Stream Channel Stability.

DTIC Science & Technology

1981-04-01

Cycles of wetting and drying are also t ,v itiue swelling and shrinkage of the soil. S 11ied blocks or peds of soil fabric ,,ks. id downslope soil creep ...hydrographs of water and sediment at the point in question. By feeding the output from the hydrology-transport model into the finite element model...the banks as undercut banks fail. Channel irregularities such as seepage zones, cattle crossings, overbank drainage, buried channels, organic deposits

Role of the Cytoplasmic N-terminal Cap and Per-Arnt-Sim (PAS) Domain in Trafficking and Stabilization of Kv11.1 Channels*

PubMed Central

Ke, Ying; Hunter, Mark J.; Ng, Chai Ann; Perry, Matthew D.; Vandenberg, Jamie I.

2014-01-01

The N-terminal cytoplasmic region of the Kv11.1a potassium channel contains a Per-Arnt-Sim (PAS) domain that is essential for the unique slow deactivation gating kinetics of the channel. The PAS domain has also been implicated in the assembly and stabilization of the assembled tetrameric channel, with many clinical mutants in the PAS domain resulting in reduced stability of the domain and reduced trafficking. Here, we use quantitative Western blotting to show that the PAS domain is not required for normal channel trafficking nor for subunit-subunit interactions, and it is not necessary for stabilizing assembled channels. However, when the PAS domain is present, the N-Cap amphipathic helix must also be present for channels to traffic to the cell membrane. Serine scan mutagenesis of the N-Cap amphipathic helix identified Leu-15, Ile-18, and Ile-19 as residues critical for the stabilization of full-length proteins when the PAS domain is present. Furthermore, mutant cycle analysis experiments support recent crystallography studies, indicating that the hydrophobic face of the N-Cap amphipathic helix interacts with a surface-exposed hydrophobic patch on the core of the PAS domain to stabilize the structure of this critical gating domain. Our data demonstrate that the N-Cap amphipathic helix is critical for channel stability and trafficking. PMID:24695734

Robust Stability of Scaled-Four-Channel Teleoperation with Internet Time-Varying Delays

PubMed Central

Delgado, Emma; Barreiro, Antonio; Falcón, Pablo; Díaz-Cacho, Miguel

2016-01-01

We describe the application of a generic stability framework for a teleoperation system under time-varying delay conditions, as addressed in a previous work, to a scaled-four-channel (γ-4C) control scheme. Described is how varying delays are dealt with by means of dynamic encapsulation, giving rise to mu-test conditions for robust stability and offering an appealing frequency technique to deal with the stability robustness of the architecture. We discuss ideal transparency problems and we adapt classical solutions so that controllers are proper, without single or double differentiators, and thus avoid the negative effects of noise. The control scheme was fine-tuned and tested for complete stability to zero of the whole state, while seeking a practical solution to the trade-off between stability and transparency in the Internet-based teleoperation. These ideas were tested on an Internet-based application with two Omni devices at remote laboratory locations via simulations and real remote experiments that achieved robust stability, while performing well in terms of position synchronization and force transparency. PMID:27128914

Linear stability analysis and nonlinear simulation of the channeling effect on viscous fingering instability in miscible displacement

NASA Astrophysics Data System (ADS)

Shahnazari, M. R.; Maleka Ashtiani, I.; Saberi, A.

2018-03-01

In this paper, the effect of channeling on viscous fingering instability of miscible displacement in porous media is studied. In fact, channeling is introduced as a solution to stabilize the viscous fingering instability. In this solution, narrow channels were placed next to the walls, and by considering an exponential function to model the channeling effect, a heterogeneous media is assumed. In linear stability analysis, the governing equations are transferred to Fourier space, and by introducing a novel numerical method, the transferred equations are analyzed. The growth rate based on the wave number diagram has been drawn up in three sections of the medium. It is found that the flow becomes more stable at the center and unstable along the walls when the permeability ratio is increased. Also when the permeability ratio is approximately equal to one, the channeling has no significant effect. In nonlinear simulations, by using stream function and vortices, new equations have been rewritten and it is shown that channeling has a profound effect on the growth of the fingers and mechanisms. In addition to the superposition of velocity vectors and concentration contours, the development of instability is investigated using the mixing length and sweep efficiency diagram. The results show that although channeling reduces instability, it increases the displacement process time.

Dynamic water patterns change the stability of the collapsed filter conformation of the KcsA K+ channel

PubMed Central

2017-01-01

The selectivity filter of the KcsA K+ channel has two typical conformations—the conductive and the collapsed conformations, respectively. The transition from the conductive to the collapsed filter conformation can represent the process of inactivation that depends on many environmental factors. Water molecules permeating behind the filter can influence the collapsed filter stability. Here we perform the molecular dynamics simulations to study the stability of the collapsed filter of the KcsA K+ channel under the different water patterns. We find that the water patterns are dynamic behind the collapsed filter and the filter stability increases with the increasing number of water molecules. In addition, the stability increases significantly when water molecules distribute uniformly behind the four monomeric filter chains, and the stability is compromised if water molecules only cluster behind one or two adjacent filter chains. The altered filter stabilities thus suggest that the collapsed filter can inactivate gradually under the dynamic water patterns. We also demonstrate how the different water patterns affect the filter recovery from the collapsed conformation. PMID:29049423

Dynamic water patterns change the stability of the collapsed filter conformation of the KcsA K+ channel.

PubMed

Wu, Di

2017-01-01

The selectivity filter of the KcsA K+ channel has two typical conformations-the conductive and the collapsed conformations, respectively. The transition from the conductive to the collapsed filter conformation can represent the process of inactivation that depends on many environmental factors. Water molecules permeating behind the filter can influence the collapsed filter stability. Here we perform the molecular dynamics simulations to study the stability of the collapsed filter of the KcsA K+ channel under the different water patterns. We find that the water patterns are dynamic behind the collapsed filter and the filter stability increases with the increasing number of water molecules. In addition, the stability increases significantly when water molecules distribute uniformly behind the four monomeric filter chains, and the stability is compromised if water molecules only cluster behind one or two adjacent filter chains. The altered filter stabilities thus suggest that the collapsed filter can inactivate gradually under the dynamic water patterns. We also demonstrate how the different water patterns affect the filter recovery from the collapsed conformation.

Stabilization of the Activated hERG Channel Voltage Sensor by Depolarization Involves the S4-S5 Linker.

PubMed

Thouta, Samrat; Hull, Christina M; Shi, Yu Patrick; Sergeev, Valentine; Young, James; Cheng, Yen M; Claydon, Thomas W

2017-01-24

Slow deactivation of hERG channels is critical for preventing cardiac arrhythmia yet the mechanistic basis for the slow gating transition is unclear. Here, we characterized the temporal sequence of events leading to voltage sensor stabilization upon membrane depolarization. Progressive increase in step depolarization duration slowed voltage-sensor return in a biphasic manner (τ fast = 34 ms, τ slow  = 2.5 s). The faster phase of voltage-sensor return slowing correlated with the kinetics of pore opening. The slower component occurred over durations that exceeded channel activation and was consistent with voltage sensor relaxation. The S4-S5 linker mutation, G546L, impeded the faster phase of voltage sensor stabilization without attenuating the slower phase, suggesting that the S4-S5 linker is important for communications between the pore gate and the voltage sensor during deactivation. These data also demonstrate that the mechanisms of pore gate-opening-induced and relaxation-induced voltage-sensor stabilization are separable. Deletion of the distal N-terminus (Δ2-135) accelerated off-gating current, but did not influence the relative contribution of either mechanism of stabilization of the voltage sensor. Lastly, we characterized mode-shift behavior in hERG channels, which results from stabilization of activated channel states. The apparent mode-shift depended greatly on recording conditions. By measuring slow activation and deactivation at steady state we found the "true" mode-shift to be ∼15 mV. Interestingly, the "true" mode-shift of gating currents was ∼40 mV, much greater than that of the pore gate. This demonstrates that voltage sensor return is less energetically favorable upon repolarization than pore gate closure. We interpret this to indicate that stabilization of the activated voltage sensor limits the return of hERG channels to rest. The data suggest that this stabilization occurs as a result of reconfiguration of the pore gate upon opening

Relation of channel stability to scour at highway bridges over waterways in Maryland

USGS Publications Warehouse

Doheny, Edward J.; ,

1993-01-01

Data from assessments of channel stability and observed-scour conditions at 876 highway bridges over Maryland waterways were entered into a database. Relations were found to exist among specific, deterministic variables and observed-scour and debris conditions. Relations were investigated between (1) high-flow angle of attack and pier- and abutment-footing exposure, (2)abutment location and abutment-footing exposure, (3) type of bed material and pier-footing exposure, (4) tree cover on channel banks and mass wasting of the channel banks, and (5) land use near the bridge and the presence of debris blockage at the bridge opening. The results of the investigation indicate the following: (1) The number of pier and abutment-footing exposures increased for increasing high-flow angles of attack, (2) the number of abutment-footing exposures increased for abutments that protrude into the channel, (3) pier-footing exposures were most common for bridges over streams with channel beds of gravel, (4) mass wasting of channel banks with tree cover of 50 percent or greater near the bridge was less than mass wasting of channel banks with tree cover of less than 50 percent near the bridge, and (5) bridges blockage than bridge in row crop and swamp basins.

The stability of a flexible cantilever in viscous channel flow

NASA Astrophysics Data System (ADS)

Cisonni, Julien; Lucey, Anthony D.; Elliott, Novak S. J.; Heil, Matthias

2017-05-01

Most studies of the flow-induced flutter instability of a flexible cantilever have assumed inviscid flow because of the high flow speeds and the large scale of the structures encountered in the wide range of applications of this fluid-structure interaction (FSI) system. However, for instance, in the fields of energy harvesting and biomechanics, low flow speeds and small- and micro-scale systems can give relatively low Reynolds numbers so that fluid viscosity needs to be explicitly accounted for to provide reliable predictions of channel-immersed-cantilever stability. In this study, we employ a numerical model coupling the Navier-Stokes equations and a one-dimensional elastic beam model. We conduct a parametric investigation to determine the conditions leading to flutter instability of a slender flexible cantilever immersed in two-dimensional viscous channel flow for Reynolds numbers lower than 1000. The large set of numerical simulations carried out allows predictions of the influence of decreasing Reynolds numbers and of the cantilever confinement on the single-mode neutral stability of the FSI system and on the pre- and post-critical cantilever motion. This model's predictions are also compared to those of a FSI model containing a two-dimensional solid model in order to assess, primarily, the effect of the cantilever slenderness in the simulations. Results show that an increasing contribution of viscosity to the hydrodynamic forces significantly alters the instability boundaries. In general, a decrease in Reynolds number is predicted to produce a stabilisation of the FSI system, which is more pronounced for high fluid-to-solid mass ratios. For particular fluid-to-solid mass ratios, viscous effects can lower the critical velocity and lead to a change in the first unstable structural mode. However, at constant Reynolds number, the effects of viscosity on the system stability are diminished by the confinement of the cantilever, which strengthens the importance of

A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.

PubMed

Tang, Cheng; Zhou, Xi; Nguyen, Phuong Tran; Zhang, Yunxiao; Hu, Zhaotun; Zhang, Changxin; Yarov-Yarovoy, Vladimir; DeCaen, Paul G; Liang, Songping; Liu, Zhonghua

2017-07-01

Voltage-gated sodium channels (Na V s) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial Na V s have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial Na V s. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic Na V s Ns V Ba (nonselective voltage-gated Bacillus alcalophilus ) and NaChBac (bacterial sodium channel from Bacillus halodurans ) (IC 50 = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of Ns V Ba, whereas the local anesthetic drug lidocaine was shown to antagonize Ns V Ba without affecting channel gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of Ns V Ba, with F98 being the critical residue in determining toxin affinity. All electrophysiological data and in silico analysis suggested that JZTx-27 trapped VSM of Ns V Ba in one of the deactivated states. In mammalian Na V s, JZTx-27 preferably inhibited the inactivation of Na V 1.5 by targeting the fourth transmembrane domain. To our knowledge, this is the first report of peptide antagonist for prokaryotic Na V s. More important, we proposed that JZTx-27 stabilized the Ns V Ba VSM in the deactivated state and may be used as a probe to determine the structure of the deactivated VSM of Na V s.-Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G., Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel. © FASEB.

The initial instability and finite-amplitude stability of alternate bars in straight channels

USGS Publications Warehouse

Nelson, J.M.

1990-01-01

The initial instability and fully developed stability of alternate bars in straight channels are investigated using linearized and nonlinear analyses. The fundamental instability leading to these features is identified through a linear stability analysis of the equations governing the flow and sediment transport fields. This instability is explained in terms of topographically induced steering of the flow and the associated pattern of erosion and deposition on the bed. While the linear theory is useful for examining the instability mechanism, this approach is shown to yield relatively little information about well-developed alternate bars and, specifically, the linear analysis is shown to yield poor predictions of the fully developed bar wavelength. A fully nonlinear approach is presented that permits computation of the evolution of these bed features from an initial perturbation to their fully developed morphology. This analysis indicates that there is typically substantial elongation of the bar wavelength during the evolution process, a result that is consistent with observations of bar development in flumes and natural channels. The nonlinear approach demonstrates that the eventual stability of these features is a result of the interplay between topographic steering effects, secondary flow production as a result of streamline curvature, and gravitationally induced modifications of sediment fluxes over a sloping bed. ?? 1990.

Stability analysis for capillary channel flow: 1d and 3d computations

NASA Astrophysics Data System (ADS)

Grah, Aleksander; Klatte, Jörg; Dreyer, Michael E.

The subject of the presentation are numerical studies on capillary channel flow, based on results of the sounding rocket TEXUS experiments. The flow through a capillary channel is established by a gear pump at the outlet. The channel, consists of two parallel glass plates with a width of 25 mm, a gap of 10 mm and a length of 12 mm. The meniscus of a compensation tube maintains a constant system pressure. Steady and dynamic pressure effects in the system force the surfaces to bend inwards. A maximum flow rate is achieved when the free surface collapses and gas ingestion occurs at the outlet. This critical flow rate depends on the channel geometry, the flow regime and the liquid properties. The aim of the experiments is the determination of the free surface shape and to find the maximum flow rate. In order to study the unsteady liquid loop behavior, a dimensionless one-dimensional model and a corresponding three-dimensional model were developed. The one-dimensional model is based on the unsteady Bernoulli equation, the unsteady continuity equation and geometrical conditions for the surface curvature and the flow cross-section. The experimental and evaluated contour data show good agreement for a sequence of transient flow rate perturbations. In the case of steady flow at maximum flow rate, when the "choking" effect occurs, the surfaces collapse and cause gas ingestion into the channel. This effect is related to the Speed Index. At the critical flow rate the Speed Index reaches the value 1, in analogy to the Mach Number. Unsteady choking does not necessarily cause surface collapse. We show, that temporarily Speed Index values exceeding One may be achieved for a perfectly stable supercritical dynamic flow. As a supercritical criterion for the dynamic free surface stability we define a Dynamic Index considering the local capillary pressure and the convective pressure, which is a function of the local velocity. The Dynamic Index is below One for stable flow while D = 1

Performance, Stability, and Plume Characterization of the HERMeS Thruster with Boron Nitride Silica Composite Discharge Channel

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Huang, Wensheng; Gilland, James H.; Haag, Thomas W.; Mackey, Jonathan; Yim, John; Pinero, Luis; Williams, George; Peterson, Peter; Herman, Daniel

2017-01-01

NASA's Hall Effect Rocket with Magnetic Shielding (HERMeS) 12.5kW Technology Demonstration Unit-3 (TDU-3) has been the subject of extensive technology maturation in preparation for flight system development. Detailed performance, stability, and plume characterization tests of the thruster were performed at NASA GRC's Vacuum Facility 5 (VF-5). The TDU-3 thruster implements a magnetic topology that is identical to TDU-1. The TDU-3 boron nitride silica composite discharge channel material is different than the TDU-1 heritage boron nitride discharge channel material. Performance and stability characterization of the TDU-3 thruster was performed at discharge voltages between 300V and 600V and at discharge currents between 5A and 21.8A. The thruster performance and stability were assessed for varying magnetic field strength, cathode flow fractions between 5% and 9%, varying harness inductance, and for reverse magnet polarity. Performance characterization test results indicate that the TDU-3 thruster performance is in family with the TDU-1 levels. TDU-3's thrust efficiency of 65% and specific impulse of 2,800sec at 600V and 12.5kW exceed performance levels of SOA Hall thrusters. Thruster stability regimes were characterized with respect to the thruster discharge current oscillations (discharge current peak-to-peak and root mean square magnitudes), discharge current waveform power spectral density analysis, and maps of the current-voltage-magnetic field. Stability characterization test results indicate a stability profile similar to TDU-1. Finally, comparison of the TDU-1 and TDU-3 plume profiles found that there were negligible differences in the plasma plume characteristics between the TDU with heritage boron nitride versus the boron nitride silica composite discharge channel.

Stability of gas channels in a dense suspension in the presence of obstacles

NASA Astrophysics Data System (ADS)

Poryles, Raphaël; Varas, Germán; Vidal, Valérie

2017-06-01

We investigate experimentally the influence of a fixed obstacle on gas rising in a dense suspension. Air is injected at a constant flow rate by a single nozzle at the bottom center of a Hele-Shaw cell. Without obstacles, previous works have shown that a fluidized zone is formed with a parabolic shape, with a central air channel and two granular convection rolls on its sides. Here, we quantify the influence of the obstacle's shape, size, and height on the location and dynamics of the central air channel. Different regimes are reported: the air channel can simply deviate (stable), or it can switch sides over time (unstable), leading to two signatures not only above the obstacle, but sometimes also below it. This feedback also influences the channel deviation when bypassing the obstacle. A wake of less or no motion is reported above the largest obstacles as well as the maximum probability of gas location, which can be interesting for practical applications. The existence of a critical height hc≃7 cm is discussed and compared with the existence of an air finger that develops from the injection nozzle and is stable in time. A dimensionless number describing the transition between air fingering and fracturing makes it possible to predict the channel's stability.

Lateral movement and stability of channel banks near four highway crossings in southwestern Mississippi

USGS Publications Warehouse

Turnipseed, D. Phil

1994-01-01

Channel meandering in alluvial streams has caused localized channel instability that has resulted in bridge failure and loss of human life in Mississippi. The U.S. Geological Survey, in coopera- tion with the Mississippi Department of Transpor- tation, conducted a study to develop a better methodology for defining and estimating channel meandering. For this report, river reaches near four bridge sites with current lateral movement of channel banks were selected for study. The lateral movement of channel banks was studied by mapping meanders from aerial photographs taken at various times, evaluating available discharge measurements, and measuring existing channel geometry and soil strength properties at these sites. Rapid, unre- stricted meander cuts and sandy banks are charac- teristic of the sites. Lateral movement was signi- ficant upstream from all four sites, and only one bridge site did not have significant lateral channel-bank movement during the study period. The development of cutbanks and localized channel-bank erosion have caused unstable conditions at three of the sites. Maps of tops of channel indicate significant lateral movement of channel banks upstream and downstream of all four sites and near the bridges at three of four sites. No significant movement occurred at the U.S. Highway 98 crossing of the Bogue Chitto near Tylertown from 1941 to 1991 despite large floods in 1983 and 1990. Slope stability analyses indicated this site to be marginally stable. The maximum lateral movement indicated from maps of tops of channel banks was 680 feet of northward movement of the right (north) bank of the Homochitto River near the State Highway 33 crossing at Rosetta from 1941 to 1983.

C-Terminal β9-Strand of the Cyclic Nucleotide-Binding Homology Domain Stabilizes Activated States of Kv11.1 Channels

PubMed Central

Ng, Chai Ann; Ke, Ying; Perry, Matthew D.; Tan, Peter S.; Hill, Adam P.; Vandenberg, Jamie I.

2013-01-01

Kv11.1 potassium channels are important for regulation of the normal rhythm of the heartbeat. Reduced activity of Kv11.1 channels causes long QT syndrome type 2, a disorder that increases the risk of cardiac arrhythmias and sudden cardiac arrest. Kv11.1 channels are members of the KCNH subfamily of voltage-gated K+ channels. However, they also share many similarities with the cyclic nucleotide gated ion channel family, including having a cyclic nucleotide-binding homology (cNBH) domain. Kv11.1 channels, however, are not directly regulated by cyclic nucleotides. Recently, crystal structures of the cNBH domain from mEAG and zELK channels, both members of the KCNH family of voltage-gated potassium channels, revealed that a C-terminal β9-strand in the cNBH domain occupied the putative cyclic nucleotide-binding site thereby precluding binding of cyclic nucleotides. Here we show that mutations to residues in the β9-strand affect the stability of the open state relative to the closed state of Kv11.1 channels. We also show that disrupting the structure of the β9-strand reduces the stability of the inactivated state relative to the open state. Clinical mutations located in this β9-strand result in reduced trafficking efficiency, which suggests that binding of the C-terminal β9-strand to the putative cyclic nucleotide-binding pocket is also important for assembly and trafficking of Kv11.1 channels. PMID:24204727

Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization

PubMed Central

Auffenberg, Eva; Jurik, Angela; Mattusch, Corinna; Stoffel, Rainer; Genewsky, Andreas; Namendorf, Christian; Schmid, Roland M.; Rammes, Gerhard; Biel, Martin; Uhr, Manfred; Moosmang, Sven; Michalakis, Stylianos; Wotjak, Carsten T.; Thoeringer, Christoph K.

2016-01-01

Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type potassium channel using the chemogenetic technique of small molecule induced protein stabilization. Based on shield1-mediated shedding of a destabilizing domain fused to a protein of interest and inhibition of protein degradation, this principle has been adopted for biomedicine, but not in neuroscience so far. Here, we apply this chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. We could show that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. We also validated this novel pharmacogenetic method in different neurobehavioral paradigms.The DD-Kir2.1 may complement the existing portfolio of pharmaco- and optogenetic techniques for specific neuron manipulation, but it may also provide an example for future applications of this principle in neuroscience research. PMID:26757616

Enhanced stability of thin film transistors with double-stacked amorphous IWO/IWO:N channel layer

NASA Astrophysics Data System (ADS)

Lin, Dong; Pi, Shubin; Yang, Jianwen; Tiwari, Nidhi; Ren, Jinhua; Zhang, Qun; Liu, Po-Tsun; Shieh, Han-Ping

2018-06-01

In this work, bottom-gate top-contact thin film transistors with double-stacked amorphous IWO/IWO:N channel layer were fabricated. Herein, amorphous IWO and N-doped IWO were deposited as front and back channel layers, respectively, by radio-frequency magnetron sputtering. The electrical characteristics of the bi-layer-channel thin film transistors (TFTs) were examined and compared with those of single-layer-channel (i.e., amorphous IWO or IWO:N) TFTs. It was demonstrated to exhibit a high mobility of 27.2 cm2 V‑1 s‑1 and an on/off current ratio of 107. Compared to the single peers, bi-layer a-IWO/IWO:N TFTs showed smaller hysteresis and higher stability under negative bias stress and negative bias temperature stress. The enhanced performance could be attributed to its unique double-stacked channel configuration, which successfully combined the merits of the TFTs with IWO and IWO:N channels. The underlying IWO thin film provided percolation paths for electron transport, meanwhile, the top IWO:N layer reduced the bulk trap densities. In addition, the IWO channel/gate insulator interface had reduced defects, and IWO:N back channel surface was insensitive to the ambient atmosphere. Overall, the proposed bi-layer a-IWO/IWO:N TFTs show potential for practical applications due to its possibly long-term serviceability.

Sediment and channel-geometry investigations for the Kansas River bank stabilization study, Kansas, Nebraska, and Colorado

USGS Publications Warehouse

Osterkamp, W.R.; Curtis, R.E.; Crowther, H.G.

1982-01-01

Analysis of hydrologic data from the Kansas River basin suggests that the channels of the lower Solomon, Saline, and Smoky Hill Rivers have narrowed and stabilized as a result of construction of upstream reservoirs. The Kansas River channel, however, remains relatively unstable and locally active. Streamflow regulation and sediment trapping by reservoirs are possible causes of changes occurring at various Kansas River sites. An inferred deficiency of the suspended-sediment load, however, is likely to cause continuing instability. Suspended sediment in the Kansas River apparently is too sparse to form and maintain stable alluvial banks. The deficiency probably results in an increase of bed material movement, general channel widening, and local braiding. Significant channel degradation is lacking at most sites, but may occur in response to long-term (decades-to-centuries) regulation. Recent degradation near Bonner Springs, Kans., may be the result of sand and gravel removal. Any imposed changes that shorten the channel or reduce the suspended-sediment discharge of the Kansas River are expected to cause additional channel instability. (USGS)

Effect of settling particles on the stability of a particle-laden flow in a vertical plane channel

NASA Astrophysics Data System (ADS)

Boronin, S. A.; Osiptsov, A. N.

2018-03-01

The stability of a viscous particle-laden flow in a vertical plane channel in the presence of the gravity force is studied. The flow is described using a two-fluid "dusty-gas" model with negligibly small volume fraction of fines and two-way coupling of the phases. Two different profiles of the particle number density in the main flow are considered: homogeneous and non-homogeneous in the form of two layers symmetric about the channel axis. The novel element of the linear-stability problem formulation is a particle velocity slip in the main flow caused by the gravity-induced settling of the dispersed phase. The eigenvalue problem for a linearized system of governing equations is solved using the orthonormalization and QZ algorithms. For a uniform particle number density distribution, it is found that there exists a domain in the plane of Froude and Stokes numbers, in which the two-phase flow in a vertical channel is stable for an arbitrary Reynolds number. This stability domain corresponds to relatively small-inertia particles and large velocity-slip in the main flow. In contrast to the flow with a uniform particle number density distribution, the stratified dusty-gas flow in a vertical channel is unstable over a wide range of governing parameters. The instability at small Reynolds numbers is determined by the gravitational mode characterized by small wavenumbers (long-wave instability), while at larger Reynolds numbers the instability is dominated by the shear mode with the time-amplification factor larger than that of the gravitational mode. The results of the study can be used for optimization of a large number of technological processes, including those in riser reactors, pneumatic conveying in pipeline systems, hydraulic fracturing, and well cementing.

