PA-6 docking in the V93I/D172N double mutant homology model of K IR 2.1 demonstrated that mutations and drug-binding site are >30 Å apart. PA-6 inhibited WT and V93I outward currents with similar potency (IC 50  = 35.5 and 43.6 nM at +50 mV for WT and V93I), whereas D172N currents were less sensitive (IC 50  = 128.9 nM at +50 mV) using inside-out patch-clamp electrophysiology. In whole cell mode, 1 μM of PA-6 inhibited outward I K1 at -50 mV by 28 ± 36%, 18 ± 20% and 10 ± 6%, for WT, V93I and D172N channels respectively. Western blot analysis demonstrated that PA-6 (5 μM, 24 h) increased K IR 2.1 expression levels of WT (6.3 ± 1.5 fold), and V93I (3.9 ± 0.9) and D172N (4.8 ± 2.0) mutants. Immunofluorescent

  18. K(ATP) channel gain-of-function leads to increased myocardial L-type Ca(2+) current and contractility in Cantu syndrome. (United States)

    Levin, Mark D; Singh, Gautam K; Zhang, Hai Xia; Uchida, Keita; Kozel, Beth A; Stein, Phyllis K; Kovacs, Atilla; Westenbroek, Ruth E; Catterall, William A; Grange, Dorothy Katherine; Nichols, Colin G


    Cantu syndrome (CS) is caused by gain-of-function (GOF) mutations in genes encoding pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) KATP channel subunits. We show that patients with CS, as well as mice with constitutive (cGOF) or tamoxifen-induced (icGOF) cardiac-specific Kir6.1 GOF subunit expression, have enlarged hearts, with increased ejection fraction and increased contractility. Whole-cell voltage-clamp recordings from cGOF or icGOF ventricular myocytes (VM) show increased basal L-type Ca(2+) current (LTCC), comparable to that seen in WT VM treated with isoproterenol. Mice with vascular-specific expression (vGOF) show left ventricular dilation as well as less-markedly increased LTCC. Increased LTCC in KATP GOF models is paralleled by changes in phosphorylation of the pore-forming α1 subunit of the cardiac voltage-gated calcium channel Cav1.2 at Ser1928, suggesting enhanced protein kinase activity as a potential link between increased KATP current and CS cardiac pathophysiology.

  19. Channelling and channelling radiation

    International Nuclear Information System (INIS)

    Soerensen, A.H.; Uggerhoej, E.


    The study of channelling phenomena has developed rapidly since the early 1960s and today channelling has found many applications. The radiation emitted by channelled megaelectronvolt and gigaelectronvolt electrons and positrons has been investigated extensively and the possibility of, for example, constructing intense tunable X- and γ-ray sources is being explored. Multi-gigaelectronvolt radiation and pair-creation processes in single crystals show similarities with strong-field effects and are of particular interest because of high production rates that persist far beyond the channelling regime. (author)

  20. Septal deviation and other factors increase the risk of barotitis media in high altitude high opening training

    Directory of Open Access Journals (Sweden)

    Yanuar T. Sastranegara


    Full Text Available Barotitis media (BM frequently occurr in High Altitude High Opening (HAHO training simulation as a result from rapid change of pressure. The aim of this study was to investigate septal deviation and other risk factors that increase the risk of BM. This experimental study was conducted at the Indonesian Center for Aviation Medicine and Health (Lakespra Saryanto during May – July 2007 involving Indonesian Armed Forces (TNI HAHO training. Medical examinations were performed before and after training. An otolaryngologist confirm the diagnosis of BM. Cox regression analysis using STATA 9.0 program was performed to identify dominant risk factors for BM. A number of 177 subjects participated in this study. We found 56.5% had BM after training. Septal deviation was found in 28.8% of the subjects and it moderately increased the risk of BM by 23% than normal septum [adjusted relative risk (RRα = 1.23; 95% confidence interval (CI = 0.95 – 1.60; p=0.123]. Those who have been smoking for 1-3 years had 70% increase risk for BM than non-smoking subjects (RRα= 1.68; 95% CI = 1.17 – 2.42. Those who have been in the force for 5 years or longer were 50% more at risk for BM than those who have been in the force less than 5 years. In addition, trainees had 40% higher risk than subjects with special qualifications for HAHO (RRα = 1.40; 95% CI = 0.99 – 1.97; p = 0.051. Special caution need to be applied for those who had septal deviation, longer working period, habit of smoking for 1-3 years, and trainees to minimize the risk of BM. (Med J Indones 2008; 17: 37-42Keywords: barotitis media, septal deviation, HAHO training simulation

  1. Increased voltage-dependent K+ channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness (United States)



    Voltage-dependent K+ channels (Kv) are involved in the proliferation and differentiation of mammalian cells, since Kv antagonists impair cell cycle progression. Although myofibers are terminally differentiated, some myoblasts may re-enter the cell cycle and proliferate. Since Kv1.3 and Kv1.5 expression is remodeled during tumorigenesis and is involved in smooth muscle proliferation, the purpose of this study was to analyze the expression of Kv1.3 and Kv1.5 in smooth muscle neoplasms. In the present study, we examined human samples of smooth muscle tumors together with healthy specimens. Thus, leiomyoma (LM) and leiomyosarcoma (LMS) tumors were analyzed. Results showed that Kv1.3 was poorly expressed in the healthy muscle and indolent LM specimens, whereas aggressive LMS showed high levels of Kv1.3 expression. Kv1.5 staining was correlated with malignancy. The findings show a remodeling of Kv1.3 and Kv1.5 in human smooth muscle sarcoma. A correlation of Kv1.3 and Kv1.5 expression with tumor aggressiveness was observed. Thus, our results indicate Kv1.5 and Kv1.3 as potential tumorigenic targets for aggressive human LMS. PMID:22844358

  2. β-adrenergic Receptor Blocker ICI 118,551 Selectively Increases Intermediate-Conductance Calcium-Activated Potassium Channel (IKCa)-Mediated Relaxations in Rat Main Mesenteric Artery. (United States)

    Ozkan, Melike Hacer; Uma, Serdar


    Endothelial IK C a and/or SK C a channels play an important role in the control of vascular tone by participating in endothelium-dependent relaxation. Whether β-AR antagonists, mainly used in hypertension, affect endothelial K C a channel function is unknown. In this study, we examined the effect of the β2-AR antagonist and inverse agonist ICI 118,551 on the IK C a /SK C a channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Sprague Dawley mounted to organ baths. Acetylcholine elicited IK C a - and SK C a -mediated relaxations that were abolished by TRAM-34 and apamin, respectively. ICI 118,551, which did not dilate the arteries per se, increased the IK C a -mediated relaxations, whereas SK C a -mediated relaxations remained unaltered. Same potentiating effect was also detected on the IK C a -mediated relaxations to carbachol and A23187, but not to NS309. Neither acetylcholine-induced nitric oxide-mediated relaxations nor SNP relaxations changed with ICI 118,551. The PKA inhibitor KT-5720, the selective β2-AR agonist salbutamol, the selective β2-AR antagonist butoxamine, the non-selective β-AR antagonist propranolol, and the inverse agonists carvedilol or nadolol failed to affect the IK C a -mediated relaxations. ICI 118,551-induced increase was not reversed by salbutamol or propranolol as well. Besides, low potassium-induced relaxations in endothelium-removed arteries remained the same in the presence of ICI 118,551. These data demonstrate a previously unrecognized action of ICI 118,551, the ability to potentiate endothelial IK C a channel-mediated vasodilation, through a mechanism independent of β2-AR antagonistic or inverse agonistic action. Instead, the enhancement of acetylcholine relaxation seems likely to occur by a mechanism secondary to endothelial calcium increase. © 2017 Nordic Association for the Publication of BCPT (former Nordic

  3. Altered Potassium Ion Channel Function as a Possible Mechanism of Increased Blood Pressure in Rats Fed Thermally Oxidized Palm Oil Diets. (United States)

    Nkanu, Etah E; Owu, Daniel U; Osim, Eme E


    Intake of thermally oxidized palm oil leads to cytotoxicity and alteration of the potassium ion channel function. This study investigated the effects of fresh and thermally oxidized palm oil diets on blood pressure and potassium ion channel function in blood pressure regulation. Male Wistar rats were randomly divided into three groups of eight rats. Control group received normal feed; fresh palm oil (FPO) and thermally oxidized palm oil (TPO) groups were fed a diet mixed with 15% (weight/weight) fresh palm oil and five times heated palm oil, respectively, for 16 weeks. Blood pressure was measured; blood samples, hearts, and aortas were collected for biochemical and histological analyses. Thermally oxidized palm oil significantly elevated basal mean arterial pressure (MAP). Glibenclamide (10 -5 mmol/L) and tetraethylammonium (TEA; 10 -3 mmol/L) significantly raised blood pressure in TPO compared with FPO and control groups. Levcromakalim (10 -6 mmol/L) significantly (p palm oil increases MAP probably due to the attenuation of adenosine triphosphate-sensitive potassium (K ATP ) and large-conductance calcium-dependent potassium (BK Ca ) channels, tissue peroxidation, and altered histological structures of the heart and blood vessels.

  4. 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


    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.

  5. Sigma-1 receptor agonist increases axon outgrowth of hippocampal neurons via voltage-gated calcium ions channels. (United States)

    Li, Dong; Zhang, Shu-Zhuo; Yao, Yu-Hong; Xiang, Yun; Ma, Xiao-Yun; Wei, Xiao-Li; Yan, Hai-Tao; Liu, Xiao-Yan


    Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig-1R agonist, SA4503. Then, electrophysiology and immunofluorescence were used to examine voltage-gated calcium ion channel (VGCCs) currents in the cell membranes and growth cones. We found that Sig-1R activation dramatically enhanced the axonal length of the naïve hippocampal neurons. Application of the Sig-1R antagonist NE100 and gene knockdown techniques both demonstrated the effects of Sig-1R. The growth-promoting effect of SA4503 was accompanied by the inhibition of voltage-gated Ca 2+ influx and was recapitulated by incubating the neurons with the L-type, N-type, and P/Q-type VGCC blockers, nimodipine, MVIIA and ω-agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of SA4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth. Sig-1R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases. © 2017 John Wiley & Sons Ltd.

  6. 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

  7. Quantum Interference and Selectivity through Biological Ion Channels. (United States)

    Salari, Vahid; Naeij, Hamidreza; Shafiee, Afshin


    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.

  8. The Five 'R's' for Developing Trusted Software Frameworks to increase confidence in, and maximise reuse of, Open Source Software. (United States)

    Fraser, Ryan; Gross, Lutz; Wyborn, Lesley; Evans, Ben; Klump, Jens


    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

  9. 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


    oxidative stress and syndecan-4 (SDC-4) in human podocytes. Human podocytes were exposed to control conditions (5.6 mmol/L D-glucose), high glucose (30 mmol/L D-glucose or L-glucose), 100 μmol/L peroxynitrite, or high glucose and the superoxide dismutase mimetic tempol (100 μmol/L). TRPC6 and SDC-4.......44±0.07 (ptempol. Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p....05) without altering SDC-4 transcripts or protein expression. In human podocytes transfected with scrambled siRNA, high D-glucose increased ROS after 90 min to 3.55±0.08 arbitrary units while 5.6 mmol/L D-glucose increased ROS to 2.49±0.09 (ptempol and by SDC...

  10. 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.

  11. On increasing the spectral efficiency and transmissivity in the data transmission channel on the spacecraft-ground tracking station line (United States)

    Andrianov, M. N.; Kostenko, V. I.; Likhachev, S. F.


    The algorithms for achieving a practical increase in the rate of data transmission on the space-craft-ground tracking station line has been considered. This increase is achieved by applying spectral-effective modulation techniques, the technology of orthogonal frequency compression of signals using millimeterrange radio waves. The advantages and disadvantages of each of three algorithms have been revealed. A significant advantage of data transmission in the millimeter range has been indicated.

  12. 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


    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.

  13. BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle

    DEFF Research Database (Denmark)

    Layne, Jeffrey J; Nausch, Bernhard; Olesen, Søren-Peter


    reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 microM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing......Large-conductance Ca(2+)-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether...... activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 microM) caused an approximately threefold increase in both single BK channel open probability (P...

  14. 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)


    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

  15. 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


    -fold within dentate gyrus (DG), CA2/3, and hilus of 12-week-old mceph/mceph versus wild type mice. In CA1, there was a tendency toward an increase in volume and in number of astrocytes. The volume estimates in newborn and p14 mice suggest that the overgrowth in mceph/mceph hippocampus starts between birth...

  16. Vascular surgery training trends from 2001-2007: A substantial increase in total procedure volume is driven by escalating endovascular procedure volume and stable open procedure volume. (United States)

    Schanzer, Andres; Steppacher, Robert; Eslami, Mohammad; Arous, Elias; Messina, Louis; Belkin, Michael


    Endovascular procedure volume has increased rapidly, and endovascular procedures have become the initial treatment option for many vascular diseases. Consequently, training in endovascular procedures has become an essential component of vascular surgery training. We hypothesized that, due to this paradigm shift, open surgical case volume may have declined, thereby jeopardizing training and technical skill acquisition in open procedures. Vascular surgery trainees are required to log both open and endovascular procedures with the Accreditation Council for Graduate Medical Education (ACGME). We analyzed the ACGME database (2001-2007), which records all cases (by Current Procedural Terminology [CPT] code) performed by graduating vascular trainees. Case volume was evaluated according to the mean number of cases performed per graduating trainee. The mean number of total major vascular procedures performed per trainee increased by 174% between 2001 and 2007 (from 298.3 to 519.2). Endovascular diagnostic and therapeutic procedures increased by 422% (from 63.7 to 269.1) and accounted for 93.0% of the increase in total procedures. The number of open aortic procedures (aneurysm, occlusive, mesenteric, renal) decreased by 17.1% (from 49.7 to 41.2), while the number of endovascular aortic aneurysm repair procedures increased by 298.8% (from 16.9 to 50.5). Specifically, open aortic aneurysm procedures decreased by 21.8%, aortobifemoral bypass increased by 3.2%, and open mesenteric or renal procedures decreased by 13%. Infrainguinal bypass procedures remained relatively constant (from 37.6 to 36.5, 2.9% decrease), and the number of carotid endarterectomy procedures performed did not change significantly (from 43.6 to 42.2, 3.2% decrease). Vascular surgery trainees are performing a vastly increased total number of procedures. This increase in total procedure volume is almost entirely attributable to the recent increase in endovascular procedures. Aside from a small decline in open

  17. High-efficient method for spectrometric data real time processing with increased resolution of a measuring channel

    International Nuclear Information System (INIS)

    Ashkinaze, S.I.; Voronov, V.A.; Nechaev, Yu.I.


    Solution of reduction problem as a mean to increase spectrometric tract resolution when it is realized using the digit-by-digit modified method and special strategy, significantly reducing the time of processing, is considered. The results presented confirm that the complex measurement tract plus microcomputer is equivalent to the use of the tract with a higher resolution, and the use of the digit-by-digit modified method permits to process spectrometric information in real time scale

  18. Lipopolysaccharide hyperpolarizes guinea pig airway epithelium by increasing the activities of the epithelial Na(+) channel and the Na(+)-K(+) pump. (United States)

    Dodrill, Michael W; Fedan, Jeffrey S


    Earlier, we found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V(t)) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. As well, LPS increased the hyperpolarization component of the response to basolateral methacholine, and potentiated the epithelium-derived relaxing factor-mediated relaxation responses to hyperosmolar solutions applied to the apical membrane. We hypothesized that LPS stimulates the transepithelial movement of Na(+) via the epithelial sodium channel (ENaC)/Na(+)-K(+) pump axis, leading to hyperpolarization of V(t). LPS increased the V(t)-depolarizing response to amiloride (10 μM), i.e., offset the effect of LPS, indicating that Na(+) transport activity was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na(+)-K(+) pump with basolateral amphotericin B (7.5 μM). LPS had no effect on the hyperpolarization response to apical trypsin (100 U/ml) in the Ussing chamber, indicating that channel-activating proteases are not involved in the LPS-induced activation of ENaC. To assess Na(+)-K(+) pump activity in the IPT, ENaC was short-circuited with apical amphotericin B. The greater V(t) in the presence of amphotericin B in tracheas from LPS-treated animals compared with controls revealed that LPS increased Na(+)-K(+) pump activity. This finding was confirmed in the Ussing chamber by inhibiting the Na(+)-K(+) pump via extracellular K(+) removal, loading the epithelium with Na(+), and observing a greater hyperpolarization response to K(+) restoration. Together, the findings of this study reveal that LPS hyperpolarizes the airway epithelium by increasing the activities of ENaC and the Na(+)-K(+) pump.

  19. Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

    Directory of Open Access Journals (Sweden)

    Jonathan Maiangwa


    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

  20. Rattlesnake Phospholipase A2 Increases CFTR-Chloride Channel Current and Corrects ∆F508CFTR Dysfunction: Impact in Cystic Fibrosis. (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


    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice. (United States)

    Liu, Lijie; Wang, Fanfan; Lu, Haiying; Ren, Xiaomei; Zou, Jihong


    Glucose-stimulated insulin secretion (GSIS) is a highly regulated process involving complex interaction of multiple factors. Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) is a susceptibility gene for type 2 diabetes (T2D) and the risk alleles of the KCNQ1 gene appear to be associated with impaired insulin secretion. The role of KCNQ1 channel in insulin secretion has been explored by previous work in clonal pancreatic β-cells but has yet to be investigated in the context of primary islets as well as intact animals. Genetic studies suggest that altered incretin glucagon-like peptide-1 (GLP-1) secretion might be a potential link between KCNQ1 variants and impaired insulin secretion, but this hypothesis has not been verified so far. In the current study, we examined KCNQ1 expression in pancreas and intestine from normal mice and then investigated the effects of chromanol 293B, a KCNQ1 channel inhibitor, on insulin secretion in vitro and in vivo. By double-immunofluorescence staining, KCNQ1 was detected in insulin-positive β-cells and GLP-1-positive L-cells. Administration of chromanol 293B enhanced GSIS in cultured islets and intact animals. Along with the potentiated insulin secretion during oral glucose tolerance tests (OGTT), plasma GLP-1 level after gastric glucose load was increased in 293B treated mice. These data not only provided new evidence for the participation of KCNQ1 in GSIS at the level of pancreatic islet and intact animal but also indicated the potential linking role of GLP-1 between KCNQ1 and insulin secretion.

  2. MCC-134, a blocker of mitochondrial and opener of sarcolemmal ATP-sensitive K+ channels, abrogates cardioprotective effects of chronic hypoxia

    Czech Academy of Sciences Publication Activity Database

    Kolář, František; Neckář, Jan; Ošťádal, Bohuslav


    Roč. 54, č. 4 (2005), s. 467-471 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/04/0465 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardioprotection * potassium channels * chronic hypoxia Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.806, year: 2005

  3. New distribution channels for advertising through computer games and mobile devices.


    Sivagnanasuntharam, Sivasathees


    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...

  4. KV7 potassium channels

    DEFF Research Database (Denmark)

    Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A


    Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

  5. Channel morphology [Chapter 5 (United States)

    Jonathan W. Long; Alvin L. Medina; Daniel G. Neary


    Channel morphology has become an increasingly important subject for analyzing the health of rivers and associated fish populations, particularly since the popularization of channel classification and assessment methods. Morphological data can help to evaluate the flows of sediment and water that influence aquatic and riparian habitat. Channel classification systems,...

  6. A novel KCNQ1 missense mutation identified in a patient with juvenile-onset atrial fibrillation causes constitutively open IKs channels. (United States)

    Hasegawa, Kanae; Ohno, Seiko; Ashihara, Takashi; Itoh, Hideki; Ding, Wei-Guang; Toyoda, Futoshi; Makiyama, Takeru; Aoki, Hisaaki; Nakamura, Yoshihide; Delisle, Brian P; Matsuura, Hiroshi; Horie, Minoru


    Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. In some patients, the disease is inheritable; however, hereditary aspects of AF remain not fully elucidated. The purpose of this study was to identify genetic backgrounds that contribute to juvenile-onset AF and to define the mechanism. In 30 consecutive juvenile-onset AF patients (onset age KCNQ1, KCNH2, KCNE1-3, KCNE5, KCNJ2, SCN5A). We analyzed the function of mutant channels using whole-cell patch-clamp techniques and computer simulations. Among the juvenile-onset AF patients, we identified three mutations (10%): SCN5A-M1875T, KCNJ2-M301K, and KCNQ1-G229D. Because KCNQ1 variant (G229D) identified in a 16-year-old boy was novel, we focused on the proband. The G229D-IKs was found to induce a large instantaneous activating component without deactivation after repolarization to -50 mV. In addition, wild-type (WT)/G229D-IKs (WT and mutant coexpression) displayed both instantaneous and time-dependent activating currents. Compared to WT-IKs, the tail current densities in WT/G229D-IKs were larger at test potentials between -130 and -40 mV but smaller at test potentials between 20 and 50 mV. Moreover, WT/G229D-IKs resulted in a negative voltage shift for current activation (-35.2 mV) and slower deactivation. WT/G229D-IKs conducted a large outward current induced by an atrial action potential waveform, and computer simulation incorporating the WT/G229D-IKs results revealed that the mutation shortened atrial but not ventricular action potential. A novel KCNQ1-G229D mutation identified in a juvenile-onset AF patient altered the IKs activity and kinetics, thereby increasing the arrhythmogenicity to AF. © 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.

  7. Increase of the cytotoxic effect of Bothrops jararacussu venom on mouse extensor digitorum longus and soleus by potassium channel blockers and by Na(+)/K(+)-ATPase inhibition. (United States)

    Tomaz, Marcelo A; Fernandes, Fabrício F A; El-Kik, Camila Z; Moraes, Raphael A M; Calil-Elias, Sabrina; Saturnino-Oliveira, Jeison; Martinez, Ana Maria B; Ownby, Charlotte L; Melo, Paulo A


    We investigated the myotoxicity of Bothrops jararacussu crude venom and other cytolytic agents on mouse isolated extensor digitorum longus (EDL) and soleus (SOL) muscles, which present distinct properties: EDL is a fast-twitch, white muscle with predominantly glycolytic fibers, while SOL is slow-twitch, red muscle with predominantly oxidative fibers. Muscles were exposed to B. jararacussu crude venom (25 microg/ml) and other crotaline venoms (Agkistrodon contortrix laticinctus; Crotalus viridis viridis; Crotalus durissus terrificus) at the same concentration. Basal creatine kinase (CK) release to bathing solution was 0.43+/-0.06 for EDL and 0.29+/-0.06 for SOL (U g(-)(1) h(-)(1), n=36 for each muscle). Sixty minutes after exposure to B. jararacussu venom, EDL presented higher increase in the rate of CK release than SOL, respectively, 13.2+/-1.5 and 2.9+/-0.7 U g(-)(1)h(-)(1), n=10-12. Muscle denervation, despite decreasing CK content, did not affect sensitivities to B. jararacussu venom. Ouabain and potassium channel blockers (TEA; clotrimazole; glibenclamide) increased the rate of CK release by B. jararacussu in EDL and SOL muscles, decreasing and almost abolishing the different sensitivity. When we exposed EDL or SOL muscles to Naja naja, Apis mellifera venoms (25 microg/ml), or Triton X-100 (0.01%), they showed similar rate of CK release. Our present data suggest that a mechanism involving intracellular calcium regulation or potassium channels may participate in the different sensitivity of EDL and SOL to B. jararacussu venom.

  8. A conserved residue cluster that governs kinetics of ATP-dependent gating of Kir6.2 potassium channels

    DEFF Research Database (Denmark)

    Zhang, Roger S; Wright, Jordan; Pless, Stephan Alexander


    elements that control the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels re-open after rapid washout of ATP with a time constant of approximately 60 ms. Extending similar kinetic measurements to numerous mutants revealed fairly...... modest effects on gating kinetics despite significant changes in ATP sensitivity and open probability. However, we identified a pair of highly conserved neighboring amino acids (Trp68, Lys170) that control the rate of channel opening and inhibition in response to ATP. Paradoxically, mutations of Trp68...... or Lys170 markedly slow the kinetics of channel opening (500 ms and 700 ms for Trp68Leu and Lys170Asn, respectively), while increasing channel open probability. Examining the functional effects of these residues using phi-value analysis revealed a steep negative slope. This finding implies...