Suspended-sediment loads, reservoir sediment trap efficiency, and upstream and downstream channel stability for Kanopolis and Tuttle Creek Lakes, Kansas, 2008-10

USGS Publications Warehouse

Juracek, Kyle E.

2011-01-01

Continuous streamflow and turbidity data collected from October 1, 2008, to September 30, 2010, at streamgage sites upstream and downstream from Kanopolis and Tuttle Creek Lakes, Kansas, were used to compute the total suspended-sediment load delivered to and released from each reservoir as well as the sediment trap efficiency for each reservoir. Ongoing sedimentation is decreasing the ability of the reservoirs to serve several purposes including flood control, water supply, and recreation. River channel stability upstream and downstream from the reservoirs was assessed using historical streamgage information. For Kanopolis Lake, the total 2-year inflow suspended-sediment load was computed to be 600 million pounds. Most of the suspended-sediment load was delivered during short-term, high-discharge periods. The total 2-year outflow suspended-sediment load was computed to be 31 million pounds. Sediment trap efficiency for the reservoir was estimated to be 95 percent. The mean annual suspended-sediment yield from the upstream basin was estimated to be 129,000 pounds per square mile per year. No pronounced changes in channel width were evident at five streamgage sites located upstream from the reservoir. At the Ellsworth streamgage site, located upstream from the reservoir, long-term channel-bed aggradation was followed by a period of stability. Current (2010) conditions at five streamgages located upstream from the reservoir were typified by channel-bed stability. At the Langley streamgage site, located immediately downstream from the reservoir, the channel bed degraded 6.15 feet from 1948 to 2010. For Tuttle Creek Lake, the total 2-year inflow suspended-sediment load was computed to be 13.3 billion pounds. Most of the suspended-sediment load was delivered during short-term, high-discharge periods. The total 2-year outflow suspended-sediment load was computed to be 327 million pounds. Sediment trap efficiency for the reservoir was estimated to be 98 percent. The mean

Protons stabilize the closed conformation of gain-of-function mutants of the TRPV1 channel.

PubMed

Boukalova, Stepana; Teisinger, Jan; Vlachova, Viktorie

2013-03-01

The vanilloid transient receptor potential channel TRPV1 is a molecular integrator of noxious stimuli, including capsaicin, heat and protons. Despite clear similarities between the overall architecture of TRPV1 and voltage-dependent potassium (Kv) channels, the extent of conservation in the molecular logic for gating is unknown. In Kv channels, a small contact surface between S1 and the pore-helix is required for channel functioning. To explore the function of S1 in TRPV1, we used tryptophan-scanning mutagenesis and characterized the responses to capsaicin and protons. Wild-type-like currents were generated in 9 out of 17 mutants; three mutants (M445W, A452W, R455W) were non-functional. The conservative mutation R455K in the extracellular extent of S1 slowed down capsaicin-induced activation and prevented normal channel closure. This mutant was neither activated nor potentiated by protons, on the contrary, protons promoted a rapid deactivation of its currents. Similar phenotypes were found in two other gain-of-function mutants and also in the pore-helix mutant T633A, known to uncouple proton activation. We propose that the S1 domain contains a functionally important region that may be specifically involved in TRPV1 channel gating, and thus be important for the energetic coupling between S1-S4 sensor activation and gate opening. Analogous to Kv channels, the S1-pore interface might serve to stabilize conformations associated with TRPV1 channel gating. Copyright © 2012 Elsevier B.V. All rights reserved.

Analysis of inter-residue contacts reveals folding stabilizers in P-loops of potassium, sodium, and TRPV channels.

PubMed

Korkosh, V S; Zhorov, B S; Tikhonov, D B

2016-05-01

The family of P-loop channels includes potassium, sodium, calcium, cyclic nucleotide-gated and TRPV channels, as well as ionotropic glutamate receptors. Despite vastly different physiological and pharmacological properties, the channels have structurally conserved folding of the pore domain. Furthermore, crystallographic data demonstrate surprisingly similar mutual disposition of transmembrane and membrane-diving helices. To understand determinants of this conservation, here we have compared available high-resolution structures of sodium, potassium, and TRPV1 channels. We found that some residues, which are in matching positions of the sequence alignment, occur in different positions in the 3D alignment. Surprisingly, we found 3D mismatches in well-packed P-helices. Analysis of energetics of individual residues in Monte Carlo minimized structures revealed cyclic patterns of energetically favorable inter- and intra-subunit contacts of P-helices with S6 helices. The inter-subunit contacts are rather conserved in all the channels, whereas the intra-subunit contacts are specific for particular types of the channels. Our results suggest that these residue-residue contacts contribute to the folding stabilization. Analysis of such contacts is important for structural and phylogenetic studies of homologous proteins.

Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

PubMed

Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

2015-09-01

Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stability assessment of QKD procedures in commercial quantum cryptography systems versus quality of dark channel

NASA Astrophysics Data System (ADS)

Jacak, Monika; Melniczuk, Damian; Jacak, Janusz; Jóźwiak, Ireneusz; Gruber, Jacek; Jóźwiak, Piotr

2015-02-01

In order to assess the susceptibility of the quantum key distribution (QKD) systems to the hacking attack including simultaneous and frequent system self-decalibrations, we analyze the stability of the QKD transmission organized in two commercially available systems. The first one employs non-entangled photons as flying qubits in the dark quantum channel for communication whereas the second one utilizes the entangled photon pairs to secretly share the cryptographic key. Applying standard methods of the statistical data analysis to the characteristic indicators of the quality of the QKD communication (the raw key exchange rate [RKER] and the quantum bit error rate [QBER]), we have estimated the pace of the self-decalibration of both systems and the repeatability rate in the case of controlled worsening of the dark channel quality.

Vegetative impacts upon bedload transport capacity and channel stability for differing alluvial planforms in the Yellow River source zone

NASA Astrophysics Data System (ADS)

Li, Zhi Wei; Yu, Guo An; Brierley, Gary; Wang, Zhao Yin

2016-07-01

The influence of vegetation upon bedload transport and channel morphodynamics is examined along a channel stability gradient ranging from meandering to anabranching to anabranching-braided to fully braided planform conditions along trunk and tributary reaches of the Upper Yellow River in western China. Although the regional geology and climate are relatively consistent across the study area, there is a distinct gradient in the presence and abundance of riparian vegetation for these reaches atop the Qinghai-Tibet Plateau (elevations in the study area range from 2800 to 3400 m a.s.l.). To date, the influence of vegetative impacts upon channel planform and bedload transport capacity of alluvial reaches of the Upper Yellow River remains unclear because of a lack of hydrological and field data. In this region, the types and pattern of riparian vegetation vary with planform type as follows: trees exert the strongest influence in the anabranching reach, the meandering reach flows through meadow vegetation, the anabranching-braided reach has a grass, herb, and sparse shrub cover, and the braided reach has no riparian vegetation. A non-linear relation between vegetative cover on the valley floor and bedload transport capacity is evident, wherein bedload transport capacity is the highest for the anabranching reach, roughly followed by the anabranching-braided, braided, and meandering reaches. The relationship between the bedload transport capacity of a reach and sediment supply from upstream exerts a significant influence upon channel stability. Bedload transport capacity during the flood season (June-September) in the braided reach is much less than the rate of sediment supply, inducing bed aggradation and dynamic channel adjustments. Rates of channel adjustment are less pronounced for the anabranching-braided and anabranching reaches, while the meandering reach is relatively stable (i.e., this is a passive meandering reach).

Benchmarking the stability of human detergent-solubilised voltage-gated sodium channels for structural studies using eel as a reference

PubMed Central

Slowik, Daria; Henderson, Richard

2015-01-01

With the ultimate goal of detailed structural analysis of mammalian and particularly human voltage-gated sodium channels (VGSCs), we have investigated the relative stability of human and rat VGSCs and compared them with electric eel VGSC. We found that NaV1.3 from rat was the most stable after detergent solubilisation. The order of stability was rNaV1.3 > hNaV1.2 > hNaV1.1 > hNaV1.6 > hNaV1.3 > hNaV1.4. However, a comparison with the VGSC from Electrophorus electricus, which is most similar to NaV1.4, shows that the eel VGSC is considerably more stable in detergent than the human VGSCs examined. We conclude that current methods of structural analysis, such as single particle electron cryomicroscopy (cryoEM), may be most usefully targeted to eel VGSC or rNaV1.3, but that structural analysis on the full spectrum of VGSCs, by methods that require greater stability such as crystallisation and X-ray crystallography, will require further stabilisation of the channel. PMID:25838126

A chimera encoding the fusion of an acetylcholine-binding protein to an ion channel is stabilized in a state close to the desensitized form of ligand-gated ion channels.

PubMed

Grutter, Thomas; Prado de Carvalho, Lia; Virginie, Dufresne; Taly, Antoine; Fischer, Markus; Changeux, Jean-Pierre

2005-03-01

To understand the mechanism of allosteric coupling between the ligand-binding domain and the ion channel of the Cys-loop ligand-gated ion channels (LGICs), we fused the soluble acetylcholine-binding protein (AChBP), which lacks an ion channel, to either the cationic serotonin type-3A ion channel (5HT(3A)) or the anionic glycine ion channel. Both linear chimeras expressed in HEK-293 cells display high affinity for the nicotinic agonist epibatidine (K(D) = 0.2-0.5 nM), but are not targeted to the cell surface. Only after substituting a ring of three loops located at the putative membrane side of the AChBP three-dimensional structure by the homologous residues of 5HT(3A), the resulting chimera AChBP(ring)/5HT(3A) (i) still displayed on intact cells an apparent high affinity for epibatidine, yet with a fourfold decrease (K(D) = 2.1 nM), (ii) displayed a high proportion of low affinity sites (11 +/- 7 microM) for the resting state stabilizing competitive antagonist alpha-bungarotoxin and (iii) was successfully targeted to the cell surface, as seen by immunofluorescence labelling. The AChBP(ring)/5HT(3A) chimera forms a pentameric structure, as revealed by sucrose gradient sedimentation. However, no whole-cell patch-clamp currents were detectable. Interestingly, binding assays with membrane fragments prepared from cells expressing AChBP(ring)/5HT(3A) showed a decrease in the apparent affinity for the agonists nicotine and epibatidine (5-fold), concomitant with an increase in the proportion of high-affinity sites (48 +/- 1 nM) for alpha-bungarotoxin. These results indicate that fusion of AChBP to an ion channel forms a pentameric receptor exposed to the cell surface and able to convert between discrete allosteric states, but stabilized in a high affinity state for epibatidine that likely corresponds to a desensitized form of LGICs. These artificial chimeras might offer a useful system to investigate signal transduction in LGICs.

Organic field-effect transistors: a combined study on short-channel effects and the influence of substrate pre-treatment on ambient stability

NASA Astrophysics Data System (ADS)

Klug, A.; Meingast, A.; Wurzinger, G.; Blümel, A.; Schmoltner, K.; Scherf, U.; List, E. J. W.

2011-10-01

For high-performance low-cost applications based on organic field-effect transistors (OFETs) and corresponding sensors essential properties of the applied semiconducting materials include solution-processability, high field-effect mobility, compatibility with adjacent layers and stability with respect to ambient conditions. In this combined study regioregular poly(3-hexylthiophene)- and pentacene-based bottom-gate bottom-contact OFETs with various channel lengths are thoroughly investigated with respect to short-channel effects and the implications of dielectric surface modification with hexamethyldisilazane (HMDS) on device performance. In addition, the influences of oxygen, moisture and HMDStreatment on the ambient stability of the devices are evaluated in detail. While OFETs without surface modification exhibited the expected degradation behavior upon air exposure mainly due to oxygen/moisture-induced doping or charge-carrier trapping, the stability of the investigated semiconductors was found to be distinctly increased when the substrate surface was hydrophobized. The presented results thoroughly summarize important issues which have to be considered when selecting semiconducting materials for high-performance OFETs and OFET-based sensors.

Dynamic stability analysis for capillary channel flow: One-dimensional and three-dimensional computations and the equivalent steady state technique

NASA Astrophysics Data System (ADS)

Grah, Aleksander; Dreyer, Michael E.

2010-01-01

Spacecraft technology provides a series of applications for capillary channel flow. It can serve as a reliable means for positioning and transport of liquids under low gravity conditions. Basically, capillary channels provide liquid paths with one or more free surfaces. A problem may be flow instabilities leading to a collapse of the liquid surfaces. A result is undesired gas ingestion and a two phase flow which can in consequence cause several technical problems. The presented capillary channel consists of parallel plates with two free liquid surfaces. The flow rate is established by a pump at the channel outlet, creating a lower pressure within the channel. Owing to the pressure difference between the liquid phase and the ambient gas phase the free surfaces bend inwards and remain stable as long as they are able to resist the steady and unsteady pressure effects. For the numerical prediction of the flow stability two very different models are used. The one-dimensional unsteady model is mainly based on the Bernoulli equation, the continuity equation, and the Gauss-Laplace equation. For three-dimensional evaluations an open source computational fluid dynamics (CFD) tool is applied. For verifications the numerical results are compared with quasisteady and unsteady data of a sounding rocket experiment. Contrary to previous experiments this one results in a significantly longer observation sequence. Furthermore, the critical point of the steady flow instability could be approached by a quasisteady technique. As in previous experiments the comparison to the numerical model evaluation shows a very good agreement for the movement of the liquid surfaces and for the predicted flow instability. The theoretical prediction of the flow instability is related to the speed index, based on characteristic velocities of the capillary channel flow. Stable flow regimes are defined by stability criteria for steady and unsteady flow. The one-dimensional computation of the speed index

A room temperature strategy towards enhanced performance and bias stability of oxide thin film transistor with a sandwich structure channel layer

NASA Astrophysics Data System (ADS)

Zeng, Yong; Ning, Honglong; Zheng, Zeke; Zhang, Hongke; Fang, Zhiqiang; Yao, Rihui; Xu, Miao; Wang, Lei; Lan, Linfeng; Peng, Junbiao; Lu, Xubing

2017-04-01

Thermal annealing is a conventional and effective way to improve the bias stress stability of oxide thin film transistors (TFT) on solid substrates. However, it is still a challenge for enhancing the bias stress stability of oxide TFTs on flexible substrates by high-temperature post-treatment due to the thermal sensitivity of flexible substrates. Here, a room temperature strategy is presented towards enhanced performance and bias stability of oxide TFTs by intentionally engineering a sandwich structure channel layer consisting of a superlattice with aluminum doped zinc oxide (AZO) and Al2O3 thin films. The Al2O3/AZO/Al2O3-TFTs not only exhibit a saturation mobility of 9.27 cm2 V-1 s-1 and a linear mobility of 11.38 cm2 V-1 s-1 but also demonstrate a better bias stress stability than AZO/Al2O3-TFT. Moreover, the underlying mechanism of this enhanced electrical performance of TFTs with a sandwich structure channel layer is that the bottom Al2O3 thin films can obviously improve the crystalline phase of AZO films while decreasing electrical trapping centers and adsorption sites for undesirable molecules such as water and oxygen.

Variable responses of fish assemblages, habitat, and stability to natural-channel-design restoration in Catskill Mountain streams

USGS Publications Warehouse

Baldigo, Barry P.; Ernst, Anne G.; Warren, Dana R.; Miller, Sarah J.

2010-01-01

Natural-channel-design (NCD) restorations were recently implemented within large segments of five first- and second-order streams in the Catskill Mountains of New York in an attempt to increase channel stability, reduce bed and bank erosion, and sustain water quality. In conjunction with these efforts, 54 fish and habitat surveys were done from 1999 to 2007 at six restored reaches and five stable control reaches to evaluate the effects of NCD restoration on fish assemblages, habitat, and bank stability. A before–after–control–impact study design and two-factor analysis of variance were used to quantify the net changes in habitat and fish population and community indices at treatment reaches relative to those at unaltered control reaches. The density and biomass of fish communities were often dominated by one or two small prey species and no or few predator species before restoration and by one or more trout (Salmonidae) species after restoration. Significant increases in community richness (30%), diversity (40%), species or biomass equitability (32%), and total biomass (up to 52%) in at least four of the six restored reaches demonstrate that NCD restorations can improve the health and sustainability of fish communities in geomorphically unstable Catskill Mountain streams over the short to marginally long term. Bank stability, stream habitat, and trout habitat suitability indices (HSIs) generally improved significantly at the restored reaches, but key habitat features and trout HSIs did not change or decreased at two of them. Fish communities and trout populations at these two reaches were not positively affected by NCD restorations. Though NCD restorations often had a positive effect on habitat and fish communities, our results show that the initial habitat conditions limit the relative improvements than can be achieved, habitat quality and stability do not necessarily respond in unison, and biotic and abiotic responses cannot always be generalized.

Inferring tidal wetland stability from channel sediment fluxes: observations and a conceptual model

USGS Publications Warehouse

Ganju, Neil K.; Nidzieko, Nicholas J.; Kirwan, Matthew L.

2013-01-01

Anthropogenic and climatic forces have modified the geomorphology of tidal wetlands over a range of timescales. Changes in land use, sediment supply, river flow, storminess, and sea level alter the layout of tidal channels, intertidal flats, and marsh plains; these elements define wetland complexes. Diagnostically, measurements of net sediment fluxes through tidal channels are high-temporal resolution, spatially integrated quantities that indicate (1) whether a complex is stable over seasonal timescales and (2) what mechanisms are leading to that state. We estimated sediment fluxes through tidal channels draining wetland complexes on the Blackwater and Transquaking Rivers, Maryland, USA. While the Blackwater complex has experienced decades of degradation and been largely converted to open water, the Transquaking complex has persisted as an expansive, vegetated marsh. The measured net export at the Blackwater complex (1.0 kg/s or 0.56 kg/m2/yr over the landward marsh area) was caused by northwesterly winds, which exported water and sediment on the subtidal timescale; tidally forced net fluxes were weak and precluded landward transport of suspended sediment from potential seaward sources. Though wind forcing also exported sediment at the Transquaking complex, strong tidal forcing and proximity to a turbidity maximum led to an import of sediment (0.031 kg/s or 0.70 kg/m2/yr). This resulted in a spatially averaged accretion of 3.9 mm/yr, equaling the regional relative sea level rise. Our results suggest that in areas where seaward sediment supply is dominant, seaward wetlands may be more capable of withstanding sea level rise over the short term than landward wetlands. We propose a conceptual model to determine a complex's tendency toward stability or instability based on sediment source, wetland channel location, and transport mechanisms. Wetlands with a reliable portfolio of sources and transport mechanisms appear better suited to offset natural and

AVHRR channel selection for land cover classification

USGS Publications Warehouse

Maxwell, S.K.; Hoffer, R.M.; Chapman, P.L.

2002-01-01

Mapping land cover of large regions often requires processing of satellite images collected from several time periods at many spectral wavelength channels. However, manipulating and processing large amounts of image data increases the complexity and time, and hence the cost, that it takes to produce a land cover map. Very few studies have evaluated the importance of individual Advanced Very High Resolution Radiometer (AVHRR) channels for discriminating cover types, especially the thermal channels (channels 3, 4 and 5). Studies rarely perform a multi-year analysis to determine the impact of inter-annual variability on the classification results. We evaluated 5 years of AVHRR data using combinations of the original AVHRR spectral channels (1-5) to determine which channels are most important for cover type discrimination, yet stabilize inter-annual variability. Particular attention was placed on the channels in the thermal portion of the spectrum. Fourteen cover types over the entire state of Colorado were evaluated using a supervised classification approach on all two-, three-, four- and five-channel combinations for seven AVHRR biweekly composite datasets covering the entire growing season for each of 5 years. Results show that all three of the major portions of the electromagnetic spectrum represented by the AVHRR sensor are required to discriminate cover types effectively and stabilize inter-annual variability. Of the two-channel combinations, channels 1 (red visible) and 2 (near-infrared) had, by far, the highest average overall accuracy (72.2%), yet the inter-annual classification accuracies were highly variable. Including a thermal channel (channel 4) significantly increased the average overall classification accuracy by 5.5% and stabilized interannual variability. Each of the thermal channels gave similar classification accuracies; however, because of the problems in consistently interpreting channel 3 data, either channel 4 or 5 was found to be a more

Stability of the Zagreb realization of the Carnegie-Mellon-Berkeley coupled-channels unitary model

NASA Astrophysics Data System (ADS)

Osmanović, H.; Ceci, S.; Švarc, A.; Hadžimehmedović, M.; Stahov, J.

2011-09-01

In Hadžimehmedović [Phys. Rev. CPRVCAN0556-281310.1103/PhysRevC.84.035204 84, 035204 (2011)] we have used the Zagreb realization of Carnegie-Melon-Berkeley coupled-channel, unitary model as a tool for extracting pole positions from the world collection of partial-wave data, with the aim of eliminating model dependence in pole-search procedures. In order that the method is sensible, we in this paper discuss the stability of the method with respect to the strong variation of different model ingredients. We show that the Zagreb CMB procedure is very stable with strong variation of the model assumptions and that it can reliably predict the pole positions of the fitted partial-wave amplitudes.

Barbiturates Bind in the GLIC Ion Channel Pore and Cause Inhibition by Stabilizing a Closed State*♦

PubMed Central

Fourati, Zaineb; Ruza, Reinis Reinholds; Laverty, Duncan; Drège, Emmanuelle; Delarue-Cochin, Sandrine; Joseph, Delphine; Koehl, Patrice; Smart, Trevor; Delarue, Marc

2017-01-01

Barbiturates induce anesthesia by modulating the activity of anionic and cationic pentameric ligand-gated ion channels (pLGICs). Despite more than a century of use in clinical practice, the prototypic binding site for this class of drugs within pLGICs is yet to be described. In this study, we present the first X-ray structures of barbiturates bound to GLIC, a cationic prokaryotic pLGIC with excellent structural homology to other relevant channels sensitive to general anesthetics and, as shown here, to barbiturates, at clinically relevant concentrations. Several derivatives of barbiturates containing anomalous scatterers were synthesized, and these derivatives helped us unambiguously identify a unique barbiturate binding site within the central ion channel pore in a closed conformation. In addition, docking calculations around the observed binding site for all three states of the receptor, including a model of the desensitized state, showed that barbiturates preferentially stabilize the closed state. The identification of this pore binding site sheds light on the mechanism of barbiturate inhibition of cationic pLGICs and allows the rationalization of several structural and functional features previously observed for barbiturates. PMID:27986812

Two-Channel Transparency-Optimized Control Architectures in Bilateral Teleoperation With Time Delay.

PubMed

Kim, Jonghyun; Chang, Pyung Hun; Park, Hyung-Soon

2013-01-01

This paper introduces transparency-optimized control architectures (TOCAs) using two communication channels. Two classes of two-channel TOCAs are found, thereby showing that two channels are sufficient to achieve transparency. These TOCAs achieve a greater level of transparency but poorer stability than three-channel TOCAs and four-channel TOCAs. Stability of the two-channel TOCAs has been enhanced while minimizing transparency degradation by adding a filter; and a combined use of the two classes of two-channel TOCAs is proposed for both free space and constrained motion, which involve switching between two TOCAs for transition between free space and constrained motions. The stability condition of the switched teleoperation system is derived for practical applications. Through the one degree-of-freedom (DOF) experiment, the proposed two-channel TOCAs were shown to operate stably, while achieving better transparency under time delay than the other TOCAs.

Two-Channel Transparency-Optimized Control Architectures in Bilateral Teleoperation With Time Delay

PubMed Central

Kim, Jonghyun; Chang, Pyung Hun; Park, Hyung-Soon

2013-01-01

This paper introduces transparency-optimized control architectures (TOCAs) using two communication channels. Two classes of two-channel TOCAs are found, thereby showing that two channels are sufficient to achieve transparency. These TOCAs achieve a greater level of transparency but poorer stability than three-channel TOCAs and four-channel TOCAs. Stability of the two-channel TOCAs has been enhanced while minimizing transparency degradation by adding a filter; and a combined use of the two classes of two-channel TOCAs is proposed for both free space and constrained motion, which involve switching between two TOCAs for transition between free space and constrained motions. The stability condition of the switched teleoperation system is derived for practical applications. Through the one degree-of-freedom (DOF) experiment, the proposed two-channel TOCAs were shown to operate stably, while achieving better transparency under time delay than the other TOCAs. PMID:23833548

Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability.

PubMed

Pedrozo, Zully; Criollo, Alfredo; Battiprolu, Pavan K; Morales, Cyndi R; Contreras-Ferrat, Ariel; Fernández, Carolina; Jiang, Nan; Luo, Xiang; Caplan, Michael J; Somlo, Stefan; Rothermel, Beverly A; Gillette, Thomas G; Lavandero, Sergio; Hill, Joseph A

2015-06-16

L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress-induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes. We subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and α1C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction-induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals PC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein. © 2015 American Heart Association, Inc.

Channelized bottom melting and stability of floating ice shelves

NASA Astrophysics Data System (ADS)

Rignot, E.; Steffen, K.

2008-01-01

The floating ice shelf in front of Petermann Glacier, in northwest Greenland, experiences massive bottom melting that removes 80% of its ice before calving into the Arctic Ocean. Detailed surveys of the ice shelf reveal the presence of 1-2 km wide, 200-400 m deep, sub-ice shelf channels, aligned with the flow direction and spaced by 5 km. We attribute their formation to the bottom melting of ice from warm ocean waters underneath. Drilling at the center of one of channel, only 8 m above sea level, confirms the presence of ice-shelf melt water in the channel. These deep incisions in ice-shelf thickness imply a vulnerability to mechanical break up and climate warming of ice shelves that has not been considered previously.

Stream Channel Stability. Appendix A. Evaluation of Streambank Erosion Control Demonstration Projects in the Bluff Line Streams of Northwest Mississippi,

DTIC Science & Technology

1981-04-01

streambanks except on very small channels and agricultural waterways. Vegetation is commonly used to stabilize small agricultural storm runoff ...subjected to severe hydrologic and plant growth stresses during 1980. Large storm runoff events, occurring early in the year, produced velocities in...than average for the prevailing conditions. The overall survival rate for the 1979 and 1980 plantings of the shrub type bristly locus (Robinia fertilis

Role of individual histidines in the pH-dependent global stability of human chloride intracellular channel 1.

PubMed

Achilonu, Ikechukwu; Fanucchi, Sylvia; Cross, Megan; Fernandes, Manuel; Dirr, Heini W

2012-02-07

Chloride intracellular channel proteins exist in both a soluble cytosolic form and a membrane-bound form. The mechanism of conversion between the two forms is not properly understood, although one of the contributing factors is believed to be the variation in pH between the cytosol (~7.4) and the membrane (~5.5). We systematically mutated each of the three histidine residues in CLIC1 to an alanine at position 74 and a phenylalanine at positions 185 and 207. We examined the effect of the histidine-mediated pH dependence on the structure and global stability of CLIC1. None of the mutations were found to alter the global structure of the protein. However, the stability of H74A-CLIC1 and H185F-CLIC1, as calculated from the equilibrium unfolding data, is no longer dependent on pH because similar trends are observed at pH 7.0 and 5.5. The crystal structures show that the mutations result in changes in the local hydrogen bond coordination. Because the mutant total free energy change upon unfolding is not different from that of the wild type at pH 7.0, despite the presence of intermediates that are not seen in the wild type, we propose that it may be the stability of the intermediate state rather than the native state that is dependent on pH. On the basis of the lower stability of the intermediate in the H74A and H185F mutants compared to that of the wild type, we conclude that both His74 and His185 are involved in triggering the pH changes to the conformational stability of wild-type CLIC1 via their protonation, which stabilizes the intermediate state.

Calculation of Linear Stability of a Stratified Gas-Liquid Flow in an Inclined Plane Channel

NASA Astrophysics Data System (ADS)

Trifonov, Yu. Ya.

2018-01-01

Linear stability of liquid and gas counterflows in an inclined channel is considered. The full Navier-Stokes equations for both phases are linearized, and the dynamics of periodic disturbances is determined by means of solving a spectral problem in wide ranges of Reynolds numbers for the liquid and vapor velocity. Two unstable modes are found in the examined ranges: surface mode (corresponding to the Kapitsa waves at small velocities of the gas) and shear mode in the gas phase. The wave length and the phase velocity of neutral disturbances of both modes are calculated as functions of the Reynolds number for the liquid. It is shown that these dependences for the surface mode are significantly affected by the gas velocity.

CHANNEL EVOLUTION IN MODIFIED ALLUVIAL STREAMS.

USGS Publications Warehouse

Simon, Andrew; Hupp, Cliff R.

1987-01-01

This study (a) assesses the channel changes and network trends of bed level response after modifications between 1959 and 1972 of alluvial channels in western Tennessee and (b) develops a conceptual model of bank slope development to qualitatively assess bank stability and potential channel widening. A six-step, semiquantitative model of channel evolution in disturbed channels was developed by quantifying bed level trends and recognizing qualitative stages of bank slope development. Development of the bank profile is defined in terms of three dynamic and observable surfaces: (a) vertical face (70 to 90 degrees), (b) upper bank (25 to 50 degrees), and (c) slough line (20 to 25 degrees).

Alcohols potentiate the function of 5-HT3 receptor–channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state

PubMed Central

Zhou, Qing; Verdoorn, Todd A; Lovinger, David M

1998-01-01

5-HT3 receptor-mediated ion current was recorded from NCB-20 neuroblastoma cells using the whole-cell patch-clamp technique. Rapid drug superfusion was used to study the mechanism of alcohol potentiation of 5-HT3 receptor function and to analyse effects of alcohols on receptor-channel kinetics in detail.Trichloroethanol (TCEt) increased in a dose-dependent way the initial slope, 20–80 % rise time and measured desensitization rate of the current induced by low concentrations (1–2 μm) of 5-HT. Ethanol (EtOH) and butanol (ButOH) had similar effects on the 5-HT3 receptor-induced current.TCEt and ButOH decreased the measured desensitization rate of current induced by 10 μm 5-HT, a maximally effective concentration of agonist. These alcohols also increased the relative amplitude of steady state to peak current induced by 2 or 10 μm 5-HT, indicating a possible decrease in the intrinsic rate of desensitization.TCEt also decreased the deactivation rate of the current activated by 2 μm 5-HT after a short pulse of agonist application.Current sweeps generated by 1 μm 5-HT in the presence or absence of 10 mm TCEt or 100 mm EtOH were well fitted using a modified standard kinetic model derived from the nicotinic acetylcholine receptor. This analysis indicated that potentiation by alcohols could be accounted for by increases in the association rate constant coupled with decreases in the dissociation and desensitization rate constants.This study suggests that alcohols potentiate 5-HT3 receptor-mediated current by both increasing the rate of channel activation and stabilizing the open state by decreasing the rates of channel deactivation and desensitization. PMID:9518697

Groundwater controls on river channel pattern

NASA Astrophysics Data System (ADS)

Bätz, Nico; Colombini, Pauline; Cherubini, Paolo; Lane, Stuart N.

2017-04-01

Braided rivers are characterized by high rates of morphological change. However, despite the potential for frequent disturbance, vegetated patches may develop within this system and influence long-term channel dynamics and channel patterns through the "engineering effects" of vegetation. The stabilizing effect of developing vegetation on morphological change has been widely shown by flume experiments and (historic) aerial pictures analysis. Thus, there is a balance between disturbance and stabilization, mediated through vegetation, that may determine the long-term geomorphic and biogeomorphic evolution of the river. It follows that with a change in disturbance frequency relative to the rate of vegetation establishment, a systematic geomorphological shift could occur. Research has addressed how changes in disturbance frequency affect river channel pattern, but has rarely addressed the way in which the stabilizing effects of biogeomorphic succession interact with disturbance frequency to maintain a river in a more dynamic or a less dynamic state. Here, we quantify how the interplay between groundwater access, disturbance frequency and vegetation succession, drive changes in channel pattern. We studied this complex interplay on a transitional gravel-bed river system (braided, wandering, meandering) close to Geneva (Switzerland) - the Allondon River. Dendroecological analysis demonstrate that vegetation growth is driven by groundwater access. Groundwater access conditions the rate of vegetation stabilization at the sub-reach scale and, due to a reduction in flood-related disturbance frequency over the last 50 years, drives a change in channel pattern. Where groundwater is shallower, vegetation encroachment rates were high and as flood-related disturbance decreased, the river has shifted towards a meandering state. Where groundwater was deeper, vegetation growth was limited by water-access and thus vegetation encroachment rates were low. Even though there was a

Nonlinear stability analysis of Darcy’s flow with viscous heating

PubMed Central

Alves, Leonardo S. de B.; Barletta, Antonio

2016-01-01

The nonlinear stability of a rectangular porous channel saturated by a fluid is here investigated. The aspect ratio of the channel is assumed to be variable. The channel walls are considered impermeable and adiabatic except for the horizontal top which is assumed to be isothermal. The viscous dissipation is acting inside the channel as internal heat generator. A basic throughflow is imposed, and the nonlinear convective stability is investigated by means of the generalized integral transform technique. The neutral stability curve is compared with the one obtained by the linear stability analysis already present in the literature. The growth rate analysis of different unstable modes is performed. The Nusselt number is investigated for several supercritical configurations in order to better understand how the system behaves when conditions far away from neutral stability are considered. The patterns of the neutrally stable convective cells are also reported. Nonlinear simulations support the results obtained by means of the linear stability analysis, confirming that viscous dissipation alone is indeed capable of inducing mixed convection. Low Gebhart or high Péclet numbers lead to a transient overheating of the originally motionless fluid before it settles in its convective steady state. PMID:27279772

Small Ion Channel Linking Molecular Simulations and Electrophysiology

NASA Technical Reports Server (NTRS)

Pohorille, Andrzej

2017-01-01

Ion channels are pore-forming protein assemblies that mediate the transport of small ions across cell membranes. Otherwise, membrane bilayers would be almost impermeable to ions incapable to traverse the low dielectric constant, hydrophobic membrane core. Ion channels are ubiquitous to all life forms. In humans and other higher organisms they play the central role in conducting nerve impulses, cardiac functions, muscle contraction and apoptosis. On the other extreme of biological complexity, viral ion channels (viroporins) influence many stages of the virus infection cycle either through regulating virus replication, such as entry, assembly and release or modulating the electrochemical balance in the subcellular compartments of host cells. Ion channels were crucial components of protocells. Their emergence facilitated adaptation of nascent life to different environmental conditions. The earliest ion channels must have been much simpler than most of their modern ancestors. Viral channels are among only a few naturally occurring models to study the structure, function and evolution of primordial channels. Experimental studies of these properties are difficult and often unreliable. In principle, computational methods, and molecular dynamics (MD) simulations in particular, can aid in providing information about both the structure and the function of ion channels. However, MD suffers from its own problems, such as inability to access sufficiently long time scales or limited accuracy of force fields. It is, therefore, essential to determine the reliability of MD simulations. We propose to do so on the basis of two criteria. One is channel stability on time scales that extend for several microseconds or longer. The other is the ability to reproduce the measured ionic conductance as a function of applied voltage. If both the stability and the calculated ionic conductance are satisfactory it will greatly increase our confidence that the structure and the function of a

Sediment transport and channel morphology of small, forested streams.

Treesearch

Marwan A. Hassan; Michael Church; Thomas E. Lisle; Francesco Brardinoni; Lee Benda; Gordon E. Grant

2005-01-01

This paper reviews sediment transport and channel morphology in small, forested streams in the Pacific Northwest region of North America to assess current knowledge of channel stability and morphology relevant to riparian management practices around small streams. Small channels are defined as ones in which morphology and hydraulics may be significantly influenced by...

Impacts of salt marsh plants on tidal channel initiation and inheritance

NASA Astrophysics Data System (ADS)

Schwarz, Christian; Ye, Qinghua; van der Wal, Daphne; Zhang, Liquan; Ysebaert, Tom; Herman, Peter MJ

2013-04-01

Tidal channel networks are the most prominent and striking features visible in tidal wetlands. They serve as major pathways for the exchange of water, sediments, nutrients and contaminants between the wetland and the adjacent open water body. Previous studies identified topography guided sheet flows, as the predominate process for tidal channel initiation. Guided through differences in local topography, sheet flows are able to locally exceed bottom shear stress thresholds, initiating scouring and incision of tidal channels, which then further grow through head ward erosion. The fate of these channels after plant colonization is described in literature as being inherited into the salt marsh through vegetation induced bank stabilization (further referred to as vegetation stabilized channel inheritance). In this study we present a combination of flume experiments and modelling simulations elucidating the impact of vegetation on tidal channel initiation. We first studied the impact of plant properties (stiff: Spartina alterniflora versus flexible: Scirpus mariqueter) on local sediment transport utilizing a flume experiment. Then a coupled hydrodynamic morphodynamic plant growth model was set up to simulate plant colonization by these two different species in the pioneer zone at the mudflat - salt marsh transition. Based on the model we investigated the ramifications of interactions between vegetation, sediment and flow on tidal channel initiation. We specifically compared the effect of vegetation properties (such as stiffness, growth velocity and stress tolerance) on emerging channel patterns, hypothesizing that vegetation mediated channel incision (vegetation induced flow routing and differential sedimentation/erosion patterns leading to tidal channel incision) plays an active role in intertidal landscape evolution. We finally extended our model simulation by imposing pre-existing mudflat channels with different maximum depths, to investigate the impact of existing

Thermal stability of Cu-Cr-Zr alloy processed by equal-channel angular pressing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abib, Khadidja

Thermal stability of a Cu-Cr-Zr alloy processed by equal-channel angular pressing up to16 passes was investigated using isochronal annealing ranging from 250 to 850 °C for 1 h. The microstructure, crystallographic texture and micro hardness of samples were characterized through electron back scatter diffraction and Vickers micro hardness measurements. The recrystallized grain size was stable between 250 °C and 500 °C then increased quickly. The achieved mean grain size, after 1, 4 and 16 ECAP passes, was around 5.5 μm. A discontinuous mode of recrystallization was found to occur and a Particle Simulated Nucleation mechanism was evidenced. The evolution ofmore » the high angle grain boundary fraction increased notably after annealing above 550 °C. The crystallographic texture after isochronal annealing was similar to that of ECAP simple shear, no change of the texture during annealing was observed but only slight intensity variations. Micro hardness of all Cu–Cr–Zr samples showed a hardening with two peaks at 400 and 500 °C associated with precipitation of Cu cluster and Cu{sub 5}Zr phase respectively, followed by a subsequent softening upon increasing the annealing temperature due to recrystallization. - Highlight: •The Cu-1Cr-0.1Zr alloy shows a very good thermal stability up to 550 °C after ECAP. •A discontinuous recrystallization was found to occur and PSN mechanism was evidenced. •The annealing texture was found weak and some new components appear. •Hardening is attributed to the Cr clustering followed by the Cu{sub 51}Zr{sub 14} precipitation. •Softening is a result of recrystallization and grain growth progressing.« less

Flame balls dynamics in divergent channel

NASA Astrophysics Data System (ADS)

Fursenko, R.; Minaev, S.

2011-12-01

A three-dimensional reaction-diffusion model for lean low-Lewis-number premixed flames with radiative heat losses propagating in divergent channel is studied numerically. Effects of inlet gas velocity and heat-loss intensity on flame structure at low Lewis numbers are investigated. It is found that continuous flame front exists at small heat losses and the separate flame balls settled within restricted domain inside the divergent channel at large heat losses. It is shown that the time averaged flame balls coordinate may be considered as important characteristic analogous to coordinate of continuous flame stabilized in divergent channel.

The Kv7 Channel and Cardiovascular Risk Factors.

PubMed

Fosmo, Andreas L; Skraastad, Øyvind B

2017-01-01

Potassium channels play a pivotal role in the regulation of excitability in cells such as neurons, cardiac myocytes, and vascular smooth muscle cells. The KCNQ (Kv7) family of voltage-activated K + channels hyperpolarizes the cell and stabilizes the membrane potential. Here, we outline how Kv7 channel activity may contribute to the development of the cardiovascular risk factors such as hypertension, diabetes, and obesity. Questions and hypotheses regarding previous and future research have been raised. Alterations in the Kv7 channel may contribute to the development of cardiovascular disease (CVD). Pharmacological modification of Kv7 channels may represent a possible treatment for CVD in the future.

The Kv7 Channel and Cardiovascular Risk Factors

PubMed Central

Fosmo, Andreas L.; Skraastad, Øyvind B.

2017-01-01

Potassium channels play a pivotal role in the regulation of excitability in cells such as neurons, cardiac myocytes, and vascular smooth muscle cells. The KCNQ (Kv7) family of voltage-activated K+ channels hyperpolarizes the cell and stabilizes the membrane potential. Here, we outline how Kv7 channel activity may contribute to the development of the cardiovascular risk factors such as hypertension, diabetes, and obesity. Questions and hypotheses regarding previous and future research have been raised. Alterations in the Kv7 channel may contribute to the development of cardiovascular disease (CVD). Pharmacological modification of Kv7 channels may represent a possible treatment for CVD in the future. PMID:29259974

Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating.

PubMed

Shen, Xin-Ming; Okuno, Tatsuya; Milone, Margherita; Otsuka, Kenji; Takahashi, Koji; Komaki, Hirofumi; Giles, Elizabeth; Ohno, Kinji; Engel, Andrew G

2016-10-01

We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating. © 2016 WILEY PERIODICALS, INC.

Mutations causing slow-channel myasthenia reveal that a valine ring in the channel pore of muscle AChR is optimized for stabilizing channel gating

PubMed Central

Shen, Xin-Ming; Okuno, Tatsuya; Milone, Margherita; Otsuka, Kenji; Takahashi, Koji; Komaki, Hirofumi; Giles, Elizabeth; Ohno, Kinji; Engel, Andrew G.

2016-01-01

We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by 4.0-fold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration 4- and 8-fold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating. PMID:27375219

Skyrmion-based multi-channel racetrack

NASA Astrophysics Data System (ADS)

Song, Chengkun; Jin, Chendong; Wang, Jinshuai; Xia, Haiyan; Wang, Jianbo; Liu, Qingfang

2017-11-01

Magnetic skyrmions are promising for the application of racetrack memories, logic gates, and other nano-devices, owing to their topologically protected stability, small size, and low driving current. In this work, we propose a skyrmion-based multi-channel racetrack memory where the skyrmion moves in the selected channel by applying voltage-controlled magnetic anisotropy gates. It is demonstrated numerically that a current-dependent skyrmion Hall effect can be restrained by the additional potential of the voltage-controlled region, and the skyrmion velocity and moving channel in the racetrack can be operated by tuning the voltage-controlled magnetic anisotropy, gate position, and current density. Our results offer a potential application of racetrack memory based on skyrmions.

Voltage-gated sodium channels

PubMed Central

Abdelsayed, Mena; Sokolov, Stanislav

2013-01-01

Epilepsy is a brain disorder characterized by seizures and convulsions. The basis of epilepsy is an increase in neuronal excitability that, in some cases, may be caused by functional defects in neuronal voltage gated sodium channels, Nav1.1 and Nav1.2. The effects of antiepileptic drugs (AEDs) as effective therapies for epilepsy have been characterized by extensive research. Most of the classic AEDs targeting Nav share a common mechanism of action by stabilizing the channel’s fast-inactivated state. In contrast, novel AEDs, such as lacosamide, stabilize the slow-inactivated state in neuronal Nav1.1 and Nav1.7 isoforms. This paper reviews the different mechanisms by which this stabilization occurs to determine new methods for treatment. PMID:23531742

Solid-cryogen-stabilized, cable-in-conduit (CIC) superconducting cables

NASA Astrophysics Data System (ADS)

Voccio, J. P.; Michael, P. C.; Bromberg, L.; Hahn, S.

2015-12-01

This paper considers the use of a solid cryogen as a means to stabilize, both mechanically and thermally, magnesium diboride (MgB2) superconducting strands within a dual-channel cable-in-conduit (CIC) cable for use in AC applications, such as a generator stator winding. The cable consists of two separate channels; the outer channel contains the superconducting strands and is filled with a fluid (liquid or gas) that becomes solid at the device operating temperature. Several options for fluid will be presented, such as liquid nitrogen, hydrocarbons and other chlorofluorocarbons (CFCs) that have a range of melting temperatures and volumetric expansions (from solid at operating temperature to fixed volume at room temperature). Implications for quench protection and conductor stability, enhanced through direct contact with the solid cryogen, which has high heat capacity and thermal conductivity (compared with helium gas), will be presented. Depending on the cryogen, the conductor will be filled initially either with liquid at atmospheric conditions or a gas at high pressure (∼100 atm). After cooldown, the cryogen in the stranded-channel will be solid, essentially locking the strands in place, preventing strand motion and degradation due to mechanical deformation while providing enhanced thermal capacity for stability and protection. The effect of cryogen porosity is also considered. The relatively high heat capacity of solid cryogens at these lower temperatures (compared to gaseous helium) enhances the thermal stability of the winding. During operation, coolant flow through the open inner channel will minimize pressure drop.

Application of amphipols for structure-functional analysis of TRP channels.

PubMed

Huynh, Kevin W; Cohen, Matthew R; Moiseenkova-Bell, Vera Y

2014-10-01

Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20 % sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high-resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven to be useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impacts of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants toward determining high-resolution structures of TRP channels.

Application of amphipols for structure-functional analysis of TRP channels

PubMed Central

Huynh, Kevin W.; Cohen, Matthew R.; Moiseenkova-Bell, Vera Y.

2014-01-01

Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20% sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impact of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane (TM) domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants towards determining high resolution structures of TRP channels. PMID:24894720

CARMENES-NIR channel spectrograph cooling system AIV: thermo-mechanical performance of the instrument

NASA Astrophysics Data System (ADS)

Becerril, S.; Mirabet, E.; Lizon, J. L.; Abril, M.; Cárdenas, C.; Ferro, I.; Morales, R.; Pérez, D.; Ramón, A.; Sánchez-Carrasco, M. A.; Quirrenbach, A.; Amado, P.; Ribas, I.; Reiners, A.; Caballero, J. A.; Seifert, W.; Herranz, J.

2016-07-01

CARMENES is the new high-resolution high-stability spectrograph built for the 3.5m telescope at the Calar Alto Observatory (CAHA, Almería, Spain) by a consortium formed by German and Spanish institutions. This instrument is composed by two separated spectrographs: VIS channel (550-1050 nm) and NIR channel (950- 1700 nm). The NIR-channel spectrograph's responsible is the Instituto de Astrofísica de Andalucía (IAACSIC). It has been manufactured, assembled, integrated and verified in the last two years, delivered in fall 2015 and commissioned in December 2015. One of the most challenging systems in this cryogenic channel involves the Cooling System. Due to the highly demanding requirements applicable in terms of stability, this system arises as one of the core systems to provide outstanding stability to the channel. Really at the edge of the state-of-the-art, the Cooling System is able to provide to the cold mass ( 1 Ton) better thermal stability than few hundredths of degree within 24 hours (goal: 0.01K/day). The present paper describes the Assembly, Integration and Verification phase (AIV) of the CARMENES-NIR channel Cooling System implemented at IAA-CSIC and later installation at CAHA 3.5m Telescope, thus the most relevant highlights being shown in terms of thermal performance. The CARMENES NIR-channel Cooling System has been implemented by the IAA-CSIC through very fruitful collaboration and involvement of the ESO (European Southern Observatory) cryo-vacuum department with Jean-Louis Lizon as its head and main collaborator. The present work sets an important trend in terms of cryogenic systems for future E-ELT (European Extremely Large Telescope) large-dimensioned instrumentation in astrophysics.

flowVS: channel-specific variance stabilization in flow cytometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Azad, Ariful; Rajwa, Bartek; Pothen, Alex

Comparing phenotypes of heterogeneous cell populations from multiple biological conditions is at the heart of scientific discovery based on flow cytometry (FC). When the biological signal is measured by the average expression of a biomarker, standard statistical methods require that variance be approximately stabilized in populations to be compared. Since the mean and variance of a cell population are often correlated in fluorescence-based FC measurements, a preprocessing step is needed to stabilize the within-population variances.

flowVS: channel-specific variance stabilization in flow cytometry

DOE PAGES

Azad, Ariful; Rajwa, Bartek; Pothen, Alex

2016-07-28

Comparing phenotypes of heterogeneous cell populations from multiple biological conditions is at the heart of scientific discovery based on flow cytometry (FC). When the biological signal is measured by the average expression of a biomarker, standard statistical methods require that variance be approximately stabilized in populations to be compared. Since the mean and variance of a cell population are often correlated in fluorescence-based FC measurements, a preprocessing step is needed to stabilize the within-population variances.

Throughput-optimal scheduling for broadcast channels

NASA Astrophysics Data System (ADS)

Eryilmaz, Atilla; Srikant, Rayadurgam; Perkins, James R.

2001-07-01

In this paper, we consider a degraded Gaussian broadcast channel, where the transmitter maintains separate queues for each receiver. We present throughput optimal policies that stabilize the queues without knowing the statistics of the arrival processes to these queues.

Riparian Vegetation: Controls on Channel Planform in Noncohesive Beds

NASA Astrophysics Data System (ADS)

Tal, M.; Paola, C.; Gran, K.

2001-12-01

Riparian vegetation has strong consequences for the channel planform and dynamics. An understanding of this role is key to accurate modeling of river systems, and may provide answers to fundamental questions concerning stream dynamics as well as bridge the various approaches to modeling channel evolution. Vegetation on the flood plain works to constrain the flow of the river to a single channel by stabilizing banks and offering resistance to overbank flow. These controls were recently established through a set of controlled experiments at the St. Anthony Falls Laboratory. The runs were designed to determine how addition of vegetation affects channel form and flow dynamics. This was achieved by holding water discharge, sediment discharge, grain size, and slope constant, while making vegetation density the only variable between runs. Plants were grown while water discharge was half its channel-forming value. This work showed that as vegetation density increased there was a decrease in braiding intensity, lateral mobility, and width to depth ratios, and an increase in maximum scour hole depth, and channel relief. While producing braiding experimentally has proven simple, no one has yet produced true dynamic meanders (i.e. high-amplitude bends that grow, cut off, and grow again). Present experimental studies at St. Anthony Falls Laboratory aim to investigate the role of vegetation in the development of a meandering river in otherwise insufficiently cohesive sand that would favor a more stable braided river system. The experiments begin with an unseeded bed into which a straight channel has been carved. Each cycle comprises a period of low discharge during which the bed is seeded with alfalfa seeds. The discharge is raised to a higher discharge only after the plants have grown to a height of about 20 mm (approximately 7 days). The duration of the high-flow stage is such that not more than 10-20% of the channel width is eroded. In addition to offering insight as to the

Laser frequency stabilization using a commercial wavelength meter

NASA Astrophysics Data System (ADS)

Couturier, Luc; Nosske, Ingo; Hu, Fachao; Tan, Canzhu; Qiao, Chang; Jiang, Y. H.; Chen, Peng; Weidemüller, Matthias

2018-04-01

We present the characterization of a laser frequency stabilization scheme using a state-of-the-art wavelength meter based on solid Fizeau interferometers. For a frequency-doubled Ti-sapphire laser operated at 461 nm, an absolute Allan deviation below 10-9 with a standard deviation of 1 MHz over 10 h is achieved. Using this laser for cooling and trapping of strontium atoms, the wavemeter scheme provides excellent stability in single-channel operation. Multi-channel operation with a multimode fiber switch results in fluctuations of the atomic fluorescence correlated to residual frequency excursions of the laser. The wavemeter-based frequency stabilization scheme can be applied to a wide range of atoms and molecules for laser spectroscopy, cooling, and trapping.