  9. Interplay of Plasma Membrane and Vacuolar Ion Channels, Together with BAK1, Elicits Rapid Cytosolic Calcium Elevations in Arabidopsis during Aphid Feeding[OPEN (United States)

    Vincent, Thomas R.; Avramova, Marieta; Canham, James; Higgins, Peter; Bilkey, Natasha; Mugford, Sam T.; Pitino, Marco; Toyota, Masatsugu


    A transient rise in cytosolic calcium ion concentration is one of the main signals used by plants in perception of their environment. The role of calcium in the detection of abiotic stress is well documented; however, its role during biotic interactions remains unclear. Here, we use a fluorescent calcium biosensor (GCaMP3) in combination with the green peach aphid (Myzus persicae) as a tool to study Arabidopsis thaliana calcium dynamics in vivo and in real time during a live biotic interaction. We demonstrate rapid and highly localized plant calcium elevations around the feeding sites of M. persicae, and by monitoring aphid feeding behavior electrophysiologically, we demonstrate that these elevations correlate with aphid probing of epidermal and mesophyll cells. Furthermore, we dissect the molecular mechanisms involved, showing that interplay between the plant defense coreceptor BRASSINOSTEROID INSENSITIVE-ASSOCIATED KINASE1 (BAK1), the plasma membrane ion channels GLUTAMATE RECEPTOR-LIKE 3.3 and 3.6 (GLR3.3 and GLR3.6), and the vacuolar ion channel TWO-PORE CHANNEL1 (TPC1) mediate these calcium elevations. Consequently, we identify a link between plant perception of biotic threats by BAK1, cellular calcium entry mediated by GLRs, and intracellular calcium release by TPC1 during a biologically relevant interaction. PMID:28559475

  10. The Os-AKT1 Channel Is Critical for K+ Uptake in Rice Roots and Is Modulated by the Rice CBL1-CIPK23 Complex[W][OPEN (United States)

    Li, Juan; Long, Yu; Qi, Guo-Ning; Li, Juan; Xu, Zi-Jian; Wu, Wei-Hua; Wang, Yi


    Potassium (K+) is one of the essential nutrient elements for plant growth and development. Plants absorb K+ ions from the environment via root cell K+ channels and/or transporters. In this study, the Shaker K+ channel Os-AKT1 was characterized for its function in K+ uptake in rice (Oryza sativa) roots, and its regulation by Os-CBL1 (Calcineurin B-Like protein1) and Os-CIPK23 (CBL-Interacting Protein Kinase23) was investigated. As an inward K+ channel, Os-AKT1 could carry out K+ uptake and rescue the low-K+-sensitive phenotype of Arabidopsis thaliana akt1 mutant plants. Rice Os-akt1 mutant plants showed decreased K+ uptake and displayed an obvious low-K+-sensitive phenotype. Disruption of Os-AKT1 significantly reduced the K+ content, which resulted in inhibition of plant growth and development. Similar to the AKT1 regulation in Arabidopsis, Os-CBL1 and Os-CIPK23 were identified as the upstream regulators of Os-AKT1 in rice. The Os-CBL1-Os-CIPK23 complex could enhance Os-AKT1-mediated K+ uptake. A phenotype test confirmed that Os-CIPK23 RNAi lines exhibited similar K+-deficient symptoms as the Os-akt1 mutant under low K+ conditions. These findings demonstrate that Os-AKT1-mediated K+ uptake in rice roots is modulated by the Os-CBL1-Os-CIPK23 complex. PMID:25096783

  11. The voltage-dependent action of pentobarbital on batrachotoxin-modified human brain sodium channels. (United States)

    Rehberg, B; Duch, D S; Urban, B W


    The voltage-dependent action of the intravenous anesthetic pentobarbital on human brain sodium channels activated by batrachotoxin was examined using planar lipid bilayer methods. Fractional open time-data were fitted by Boltzmann functions to yield simple parameters characterizing the voltage-dependence of the fractional open time. Pentobarbital caused a dose-dependent reduction of the maximum fractional open time of the sodium channel and a shift of the potential of half-maximal open time towards hyperpolarized potentials, whereas the slope parameter of the Boltzmann-fits was unaffected. A statistically significant increase of the variability of these parameters was found only in the case of the maximum fractional open time, indicating a random fluctuation of pentobarbital-induced suppression of the sodium channels over time. The voltage-dependent action of pentobarbital probably results from either a pentobarbital-modification of channel activation gating and/or a modification of the pentobarbital action by the gating process itself.

  12. The increased cost of medical services for people diagnosed with primary open-angle glaucoma: a decision analytic approach. (United States)

    Kymes, Steven M; Plotzke, Michael R; Li, Jim Z; Nichol, Michael B; Wu, Joanne; Fain, Joel


    Glaucoma accounts for more than 11% of all cases of blindness in the United States, but there have been few studies of economic impact. We examine incremental cost of primary open-angle glaucoma considering both visual and nonvisual medical costs over a lifetime of glaucoma. A decision analytic approach taking the payor's perspective with microsimulation estimation. We constructed a Markov model to replicate health events over the remaining lifetime of someone newly diagnosed with glaucoma. Costs of this group were compared with those estimated for a control group without glaucoma. The cost of management of glaucoma (including medications) before the onset of visual impairment was not considered. The model was populated with probability data estimated from Medicare claims data (1999 through 2005). Cost of nonocular medications and nursing home use was estimated from California Medicare claims, and all other costs were estimated from Medicare claims data. We found modest differences in the incidence of comorbid conditions and health service use between people with glaucoma and the control group. Over their expected lifetime, the cost of care for people with primary open-angle glaucoma was higher than that of people without primary open-angle glaucoma by $1688 or approximately $137 per year. Among Medicare beneficiaries, glaucoma diagnosis not found to be associated with significant risk of comorbidities before development of visual impairment. Further study is necessary to consider the impact of glaucoma on quality of life, as well as aspects of physical and visual function not captured in this claims-based analysis. 2010 Elsevier Inc. All rights reserved.

  13. 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: [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)


    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.

  14. Parsing the Mechanisms that Increase Relational Intimacy: The Effects of Uncertainty Amount, Open Communication about Uncertainty, and the Reduction of Uncertainty (United States)

    Theiss, Jennifer A.; Solomon, Denise Haunani


    This study examined amount of uncertainty, openness of communication about uncertainty, and the uncertainty reduction process as three competing mechanisms that account for increased intimacy in romantic relationships. To test these competing mechanisms, we used multilevel modeling to analyze longitudinal data that were collected from individuals…

  15. Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia. (United States)

    Farrag, Mohamed; Drobish, Julie K; Puhl, Henry L; Kim, Joyce S; Herold, Paul B; Kaufman, Marc P; Ruiz-Velasco, Victor


    Chronic limb ischaemia, characterized by inflammatory mediator release and a low extracellular pH, leads to acid-sensing ion channel (ASIC) activation and reflexively increases mean arterial pressure; endomorphin release is also increased under inflammatory conditions. We examined the modulation of ASIC currents by endomorphins in sensory neurons from rats with freely perfused and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins potentiated sustained ASIC currents in both groups of dorsal root ganglion neurons, independent of mu opioid receptor stimulation or G protein activation. Intra-arterial administration of lactic acid (to simulate exercising muscle and evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly greater pressor response than lactic acid alone, while administration of APETx2 inhibited endomorphin's enhancing effect in both groups. These results suggest a novel role for endomorphins in modulating ASIC function to effect lactic acid-mediated reflex increase in arterial pressure in patients with PAD. Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed

  16. An experimental and simulation study of novel channel designs for open-cathode high-temperature polymer electrolyte membrane fuel cells

    DEFF Research Database (Denmark)

    Thomas, Sobi; Bates, Alex; Park, Sam


    without pins and another with pins. A five-cell stack was fabricated in the lab based on the new design. Performance and flow distribution studies revealed better performance, uniform flow distribution, and a reduced temperature gradient across the stack; improving overall system efficiency.......A minimum balance of plant (BOP) is desired for an open-cathode high temperature polymer electrolyte membrane (HTPEM) fuel cell to ensure low parasitic losses and a compact design. The advantage of an open-cathode system is the elimination of the coolant plate and incorporation of a blower...... for oxidant and coolant supply, which reduces the overall size of the stack, power losses, and results in a lower system volume. In the present study, we present unique designs for an open-cathode system which offers uniform temperature distribution with a minimum temperature gradient and a uniform flow...

  17. 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.

  18. p53 increases intra-cellular calcium release by transcriptional regulation of calcium channel TRPC6 in GaQ3-treated cancer cells. (United States)

    Madan, Esha; Gogna, Rajan; Keppler, Bernhard; Pati, Uttam


    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.

  19. Influence of shallowness, bank inclination and bank roughness on the variability of flow patterns and boundary shear stress due to secondary currents in straight open-channels (United States)

    Blanckaert, K.; Duarte, A.; Schleiss, A. J.


    Boundary shear stress and flow variability due to its interaction with main flow and secondary currents were investigated under conditions that extend previous research on trapezoidal channels. Secondary currents that scale with the flow depth were found over the entire width in all experiments. These findings contradict the widespread perception that secondary currents die out at a distance of 2.5 times the flow depth from the bank, a perception which is largely based on experiments with smooth boundaries. The reported results indicate that a stable pattern of secondary currents over the entire channel width can only be sustained over a fixed horizontal bed if the bed's roughness is sufficient to provide the required transverse oscillations in the turbulent shear stresses. Contrary to laboratory flumes, alluvial river bed always provide sufficient roughness. The required external forcing of this hydrodynamic instability mechanism is provided by the turbulence-generated near-bank secondary currents. The pattern of near-bank secondary currents depends on the inclination and the roughness of the bank. In all configurations, secondary currents result in a reduction of the bed shear stress in the vicinity of the bank and a heterogeneous bank shear stress that reaches a maximum close to the toe of the bank. Moreover, these currents cause transverse variability of 10-15% for the streamwise velocities and 0.2 u*2-0.3 u* 2 for the bed shear stress. These variations are insufficient to provide the flow variability required in river restoration projects, but nevertheless must be accounted for in the design of stable channels.

  20. The Oxidative Stress-Induced Increase in the Membrane Expression of the Water-Permeable Channel Aquaporin-4 in Astrocytes Is Regulated by Caveolin-1 Phosphorylation

    Directory of Open Access Journals (Sweden)

    Chongshan Bi


    Full Text Available The reperfusion of ischemic brain tissue following a cerebral stroke causes oxidative stress, and leads to the generation of reactive oxygen species (ROS. Apart from inflicting oxidative damage, the latter may also trigger the upregulation of aquaporin 4 (AQP4, a water-permeable channel expressed by astroglial cells of the blood-brain barrier (BBB, and contribute to edema formation, the severity of which is known to be the primary determinant of mortality and morbidity. The mechanism through which this occurs remains unknown. In the present study, we have attempted to address this question using primary astrocyte cultures treated with hydrogen peroxide (H2O2 as a model system. First, we showed that H2O2 induces a significant increase in AQP4 protein levels and that this is inhibited by the antioxidant N-acetylcysteine (NAC. Second, we demonstrated using cell surface biotinylation that H2O2 increases AQP4 cell-surface expression independently of it’s increased synthesis. In parallel, we found that caveolin-1 (Cav1 is phosphorylated in response to H2O2 and that this is reversed by the Src kinase inhibitor 4-Amino-5-(4-chlorophenyl-7-(t-butylpyrazolo[3,4-d]pyrimidine (PP2. PP2 also abrogated the H2O2-induced increase in AQP4 surface levels, suggesting that  the phosphorylation of tyrosine-14 of Cav1 regulates  this  process. We  further  showed  that dominant-negative Y14F and phosphomimetic Y14D mutants caused a decrease and increase in AQP4 membrane expression respectively, and that the knockdown of Cav1 inhibits the increase in AQP4 cell-surface, expression following H2O2 treatment. Together, these findings suggest that oxidative stress-induced Cav1 phosphorylation modulates AQP4 subcellular distribution and therefore may indirectly regulate AQP4-mediated water transport.

  1. Co-expression of mCysLT1 receptors and IK channels in Xenopus laevis oocytes elicits LTD4-stimulated IK current, independent of an increase in [Ca2+]i

    DEFF Research Database (Denmark)

    Wulff, Tune; Hougaard, Charlotte; Klaerke, Dan A


    Addition of LTD4 (10 nM) to Xenopus laevis oocytes expressing the mCysLT1 receptor together with hBK or hIK channels resulted in the activation of both channels secondary to an LTD4-induced increase in [Ca2+]i. In addition, the hIK channel is activated by low concentrations of LTD4 (0.1 nM), which...... to LTD4. Neither hTBAK1 nor hTASK2 was activated following stimulations with LTD4 (0.1 and 100 nM)....

  2. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter


    . The underlying posttranscriptional and posttranslational remodeling of the individual K(+) channels changes their activity and significance relative to each other, and they must be viewed together to understand their role in keeping a stable heart rhythm, also under menacing conditions like attacks of reentry......About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...

  3. Le Chatelier's principle with multiple relaxation channels (United States)

    Gilmore, R.; Levine, R. D.


    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.

  4. Cl- channels in apoptosis

    DEFF Research Database (Denmark)

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida


    A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K(+), Cl(-), and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl(-) channels LRRC8, TMEM16/anoctamin......, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also...

  5. The SpikerBox: a low cost, open-source bioamplifier for increasing public participation in neuroscience inquiry.

    Directory of Open Access Journals (Sweden)

    Timothy C Marzullo

    Full Text Available Although people are generally interested in how the brain functions, neuroscience education for the public is hampered by a lack of low cost and engaging teaching materials. To address this, we developed an open-source tool, the SpikerBox, which is appropriate for use in middle/high school educational programs and by amateurs. This device can be used in easy experiments in which students insert sewing pins into the leg of a cockroach, or other invertebrate, to amplify and listen to the electrical activity of neurons. With the cockroach leg preparation, students can hear and see (using a smartphone oscilloscope app we have developed the dramatic changes in activity caused by touching the mechanosensitive barbs. Students can also experiment with other manipulations such as temperature, drugs, and microstimulation that affect the neural activity. We include teaching guides and other resources in the supplemental materials. These hands-on lessons with the SpikerBox have proven to be effective in teaching basic neuroscience.

  6. The SpikerBox: A Low Cost, Open-Source BioAmplifier for Increasing Public Participation in Neuroscience Inquiry (United States)

    Marzullo, Timothy C.; Gage, Gregory J.


    Although people are generally interested in how the brain functions, neuroscience education for the public is hampered by a lack of low cost and engaging teaching materials. To address this, we developed an open-source tool, the SpikerBox, which is appropriate for use in middle/high school educational programs and by amateurs. This device can be used in easy experiments in which students insert sewing pins into the leg of a cockroach, or other invertebrate, to amplify and listen to the electrical activity of neurons. With the cockroach leg preparation, students can hear and see (using a smartphone oscilloscope app we have developed) the dramatic changes in activity caused by touching the mechanosensitive barbs. Students can also experiment with other manipulations such as temperature, drugs, and microstimulation that affect the neural activity. We include teaching guides and other resources in the supplemental materials. These hands-on lessons with the SpikerBox have proven to be effective in teaching basic neuroscience. PMID:22470415

  7. The SpikerBox: a low cost, open-source bioamplifier for increasing public participation in neuroscience inquiry. (United States)

    Marzullo, Timothy C; Gage, Gregory J


    Although people are generally interested in how the brain functions, neuroscience education for the public is hampered by a lack of low cost and engaging teaching materials. To address this, we developed an open-source tool, the SpikerBox, which is appropriate for use in middle/high school educational programs and by amateurs. This device can be used in easy experiments in which students insert sewing pins into the leg of a cockroach, or other invertebrate, to amplify and listen to the electrical activity of neurons. With the cockroach leg preparation, students can hear and see (using a smartphone oscilloscope app we have developed) the dramatic changes in activity caused by touching the mechanosensitive barbs. Students can also experiment with other manipulations such as temperature, drugs, and microstimulation that affect the neural activity. We include teaching guides and other resources in the supplemental materials. These hands-on lessons with the SpikerBox have proven to be effective in teaching basic neuroscience.

  8. 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


    demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation...... mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce...... VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline: 1.0 +/- 0.2 nM: 6/12 vs 0/12; 7.7 +/- 0.6 nM: 7/13 vs 1...

  9. Trusted Communication in SDN OpenFlow Channel : Investigating Assumed Trusted Communication between SDN Controller and Switch and Possible Attack Scenarios


    Haapajärvi, Marika


    Originally the subject of the research was Software Defined Networking (SDN) and particularly the threats towards the architecture and the SDN controller. However, during the research, it became evident that the protocol under research, OpenFlow itself had features which may turn into threats under the hands of a malicious actor outside the SDN network. The features may have vulnerabilities that may transform into threats should an attacker gain access to the SDN network. The verification ...

  10. Voltage-gated lipid ion channels

    DEFF Research Database (Denmark)

    Blicher, Andreas; Heimburg, Thomas Rainer


    probability as a function of voltage. The voltage-dependence of the lipid pores is found comparable to that of protein channels. Lifetime distributions of open and closed events indicate that the channel open distribution does not follow exponential statistics but rather power law behavior for long open times...

  11. The KATP channel in migraine pathophysiology

    DEFF Research Database (Denmark)

    Al-Karagholi, Mohammad Al-Mahdi; Hansen, Jakob Møller; Severinsen, Johanne


    BACKGROUND: To review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. DISCUSSION: KATP channels are widely present in the trigeminovascular system and play...... an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic KATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that KATP channel opening may cause headache, possibly due to vascular mechanisms. Whether KATP...... channel openers can provoke migraine in migraine sufferers is not known. CONCLUSION: We suggest that KATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target....

  12. Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat

    DEFF Research Database (Denmark)

    Stankevicius, Edgaras; Dalsgaard, Thomas; Kroigaard, Christel


    This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium-derived hyperpolar......This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium...... in human umbilical vein endothelial cells (HUVECs), and calcium concentrations were investigated in both HUVECs and mesenteric arterial endothelial cells. In both superior (∼1093 μm) and small mesenteric (∼300 μm) arteries, NS309 evoked endothelium- and concentration-dependent relaxations. In superior....... In small mesenteric arteries, NS309 relaxations were reduced slightly by ADMA, whereas apamin plus an IK(Ca) channel blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation. HUVECs expressed mRNA for SK(Ca) and IK(Ca) channels, and NS309 induced increases in calcium, outward...

  13. Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1). (United States)

    Musrap, Natasha; Tuccitto, Alessandra; Karagiannis, George S; Saraon, Punit; Batruch, Ihor; Diamandis, Eleftherios P


    Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs. Given that the presence of metastatic implants is a predictor of poor survival, a better understanding of how spheroids form is critical to improving patient outcome, and may result in the identification of novel therapeutic targets. Thus, we attempted to gain insight into the proteomic changes that occur during anchorage-independent cancer cell aggregation. As such, an ovarian cancer cell line, OV-90, was cultured in adherent and non-adherent conditions using stable isotope labeling with amino acids in cell culture (SILAC). Anchorage-dependent cells (OV-90AD) were grown in tissue culture flasks, whereas anchorage-independent cells (OV-90AI) were grown in suspension using the hanging-drop method. Cellular proteins from both conditions were then identified using LC-MS/MS, which resulted in the quantification of 1533 proteins. Of these, 13 and 6 proteins were up-regulated and down-regulated, respectively, in aggregate-forming cells compared with cells grown as monolayers. Relative gene expression and protein expression of candidates were examined in other cell line models of aggregate formation (TOV-112D and ES-2), which revealed an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). Moreover, inhibitor and siRNA transfection studies demonstrated an apparent effect of CLCA1 on cancer cell aggregation. Further elucidation of the role of CLCA1 in the pathogenesis of ovarian cancer is warranted. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Oxaliplatin administration increases expression of the voltage-dependent calcium channel α2δ-1 subunit in the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Ken Yamamoto


    Full Text Available Oxaliplatin is a chemotherapeutic agent that is effective against various types of cancer including colorectal cancer. Acute cold hyperalgesia is a serious side effect of oxaliplatin treatment. Although the therapeutic drug pregabalin is beneficial for preventing peripheral neuropathic pain by targeting the voltage-dependent calcium channel α2δ-1 (Cavα2δ-1 subunit, the effect of oxaliplatin-induced acute cold hypersensitivity is uncertain. To analyze the contribution of the Cavα2δ-1 subunit to the development of oxaliplatin-induced acute cold hypersensitivity, Cavα2δ-1 subunit expression in the rat spinal cord was analyzed after oxaliplatin treatment. Behavioral assessment using the acetone spray test showed that 6 mg/kg oxaliplatin-induced cold hypersensitivity 2 and 4 days later. Oxaliplatin-induced acute cold hypersensitivity 4 days after treatment was significantly inhibited by pregabalin (50 mg/kg, p.o.. Oxaliplatin (6 mg/kg, i.p. treatment increased the expression level of Cavα2δ-1 subunit mRNA and protein in the spinal cord 2 and 4 days after treatment. Immunohistochemistry showed that oxaliplatin increased Cavα2δ-1 subunit protein expression in superficial layers of the spinal dorsal horn 2 and 4 days after treatment. These results suggest that oxaliplatin treatment increases Cavα2δ-1 subunit expression in the superficial layers of the spinal cord and may contribute to functional peripheral acute cold hypersensitivity.

  15. The temperature dependence of the BK channel activity - kinetics, thermodynamics, and long-range correlations. (United States)

    Wawrzkiewicz-Jałowiecka, Agata; Dworakowska, Beata; Grzywna, Zbigniew J


    Large-conductance, voltage dependent, Ca 2+ -activated potassium channels (BK) are transmembrane proteins that regulate many biological processes by controlling potassium flow across cell membranes. Here, we investigate to what extent temperature (in the range of 17-37°C with ΔT=5°C step) is a regulating parameter of kinetic properties of the channel gating and memory effect in the series of dwell-time series of subsequent channel's states, at membrane depolarization and hyperpolarization. The obtained results indicate that temperature affects strongly the BK channels' gating, but, counterintuitively, it exerts no effect on the long-range correlations, as measured by the Hurst coefficient. Quantitative differences between dependencies of appropriate channel's characteristics on temperature are evident for different regimes of voltage. Examining the characteristics of BK channel activity as a function of temperature allows to estimate the net activation energy (E act ) and changes of thermodynamic parameters (ΔH, ΔS, ΔG) by channel opening. Larger E act corresponds to the channel activity at membrane hyperpolarization. The analysis of entropy and enthalpy changes of closed to open channel's transition suggest the entropy-driven nature of the increase of open state probability during voltage activation and supports the hypothesis about the voltage-dependent geometry of the channel vestibule. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Mechanosensitive gating of Kv channels.

    Directory of Open Access Journals (Sweden)

    Catherine E Morris

    Full Text Available K-selective voltage-gated channels (Kv are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS Popen(V implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses to a cooperative V-dependent closed-closed expansion↔compaction transition near the open state, Mackinnon and colleagues invoke expansion during a V-independent closed↔open transition. With increasing membrane tension, they suggest, the closed↔open equilibrium constant, L, can increase >100-fold, thereby taking steady-state Popen from 0→1; "exquisite sensitivity to small…mechanical perturbations", they state, makes a Kv "as much a mechanosensitive…as…a voltage-dependent channel". Devised to explain successive gK(V curves in excised patches where tension spontaneously increased until lysis, their L-based model falters in part because of an overlooked IK feature; with recovery from slow inactivation factored in, their g(V datasets are fully explained by the earlier model (a MS V-dependent closed-closed transition, invariant L≥4. An L-based MS-Kv predicts neither known Kv time courses nor the distinctive MS responses of Kv-ILT. It predicts Kv densities (hence gating charge per V-sensor several-fold different from established values. If opening depended on elevated tension (L-based model, standard gK(V operation would be compromised by animal cells' membrane flaccidity. A MS V-dependent transition is, by contrast, unproblematic on all counts. Since these issues bear directly on recent findings that mechanically-modulated Kv channels subtly tune pain-related excitability in peripheral mechanoreceptor neurons we undertook excitability modeling (evoked action potentials. Kvs with MS V-dependent closed-closed transitions produce nuanced mechanically-modulated excitability whereas an L-based MS-Kv yields extreme, possibly excessive

  17. 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


    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

  18. Model Based Open-Loop Wind Farm Control Using Active Power for Power Increase and Load Reduction


    Hyungyu Kim; Kwansu Kim; Insu Paek


    A new wind farm control algorithm that adjusts the power output of the most upstream wind turbine in a wind farm for power increase and load reduction was developed in this study. The algorithm finds power commands to individual wind turbines to maximize the total power output from the wind farm when the power command from the transmission system operator is larger than the total available power from the wind farm. To validate this wind farm control algorithm, a relatively high fidelity wind ...

  19. Crystal structure of snake venom acetylcholinesterase in complex with inhibitory antibody fragment Fab410 bound at the peripheral site: evidence for open and closed states of a back door channel. (United States)

    Bourne, Yves; Renault, Ludovic; Marchot, Pascale


    The acetylcholinesterase found in the venom of Bungarus fasciatus (BfAChE) is produced as a soluble, non-amphiphilic monomer with a canonical catalytic domain but a distinct C terminus compared with the other vertebrate enzymes. Moreover, the peripheral anionic site of BfAChE, a surface site located at the active site gorge entrance, bears two substitutions altering sensitivity to cationic inhibitors. Antibody Elec410, generated against Electrophorus electricus acetylcholinesterase (EeAChE), inhibits EeAChE and BfAChE by binding to their peripheral sites. However, both complexes retain significant residual catalytic activity, suggesting incomplete gorge occlusion by bound antibody and/or high frequency back door opening. To explore a novel acetylcholinesterase species, ascertain the molecular bases of inhibition by Elec410, and document the determinants and mechanisms for back door opening, we solved a 2.7-Å resolution crystal structure of natural BfAChE in complex with antibody fragment Fab410. Crystalline BfAChE forms the canonical dimer found in all acetylcholinesterase structures. Equally represented open and closed states of a back door channel, associated with alternate positions of a tyrosine phenol ring at the active site base, coexist in each subunit. At the BfAChE molecular surface, Fab410 is seated on the long Ω-loop between two N-glycan chains and partially occludes the gorge entrance, a position that fully reflects the available mutagenesis and biochemical data. Experimentally based flexible molecular docking supports a similar Fab410 binding mode onto the EeAChE antigen. These data document the molecular and dynamic peculiarities of BfAChE with high frequency back door opening, and the mode of action of Elec410 as one of the largest peptidic inhibitors targeting the acetylcholinesterase peripheral site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Batrachotoxin-modified sodium channels from squid optic nerve in planar bilayers. Ion conduction and gating properties (United States)


    Squid optic nerve sodium channels were characterized in planar bilayers in the presence of batrachotoxin (BTX). The channel exhibits a conductance of 20 pS in symmetrical 200 mM NaCl and behaves as a sodium electrode. The single-channel conductance saturates with increasing the concentration of sodium and the channel conductance vs. sodium concentration relation is well described by a simple rectangular hyperbola. The apparent dissociation constant of the channel for sodium is 11 mM and the maximal conductance is 23 pS. The selectivity determined from reversal potentials obtained in mixed ionic conditions is Na+ approximately Li+ greater than K+ greater than Rb+ greater than Cs+. Calcium blocks the channel in a voltage-dependent manner. Analysis of single-channel membranes showed that the probability of being open (Po) vs. voltage relation is sigmoidal with a value of 0.5 between -90 and -100 mV. The fitting of Po requires at least two closed and one open state. The apparent gating charge required to move through the whole transmembrane voltage during the closed-open transition is four to five electronic charges per channel. Distribution of open and closed times are well described by single exponentials in most of the voltage range tested and mean open and mean closed times are voltage dependent. The number of charges associated with channel closing is 1.6 electronic charges per channel. Tetrodotoxin blocked the BTX-modified channel being the blockade favored by negative voltages. The apparent dissociation constant at zero potential is 16 nM. We concluded that sodium channels from the squid optic nerve are similar to other BTX- modified channels reconstituted in bilayers and to the BTX-modified sodium channel detected in the squid giant axon. PMID:2536797

  1. Course on Ionic Channels

    CERN Document Server


    This book is based on a series of lectures for a course on ionic channels held in Santiago, Chile, on November 17-20, 1984. It is intended as a tutorial guide on the properties, function, modulation, and reconstitution of ionic channels, and it should be accessible to graduate students taking their first steps in this field. In the presentation there has been a deliberate emphasis on the spe­ cific methodologies used toward the understanding of the workings and function of channels. Thus, in the first section, we learn to "read" single­ channel records: how to interpret them in the theoretical frame of kinetic models, which information can be extracted from gating currents in re­ lation to the closing and opening processes, and how ion transport through an open channel can be explained in terms of fluctuating energy barriers. The importance of assessing unequivocally the origin and purity of mem­ brane preparations and the use of membrane vesicles and optical tech­ niques in the stUGY of ionic channels a...

  2. Insulin activates single amiloride-blockable Na channels in a distal nephron cell line (A6). (United States)

    Marunaka, Y; Hagiwara, N; Tohda, H


    Using the patch-clamp technique, we studied the effect of insulin on an amiloride-blockable Na channel in the apical membrane of a distal nephron cell line (A6) cultured on permeable collagen films for 10-14 days. NPo (N, number of channels per patch membrane; Po, average value of open probability of individual channels in the patch) under baseline conditions was 0.88 +/- 0.12 (SE)(n = 17). After making cell-attached patches on the apical membrane which contained Na channels, insulin (1 mU/ml) was applied to the serosal bath. While maintaining the cell-attached patch, NPo significantly increased to 1.48 +/- 0.19 (n = 17; P less than 0.001) after 5-10 min of insulin application. The open probability of Na channels was 0.39 +/- 0.01 (n = 38) under baseline condition, and increased to 0.66 +/- 0.03 (n = 38, P less than 0.001) after addition of insulin. The baseline single-channel conductance was 4pS, and neither the single-channel conductance nor the current-voltage relationship was significantly changed by insulin. These results indicate that insulin increases Na absorption in the distal nephron by increasing the open probability of the amiloride-blockable Na channel.

  3. Regulation of BK channels by auxiliary γ subunits

    Directory of Open Access Journals (Sweden)

    Jiyuan eZhang


    Full Text Available The large-conductance, calcium- and voltage-activated potassium (BK channel has the largest single-channel conductance among potassium channels and can be activated by both membrane depolarization and increases in intracellular calcium concentration. BK channels consist of pore-forming, voltage- and calcium-sensing α subunits, either alone or in association with regulatory subunits. BK channels are widely expressed in various tissues and cells including both excitable and non-excitable cells and display diverse biophysical and pharmacological characteristics. This diversity can be explained in part by posttranslational modifications and alternative splicing of the α subunit, which is encoded by a single gene, KCNMA1, as well as by tissue-specific β subunit modulation. Recently, a leucine-rich repeat-containing membrane protein, LRRC26, was found to interact with BK channels and cause an unprecedented large negative shift (~-140 mV in the voltage dependence of the BK channel activation. LRRC26 allows BK channels to open even at near-physiological calcium concentration and membrane voltage in non-excitable cells. Three LRRC26-related proteins, LRRC52, LRRC55, and LRRC38, were subsequently identified as BK channel modulators. These LRRC proteins are structurally and functionally distinct from the BK channel β subunits and were designated as γ subunits. The discovery of the γ subunits adds a new dimension to BK channel regulation and improves our understanding of the physiological functions of BK channels in various tissues and cell types. Unlike BK channel β subunits, which have been intensively investigated both mechanistically and physiologically, our understanding of the γ subunits is very limited at this stage. This article reviews the structure, modulatory mechanisms, physiological relevance, and potential therapeutic implications of γ subunits as they are currently understood.

  4. Nerve injury-induced calcium channel alpha-2-delta-1 protein dysregulation leads to increased pre-synaptic excitatory input into deep dorsal horn neurons and neuropathic allodynia (United States)

    Zhou, Chunyi; Luo, Z. David


    Background Upregulation of voltage-gated-calcium-channel α2δ1 subunit post spinal nerve ligation injury (SNL) or in α2δ1-overexpressing transgenic (Tg) mice correlates with tactile allodynia, a pain state mediated mainly by Aβ sensory fibers forming synaptic connections with deep dorsal horn neurons. It is not clear however whether dysregulated α2δ1 alters deep dorsal horn synaptic neurotransmission that underlies tactile allodynia development post nerve injury. Methods Tactile allodynia was tested in the SNL and α2δ1 Tg models. Miniature excitatory/inhibitory postsynaptic currents were recorded in deep dorsal horn (DDH) neurons from these animal models using whole cell patch clamp slice recording techniques.. Results There was a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSC) in DDH neurons that correlated with tactile allodynia in SNL and α2δ1 Tg mice. Gabapentin, an α2δ1 ligand that is known to block tactile allodynia in these models, also normalized mEPSC frequency dose-dependently in DDH neurons from SNL and α2δ1 Tg mice. In contrast, neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSC) was altered in DDH neurons from SNL and α2δ1 Tg mice. Conclusion Our data suggest that α2δ1 dysregulation is highly likely contributing to tactile allodynia through a pre-synaptic mechanism involving facilitation of excitatory synaptic neurotransmission in deep dorsal horn of spinal cord. PMID:25691360

  5. Differential effect of brief electrical stimulation on voltage-gated potassium channels. (United States)

    Cameron, Morven A; Al Abed, Amr; Buskila, Yossi; Dokos, Socrates; Lovell, Nigel H; Morley, John W


    Electrical stimulation of neuronal tissue is a promising strategy to treat a variety of neurological disorders. The mechanism of neuronal activation by external electrical stimulation is governed by voltage-gated ion channels. This stimulus, typically brief in nature, leads to membrane potential depolarization, which increases ion flow across the membrane by increasing the open probability of these voltage-gated channels. In spiking neurons, it is activation of voltage-gated sodium channels (Na V channels) that leads to action potential generation. However, several other types of voltage-gated channels are expressed that also respond to electrical stimulation. In this study, we examine the response of voltage-gated potassium channels (K V channels) to brief electrical stimulation by whole cell patch-clamp electrophysiology and computational modeling. We show that nonspiking amacrine neurons of the retina exhibit a large variety of responses to stimulation, driven by different K V -channel subtypes. Computational modeling reveals substantial differences in the response of specific K V -channel subtypes that is dependent on channel kinetics. This suggests that the expression levels of different K V -channel subtypes in retinal neurons are a crucial predictor of the response that can be obtained. These data expand our knowledge of the mechanisms of neuronal activation and suggest that K V -channel expression is an important determinant of the sensitivity of neurons to electrical stimulation. NEW & NOTEWORTHY This paper describes the response of various voltage-gated potassium channels (K V channels) to brief electrical stimulation, such as is applied during prosthetic electrical stimulation. We show that the pattern of response greatly varies between K V channel subtypes depending on activation and inactivation kinetics of each channel. Our data suggest that problems encountered when artificially stimulating neurons such as cessation in firing at high frequencies, or

  6. BK channel modulators: a comprehensive overview

    DEFF Research Database (Denmark)

    Nardi, Antonio; Olesen, Søren-Peter


    The large Ca(2+)-activated K(+) channel (BK channel) reflects per excellence the dilemma of the molecular target driven drug discovery process. Significant experimental evidence suggests that the BK channels play a pivotal and specific role in many pathophysiological conditions supporting...... the notion that the channel represents an innovative and promising drug target. However, after more than ten years of intense research effort both in academia and industry, scientists have yet to witness the approval of a single BK channel modulator for clinical use. On the contrary, three BK openers...... 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...

  7. Insights into an intriguing gas sorption mechanism in a polar metal–organic framework with open-metal sites and narrow channels

    KAUST Repository

    Forrest, Katherine A.


    Simulations of H2 and CO2 sorption were performed in the metal-organic framework (MOF), [Cu(Me-4py-trz-ia)]. This MOF was recently shown experimentally to exhibit high uptake for H2 and CO2 sorption and this was reproduced and elucidated through the simulations performed herein. Consistent with experiment, the theoretical isosteric heat of adsorption, Qst, values were nearly constant across all loadings for both sorbates. The simulations revealed that sorption directly onto the open-metal sites was not observed in this MOF, ostensibly a consequence of the low partial positive charges of the Cu2+ ions as determined through electronic structure calculations. Sorption was primarily observed between adjacent carboxylate oxygen atoms (site 1) and between nearby methyl groups (site 2) of the organic linkers. In addition, saturation of the most energetically favorable sites (site 1) is possible only after filling a nearby site (site 2) first due to the MOF topology. This suggests that the lack of dependence on loading for the Qst is due to the concurrent filling of sites 1 and 2, leading to an observed average Qst value. © 2014 the Partner Organisations.


    Directory of Open Access Journals (Sweden)

    S.V. Isayenkov


    Full Text Available The main aim of this study was to investigate the role of potassium TPK channel (OsTPKa from rice in regulation of salinity and drought stresses, potassium deficiency. In order to elevate the expression level of gene encoding two-pore potassium channel OsTPKa, the stable agrobacterium mediated transformation of plants was performed. The elevation of OsTPKa expression level in transformed plants leads to improvement of salt and drought tolerance of transformed plants was found during experiments. In conditions of potassium deficiency or salt stress the plants with elevated OsTPKa expression level exhibit better growth rates, decreasing of sodium accumulation in plant tissues.

  9. El Tor hemolysin of Vibrio cholerae O1 forms channels in planar lipid bilayer membranes. (United States)

    Ikigai, H; Ono, T; Iwata, M; Nakae, T; Shimamura, T


    We investigated the channel formation by El Tor hemolysin (molecular mass, 65 kDa) of Vibrio cholerae O1 biotype El Tor in planar lipid bilayers. The El Tor hemolysin channel exhibited asymmetric and hyperbolic membrane current with increasing membrane potential, meaning that the channel is voltage dependent. The zero-current membrane potential measured in KCI solution showed that permeability ratio PK+/PCl- was 0.16, indicating that the channel is 6-fold more anion selective over cation. The hemolysin channel frequently flickered in the presence of divalent cations, suggesting that the channel spontaneously opens and closes. These data imply that the El Tor hemolysin damages target cells by the formation of transmembrane channels and, consequently, is the cause of osmotic cytolysis.

  10. Batrachotoxin-activated Na+ channels in planar lipid bilayers. Competition of tetrodotoxin block by Na+. (United States)

    Moczydlowski, E; Garber, S S; Miller, C


    Single Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers formed from neutral phospholipids and were observed in the presence of batrachotoxin. The batrachotoxin-modified channel activates in the voltage range -120 to -80 mV and remains open almost all the time at voltages positive to -60 mV. Low levels of tetrodotoxin (TTX) induce slow fluctuations of channel current, which represent the binding and dissociation of single TTX molecules to single channels. The rates of association and dissociation of TTX are both voltage dependent, and the association rate is competitively inhibited by Na+. This inhibition is observed only when Na+ is increased on the TTX binding side of the channel. The results suggest that the TTX receptor site is located at the channel's outer mouth, and that the Na+ competition site is not located deeply within the channel's conduction pathway.

  11. [[Durable persistence of a biocompatible foreign body in a vertebral channel in open penetrating trauma of a spinal cord: clinico-experimental and pathomorphological peculiarities]. (United States)

    Tsymbalyuk, V I; Medvedyev, V V; Semenova, V M; Grydina, N Ya; Yaminskyi, Yu Ya; Senchyk, Yu Yu; Draguntsova, N G; Rybachuk, O A; Dychko, S M; Petriv, T I


    Simulation model of open penetrating wound of a spinal cord (SC) with its durable com- pression by biocompatible foreign body, was tasted. Experimental animals - mature male rats (inbred line, descendent from a Wistar breed); the trauma simulation model - a left- sided transsection of the SC half on the Txi level; experimental groups: the main (a SC trau- ma + homotopic implantation of microporous hydrogel fragment - foreign body [n=10]), groups of comparison (the SC trauma [n=16]; the SC trauma + homotopic implantation of chemically identical analogue of hydrogel - NeuroGelTM [n=20]). A SC compression by a foreign body worsens the regeneration process course essentially: during first 2 mo the function index of a hind ipsilateral extremity in experimental animals of the main group was the lowest in the experiment - (1.30 ? 0.94) points in accordance to BBB scale, during 3 - 4 mo - the function index had enhanced trustworthy - up to (2.35 ? 0.95) points in accor- dance to BBB scale, what is connected with lowering of a local pressure on a SC tissue due to change of the foreign body form and volume. In 24 weeks the function index of hind ipsi- lateral extremity had constituted (8.45 ? 0.92) points - while application of NeuroGeTM and (2.35 ? 0.95) points - of the foreign body; the tissue processes in the implants localization zone had differed essentially. The tasted simulation model reproduces satisfactory a mechanical component of the foreign body impact on a SC tissue. The SC compression reduction, even in a late follow-up period, had improved the conditions and results of recenerative process essentially.

  12. Contribution of Ca2+-Dependent Cl- Channels to Norepinephrine-Induced Contraction of Femoral Artery Is Replaced by Increasing EDCF Contribution during Ageing

    Czech Academy of Sciences Publication Activity Database

    Líšková, Silvia; Petrová, M.; Karen, Petr; Behuliak, Michal; Zicha, Josef


    Roč. 2014, č. 2014 (2014), s. 289361 ISSN 2314-6133 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : calcium-dependent chloride channels * endothelium-derived contracting factor * ageing Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.579, year: 2014

  13. Automated patch-clamp technique: increased throughput in functional characterization and in pharmacological screening of small-conductance Ca2+ release-activated Ca2+ channels

    DEFF Research Database (Denmark)

    Schrøder, Rikke L; Friis, Søren; Sunesen, Morten


    The suitability of an automated patch clamp for the characterization and pharmacological screening of calcium release-activated calcium (CRAC) channels endogenously expressed in RBL-2H3 cells was explored with the QPatch system. CRAC currents (I( CRAC)) are small, and thus precise recordings requ...

  14. Tasks related to increase of RA reactor exploitation and experimental potential, 03. Crane for handling the vertical experimental channels of the RA reactor - design project

    International Nuclear Information System (INIS)

    Pavicevic, M.


    Within the work related to improvement of experimental potential of the RA reactor, this document describes the design project of the new crane for handling the vertical experimental channels of the RA reactor, engineering drawings of the crane main elements, mechanical part, design project of the electrical part of the crane and cost estimation

  15. Does osteoporosis increase complication risk in surgical fracture treatment? A protocol combining new endpoints for two prospective multicentre open cohort studies

    Directory of Open Access Journals (Sweden)

    Marent Marta


    Full Text Available Abstract Background With an ever-increasing elderly population, orthopaedic surgeons are faced with treating a high number of fragility fractures. Biomechanical tests have demonstrated the potential role of osteoporosis in the increased risk of fracture fixation complications, yet this has not been sufficiently proven in clinical practice. Based on this knowledge, two clinical studies were designed to investigate the influence of local bone quality on the occurrence of complications in elderly patients with distal radius and proximal humerus fractures treated by open reduction and internal fixation. Methods/Design The studies were planned using a prospective multicentre open cohort design and included patients between 50 and 90 years of age. Distal radius and proximal humerus fractures were treated with locking compression 2.4 mm and proximal humerus internal locking plates, respectively. Follow-up examinations were planned for 6 weeks, 3 and 12 months as well as a telephone interview at 6 months. The primary outcome focuses on the occurrence of at least one local bone quality related complication. Local bone quality is determined by measuring bone mineral density and bone mineral content at the contralateral radius. Primary complications are categorised according to predefined factors directly related to the bone/fracture or the implant/surgical technique. Secondary outcomes include the documentation of soft tissue/wound or general/systemic complications, clinical assessment of range of motion, and patient-rated evaluations of upper limb function and quality of life using both objective and subjective measures. Discussion The prospective multicentre open cohort studies will determine the value of local bone quality as measured by bone mineral density and content, and compare the quality of local bone of patients who experience a complication (cases following surgery with that of patients who do not (controls. These measurements are novel and

  16. 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.

  17. Characteristics of single large-conductance Ca2+-activated K+ channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus. (United States)

    Lin, Min; Hatcher, Jeff T; Wurster, Robert D; Chen, Qin-Hui; Cheng, Zixi Jack


    Large-conductance Ca2(+)-activated K+ channels (BK) regulate action potential (AP) properties and excitability in many central neurons. However, the properties and functional roles of BK channels in parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal 7-9 days. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. Using excised patch single-channel recordings, we identified voltage-gated and Ca(2+)-dependent BK channels in PCMNs. The majority of BK channels exhibited persistent channel opening during voltage holding. These BK channels had a conductance of 237 pS and a 50% opening probability at +27.9 mV, the channel open time constant was 3.37 ms at +20 mV, and dwell time increased exponentially as the membrane potential depolarized. At the +20-mV holding potential, the [Ca2+]50 was 15.2 μM with a P0.5 of 0.4. Occasionally, some BK channels showed a transient channel opening and fast inactivation. Using whole cell voltage clamp, we found that BK channel mediated outward currents and afterhyperpolarization currents (IAHP). Using whole cell current clamp, we found that application of BK channel blocker iberiotoxin (IBTX) increased spike half-width and suppressed fast afterhyperpolarization (fAHP) amplitude following single APs. In addition, IBTX application increased spike half-width and reduced the spike frequency-dependent AP broadening in trains and spike frequency adaption (SFA). Furthermore, BK channel blockade decreased spike frequency. Collectively, these results demonstrate that PCMNs have BK channels that significantly regulate AP repolarization, fAHP, SFA, and spike frequency. We conclude that activation of BK channels underlies one of the mechanisms for facilitation of PCMN excitability.

  18. Identification and characterization of hydrophobic gate residues in TRP channels. (United States)

    Zheng, Wang; Hu, Ruikun; Cai, Ruiqi; Hofmann, Laura; Hu, Qiaolin; Fatehi, Mohammad; Long, Wentong; Kong, Tim; Tang, Jingfeng; Light, Peter; Flockerzi, Veit; Cao, Ying; Chen, Xing-Zhen


    Transient receptor potential (TRP) channels, subdivided into 6 subfamilies in mammals, have essential roles in sensory physiology. They respond to remarkably diverse stimuli, comprising thermal, chemical, and mechanical modalities, through opening or closing of channel gates. In this study, we systematically substituted the hydrophobic residues within the distal fragment of pore-lining helix S6 with hydrophilic residues and, based on Xenopus oocyte and mammalian cell electrophysiology and a hydrophobic gate theory, identified hydrophobic gates in TRPV6/V5/V4/C4/M8. We found that channel activity drastically increased when TRPV6 Ala616 or Met617 or TRPV5 Ala576 or Met577 , but not any of their adjacent residues, was substituted with hydrophilic residues. Channel activity strongly correlated with the hydrophilicity of the residues at those sites, suggesting that consecutive hydrophobic residues TRPV6 Ala616-Met617 and TRPV5 Ala576-Met577 form a double-residue gate in each channel. By the same strategy, we identified a hydrophobic single-residue gate in TRPV4 Iso715 , TRPC4 Iso617 , and TRPM8 Val976 . In support of the hydrophobic gate theory, hydrophilic substitution at the gate site, which removes the hydrophobic gate seal, substantially increased the activity of TRP channels in low-activity states but had little effect on the function of activated channels. The double-residue gate channels were more sensitive to small changes in the gate's hydrophobicity or size than single-residue gate channels. The unconventional double-reside gating mechanism in TRP channels may have been evolved to respond especially to physiologic stimuli that trigger relatively small gate conformational changes.-Zheng, W., Hu, R., Cai, R., Hofmann, L., Hu, Q., Fatehi, M., Long, W., Kong, T., Tang, J., Light, P., Flockerzi, V., Cao, Y., Chen, X.-Z. Identification and characterization of hydrophobic gate residues in TRP channels.

  19. Sodium channels in planar lipid bilayers. Channel gating kinetics of purified sodium channels modified by batrachotoxin (United States)


    Single channel currents of sodium channels purified from rat brain and reconstituted into planar lipid bilayers were recorded. The kinetics of channel gating were investigated in the presence of batrachotoxin to eliminate inactivation and an analysis was conducted on membranes with a single active channel at any given time. Channel opening is favored by depolarization and is strongly voltage dependent. Probability density analysis of dwell times in the closed and open states of the channel indicates the occurrence of one open state and several distinct closed states in the voltage (V) range-120 mV less than or equal to V less than or equal to +120 mV. For V less than or equal to 0, the transition rates between stages are exponentially dependent on the applied voltage, as described in mouse neuroblastoma cells (Huang, L. M., N. Moran, and G. Ehrenstein. 1984. Biophysical Journal. 45:313- 322). In contrast, for V greater than or equal to 0, the transition rates are virtually voltage independent. Autocorrelation analysis (Labarca, P., J. Rice, D. Fredkin, and M. Montal. 1985. Biophysical Journal. 47:469-478) shows that there is no correlation in the durations of successive open or closing events. Several kinetic schemes that are consistent with the experimental data are considered. This approach may provide information about the mechanism underlying the voltage dependence of channel activation. PMID:2426388

  20. Coupling and cooperativity in voltage activation of a limited-state BK channel gating in saturating Ca2+. (United States)

    Shelley, Christopher; Niu, Xiaowei; Geng, Yanyan; Magleby, Karl L


    Voltage-dependent gating mechanisms of large conductance Ca(2+) and voltage-activated (BK) channels were investigated using two-dimensional maximum likelihood analysis of single-channel open and closed intervals. To obtain sufficient data at negative as well as positive voltages, single-channel currents were recorded at saturating Ca(2+) from BK channels mutated to remove the RCK1 Ca(2+) and Mg(2+) sensors. The saturating Ca(2+) acting on the Ca(2+) bowl sensors of the resulting BK(B) channels increased channel activity while driving the gating into a reduced number of states, simplifying the model. Five highly constrained idealized gating mechanisms based on extensions of the Monod-Wyman-Changeux model for allosteric proteins were examined. A 10-state model without coupling between the voltage sensors and the opening/closing transitions partially described the voltage dependence of Po but not the single-channel kinetics. With allowed coupling, the model gave improved descriptions of Po and approximated the single-channel kinetics; each activated voltage sensor increased the opening rate approximately an additional 23-fold while having little effect on the closing rate. Allowing cooperativity among voltage sensors further improved the description of the data: each activated voltage sensor increased the activation rate of the remaining voltage sensors approximately fourfold, with little effect on the deactivation rate. The coupling factor was decreased in models with cooperativity from approximately 23 to approximately 18. Whether the apparent cooperativity among voltage sensors arises from imposing highly idealized models or from actual cooperativity will require additional studies to resolve. For both cooperative and noncooperative models, allowing transitions to five additional brief (flicker) closed states further improved the description of the data. These observations show that the voltage-dependent single-channel kinetics of BK(B) channels can be approximated

  1. Impact of increasing prevalence of minimally invasive prostatectomy on open prostatectomy observed in the national inpatient sample and national surgical quality improvement program. (United States)

    Hofer, Matthias D; Meeks, Joshua J; Cashy, John; Kundu, Shilajit; Zhao, Lee C


    Laparoscopic and especially robot-assisted minimally invasive prostatectomy (MIP) has increased in popularity over the past decade. We analyzed how the increasing prevalence of MIP has affected the outcomes of MIP and open radical prostatectomy (RRP). In the Nationwide Inpatient Sample, 23,473 patients undergoing MIP and 118,266 undergoing RRP between 2002 and 2008 are reported. We analyzed length of stay (LOS), hospital charges (THC), complication rates (CR), and socioeconomic characteristics. We used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) to identify complication rates (RRP n=666, and MIP n=2205). The proportion of MIP increased from 1.4% in 2002 to 29.5% in 2008. Mean LOS decreased for MIP (2.4 days in 2002, 1.6 days in 2008) and RRP (3.1 days in 2002, 2.1 days in 2008). Mean THC for MIP decreased ($46k in 2002, $34k in 2008) and increased for RRP ($18k in 2002, $32k in 2008). After 2005, overall CRs of MIP were lower than for RRP. High-volume centers reported lower CRs for both procedures. MIP was associated with fewer transfusions and wound complications. Men living in ZIP codes with the top quartile of yearly mean household income were more likely to undergo MIP than RRP (P<0.001). Although there were more white patients receiving MIP and black or Hispanic patients more frequently underwent RRP, there was no statistically significant difference. Increasing use of MIP led to decreased hospital stay for all patients, increase charges for RRP, and decreased CRs for both MIP and RRP. In recent years, MIP was associated with fewer complications. Charges for RRP have increased over time to approach those for MIP, and patients with increased socio-economic status were more likely to undergo MIP.