River channel adjustments in Southern Italy over the past 150 years and implications for channel recovery

NASA Astrophysics Data System (ADS)

Scorpio, Vittoria; Aucelli, Pietro P. C.; Giano, Salvatore I.; Pisano, Luca; Robustelli, Gaetano; Rosskopf, Carmen M.; Schiattarella, Marcello

2015-12-01

Multi-temporal GIS analysis of topographic maps and aerial photographs along with topographic and geomorphological surveys are used to assess evolutionary trends and key control factors of channel adjustments for five major rivers in southern Italy (the Trigno, Biferno, Volturno, Sinni and Crati rivers) to support assessment of channel recovery and river restoration. Three distinct phases of channel adjustment are identified over the past 150 years primarily driven by human disturbances. Firstly, slight channel widening dominated from the last decades of the nineteenth century to the 1950s. Secondly, from the 1950s to the end of the 1990s, altered sediment fluxes induced by in-channel mining and channel works brought about moderate to very intense incision (up to 6-7 m) accompanied by strong channel narrowing (up to 96%) and changes in channel configuration from multi-threaded to single-threaded patterns. Thirdly, the period from around 2000 to 2015 has been characterized by channel stabilization and local widening. Evolutionary trajectories of the rivers studied are quite similar to those reconstructed for other Italian rivers, particularly regarding the second phase of channel adjustments and ongoing transitions towards channel recovery in some reaches. Analyses of river dynamics, recovery potential and connectivity with sediment sources of the study reaches, framed in their catchment context, can be used as part of a wider interdisciplinary approach that views effective river restoration alongside sustainable and risk-reduced river management.

Channel widening due to urbanization and a major flood can alter bed particle organization and bed stability in an urban boulder-bed channel

NASA Astrophysics Data System (ADS)

Prestegaard, K. L.; Behrns, K.; Blanchet, Z.; Hankin, E.

2007-12-01

The Anacostia River is a tributary of the Potomac River north of Washington D.C. that has become progressively more urbanized in the past 50 years. Bankfull discharge and bankfull width in the Anacostia have increased by 3- 4x in the past 50 years. Nearby watersheds of similar size and geology, but without significant urbanization, contain threshold gravel-bed streams. The Anacostia, however, is not a threshold channel; it exhibits break-up of boulder-bed channels in upstream reaches and significant gravel bar formation in downstream reaches. These gravel bars have grown and migrated considerably in the past 10-15 years, contributing significantly to local channel widening that can be twice that of adjacent reaches. The purpose of this study is to determine bedload transport rates and grain size distributions and their relationship to discharge, bed organization and sediment supply. Bed mobility data come from both bedload transport measurements and measurements of channel bed changes. Channel bed changes were obtained from a) repeated channel cross section surveys, b) surface and subsurface size distributions, and c) bed particle organization measurements (measurements of location of particles within reaches). These measurements were made prior to and after the floods of 2006, which equalled the largest floods on record for most parts of the Anacostia River. In some boulder bed reaches, boulders were removed from the center of the channel and deposited along and on the channel banks. The mid-channel boulders were replaced by sheets of gravel and cobbles, significantly altering the bed mobility of the channels.

An extremely high stability cooling system for planet hunter

NASA Astrophysics Data System (ADS)

l'Allemand, J. L. Lizon a.; Becerril, S.; Mirabet, E.

2017-12-01

The detection of exoplanets is done by measuring very tiny periodical variations of the radial velocity of the parent star. Extremely stable spectrographs are required in order to enhance the wavelength variations of the spectral lines due to Doppler effect. CARMENES is the new high-resolution, high-stability spectrograph built for the 3.5 m telescope at the Calar Alto Observatory (CAHA, Almería, Spain) by a consortium formed by German and Spanish institutions. This instrument is composed of two separated spectrographs: VIS channel (550-1050 nm) and NIR channel (950-1700 nm). The NIR-channel spectrograph’s has been built under the responsibility of the Instituto de Astrofísica de Andalucía (IAA-CSIC). It has been manufactured, assembled, integrated and verified in the last two years, delivered in fall 2015 and commissioned in December 2015. Beside the various opto-mechanical challenges, the cooling system was one of the most demanding sub-systems of the NIR channel. Due to the highly demanding requirements applicable in terms of stability, this system arises as one of the core systems to provide outstanding stability to the channel at an operating temperature finally fixed at 140 K. Really at the edge of the state-of-the-art, the Cooling System is able to provide to the cold mass (˜1 Ton) better thermal stability than few hundredths of a degree over 24 hours (goal: 0.01K/day). The present paper describes the main technical approach, which has been taken in order to reach this very ambitious performance.

Mechanical stability of ordered droplet packings in microfluidic channels

NASA Astrophysics Data System (ADS)

Fleury, Jean-Baptiste; Claussen, Ohle; Herminghaus, Stephan; Brinkmann, Martin; Seemann, Ralf

2011-12-01

The mechanical response and stability of one and two-row packing of monodisperse emulsion droplets are studied in quasi 2d microchannels under longitudinal compression. Depending on the choice of parameter, a considered droplet arrangement is either transformed continuously into another packing under longitudinal compression or becomes mechanically unstable and segregates into domains of higher and lower packing fraction. Our experimental results are compared to analytical calculations for 2d-droplet arrangements with good quantitative agreement. This study also predicts important consequences for the stability of droplet arrangements in flowing systems.

Ambient condition bias stress stability of vanadium (IV) oxide phthalocyanine based p-channel organic field-effect transistors

NASA Astrophysics Data System (ADS)

Obaidulla, Sk Md; Singh, Subhash; Mohapatra, Y. N.; Giri, P. K.

2018-01-01

High bias-stress stability and low threshold voltage (V th) shift under ambient conditions are highly desirable for practical applications of organic field-effect transistors (OFETs). We demonstrate here a 20-fold enhancement in the bias-stress stability for hexamethyledisilazane (HMDS) treated vanadium (IV) oxide phthalocyanine (VOPc) based OFETs as compared to the bare VOPc case under ambient conditions. VOPc based OFETs were fabricated on bare (non treated) SiO2 and a HMDS monolayer passivated SiO2 layer, with an operating voltage of 40 V. The devices with top contact gold (Au) electrodes exhibit excellent p-channel behavior with a moderate hole mobility for the HMDS-treated device. It is demonstrated that the time dependent ON-current decay and V th shift can be effectively controlled by using self-assembled monolayers of HMDS on the VOPc layer. For the HMDS-treated case, the bias stress stability study shows the stretched exponential decay of drain current by only ~15% during the long-term operation with constant bias voltage under ambient conditions, while it shows a large decay of  >70% for the nontreated devices operated for 1000 s. The corresponding characteric decay time constant (τ) is 104 s for the HMDS treated case, while that of the the non-treated SiO2 case is only ~480 s under ambient conditions. The inferior performance of the device with bare SiO2 is traced to the charge trapping at the voids in the inter-grain region of the films, while it is almost negligible for the HMDS-treated case, as confirmed from the AFM and XRD analyses. It is believed that HMDS treatment provides an excellent interface with a low density of traps and passivates the dangling bonds, which improve the charge transport characteristics. Also, the surface morphology of the VOPc film clearly influences the device performance. Thus, the HMDS treatment provides a very attractive approach for attaining long-term air stability and a low V th shift for the VOPc based OFET

A spectral approach for the stability analysis of turbulent open-channel flows over granular beds

NASA Astrophysics Data System (ADS)

Camporeale, C.; Canuto, C.; Ridolfi, L.

2012-01-01

A novel Orr-Sommerfeld-like equation for gravity-driven turbulent open-channel flows over a granular erodible bed is here derived, and the linear stability analysis is developed. The whole spectrum of eigenvalues and eigenvectors of the complete generalized eigenvalue problem is computed and analyzed. The fourth-order eigenvalue problem presents singular non-polynomial coefficients with non-homogenous Robin-type boundary conditions that involve first and second derivatives. Furthermore, the Exner condition is imposed at an internal point. We propose a numerical discretization of spectral type based on a single-domain Galerkin scheme. In order to manage the presence of singular coefficients, some properties of Jacobi polynomials have been carefully blended with numerical integration of Gauss-Legendre type. The results show a positive agreement with the classical experimental data and allow one to relate the different types of instability to such parameters as the Froude number, wavenumber, and the roughness scale. The eigenfunctions allow two types of boundary layers to be distinguished, scaling, respectively, with the roughness height and the saltation layer for the bedload sediment transport.

Experiments with a Supersonic Multi-Channel Radial Diffuser.

DTIC Science & Technology

1980-09-01

unlimited. 17 . DISTRIBUTION STATEMENT (o the *bsta~c entered nRItok 20, it dffttt Iton, Report) IS. SUPPLEMENTARY NOTES 19. KEY WORDS (Continue o...Improvements 17 VI SIGNIFICANT TEST RESULTS 20 1. General Considerations 20 2. Typical Radial Diffuser Performance 20 3. Flow Stability Experiments 22 VIII...Adjustments Indicated 39 16 Comparison of the Single Channel Performances for Two Extreme Channel Geometries 40 17 Typical Radial Diffuser Performance

Geomorphic and vegetative recovery processes along modified stream channels of West Tennessee

USGS Publications Warehouse

Simon, Andrew; Hupp, C.R. Tennessee

1992-01-01

Hundreds of miles of streams in West Tennessee have been channelized or otherwise modt@ed since the turn of century. After all or parts of a stream are straightened, dredged, or cleared, systematic hydrologic, geomorphic, and ecologic processes collectively begin to reduce energy conditions towards the premodified state. One hundred and five sites along 15 streams were studied in the Obion, Forked Deer, Hatchie, and Wolf River basins. All studied streams, except the Hatchie River, have had major channel modi@cation along all or parts of their courses. Bank material shear-strength properties were determined through drained borehole-shear testing (168 tests) and used to interpret present critical bank conditions and factors of safety, and to estimate future channel-bank stability. Mean values of cohesive strength and angle of internal friction were 1.26 pounds per square inch and 30.1 degrees, respectively. Dendrogeomorphic analyses were made using botanical evidence of channel-bank failures to determine rates of channel widening; buried riparian stems were analyzed to determine rates of bank accretion. Channel bed-level changes through time and space were represented by a power equation. Plant ecological analyses were ma& to infer relative bank stability, to identify indicator species of the stage of bank recovery, and to determine patterns of vegetation development through the course of channel evolution. Quantitative data on morphologic changes were used with previously developed six-stage models of channel evolution and bank-slope development to estimate trends of geomorphic and ecologic processes and forms through time. Immediately after channel modr@cations, a 10- to 1%yearperiod of channel-bed degradation ensues at and upstream from the most recent modifications (area of maximum disturbance). Channel-bed lowering by &gradation was as much as 20 feet along some stream reaches. Downstream from the area of maximum disturbance, the bed was aggraded by the

Highly permeable artificial water channels that can self-assemble into two-dimensional arrays

PubMed Central

Shen, Yue-xiao; Si, Wen; Erbakan, Mustafa; Decker, Karl; De Zorzi, Rita; Saboe, Patrick O.; Kang, You Jung; Majd, Sheereen; Butler, Peter J.; Walz, Thomas; Aksimentiev, Aleksei; Hou, Jun-li; Kumar, Manish

2015-01-01

Bioinspired artificial water channels aim to combine the high permeability and selectivity of biological aquaporin (AQP) water channels with chemical stability. Here, we carefully characterized a class of artificial water channels, peptide-appended pillar[5]arenes (PAPs). The average single-channel osmotic water permeability for PAPs is 1.0(±0.3) × 10−14 cm3/s or 3.5(±1.0) × 108 water molecules per s, which is in the range of AQPs (3.4∼40.3 × 108 water molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0 × 108 water molecules per s). This permeability is an order of magnitude higher than first-generation artificial water channels (20 to ∼107 water molecules per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into 2D arrays. Relevant to permeable membrane design, the pore density of PAP channel arrays (∼2.6 × 105 pores per μm2) is two orders of magnitude higher than that of CNT membranes (0.1∼2.5 × 103 pores per μm2). PAP channels thus combine the advantages of biological channels and CNTs and improve upon them through their relatively simple synthesis, chemical stability, and propensity to form arrays. PMID:26216964

Two-Channel Kondo Effect in a Modified Single Electron Transistor

NASA Astrophysics Data System (ADS)

Oreg, Yuval; Goldhaber-Gordon, David

2003-04-01

We suggest a simple system of two electron droplets which should display two-channel Kondo behavior at experimentally accessible temperatures. Stabilization of the two-channel Kondo fixed point requires fine control of the electrochemical potential in each droplet, which can be achieved by adjusting voltages on nearby gate electrodes. We study the conditions for obtaining this type of two-channel Kondo behavior, discuss the experimentally observable consequences, and explore the gener­alization to the multichannel Kondo case.

Early stages of transition in viscosity-stratified channel flow

NASA Astrophysics Data System (ADS)

Govindarajan, Rama; Jose, Sharath; Brandt, Luca

2013-11-01

In parallel shear flows, it is well known that transition to turbulence usually occurs through a subcritical process. In this work we consider a flow through a channel across which there is a linear temperature variation. The temperature gradient leads to a viscosity variation across the channel. A large body of work has been done in the linear regime for this problem, and it has been seen that viscosity stratification can lead to considerable changes in stability and transient growth characteristics. Moreover contradictory effects of introducing a non uniform viscosity in the system have been reported. We conduct a linear stability analysis and direct numerical simulations (DNS) for this system. We show that the optimal initial structures in the viscosity-stratified case, unlike in unstratified flow, do not span the width of the channel, but are focussed near one wall. The nonlinear consequences of the localisation of the structures will be discussed.

Voltage-gated sodium channels: pharmaceutical targets via anticonvulsants to treat epileptic syndromes.

PubMed

Abdelsayed, Mena; Sokolov, Stanislav

2013-01-01

Epilepsy is a brain disorder characterized by seizures and convulsions. The basis of epilepsy is an increase in neuronal excitability that, in some cases, may be caused by functional defects in neuronal voltage gated sodium channels, Nav1.1 and Nav1.2. The effects of antiepileptic drugs (AEDs) as effective therapies for epilepsy have been characterized by extensive research. Most of the classic AEDs targeting Nav share a common mechanism of action by stabilizing the channel's fast-inactivated state. In contrast, novel AEDs, such as lacosamide, stabilize the slow-inactivated state in neuronal Nav1.1 and Nav1.7 isoforms. This paper reviews the different mechanisms by which this stabilization occurs to determine new methods for treatment.

Time domain passivity controller for 4-channel time-delay bilateral teleoperation.

PubMed

Rebelo, Joao; Schiele, Andre

2015-01-01

This paper presents an extension of the time-domain passivity control approach to a four-channel bilateral controller under the effects of time delays. Time-domain passivity control has been used successfully to stabilize teleoperation systems with position-force and position-position controllers; however, the performance with such control architectures is sub-optimal both with and without time delays. This work extends the network representation of the time-domain passivity controller to the four-channel architecture, which provides perfect transparency to the user without time delay. The proposed architecture is based on modelling the controllers as dependent voltage sources and using only series passivity controllers. The obtained results are shown on a one degree-of-freedom setup and illustrate the stabilization behaviour of the proposed controller when time delay is present in the communication channel.

Man-induced channel adjustment in Tennessee streams

USGS Publications Warehouse

Robbins, C.H.; Simon, Andrew

1983-01-01

Channel modifications in Tennessee, particularly in the western part, have led to large-scale instabilities in the channelized rivers and may have contributed to several bridge failures. These modifications, together with land-use practices, led to downcutting, headward erosion, downstream aggradation, accelerated scour, and bank instabilities. Changes in gradient by channel straightening caused more severe channel response than did dredging or clearing. Large-scale changes continue to occur in all the channelized rivers: the Obion River, its forks, and the South Fork Forked Deer River. However, the non-channelized Hatchie River in west Tennessee not only withstood the natural stresses imposed by the wet years of 1973 to 1975 but continues to exhibit characteristics of stability. Water-surface slope, the primary dependent variable, proved to be a sensitive and descriptive parameter useful in determining channel adjustment. Adjustments to man-induced increases in channel-slope are described by inverse exponential functions of the basic form S=ae(-b(t)); where ' S ' is some function describing channel-slope, ' t ' is the number of years since completion of channel work, and ' a ' and ' b ' are coefficients. Response times for the attainment of ' equilibrium ' channel slopes are a function of the magnitude and extent of the imposed modifications. The adjusted profile gradients attained by the streams following channelization are similar to the predisturbed profile gradients, where no alteration to channel length was made. Where the channels were straightened by constructing cut-offs, thus shortening channel length, then slope adjustments (reduction) proceed past the predisturbed profile gradients, to new profiles with lower gradients. (USGS)

Quantum resource theory of non-stabilizer states in the one-shot regime

NASA Astrophysics Data System (ADS)

Ahmadi, Mehdi; Dang, Hoan; Gour, Gilad; Sanders, Barry

Universal quantum computing is known to be impossible using only stabilizer states and stabilizer operations. However, addition of non-stabilizer states (also known as magic states) to quantum circuits enables us to achieve universality. The resource theory of non-stablizer states aims at quantifying the usefulness of non-stabilizer states. Here, we focus on a fundamental question in this resource theory in the so called single-shot regime: Given two resource states, is there a free quantum channel that will (approximately or exactly) convert one to the other?. To provide an answer, we phrase the question as a semidefinite program with constraints on the Choi matrix of the corresponding channel. Then, we use the semidefinite version of the Farkas lemma to derive the necessary and sufficient conditions for the conversion between two arbitrary resource states via a free quantum channel. BCS appreciates financial support from Alberta Innovates, NSERC, China's 1000 Talent Plan and the Institute for Quantum Information and Matter.

Information geometry of Gaussian channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monras, Alex; CNR-INFM Coherentia, Napoli; CNISM Unita di Salerno

2010-06-15

We define a local Riemannian metric tensor in the manifold of Gaussian channels and the distance that it induces. We adopt an information-geometric approach and define a metric derived from the Bures-Fisher metric for quantum states. The resulting metric inherits several desirable properties from the Bures-Fisher metric and is operationally motivated by distinguishability considerations: It serves as an upper bound to the attainable quantum Fisher information for the channel parameters using Gaussian states, under generic constraints on the physically available resources. Our approach naturally includes the use of entangled Gaussian probe states. We prove that the metric enjoys some desirablemore » properties like stability and covariance. As a by-product, we also obtain some general results in Gaussian channel estimation that are the continuous-variable analogs of previously known results in finite dimensions. We prove that optimal probe states are always pure and bounded in the number of ancillary modes, even in the presence of constraints on the reduced state input in the channel. This has experimental and computational implications. It limits the complexity of optimal experimental setups for channel estimation and reduces the computational requirements for the evaluation of the metric: Indeed, we construct a converging algorithm for its computation. We provide explicit formulas for computing the multiparametric quantum Fisher information for dissipative channels probed with arbitrary Gaussian states and provide the optimal observables for the estimation of the channel parameters (e.g., bath couplings, squeezing, and temperature).« less

A multi-channel isolated power supply in non-equipotential circuit

NASA Astrophysics Data System (ADS)

Li, Xiang; Zhao, Bo-Wen; Zhang, Yan-Chi; Xie, Da

2018-04-01

A multi-channel isolation power supply is designed for the problems of different MOSFET or IGBT in the non-equipotential circuit in this paper. It mainly includes the square wave generation circuit, the high-frequency transformer and the three-terminal stabilized circuit. The first part is used to generate the 24V square wave, and as the input of the magnetic ring transformer. In the second part, the magnetic ring transformer consists of one input and three outputs to realize multi-channel isolation output. The third part can output different potential and realize non-equal potential function through the three-terminal stabilized chip. In addition, the multi-channel isolation power source proposed in this paper is Small size, high reliability and low price, and it is convenient for power electronic switches that operate on multiple different potentials. Therefore, the research on power supply of power electronic circuit has practical significance.

Understanding carbon nanotube channel formation in the lipid membrane

NASA Astrophysics Data System (ADS)

Choi, Moon-ki; Kim, Hyunki; Lee, Byung Ho; Kim, Teayeop; Rho, Junsuk; Kim, Moon Ki; Kim, Kyunghoon

2018-03-01

Carbon nanotubes (CNTs) have been considered a prominent nano-channel in cell membranes because of their prominent ion-conductance and ion-selectivity, offering agents for a biomimetic channel platform. Using a coarse-grained molecular dynamics simulation, we clarify a construction mechanism of vertical CNT nano-channels in a lipid membrane for a long period, which has been difficult to observe in previous CNT-lipid interaction simulations. The result shows that both the lipid coating density and length of CNT affect the suitable fabrication condition for a vertical and stable CNT channel. Also, simulation elucidated that a lipid coating on the surface of the CNT prevents the CNT from burrowing into the lipid membrane and the vertical channel is stabilized by the repulsion force between the lipids in the coating and membrane. Our study provides an essential understanding of how CNTs can form stable and vertical channels in the membrane, which is important for designing new types of artificial channels as biosensors for bio-fluidic studies.

Channel Responses and Hydromodification in Southern California

NASA Astrophysics Data System (ADS)

Hawley, R. J.; Dust, D. W.; Bledsoe, B. P.

2007-12-01

Hydromodification (changes in watershed hydrologic characteristics, and the resulting hydraulics and channel forms due to urbanization) is ubiquitous in Southern California. In this region, the effects of hydromodification are driven and compounded by the arid/semiarid climate, high relief, erodible soils, high urbanization rates, and relatively low frequency of retention/detention. We conducted a preliminary survey of over 50 stream reaches along a gradient from least disturbed to fully urbanized. All stages of the Channel Evolution Model (CEM) of Schumm et al. (1984) were observed, from stable to degrading, widening, aggrading, and quasi-equilibrium channels. Several sites have CEM stages II through V in close proximity due to headcutting, hardpoints, and infrastructure. We also observed channels in undeveloped watersheds impacted by downstream urbanization via headcutting. A range of intervention measures was observed, with the frequent evolutionary endpoint as a concrete engineered flood control channel. We also observed multiple channel evolution sequences that deviate from the CEM for single-thread, incising channels. An alternative channel response, particularly on smaller urbanized streams is a stabilized, vegetation encroached low-flow channel with regular baseflow supplied by residential irrigation runoff. The limited cases of unimpacted streams that remain tend to be high gradient, high energy systems that are naturally proximate to the transition between braided and meandering form for a given sediment size.

The interaction between vegetation and channel dynamics based on experimental findings

NASA Astrophysics Data System (ADS)

Teske, R.; Van Dijk, W. M.; Van De Lageweg, W.; Kleinhans, M. G.

2012-12-01

Strong feedbacks exist between river channel dynamics, floodplain development and riparian vegetation. Several experimental studies showed how uniformly sown vegetation causes a shift from a braided river to a single-thread and sometimes meandering river. The objective of this study is to test what the effect of fluvially distributed seeds and vegetation settling is on channel pattern change and channel dynamics. The experiments were carried out in a flume of 3 m wide and 10 m long. We tested where the vegetation deposited in a braided and meandering river and how the morphology changed. We used a simple hydrograph of 0.25 hour high flow and 3.75 hour low flow, where alfalfa seeds were added during high flow. The bed sediment consisted of a poorly sorted sediment mixture ranging from fine sand to fine gravel. The evolution was recorded by a high-resolution laser-line scanner and a Digital Single Lens Reflex (DSLR) camera used for channel floodplain segmentation, water depth approximation and vegetation distribution. In an initially braided river, vegetation settled on the higher banks and stabilized the banks. In an initially meandering river, vegetation settled in the inner scrolls, and also on the outer banks when water level exceeded bankfull conditions. In agreement with earlier work, the outer bank was stabilized; erosion rate decreased and bends became sharper. The inner bend vegetation stabilized a part of the point bar and hydraulic resistance of the vegetation steered water in the channel and to the non-vegetated part of the inner bend. As result the meander bend became braided as water flows along the vegetation. Vegetation formed patches that grew over time and reduced channel dynamics. We conclude that self-settling vegetation decreased local bank erosion and that vegetated islands leads to a multi-thread system instead of single-threaded.

Thermal Microstructural Stability of AZ31 Magnesium after Severe Plastic Deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, John P.; Askari, Hesam A.; Hovanski, Yuri

2015-03-01

Both equal channel angular pressing and friction stir processing have the ability to refine the grain size of twin roll cast AZ31 magnesium and potentially improve its superplastic properties. This work used isochronal and isothermal heat treatments to investigate the microstructural stability of twin roll cast, equal channel angular pressed and friction stir processed AZ31 magnesium. For both heat treatment conditions, it was found that the twin roll casted and equal channel angular pressed materials were more stable than the friction stir processed material. Calculations of the grain growth kinetics showed that severe plastic deformation processing decreased the activation energymore » for grain boundary motion with the equal channel angular pressed material having the greatest Q value of the severely plastically deformed materials and that increasing the tool travel speed of the friction stir processed material improved microstructural stability. The Hollomon-Jaffe parameter was found to be an accurate means of identifying the annealing conditions that will result in substantial grain growth and loss of potential superplastic properties in the severely plastically deformed materials. In addition, Humphreys’s model of cellular microstructural stability accurately predicted the relative microstructural stability of the severely plastically deformed materials and with some modification, closely predicted the maximum grain size ratio achieved by the severely plastically deformed materials.« less

Instream wood in a steep headwater channel: geomorphic significance of large and small wood

NASA Astrophysics Data System (ADS)

Galia, Tomáš; Šilhán, Karel; Ruiz-Villanueva, Virginia; Tichavský, Radek

2016-04-01

Besides the well-known significance of large wood (LW), also small woody pieces (SW; here defined as pieces with dimensions at least 0.5 m length and 0.05 m diameter), can play an important role in steep narrow headwaters. We inventoried instream wood in the 0.4 km long Mazák headwater channel, Moravskoslezské Beskydy Mts, Czech Republic (2stability (unattached/contact with hillslopes/attached by bed sediments or other wood), % of influenced channel width by a wood, the geomorphic function of a wood (step, wood jam) and % of length of a wood in channel were assessed. The total number of inventoried instream wood was 90 LWs and 199 SWs. In addition, dendrogeomorphic dating of 36 LWs and 17 SWs was performed to obtain residence time of local instream wood and to provide some insights into its mobility. Practically all investigated pieces were European beeches (Fagus sylvatica L.); only two pieces were Norway spruces (Picea abies (L.) Karst.). First results showed an increase in the number of LWs in channel-reaches confined by the steepest adjacent hillslopes (especially at 0.15-0.20 km). Increasing downstream amount of SW most likely reflected transport processes in the stream, and the later deposition of SWs on the lowest channel gradients. Also LWs and SWs in the downstream channel-reaches were more decayed than wood presented in the upper reaches. The orientation of instream wood was connected with its length and stability, and LWs longer than 5 m were usually attached to adjacent hillslopes. Pieces longer than 2 m, which were unattached or were somehow stabilized in the channel bed, had often orientation of 0° or 337°. LWs were mostly unattached in the upstream channel-reaches, while often stabilized by adjacent hillslopes in the middle part. At 0.05-0.10 km, there were also many logs stabilized by

Use of geomorphic regime diagrams in channel restoration

NASA Astrophysics Data System (ADS)

Buffington, J. M.; Parker, G.

2005-12-01

Regime diagrams can be used to predict channel characteristics (depth, grain size, slope) and reach-scale channel morphology (pool-riffle, plane-bed, etc.) as a function imposed values of discharge and bedload sediment supply. In terms of stream restoration, these diagrams can be used to set target values for creating or maintaining desired channel types and associated aquatic habitats or to assess the stable channel morphology for imposed watershed conditions. However, alluvial channels are dynamic and may move toward new states with interannual changes in discharge or sediment supply. These changes may be small-scale adjustments of channel dimensions, grain size, or slope, or they may be whole-sale metamorphosis to a new reach type. The degree of change likely depends on local physiography and the associated characteristic variations of discharge and sediment supply. We propose a framework for assessing the relative degree of channel stability in different physiographic settings using a regime diagram that is explicitly linked to rational equations for discharge and sediment supply. This approach allows a more dynamic representation of potential channel conditions that can be expected for a given restoration design (or for an existing channel), and links site conditions to discharge and sediment supply variability imposed by larger-scale basin conditions and physiography.

Outward stabilization of the voltage sensor in domain II but not domain I speeds inactivation of voltage-gated sodium channels.

PubMed

Sheets, Michael F; Chen, Tiehua; Hanck, Dorothy A

2013-10-15

To determine the roles of the individual S4 segments in domains I and II to activation and inactivation kinetics of sodium current (INa) in NaV1.5, we used a tethered biotin and avidin approach after a site-directed cysteine substitution was made in the second outermost Arg in each S4 (DI-R2C and DII-R2C). We first determined the fraction of gating charge contributed by the individual S4's to maximal gating current (Qmax), and found that the outermost Arg residue in each S4 contributed ∼19% to Qmax with minimal contributions by other arginines. Stabilization of the S4's in DI-R2C and DII-R2C was confirmed by measuring the expected reduction in Qmax. In DI-R2C, stabilization resulted in a decrease in peak INa of ∼45%, while its peak current-voltage (I-V) and voltage-dependent Na channel availability (SSI) curves were nearly unchanged from wild type (WT). In contrast, stabilization of the DII-R2C enhanced activation with a negative shift in the peak I-V relationship by -7 mV and a larger -17 mV shift in the voltage-dependent SSI curve. Furthermore, its INa decay time constants and time-to-peak INa became more rapid than WT. An explanation for these results is that the depolarized conformation of DII-S4, but not DI-S4, affects the receptor for the inactivation particle formed by the interdomain linker between DIII and IV. In addition, the leftward shifts of both activation and inactivation and the decrease in Gmax after stabilization of the DII-S4 support previous studies that showed β-scorpion toxins trap the voltage sensor of DII in an activated conformation.

The C-terminal coiled-coil of the bacterial voltage-gated sodium channel NaChBac is not essential for tetramer formation, but stabilizes subunit-to-subunit interactions.

PubMed

Mio, Kazuhiro; Mio, Muneyo; Arisaka, Fumio; Sato, Masahiko; Sato, Chikara

2010-09-01

The NaChBac is a prokaryotic homologue of the voltage-gated sodium channel found in the genome of the alkalophilic bacterium Bacillus halodurans C-125. Like a repeating cassette of mammalian sodium channel, the NaChBac possesses hydrophobic domains corresponding to six putative transmembrane segments and a pore loop, and exerts channel function by forming a tetramer although detailed mechanisms of subunit assembly remain unclear. We generated truncated mutants from NaChBac, and investigated their ability to form tetramers in relation to their channel functions. A mutant that deletes almost all of the C-terminal coiled-coil structure lost its voltage-dependent ion permeability, although it was properly translocated to the cell surface. The mutant protein was purified as a tetramer using a reduced concentration of detergent, but the association between the subunits was shown to be much weaker than the wild type. The chemical cross-linking, blue native PAGE, sedimentation velocity experiments, size exclusion chromatography, immunoprecipitation, and electron microscopy all supported its tetrameric assembly. We further purified the C-terminal cytoplasmic domain alone and confirmed its self-oligomerization. These data suggest that the C-terminal coiled-coil structure stabilizes subunit-to-subunit interactions of NaChBac, but is not critical for their tetramer formation. 2010 Elsevier Ltd. All rights reserved.

The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel.

PubMed

Minor, D L; Lin, Y F; Mobley, B C; Avelar, A; Jan, Y N; Jan, L Y; Berger, J M

2000-09-01

Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the closed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.

Critical capillary channel flow

NASA Astrophysics Data System (ADS)

Grah, Aleksander; Klatte, Jörg; Dreyer, Michael E.

, that temporarily Speed Index values exceeding One may be achieved for a perfectly stable supercritical dynamic flow. As a supercritical criterion for the dynamic free surface stability we define a Dynamic Index D considering the local capillary pressure and the convective pressure, which is a function of the local velocity. The Dynamic Index is below One for stable flow while D = 1 indicates surface collapse. This studies result in a stability diagram, which defines the limits of flow dynamics and the maximum unsteady flow rate. It may serve as a road map for open capillary channel flow control.

Supraglacial channel inception: Modeling and processes

NASA Astrophysics Data System (ADS)

Mantelli, E.; Camporeale, C.; Ridolfi, L.

2015-09-01

Supraglacial drainage systems play a key role in glacial hydrology. Nevertheless, physical processes leading to spatial organization in supraglacial networks are still an open issue. In the present work we thus address from a quantitative point of view the question of what is the physics leading to widely observed patterns made up of evenly spaced channels. To this aim, we set up a novel mathematical model describing a condition antecedent channel formation, i.e., the down-glacier flow of a distributed meltwater film. We then perform a linear stability analysis to assess whether the ice-water interface undergoes a morphological instability compatible with observed patterns. The instability is detected, its features depending on glacier surface slope, ice friction factor, and water as well as ice thermal conditions. By contrast, in our model channel spacing is solely hydrodynamically driven and relies on the interplay between pressure perturbations, flow depth response, and Reynolds stresses. Geometrical features of the predicted pattern are quantitatively consistent with available field data. The hydrodynamic origin of supraglacial channel morphogenesis suggests that alluvial patterns might share the same physical controls.

Formation of a compound flux rope by the merging of two filament channels, the associated dynamics, and its stability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joshi, Navin Chandra; Inoue, Satoshi; Magara, Tetsuya, E-mail: navin@khu.ac.kr, E-mail: njoshi98@gmail.com

2014-11-01

We present observations of compound flux rope formation, which occurred on 2014 January 1, via merging of two nearby filament channels, the associated dynamics, and its stability using multiwavelength data. We also discuss the dynamics of cool and hot plasma moving along the newly formed compound flux rope. The merging started after the interaction between the southern leg of the northward filament and the northern leg of the southward filament at ≈01:21 UT and continued until a compound flux rope formed at ≈01:33 UT. During the merging, the cool filament plasma heated up and started to move along both sidesmore » of the compound flux rope, i.e., toward the north (≈265 km s{sup –1}) and south (≈118 km s{sup –1}) from the point of merging. After traveling a distance of ≈150 Mm toward the north, the plasma cooled down and started to return back to the south (≈14 km s{sup –1}) after ≈02:00 UT. The observations provide a clear example of compound flux rope formation via merging of two different flux ropes and the occurrence of a flare through tether cutting reconnection. However, the compound flux rope remained stable in the corona and had a confined eruption. The coronal magnetic field decay index measurements revealed that both the filaments and the compound flux rope axis lie within the stability domain (decay index <1.5), which may be the possible cause for their stability. The present study also deals with the relationship between the filament's chirality (sinistral) and the helicity (positive) of the surrounding flux rope.« less

The Role of Basal Channels in Ice Shelf Calving.

NASA Astrophysics Data System (ADS)

Dow, C. F.; Lee, W. S.; Greenbaum, J. S.; Greene, C. A.; Blankenship, D. D.; Poinar, K.; Forrest, A.; Young, D. A.; Zappa, C. J.

2017-12-01

Increased rates of ice shelf break-up drives acceleration of grounded glacial ice into the ocean, resulting in sea-level rise. Ice shelves are vulnerable to thinning, which make them more susceptible to calving. Here, we examine basal channels under three ice shelves that locally thin the ice and drive formation of transverse ice shelf fractures. The basal channels also cause surface depressions due to hydrostatic buoyancy effects and can draw in surface water to form rivers. These rivers exacerbate thinning by surface melting and hydraulic loading, and can accelerate rifting when they flow into the transverse fractures. Our investigation focuses on Nansen Ice Shelf in the Ross Sea Embayment, East Antarctica. We use ice-sounding radar and single-beam laser altimeter data from two aerogeophysical campaigns conducted in 2011 and 2014, ice surface DEM reconstruction, and satellite imagery analysis, to examine the role of a substantial basal channel in the stability of this ice shelf. Nansen Ice Shelf calved two large icebergs totaling 214 km2 in area in April 2016. The transverse fracture that eventually rifted to form these icebergs initiated directly over the basal channel in 1987. In years when surface water formed on Nansen Ice Shelf, a river flowed into the transverse fracture. In November 2016, we identified a new fracture over the basal channel during in-situ data collection. We compare the Nansen Ice Shelf fractures with those at other vulnerable ice-shelf systems, including Petermann Glacier in Greenland and Totten Glacier in East Antarctica, to evaluate the role that basal channels may play in simultaneous basal and surface weakening and their consequent effect on ice-shelf rifting and stability.

A Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of β2,3-Sheet Essential for Channel Function of P2X4 Receptors.

PubMed

Zhao, Wen-Shan; Sun, Meng-Yang; Sun, Liang-Fei; Liu, Yan; Yang, Yang; Huang, Li-Dong; Fan, Ying-Zhe; Cheng, Xiao-Yang; Cao, Peng; Hu, You-Min; Li, Lingyong; Tian, Yun; Wang, Rui; Yu, Ye

2016-04-08

Significant progress has been made in understanding the roles of crucial residues/motifs in the channel function of P2X receptors during the pre-structure era. The recent structural determination of P2X receptors allows us to reevaluate the role of those residues/motifs. Residues Arg-309 and Asp-85 (rat P2X4 numbering) are highly conserved throughout the P2X family and were involved in loss-of-function polymorphism in human P2X receptors. Previous studies proposed that they participated in direct ATP binding. However, the crystal structure of P2X demonstrated that those two residues form an intersubunit salt bridge located far away from the ATP-binding site. Therefore, it is necessary to reevaluate the role of this salt bridge in P2X receptors. Here, we suggest the crucial role of this structural element both in protein stability and in channel gating rather than direct ATP interaction and channel assembly. Combining mutagenesis, charge swap, and disulfide cross-linking, we revealed the stringent requirement of this salt bridge in normal P2X4 channel function. This salt bridge may contribute to stabilizing the bending conformation of the β2,3-sheet that is structurally coupled with this salt bridge and the α2-helix. Strongly kinked β2,3 is essential for domain-domain interactions between head domain, dorsal fin domain, right flipper domain, and loop β7,8 in P2X4 receptors. Disulfide cross-linking with directions opposing or along the bending angle of the β2,3-sheet toward the α2-helix led to loss-of-function and gain-of-function of P2X4 receptors, respectively. Further insertion of amino acids with bulky side chains into the linker between the β2,3-sheet or the conformational change of the α2-helix, interfering with the kinked conformation of β2,3, led to loss-of-function of P2X4 receptors. All these findings provided new insights in understanding the contribution of the salt bridge between Asp-85 and Arg-309 and its structurally coupled β2,3-sheet to the

Channel Stability and Water Quality of the Alagnak River, Southwestern Alaska

USGS Publications Warehouse

Curran, Janet H.

2003-01-01

The Alagnak River, a National Wild River located in southwestern Alaska, drains an area of 3,600 square kilometers and is used for recreational and subsistence activities, primarily angling, camping, rafting, and hunting by visitors and seasonal residents, and for commercial guiding by several lodges. Increases in visitor use in the 1990s included an increase in the use of high-horsepower motorboats on the river, primarily for angling, and raised concerns regarding human impacts on water quality. Downstream from its confluence with the Nonvianuk River at river kilometer (RK) 93, the Alagnak River is formed in glacial drift and outwash with a single, low bedrock outcrop. Analysis of aerial photography from 1951, 1982, and 2001 shows that the river's multiple channels from RK 57 to 93 have been relatively stable. In contrast, long reaches of multiple channels from RK 35 to 57 changed substantially between 1951 and 1982, creating a new complex of channels. Downstream from RK 35, channel changes in the past 50 years consist largely of minor meander migration. Analysis of water samples collected during this study at RK 21, 46, and 93 and in the Alagnak and Nonvianuk Rivers at the outlets of the lakes that form their source shows that the Alagnak River is a nutrient-poor, calcium-bicarbonate water with low suspended-sediment concentrations. Water chemistry changes little over time or in a downstream direction. Weak patterns over time include high late May/early June concentrations of some nutrients, carbon, and iron. Weak patterns over distance include downstream increases in iron, manganese, and phosphorous. No pervasive human impacts on Alagnak River water chemistry were detected. Local effects that could be diluted within a kilometer downstream of the source were not detectable by this study. Data collected at three continuously recording wake gaging stations at RK 21, 46, and 93 showed that 1999-2000 motorboat use was heaviest in the lower reaches of the river

Molecular basis of slow activation of the human ether-á-go-go related gene potassium channel

PubMed Central

Subbiah, Rajesh N; Clarke, Catherine E; Smith, David J; Zhao, JingTing; Campbell, Terence J; Vandenberg, Jamie I

2004-01-01

The human ether-á-go-go related gene (HERG) encodes the pore forming α-subunit of the rapid delayed rectifier K+ channel which is central to the repolarization phase of the cardiac action potential. HERG K+ channels have unusual kinetics characterized by slow activation and deactivation, yet rapid inactivation. The fourth transmembrane domain (S4) of HERG, like other voltage-gated K+ channels, contains multiple positive charges and is the voltage sensor for activation. In this study, we mutated each of the positively charged residues in this region to glutamine (Q), expressed the mutant and wild-type (WT) channels in Xenopus laevis oocytes and studied them using two-electrode voltage clamp methods. K525Q channels activated at more hyperpolarized potentials than WT, whereas all the other mutant channels activated at more depolarized potentials. All mutants except for R531Q also had a reduction in apparent gating charge associated with activation. Mutation of K525 to cysteine (C) resulted in a less dramatic phenotype than K525Q. The addition of the positively charged MTSET to K525C altered the phenotype to one more similar to K525Q than to WT. Therefore it is not charge per se, but the specific lysine side chain at position 525, that is crucial for stabilizing the closed state. When rates of activation and deactivation for WT and mutant channels were compared at equivalent total (chemical + electrostatic) driving forces, K525Q and R528Q accelerated activation but had no effect on deactivation, R531Q slowed activation and deactivation, R534Q accelerated activation but slowed deactivation and R537Q accelerated deactivation but had no effect on activation. The main conclusions we can draw from these data are that in WT channels K525 stabilizes the closed state, R531 stabilizes the open state and R534 participates in interactions that stabilize pre-open closed states. PMID:15181157

Long-term morphological developments of river channels separated by a longitudinal training wall

NASA Astrophysics Data System (ADS)

Le, T. B.; Crosato, A.; Uijttewaal, W. S. J.

2018-03-01

Rivers have been trained for centuries by channel narrowing and straightening. This caused important damages to their ecosystems, particularly around the bank areas. We analyze here the possibility to train rivers in a new way by subdividing their channel in main and ecological channel with a longitudinal training wall. The effectiveness of longitudinal training walls in achieving this goal and their long-term effects on the river morphology have not been thoroughly investigated yet. In particular, studies that assess the stability of the two parallel channels separated by the training wall are still lacking. This work studies the long-term morphological developments of river channels subdivided by a longitudinal training wall in the presence of steady alternate bars. This type of bars, common in alluvial rivers, alters the flow field and the sediment transport direction and might affect the stability of the bifurcating system. The work comprises both laboratory experiments and numerical simulations (Delft3D). The results show that a system of parallel channels divided by a longitudinal training wall has the tendency to become unstable. An important factor is found to be the location of the upstream termination of the longitudinal wall with respect to a neighboring steady bar. The relative widths of the two parallel channels separated by the wall and variable discharge do not substantially change the final evolution of the system.

Mood stabilizer psychopharmacology

PubMed Central

Gould, Todd D.; Chen, Guang; Manji, Husseini K.

2012-01-01

Mood stabilizers represent a class of drugs that are efficacious in the treatment of bipolar disorder. The most established medications in this class are lithium, valproic acid, and carbamazepine. In addition to their therapeutic effects for treatment of acute manic episodes, these medications often are useful as prophylaxis against future episodes and as adjunctive antidepressant medications. While important extracellular effects have not been excluded, most available evidence suggests that the therapeutically relevant targets of this class of medications are in the interior of cells. Herein we give a prospective of a rapidly evolving field, discussing common effects of mood stabilizers as well as effects that are unique to individual medications. Mood stabilizers have been shown to modulate the activity of enzymes, ion channels, arachidonic acid turnover, G protein coupled receptors and intracellular pathways involved in synaptic plasticity and neuroprotection. Understanding the therapeutic targets of mood stabilizers will undoubtedly lead to a better understanding of the pathophysiology of bipolar disorder and to the development of improved therapeutics for the treatment of this disease. Furthermore, the involvement of mood stabilizers in pathways operative in neuroprotection suggests that they may have utility in the treatment of classical neurodegenerative disorders. PMID:22707923

Molecular dynamics simulations reveal highly permeable oxygen exit channels shared with water uptake channels in photosystem II.

PubMed

Vassiliev, Serguei; Zaraiskaya, Tatiana; Bruce, Doug

2013-10-01

Photosystem II (PSII) catalyzes the oxidation of water in the conversion of light energy into chemical energy in photosynthesis. Water delivery and oxygen removal from the oxygen evolving complex (OEC), buried deep within PSII, are critical requirements to facilitate the reaction and minimize reactive oxygen damage. It has often been assumed that water and oxygen travel through separate channels within PSII, as demonstrated in cytochrome c oxidase. This study describes all-atom molecular dynamics simulations of PSII designed to investigate channels by fully characterizing the distribution and permeation of both water and oxygen. Interestingly, most channels found in PSII were permeable to both oxygen and water, however individual channels exhibited different energetic barriers for the two solutes. Several routes for oxygen diffusion within PSII with low energy permeation barriers were found, ensuring its fast removal from the OEC. In contrast, all routes for water showed significant energy barriers, corresponding to a much slower permeation rate for water through PSII. Two major factors were responsible for this selectivity: (1) hydrogen bonds between water and channel amino acids, and (2) steric restraints. Our results reveal the presence of a shared network of channels in PSII optimized to both facilitate the quick removal of oxygen and effectively restrict the water supply to the OEC to help stabilize and protect it from small water soluble inhibitors. Copyright © 2013 Elsevier B.V. All rights reserved.

A Change in the Ion Selectivity of Ligand-Gated Ion Channels Provides a Mechanism to Switch Behavior.

PubMed

Pirri, Jennifer K; Rayes, Diego; Alkema, Mark J

2015-01-01

Behavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections. However, it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network. Here we show that switching the sign of a synapse within a neural circuit can reverse the behavioral output. The inhibitory tyramine-gated chloride channel, LGC-55, induces head relaxation and inhibits forward locomotion during the Caenorhabditis elegans escape response. We switched the ion selectivity of an inhibitory LGC-55 anion channel to an excitatory LGC-55 cation channel. The engineered cation channel is properly trafficked in the native neural circuit and results in behavioral responses that are opposite to those produced by activation of the LGC-55 anion channel. Our findings indicate that switches in ion selectivity of ligand-gated ion channels (LGICs) do not affect network connectivity or stability and may provide an evolutionary and a synthetic mechanism to change behavior.

Molecular and kinetic determinants of local anaesthetic action on sodium channels.

PubMed

French, R J; Zamponi, G W; Sierralta, I E

1998-11-23

(1) Local anaesthetics (LA) rely for their clinical actions on state-dependent inhibition of voltage-dependent sodium channels. (2) Single, batrachoxin-modified sodium channels in planar lipid bilayers allow direct observation of drug-channel interactions. Two modes of inhibition of single-channel current are observed: fast block of the open channels and prolongation of a long-lived closed state, some of whose properties resemble those of the inactivated state of unmodified channels. (3) Analogues of different parts of the LA molecule separately mimic each blocking mode: amines--fast block, and water-soluble aromatics--closed state prolongation. (4) Interaction between a mu-conotoxin derivative and diethylammonium indicate an intrapore site of fast, open-state block. (5) Site-directed mutagenesis studies suggest that hydrophobic residues in transmembrane segment 6 of repeat domain 4 of sodium channels are critical for both LA binding and stabilization of the inactivated state.

Stream Channel Stability. Appendix J. Numerical Model for Routing Graded Sediments in Alluvial Channels,

DTIC Science & Technology

1981-04-01

expressed as volume of dry sediment per unit length of channel. RHB Hydraulic radius. ft SCAP(IF) Potential transport capacity of ft 3/ft material...GO) TO iSO I6=0 DO 104 IC=i,INL IA=IC+ICST-IS IF(KI(I)EQOORI(ICI).E.Q(IC2))GO TO 105 L PROPAGATION OF SHOCK WAVE AA=(QI(IC,i)/KIN)**BET AAF=AA+QL*DTS...KSI(IC).GT.0) GO Tn £09 IF(IA.EQ.i) GO TO 140 IF(XC(IA).L.E.XC(IA-i)) GO TO 11.0 C NO SHOCK IS FORMED 140 KSC(IA)=0 CO TO 104 C SHOCK IS FORMED 110

Active integrated filters for RF-photonic channelizers.

PubMed

El Nagdi, Amr; Liu, Ke; LaFave, Tim P; Hunt, Louis R; Ramakrishna, Viswanath; Dabkowski, Mieczyslaw; MacFarlane, Duncan L; Christensen, Marc P

2011-01-01

A theoretical study of RF-photonic channelizers using four architectures formed by active integrated filters with tunable gains is presented. The integrated filters are enabled by two- and four-port nano-photonic couplers (NPCs). Lossless and three individual manufacturing cases with high transmission, high reflection, and symmetric couplers are assumed in the work. NPCs behavior is dependent upon the phenomenon of frustrated total internal reflection. Experimentally, photonic channelizers are fabricated in one single semiconductor chip on multi-quantum well epitaxial InP wafers using conventional microelectronics processing techniques. A state space modeling approach is used to derive the transfer functions and analyze the stability of these filters. The ability of adapting using the gains is demonstrated. Our simulation results indicate that the characteristic bandpass and notch filter responses of each structure are the basis of channelizer architectures, and optical gain may be used to adjust filter parameters to obtain a desired frequency magnitude response, especially in the range of 1-5 GHz for the chip with a coupler separation of ∼9 mm. Preliminarily, the measurement of spectral response shows enhancement of quality factor by using higher optical gains. The present compact active filters on an InP-based integrated photonic circuit hold the potential for a variety of channelizer applications. Compared to a pure RF channelizer, photonic channelizers may perform both channelization and down-conversion in an optical domain.

Packings of monodisperse emulsions in flat microfluidic channels

NASA Astrophysics Data System (ADS)

Claussen, Ohle; Herminghaus, Stephan; Brinkmann, Martin

2012-06-01

In the lateral confinement of a flat microfluidic channel, monodisperse emulsion droplets spontaneously self-organize in a variety of topologically different packings. The explicit construction of mechanically equilibrated arrangements of effectively two-dimensional congruent droplet shapes reveals the existence of multiple mechanical equilibria depending on channel width W, droplet area Ad, and volume fraction φ of the dispersed phase. The corresponding boundaries of local or global stability are summarized in a packing diagram for congruent droplet shapes in terms of the dimensionless channel width w=W/Ad and φ. In agreement with experimental results, an increasingly strong hysteresis of the transition between single-row and two-row packings is observed during changes of w above a threshold volume fraction of φ*≃0.813.

Morphodynamic modeling of erodible laminar channels.

PubMed

Devauchelle, Olivier; Josserand, Christophe; Lagrée, Pierre-Yves; Zaleski, Stéphane

2007-11-01

A two-dimensional model for the erosion generated by viscous free-surface flows, based on the shallow-water equations and the lubrication approximation, is presented. It has a family of self-similar solutions for straight erodible channels, with an aspect ratio that increases in time. It is also shown, through a simplified stability analysis, that a laminar river can generate various bar instabilities very similar to those observed in natural rivers. This theoretical similarity reflects the meandering and braiding tendencies of laminar rivers indicated by F. Métivier and P. Meunier [J. Hydrol. 27, 22 (2003)]. Finally, we propose a simple scenario for the transition between patterns observed in experimental erodible channels.

Shaped Apertures in Photoresist Films Enhance the Lifetime and Mechanical Stability of Suspended Lipid Bilayers

PubMed Central

Kalsi, Sumit; Powl, Andrew M.; Wallace, B.A.; Morgan, Hywel; de Planque, Maurits R.R.