  2. Ion channeling

    International Nuclear Information System (INIS)

    Erramli, H.; Blondiaux, G.


    Channeling phenomenon was predicted, many years ago, by stark. The first channeling experiments were performed in 1963 by Davies and his coworkers. Parallely Robinson and Oen have investigated this process by simulating trajectories of ions in monocrystals. This technique has been combined with many methods like Rutherford Backscattering Spectrometry (R.B.S.), Particles Induced X-rays Emission (P.I.X.E) and online Nuclear Reaction (N.R.A.) to localize trace elements in the crystal or to determine crystalline quality. To use channeling for material characterization we need data about the stopping power of the incident particle in the channeled direction. The ratios of channeled to random stopping powers of silicon for irradiation in the direction have been investigated and compared to the available theoretical results. We describe few applications of ion channeling in the field of materials characterization. Special attention is given to ion channeling combined with Charged Particle Activation Analysis (C.P.A.A.) for studying the behaviour of oxygen atoms in Czochralski silicon lattices under the influence of internal gettering and in different gaseous atmospheres. Association between ion channeling and C.P.A.A was also utilised for studying the influence of the growing conditions on concentration and position of carbon atoms at trace levels in the MOVPE Ga sub (1-x) Al sub x lattice. 6 figs., 1 tab., 32 refs. (author)

  3. Ion channelling in diamond

    International Nuclear Information System (INIS)

    Derry, T.E.


    Diamond is one of the most extreme cases from a channelling point of view, having the smallest thermal vibration amplitude and the lowest atomic number of commonly-encountered crystals. These are the two parameters most important for determining channelling behaviour. It is of consiberable interest therefore to see how well the theories explaining and predicting the channeling properties of other substance, succeed with diamond. Natural diamond, although the best available form for these experiments, is rather variable in its physical properties. Part of the project was devoted to considering and solving the problem of obtaining reproducible results representative of the ideal crystal. Channelling studies were performed on several good crystals, using the Rutherford backscattering method. Critical angles for proton channelling were measured for incident energies from 0.6 to 4.5 MeV, in the three most open axes and three most open planes of the diamond structure, and for α-particle channelling at 0.7 and 1.0 MeV (He + ) in the same axes and planes. For 1.0 MeV protons, the crystal temperature was varied from 20 degrees Celsius to 700 degrees Celsius. The results are presented as curves of backscattered yield versus angle in the region of each axis or plane, and summarised in the form of tables and graphs. Generally the critical angles, axial minimum yields, and temperature dependence are well predicted by the accepted theories. The most valuable overall conclusion is that the mean thermal vibration amplitude of the atoms in a crytical determines the critical approach distance to the channel walls at which an ion can remain channelled, even when this distance is much smaller than the Thomas-Fermi screening distance of the atomic potential, as is the case in diamond. A brief study was made of the radiation damage caused by α-particle bombardment, via its effect on the channelling phenomenon. It was possible to hold damage down to negligible levels during the

  4. Microbial contamination along the main open wastewater and storm water channel of Hanoi, Vietnam, and potential health risks for urban farmers. (United States)

    Fuhrimann, Samuel; Pham-Duc, Phuc; Cissé, Guéladio; Tram, Nguyen Thuy; Thu Ha, Hoang; Dung, Do Trung; Ngoc, Pham; Nguyen-Viet, Hung; Anh Vuong, Tuan; Utzinger, Jürg; Schindler, Christian; Winkler, Mirko S


    The use of wastewater in agriculture and aquaculture has a long tradition throughout Asia. For example, in Hanoi, it creates important livelihood opportunities for >500,000 farmers in peri-urban communities. Discharge of domestic effluents pollute the water streams with potential pathogenic organisms posing a public health threat to farmers and consumers of wastewater-fed foodstuff. We determined the effectiveness of Hanoi's wastewater conveyance system, placing particular emphasis on the quality of wastewater used in agriculture and aquaculture. Between April and June 2014, a total of 216 water samples were obtained from 24 sampling points and the concentrations of total coliforms (TC), Escherichia coli, Salmonella spp. and helminth eggs determined. Despite applied wastewater treatment, agricultural field irrigation water was heavily contaminated with TC (1.3×10(7)colony forming unit (CFU)/100mL), E. coli (1.1×10(6)CFU/100mL) and Salmonella spp. (108 most probable number (MPN)/100mL). These values are 110-fold above Vietnamese discharge limits for restricted agriculture and 260-fold above the World Health Organization (WHO)'s tolerable safety limits for unrestricted agriculture. Mean helminth egg concentrations were below WHO tolerable levels in all study systems (population groups without compromising current urban farming activities. This study presents an important example for sanitation safety planning in a rapidly expanding Asian city and can guide public and private entities working towards Sustainable Development Goal target 6.3, that is to improve water quality by reducing pollution, halving the proportion of untreated wastewater and increasing recycling and safe reuse globally. Copyright © 2016. Published by Elsevier B.V.

  5. Increase in leaf temperature opens stomata and decouples net photosynthesis from stomatal conductance in Pinus taeda and Populus deltoides x nigra. (United States)

    Urban, Josef; Ingwers, Miles W; McGuire, Mary Anne; Teskey, Robert O


    The effect of temperature on stomatal conductance (gs) and corresponding gas exchange parameters was studied in two tree species with contrasting leaf anatomy and ecophysiology-a broadleaf angiosperm, Populus deltoides x nigra (poplar), and a needle-leaf gymnosperm, Pinus taeda (loblolly pine). Experiments were conducted in growth chambers across a leaf temperature range of 19-48°C. Manipulations of temperature were done in well-watered and drought soil conditions and under ambient (400 ppm) and elevated (800 ppm) air CO2 concentrations. Increases in leaf temperature caused stomatal opening at both ambient and elevated [CO2]. The gs increased by 42% in poplar and by 40% in loblolly pine when leaf temperature increased from 30°C to 40°C at a vapour pressure difference of 1 kPa. Stomatal limitation to photosynthesis decreased in elevated temperature in loblolly pine but not in poplar. The ratio of net photosynthesis to gs depended on leaf temperature, especially at high temperatures. Evaporative cooling of transpiring leaves resulted in reductions in leaf temperature up to 9°C in well-watered poplar but only 1°C in drought-stressed poplar and in loblolly pine. As global mean temperatures rise and temperature extremes become more frequent and severe, understanding the effect of temperature on gs, and modelling that relationship, will become increasingly important. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  6. Introduction: Applying Chemical Biology to Ion Channels. (United States)

    Pless, Stephan A; Ahern, Christopher A


    Ion channels are membrane-spanning proteins that control the flow of ions across biological membranes through an aqueous pathway. The opening or closing of this pore can be controlled by a myriad of physiological inputs (voltage, ligands, temperature, metabolites, pH), which in turn allow for the controlled flux of ions across membranes, resulting in the generation of minute electrical signals. The functional implications of ion channel function on physiological processes are vast. Electrical impulses, in the form of action potentials or diverse chemo-electrical signals, coordinate the syncytium of the heart beat, support a myriad of neuronal communication pathways, insulin secretion, and are central to the immune response, with more roles being discovered virtually everyday. Thus, ion channel function is a biophysical process that is central to biological life at many levels. And with over 500 channel-forming subunits known today in humans, this large class of proteins is also increasingly recognised as important drug targets, as inherited or acquired ion channel dysfunction are known causes of disease.

  7. Microbial contamination along the main open wastewater and storm water channel of Hanoi, Vietnam, and potential health risks for urban farmers

    Energy Technology Data Exchange (ETDEWEB)

    Fuhrimann, Samuel, E-mail: [Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel (Switzerland); University of Basel, Basel (Switzerland); Pham-Duc, Phuc [Center for Public Health and Ecosystem Research, Hanoi School of Public Health, Hanoi (Viet Nam); Cissé, Guéladio [Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel (Switzerland); University of Basel, Basel (Switzerland); Tram, Nguyen Thuy; Thu Ha, Hoang [Department of Microbiology, National Institute of Hygiene and Epidemiology, Hanoi (Viet Nam); Dung, Do Trung [Department of Parasitology, National Institute of Malaria, Parasitology, and Entomology, Hanoi (Viet Nam); Ngoc, Pham [Department of Animal Hygiene, National Institute for Veterinary Research, Hanoi (Viet Nam); Nguyen-Viet, Hung [Center for Public Health and Ecosystem Research, Hanoi School of Public Health, Hanoi (Viet Nam); International Livestock Research Institute, Hanoi (Viet Nam); Anh Vuong, Tuan [Department of Microbiology, National Institute of Hygiene and Epidemiology, Hanoi (Viet Nam); Utzinger, Jürg; Schindler, Christian; Winkler, Mirko S. [Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel (Switzerland); University of Basel, Basel (Switzerland)


    The use of wastewater in agriculture and aquaculture has a long tradition throughout Asia. For example, in Hanoi, it creates important livelihood opportunities for > 500,000 farmers in peri-urban communities. Discharge of domestic effluents pollute the water streams with potential pathogenic organisms posing a public health threat to farmers and consumers of wastewater-fed foodstuff. We determined the effectiveness of Hanoi's wastewater conveyance system, placing particular emphasis on the quality of wastewater used in agriculture and aquaculture. Between April and June 2014, a total of 216 water samples were obtained from 24 sampling points and the concentrations of total coliforms (TC), Escherichia coli, Salmonella spp. and helminth eggs determined. Despite applied wastewater treatment, agricultural field irrigation water was heavily contaminated with TC (1.3 × 10{sup 7} colony forming unit (CFU)/100 mL), E. coli (1.1 × 10{sup 6} CFU/100 mL) and Salmonella spp. (108 most probable number (MPN)/100 mL). These values are 110-fold above Vietnamese discharge limits for restricted agriculture and 260-fold above the World Health Organization (WHO)'s tolerable safety limits for unrestricted agriculture. Mean helminth egg concentrations were below WHO tolerable levels in all study systems (< 1 egg/L). Hence, elevated levels of bacterial contamination, but not helminth infections, pose a major health risk for farmers and consumers of wastewater fed-products. We propose a set of control measures that might protect the health of exposed population groups without compromising current urban farming activities. This study presents an important example for sanitation safety planning in a rapidly expanding Asian city and can guide public and private entities working towards Sustainable Development Goal target 6.3, that is to improve water quality by reducing pollution, halving the proportion of untreated wastewater and increasing recycling and safe reuse globally

  8. Microbial contamination along the main open wastewater and storm water channel of Hanoi, Vietnam, and potential health risks for urban farmers

    International Nuclear Information System (INIS)

    Fuhrimann, Samuel; Pham-Duc, Phuc; Cissé, Guéladio; Tram, Nguyen Thuy; Thu Ha, Hoang; Dung, Do Trung; Ngoc, Pham; Nguyen-Viet, Hung; Anh Vuong, Tuan; Utzinger, Jürg; Schindler, Christian; Winkler, Mirko S.


    The use of wastewater in agriculture and aquaculture has a long tradition throughout Asia. For example, in Hanoi, it creates important livelihood opportunities for > 500,000 farmers in peri-urban communities. Discharge of domestic effluents pollute the water streams with potential pathogenic organisms posing a public health threat to farmers and consumers of wastewater-fed foodstuff. We determined the effectiveness of Hanoi's wastewater conveyance system, placing particular emphasis on the quality of wastewater used in agriculture and aquaculture. Between April and June 2014, a total of 216 water samples were obtained from 24 sampling points and the concentrations of total coliforms (TC), Escherichia coli, Salmonella spp. and helminth eggs determined. Despite applied wastewater treatment, agricultural field irrigation water was heavily contaminated with TC (1.3 × 10 7 colony forming unit (CFU)/100 mL), E. coli (1.1 × 10 6 CFU/100 mL) and Salmonella spp. (108 most probable number (MPN)/100 mL). These values are 110-fold above Vietnamese discharge limits for restricted agriculture and 260-fold above the World Health Organization (WHO)'s tolerable safety limits for unrestricted agriculture. Mean helminth egg concentrations were below WHO tolerable levels in all study systems (< 1 egg/L). Hence, elevated levels of bacterial contamination, but not helminth infections, pose a major health risk for farmers and consumers of wastewater fed-products. We propose a set of control measures that might protect the health of exposed population groups without compromising current urban farming activities. This study presents an important example for sanitation safety planning in a rapidly expanding Asian city and can guide public and private entities working towards Sustainable Development Goal target 6.3, that is to improve water quality by reducing pollution, halving the proportion of untreated wastewater and increasing recycling and safe reuse globally. - Highlights

  9. Open Geospatial Education

    Directory of Open Access Journals (Sweden)

    Mariana Belgiu


    Full Text Available The advances in open data, free and open source software solutions and open access to research publications have influenced the emergence of open educational resources (OER initiatives. These initiatives permit access to openly licensed learning resources including courses, webinars, training materials and textbooks. Thereby, an increasing number of users has the opportunity to broaden their knowledge and gain new skills. The goal of this paper is to evaluate open education initiatives in the geospatial domain and its synergies with open spatial data and software movements. The paper is focusing on the Massive Open Online Course (MOOCs movement. The advantages and challenges of open geospatial education will be thoroughly discussed.

  10. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries. (United States)

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina


    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 open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Bicuculline, pentobarbital and diazepam modulate spontaneous GABAA channels in rat hippocampal neurons (United States)

    Birnir, Bryndis; Eghbali, Mansoureh; Everitt, Andrea B; Gage, Peter W


    Spontaneously opening, chloride-selective channels that showed outward rectification were recorded in ripped-off patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. In both preparations, channels had multiple conductance states and the most common single-channel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (−Vp=80 mV). Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 μM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate effect on single-channel conductance. Exposure of the patches to 100 μM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower in the outside-out than in the cell-attached patches. Application of 100 μM pentobarbital or 1 μM diazepam caused 2–4 fold increase in the maximum channel conductance of low conductance (<40 pS) spontaneously active channels. The observation of spontaneously opening GABAA channels in cell-attached patches on neurons in slices suggests that they may have a role in neurons in vivo and could be an important site of action for some drugs such as benzodiazepines, barbiturates and general anaesthetics. PMID:11030718

  12. Ion channel permeable for divalent and monovalent cations in native spinach thylakoid membranes. (United States)

    Pottosin, I I; Schönknecht, G


    A cation-selective channel was characterized in isolated patches from osmotically swollen thylakoids of spinach (Spinacea oleracea). This channel was permeable for K+ as well as for Mg2+ and Ca2+ but not for Cl-. When K+ was the main permeant ion (symmetrical 105 mM KCl) the conductance of the channel was about 60 pS. The single channel conductance for different cations followed a sequence K+ > Mg2+ >/= Ca2+. The permeabilities determined by reversal potential measurements were comparable for K+, Ca2+, and Mg2+. The cation channel displayed bursting behavior. The total open probability of the channel increased at more positive membrane potentials. Kinetic analysis demonstrated that voltage dependence of the total open probability was determined by the probability of bursts formation while the probability to find the channel in open state within a burst of activity was hardly voltage-dependent. The cation permeability of intact spinach thylakoids can be explained on the single channel level by the data presented here.

  13. Role of Entrepreneurs in Managing Open Innovation in SMEs


    Karamat, Sehrish


    It is nowadays quite logical for SMEs to engage in open innovation activities to combat the internal and external challenges they are facing such as fewer sources for R&D, limited financial resources and technical capabilities, lack of production facilities and distribution channels etc. Studies show that open innovation experienced a rapid increase in recent years. Recently researchers have also shown keen interest in research on SMEs whereas previously only the large companies remained focu...

  14. An open-label prospective clinical study to assess the efficacy of increasing levocetirizine dose up to four times in chronic spontaneous urticaria not controlled with standard dose. (United States)

    Sharma, Vinod Kumar; Gupta, Vishal; Pathak, Mona; Ramam, M


    The EAACI/GA 2 LEN/EDF/WAO recommendation of increasing antihistamines' dose up to four times in urticaria not adequately controlled with the standard dose is largely based on expert opinion. The objective of this study is to test the current urticaria guidelines of up-dosing antihistamines as second-line treatment. This was an open-label study conducted prospectively on 113 patients with chronic spontaneous urticaria. All patients were treated with sequentially increasing doses of levocetrizine (5 mg, 10 mg, 15 mg and 20 mg/day) every week till the patients became completely asymptomatic or dose of 20 mg/day reached. Urticaria Activity Score (UAS)-7, urticaria-related quality-of-life (CU-Q2oL) and patients' global assessment were used to assess treatment response. Twenty-one (18.58%) patients became asymptomatic with levocetirizine 5 mg/day, while 50 required higher doses of levocetirizine for complete control: 29/92 (31.52%), 6/63 (9.52%) and 15/57 (26.31%) with 10 mg, 15 mg and 20 mg/day, respectively. The percentage of patients experiencing >75% improvement increased with increasing doses of levocetirizine: 26.54%, 53.98%, 60.17% and 69.91% with 5 mg, 10 mg, 15 mg and 20 mg/day, respectively. Sequential up-dosing of levocetirizine produced a progressive improvement in both urticaria control (UAS-7) and quality-of-life (CU-Q2oL) without significantly increasing somnolence. Our results support the current recommendations of increasing antihistamines up to four times the standard dose in patients who fail the first-line treatment.

  15. Effects of increase in temperature and open water on transmigration and access to health care by the Nenets reindeer herders in northern Russia

    Directory of Open Access Journals (Sweden)

    Philippe Amstislavski


    Full Text Available Background . The indigenous Nenets reindeer herders in northern Russia annually migrate several hundred kilometers between summer and winter pastures. In the warming climate, ice-rich permafrost and glaciers are being significantly reduced and will eventually disappear from parts of the Arctic. The emergent changes in hydrological cycles have already led to substantial increases in open water that stays unfrozen for longer periods of time. This environmental change has been reported to compromise the nomadic Nenets’ traditional way of life because the presence of new water in the tundra reduces the Nenets’ ability to travel by foot, sled, or motor vehicle from the summer transitory tundra campsites in order to access healthcare centers in villages. New water can also impede their access to family and community at other herder camps and in the villages. Although regional and global models predicting hydrologic changes due to climate changes exist, the spatial resolution of these models is too coarse for studying how increases in open water affect health and livelihoods. To anticipate the full health impact of hydrologic changes, the current gap between globally forecasted scenarios and locally forecasted hydrologic scenarios needs to be bridged. Objectives . We studied the effects of the autumn temperature anomalies and increases in open water on health care access and transmigration of reindeer herders on the Kanin Peninsula. Design . Correlational and time series analyses were completed. Methods . The study population consisted of 370 full-time, nomadic reindeer herders. We utilized clinical visit records, studied surface temperature anomalies during autumn migrations, and used remotely sensed imagery to detect water bodies. Spearman correlation was used to measure the relationship between temperature anomalies and the annual arrival of the herders at the Nes clinic for preventive and primary care. Piecewise regression was used to model

  16. Effects of increase in temperature and open water on transmigration and access to health care by the Nenets reindeer herders in northern Russia (United States)

    Amstislavski, Philippe; Zubov, Leonid; Chen, Herman; Ceccato, Pietro; Pekel, Jean-Francois; Weedon, Jeremy


    Background The indigenous Nenets reindeer herders in northern Russia annually migrate several hundred kilometers between summer and winter pastures. In the warming climate, ice-rich permafrost and glaciers are being significantly reduced and will eventually disappear from parts of the Arctic. The emergent changes in hydrological cycles have already led to substantial increases in open water that stays unfrozen for longer periods of time. This environmental change has been reported to compromise the nomadic Nenets’ traditional way of life because the presence of new water in the tundra reduces the Nenets’ ability to travel by foot, sled, or motor vehicle from the summer transitory tundra campsites in order to access healthcare centers in villages. New water can also impede their access to family and community at other herder camps and in the villages. Although regional and global models predicting hydrologic changes due to climate changes exist, the spatial resolution of these models is too coarse for studying how increases in open water affect health and livelihoods. To anticipate the full health impact of hydrologic changes, the current gap between globally forecasted scenarios and locally forecasted hydrologic scenarios needs to be bridged. Objectives We studied the effects of the autumn temperature anomalies and increases in open water on health care access and transmigration of reindeer herders on the Kanin Peninsula. Design Correlational and time series analyses were completed. Methods The study population consisted of 370 full-time, nomadic reindeer herders. We utilized clinical visit records, studied surface temperature anomalies during autumn migrations, and used remotely sensed imagery to detect water bodies. Spearman correlation was used to measure the relationship between temperature anomalies and the annual arrival of the herders at the Nes clinic for preventive and primary care. Piecewise regression was used to model change in mean autumnal

  17. Modification of cloned brain Na+ channels by batrachotoxin. (United States)

    Wang, G K; Wang, S Y


    The effects of batrachotoxin (BTX) on cloned alpha-subunit Na+ channels were examined in CHO-K1 cells (a chinese hamster ovary cell line) transfected with rat brain NaIIA cDNA. Under whole-cell patch clamp conditions, BTX shifted the voltage dependence of the activation process by about 45 mV towards the hyperpolarizing direction and eliminated the inactivating phase of Na+ currents. Repetitive depolarizations greatly facilitated the binding of BTX with NaIIA channels while the membrane was held at -100 mV. In chloramine-T-pretreated cells, the association rate of BTX binding with the NaIIA channel was 6.5-fold faster than that in untreated cells. The estimated association rate constant for BTX binding with the open form of NaIIA channel was 1.11 x 10(6) mol-1.s-1 at room temperature. BTX-modified NaIIA channels were blocked by tetrodotoxin (TTX) in a complicated manner. First, the TTX binding to the closed state of BTX-modified NaIIA channels was not voltage dependent. The KD value of TTX was measured at 8.9 nM, which was similar to that of unmodified channels (KD = 14.2 nM). Second, the block of the open state of BTX-modified NaIIA channels by TTX was voltage dependent; depolarization reduced the potency of TTX block between -20 mV to +50 mV. Below -30 mV, the TTX affinity began to level off, probably because of the increased presence of the closed state. Unexpectedly, steady-state inactivation of BTX-modified NaIIA channels was minimal as measured by the two-pulse protocol, a phenomenon distinctly different from that found in GH3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart

    DEFF Research Database (Denmark)

    Diness, Jonas Goldin; Kirchhoff, Jeppe Egedal; Sheykhzade, Majid


    channels are predominantly coming into play during arrhythmogenic events where intracellular concentration of Ca is increased. During ventricular fibrillation a surge of [Ca]i has the potential to bind to and open SK channels. To obtain mechanistic insight into possible roles of SK channels during...... ventricular fibrillation we conducted experiments with a SK channel pore blocker (ICA) and a negatively allosteric modulator (NS8395) in a Langendorff perfused heart model. Both compounds increased the action potential duration (APD), effective refractory period (ERP) and Wenckebach cycle length (WCL......) to comparable extents. Despite these similarities, the SK channel modulator was found to revert and prevent ventricular fibrillation (VF) more efficiently than the SK channel pore blocker. In conclusion, either negative allosteric modulation of the SK channel with NS8593 is more favorable than pure channel...

  19. Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels.

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Gnanasambandam

    Full Text Available Members of the eukaryotic PIEZO family (the human orthologs are noted hPIEZO1 and hPIEZO2 form cation-selective mechanically-gated channels. We characterized the selectivity of human PIEZO1 (hPIEZO1 for alkali ions: K+, Na+, Cs+ and Li+; organic cations: TMA and TEA, and divalents: Ba2+, Ca2+, Mg2+ and Mn2+. All monovalent ions permeated the channel. At a membrane potential of -100 mV, Cs+, Na+ and K+ had chord conductances in the range of 35-55 pS with the exception of Li+, which had a significantly lower conductance of ~ 23 pS. The divalents decreased the single-channel permeability of K+, presumably because the divalents permeated slowly and occupied the open channel for a significant fraction of the time. In cell-attached mode, 90 mM extracellular divalents had a conductance for inward currents carried by the divalents of: 25 pS for Ba2+ and 15 pS for Ca2+ at -80 mV and 10 pS for Mg2+ at -50 mV. The organic cations, TMA and TEA, permeated slowly and attenuated K+ currents much like the divalents. As expected, the channel K+ conductance increased with K+ concentration saturating at ~ 45 pS and the KD of K+ for the channel was 32 mM. Pure divalent ion currents were of lower amplitude than those with alkali ions and the channel opening rate was lower in the presence of divalents than in the presence of monovalents. Exposing cells to the actin disrupting reagent cytochalasin D increased the frequency of openings in cell-attached patches probably by reducing mechanoprotection.