2014-01-01

Planar lipid bilayers suspended in apertures provide a controlled environment for ion channel studies. However, short lifetimes and poor mechanical stability of suspended bilayers limit the experimental throughput of bilayer electrophysiology experiments. Although bilayers are more stable in smaller apertures, ion channel incorporation through vesicle fusion with the suspended bilayer becomes increasingly difficult. In an alternative bilayer stabilization approach, we have developed shaped apertures in SU8 photoresist that have tapered sidewalls and a minimum diameter between 60 and 100 μm. Bilayers formed at the thin tip of these shaped apertures, either with the painting or the folding method, display drastically increased lifetimes, typically >20 h, and mechanical stability, being able to withstand extensive perturbation of the buffer solution. Single-channel electrical recordings of the peptide alamethicin and of the proteoliposome-delivered potassium channel KcsA demonstrate channel conductance with low noise, made possible by the small capacitance of the 50 μm thick SU8 septum, which is only thinned around the aperture, and unimpeded proteoliposome fusion, enabled by the large aperture diameter. We anticipate that these shaped apertures with micrometer edge thickness can substantially enhance the throughput of channel characterization by bilayer lipid membrane electrophysiology, especially in combination with automated parallel bilayer platforms. PMID:24739164

Riparian vegetation recovery patterns following stream channelization: a geomorphic perspective

USGS Publications Warehouse

Hupp, C.R.

1992-01-01

Hundreds of kilometres of West Tennessee streams have been channelized since the turn of the century. After a stream is straightened, dredged, or cleared, basin-wide ecologic, hydrologic, and geomorphic processes bring about an integrated, characteristic recovery sequence. The rapid pace of channel responses to channelization provides an opportunity to document and interpret vegetation recovery patterns relative to otherwise long-term, concomitant evolution of river geomorphology. The linkage of channel bed aggradation, woody vegetation establishment, and bank accretion all lead to recovery of the channel. Pioneer species are hardy and fast growing, and can tolerate moderate amounts of slope instability and sediment deposition; these species include river birch (Betula nigra), black willow (Salix nigra), boxelder (Acer negundo), and silver maple (Acer saccharinum). High stem densities and root-mass development appear to enhance bank stability. Tree-ring analyses suggest that on average 65 yr may be required for recovery after channelization. -from Author

Regulation of Ion Channels by Pyridine Nucleotides

PubMed Central

Kilfoil, Peter J.; Tipparaju, Srinivas M.; Barski, Oleg A.; Bhatnagar, Aruni

2014-01-01

Recent research suggests that in addition to their role as soluble electron carriers, pyridine nucleotides [NAD(P)(H)] also regulate ion transport mechanisms. This mode of regulation seems to have been conserved through evolution. Several bacterial ion–transporting proteins or their auxiliary subunits possess nucleotide-binding domains. In eukaryotes, the Kv1 and Kv4 channels interact with pyridine nucleotide–binding β-subunits that belong to the aldo-keto reductase superfamily. Binding of NADP+ to Kvβ removes N-type inactivation of Kv currents, whereas NADPH stabilizes channel inactivation. Pyridine nucleotides also regulate Slo channels by interacting with their cytosolic regulator of potassium conductance domains that show high sequence homology to the bacterial TrkA family of K+ transporters. These nucleotides also have been shown to modify the activity of the plasma membrane KATP channels, the cystic fibrosis transmembrane conductance regulator, the transient receptor potential M2 channel, and the intracellular ryanodine receptor calcium release channels. In addition, pyridine nucleotides also modulate the voltage-gated sodium channel by supporting the activity of its ancillary subunit—the glycerol-3-phosphate dehydrogenase-like protein. Moreover, the NADP+ metabolite, NAADP+, regulates intracellular calcium homeostasis via the 2-pore channel, ryanodine receptor, or transient receptor potential M2 channels. Regulation of ion channels by pyridine nucleotides may be required for integrating cell ion transport to energetics and for sensing oxygen levels or metabolite availability. This mechanism also may be an important component of hypoxic pulmonary vasoconstriction, memory, and circadian rhythms, and disruption of this regulatory axis may be linked to dysregulation of calcium homeostasis and cardiac arrhythmias. PMID:23410881

Effects of spanwise rotation on the structure of two-dimensional fully developed turbulent channel flow.

NASA Technical Reports Server (NTRS)

Johnston, J. P.; Halleen, R. M.; Lezius, D. K.

1972-01-01

Experiments on fully developed turbulent flow in a channel which is rotating at a steady rate about a spanwise axis are described. The Coriolis force components in the region of two-dimensional mean flow affect both local and global stability. Three stability-related phenomena were observed or inferred: (1) the reduction (increase) of the rate of wall-layer streak bursting in locally stabilized (destabilized) wall layers; (2) the total suppression of transition to turbulence in a stabilized layer; (3) the development of large-scale roll cells on the destabilized side of the channel by growth of a Taylor-Gortler vortex instability. Local effects of rotational stabilization, such as reduction of the turbulent stress in wall layers, can be related to the local Richardson number in a simple way. This paper not only investigates this effect, but also, by methods of flow visualization, exposes some of the underlying structure changes caused by rotation.-

Heme Regulates Allosteric Activation of the Slo1 BK Channel

PubMed Central

Horrigan, Frank T.; Heinemann, Stefan H.; Hoshi, Toshinori

2005-01-01

Large conductance calcium-dependent (Slo1 BK) channels are allosterically activated by membrane depolarization and divalent cations, and possess a rich modulatory repertoire. Recently, intracellular heme has been identified as a potent regulator of Slo1 BK channels (Tang, X.D., R. Xu, M.F. Reynolds, M.L. Garcia, S.H. Heinemann, and T. Hoshi. 2003. Nature. 425:531–535). Here we investigated the mechanism of the regulatory action of heme on heterologously expressed Slo1 BK channels by separating the influences of voltage and divalent cations. In the absence of divalent cations, heme generally decreased ionic currents by shifting the channel's G–V curve toward more depolarized voltages and by rendering the curve less steep. In contrast, gating currents remained largely unaffected by heme. Simulations suggest that a decrease in the strength of allosteric coupling between the voltage sensor and the activation gate and a concomitant stabilization of the open state account for the essential features of the heme action in the absence of divalent ions. At saturating levels of divalent cations, heme remained similarly effective with its influence on the G–V simulated by weakening the coupling of both Ca2+ binding and voltage sensor activation to channel opening. The results thus show that heme dampens the influence of allosteric activators on the activation gate of the Slo1 BK channel. To account for these effects, we consider the possibility that heme binding alters the structure of the RCK gating ring and thereby disrupts both Ca2+- and voltage-dependent gating as well as intrinsic stability of the open state. PMID:15955873

Two Small Molecules Restore Stability to a Subpopulation of the Cystic Fibrosis Transmembrane Conductance Regulator with the Predominant Disease-causing Mutation.

PubMed

Meng, Xin; Wang, Yiting; Wang, Xiaomeng; Wrennall, Joe A; Rimington, Tracy L; Li, Hongyu; Cai, Zhiwei; Ford, Robert C; Sheppard, David N

2017-03-03

Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation. To study individual CFTR Cl - channels, we performed single-channel recording, whereas to assess entire CFTR populations, we used purified CFTR proteins and macroscopic CFTR Cl - currents. At 37 °C, low temperature-rescued F508del-CFTR more rapidly lost function in cell-free membrane patches and showed altered channel gating and current flow through open channels. Compared with purified wild-type CFTR, the full-length F508del-CFTR was about 10 °C less thermostable. Lumacaftor partially stabilized purified full-length F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl - channels. By contrast, ivacaftor further destabilized full-length F508del-CFTR and accelerated channel deactivation. Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl - currents. However, at the single-channel level, chronic co-incubation greatly increased F508del-CFTR channel activity and temporal stability in most, but not all, cell-free membrane patches. We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability in a small subpopulation of F508del-CFTR Cl - channels but that the majority remain destabilized. A fuller understanding of these effects and the characterization of the small F508del-CFTR subpopulation might be crucial for CF therapy development. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Digital multi-channel stabilization of four-mode phase-sensitive parametric multicasting.

PubMed

Liu, Lan; Tong, Zhi; Wiberg, Andreas O J; Kuo, Bill P P; Myslivets, Evgeny; Alic, Nikola; Radic, Stojan

2014-07-28

Stable four-mode phase-sensitive (4MPS) process was investigated as a means to enhance two-pump driven parametric multicasting conversion efficiency (CE) and signal to noise ratio (SNR). Instability of multi-beam, phase sensitive (PS) device that inherently behaves as an interferometer, with output subject to ambient induced fluctuations, was addressed theoretically and experimentally. A new stabilization technique that controls phases of three input waves of the 4MPS multicaster and maximizes CE was developed and described. Stabilization relies on digital phase-locked loop (DPLL) specifically was developed to control pump phases to guarantee stable 4MPS operation that is independent of environmental fluctuations. The technique also controls a single (signal) input phase to optimize the PS-induced improvement of the CE and SNR. The new, continuous-operation DPLL has allowed for fully stabilized PS parametric broadband multicasting, demonstrating CE improvement over 20 signal copies in excess of 10 dB.

Physiology and pathophysiology of ClC-K/barttin channels.

PubMed

Fahlke, Christoph; Fischer, Martin

2010-01-01

ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology, and pathophysiology of ClC-K/barttin channels.

Physically Modeling Stream Channel Adjustment to Woody Riparian Vegetation

NASA Astrophysics Data System (ADS)

Bennett, S. J.; Alonso, C. V.

2003-12-01

Stream restoration designs often use vegetation to promote bank and channel stability, to facilitate point-bar development, and to encourage natural colonization of riparian species. Here we examine the adjustment of an alluvial channel to in-stream and riparian vegetation using a distorted Froude-scale flume model with a movable boundary. A decimeter-scale trapezoidal channel comprised of 0.8-mm diameter sand was systematically vegetated with emergent, rigid dowels (3-mm in diameter) in rectangular and hemispherical patterns with varying vegetation densities while conserving the shape of the zone and the geometry of the vegetal patterns. Alternate sides of the channel were vegetated at the prescribed spacing of equilibrium alternate bars, ca. 5 to 7 times the channel width. Using flow conditions just below the threshold of sediment motion, flow obstruction, deflection, and acceleration caused bed erosion, bank failure, and morphologic channel adjustments that were wholly attributable to the managed plantings. As vegetation density increased, the magnitude and rate of scaled channel adjustment increased, which included increased channel widths, bankline steepening and meandering, and thalweg meandering. As the modeled channel began to meander, the stream bed aggraded and flow depth decreased markedly, creating a continuously connected, inter-reach complex of mid-channel bars. This study demonstrates the utility of using managed vegetations in stream corridor design and meander development, and it provides the practitioner with guidance on the magnitude of channel adjustment as it relates to vegetation density, shape, and spacing.

Sedimentation, sediment quality, and upstream channel stability, John Redmond Reservoir, east-central Kansas, 1964-2009

USGS Publications Warehouse

Juracek, Kyle E.

2010-01-01

A combination of available bathymetric-survey information, bottom-sediment coring, and historical streamgage information was used to investigate sedimentation, sediment quality, and upstream channel stability for John Redmond Reservoir, east-central Kansas. Ongoing sedimentation is reducing the ability of the reservoir to serve several purposes including flood control, water supply, and recreation. The total estimated volume and mass of bottom sediment deposited between 1964 and 2009 in the conservation pool of the reservoir was 1.46 billion cubic feet and 55.8 billion pounds, respectively. The estimated sediment volume occupied about 41 percent of the conservation-pool, water-storage capacity of the reservoir. Water-storage capacity in the conservation pool has been lost to sedimentation at a rate of about 1 percent annually. Mean annual net sediment deposition since 1964 in the conservation pool of the reservoir was estimated to be 1.24 billion pounds per year. Mean annual net sediment yield from the reservoir basin was estimated to be 411,000 pounds per square mile per year Information from sediment cores shows that throughout the history of John Redmond Reservoir, total nitrogen concentrations in the deposited sediment generally were uniform indicating consistent nitrogen inputs to the reservoir. Total phosphorus concentrations in the deposited sediment were more variable than total nitrogen indicating the possibility of changing phosphorus inputs to the reservoir. As the principal limiting factor for primary production in most freshwater environments, phosphorus is of particular importance because increased inputs can contribute to accelerated reservoir eutrophication and the production of algal toxins and taste-and-odor compounds. The mean annual net loads of total nitrogen and total phosphorus deposited in the bottom sediment of the reservoir were estimated to be 2,350,000 pounds per year and 1,030,000 pounds per year, respectively. The estimated mean annual

Preliminary assessment of channel stability and bed-material transport along Hunter Creek, southwestern Oregon

USGS Publications Warehouse

Jones, Krista L.; Wallick, J. Rose; O'Connor, Jim E.; Keith, Mackenzie K.; Mangano, Joseph F.; Risley, John C.

2011-01-01

This preliminary assessment of (1) bed-material transport in the Hunter Creek basin, (2) historical changes in channel condition, and (3) supplementary data needed to inform permitting decisions regarding instream gravel extraction revealed the following: Along the lower 12.4 km (kilometers) of Hunter Creek from its confluence with the Little South Fork Hunter Creek to its mouth, the river has confined and unconfined segments and is predominately alluvial in its lowermost 11 km. This 12.4-km stretch of river can be divided into two geomorphically distinct study reaches based primarily on valley physiography. In the Upper Study Reach (river kilometer [RKM] 12.4-6), the active channel comprises a mixed bed of bedrock, boulders, and smaller grains. The stream is confined in the upper 1.4 km of the reach by a bedrock canyon and in the lower 2.4 km by its valley. In the Lower Study Reach (RKM 6-0), where the area of gravel bars historically was largest, the stream flows over bed material that is predominately alluvial sediments. The channel alternates between confined and unconfined segments. The primary human activities that likely have affected bed-material transport and the extent and area of gravel bars are (1) historical and ongoing aggregate extraction from gravel bars in the study area and (2) timber harvest and associated road construction throughout the basin. These anthropogenic activities likely have varying effects on sediment transport and deposition throughout the study area and over time. Although assessing the relative effects of these anthropogenic activities on sediment dynamics would be challenging, the Hunter Creek basin may serve as a case study for such an assessment because it is mostly free of other alterations to hydrologic and geomorphic processes such as flow regulation, dredging, and other navigation improvements that are common in many Oregon coastal basins. Several datasets are available that may support a more detailed physical assessment

2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel.

PubMed

Ghosh, Ayanjeet; Wang, Jun; Moroz, Yurii S; Korendovych, Ivan V; Zanni, Martin; DeGrado, William F; Gai, Feng; Hochstrasser, Robin M

2014-06-21

Water is an integral part of the homotetrameric M2 proton channel of the influenza A virus, which not only assists proton conduction but could also play an important role in stabilizing channel-blocking drugs. Herein, we employ two dimensional infrared (2D IR) spectroscopy and site-specific IR probes, i.e., the amide I bands arising from isotopically labeled Ala30 and Gly34 residues, to probe how binding of either rimantadine or 7,7-spiran amine affects the water dynamics inside the M2 channel. Our results show, at neutral pH where the channel is non-conducting, that drug binding leads to a significant increase in the mobility of the channel water. A similar trend is also observed at pH 5.0 although the difference becomes smaller. Taken together, these results indicate that the channel water facilitates drug binding by increasing its entropy. Furthermore, the 2D IR spectral signatures obtained for both probes under different conditions collectively support a binding mechanism whereby amantadine-like drugs dock in the channel with their ammonium moiety pointing toward the histidine residues and interacting with a nearby water cluster, as predicted by molecular dynamics simulations. We believe these findings have important implications for designing new anti-influenza drugs.

2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Ayanjeet, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Gai, Feng, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Hochstrasser, Robin M.

Water is an integral part of the homotetrameric M2 proton channel of the influenza A virus, which not only assists proton conduction but could also play an important role in stabilizing channel-blocking drugs. Herein, we employ two dimensional infrared (2D IR) spectroscopy and site-specific IR probes, i.e., the amide I bands arising from isotopically labeled Ala30 and Gly34 residues, to probe how binding of either rimantadine or 7,7-spiran amine affects the water dynamics inside the M2 channel. Our results show, at neutral pH where the channel is non-conducting, that drug binding leads to a significant increase in the mobility ofmore » the channel water. A similar trend is also observed at pH 5.0 although the difference becomes smaller. Taken together, these results indicate that the channel water facilitates drug binding by increasing its entropy. Furthermore, the 2D IR spectral signatures obtained for both probes under different conditions collectively support a binding mechanism whereby amantadine-like drugs dock in the channel with their ammonium moiety pointing toward the histidine residues and interacting with a nearby water cluster, as predicted by molecular dynamics simulations. We believe these findings have important implications for designing new anti-influenza drugs.« less

Channel Rehabilitation: Processes, Design, and Implementation

DTIC Science & Technology

1999-07-01

Export coefficients or Universal Soil Loss Equation parameters associated with sediment delivery from different land covers / uses and conservation...operate at submerged conditions where the tailwater (T’) does not fall below 0.8 of the critical depth (Dc) at the crest section ( Linder , 1963...natural channels. Washington, DC: U.S. Geological Survey Water-Supply Paper, 1898-B, 47 p. Linder , W.M. (1963). Stabilization of Stream Beds with

The NH2 terminus regulates voltage-dependent gating of CALHM ion channels.

PubMed

Tanis, Jessica E; Ma, Zhongming; Foskett, J Kevin

2017-08-01

Calcium homeostasis modulator protein-1 (CALHM1) and its Caenorhabditis elegans (ce) homolog, CLHM-1, belong to a new family of physiologically important ion channels that are regulated by voltage and extracellular Ca 2+ (Ca 2+ o ) but lack a canonical voltage-sensing domain. Consequently, the intrinsic voltage-dependent gating mechanisms for CALHM channels are unknown. Here, we performed voltage-clamp experiments on ceCLHM-1 chimeric, deletion, insertion, and point mutants to assess the role of the NH 2 terminus (NT) in CALHM channel gating. Analyses of chimeric channels in which the ceCLHM-1 and human (h)CALHM1 NH 2 termini were interchanged showed that the hCALHM1 NT destabilized channel-closed states, whereas the ceCLHM-1 NT had a stabilizing effect. In the absence of Ca 2+ o , deletion of up to eight amino acids from the ceCLHM-1 NT caused a hyperpolarizing shift in the conductance-voltage relationship with little effect on voltage-dependent slope. However, deletion of nine or more amino acids decreased voltage dependence and induced a residual conductance at hyperpolarized voltages. Insertion of amino acids into the NH 2 -terminal helix also decreased voltage dependence but did not prevent channel closure. Mutation of ceCLHM-1 valine 9 and glutamine 13 altered half-maximal activation and voltage dependence, respectively, in 0 Ca 2+ In 2 mM Ca 2+ o , ceCLHM-1 NH 2 -terminal deletion and point mutant channels closed completely at hyperpolarized voltages with apparent affinity for Ca 2+ o indistinguishable from wild-type ceCLHM-1, although the ceCLHM-1 valine 9 mutant exhibited an altered conductance-voltage relationship and kinetics. We conclude that the NT plays critical roles modulating voltage dependence and stabilizing the closed states of CALHM channels. Copyright © 2017 the American Physiological Society.

Chloride channels as tools for developing selective insecticides.

PubMed

Bloomquist, Jeffrey R

2003-12-01

Ligand-gated chloride channels underlie inhibition in excitable membranes and are proven target sites for insecticides. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for a number of currently used insecticides, such as lindane, endosulfan, and fipronil. These compounds act as antagonists by stabilizing nonconducting conformations of the chloride channel. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system, convulsions, and death. We recently investigated the mode of action of the silphinenes, plant-derived natural compounds that structurally resemble picrotoxinin. These materials antagonize the action of GABA on insect neurons and block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner. In mammals, avermectins have a blocking action on the GABA-gated chloride channel consistent with a coarse tremor, whereas at longer times and higher concentrations, activation of the channel suppresses neuronal activity. Invertebrates display ataxia, paralysis, and death as the predominant signs of poisoning, with a glutamate-gated chloride channel playing a major role. Additional target sites for the avermectins or other chloride channel-directed compounds might include receptors gated by histamine, serotonin, or acetylcholine.The voltage-sensitive chloride channels form another large gene family of chloride channels. Voltage-dependent chloride channels are involved in a number of physiological processes including: maintenance of electrical excitability, chloride ion secretion and resorption, intravesicular acidification, and cell volume regulation. A subset of these channels is affected by convulsants and insecticides in mammals, although the role they play in acute lethality in insects is unclear. Given the wide range of functions that they mediate, these channels are also potential targets for

Historical and simulated changes in channel characteristics of the Kalamazoo River, Plainwell to Otesgo, Michigan

USGS Publications Warehouse

Rachol, Cynthia M.; Fitzpatrick, Faith A.; Rossi, Tiffiny

2005-01-01

In a study to understand the historical effects of the construction and decommissioning of dams on the Kalamazoo River, Plainwell to Otesgo, Michigan, and to simulate channel changes that may result if the dams were removed, early to mid-1800s General Land Office surveys and aerial photographs from 1938, 1981, and 1999 were compared in order to identify historical changes in the river’s planform. This analysis of the 80-mile reach from Morrow Dam to the river mouth at Saugatuck provided insight into how susceptible the river has been to channel migration. The comparison showed that changes in channel width and location were caused mainly by construction of dams and subsequent water-level adjustments in the impounded reaches upstream from the dams. Braiding also occurred downstream from one of the dams. Minor changes in channel form that were not caused by the dams, such as the development and cutoff of meander bends, were observed. A more detailed study in a 5-mile reach passing through the Plainwell and Otsego City Dams included compiling existing valley cross section and longitudinal profile data into a database, assessing bank stability, and using a hydrologic model to simulate the channel as if the dams were removed. Fifty-four valley cross sections compiled from United States Geological Survey and consultant data sets were used as a base for a bank-stability assessment and to design a hypothetical stable channel without the two dams. The channel design involved adjusting the slope, hydraulic geometry, and floodplain width to ensure that water could be transferred through the reach without increasing flooding or erosion problems. The bank-stability assessment focused on conditions that are critical to failure. This was accomplished through the use of a two step process. The first involved evaluating the sediment removed from the bank toe when the stage is high. The second involved calculating the factor of safety for the bank based on the water table being

DC/DC Converter Stability Testing Study

NASA Technical Reports Server (NTRS)

Wang, Bright L.

2008-01-01

This report presents study results on hybrid DC/DC converter stability testing methods. An input impedance measurement method and a gain/phase margin measurement method were evaluated to be effective to determine front-end oscillation and feedback loop oscillation. In particular, certain channel power levels of converter input noises have been found to have high degree correlation with the gain/phase margins. It becomes a potential new method to evaluate stability levels of all type of DC/DC converters by utilizing the spectral analysis on converter input noises.

Electrical Conductivity, Thermal Stability, and Lattice Defect Evolution During Cyclic Channel Die Compression of OFHC Copper

NASA Astrophysics Data System (ADS)

Satheesh Kumar, S. S.; Raghu, T.

2015-02-01

Oxygen-free high-conductivity (OFHC) copper samples are severe plastically deformed by cyclic channel die compression (CCDC) technique at room temperature up to an effective plastic strain of 7.2. Effect of straining on variation in electrical conductivity, evolution of deformation stored energy, and recrystallization onset temperatures are studied. Deformation-induced lattice defects are quantified using three different methodologies including x-ray diffraction profile analysis employing Williamson-Hall technique, stored energy based method, and electrical resistivity-based techniques. Compared to other severe plastic deformation techniques, electrical conductivity degrades marginally from 100.6% to 96.6% IACS after three cycles of CCDC. Decrease in recrystallization onset and peak temperatures is noticed, whereas stored energy increases and saturates at around 0.95-1.1J/g after three cycles of CCDC. Although drop in recrystallization activation energy is observed with the increasing strain, superior thermal stability is revealed, which is attributed to CCDC process mechanics. Low activation energy observed in CCDC-processed OFHC copper is corroborated to synergistic influence of grain boundary characteristics and lattice defects distribution. Estimated defects concentration indicated continuous increase in dislocation density and vacancy with strain. Deformation-induced vacancy concentration is found to be significantly higher than equilibrium vacancy concentration ascribed to hydrostatic stress states experienced during CCDC.

Effects of phenylalanine substitutions in gramicidin A on the kinetics of channel formation in vesicles and channel structure in SDS micelles.

PubMed

Jordan, J B; Easton, P L; Hinton, J F

2005-01-01

The common occurrence of Trp residues at the aqueous-lipid interface region of transmembrane channels is thought to be indicative of its importance for insertion and stabilization of the channel in membranes. To further investigate the effects of Trp-->Phe substitution on the structure and function of the gramicidin channel, four analogs of gramicidin A have been synthesized in which the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced with phenylalanine. The three-dimensional structure of each viable analog has been determined using a combination of two-dimensional NMR techniques and distance geometry-simulated annealing structure calculations. These phenylalanine analogs adopt a homodimer motif, consisting of two beta6.3 helices joined by six hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues does not have a significant effect on the backbone structure of the channels when compared to native gramicidin A, and only small effects are seen on side-chain conformations. Single-channel conductance measurements have shown that the conductance and lifetime of the channels are significantly affected by the replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The variation in conductance appears to be caused by the sequential removal of a tryptophan dipole, thereby removing the ion-dipole interaction at the channel entrance and at the ion binding site. Channel lifetime variations appear to be related to changing side chain-lipid interactions. This is supported by data relating to transport and incorporation kinetics.