  20. 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...... defined yet. In the present study we hypothesized that T-cell KV1.3 and KCa3.1 expression may serve as novel molecular marker for T-cell infiltration, inflammatory activity, and possibly disease progression. AIMS & METHODS: Biopsies were obtained from the rectal mucosa in seven UC patients with clinical...... and endoscopic active disease and seven non-UC patients. Active inflammation in the rectal mucosa in patients with UC was verified histologically. Expression of KV1.3 and KCa3.1 genes and of INFγ as a classical marker of inflammation was investigated in mRNA-extracts from biopsies by quantitative RT-PCR (q...

  1. Effects of channel blocking on information transmission and energy efficiency in squid giant axons. (United States)

    Liu, Yujiang; Yue, Yuan; Yu, Yuguo; Liu, Liwei; Yu, Lianchun


    Action potentials are the information carriers of neural systems. The generation of action potentials involves the cooperative opening and closing of sodium and potassium channels. This process is metabolically expensive because the ions flowing through open channels need to be restored to maintain concentration gradients of these ions. Toxins like tetraethylammonium can block working ion channels, thus affecting the function and energy cost of neurons. In this paper, by computer simulation of the Hodgkin-Huxley neuron model, we studied the effects of channel blocking with toxins on the information transmission and energy efficiency in squid giant axons. We found that gradually blocking sodium channels will sequentially maximize the information transmission and energy efficiency of the axons, whereas moderate blocking of potassium channels will have little impact on the information transmission and will decrease the energy efficiency. Heavy blocking of potassium channels will cause self-sustained oscillation of membrane potentials. Simultaneously blocking sodium and potassium channels with the same ratio increases both information transmission and energy efficiency. Our results are in line with previous studies suggesting that information processing capacity and energy efficiency can be maximized by regulating the number of active ion channels, and this indicates a viable avenue for future experimentation.

  2. Structural Changes Fundamental to Gating of the Cystic Fibrosis Transmembrane Conductance Regulator Anion Channel Pore. (United States)

    Linsdell, Paul


    Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial cell anion channel. Potentiator drugs used in the treatment of cystic fibrosis act on the channel to increase overall channel function, by increasing the stability of its open state and/or decreasing the stability of its closed state. The structure of the channel in either the open state or the closed state is not currently known. However, changes in the conformation of the protein as it transitions between these two states have been studied using functional investigation and molecular modeling techniques. This review summarizes our current understanding of the architecture of the transmembrane channel pore that controls the movement of chloride and other small anions, both in the open state and in the closed state. Evidence for different kinds of changes in the conformation of the pore as it transitions between open and closed states is described, as well as the mechanisms by which these conformational changes might be controlled to regulate normal channel gating. The ways that key conformational changes might be targeted by small compounds to influence overall CFTR activity are also discussed. Understanding the changes in pore structure that might be manipulated by such small compounds is key to the development of novel therapeutic strategies for the treatment of cystic fibrosis.

  3. 9-Phenanthrol inhibits recombinant and arterial myocyte TMEM16A channels (United States)

    Burris, Sarah K; Wang, Qian; Bulley, Simon; Neeb, Zachary P; Jaggar, Jonathan H


    Background and Purpose In arterial smooth muscle cells (myocytes), intravascular pressure stimulates membrane depolarization and vasoconstriction (the myogenic response). Ion channels proposed to mediate pressure-induced depolarization include several transient receptor potential (TRP) channels, including TRPM4, and transmembrane protein 16A (TMEM16A), a Ca2+-activated Cl− channel (CaCC). 9-Phenanthrol, a putative selective TRPM4 channel inhibitor, abolishes myogenic tone in cerebral arteries, suggesting that either TRPM4 is essential for pressure-induced depolarization, upstream of activation of other ion channels or that 9-phenanthrol is non-selective. Here, we tested the hypothesis that 9-phenanthrol is also a TMEM16A channel blocker, an ion channel for which few inhibitors have been identified. Experimental Approach Patch clamp electrophysiology was used to measure rat cerebral artery myocyte and human recombinant TMEM16A (rTMEM16A) currents or currents generated by recombinant bestrophin-1, another Ca2+-activated Cl− channel, expressed in HEK293 cells. Key Results 9-Phenanthrol blocked myocyte TMEM16A currents activated by either intracellular Ca2+ or Eact, a TMEM16A channel activator. In contrast, 9-phenanthrol did not alter recombinant bestrophin-1 currents. 9-Phenanthrol reduced arterial myocyte TMEM16A currents with an IC50 of ∼12 μM. Cell-attached patch recordings indicated that 9-phenanthrol reduced single rTMEM16A channel open probability and mean open time, and increased mean closed time without affecting the amplitude. Conclusions and Implications These data identify 9-phenanthrol as a novel TMEM16A channel blocker and provide an explanation for the previous observation that 9-phenanthrol abolishes myogenic tone when both TRPM4 and TMEM16A channels contribute to this response. 9-Phenanthrol may be a promising candidate from which to develop TMEM16A channel-specific inhibitors. PMID:25573456

  4. Simultaneous Increase in Open-Circuit Voltage and Efficiency of Fullerene-Free Solar Cells through Chlorinated Thieno[3,4- b ]thiophene Polymer Donor

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huan [Department; Chao, Pengjie [Department; Chen, Hui [Department; Mu, Zhao [Department; Chen, Wei [Materials; Institute; He, Feng [Department


    The chlorinated polymer, PBTCl, has been found to be an efficient donor in nonfullerene polymer solar cells (PSCs), which showed a blue-shifted absorbance compared to that of its fluorine analogue (PTB7-th) and resulted in more complementary light absorption with a nonfullerene acceptor, such as ITIC. Meanwhile, chlorine substitution lowered the HOMO level of PBTCl, which increased the open-circuit voltage of the corresponding polymer-based devices. The 2D GIWAXS analysis illustrated that the PBTCl/ITIC blend film exhibited a “face-on” orientation and scattering features of both PBTCl and ITIC, suggesting that the blend of PBTCl and ITIC was phase-separated and formed individual crystalline domains of the donor and acceptor, which promoted charge transfer in the bicontinuous film and eventually elevated the solar energy conversion efficiency. The PBTCl-based nonfullerene PSC exhibited a maximum PCE of 7.57% with a Voc of 0.91 V, which was an approximately 13% increasing in the PCE compared to that of the fluorine-analogue-based device.

  5. Prolongation of action potential duration and QT interval during epilepsy linked to increased contribution of neuronal sodium channels to cardiac late Na+ current: potential mechanism for sudden death in epilepsy. (United States)

    Biet, Michael; Morin, Nathalie; Lessard-Beaudoin, Melissa; Graham, Rona K; Duss, Sandra; Gagné, Jonathan; Sanon, Nathalie T; Carmant, Lionel; Dumaine, Robert


    Arrhythmias associated with QT prolongation on the ECG often lead to sudden unexpected death in epilepsy. The mechanism causing a prolongation of the QT interval during epilepsy remains unknown. Based on observations showing an upregulation of neuronal sodium channels in the brain during epilepsy, we tested the hypothesis that a similar phenomenon occurs in the heart and contributes to QT prolongation by altering cardiac sodium current properties (INa). We used the patch clamp technique to assess the effects of epilepsy on the cardiac action potential and INa in rat ventricular myocytes. Consistent with QT prolongation, epileptic rats had longer ventricular action potential durations attributable to a sustained component of INa (INaL). The increase in INaL was because of a larger contribution of neuronal Na channels characterized by their high sensitivity to tetrodotoxin. As in the brain, epilepsy was associated with an enhanced expression of the neuronal isoform NaV1.1 in cardiomyocyte. Epilepsy was also associated with a lower INa activation threshold resulting in increased cell excitability. This is the first study correlating increased expression of neuronal sodium channels within the heart to epilepsy-related cardiac arrhythmias. This represents a new paradigm in our understanding of cardiac complications related to epilepsy. © 2015 American Heart Association, Inc.

  6. Roughness coefficients for stream channels in Arizona (United States)

    Aldridge, B.N.; Garrett, J.M.


    When water flows in an open channel, energy is lost through friction along the banks and bed of the channel and through turbulence within the channel. The amount of energy lost is governed by channel roughness, which is expressed in terms of a roughness coefficient. An evaluation of the roughness coefficient is necessary in many hydraulic computations that involve flow in an open channel. Owing to the lack of satisfactory quantitative procedure, the ability of evaluate roughness coefficients can be developed only through experience; however, a basic knowledge of the methods used to assign the coefficients and the factors affecting them will be a great help. One of the most commonly used equations in open-channel hydraulics is that of Manning. The Manning equation is       1.486

  7. Effects of donepezil on hERG potassium channels. (United States)

    Chae, Yun Ju; Lee, Hong Joon; Jeon, Ji Hyun; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June


    Donepezil is a potent, selective inhibitor of acetylcholinesterase, which is used for the treatment of Alzheimer's disease. Whole-cell patch-clamp technique and Western blot analyses were used to study the effects of donepezil on the human ether-a-go-go-related gene (hERG) channel. Donepezil inhibited the tail current of the hERG in a concentration-dependent manner with an IC50 of 1.3 μM. The metabolites of donepezil, 6-ODD and 5-ODD, inhibited the hERG currents in a similar concentration-dependent manner; the IC50 values were 1.0 and 1.5 μM, respectively. A fast drug perfusion system demonstrated that donepezil interacted with both the open and inactivated states of the hERG. A fast application of donepezil during the tail currents inhibited the open state of the hERG in a concentration-dependent manner with an IC50 of 2.7 μM. Kinetic analysis of donepezil in an open state of the hERG yielded blocking and unblocking rate constants of 0.54 µM(-1)s(-1) and 1.82 s(-1), respectively. The block of the hERG by donepezil was voltage-dependent with a steep increase across the voltage range of channel activation. Donepezil caused a reduction in the hERG channel protein trafficking to the plasma membrane at low concentration, but decreased the channel protein expression at higher concentrations. These results suggest that donepezil inhibited the hERG at a supratherapeutic concentration, and that it did so by preferentially binding to the activated (open and/or inactivated) states of the channels and by inhibiting the trafficking and expression of the hERG channel protein in the plasma membrane. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Pannexin-1 channels in epilepsy. (United States)

    Aquilino, Mark S; Whyte-Fagundes, Paige; Zoidl, Georg; Carlen, Peter L


    Pannexin-1 (Panx1) expression is raised in several animal seizure models and in resected human epileptic brain tissue, suggesting relevance to epilepsy. Multiple factors that are characteristic of seizures are thought to regulate Panx1 channel opening, including elevated levels of extracellular K + . Panx1, when open, 1) releases ATP, glutamate, and other metabolites into the extracellular medium, and 2) may depolarize the membrane due to a channel reversal potential around 0mV. Resultant ATP release from stimulated Panx1 can activate purinergic receptors, including P2X7 receptors. Glutamate and other signaling molecules released by Panx1 opening may have both excitatory and inhibitory actions on seizure generation. This review examines the critical and complex roles of Panx1 channels in epilepsy, which could provide a basis for future therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Quantification of shear stress in a meandering native topographic channel using a physical hydraulic model (United States)

    Michael E. Ursic


    Current guidelines for predicting increases in shear stress in open-channel bends were developed from investigations that were primarily prismatic in cross section. This study provides possible increases in shear stress relative to approach flow conditions resulting from planimetric and topographic geometric features. Boundary shear stress estimates were determined by...

  10. Ca(2+)-activated anion channels and membrane depolarizations induced by blue light and cold in Arabidopsis seedlings (United States)

    Lewis, B. D.; Karlin-Neumann, G.; Davis, R. W.; Spalding, E. P.; Evans, M. L. (Principal Investigator)


    The activation of an anion channel in the plasma membrane of Arabidopsis thaliana hypocotyls by blue light (BL) is believed to be a signal-transducing event leading to growth inhibition. Here we report that the open probability of this particular anion channel depends on cytoplasmic Ca2+ ([Ca2+]cyt) within the concentration range of 1 to 10 microM, raising the possibility that BL activates the anion channel by increasing [Ca2+]cyt. Arabidopsis seedlings cytoplasmically expressing aequorin were generated to test this possibility. Aequorin luminescence did not increase during or after BL, providing evidence that Ca2+ does not play a second-messenger role in the activation of anion channels. However, cold shock simultaneously triggered a large increase in [Ca2+]cyt and a 110-mV transient depolarization of the plasma membrane. A blocker of the anion channel, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, blocked 61% of the cold-induced depolarization without affecting the increase in [Ca2+]cyt. These data led us to propose that cold shock opens Ca2+ channels at the plasma membrane, allowing an inward, depolarizing Ca2+ current. The resulting large increase in [Ca2+]cyt activates the anion channel, which further depolarizes the membrane. Although an increase in [Ca2+]cyt may activate anion channels in response to cold, it appears that BL does so via a Ca(2+)-independent pathway.

  11. Nanobody mediated crystallization of an archeal mechanosensitive channel.

    Directory of Open Access Journals (Sweden)

    Christian Löw

    Full Text Available Mechanosensitive channels (MS are integral membrane proteins and allow bacteria to survive sudden changes in external osmolarity due to transient opening of their pores. The efflux of cytoplasmic osmolytes reduces the membrane tension and prevents membrane rupture. Therefore these channels serve as emergency valves when experiencing significant environmental stress. The preparation of high quality crystals of integral membrane proteins is a major bottleneck for structure determination by X-ray crystallography. Crystallization chaperones based on various protein scaffolds have emerged as promising tool to increase the crystallization probability of a selected target protein. So far archeal mechanosensitive channels of small conductance have resisted crystallization in our hands. To structurally analyse these channels, we selected nanobodies against an archeal MS channel after immunization of a llama with recombinant expressed, detergent solubilized and purified protein. Here we present the characterization of 23 different binders regarding their interaction with the channel protein using analytical gel filtration, western blotting and surface plasmon resonance. Selected nanobodies bound the target with affinities in the pico- to nanomolar range and some binders had a profound effect on the crystallization of the MS channel. Together with previous data we show that nanobodies are a versatile and valuable tool in structural biology by widening the crystallization space for highly challenging proteins, protein complexes and integral membrane proteins.

  12. Standard compliant channel selection scheme for TV white space networks

    CSIR Research Space (South Africa)

    Masonta, MT


    Full Text Available an open issue. In this paper, an Analytic Hierarchy Process (AHP) based scheme is proposed for optimal channel decision. The best channel is selected from a pool of available channels provided by the GSDB. Each channel is ranked based on the current class...

  13. Monitoring single-channel water permeability in polarized cells. (United States)

    Erokhova, Liudmila; Horner, Andreas; Kügler, Philipp; Pohl, Peter


    So far the determination of unitary permeability (p(f)) of water channels that are expressed in polarized cells is subject to large errors because the opening of a single water channel does not noticeably increase the water permeability of a membrane patch above the background. That is, in contrast to the patch clamp technique, where the single ion channel conductance may be derived from a single experiment, two experiments separated in time and/or space are required to obtain the single-channel water permeability p(f) as a function of the incremental water permeability (P(f,c)) and the number (n) of water channels that contributed to P(f,c). Although the unitary conductance of ion channels is measured in the native environment of the channel, p(f) is so far derived from reconstituted channels or channels expressed in oocytes. To determine the p(f) of channels from live epithelial monolayers, we exploit the fact that osmotic volume flow alters the concentration of aqueous reporter dyes adjacent to the epithelia. We measure these changes by fluorescence correlation spectroscopy, which allows the calculation of both P(f,c) and osmolyte dilution within the unstirred layer. Shifting the focus of the laser from the aqueous solution to the apical and basolateral membranes allowed the FCS-based determination of n. Here we validate the new technique by determining the p(f) of aquaporin 5 in Madin-Darby canine kidney cell monolayers. Because inhibition and subsequent activity rescue are monitored on the same sample, drug effects on exocytosis or endocytosis can be dissected from those on p(f).

  14. Increasing the open-circuit voltage of photoprotein-based photoelectrochemical cells by manipulation of the vacuum potential of the electrolytes. (United States)

    Tan, Swee Ching; Crouch, Lucy I; Mahajan, Sumeet; Jones, Michael R; Welland, Mark E


    The innately highly efficient light-powered separation of charge that underpins natural photosynthesis can be exploited for applications in photoelectrochemistry by coupling nanoscale protein photoreaction centers to man-made electrodes. Planar photoelectrochemical cells employing purple bacterial reaction centers have been constructed that produce a direct current under continuous illumination and an alternating current in response to discontinuous illumination. The present work explored the basis of the open-circuit voltage (V(OC)) produced by such cells with reaction center/antenna (RC-LH1) proteins as the photovoltaic component. It was established that an up to ~30-fold increase in V(OC) could be achieved by simple manipulation of the electrolyte connecting the protein to the counter electrode, with an approximately linear relationship being observed between the vacuum potential of the electrolyte and the resulting V(OC). We conclude that the V(OC) of such a cell is dependent on the potential difference between the electrolyte and the photo-oxidized bacteriochlorophylls in the reaction center. The steady-state short-circuit current (J(SC)) obtained under continuous illumination also varied with different electrolytes by a factor of ~6-fold. The findings demonstrate a simple way to boost the voltage output of such protein-based cells into the hundreds of millivolts range typical of dye-sensitized and polymer-blend solar cells, while maintaining or improving the J(SC). Possible strategies for further increasing the V(OC) of such protein-based photoelectrochemical cells through protein engineering are discussed.

  15. Ankyrin regulates KATP channel membrane trafficking and gating in excitable cells (United States)

    Kline, Crystal F.; Hund, Thomas J.; Mohler, Peter J.


    K(ATP) channels play critical roles in many cellular functions by coupling cell metabolic status to electrical activity. First discovered in cardiomyocytes,1 KATP channels (comprised of Kir6.x and SUR subunits) have since been found in many other tissues, including pancreatic beta cells, skeletal muscle, smooth muscle, brain, pituitary and kidney. By linking cellular metabolic state with membrane potential, KATP channels are able to regulate a number of cellular functions such as hormone secretion, vascular tone and excitability. Specifically, a reduction in metabolism causes a decrease in the ATP:ADP ratio, opening of KATP channels, K+ efflux, membrane hyperpolarization, and suppression of electrical activity. Conversely, increased cellular metabolism causes an increase in the ATP:ADP ratio that leads to closure of the KATP channel, membrane depolarization, and stimulation of cell electrical activity. PMID:19901534

  16. Organic matter production response to CO2 increase in open subarctic plankton communities: Comparison of six microcosm experiments under iron-limited and -enriched bloom conditions (United States)

    Yoshimura, Takeshi; Sugie, Koji; Endo, Hisashi; Suzuki, Koji; Nishioka, Jun; Ono, Tsuneo


    Increase in seawater pCO2 and the corresponding decrease in pH caused by the increasing atmospheric CO2 concentration (i.e., ocean acidification) may affect organic matter production by phytoplankton communities. Organic matter production forms the basis of marine food webs and plays a crucial role in oceanic CO2 uptake through the biological carbon pump, and hence will potentially affect future marine ecosystem dynamics. However, responses of organic matter production in open ocean plankton ecosystems to CO2 increase have not been fully examined. We conducted on-deck microcosm experiments using high nutrient, low chlorophyll (HNLC) waters in the western subarctic Pacific and oceanic Bering Sea basin in summer 2008 and 2009, respectively, to examine the impacts of elevated CO2 on particulate and dissolved organic matter (i.e., POM and DOM, respectively) production. Iron deficient natural plankton communities were incubated for 7-14 days under multiple CO2 levels with and without iron enrichments (hereafter +Fe and -Fe treatments, respectively). By combining with our previous experiments at two sites, we created a comprehensive dataset on responses of organic matter production to CO2 increase during macronutrient replete conditions in HNLC waters. Significant differences in net particulate organic carbon production among CO2 treatments were observed only in the -Fe treatments, whereas that in net dissolved organic carbon production were mainly observed in the +Fe treatments, suggesting that CO2 may affect different processes depending on the Fe nutritional status. However, impacts of CO2 were not consistent among experiments and were much smaller than the consistent positive effects of Fe enrichment. In contrast, no significant differences among the CO2 treatments were observed for organic carbon partitioning into POM and DOM, and carbon to nitrogen ratio of net produced POM. We conclude that CO2 does not play a primary role, but could have secondary effects on


    Directory of Open Access Journals (Sweden)

    Ljiljana Stošić Mihajlović


    Full Text Available Marketing channel is a set of entities and institutions, completion of distribution and marketing activities, attend the efficient and effective networking of producers and consumers. Marketing channels include the total flows of goods, money and information taking place between the institutions in the system of marketing, establishing a connection between them. The functions of the exchange, the physical supply and service activities, inherent in the system of marketing and trade. They represent paths which products and services are moving after the production, which will ultimately end up buying and eating by the user.

  18. Comparison of Langevin and Markov channel noise models for neuronal signal generation. (United States)

    Sengupta, B; Laughlin, S B; Niven, J E


    The stochastic opening and closing of voltage-gated ion channels produce noise in neurons. The effect of this noise on the neuronal performance has been modeled using either an approximate or Langevin model based on stochastic differential equations or an exact model based on a Markov process model of channel gating. Yet whether the Langevin model accurately reproduces the channel noise produced by the Markov model remains unclear. Here we present a comparison between Langevin and Markov models of channel noise in neurons using single compartment Hodgkin-Huxley models containing either Na+ and K+, or only K+ voltage-gated ion channels. The performance of the Langevin and Markov models was quantified over a range of stimulus statistics, membrane areas, and channel numbers. We find that in comparison to the Markov model, the Langevin model underestimates the noise contributed by voltage-gated ion channels, overestimating information rates for both spiking and nonspiking membranes. Even with increasing numbers of channels, the difference between the two models persists. This suggests that the Langevin model may not be suitable for accurately simulating channel noise in neurons, even in simulations with large numbers of ion channels.

  19. Pharmacological activation and inhibition of Slack (Slo2.2) channels. (United States)

    Yang, Bo; Gribkoff, Valentin K; Pan, Jennifer; Damagnez, Veronique; Dworetzky, Steven I; Boissard, Christopher G; Bhattacharjee, Arin; Yan, Yangyang; Sigworth, Fred J; Kaczmarek, Leonard K


    The Slack (Sequence like a calcium-activated K channel) (Slo2.2) gene is abundantly expressed in the mammalian brain and encodes a sodium-activated K+ (KNa) channel. Although the specific roles of Slack channel subunits in neurons remain to be identified, they may play a role in the adaptation of firing rate and in protection against ischemic injury. In the present study, we have generated a stable cell line expressing the Slack channel, and have analyzed the pharmacological properties of these channels in these cells and in Xenopus oocytes. Two known blockers of KNa channels, bepridil and quinidine, inhibited Slack currents in a concentration-dependent manner and decreased channel activity in excised membrane patches. The inhibition by bepridil was potent, with an IC50 of 1.0 microM for inhibition of Slack currents in HEK cells. In contrast, bithionol was found to be a robust activator of Slack currents. When applied to the extracellular face of excised patches, bithionol rapidly induced a reversible increase in channel opening, suggesting that it acts on Slack channels relatively directly. These data establish an important early characterization of agents that modulate Slack channels, a process essential for the experimental manipulation of Slack currents in neurons.

  20. Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity.

    Directory of Open Access Journals (Sweden)

    Abdelrahman Alharazneh

    Full Text Available Aminoglycosides (AG are commonly prescribed antibiotics with potent bactericidal activities. One main side effect is permanent sensorineural hearing loss, induced by selective inner ear sensory hair cell death. Much work has focused on AG's initiating cell death processes, however, fewer studies exist defining mechanisms of AG uptake by hair cells. The current study investigated two proposed mechanisms of AG transport in mammalian hair cells: mechanotransducer (MET channels and endocytosis. To study these two mechanisms, rat cochlear explants were cultured as whole organs in gentamicin-containing media. Two-photon imaging of Texas Red conjugated gentamicin (GTTR uptake into live hair cells was rapid and selective. Hypocalcemia, which increases the open probability of MET channels, increased AG entry into hair cells. Three blockers of MET channels (curare, quinine, and amiloride significantly reduced GTTR uptake, whereas the endocytosis inhibitor concanavalin A did not. Dynosore quenched the fluorescence of GTTR and could not be tested. Pharmacologic blockade of MET channels with curare or quinine, but not concanavalin A or dynosore, prevented hair cell loss when challenged with gentamicin for up to 96 hours. Taken together, data indicate that the patency of MET channels mediated AG entry into hair cells and its toxicity. Results suggest that limiting permeation of AGs through MET channel or preventing their entry into endolymph are potential therapeutic targets for preventing hair cell death and hearing loss.


    Directory of Open Access Journals (Sweden)

    Enrique eBalderas


    Full Text Available Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa channel (mitoBKCa has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+ conductance (~300 pS, voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCa have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with β subunits. Notoriously, β1 subunit directly interacts with cytochrome c oxidase and mitoBKCa can be modulated by substrates of the respiratory chain. mitoBKCa channel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+ preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain. Some of them are: how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these questions are essential to define the impact of mitoBKCa channel in mitochondria biology and disease.

  2. A Ca-activated K channel from rabbit renal brush-border membrane vesicles in planar lipid bilayers. (United States)

    Zweifach, A; Desir, G V; Aronson, P S; Giebisch, G H


    Rabbit renal brush-border membranes were fused to planar lipid bilayers to gain insight into the nature and properties of ion channels from the luminal membrane of the proximal tubule. Fusion was obtained using osmotic gradients. A large conductance channel was commonly observed. Measurements of reversal potentials indicated that the channel was selective for K over Rb, Na, and Cl. Channel open probability was increased by membrane depolarization and by increased Ca activity on the intracellular face of the channel. The channel was inhibited by charybdotoxin (CTX), a protein from leiurus venom, from the external side of the channel. The channel was also blocked by Ba and quinidine added to the intracellular bathing solution. Na added to the intracellular bathing solution reduced current amplitude in a voltage-dependent fashion. In addition, methylisobutyl amiloride, an analogue of the K-sparing diuretic amiloride, inhibited channel activity when added to the external solution. The possible physiological role of the channel is discussed. The usefulness to the study of renal ion channels of the technique of fusing membrane vesicles to planar lipid bilayers is evaluated.