Modulation of BK channel voltage gating by different auxiliary β subunits

PubMed Central

Contreras, Gustavo F.; Neely, Alan; Alvarez, Osvaldo; Gonzalez, Carlos; Latorre, Ramon

2012-01-01

Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating mechanisms are allosterically coupled. In most instances the pore forming α subunit of BK is associated with one of four alternative β subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, β1 stabilizes the active configuration of the BK voltage sensor having a large effect on BK Ca2+ sensitivity. To determine the extent to which β subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK α subunit alone and with the different β subunits expressed in Xenopus oocytes (β1, β2IR, β3b, and β4). We found that β1, β2, and β4 stabilize the BK voltage sensor in the active conformation. β3 has no effect on voltage sensor equilibrium. In addition, β4 decreases the apparent number of charges per voltage sensor. The decrease in the charge associated with the voltage sensor in α β4 channels explains most of their biophysical properties. For channels composed of the α subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K+ current activation. In the presence of β1, β2, and β4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps. PMID:23112204

Grazed Riparian Management and Stream Channel Response in Southeastern Minnesota (USA) Streams

NASA Astrophysics Data System (ADS)

Magner, Joseph A.; Vondracek, Bruce; Brooks, Kenneth N.

2008-09-01

The U.S. Department of Agriculture-Natural Resources Conservation Service has recommended domestic cattle grazing exclusion from riparian corridors for decades. This recommendation was based on a belief that domestic cattle grazing would typically destroy stream bank vegetation and in-channel habitat. Continuous grazing (CG) has caused adverse environmental damage, but along cohesive-sediment stream banks of disturbed catchments in southeastern Minnesota, short-duration grazing (SDG), a rotational grazing system, may offer a better riparian management practice than CG. Over 30 physical and biological metrics were gathered at 26 sites to evaluate differences between SDG, CG, and nongrazed sites (NG). Ordinations produced with nonmetric multidimensional scaling (NMS) indicated a gradient with a benthic macroinvertebrate index of biotic integrity (IBI) and riparian site management; low IBI scores associated with CG sites and higher IBI scores associated with NG sites. Nongrazed sites were associated with reduced soil compaction and higher bank stability, as measured by the Pfankuch stability index; whereas CG sites were associated with increased soil compaction and lower bank stability, SDG sites were intermediate. Bedrock geology influenced NMS results: sites with carbonate derived cobble were associated with more stable channels and higher IBI scores. Though current riparian grazing practices in southeastern Minnesota present pollution problems, short duration grazing could reduce sediment pollution if managed in an environmentally sustainable fashion that considers stream channel response.

Grazed riparian management and stream channel response in southeastern Minnesota (USA) streams

USGS Publications Warehouse

Magner, J.A.; Vondracek, B.; Brooks, K.N.

2008-01-01

The U.S. Department of Agriculture-Natural Resources Conservation Service has recommended domestic cattle grazing exclusion from riparian corridors for decades. This recommendation was based on a belief that domestic cattle grazing would typically destroy stream bank vegetation and in-channel habitat. Continuous grazing (CG) has caused adverse environmental damage, but along cohesive-sediment stream banks of disturbed catchments in southeastern Minnesota, short-duration grazing (SDG), a rotational grazing system, may offer a better riparian management practice than CG. Over 30 physical and biological metrics were gathered at 26 sites to evaluate differences between SDG, CG, and nongrazed sites (NG). Ordinations produced with nonmetric multidimensional scaling (NMS) indicated a gradient with a benthic macroinvertebrate index of biotic integrity (IBI) and riparian site management; low IBI scores associated with CG sites and higher IBI scores associated with NG sites. Nongrazed sites were associated with reduced soil compaction and higher bank stability, as measured by the Pfankuch stability index; whereas CG sites were associated with increased soil compaction and lower bank stability, SDG sites were intermediate. Bedrock geology influenced NMS results: sites with carbonate derived cobble were associated with more stable channels and higher IBI scores. Though current riparian grazing practices in southeastern Minnesota present pollution problems, short duration grazing could reduce sediment pollution if managed in an environmentally sustainable fashion that considers stream channel response. ?? 2008 Springer Science+Business Media, LLC.

Linear time-invariant controller design for two-channel decentralized control systems

NASA Technical Reports Server (NTRS)

Desoer, Charles A.; Gundes, A. Nazli

1987-01-01

This paper analyzes a linear time-invariant two-channel decentralized control system with a 2 x 2 strictly proper plant. It presents an algorithm for the algebraic design of a class of decentralized compensators which stabilize the given plant.

Effects of Phenylalanine Substitutions in Gramicidin A on the Kinetics of Channel Formation in Vesicles and Channel Structure in SDS Micelles

PubMed Central

Jordan, J. B.; Easton, P. L.; Hinton, J. F.

2005-01-01

The common occurrence of Trp residues at the aqueous-lipid interface region of transmembrane channels is thought to be indicative of its importance for insertion and stabilization of the channel in membranes. To further investigate the effects of Trp→Phe substitution on the structure and function of the gramicidin channel, four analogs of gramicidin A have been synthesized in which the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced with phenylalanine. The three-dimensional structure of each viable analog has been determined using a combination of two-dimensional NMR techniques and distance geometry-simulated annealing structure calculations. These phenylalanine analogs adopt a homodimer motif, consisting of two β6.3 helices joined by six hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues does not have a significant effect on the backbone structure of the channels when compared to native gramicidin A, and only small effects are seen on side-chain conformations. Single-channel conductance measurements have shown that the conductance and lifetime of the channels are significantly affected by the replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The variation in conductance appears to be caused by the sequential removal of a tryptophan dipole, thereby removing the ion-dipole interaction at the channel entrance and at the ion binding site. Channel lifetime variations appear to be related to changing side chain-lipid interactions. This is supported by data relating to transport and incorporation kinetics. PMID:15501932

The effect of basal channels on oceanic ice-shelf melting

NASA Astrophysics Data System (ADS)

Millgate, Thomas; Holland, Paul R.; Jenkins, Adrian; Johnson, Helen L.

2013-12-01

The presence of ice-shelf basal channels has been noted in a number of Antarctic and Greenland ice shelves, but their impact on basal melting is not fully understood. Here we use the Massachusetts Institute of Technology general circulation model to investigate the effect of ice-shelf basal channels on oceanic melt rate for an idealized ice shelf resembling the floating tongue of Petermann Glacier in Greenland. The introduction of basal channels prevents the formation of a single geostrophically balanced boundary current; instead the flow is diverted up the right-hand (Coriolis-favored) side of each channel, with a return flow in the opposite direction on the left-hand side. As the prescribed number of basal channels is increased the mean basal melt rate decreases, in agreement with previous studies. For a small number of relatively wide channels the subice flow is found to be a largely geostrophic horizontal circulation. The reduction in melt rate is then caused by an increase in the relative contribution of weakly melting channel crests and keels. For a larger number of relatively narrow channels, the subice flow changes to a vertical overturning circulation. This change in circulation results in a weaker sensitivity of melt rates to channel size. The transition between the two regimes is governed by the Rossby radius of deformation. Our results explain why basal channels play an important role in regulating basal melting, increasing the stability of ice shelves.

Structural Changes Fundamental to Gating of the Cystic Fibrosis Transmembrane Conductance Regulator Anion Channel Pore.

PubMed

Linsdell, Paul

2017-01-01

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.

Rapid Fabrication Techniques for Liquid Rocket Channel Wall Nozzles

NASA Technical Reports Server (NTRS)

Gradl, Paul R.

2016-01-01

The functions of a regeneratively-cooled nozzle are to (1) expand combustion gases to increase exhaust gas velocity while, (2) maintaining adequate wall temperatures to prevent structural failure, and (3) transfer heat from the hot gases to the coolant fluid to promote injector performance and stability. Regeneratively-cooled nozzles are grouped into two categories: tube-wall nozzles and channel wall nozzles. A channel wall nozzle is designed with an internal liner containing a series of integral coolant channels that are closed out with an external jacket. Manifolds are attached at each end of the nozzle to distribute coolant to and away from the channels. A variety of manufacturing techniques have been explored for channel wall nozzles, including state of the art laser-welded closeouts and pressure-assisted braze closeouts. This paper discusses techniques that NASA MSFC is evaluating for rapid fabrication of channel wall nozzles that address liner fabrication, slotting techniques and liner closeout techniques. Techniques being evaluated for liner fabrication include large-scale additive manufacturing of freeform-deposition structures to create the liner blanks. Abrasive water jet milling is being evaluated for cutting the complex coolant channel geometries. Techniques being considered for rapid closeout of the slotted liners include freeform deposition, explosive bonding and Cold Spray. Each of these techniques, development work and results are discussed in further detail in this paper.

Influence of membrane thickness and ion concentration on the properties of the gramicidin a channel. Autocorrelation, spectral power density, relaxation and single-channel studies.

PubMed

Kolb, H A; Bamberg, E

1977-01-04

The properties of the gramicidin A channel in membranes made from a series of monoglycerides have been studied. In agreement with previous studies, the dissociation rate constant kD of the dimeric channel was found to increase strongly with increasing chain length of the monoglyceride, corresponding to a decrease of the mean life-time of the channel. The value of kD, however, was not strictly correlated with the membrane thickness, as seen from a comparison of membranes with different solvent content. Furthermore, the life-time of the channel increased with the concentration of the permeable ion. This effect was tentatively explained by an electrostatic stabilization of the channel. The single-channel conductance lambda was found to decrease with increasing membrane thickness d, if d was varied by increasing the chain length of the lipid. On the other hand, if d was changed by varying the solvent content of the membranes formed from one and the same lipid, lambda remained constant. These observations were explained by the assumption of local inhomogeneities in the membrane thickness. A striking difference between the lambda values obtained from autocorrelation analysis in the presence of many presence of many channels (lambda a) and those obtained from single-channel experiments (lambda sc) occurred with membranes from longer chain-length monoglycerides. This difference disappeared at low ion concentrations. Electrostatic interactions between channels in local clusters were proposed for an interpretation of these findings.

Continuous Diffusion Flames and Flame Streets in Micro-Channels

NASA Astrophysics Data System (ADS)

Mohan, Shikhar; Matalon, Moshe

2015-11-01

Experiments of non-premixed combustion in micro-channels have shown different modes of burning. Normally, a flame is established along, or near the axis of a channel that spreads the entire mixing layer and separates a region of fuel but no oxidizer from a region with only oxidizer. Often, however, a periodic sequence of extinction and reignition events, termed collectively as ``flame streets'', are observed. They constitute a series of diffusion flames, each with a tribrachial leading edge stabilized along the channel. This work focuses on understanding the underlying mechanism responsible for these distinct observations. Numerical simulations were conducted in the thermo-diffusive limit in order to study the effects of confinement and heat loss on non-premixed flames in three-dimensional micro-channels with low aspect ratios. The three dimensionality of the channel was captured qualitatively through a systematic asymptotic analysis that led to a two dimensional problem with an effective parameter representing heat losses in the vertical direction. There exist three key flame regimes: (1) a stable continuous diffusion flame, (2) an unsteady flame, and (3) a stable ``flame street'' the transition between regimes demarcated primarily by Reynolds and Nusselt numbers.

Back-channel-etch amorphous indium-gallium-zinc oxide thin-film transistors: The impact of source/drain metal etch and final passivation

NASA Astrophysics Data System (ADS)

Nag, Manoj; Bhoolokam, Ajay; Steudel, Soeren; Chasin, Adrian; Myny, Kris; Maas, Joris; Groeseneken, Guido; Heremans, Paul

2014-11-01

We report on the impact of source/drain (S/D) metal (molybdenum) etch and the final passivation (SiO2) layer on the bias-stress stability of back-channel-etch (BCE) configuration based amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). It is observed that the BCE configurations TFTs suffer poor bias-stability in comparison to etch-stop-layer (ESL) TFTs. By analysis with transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS), as well as by a comparative analysis of contacts formed by other metals, we infer that this poor bias-stability for BCE transistors having Mo S/D contacts is associated with contamination of the back channel interface, which occurs by Mo-containing deposits on the back channel during the final plasma process of the physical vapor deposited SiO2 passivation.

Self-Assembling Organic Nanopores as Synthetic Transmembrane Channels with Tunable Functions

NASA Astrophysics Data System (ADS)

Wei, Xiaoxi

A long-standing goal in the area of supramolecular self-assembly involves the development of synthetic ion/water channels capable of mimicking the mass-transport characteristics of biological channels and pores. Few examples of artificial transmembrane channels with large lumen, high conductivity and selectivity are known. A review of pronounced biological transmembrane protein channels and some representative synthetic models have been provided in Chapter 1, followed by our discovery and initial investigation of shape-persistent oligoamide and phenylene ethynylene macrocycles as synthetic ion/water channels. In Chapter 2, the systematic structural modification of oligoamide macrocycles 1, the so-called first-generation of these shape-persistent macrocycles, has led to third-generation macrocycles 3. The third generation was found to exhibit unprecedented, strong intermolecular association in both the solid state and solution via multiple techniques including X-ray diffraction (XRD), SEM, and 1H NMR. Fluorescence spectroscopy paired with dynamic light scattering (DLS) revealed that macrocycles 3 can assemble into a singly dispersed nanotubular structure in solution. The resultant self-assembling pores consisting of 3 were examined by HPTS-LUVs assays and BLM studies (Chapter 3) and found to form cation-selective (PK+/PCl- = 69:1) transmembrane ion channels with large conductance (200 ˜ 2000 pS for alkali cations) and high stability with open times reaching to 103 seconds. Tuning the aggregation state of macrocycles by choosing an appropriate polar solvent mixture (i.e., 3:1, THF:DMF, v/v) and concentration led to the formation of ion channels with well-defined square top behavior. A parallel study using DLS to examine the size of aggregates was used in conjunction with channel activity assays (LUVs/BLM) to reveal the effects of the aggregation state on channel activity. Empirical evidence now clearly indicates that a preassembled state, perhaps that of a

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture.

PubMed

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong; Kim, Sunghoon; She, Ji; Cang, Chunlei; Ren, Dejian; Jiang, Youxing

2017-07-27

TMEM175 is a lysosomal K + channel that is important for maintaining the membrane potential and pH stability in lysosomes. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K + channels and lacks the TVGYG selectivity filter motif found in these channels. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completely different fold from that of canonical K + channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K + channel family.

Assessment of the effects of regional channel stability and sediment transport on roadway hydraulic structures : final report.

DOT National Transportation Integrated Search

2014-06-01

Rivers and streams evolve all the time. As a result, no stream channel is absolutely stable. Channels evolve at various speeds both vertically (degradation/aggradation) and horizontally (meander : migration). They also respond to man-made changes ran...

Single-channel stereoscopic ophthalmology microscope based on TRD

NASA Astrophysics Data System (ADS)

Radfar, Edalat; Park, Jihoon; Lee, Sangyeob; Ha, Myungjin; Yu, Sungkon; Jang, Seulki; Jung, Byungjo

2016-03-01

A stereoscopic imaging modality was developed for the application of ophthalmology surgical microscopes. A previous study has already introduced a single-channel stereoscopic video imaging modality based on a transparent rotating deflector (SSVIM-TRD), in which two different view angles, image disparity, are generated by imaging through a transparent rotating deflector (TRD) mounted on a stepping motor and is placed in a lens system. In this case, the image disparity is a function of the refractive index and the rotation angle of TRD. Real-time single-channel stereoscopic ophthalmology microscope (SSOM) based on the TRD is improved by real-time controlling and programming, imaging speed, and illumination method. Image quality assessments were performed to investigate images quality and stability during the TRD operation. Results presented little significant difference in image quality in terms of stability of structural similarity (SSIM). A subjective analysis was performed with 15 blinded observers to evaluate the depth perception improvement and presented significant improvement in the depth perception capability. Along with all evaluation results, preliminary results of rabbit eye imaging presented that the SSOM could be utilized as an ophthalmic operating microscopes to overcome some of the limitations of conventional ones.

Turning the tide: estuarine bars and mutually evasive ebb- and flood-dominated channels

NASA Astrophysics Data System (ADS)

Kleinhans, M. G.; Leuven, J.; van der Vegt, M.; Baar, A. W.; Braat, L.; Bergsma, L.; Weisscher, S.

2015-12-01

Estuaries have perpetually changing and interacting channels and shoals formed by ebb and flood currents, but we lack a descriptive taxonomy and forecasting model. We explore the hypotheses that the great variation of bar and shoal morphologies are explained by similar factors as river bars, namely channel aspect ratio, sediment mobility and limits on bar erosion and chute cutoff caused by cohesive sediment. Here we use remote sensing data and a novel tidal flume setup, the Metronome, to create estuaries or short estuarine reaches from idealized initial conditions, with and without mud supply at the fluvial boundary. Bar width-depth ratios in estuaries are similar to those in braided rivers. In unconfined (cohesionless) experimental estuaries, bar- and channel dynamics increase with increasing river discharge. Ebb- and flood-dominated channels are ubiquitous even in entirely straight sections. The apparent stability of ebb- and flood channels is partly explained by the inherent instability of symmetrical channel bifurcations as in rivers.

Schlieren, Phase-Contrast, and Spectroscopy Diagnostics for the LBNL HIF Plasma Channel Experiment

NASA Astrophysics Data System (ADS)

Ponce, D. M.; Niemann, C.; Fessenden, T. J.; Leemans, W.; Vandersloot, K.; Dahlbacka, G.; Yu, S. S.; Sharp, W. M.; Tauschwitz, A.

1999-11-01

The LBNL Plasma Channel experiment has demonstrated stable 42-cm Z-pinch discharge plasma channels with peak currents in excess of 50 kA for a 7 torr nitrogen, 30 kV discharge. These channels offer the possibility of transporting heavy-ion beams for inertial fusion. We postulate that the stability of these channels resides in the existance of a neutral-gas density depresion created by a pre-pulse discharge before the main capacitor bank discharge is created. Here, we present the results and experimental diagnostics setup used for the study of the pre-pulse and main bank channels. Observation of both the plasma and neutral gas dynamics is achieved. Schlieren, Zernike's phase-contrast, and spectroscopic techniques are used. Preliminary Schlieren results show a gas shockwave moving radially at a rate of ≈ 10^6 mm/sec as a result of the fast and localized deposited energy during the evolution of the pre-pulse channel. This data will be used to validate simulation codes (BUCKY and CYCLOPS).

Estimating design-flood discharges for streams in Iowa using drainage-basin and channel-geometry characteristics

USGS Publications Warehouse

Eash, D.A.

1993-01-01

Procedures provided for applying the drainage-basin and channel-geometry regression equations depend on whether the design-flood discharge estimate is for a site on an ungaged stream, an ungaged site on a gaged stream, or a gaged site. When both a drainage-basin and a channel-geometry regression-equation estimate are available for a stream site, a procedure is presented for determining a weighted average of the two flood estimates. The drainage-basin regression equations are applicable to unregulated rural drainage areas less than 1,060 square miles, and the channel-geometry regression equations are applicable to unregulated rural streams in Iowa with stabilized channels.

Highly stable thin film transistors using multilayer channel structure

NASA Astrophysics Data System (ADS)

Nayak, Pradipta K.; Wang, Zhenwei; Anjum, D. H.; Hedhili, M. N.; Alshareef, H. N.

2015-03-01

We report highly stable gate-bias stress performance of thin film transistors (TFTs) using zinc oxide (ZnO)/hafnium oxide (HfO2) multilayer structure as the channel layer. Positive and negative gate-bias stress stability of the TFTs was measured at room temperature and at 60 °C. A tremendous improvement in gate-bias stress stability was obtained in case of the TFT with multiple layers of ZnO embedded between HfO2 layers compared to the TFT with a single layer of ZnO as the semiconductor. The ultra-thin HfO2 layers act as passivation layers, which prevent the adsorption of oxygen and water molecules in the ZnO layer and hence significantly improve the gate-bias stress stability of ZnO TFTs.

Optimization of the Solution-Based Indium-Zinc Oxide/Zinc-Tin Oxide Channel Layer for Thin-Film Transistors.

PubMed

Lim, Kiwon; Choi, Pyungho; Kim, Sangsub; Kim, Hyunki; Kim, Minsoo; Lee, Jeonghyun; Hyeon, Younghwan; Koo, Kwangjun; Choi, Byoungdeog

2018-09-01

Double stacked indium-zinc oxide (IZO)/zinc-tin oxide (ZTO) active layers were employed in amorphous-oxide-semiconductor thin-film transistors (AOS TFTs). Channel layers of the TFTs were optimized by varying the molarity of ZTO back channel layers (0.05, 0.1, 0.2, 0.3 M) and the electrical properties of IZO/ZTO double stacked TFTs were compared to single IZO and ZTO TFTs with varying the molarity and molar ratio. On the basis of the results, IZO/ZTO (0.1 M) TFTs showed the excellent electrical properties of saturation mobility (13.6 cm2/V·s), on-off ratio (7×106), and subthreshold swing (0.223 V/decade) compared to ZTO (0.1 M) of 0.73 cm2/V · s, 1 × 107, 0.416 V/decade and IZO (0.04 M) of 0.10 cm2/V · s, 5 × 106, 0.60 V/decade, respectively. This may be attributed to diffusing Sn into front layer during annealing process. In addition, with varying molarity of ZTO back channel layer, from 0.1 M to 0.3 M ZTO back channel TFTs, electrical properties and positive bias stability deteriorated with increasing molarity of back channel layer because of increasing total trap states. On the other hand, 0.05 M ZTO back channel TFT had inferior electrical properties than that of 0.1 M ZTO back channel TFT. It was related to back channel effect because of having thin thickness of channel layer. Among these devices, 0.1 M ZTO back channel TFT had a lowest total trap density, outstanding electrical properties and stability. Therefore, we recommended IZO/ZTO (0.1 M) TFT as a promising channel structure for advanced display applications.

Voltage-Dependent Gating of hERG Potassium Channels

PubMed Central

Cheng, Yen May; Claydon, Tom W.

2012-01-01

The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv) channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4–S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-à-go-go related gene, hERG), which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure–function relationships underlying activation and deactivation gating in Shaker and hERG channels, with a focus on the roles of the voltage-sensing domain and the S4–S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter-charge interactions. More recent data suggest that key amino acid differences in the hERG voltage-sensing unit and S4–S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor. PMID:22586397

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong

TMEM175 is a lysosomal K+ channel that is important for maintaining the membrane potential and pH stability in lysosomes1. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K+ channels and lacks the TVGYG selectivity filter motif found in these channels2, 3, 4. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completelymore » different fold from that of canonical K+ channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K+ channel family.« less

Effects of natural-channel-design restoration on habitat quality in Catskill Mountain streams, New York

USGS Publications Warehouse

Ernst, Anne G.; Baldigo, Barry P.; Mulvihill, Christiane; Vian, Mark

2010-01-01

Stream restoration has received much attention in recent years, yet there has been little effort to evaluate its impacts on physical habitat, stability, and biota. A popular but controversial stream restoration approach is natural channel design (NCD), which cannot be adequately evaluated without a long-term, independent assessment of its effects on stream habitat. Six reaches of five Catskill Mountain streams in southeastern New York were restored during 2000–2003 following NCD techniques to decrease bed and bank degradation, decrease sediment loads, and improve water quality. Habitat surveys were conducted during summer low flows from 2001 to 2007. The effects of the NCD projects on stream condition were assessed via a before–after–control–impact study design to quantify the net changes in stream and bank habitat variables relative to those in unaltered control reaches. Analysis of variance tests of three different measures of bank stability show that on average stream stability increased at treatment sites for 2–5 years after restoration. Mean channel depth, thalweg depth, and the pool–riffle ratio generally increased, whereas mean channel width, percent streambank coverage by trees, and shade decreased. Habitat suitability indices for local salmonid species increased at four of six reaches after restoration. The changes in channel dimensions rendered them generally more characteristic of stabler stream forms in the given valley settings. Although these studies were done relatively soon after project completion, our findings demonstrate that habitat conditions can be improved in degraded Catskill Mountain streams through NCD restoration.

Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study

PubMed Central

Karoly, Robert; Lenkey, Nora; Juhasz, Andras O.; Vizi, E. Sylvester; Mike, Arpad

2010-01-01

Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the “steady-state slow inactivation curve”), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions

Phosphorus Doping Effect in a Zinc Oxide Channel Layer to Improve the Performance of Oxide Thin-Film Transistors

NASA Astrophysics Data System (ADS)

Han, Dong-Suk; Moon, Yeon-Keon; Lee, Sih; Kim, Kyung-Taek; Moon, Dae-Yong; Lee, Sang-Ho; Kim, Woong-Sun; Park, Jong-Wan

2012-09-01

In this study, we fabricated phosphorus-doped zinc oxide-based thin-film transistors (TFTs) using direct current (DC) magnetron sputtering at a relatively low temperature of 100°C. To improve the TFT device performance, including field-effect mobility and bias stress stability, phosphorus dopants were employed to suppress the generation of intrinsic defects in the ZnO-based semiconductor. The positive and negative bias stress stabilities were dramatically improved by introducing the phosphorus dopants, which could prevent turn-on voltage ( V ON) shift in the TFTs caused by charge trapping within the active channel layer. The study showed that phosphorus doping in ZnO was an effective method to control the electrical properties of the active channel layers and improve the bias stress stability of oxide-based TFTs.

Inter-subunit interactions across the upper voltage sensing-pore domain interface contribute to the concerted pore opening transition of Kv channels.

PubMed

Shem-Ad, Tzilhav; Irit, Orr; Yifrach, Ofer

2013-01-01

The tight electro-mechanical coupling between the voltage-sensing and pore domains of Kv channels lies at the heart of their fundamental roles in electrical signaling. Structural data have identified two voltage sensor pore inter-domain interaction surfaces, thus providing a framework to explain the molecular basis for the tight coupling of these domains. While the contribution of the intra-subunit lower domain interface to the electro-mechanical coupling that underlies channel opening is relatively well understood, the contribution of the inter-subunit upper interface to channel gating is not yet clear. Relying on energy perturbation and thermodynamic coupling analyses of tandem-dimeric Shaker Kv channels, we show that mutation of upper interface residues from both sides of the voltage sensor-pore domain interface stabilizes the closed channel state. These mutations, however, do not affect slow inactivation gating. We, moreover, find that upper interface residues form a network of state-dependent interactions that stabilize the open channel state. Finally, we note that the observed residue interaction network does not change during slow inactivation gating. The upper voltage sensing-pore interaction surface thus only undergoes conformational rearrangements during channel activation gating. We suggest that inter-subunit interactions across the upper domain interface mediate allosteric communication between channel subunits that contributes to the concerted nature of the late pore opening transition of Kv channels.