  3. Tomato juice intake increases resting energy expenditure and improves hypertriglyceridemia in middle-aged women: an open-label, single-arm study. (United States)

    Hirose, Asuka; Terauchi, Masakazu; Tamura, Moe; Akiyoshi, Mihoko; Owa, Yoko; Kato, Kiyoko; Kubota, Toshiro


    Tomato-based food products have health-promoting and disease-preventing effects. Some tomato juice ingredients may have health benefits for middle-aged women, including women with menopausal symptoms and cardiovascular diseases. We investigated the net effect of tomato juice intake on several health parameters in women in this age group. An open-label, single-arm study was conducted, involving 95 women (40-60-years-old) who had at least one menopausal symptom. The participants refrained from foods and drinks rich in tomato and tomato-based products for 2 weeks prior to the study and during the 8 weeks of tomato juice consumption. After the run-in period, the women were asked to consume 200 mL of unsalted tomato juice, twice daily for 8 weeks. Their menopausal symptoms were evaluated using the Menopausal Symptom Scale (MSS), Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) before the study, and at 4 and 8 weeks after study commencement. At the same times, body composition; blood pressure; heart rate; resting energy expenditures (REEs); and serum levels of triglyceride (TG), cholesterol, glucose, and hemoglobin A1c were measured. Ninety-three women (98%) completed the study. The following parameters showed significant changes, compared with baseline, at study weeks 4 and 8 (mean ± standard deviation at baseline, week 4, and week 8): (1) the MSS score improved (9.9 ± 5.2, 8.5 ± 5.0, 8.3 ± 5.0; P Tomato juice intake alleviated menopausal symptoms, including anxiety, increased REEs and heart rate, and lowered high baseline serum TG levels in middle-aged women. UMIN-CTR UMIN000011877 .

  4. ``Just Another Distribution Channel?'' (United States)

    Lemstra, Wolter; de Leeuw, Gerd-Jan; van de Kar, Els; Brand, Paul

    The telecommunications-centric business model of mobile operators is under attack due to technological convergence in the communication and content industries. This has resulted in a plethora of academic contributions on the design of new business models and service platform architectures. However, a discussion of the challenges that operators are facing in adopting these models is lacking. We assess these challenges by considering the mobile network as part of the value system of the content industry. We will argue that from the perspective of a content provider the mobile network is ‘just another’ distribution channel. Strategic options available for the mobile communication operators are to deliver an excellent distribution channel for content delivery or to move upwards in the value chain by becoming a content aggregator. To become a mobile content aggregator operators will have to develop or acquire complementary resources and capabilities. Whether this strategic option is sustainable remains open.

  5. Open Payments Data (United States)

    U.S. Department of Health & Human Services — Open Payments (otherwise known as the Sunshine Act) - Open Payments is a Congressionally-mandated transparency program that increases awareness of financial...

  6. Tonoplast anion channel activity modulation by pH in Chara corallina. (United States)

    Berecki, G; Eijken, M; Van Iren, F; Van Duijn, B


    The patch-clamp technique was used to investigate regulation of anion channel activity in the tonoplast of Chara corallina in response to changing proton and calcium concentrations on both sides of the membrane. These channels are known to be Ca2+-dependent, with conductances in the range of 37 to 48 pS at pH 7.4. By using low pH at the vacuolar side (either pH(vac) 5.3 or 6.0) and a cytosolic pH (pH(cyt)) varying in a range of 4.3 to 9.0, anion channel activity and single-channel conductance could be reversibly modulated. In addition, Ca2+-sensitivity of the channels was markedly influenced by pH changes. At pH(cyt) values of 7.2 and 7.4 the half-maximal concentration (EC50) for calcium activation was 100-200 microm, whereas an EC(50) of about 5 microm was found at a pH(cyt) of 6.0. This suggests an improved binding of Ca2+ ions to the channel protein at more acidic cytoplasm. At low pH(cyt), anion channel activity and mean open times were voltage-dependent. At pipette potentials (V(p)) of +100 mV, channel activity was approximately 15-fold higher than activity at negative pipette potentials and the mean open time of the channel increased. In contrast, at pH(cyt) 7.2, anion channel activity and the opening behavior seemed to be independent of the applied V(p). The kinetics of the channel could be further controlled by the Ca2+ concentration at the cytosolic membrane side: the mean open time significantly increased in the presence of a high cytosolic Ca2+ concentration. These results show that tonoplast anion channels are maintained in a highly active state in a narrow pH range, below the resting pH(cyt). A putative physiological role of the pH-dependent modulation of these anion channels is discussed.

  7. The K+ channel KZM2 is involved in stomatal movement by modulating inward K+ currents in maize guard cells. (United States)

    Gao, Yong-Qiang; Wu, Wei-Hua; Wang, Yi


    Stomata are the major gates in plant leaf that allow water and gas exchange, which is essential for plant transpiration and photosynthesis. Stomatal movement is mainly controlled by the ion channels and transporters in guard cells. In Arabidopsis, the inward Shaker K + channels, such as KAT1 and KAT2, are responsible for stomatal opening. However, the characterization of inward K + channels in maize guard cells is limited. In the present study, we identified two KAT1-like Shaker K + channels, KZM2 and KZM3, which were highly expressed in maize guard cells. Subcellular analysis indicated that KZM2 and KZM3 can localize at the plasma membrane. Electrophysiological characterization in HEK293 cells revealed that both KZM2 and KZM3 were inward K + (K in ) channels, but showing distinct channel kinetics. When expressed in Xenopus oocytes, only KZM3, but not KZM2, can mediate inward K + currents. However, KZM2 can interact with KZM3 forming heteromeric K in channel. In oocytes, KZM2 inhibited KZM3 channel conductance and negatively shifted the voltage dependence of KZM3. The activation of KZM2-KZM3 heteromeric channel became slower than the KZM3 channel. Patch-clamping results showed that the inward K + currents of maize guard cells were significantly increased in the KZM2 RNAi lines. In addition, the RNAi lines exhibited faster stomatal opening after light exposure. In conclusion, the presented results demonstrate that KZM2 functions as a negative regulator to modulate the K in channels in maize guard cells. KZM2 and KZM3 may form heteromeric K in channel and control stomatal opening in maize. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  8. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

    M.G. Dekimpe (Marnik); B. Skiera (Bernd)


    textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

  9. Upgrading a marketing channels role

    Directory of Open Access Journals (Sweden)

    Tišma-Borota Ankica


    Full Text Available As one of the marketing mix instruments, marketing channels were usually behind other instruments (product, price and promotion. Many companies regarded marketing channels as something that was 'left' after more important strategies of price, product and promotion were created. In recent past, things have changed and marketing channels became more interesting for research. This change came as a result of change in global market functioning especially in competitive advantage, distributors' strength and increasing technology.

  10. Pull Promotions and Channel Coordination


    Eitan Gerstner; James D. Hess


    This paper recommends that manufacturers consider a pull price promotion as a coordination device in an independent channel of distribution. Uncoordinated decisions of both manufacturer and retailer to charge high prices can break down the effort to expand the market, resulting in losses to the channel as a whole. We show that manufacturers can enhance channel price coordination by designing pull price discounts that target price-conscious consumers. The increased price coordination improves ...

  11. Starburst Channels (United States)


    [figure removed for brevity, see original site] Figure 1 Translucent carbon dioxide ice covers the polar regions of Mars seasonally. It is warmed and sublimates (evaporates) from below, and escaping gas carves a numerous channel morphologies. In this example (figure 1) the channels form a 'starburst' pattern, radiating out into feathery extensions. The center of the pattern is being buried with dust and new darker dust fans ring the outer edges. This may be an example of an expanding morphology, where new channels are formed as the older ones fill and are no longer efficiently channeling the subliming gas out. Observation Geometry Image PSP_003443_0980 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 21-Apr-2007. The complete image is centered at -81.8 degrees latitude, 76.2 degrees East longitude. The range to the target site was 247.1 km (154.4 miles). At this distance the image scale is 24.7 cm/pixel (with 1 x 1 binning) so objects 74 cm across are resolved. The image shown here has been map-projected to 25 cm/pixel. The image was taken at a local Mars time of 04:52 PM and the scene is illuminated from the west with a solar incidence angle of 71 degrees, thus the sun was about 19 degrees above the horizon. At a solar longitude of 223.4 degrees, the season on Mars is Northern Autumn.

  12. Gating kinetics of batrachotoxin-modified sodium channels in neuroblastoma cells determined from single-channel measurements


    Huang, L.Y.; Moran, N.; Ehrenstein, G.


    We have observed the opening and closing of single batrachotoxin (BTX)-modified sodium channels in neuroblastoma cells using the patch-clamp method. The conductance of a single BTX-modified channel is approximately 10 pS. At a given membrane potential, the channels are open longer than are normal sodium channels. As is the case for normal sodium channels, the open dwell times become longer as the membrane is depolarized. For membrane potentials more negative than about -70 mV, histograms of b...

  13. Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells.

    Directory of Open Access Journals (Sweden)

    Erin K Purcell

    Full Text Available The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitability are unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type potassium current by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (~30%, ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.

  14. Escitalopram block of hERG potassium channels. (United States)

    Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June


    Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

  15. Open Chemistry: Realizing Open Data, Open Standards, and Open Source


    Hanwell, Marcus; Harris, Chris; Lonie, David; Lutz, Kyle; Cole, David


    The Blue Obelisk has brought together the computational chemistry community and those who are passionate about Open Chemistry and realizing the promise of Open Data, Open Standards, and Open Software (ODOSOS); the three pillars the group promotes. We will present current work that has taken place over the past five years, which is inspired by these pillars, and present plans for future work.The group is actively engaged in multiple open source projects that rely on and promote open standards ...

  16. [Reconstitution of large conductance calcium-activated potassium channels into artificial planar lipid bilayers]. (United States)

    Cheng, Jun; Zeng, Xiao-Rong; Tan, Xiao-Qiu; Li, Peng-Yun; Wen, Jing; Mao, Liang; Yang, Yan


    This study was aimed to establish a method to create a stable planar lipid bilayer membranes (PLBMs), in which large conductance calcium-activated potassium channels (BK Ca ) were reconstituted. Using spreading method, PLBMs were prepared by decane lipid fluid consisting of N 2 -weathered mixture of phosphatidylcholine and cholesterol at 3:1 ratio. After successful incorporation of BK Ca channel into PLBMs, single channel characteristics of BK Ca were studied by patch clamp method. The results showed that i) the single channel conductance of BK Ca was (206.8 ± 16.9) pS; ii) the activities of BK Ca channel were voltage dependent; iii) in the bath solution without Ca 2+ , there was almost no BK Ca channel activities regardless of under hyperpolarization or repolarization conditions; iv) under the condition of +40 mV membrane potential, BK Ca channels were activated in a Ca 2+ concentration dependent manner; v) when [Ca 2+ ] was increased from 1 μmol/L to 100 μmol/L, both the channel open probability and the average open time were increased, and the average close time was decreased from (32.2 ± 2.8) ms to (2.1 ± 1.8) ms; vi) the reverse potential of the reconstituted BK Ca was -30 mV when [K + ] was at 40/140 mmol/L (Cis/Trans). These results suggest that the spreading method could serve as a new method for preparing PLBMs and the reconstituted BK Ca into PLBMs showed similar electrophysiological characteristics to natural BK Ca channels, so the PLBMs with incorporated BK Ca can be used in the studies of pharmacology and dynamics of BK Ca channel.

  17. Modulation of GABAA receptor channel gating by pentobarbital (United States)

    Steinbach, Joe Henry; Akk, Gustav


    We have studied the kinetic properties of channel gating of recombinant α1β2γ2L GABAA receptors transiently expressed in human embryonic kidney 293 cells, using the cell-attached, single-channel patch-clamp technique. The receptors were activated by GABA, β-alanine or piperidine-4-sulfonic acid (P4S), and the effects of pentobarbital (PB) on single-channel activity were examined. At relatively high concentrations of agonist, single-channel activity occurred in well-defined clusters. In global terms, PB increased the mean open time for events in clusters, without changing the mean closed time. The addition of PB shifted the curve relating the probability of being open in a cluster (Po) to lower agonist concentrations, and that shift could be accounted for by the changes in mean open time. The intracluster closed-time histograms contained four components. The durations and relative frequencies of these closed-dwell components were not affected by the presence of 40 μm PB, at any agonist concentration. The duration of one component was dependent upon the concentration of agonist used to activate the receptor. Accordingly, the inverse of the mean duration of this component will be called the effective opening rate. The channel-opening rate constant (β) was determined from the value of the effective opening rate at a saturating agonist concentration. β was about 1900 s−1 when the receptors were activated by GABA, 1500 s−1 when activated by β-alanine, and too low to be determined when P4S was administered. In the presence of 40 μm PB, β was about 1500 s−1 when the receptors were activated by GABA, 1400 s−1 when activated by β-alanine, and 50 s−1 when activated by P4S. Hence, the potentiating effect of PB is not mediated by a change in β. The concentration of agonist producing a half-maximal effective opening rate also remained unaffected in the presence of PB, indicating that receptor affinity for agonists is not influenced by PB. The distributions

  18. The Molecular Basis of Polyunsaturated Fatty Acid Interactions with the Shaker Voltage-Gated Potassium Channel.

    Directory of Open Access Journals (Sweden)

    Samira Yazdi


    Full Text Available Voltage-gated potassium (KV channels are membrane proteins that respond to changes in membrane potential by enabling K+ ion flux across the membrane. Polyunsaturated fatty acids (PUFAs induce channel opening by modulating the voltage-sensitivity, which can provide effective treatment against refractory epilepsy by means of a ketogenic diet. While PUFAs have been reported to influence the gating mechanism by electrostatic interactions to the voltage-sensor domain (VSD, the exact PUFA-protein interactions are still elusive. In this study, we report on the interactions between the Shaker KV channel in open and closed states and a PUFA-enriched lipid bilayer using microsecond molecular dynamics simulations. We determined a putative PUFA binding site in the open state of the channel located at the protein-lipid interface in the vicinity of the extracellular halves of the S3 and S4 helices of the VSD. In particular, the lipophilic PUFA tail covered a wide range of non-specific hydrophobic interactions in the hydrophobic central core of the protein-lipid interface, while the carboxylic head group displayed more specific interactions to polar/charged residues at the extracellular regions of the S3 and S4 helices, encompassing the S3-S4 linker. Moreover, by studying the interactions between saturated fatty acids (SFA and the Shaker KV channel, our study confirmed an increased conformational flexibility in the polyunsaturated carbon tails compared to saturated carbon chains, which may explain the specificity of PUFA action on channel proteins.

  19. Substrate channeling in proline metabolism (United States)

    Arentson, Benjamin W.; Sanyal, Nikhilesh; Becker, Donald F.


    Proline metabolism is an important pathway that has relevance in several cellular functions such as redox balance, apoptosis, and cell survival. Results from different groups have indicated that substrate channeling of proline metabolic intermediates may be a critical mechanism. One intermediate is pyrroline-5-carboxylate (P5C), which upon hydrolysis opens to glutamic semialdehyde (GSA). Recent structural and kinetic evidence indicate substrate channeling of P5C/GSA occurs in the proline catabolic pathway between the proline dehydrogenase and P5C dehydrogenase active sites of bifunctional proline utilization A (PutA). Substrate channeling in PutA is proposed to facilitate the hydrolysis of P5C to GSA which is unfavorable at physiological pH. The second intermediate, gamma-glutamyl phosphate, is part of the proline biosynthetic pathway and is extremely labile. Substrate channeling of gamma-glutamyl phosphate is thought to be necessary to protect it from bulk solvent. Because of the unfavorable equilibrium of P5C/GSA and the reactivity of gamma-glutamyl phosphate, substrate channeling likely improves the efficiency of proline metabolism. Here, we outline general strategies for testing substrate channeling and review the evidence for channeling in proline metabolism. PMID:22201749

  20. Exposure to an open-field arena increases c-Fos expression in a distributed anxiety-related system projecting to the basolateral amygdaloid complex

    DEFF Research Database (Denmark)

    Hale, M.W.; Hay-Schmidt, A.; Mikkelsen, J.D.


    Anxiety states and anxiety-related behaviors appear to be regulated by a distributed and highly interconnected system of brain structures including the basolateral amygdala. Our previous studies demonstrate that exposure of rats to an open-field in high- and low-light conditions results in a marked...... of specific afferent input to this region of the amygdala. In order to identify candidate brain regions mediating anxiety-induced activation of the basolateral amygdaloid complex in rats, we used cholera toxin B subunit (CTb) as a retrograde tracer to identify neurons with direct afferent projections....... These data are consistent with the hypothesis that exposure to the open-field arena activates an anxiety-related neuronal system with convergent input to the basolateral amygdaloid complex Udgivelsesdato: 2008/8/26...

  1. Single Channel Analysis of Isoflurane and Ethanol Enhancement of Taurine-Activated Glycine Receptors. (United States)

    Kirson, Dean; Todorovic, Jelena; Mihic, S John


    The amino acid taurine is an endogenous ligand acting on glycine receptors (GlyRs), which is released by astrocytes in many brain regions, such as the nucleus accumbens and prefrontal cortex. Taurine is a partial agonist with an efficacy significantly lower than that of glycine. Allosteric modulators such as ethanol and isoflurane produce leftward shifts of glycine concentration-response curves but have no effects at saturating glycine concentrations. In contrast, in whole-cell electrophysiology studies these modulators increase the effects of saturating taurine concentrations. A number of possible mechanisms may explain these enhancing effects, including modulator effects on conductance, channel open times, or channel closed times. We used outside-out patch-clamp single channel electrophysiology to investigate the mechanism of action of 200 mM ethanol and 0.55 mM isoflurane in enhancing the effects of a saturating concentration of taurine. Neither modulator enhanced taurine-mediated conductance. Isoflurane increased the probability of channel opening. Isoflurane also increased the lifetimes of the two shortest open dwell times while both agents decreased the likelihood of occurrence of the longest-lived intracluster channel-closing events. The mechanism of enhancement of GlyR functioning by these modulators is dependent on the efficacy of the agonist activating the receptor and the concentration of agonist tested. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance. (United States)

    Linsdell, Paul


    Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel causes cystic fibrosis, while inappropriate activity of this channel occurs in secretory diarrhea and polycystic kidney disease. Drugs that interact directly with CFTR are therefore of interest in the treatment of a number of disease states. This review focuses on one class of small molecules that interacts directly with CFTR, namely inhibitors that act by directly blocking chloride movement through the open channel pore. In theory such compounds could be of use in the treatment of diarrhea and polycystic kidney disease, however in practice all known substances acting by this mechanism to inhibit CFTR function lack either the potency or specificity for in vivo use. Nevertheless, this theoretical pharmacological usefulness set the scene for the development of more potent, specific CFTR inhibitors. Biophysically, open channel blockers have proven most useful as experimental probes of the structure and function of the CFTR chloride channel pore. Most importantly, the use of these blockers has been fundamental in developing a functional model of the pore that includes a wide inner vestibule that uses positively charged amino acid side chains to attract both permeant and blocking anions from the cell cytoplasm. CFTR channels are also subject to this kind of blocking action by endogenous anions present in the cell cytoplasm, and recently this blocking effect has been suggested to play a role in the physiological control of CFTR channel function, in particular as a novel mechanism linking CFTR function dynamically to the composition of epithelial cell secretions. It has also been suggested that future drugs could target this same pathway as a way of pharmacologically increasing CFTR activity in cystic fibrosis. Studying open channel blockers and their mechanisms of action has resulted in significant advances in our understanding of CFTR as a pharmacological target in disease

  3. BK channel modulators: a comprehensive overview

    DEFF Research Database (Denmark)

    Nardi, Antonio; Olesen, Søren-Peter


    channels as a potentially attractive target, the design and synthesis of potent and selective BK modulators continue based on novel chemical ideas. A comprehensive overview of BK channel modulators is therefore timely and important to the current medicinal chemist for review, summary, and classification......The large Ca(2+)-activated K(+) channel (BK channel) reflects per excellence the dilemma of the molecular target driven drug discovery process. Significant experimental evidence suggests that the BK channels play a pivotal and specific role in many pathophysiological conditions supporting...... the notion that the channel represents an innovative and promising drug target. However, after more than ten years of intense research effort both in academia and industry, scientists have yet to witness the approval of a single BK channel modulator for clinical use. On the contrary, three BK openers...

  4. Regulation of KV channel voltage-dependent activation by transmembrane β subunits

    Directory of Open Access Journals (Sweden)

    Xiaohui eSun


    Full Text Available Voltage-activated K+ (KV channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD surrounded by four voltage-sensing domains (VSD. The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

  5. Simultaneous optical and electrical recording of single gramicidin channels. (United States)

    Borisenko, V; Lougheed, T; Hesse, J; Füreder-Kitzmüller, E; Fertig, N; Behrends, J C; Woolley, G A; Schütz, G J


    We report here an approach for simultaneous fluorescence imaging and electrical recording of single ion channels in planar bilayer membranes. As a test case, fluorescently labeled (Cy3 and Cy5) gramicidin derivatives were imaged at the single-molecule level using far-field illumination and cooled CCD camera detection. Gramicidin monomers were observed to diffuse in the plane of the membrane with a diffusion coefficient of 3.3 x 10(-8) cm(2)s(-1). Simultaneous electrical recording detected gramicidin homodimer (Cy3/Cy3, Cy5/Cy5) and heterodimer (Cy3/Cy5) channels. Heterodimer formation was observed optically by the appearance of a fluorescence resonance energy transfer (FRET) signal (irradiation of Cy3, detection of Cy5). The number of FRET signals was significantly smaller than the number of Cy3 signals (Cy3 monomers plus Cy3 homodimers) as expected. The number of FRET signals increased with increasing channel activity. In numerous cases the appearance of a FRET signal was observed to correlate with a channel opening event detected electrically. The heterodimers also diffused in the plane of the membrane with a diffusion coefficient of 3.0 x 10(-8) cm(2)s(-1). These experiments demonstrate the feasibility of simultaneous optical and electrical detection of structural changes in single ion channels as well as suggesting strategies for improving the reliability of such measurements.

  6. Sub-chronic testosterone treatment increases the levels of epithelial sodium channel (ENaC-α, β and γ in the kidney of orchidectomized adult male Sprague–Dawley rats

    Directory of Open Access Journals (Sweden)

    Su Yi Loh


    Full Text Available Testosterone has been reported to cause blood pressure to increase. However mechanisms that underlie the effect of this hormone on this physiological parameter are currently not well understood. The aims of this study were to investigate effects of testosterone on expression of α, β and γ-epithelial sodium channel (ENaC proteins and messenger RNAs (mRNAs in kidneys, the channel known to be involved in Na+ reabsorption, which subsequently can affect the blood pressure. Methods. Adult male Sprague–Dawley (SD rats were orchidectomized fourteen days prior to receiving seven days treatment with testosterone propionate (125 µg/kg/day or 250 µg/kg/day with or without flutamide (androgen receptor blocker or finasteride (5α-reductase inhibitor. Following sacrifice, the kidneys were removed and were subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time PCR (qPCR respectively. The distribution of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Results. The α, β and γ-ENaC proteins and mRNA levels in kidneys were enhanced in rats which received testosterone-only treatment. In these rats, α, β and γ-ENaC proteins were distributed in the distal tubules and collecting ducts of the nephrons. Co-treatment with flutamide or finasteride resulted in the levels of α, β and γ-ENaC proteins and mRNAs in kidneys to decrease. In conclusions, increases in α, β and γ-ENaC protein and mRNA levels in kidneys mainly in the distal tubules and collecting ducts under testosterone influence might lead to enhance Na+ reabsorption which subsequently might cause an increase in blood pressure.

  7. Exposure to an open-field arena increases c-Fos expression in a distributed anxiety-related system projecting to the basolateral amygdaloid complex

    DEFF Research Database (Denmark)

    Hale, M.W.; Hay-Schmidt, A.; Mikkelsen, J.D.


    Anxiety states and anxiety-related behaviors appear to be regulated by a distributed and highly interconnected system of brain structures including the basolateral amygdala. Our previous studies demonstrate that exposure of rats to an open-field in high- and low-light conditions results in a marked...... of specific afferent input to this region of the amygdala. In order to identify candidate brain regions mediating anxiety-induced activation of the basolateral amygdaloid complex in rats, we used cholera toxin B subunit (CTb) as a retrograde tracer to identify neurons with direct afferent projections...

  8. Ca(v)1.2 calcium channel is glutathionylated during oxidative stress in guinea pig and ischemic human heart. (United States)

    Tang, Helen; Viola, Helena M; Filipovska, Aleksandra; Hool, Livia C


    Glutathionylation as a posttranslational modification of proteins is becoming increasingly recognized, but its role in many diseases has not been demonstrated. Oxidative stress and alterations in calcium homeostasis are associated with the development of cardiac hypertrophy. Because the cardiac L-type Ca(2+) channel can be persistently activated after exposure to H(2)O(2), the aim of this study was to determine whether alterations in channel function were associated with glutathionylation of the α(1C) subunit (Ca(v)1.2) channel protein. Immunoblot analysis indicated that Ca(v)1.2 protein is significantly glutathionylated after exposure to H(2)O(2) and glutathione in vitro and after ischemia-reperfusion injury. L-type Ca(2+) channel macroscopic current and intracellular calcium were significantly increased in myocytes after exposure to oxidized glutathione and reversed by glutaredoxin. The increase in current correlated with an increase in open probability of the channel assessed as changes in single-channel activity after exposing the human long N-terminal Ca(v)1.2 to H(2)O(2) or oxidized glutathione. We also demonstrate that the Ca(v)1.2 channel is significantly glutathionylated in ischemic human heart. We conclude that oxidative stress is associated with an increase in glutathionylation of the Ca(v)1.2 channel protein. We suggest that the associated constitutive activity contributes to the development of pathology in ischemic heart disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Burst activity and ultrafast activation kinetics of CaV1.3 Ca²⁺ channels support presynaptic activity in adult gerbil hair cell ribbon synapses. (United States)

    Zampini, Valeria; Johnson, Stuart L; Franz, Christoph; Knipper, Marlies; Holley, Matthew C; Magistretti, Jacopo; Masetto, Sergio; Marcotti, Walter


    Auditory information transfer to afferent neurons relies on precise triggering of neurotransmitter release at the inner hair cell (IHC) ribbon synapses by Ca²⁺ entry through CaV1.3 Ca²⁺ channels. Despite the crucial role of CaV1.3 Ca²⁺ channels in governing synaptic vesicle fusion, their elementary properties in adult mammals remain unknown. Using near-physiological recording conditions we investigated Ca²⁺ channel activity in adult gerbil IHCs. We found that Ca²⁺ channels are partially active at the IHC resting membrane potential (-60 mV). At -20 mV, the large majority (>70%) of Ca²⁺ channel first openings occurred with an estimated delay of about 50 μs in physiological conditions, with a mean open time of 0.5 ms. Similar to other ribbon synapses, Ca²⁺ channels in IHCs showed a low mean open probability (0.21 at -20 mV), but this increased significantly (up to 0.91) when Ca²⁺ channel activity switched to a bursting modality. We propose that IHC Ca²⁺ channels are sufficiently rapid to transmit fast signals of sound onset and support phase-locking. Short-latency Ca²⁺ channel opening coupled to multivesicular release would ensure precise and reliable signal transmission at the IHC ribbon synapse.

  10. ZnO-channel thin-film transistors: Channel mobility

    International Nuclear Information System (INIS)

    Hoffman, R.L.


    ZnO-channel thin-film transistor (TFT) test structures are fabricated using a bottom-gate structure on thermally oxidized Si; ZnO is deposited via RF sputtering from an oxide target, with an unheated substrate. Electrical characteristics are evaluated, with particular attention given to the extraction and interpretation of transistor channel mobility. ZnO-channel TFT mobility exhibits severe deviation from that assumed by ideal TFT models; mobility extraction methodology must accordingly be recast so as to provide useful insight into device operation. Two mobility metrics, μ avg and μ inc , are developed and proposed as relevant tools in the characterization of nonideal TFTs. These mobility metrics are employed to characterize the ZnO-channel TFTs reported herein; values for μ inc as high as 25 cm2/V s are measured, comprising a substantial increase in ZnO-channel TFT mobility as compared to previously reported performance for such devices

  11. A note on critical flow section in collector channels

    Indian Academy of Sciences (India)

    Springer Verlag Heidelberg #4 2048 1996 Dec 15 10:16:45

    For a complete rough regime, the von Karman equation of flow resistance can be used for the determination of friction slope Sc, as was done by Dey (1998a,b). It is important to mention that the ASCE Task Force (1963) on the friction factor in open channels recommended that, for open channel roughness similar to that ...

  12. Negative particle planar and axial channeling and channeling collimation

    Energy Technology Data Exchange (ETDEWEB)

    Carrigan, Richard A., Jr.; /Fermilab


    While information exists on high energy negative particle channeling there has been little study of the challenges of negative particle bending and channeling collimation. Partly this is because negative dechanneling lengths are relatively much shorter. Electrons are not particularly useful for investigating negative particle channeling effects because their material interactions are dominated by channeling radiation. Another important factor is that the current central challenge in channeling collimation is the proton-proton Large Hadron Collider (LHC) where both beams are positive. On the other hand in the future the collimation question might reemerge for electon-positron or muon colliders. Dechanneling lengths increase at higher energies so that part of the negative particle experimental challenge diminishes. In the article different approaches to determining negative dechanneling lengths are reviewed. The more complicated case for axial channeling is also discussed. Muon channeling as a tool to investigate dechanneling is also discussed. While it is now possible to study muon channeling it will probably not illuminate the study of negative dechanneling.

  13. Open Open Fo

    African Journals Online (AJOL)

    whether abstinence and fidelity work as HIV/AIDS prevention strategies among young people was never answered with con- ... Abstinence offers adolescents, .... abstained from sex. This high rate of sexual abstinence was mainly a result of the increasing number of young Ugandans postponing their first sexual activity.

  14. Quantum Correlations Evolution Asymmetry in Quantum Channels

    International Nuclear Information System (INIS)

    Li Meng; Huang Yun-Feng; Guo Guang-Can


    It was demonstrated that the entanglement evolution of a specially designed quantum state in the bistochastic channel is asymmetric. In this work, we generalize the study of the quantum correlations, including entanglement and quantum discord, evolution asymmetry to various quantum channels. We found that the asymmetry of entanglement and quantum discord only occurs in some special quantum channels, and the behavior of the entanglement evolution may be quite different from the behavior of the quantum discord evolution. To quantum entanglement, in some channels it decreases monotonously with the increase of the quantum channel intensity. In some other channels, when we increase the intensity of the quantum channel, it decreases at first, then keeps zero for some time, and then rises up. To quantum discord, the evolution becomes more complex and you may find that it evolutes unsmoothly at some points. These results illustrate the strong dependence of the quantum correlations evolution on the property of the quantum channels. (paper)

  15. Effect of Trimethyltin Chloride on Slow Vacuolar (SV) Channels in Vacuoles from Red Beet (Beta vulgaris L.) Taproots. (United States)

    Trela, Zenon; Burdach, Zbigniew; Siemieniuk, Agnieszka; Przestalski, Stanisław; Karcz, Waldemar


    In the present study, patch-clamp techniques have been used to investigate the effect of trimethyltin chloride (Met3SnCl) on the slow vacuolar (SV) channels in vacuoles from red beet (Beta vulgaris L.) taproots. Activity of SV channels has been measured in whole-vacuole and cytosolic side-out patch configurations. It was found that addition of trimethyltin chloride to the bath solution suppressed, in a concentration-dependent manner, SV currents in red beet vacuoles. The time constant, τ, increased significantly in the presence of the organotin. When single channel activity was analyzed, only little channel activity could be recorded at 100 μM Met3SnCl. Trimethyltin chloride added to the bath medium significantly decreased (by ca. threefold at 100 μM Met3SnCl and at 100 mV voltage, as compared to the control medium) the open probability of single channels. Single channel recordings obtained in the presence and absence of trimethyltin chloride showed that the organotin only slightly (by <10%) decreased the unitary conductance of single channels. It was also found that Met3SnCl significantly diminished the number of SV channel openings, whereas it did not change the opening times of the channels. Taking into account the above and the fact that under the here applied experimental conditions (pH = 7.5) Met3SnCl is a non-dissociated (more lipophilic) compound, we suggest that the suppression of SV currents observed in the presence of the organotin results probably from its hydrophobic properties allowing this compound to translocate near the selectivity filter of the channel.

  16. Automated parallel recordings of topologically identified single ion channels. (United States)

    Kawano, Ryuji; Tsuji, Yutaro; Sato, Koji; Osaki, Toshihisa; Kamiya, Koki; Hirano, Minako; Ide, Toru; Miki, Norihisa; Takeuchi, Shoji


    Although ion channels are attractive targets for drug discovery, the systematic screening of ion channel-targeted drugs remains challenging. To facilitate automated single ion-channel recordings for the analysis of drug interactions with the intra- and extracellular domain, we have developed a parallel recording methodology using artificial cell membranes. The use of stable lipid bilayer formation in droplet chamber arrays facilitated automated, parallel, single-channel recording from reconstituted native and mutated ion channels. Using this system, several types of ion channels, including mutated forms, were characterised by determining the protein orientation. In addition, we provide evidence that both intra- and extracellular amyloid-beta fragments directly inhibit the channel open probability of the hBK channel. This automated methodology provides a high-throughput drug screening system for the targeting of ion channels and a data-intensive analysis technique for studying ion channel gating mechanisms.

  17. Magnetocardiography System in Open-door Magnetically-shielded Room

    International Nuclear Information System (INIS)

    Kim, J. M.; Lee, Y. H.; Kwon, H.; Yu, K. K.; Kim, K.; Park, Y. K.; Sasada, I.


    We have installed a 61-channel magnetocardiography (MCG) system inside a magnetically shielded room (MSR) with a size of 24 m x 24 m x 24 m. The MCG system consists of 1st-order axial gradiometers containing double relaxation oscillation SQUIDs (DROSs) with pick-up coils of a base line of 70 mm. The MSR holds a shielding factor of 50 at 0.1 Hz and 10000 at 100 Hz, when its door in the middle on a front wall is closed. On opening the MSR door, we have obtained the characteristics of the MCG system with a 2.9 Hz noise generated from an air conditioning unit at 13 m distance off the MSR. In an open-door MSR (140 degrees opening), a noise at the center channel increases up to 700 fT/Hz 1/2 at 2.9 Hz and 1.7fT/Hz 1/2 at 60 Hz. MCG signals for a healthy human do not show distortion until the door opens to 45 degrees, but show the effect of noise when the door opens further at 90 degrees and 140 degrees. With the door opens to 45 degrees, MCG measurement can be performed with ease of door operation and without creating claustrophobia for the patient.

  18. Magnetocardiography System in Open-door Magnetically-shielded Room

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. M.; Lee, Y. H.; Kwon, H.; Yu, K. K.; Kim, K.; Park, Y. K. [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of); Sasada, I. [Kyushu University, Fukuoka (Japan)


    We have installed a 61-channel magnetocardiography (MCG) system inside a magnetically shielded room (MSR) with a size of 24 m x 24 m x 24 m. The MCG system consists of 1st-order axial gradiometers containing double relaxation oscillation SQUIDs (DROSs) with pick-up coils of a base line of 70 mm. The MSR holds a shielding factor of 50 at 0.1 Hz and 10000 at 100 Hz, when its door in the middle on a front wall is closed. On opening the MSR door, we have obtained the characteristics of the MCG system with a 2.9 Hz noise generated from an air conditioning unit at 13 m distance off the MSR. In an open-door MSR (140 degrees opening), a noise at the center channel increases up to 700 fT/Hz{sup 1/2} at 2.9 Hz and 1.7fT/Hz{sup 1/2} at 60 Hz. MCG signals for a healthy human do not show distortion until the door opens to 45 degrees, but show the effect of noise when the door opens further at 90 degrees and 140 degrees. With the door opens to 45 degrees, MCG measurement can be performed with ease of door operation and without creating claustrophobia for the patient.

  19. Pore size matters for potassium channel conductance (United States)

    Moldenhauer, Hans; Pincuntureo, Matías


    Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance. PMID:27619418

  20. Villin promoter-mediated transgenic expression of transient receptor potential cation channel, subfamily V, member 6 (TRPV6) increases intestinal calcium absorption in wild-type and vitamin D receptor knockout mice. (United States)

    Cui, Min; Li, Qiang; Johnson, Robert; Fleet, James C


    Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an apical membrane calcium (Ca) channel in the small intestine proposed to be essential for vitamin D-regulated intestinal Ca absorption. Recent studies have challenged the proposed role for TRPV6 in Ca absorption. We directly tested intestinal TRPV6 function in Ca and bone metabolism in wild-type (WT) and vitamin D receptor knockout (VDRKO) mice. TRPV6 transgenic mice (TG) were made with intestinal epithelium-specific expression of a 3X Flag-tagged human TRPV6 protein. TG and VDRKO mice were crossed to make TG-VDRKO mice. Ca and bone metabolism was examined in WT, TG, VDRKO, and TG-VDRKO mice. TG mice developed hypercalcemia and soft tissue calcification on a chow diet. In TG mice fed a 0.25% Ca diet, Ca absorption was more than three-fold higher and femur bone mineral density (BMD) was 26% higher than WT. Renal 1α hydroxylase (CYP27B1) mRNA and intestinal expression of the natural mouse TRPV6 gene were reduced to intestine calbindin-D(9k) expression was elevated >15 times in TG mice. TG-VDRKO mice had high Ca absorption that prevented the low serum Ca, high renal CYP27B1 mRNA, low BMD, and abnormal bone microarchitecture seen in VDRKO mice. In addition, small intestinal calbindin D(9K) mRNA and protein levels were elevated in TG-VDRKO. Transgenic TRPV6 expression in intestine is sufficient to increase Ca absorption and bone density, even in VDRKO mice. VDR-independent upregulation of intestinal calbindin D(9k) in TG-VDRKO suggests this protein may buffer intracellular Ca during Ca absorption. © 2012 American Society for Bone and Mineral Research. Copyright © 2012 American Society for Bone and Mineral Research.

  1. Dynamic Channel Allocation (United States)


    21 9. Beowulf Ethernet Channel Bonding.................................................22 F. SUMMARY...on demand, hybrid channel allocation in wireless networks, and 3 Beowulf Ethernet channel bonding. The background information presented in this...channels are available for dynamic allocation [Ref 32]. 9. Beowulf Ethernet Channel Bonding A by-product of using older computers in a NASA research lab

  2. Melt Channel Formation in Paraffin With Applications to Lava Channels (United States)

    Whitehead, J. A.; Mills, C. J.


    We present the results from laboratory experiments designed to explore channel formation caused by instabilities in fluid flow, and to provide a simple experimental basis to facilitate the extension of lava channel theory. Kelemen et. al. [1995] reported on a series of experiments that explored channel formation resulting from fluid instabilities caused by the ``reactive infiltration instability'' (RII). However, the material used in portions of their experiments was undesirable because of a poorly suited rheology. Therefore, our experiments were initiated as an extension of those earlier experiments, using instead a material with more robust rheological properties. The material chosen for this series of experiments is a paraffin with a freezing temperature of 4°C, which is transparent when liquid and opaque-white when frozen. The paraffin is pumped at a constant and controlled rate into a narrow gap between two circular plates, both with a diameter of ~51cm. The gap is open along the circumference of the plates, allowing the paraffin to flow out of the gap once it reaches the edge of the plate. The upper plate is constructed of Plexiglas to allow observation of the wax below, and it has a hole in the center through which the paraffin is pumped. The lower plate is constructed of aluminum, painted black, and kept at -5°C by circulating coolant through a reservoir below the it. As the paraffin, which is kept at 20°C before being pumped into the gap, flows over the cold lower plate, it begins to freeze and eventually fills up the gap between the plates. A single channel then forms, surrounded by solid paraffin, and the liquid being pumped in is transported via this channel to the edge of the plate. This is a stable state for all but the lowest flow rates attempted and verifies the results from the earlier work exploring the RII. We conducted experiments at different flows rates from 270mL/min to <30mL/min, and recorded the dimensions of the steady state channel

  3. The OpenPlanetary initiative (United States)

    Manaud, Nicolas; Rossi, Angelo Pio; Hare, Trent; Aye, Michael; Galluzzi, Valentina; van Gasselt, Stephan; Martinez, Santa; McAuliffe, Jonathan; Million, Chase; Nass, Andrea; Zinzi, Angelo


    "Open" has become attached to several concepts: science, data, and software are some of the most obvious. It is already common practice within the planetary science community to share spacecraft missions data freely and openly [1]. However, this is not historically the case for software tools, source code, and derived data sets, which are often reproduced independently by multiple individuals and groups. Sharing data, tools and overall knowledge would increase scientific return and benefits [e.g. 2], and recent projects and initiatives are helping toward this goal [e.g. 3,4,5,6].OpenPlanetary is a bottom-up initiative to address the need of the planetary science community for sharing ideas and collaborating on common planetary research and data analysis problems, new challenges, and opportunities. It started from an initial participants effort to stay connected and share information related to and beyond the ESA's first Planetary GIS Workshop [7]. It then continued during the 2nd (US) Planetary Data Workshop [8], and aggregated more people.Our objective is to build an online distributed framework enabling open collaborations within the planetary science community. We aim to co-create, curate and publish resource materials and data sets; to organise online events, to support community-based projects development; and to offer a real-time communication channel at and between conferences and workshops.We will present our current framework and resources, developing projects and ideas, and solicit for feedback and participation. OpenPlanetary is intended for research and education professionals: scientists, engineers, designers, teachers and students, as well as the general public that includes enthusiasts and citizen scientists. All are welcome to join and contribute at[1] International Planetary Data Alliance, [2] Nosek et al (2015), [3] Erard S. et al. (2016), EGU2016-17527. [4] Proposal for a PDS

  4. Detection of TRPV4 channel current-like activity in Fawn Hooded hypertensive (FHH rat cerebral arterial muscle cells.

    Directory of Open Access Journals (Sweden)

    Debebe Gebremedhin

    activation of which increased the open state probability of KCa single-channel current in these arterial myocytes.

  5. Modulation of TRESK background K+ channel by membrane stretch.

    Directory of Open Access Journals (Sweden)

    Gerard Callejo

    Full Text Available The two-pore domain K(+ channel TRESK is expressed in dorsal root ganglion and trigeminal sensory neurons where it is a major contributor to background K(+ current. TRESK acts as a break to prevent excessive sensory neuron activation and decreases in its expression or function have been involved in neuronal hyperexcitability after injury/inflammation, migraine or altered sensory perception (tingling, cooling and pungent burning sensations. All these effects have implicated this channel in nociception and mechanotransduction. To determine the role of TRESK in sensory transduction, we studied its sensitivity to changes in membrane tension (stretch in heterologous systems, F-11 cells and trigeminal neurons. Laminar shear stress increased TRESK currents by 22-30%. An increase in membrane tension induced by cell swelling (hypotonic medium produced a reversible elevation of TRESK currents (39.9%. In contrast, cell shrinkage (hypertonic solution produced the opposite effect. Membrane crenators or cup-formers produced equivalent effects. In trigeminal sensory neurons, TRESK channels were mechanically stimulated by negative pressure, which led to a 1.51-fold increase in channel open probability. TRESK-like currents in trigeminal neurons were additively inhibited by arachidonic acid, acidic pH and hypertonic stimulation, conditions usually found after tissue inflammation. Our results show that TRESK is modulated by changes in cell membrane tension and/or cell volume. Several key players released during inflammation or tissue injury could modulate sensory neuron activation through small changes in membrane tension.

  6. Amazon floodplain channels regulate channel-floodplain water exchange (United States)

    Bates, P. D.; Baugh, C.; Trigg, M.


    We examine the role of floodplain channels in regulating the exchange of water between the Amazon main stem and its extensive floodplains using a combination of field survey, remote sensing and numerical modelling for a 30,000 km2 area around the confluence of the Solimões and Purus rivers. From Landsat imagery we identified 1762 individual floodplain channel reaches with total length of nearly 9300 line km that range in width from 900m to 20m. Using a boat survey we measured width and depth along 509 line km of floodplain channels in 45 separate reaches and used these data to develop geomorphic relationships between width and depth. This enabled reconstruction of the depth of all other channels in the Landsat survey to an RMSE of 2.5m. We then constructed a 2D hydraulic model of this site which included all 9300km of floodplain channels as sub-grid scale features using a recently developed version of the LISFLOOD-FP code. The DEM for the model was derived from a version of the SRTM Digital Elevation Model that was processed to remove vegetation artefacts. The model was run at 270m resolution over the entire 30,000 km2 domain for the period from 2002-2009. Simulations were run with and without floodplain channels to examine the impact of these features on floodplain flow dynamics and storage. Simulated floodplain channel hydraulics were validated against a combination of in-situ and remotely sensed data. Our results show that approximately 100 km3 of water is exchanged between the channel and the floodplain during a typical annual cycle, and 8.5±2.1% of mainstem flows is routed through the floodplain. The overall effect of floodplains channels was to increase the duration of connections between the Amazon River and the floodplain. Inclusion of floodplain channels in the model increased inundation volume by 7.3% - 11.3% at high water, and decreased it at low water by 4.0% - 16.6%, with the range in these estimates due to potential errors in floodplain channel

  7. Channeling through Bent Crystals

    Energy Technology Data Exchange (ETDEWEB)

    Mack, Stephanie; /Ottawa U. /SLAC


    Bent crystals have demonstrated potential for use in beam collimation. A process called channeling is when accelerated particle beams are trapped by the nuclear potentials in the atomic planes within a crystal lattice. If the crystal is bent then the particles can follow the bending angle of the crystal. There are several different effects that are observed when particles travel through a bent crystal including dechanneling, volume capture, volume reflection and channeling. With a crystal placed at the edge of a particle beam, part of the fringe of the beam can be deflected away towards a detector or beam dump, thus helping collimate the beam. There is currently FORTRAN code by Igor Yazynin that has been used to model the passage of particles through a bent crystal. Using this code, the effects mentioned were explored for beam energy that would be seen at the Facility for Advanced Accelerator Experimental Tests (FACET) at a range of crystal orientations with respect to the incoming beam. After propagating 5 meters in vacuum space past the crystal the channeled particles were observed to separate from most of the beam with some noise due to dechanneled particles. Progressively smaller bending radii, with corresponding shorter crystal lengths, were compared and it was seen that multiple scattering decreases with the length of the crystal therefore allowing for cleaner detection of the channeled particles. The input beam was then modified and only a portion of the beam sent through the crystal. With the majority of the beam not affected by the crystal, most particles were not deflected and after propagation the channeled particles were seen to be deflected approximately 5mm. After a portion of the beam travels through the crystal, the entire beam was then sent through a quadrupole magnet, which increased the separation of the channeled particles from the remainder of the beam to a distance of around 20mm. A different code, which was developed at SLAC, was used to

  8. Ca2+ current versus Ca2+ channel cooperativity of exocytosis. (United States)

    Matveev, Victor; Bertram, Richard; Sherman, Arthur


    Recently there has been significant interest and progress in the study of spatiotemporal dynamics of Ca(2+) that triggers exocytosis at a fast chemical synapse, which requires understanding the contribution of individual calcium channels to the release of a single vesicle. Experimental protocols provide insight into this question by probing the sensitivity of exocytosis to Ca(2+) influx. While varying extracellular or intracellular Ca(2+) concentration assesses the intrinsic biochemical Ca(2+) cooperativity of neurotransmitter release, varying the number of open Ca(2+) channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca(2+) channels in triggering exocytosis. Despite the wide use of these Ca(2+) sensitivity measurements, their interpretation often relies on heuristic arguments. Here we provide a detailed analysis of the Ca(2+) sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca(2+) current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca(2+) current magnitude, and the underlying Ca(2+) channel cooperativity, defined as the average number of channels involved in the release of a single vesicle. We find simple algebraic expressions that show that the two are different but linearly related. Further, we use three-dimensional computational modeling of buffered Ca(2+) diffusion to analyze these distinct Ca(2+) cooperativity measures, and demonstrate the role of endogenous Ca(2+) buffers on such measures. We show that buffers can either increase or decrease the Ca(2+) current cooperativity of exocytosis, depending on their concentration and the single-channel Ca(2+) current.

  9. An Effective Channel Allocation Scheme to Reduce Co-Channel and Adjacent Channel Interference for WMN Backhaul

    International Nuclear Information System (INIS)

    Abbasi, S.; Ismaili, I.A.; Khuhawar, F.Y.


    Two folded work presents channel allocation scheme sustaining channel orthogonality and channel spacing to reduce CCI (Co-Channel Interference) and ACI (Adjacent Channel Interference) for inter flow of an intra-flow link. Proposed scheme as a part of radio resource allocation is applied on infrastructure based backhaul of wireless mesh network using directional antennas. The proposed approach is applied separately on 2.4 and 5GHz bands. Interference of connectivity graph is modelled by strongly connected directed graph and greedy algorithms are used for channel allocation. We have used OPNET Modeller suite to simulate network models for this research. The proposed arrangement reduces the channel interference and increases system throughput. In this research, the influence of channel is computed in terms of network throughput and delay. (author)

  10. Relationship between Pore Occupancy and Gating in BK Potassium Channels


    Piskorowski, Rebecca A.; Aldrich, Richard W.


    Permeant ions can have significant effects on ion channel conformational changes. To further understand the relationship between ion occupancy and gating conformational changes, we have studied macroscopic and single-channel gating of BK potassium channels with different permeant monovalent cations. While the slopes of the conductance?voltage curve were reduced with respect to potassium for all permeant ions, BK channels required stronger depolarization to open only when thallium was the perm...

  11. Stabilization of inactive braid channels by vegetation as a mechanism for suppressing braiding and reinforcing the dominant channels in a braided network (United States)

    Egozi, R.; Tal, M.


    channels remained open for reoccupation. This resulted in a fluid, constantly shifting distribution of flow among channels in the braided network. As vegetation cover increased, the river became organized into a distinct channel and non-channel area (i.e., floodplain). Channel switching was less frequent and involved wholesale diversion of flow by avulsions and cutoffs. The results of these separate sets of experiments suggest that the overall morphodynamics of braiding may not be substantially different from that of single-thread channels, and that braided rivers might actually behave like unstable single-thread channels. When vegetation is introduced, the effect of the plants is to stabilize the non-active channels in the braided network, which tend to be abandoned during low flow and reinforce the location of the active transport zone. In other words, the plants opportunistically colonize the area equivalent to the difference between ABI and TBI.

  12. Open Content in Open Context (United States)

    Kansa, Sarah Whitcher; Kansa, Eric C.


    This article presents the challenges and rewards of sharing research content through a discussion of Open Context, a new open access data publication system for field sciences and museum collections. Open Context is the first data repository of its kind, allowing self-publication of research data, community commentary through tagging, and clear…

  13. Building the Open Elements of an Open Data Competition

    NARCIS (Netherlands)

    d'Aquin, Mathieu; Dietze, Stefan; Drachsler, Hendrik; Guy, Marieke; Herder, Eelco; Parodi, Elisabetta


    The European Union is increasingly committed to pushing forward open approaches as indicated by the G8 Open Data Charter, the Opening Up Education initiative, the launch of the Open Education Europa Portal for OER resources and other similar initiatives. The EU-funded LinkedUp Project (Linking Web

  14. Voltage-gated Proton Channels (United States)

    DeCoursey, Thomas E.


    Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance ~103 smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn2+ (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H+ for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens. PMID:23798303

  15. Tyrosine phosphatases epsilon and alpha perform specific and overlapping functions in regulation of voltage-gated potassium channels in Schwann cells

    DEFF Research Database (Denmark)

    Tiran, Zohar; Peretz, Asher; Sines, Tal


    Tyrosine phosphatases (PTPs) epsilon and alpha are closely related and share several molecular functions, such as regulation of Src family kinases and voltage-gated potassium (Kv) channels. Functional interrelationships between PTPepsilon and PTPalpha and the mechanisms by which they regulate K......+ channels and Src were analyzed in vivo in mice lacking either or both PTPs. Lack of either PTP increases Kv channel activity and phosphorylation in Schwann cells, indicating these PTPs inhibit Kv current amplitude in vivo. Open probability and unitary conductance of Kv channels are unchanged, suggesting...... an effect on channel number or organization. PTPalpha inhibits Kv channels more strongly than PTPepsilon; this correlates with constitutive association of PTPalpha with Kv2.1, driven by membranal localization of PTPalpha. PTPalpha, but not PTPepsilon, activates Src in sciatic nerve extracts, suggesting Src...

  16. Open Data and Beyond

    Directory of Open Access Journals (Sweden)

    Frederika Welle Donker


    Full Text Available In recent years, there has been an increasing trend of releasing public sector information as open data. Governments worldwide see the potential benefits of opening up their data. The potential benefits are more transparency, increased governmental efficiency and effectiveness, and external benefits, including societal and economic benefits. The private sector also recognizes potential benefits of making their datasets available as open data. One such company is Liander, an energy network administrator in the Netherlands. Liander views open data as a contributing factor to energy conservation. However, to date there has been little research done into the actual effects of open data. This research has developed a monitoring framework to assess the effects of open data, and has applied the framework to Liander’s small-scale energy consumption dataset.

  17. Weak openness and almost openness

    Directory of Open Access Journals (Sweden)

    David A. Rose


    Full Text Available Weak openness and almost openness for arbitrary functions between topological spaces are defined as duals to the weak continuity of Levine and the almost continuity of Husain respectively. Independence of these two openness conditions is noted and comparison is made between these and the almost openness of Singal and Singal. Some results dual to those known for weak continuity and almost continuity are obtained. Nearly almost openness is defined and used to obtain an improved link from weak continuity to almost continuity.

  18. An Improved Variant of Soybean Type 1 Diacylglycerol Acyltransferase Increases the Oil Content and Decreases the Soluble Carbohydrate Content of Soybeans[OPEN (United States)

    Shen, Bo; Damude, Howard G.; Everard, John D.; Booth, John R.


    Kinetically improved diacylglycerol acyltransferase (DGAT) variants were created to favorably alter carbon partitioning in soybean (Glycine max) seeds. Initially, variants of a type 1 DGAT from a high-oil, high-oleic acid plant seed, Corylus americana, were screened for high oil content in Saccharomyces cerevisiae. Nearly all DGAT variants examined from high-oil strains had increased affinity for oleoyl-CoA, with S0.5 values decreased as much as 4.7-fold compared with the wild-type value of 0.94 µm. Improved soybean DGAT variants were then designed to include amino acid substitutions observed in promising C. americana DGAT variants. The expression of soybean and C. americana DGAT variants in soybean somatic embryos resulted in oil contents as high as 10% and 12%, respectively, compared with only 5% and 7.6% oil achieved by overexpressing the corresponding wild-type DGATs. The affinity for oleoyl-CoA correlated strongly with oil content. The soybean DGAT variant that gave the greatest oil increase contained 14 amino acid substitutions out of a total of 504 (97% sequence identity with native). Seed-preferred expression of this soybean DGAT1 variant increased oil content of soybean seeds by an average of 3% (16% relative increase) in highly replicated, single-location field trials. The DGAT transgenes significantly reduced the soluble carbohydrate content of mature seeds and increased the seed protein content of some events. This study demonstrated that engineering of the native DGAT enzyme is an effective strategy to improve the oil content and value of soybeans. PMID:27208257

  19. Functional coupling between sodium-activated potassium channels and voltage-dependent persistent sodium currents in cricket Kenyon cells. (United States)

    Takahashi, Izumi; Yoshino, Masami


    In this study, we examined the functional coupling between Na(+)-activated potassium (KNa) channels and Na(+) influx through voltage-dependent Na(+) channels in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Single-channel activity of KNa channels was recorded with the cell-attached patch configuration. The open probability (Po) of KNa channels increased with increasing Na(+) concentration in a bath solution, whereas it decreased by the substitution of Na(+) with an equimolar concentration of Li(+). The Po of KNa channels was also found to be reduced by bath application of a high concentration of TTX (1 μM) and riluzole (100 μM), which inhibits both fast (INaf) and persistent (INaP) Na(+) currents, whereas it was unaffected by a low concentration of TTX (10 nM), which selectively blocks INaf. Bath application of Cd(2+) at a low concentration (50 μM), as an inhibitor of INaP, also decreased the Po of KNa channels. Conversely, bath application of the inorganic Ca(2+)-channel blockers Co(2+) and Ni(2+) at high concentrations (500 μM) had little effect on the Po of KNa channels, although Cd(2+) (500 μM) reduced the Po of KNa channels. Perforated whole cell clamp analysis further indicated the presence of sustained outward currents for which amplitude was dependent on the amount of Na(+) influx. Taken together, these results indicate that KNa channels could be activated by Na(+) influx passing through voltage-dependent persistent Na(+) channels. The functional significance of this coupling mechanism was discussed in relation to the membrane excitability of Kenyon cells and its possible role in the formation of long-term memory. Copyright © 2015 the American Physiological Society.

  20. Opening keynote

    International Nuclear Information System (INIS)

    Rae, B.


    In his opening address, the former premier of Ontario summarized the background of the Macdonald Committee which was appointed by his government after it became increasingly apparent that the infrastructure of Hydro Ontario was far bigger than the province and the economy could afford, and that the service that had once given Ontario tremendous competitive advantage, in the form of relatively cheap electric power, had become unsustainable in an era of economic downturn and zero inflation. He stated that the debate about Hydro is part of a broader issue, and it is no longer possible to manage our electricity system as if we were a self-enclosed universe. He predicted that the North American electricity grid will become increasingly interdependent, and that Hydro will have to develop competitive price structures, both to hold its domestic market share and to compete for export sales. He outlined the most pressing issues for Hydro as being debt reduction, while pursuing internal changes to make the organization more efficient. Organizational changes such as the creation of Ontario Hydro International, Ontario Hydro Research, separation of generation operations from the grid, and establishment of separate price and efficiency targets for the autonomous organizations within the utility family, were moves in the right direction. Equally important is to make sure that however Hydro might develop in the future, it is going to be fair to customers, and that the billions of dollars invested in Hydro by Ontario taxpayers over the years, are safeguarded

  1. The Channel Tunnel (United States)


    The Channel Tunnel is a 50.5 km-long rail tunnel beneath the English Channel at the Straits of Dover. It connects Dover, Kent in England with Calais, northern France. The undersea section of the tunnel is unsurpassed in length in the world. A proposal for a Channel tunnel was first put forward by a French engineer in 1802. In 1881, a first attempt was made at boring a tunnel from the English side; the work was halted after 800 m. Again in 1922, English workers started boring a tunnel, and advanced 120 m before it too was halted for political reasons. The most recent attempt was begun in 1987, and the tunnel was officially opened in 1994. At completion it was estimated that the project cost around $18 billion. It has been operating at a significant loss since its opening, despite trips by over 7 million passengers per year on the Eurostar train, and over 3 million vehicles per year. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet. ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. The broad spectral coverage and high spectral resolution of ASTER provides scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and geology; and measuring surface heat balance. The

  2. Open Innovation


    Gassmann, Oliver; Enkel, Ellen


    In the past 10 years, numerous interesting articles, book chapters, and books have been written on open innovation strategies in mainly large companies. While closed innovation models have resulted in important breakthrough innovations, many large companies have abandoned vertical integration strategies in recent years and have moved toward a combination of both closed and open innovation models that are used for reaching different sets of innovative goals. The definition of open innovation a...

  3. Combined Increases in Mitochondrial Cooperation and Oxygen Photoreduction Compensate for Deficiency in Cyclic Electron Flow in Chlamydomonas reinhardtii[W][OPEN (United States)

    Dang, Kieu-Van; Plet, Julie; Tolleter, Dimitri; Jokel, Martina; Cuiné, Stéphan; Carrier, Patrick; Auroy, Pascaline; Richaud, Pierre; Johnson, Xenie; Alric, Jean; Allahverdiyeva, Yagut; Peltier, Gilles


    During oxygenic photosynthesis, metabolic reactions of CO2 fixation require more ATP than is supplied by the linear electron flow operating from photosystem II to photosystem I (PSI). Different mechanisms, such as cyclic electron flow (CEF) around PSI, have been proposed to participate in reequilibrating the ATP/NADPH balance. To determine the contribution of CEF to microalgal biomass productivity, here, we studied photosynthesis and growth performances of a knockout Chlamydomonas reinhardtii mutant (pgrl1) deficient in PROTON GRADIENT REGULATION LIKE1 (PGRL1)–mediated CEF. Steady state biomass productivity of the pgrl1 mutant, measured in photobioreactors operated as turbidostats, was similar to its wild-type progenitor under a wide range of illumination and CO2 concentrations. Several changes were observed in pgrl1, including higher sensitivity of photosynthesis to mitochondrial inhibitors, increased light-dependent O2 uptake, and increased amounts of flavodiiron (FLV) proteins. We conclude that a combination of mitochondrial cooperation and oxygen photoreduction downstream of PSI (Mehler reactions) supplies extra ATP for photosynthesis in the pgrl1 mutant, resulting in normal biomass productivity under steady state conditions. The lower biomass productivity observed in the pgrl1 mutant in fluctuating light is attributed to an inability of compensation mechanisms to respond to a rapid increase in ATP demand. PMID:24989042

  4. Opening the mind to close it: considering a message in light of important values increases message processing and later resistance to change. (United States)

    Blankenship, Kevin L; Wegener, Duane T


    Past research showed that considering a persuasive message in light of important rather than unimportant values creates attitudes that resist later attack. The traditional explanation is that the attitudes come to express the value or that a cognitive link between the value and attitude enhances resistance. However, the current research showed that another explanation is plausible. Similar to other sources of involvement, considering important rather than unimportant values increases processing of the message considered in light of those values. This occurs when the values are identified as normatively high or low in importance and when the perceived importance differs across participants for the same values. The increase in processing creates resistance to later attacks, and unlike past research, individual-level measures of initial amount of processing mediate value importance effects on later resistance to change. Important values motivate processing because they increase personal involvement with the issue, rather than creating attitudes that represent or express core values. (c) 2008 APA, all rights reserved

  5. Stress-Induced Cytokinin Synthesis Increases Drought Tolerance through the Coordinated Regulation of Carbon and Nitrogen Assimilation in Rice1[C][W][OPEN (United States)

    Reguera, Maria; Peleg, Zvi; Abdel-Tawab, Yasser M.; Tumimbang, Ellen B.; Delatorre, Carla A.; Blumwald, Eduardo


    The effects of water deficit on carbon and nitrogen metabolism were investigated in flag leaves of wild-type and transgenic rice (Oryza sativa japonica ‘Kitaake’) plants expressing ISOPENTENYLTRANSFERASE (IPT; encoding the enzyme that mediates the rate-limiting step in cytokinin synthesis) under the control of PSARK, a maturation- and stress-induced promoter. While the wild-type plants displayed inhibition of photosynthesis and nitrogen assimilation during water stress, neither carbon nor nitrogen assimilation was affected by stress in the transgenic PSARK::IPT plants. In the transgenic plants, photosynthesis was maintained at control levels during stress and the flag leaf showed increased sucrose (Suc) phosphate synthase activity and reduced Suc synthase and invertase activities, leading to increased Suc contents. The sustained carbon assimilation in the transgenic PSARK::IPT plants was well correlated with enhanced nitrate content, higher nitrate reductase activity, and sustained ammonium contents, indicating that the stress-induced cytokinin synthesis in the transgenic plants played a role in maintaining nitrate acquisition. Protein contents decreased and free amino acids increased in wild-type plants during stress, while protein content was preserved in the transgenic plants. Our results indicate that the stress-induced cytokinin synthesis in the transgenic plants promoted sink strengthening through a cytokinin-dependent coordinated regulation of carbon and nitrogen metabolism that facilitates an enhanced tolerance of the transgenic plants to water deficit. PMID:24101772

  6. Open innovation

    DEFF Research Database (Denmark)

    Bogers, Marcel; Chesbrough, Henry; Moedas, Carlos


    Open innovation is now a widely used concept in academia, business, and policy making. This article describes the state of open innovation at the intersection of research, practice, and policy. It discusses some key trends (e.g., digital transformation), challenges (e.g., uncertainty......), and potential solutions (e.g., EU funding programs) in the context of open innovation and innovation policy. With this background, the authors introduce select papers published in this Special Section of California Management Review that were originally presented at the second annual World Open Innovation...

  7. Increased Ratio of Electron Transport to Net Assimilation Rate Supports Elevated Isoprenoid Emission Rate in Eucalypts under Drought1[W][OPEN (United States)

    Dani, Kaidala Ganesha Srikanta; Jamie, Ian McLeod; Prentice, Iain Colin; Atwell, Brian James


    Plants undergoing heat and low-CO2 stresses emit large amounts of volatile isoprenoids compared with those in stress-free conditions. One hypothesis posits that the balance between reducing power availability and its use in carbon assimilation determines constitutive isoprenoid emission rates in plants and potentially even their maximum emission capacity under brief periods of stress. To test this, we used abiotic stresses to manipulate the availability of reducing power. Specifically, we examined the effects of mild to severe drought on photosynthetic electron transport rate (ETR) and net carbon assimilation rate (NAR) and the relationship between estimated energy pools and constitutive volatile isoprenoid emission rates in two species of eucalypts: Eucalyptus occidentalis (drought tolerant) and Eucalyptus camaldulensis (drought sensitive). Isoprenoid emission rates were insensitive to mild drought, and the rates increased when the decline in NAR reached a certain species-specific threshold. ETR was sustained under drought and the ETR-NAR ratio increased, driving constitutive isoprenoid emission until severe drought caused carbon limitation of the methylerythritol phosphate pathway. The estimated residual reducing power unused for carbon assimilation, based on the energetic status model, significantly correlated with constitutive isoprenoid emission rates across gradients of drought (r2 > 0.8) and photorespiratory stress (r2 > 0.9). Carbon availability could critically limit emission rates under severe drought and photorespiratory stresses. Under most instances of moderate abiotic stress levels, increased isoprenoid emission rates compete with photorespiration for the residual reducing power not invested in carbon assimilation. A similar mechanism also explains the individual positive effects of low-CO2, heat, and drought stresses on isoprenoid emission. PMID:25139160

  8. Dividing Streamline Formation Channel Confluences by Physical Modeling

    Directory of Open Access Journals (Sweden)

    Minarni Nur Trilita


    Full Text Available Confluence channels are often found in open channel network system and is the most important element. The incoming flow from the branch channel to the main cause various forms and cause vortex flow. Phenomenon can cause erosion of the side wall of the channel, the bed channel scour and sedimentation in the downstream confluence channel. To control these problems needed research into the current width of the branch channel. The incoming flow from the branch channel to the main channel flow bounded by a line distributors (dividing streamline. In this paper, the wide dividing streamline observed in the laboratory using a physical model of two open channels, a square that formed an angle of 30º. Observations were made with a variety of flow coming from each channel. The results obtained in the laboratory observation that the width of dividing streamline flow is influenced by the discharge ratio between the channel branch with the main channel. While the results of a comparison with previous studies showing that the observation in the laboratory is smaller than the results of previous research.

  9. Open hardware for open science

    CERN Document Server

    CERN Bulletin


    Inspired by the open source software movement, the Open Hardware Repository was created to enable hardware developers to share the results of their R&D activities. The recently published CERN Open Hardware Licence offers the legal framework to support this knowledge and technology exchange.   Two years ago, a group of electronics designers led by Javier Serrano, a CERN engineer, working in experimental physics laboratories created the Open Hardware Repository (OHR). This project was initiated in order to facilitate the exchange of hardware designs across the community in line with the ideals of “open science”. The main objectives include avoiding duplication of effort by sharing results across different teams that might be working on the same need. “For hardware developers, the advantages of open hardware are numerous. For example, it is a great learning tool for technologies some developers would not otherwise master, and it avoids unnecessary work if someone ha...

  10. Mitigation of atmospheric carbon emissions through increased energy efficiency versus increased non-carbon energy sources: A trade study using a simplified {open_quotes}market-free{close_quotes} exogenously driven model

    Energy Technology Data Exchange (ETDEWEB)

    Krakowski, R.A.


    A simplified model of global, long-term energy use is described and used to make a `top-level` comparison of two generic approaches for mitigating atmospheric carbon emissions: (a) those based on increased energy efficiency; and (b) those based on increased use of reduced- or non-carbon fuels. As approximate as is the model, first-order estimates of and trade offs between increasing non-carbon generation capacities (e.g., supply-side solutions) versus energy-use efficiency (e.g., demand-side solutions) to stem atmospheric carbon accumulations can be useful in guiding more elaborate models. At the level of this analysis, both the costs of abatement and the costs of damage can be large, with the formation of benefit-to-cost ratios as a means of assessment being limited by uncertainties associated with relating given climatic responses to greenhouse warming to aggregate damage cost, as well as uncertainties associated with procedures used for multi-generation discounting of both abatement and damage costs. In view of uncertainties associated with both supply-side and demand-side approaches, as well as the estimation of greenhouse-warming responses per se, a combination of solutions seems prudent. Key findings are: (a) the relative insensitivity of the benefit-to-cost ratio adopted in this study to supply-side versus demand-side approaches to abating atmospheric carbon-dioxide emissions; (b) the extreme sensitivity of damage costs, abatement costs, and the related benefit-to-cost ratios to the combination of discounting procedure and the (time) concavity of the function used to relate global temperature rise to damage costs; and (c) no matter the discounting procedure and/or functional relationship between average temperature rise and a damage cost, a goal of increased per-capita gross world product at minimum damage suggests action now rather than delay.

  11. Open Revolution.

    Directory of Open Access Journals (Sweden)

    Sean R Eddy


    Full Text Available Sean Eddy reviews "Opening Up Education," a collection of essays that explores how leaders in the "open education movement" intend to exploit digital communications technology, develop innovative and freely redistributable educational methods and resources, and improve education on a global level.

  12. Open Access (United States)

    Suber, Peter


    The Internet lets us share perfect copies of our work with a worldwide audience at virtually no cost. We take advantage of this revolutionary opportunity when we make our work "open access": digital, online, free of charge, and free of most copyright and licensing restrictions. Open access is made possible by the Internet and copyright-holder…

  13. 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


    for the beta-cell potassium channel SUR1/Kir6.2, on glucose- and IL-1beta-induced apoptosis and impaired function in human beta-cells. Exposure of human islets for 4 days to 11.1 and 33.3 mmol/l glucose, 2 ng/ml IL-1beta, or 10 and 100 micromol/l of the sulfonylurea tolbutamide induced beta-cell apoptosis...

  14. K-ATP channel expression and pharmacological in vivo and in vitro studies of the K-ATP channel blocker PNU-37883A in rat middle meningeal arteries

    DEFF Research Database (Denmark)

    Ploug, K.B.; Boni, L.J.; Baun, M.


    Background and purpose: Dilatation of cerebral and dural arteries causes a throbbing, migraine-like pain, indicating that these structures are involved in migraine. Clinical trials suggest that adenosine 5'-triphosphate-sensitive K+ (K-ATP) channel opening may cause migraine by dilatating...... intracranial arteries, including the middle meningeal artery (MMA). We studied the K-ATP channel expression profile in rat MMA and examined the potential inhibitory effects of the K-ATP channel blocker PNU-37883A on K-ATP channel opener-induced relaxation of the rat MMA, using the three K-ATP channel openers...

  15. Ca2+ and voltage dependence of cardiac ryanodine receptor channel block by sphingosylphosphorylcholine. (United States)

    Yasukochi, Midori; Uehara, Akira; Kobayashi, Sei; Berlin, Joshua R


    The effect of sphingosylphosphorylcholine (SPC) on the cytoplasmic Ca(2+) and voltage dependence of channel gating by cardiac ryanodine receptors (RyR) was examined in lipid bilayer experiments. Micromolar concentrations of the lysosphingolipid SPC added to cis solutions rapidly and reversibly decreased the single-channel open probability (P(o)) of reconstituted RyR channels. The SPC-induced decrease in P(o) was marked by an increase in mean closed time and burst-like channel gating. Gating kinetics during intraburst periods were unchanged from those observed in the absence of the sphingolipid, although SPC induced a long-lived closed state that appeared to explain the observed decrease in channel P(o). SPC effects were observed over a broad range of cis [Ca(2+)] but were not competitive with Ca(2+). Interestingly, the sphingolipid-induced, long-lived closed state displayed voltage-dependent kinetics, even though other channel gating kinetics were not sensitive to voltage. Assuming SPC effects represent channel blockade, these results suggest that the blocking rate is independent of voltage whereas the unblocking rate is voltage dependent. Together, these results suggest that SPC binds directly to the cytoplasmic side of the RyR protein in a location in or near the membrane dielectric, but distinct from cytoplasmic Ca(2+) binding sites on the protein.

  16. Lateral transfer of streamwise momentum caused by a roughness transition across a shallow channel

    NARCIS (Netherlands)

    Vermaas, D.A.; Uijttewaal, W.S.J.; Hoitink, A.J.F.


    Research on lateral exchange of streamwise momentum between parallel flows in open channels has mainly been focused on compound channels composed of a main channel and a floodplain, on mixing layer development downstream of river confluences, and on partially vegetated channels. This study aims to

  17. Migration to Current Open Source Technologies by MagIC Enables a More Responsive Website, Quicker Development Times, and Increased Community Engagement (United States)

    Jarboe, N.; Minnett, R.; Koppers, A.; Constable, C.; Tauxe, L.; Jonestrask, L.


    The Magnetics Information Consortium (MagIC) supports an online database for the paleo, geo, and rock magnetic communities ( ). Researchers can upload data into the archive and download data as selected with a sophisticated search system. MagIC has completed the transition from an Oracle backed, Perl based, server oriented website to an ElasticSearch backed, Meteor based thick client website technology stack. Using JavaScript on both the sever and the client enables increased code reuse and allows easy offloading many computational operations to the client for faster response. On-the-fly data validation, column header suggestion, and spreadsheet online editing are some new features available with the new system. The 3.0 data model, method codes, and vocabulary lists can be browsed via the MagIC website and more easily updated. Source code for MagIC is publicly available on GitHub ( ). The MagIC file format is natively compatible with the PmagPy ( paleomagnetic analysis software. MagIC files can now be downloaded from the database and viewed and interpreted in the PmagPy GUI based tool, pmag_gui. Changes or interpretations of the data can then be saved by pmag_gui in the MagIC 3.0 data format and easily uploaded to the MagIC database. The rate of new contributions to the database has been increasing with many labs contributing measurement level data for the first time in the last year. Over a dozen file format conversion scripts are available for translating non-MagIC measurement data files into the MagIC format for easy uploading. We will continue to work with more labs until the whole community has a manageable workflow for contributing their measurement level data. MagIC will continue to provide a global repository for archiving and retrieving paleomagnetic and rock magnetic data and, with the new system in place, be able to more quickly respond to the community

  18. Multi-channel Kondo necklace

    International Nuclear Information System (INIS)

    Fazekas, P.; Kee Haeyoung.


    A multi-channel generalization of Doniach's Kondo necklace model is formulated, and its phase diagram studied in the mean-field approximation. Our intention is to introduce the possible simplest model which displays some of the features expected from the overscreened Kondo lattice. The N conduction electron channels are represented by N sets of pseudospins τ J , j = 1 1,..., N which are all antiferromagnetically coupled to a periodic array of modul S = 1/2 spins. Exploiting permutation symmetry in the channel index j allows us to write down the self-consistency equation for general N. For N > 2, we find that the critical temperature is