An RF Sensor for Gauging Screen-Channel Liquid Acquisition Devices for Cryogenic Propellants

NASA Technical Reports Server (NTRS)

Zimmerli, Gregory A.; Metzger, Scott; Asipauskas, Marius

2014-01-01

A key requirement of a low-gravity screen-channel liquid acquisition device (LAD) is the need to retain 100% liquid in the channel in response to propellant outflow and spacecraft maneuvers. The point at which a screen-channel LAD ingests vapor is known as breakdown, and can be measured several different ways such as: visual observation of bubbles in the LAD channel outflow; a sudden change in pressure drop between the propellant tank and LAD sump outlet; or, an indication by wet-dry sensors placed in the LAD channel or outflow stream. Here we describe a new type of sensor for gauging a screen-channel LAD, the Radio Frequency Mass Gauge (RFMG). The RFMG measures the natural electromagnetic modes of the screen-channel LAD, which is very similar to an RF waveguide, to determine the amount of propellant in the channel. By monitoring several of the RF modes, we show that the RFMG acts as a global sensor of the LAD channel propellant fill level, and enables detection of LAD breakdown even in the absence of outflow. This paper presents the theory behind the RFMG-LAD sensor, measurements and simulations of the RF modes of a LAD channel, and RFMG detection of LAD breakdown in a channel using a simulant fluid during inverted outflow and long-term stability tests.

Physical habitat dynamics in four side-channel chutes, lower Missouri River

USGS Publications Warehouse

Jacobson, Robert B.; Johnson, Harold E.; Laustrup, Mark S.; D'Urso, Gary J.; Reuter, Joanna M.

2004-01-01

Construction of the side-channel chutes has become a popular means to rehabilitate habitate of the Lower Missouri River. We studied various aspects of hydrology, hydraulics, and geomorphology of four side-channel chutes to document a range of existing conditions in the Lower Missouri River. The Cranberry Bend side-channel chute has existed for at least 40 years and is an example of a persistent, minimally engineered chute. The Lisbon Bottom side-channel chute is a young chute, created by extreme floods during 1993-1996, and allowed to evolve with minimum engineering of inlet and outlet structures. The Hamburg Bend and North Overton Bottom side-channel chutes were constructed in 1996 and 2000, respectively, as part of the Missouri River Bank Stabilization and navigation Fish and Wildlife Mitigation Project. These side-channel chutes provide increased areas of sandbars and shallow, slow water -- habitats thought to be substantially diminished in the modern Missouri River. Depths and velocities measured in side-channel chutes are also present in the main channel, but the chutes provide more areas of slow, shallow water and they increase the range of discharges over which shallow, slow water is present. The 3.6 km long Lisbon Bottom chute provides as much as 50% of the entire shallow water habitat that exists in the encompassing 15 km reach of the river. At Cranberry Bend and Lisbon Bottom, the side-channel chutes provided 10-40% of the availabile sandbar area in the reach, depending on discharge. Each of the side-channel chutes shows evidence of continuing erosion and deposition. The longevity and the Cranberry Bend chute attests to dynamic stability -- that is, a chute that maintains form and processes while shifting in position. The Hamburg chute similarly shows evidence of lateral movement and construction of flood plain to compensate for erosion. The Lisbon Bottom chute -- the most intensively studied chute -- appears to have achieved an equilibrium width and

Lightning energetics: Estimates of energy dissipation in channels, channel radii, and channel-heating risetimes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borovsky, J.E.

1998-05-01

In this report, several lightning-channel parameters are calculated with the aid of an electrodynamic model of lightning. The electrodynamic model describes dart leaders and return strokes as electromagnetic waves that are guided along conducting lightning channels. According to the model, electrostatic energy is delivered to the channel by a leader, where it is stored around the outside of the channel; subsequently, the return stroke dissipates this locally stored energy. In this report this lightning-energy-flow scenario is developed further. Then the energy dissipated per unit length in lightning channels is calculated, where this quantity is now related to the linear chargemore » density on the channel, not to the cloud-to-ground electrostatic potential difference. Energy conservation is then used to calculate the radii of lightning channels: their initial radii at the onset of return strokes and their final radii after the channels have pressure expanded. Finally, the risetimes for channel heating during return strokes are calculated by defining an energy-storage radius around the channel and by estimating the radial velocity of energy flow toward the channel during a return stroke. In three appendices, values for the linear charge densities on lightning channels are calculated, estimates of the total length of branch channels are obtained, and values for the cloud-to-ground electrostatic potential difference are estimated. {copyright} 1998 American Geophysical Union« less

Enhancement of proton transfer in ion channels by membrane phosphate headgroups.

PubMed

Wyatt, Debra L; de Godoy, Carlos Marcelo G; Cukierman, Samuel

2009-05-14

The transfer of protons (H+) in gramicidin (gA) channels is markedly distinct in monoglyceride and phospholipid membranes. In this study, the molecular groups that account for those differences were investigated using a new methodology. The rates of H+ transfer were measured in single gA channels reconstituted in membranes made of plain ceramides or sphingomyelins and compared to those in monoglyceride and phospholipid bilayers. Single-channel conductances to protons (gH) were significantly larger in sphingomyelin than in ceramide membranes. A novel and unsuspected finding was that H+ transfer was heavily attenuated or completely blocked in ceramide (but not in sphingomyelin) membranes in low-ionic-strength solutions. It is reasoned that H-bond dynamics at low ionic strengths between membrane ceramides and gA makes channels dysfunctional. The rate of H+ transfer in gA channels in ceramide membranes is significantly higher than that in monoglyceride bilayers. This suggests that solvation of the hydrophobic surface of gA channels by two acyl chains in ceramides stabilizes the gA channels and the water wire inside the pore, leading to an enhancement of H+ transfer in relation to that occurring in monoglyceride membranes. gH values in gA channels are similar in ceramide and monoglyceride bilayers and in sphingomyelin and phospholipid membranes. It is concluded that phospho headgroups in membranes have significant effects on the rate of H+ transfer at the membrane gA channel/solution interfaces, enhancing the entry and exit rates of protons in channels.

Stability condition for the drive bunch in a collinear wakefield accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baturin, S. S.; Zholents, A.

The beam breakup instability of the drive bunch in the structure-based collinear wakefield accelerator is considered and a stabilizing method is proposed. The method includes using the specially designed beam focusing channel, applying the energy chirp along the electron bunch, and keeping energy chirp constant during the drive bunch deceleration. A stability condition is derived that defines the limit on the accelerating field for the witness bunch.

Preliminary assessment of channel stability and bed-material transport in the Rogue River basin, southwestern Oregon

USGS Publications Warehouse

Jones, Krista L.; O'Connor, Jim E.; Keith, Mackenzie K.; Mangano, Joseph F.; Wallick, J. Rose

2012-01-01

This report summarizes a preliminary assessment of bed-material transport, vertical and lateral channel changes, and existing datasets for the Rogue River basin, which encompasses 13,390 square kilometers (km2) along the southwestern Oregon coast. This study, conducted to inform permitting decisions regarding instream gravel mining, revealed that: * The Rogue River in its lowermost 178.5 kilometers (km) alternates between confined and unconfined segments, and is predominately alluvial along its lowermost 44 km. The study area on the mainstem Rogue River can be divided into five reaches based on topography, hydrology, and tidal influence. The largely confined, active channel flows over bedrock and coarse bed material composed chiefly of boulders and cobbles in the Grants Pass (river kilometers [RKM] 178.5-152.8), Merlin (RKM 152.8-132.7), and Galice Reaches (RKM 132.7-43.9). Within these confined reaches, the channel contains few bars and has stable planforms except for locally wider segments such as the Brushy Chutes area in the Merlin Reach. Conversely, the active channel flows over predominately alluvial material and contains nearly continuous gravel bars in the Lobster Creek Reach (RKM 43.9-6.7). The channel in the Tidal Reach (RKM 6.7-0) is also alluvial, but tidally affected and unconfined until RKM 2. The Lobster Creek and Tidal Reaches contain some of the most extensive bar deposits within the Rogue River study area. * For the 56.6-km-long segment of the Applegate River included in this study, the river was divided into two reaches based on topography. In the Upper Applegate River Reach (RKM 56.6-41.6), the confined, active channel flows over alluvium and bedrock and has few bars. In the Lower Applegate River Reach (RKM 41.6-0), the active channel alternates between confined and unconfined segments, flows predominantly over alluvium, shifts laterally in unconfined sections, and contains more numerous and larger bars. * The 6.5-km segment of the lower

Top-gate organic depletion and inversion transistors with doped channel and injection contact

NASA Astrophysics Data System (ADS)

Liu, Xuhai; Kasemann, Daniel; Leo, Karl

2015-03-01

Organic field-effect transistors constitute a vibrant research field and open application perspectives in flexible electronics. For a commercial breakthrough, however, significant performance improvements are still needed, e.g., stable and high charge carrier mobility and on-off ratio, tunable threshold voltage, as well as integrability criteria such as n- and p-channel operation and top-gate architecture. Here, we show pentacene-based top-gate organic transistors operated in depletion and inversion regimes, realized by doping source and drain contacts as well as a thin layer of the transistor channel. By varying the doping concentration and the thickness of the doped channel, we control the position of the threshold voltage without degrading on-off ratio or mobility. Capacitance-voltage measurements show that an inversion channel can indeed be formed, e.g., an n-doped channel can be inverted to a p-type inversion channel with highly p-doped contacts. The Cytop polymer dielectric minimizes hysteresis, and the transistors can be biased for prolonged cycles without a shift of threshold voltage, indicating excellent operation stability.

Polycystin-1 is a Cardiomyocyte Mechanosensor That Governs L-type Ca2+ Channel Protein Stability

PubMed Central

Pedrozo, Zully; Criollo, Alfredo; Battiprolu, Pavan K.; Morales, Cyndi R.; Contreras, Ariel; Fernández, Carolina; Jiang, Nan; Luo, Xiang; Caplan, Michael J.; Somlo, Stefan; Rothermel, Beverly A.; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.

2015-01-01

Background L-type calcium channel (LTCC) activity is critical to afterload-induced hypertrophic growth of the heart. However, mechanisms governing mechanical stress-induced activation of LTCC activity are obscure. Polycystin-1 (PC-1) is a G-protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes. Methods and Results We subjected neonatal rat ventricular myocytes (NRVMs) to mechanical stretch by exposing them to hypo-osmotic (HS) medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on LTCC activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Over-expression of a C-terminal fragment of PC-1 was sufficient to trigger NRVM hypertrophy. Exposing NRVMs to HS medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 KO) and subjected them to mechanical stress in vivo (transverse aortic constriction, TAC). At baseline, PC-1 KO mice manifested decreased cardiac function relative to littermate controls, and α1C LTCC protein levels were significantly lower in PC-1 KO hearts. Whereas control mice manifested robust TAC-induced increases in cardiac mass, PC-1 KO mice showed no significant growth. Likewise, TAC-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals Conclusions PC-1 is a cardiomyocyte mechanosensor and is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein. PMID:25888683

A geomorphic explanation for a meander cutoff following channel relocation of a coarse-bedded river.

PubMed

Thompson, Douglas M

2003-03-01

The Veteran's Fishing section of the Blackledge River in central Connecticut was relocated in the late 1950s. The relocation resulted in an unstable channel despite extensive efforts to prevent erosion. Overbank erosion and meander cutoffs were investigated using detailed survey data, characterizations of sediment deposits, flow modeling, and a moment-stability analysis. Limited reworking of revetment boulders indicate that riprap bank material was immobile during a 1979 flood event responsible for the formation of the cutoff channel. A moment-stability analysis factor-of-safety value of 1.1 supports the conclusion that riprap was not directly eroded from the banks. Alluvial particles with d(95) values ranging up to 120 mm were deposited along a bar downstream from the cutoff channel at flows estimated to be below a 1.5-year recurrence interval flow. Development of the bar deposit resulted in locally elevated water surfaces at high flow. The resulting overbank flow across the meander neck to the adjacent downstream bend led to the creation of an upstream migrating knickpoint, the erosion of approximately 16,000-year-old sediments, and the subsequent meander cutoff. The results of the study indicate that traditional erosion-control measures cannot prevent extreme channel adjustments if the geomorphic processes that control sediment continuity also are not considered.

A 16-Channel CMOS Chopper-Stabilized Analog Front-End ECoG Acquisition Circuit for a Closed-Loop Epileptic Seizure Control System.

PubMed

Wu, Chung-Yu; Cheng, Cheng-Hsiang; Chen, Zhi-Xin

2018-06-01

In this paper, a 16-channel analog front-end (AFE) electrocorticography signal acquisition circuit for a closed-loop seizure control system is presented. It is composed of 16 input protection circuits, 16 auto-reset chopper-stabilized capacitive-coupled instrumentation amplifiers (AR-CSCCIA) with bandpass filters, 16 programmable transconductance gain amplifiers, a multiplexer, a transimpedance amplifier, and a 128-kS/s 10-bit delta-modulated successive-approximation-register analog-to-digital converter (SAR ADC). In closed-loop seizure control system applications, the stimulator shares the same electrode with the AFE amplifier for effective suppression of epileptic seizures. To prevent from overstress in MOS devices caused by high stimulation voltage, an input protection circuit with a high-voltage-tolerant switch is proposed for the AFE amplifier. Moreover, low input-referred noise is achieved by using the chopper modulation technique in the AR-CSCCIA. To reduce the undesired effects of chopper modulation, an improved offset reduction loop is proposed to reduce the output offset generated by input chopper mismatches. The digital ripple reduction loop is also used to reduce the chopper ripple. The fabricated AFE amplifier has 49.1-/59.4-/67.9-dB programmable gain and 2.02-μVrms input referred noise in a bandwidth of 0.59-117 Hz. The measured power consumption of the AFE amplifier is 3.26 μW per channel, and the noise efficiency factor is 3.36. The in vivo animal test has been successfully performed to verify the functions. It is shown that the proposed AFE acquisition circuit is suitable for implantable closed-loop seizure control systems.

Channel response to a new hydrological regime in southwestern Australia

NASA Astrophysics Data System (ADS)

Callow, J. N.; Smettem, K. R. J.

2007-02-01

The Kent River flows from semi-arid headwaters in the agricultural (wheatbelt) region of Western Australia to a wetter and forested lower-catchment. It is set in an atypical fluvial environment, with rainfall decreasing inland towards a low-relief upper catchment. Replacement of native deep-rooted perennial vegetation with shallow-rooted seasonal crops has altered the hydrology of the upper catchment. Clearing for agriculture has also increased recharge of regional groundwater systems causing groundwater to rise and mobilise salt stores. This has increased stream salinity which has degradation riparian vegetation and decreased flow resistance. Elevated groundwater has also affected streamflow, increasing flow duration and annual discharge. The altered hydrological regime has affected geomorphic stability, resulting in channel responses that include incision and removal of uncohesive material. Channel response is variable, showing a high dependence on channel morphotype, channel boundary material and severity of salinity (degree of vegetation degradation). Response in confined reaches bounded by sandy material has been characterised by minor lateral bank erosion. In the fine-grained, wider, low-gradient reaches, mid-channel islands have been stripped of sandy sediment where vegetation has degraded. Following an initial period of high erosion rates in these reaches, the channel is now slowly adjusting to a new set of boundary conditions. The variable response has significant implications for management of salt affected rivers in southwestern Australia.

47 CFR 90.213 - Frequency stability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... range (MHz) Fixed and base stations Mobile stations Over 2 watts output power 2 watts or less output...-930 1.5 935-940 0.1 1.5 1.5 1427-1435 9 300 300 300 Above 2450 10 1 Fixed and base stations with over... stability of 5 ppm. 5 In the 150-174 MHz band, fixed and base stations with a 12.5 kHz channel bandwidth...

Calcium channel-dependent molecular maturation of photoreceptor synapses.

PubMed

Zabouri, Nawal; Haverkamp, Silke

2013-01-01

Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V)1.4(α(1F)) knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V)1.4(α(1F)) knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V)1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V)1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V)1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

A Direct Demonstration of Closed-State Inactivation of K+ Channels at Low pH

PubMed Central

Claydon, Thomas W.; Vaid, Moni; Rezazadeh, Saman; Kwan, Daniel C.H.; Kehl, Steven J.; Fedida, David

2007-01-01

Lowering external pH reduces peak current and enhances current decay in Kv and Shaker-IR channels. Using voltage-clamp fluorimetry we directly determined the fate of Shaker-IR channels at low pH by measuring fluorescence emission from tetramethylrhodamine-5-maleimide attached to substituted cysteine residues in the voltage sensor domain (M356C to R362C) or S5-P linker (S424C). One aspect of the distal S3-S4 linker α-helix (A359C and R362C) reported a pH-induced acceleration of the slow phase of fluorescence quenching that represents P/C-type inactivation, but neither site reported a change in the total charge movement at low pH. Shaker S424C fluorescence demonstrated slow unquenching that also reflects channel inactivation and this too was accelerated at low pH. In addition, however, acidic pH caused a reversible loss of the fluorescence signal (pKa = 5.1) that paralleled the reduction of peak current amplitude (pKa = 5.2). Protons decreased single channel open probability, suggesting that the loss of fluorescence at low pH reflects a decreased channel availability that is responsible for the reduced macroscopic conductance. Inhibition of inactivation in Shaker S424C (by raising external K+ or the mutation T449V) prevented fluorescence loss at low pH, and the fluorescence report from closed Shaker ILT S424C channels implied that protons stabilized a W434F-like inactivated state. Furthermore, acidic pH changed the fluorescence amplitude (pKa = 5.9) in channels held continuously at −80 mV. This suggests that low pH stabilizes closed-inactivated states. Thus, fluorescence experiments suggest the major mechanism of pH-induced peak current reduction is inactivation of channels from closed states from which they can activate, but not open; this occurs in addition to acceleration of P/C-type inactivation from the open state. PMID:17470663

Channel Gating Dependence on Pore Lining Helix Glycine Residues in Skeletal Muscle Ryanodine Receptor.

PubMed

Mei, Yingwu; Xu, Le; Mowrey, David D; Mendez Giraldez, Raul; Wang, Ying; Pasek, Daniel A; Dokholyan, Nikolay V; Meissner, Gerhard

2015-07-10

Type 1 ryanodine receptors (RyR1s) release Ca(2+) from the sarcoplasmic reticulum to initiate skeletal muscle contraction. The role of RyR1-G4934 and -G4941 in the pore-lining helix in channel gating and ion permeation was probed by replacing them with amino acid residues of increasing side chain volume. RyR1-G4934A, -G4941A, and -G4941V mutant channels exhibited a caffeine-induced Ca(2+) release response in HEK293 cells and bound the RyR-specific ligand [(3)H]ryanodine. In single channel recordings, significant differences in the number of channel events and mean open and close times were observed between WT and RyR1-G4934A and -G4941A. RyR1-G4934A had reduced K(+) conductance and ion selectivity compared with WT. Mutations further increasing the side chain volume at these positions (G4934V and G4941I) resulted in reduced caffeine-induced Ca(2+) release in HEK293 cells, low [(3)H]ryanodine binding levels, and channels that were not regulated by Ca(2+) and did not conduct Ca(2+) in single channel measurements. Computational predictions of the thermodynamic impact of mutations on protein stability indicated that although the G4934A mutation was tolerated, the G4934V mutation decreased protein stability by introducing clashes with neighboring amino acid residues. In similar fashion, the G4941A mutation did not introduce clashes, whereas the G4941I mutation resulted in intersubunit clashes among the mutated isoleucines. Co-expression of RyR1-WT with RyR1-G4934V or -G4941I partially restored the WT phenotype, which suggested lessening of amino acid clashes in heterotetrameric channel complexes. The results indicate that both glycines are important for RyR1 channel function by providing flexibility and minimizing amino acid clashes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Highly Sensitive and Patchable Pressure Sensors Mimicking Ion-Channel-Engaged Sensory Organs.

PubMed

Chun, Kyoung-Yong; Son, Young Jun; Han, Chang-Soo

2016-04-26

Biological ion channels have led to much inspiration because of their unique and exquisite operational functions in living cells. Specifically, their extreme and dynamic sensing abilities can be realized by the combination of receptors and nanopores coupled together to construct an ion channel system. In the current study, we demonstrated that artificial ion channel pressure sensors inspired by nature for detecting pressure are highly sensitive and patchable. Our ion channel pressure sensors basically consisted of receptors and nanopore membranes, enabling dynamic current responses to external forces for multiple applications. The ion channel pressure sensors had a sensitivity of ∼5.6 kPa(-1) and a response time of ∼12 ms at a frequency of 1 Hz. The power consumption was recorded as less than a few μW. Moreover, a reliability test showed stability over 10 000 loading-unloading cycles. Additionally, linear regression was performed in terms of temperature, which showed no significant variations, and there were no significant current variations with humidity. The patchable ion channel pressure sensors were then used to detect blood pressure/pulse in humans, and different signals were clearly observed for each person. Additionally, modified ion channel pressure sensors detected complex motions including pressing and folding in a high-pressure range (10-20 kPa).

Stability Analysis of Multi-Sensor Kalman Filtering over Lossy Networks

PubMed Central

Gao, Shouwan; Chen, Pengpeng; Huang, Dan; Niu, Qiang

2016-01-01

This paper studies the remote Kalman filtering problem for a distributed system setting with multiple sensors that are located at different physical locations. Each sensor encapsulates its own measurement data into one single packet and transmits the packet to the remote filter via a lossy distinct channel. For each communication channel, a time-homogeneous Markov chain is used to model the normal operating condition of packet delivery and losses. Based on the Markov model, a necessary and sufficient condition is obtained, which can guarantee the stability of the mean estimation error covariance. Especially, the stability condition is explicitly expressed as a simple inequality whose parameters are the spectral radius of the system state matrix and transition probabilities of the Markov chains. In contrast to the existing related results, our method imposes less restrictive conditions on systems. Finally, the results are illustrated by simulation examples. PMID:27104541

Stability of parallel electroosmotic flow subject to an axial modulated electric field

NASA Astrophysics Data System (ADS)

Suresh, Vinod; Homsy, George

2001-11-01

The stability of parallel electroosmotic flow in a micro-channel subjected to an AC electric field is studied. A spatially uniform time harmonic electric field is applied along the length of a two-dimensional micro-channel containing a dilute electrolytic solution, resulting in a time periodic parallel flow. The top and bottom walls of the channel are maintained at constant potential. The base state ion concentrations and double layer potential are determined using the Poisson-Boltzmann equation in the Debye-Hückel approximation. Experiments by other workers (Santiago et. al., unpublished) have shown that such a system can exhibit instabilities that take the form of mixing motion occurring in the bulk flow outside the double layer. It is shown that such instabilities can potentially result from the coupling of disturbances in the ion concentrations or electric potential to the base state velocity or ion concentrations, respectively. The stability boundary of the system is determined using Floquet theory and its dependence on the modulation frequency and amplitude of the axial electric field is studied.

Dean vortices with wall flux in a curved channel membrane system. 2: The velocity field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, K.Y.; Brewster, M.E.; Belfort, G.

1996-02-01

The velocity and pressure fields and the effect of wall flux on these fields in a spiral channel are presented. As fluid flows inward through a spiral channel with constant gap and permeable walls, the streamwise flux decreases while the curvature increases. Thus, by balancing the stabilizing effect of wall suction with the destabilizing effect of increasing curvature, established vortices can be maintained along the spiral channel. This approach is used to prescribe spiral geometries with different wall fluxes. Using a weakly nonlinear stability analysis, the influence of wall flux on the characteristics of Dean vortices is obtained. The criticalmore » Dean number is reduced when suction is through the inner wall only, is slightly reduced when suction is equal through both walls, and is increased when suction is through the outer wall only. The magnitude of change is proportional to a ratio of small numbers that measures the importance of the effect of curvature. In membrane filtration applications the wall flux is typically 2 to 5 orders of magnitude less than the streamwise flow. If the radius of curvature of the channel is of the order of 100 times the channel gap, the effect on the critical Dean number is within 2% of the no-wall flux case. If the radius of curvature is sufficiently large, however, it is possible to observe effects on the critical Dean number that approach O(1) in magnitude for certain parameter ranges.« less

Vertical Stability of Ephemeral Step-Pool Streams Largely Controlled By Tree Roots, Central Kentucky, USA

NASA Astrophysics Data System (ADS)

Macmannis, K. R.; Hawley, R. J.

2013-12-01

The mechanisms controlling stability on small streams in steep settings are not well documented but have many implications related to stream integrity and water quality. For example, channel instability on first and second order streams is a potential source of sediment in regulated areas with Total Maximum Daily Loads (TMDLs) on water bodies that are impaired for sedimentation, such as the Chesapeake Bay. Management strategies that preserve stream integrity and protect channel stability are critical to communities that may otherwise require large capital investments to meet TMDLs and other water quality criteria. To contribute to an improved understanding of ephemeral step-pool systems, we collected detailed hydrogeomorphic data on 4 steep (0.06 - 0.12 meter/meter) headwater streams draining to lower relief alluvial valleys in Spencer County, Kentucky, USA. The step-pool streams (mean step height of 0.47 meter, mean step spacing of 4 meters) drained small undeveloped catchments dominated by early successional forest. Data collection for each of the 4 streams included 2 to 3 cross section surveys, bed material particle counts at cross section locations, and profile surveys ranging from approximately 125 to 225 meters in length. All survey data was systematically processed to understand geometric parameters such as cross sectional area, depth, and top width; bed material gradations; and detailed profile measurements such as slope, pool and riffle lengths, pool spacing, pool depth, step height, and step length. We documented the location, frequency, and type of step-forming materials (i.e., large woody debris (LWD), rock, and tree roots), compiling a database of approximately 130 total steps. Lastly, we recorded a detailed tree assessment of all trees located within 2 meters of the top of bank, detailing the species of tree, trunk diameter, and approximate distance from the top of bank. Analysis of geometric parameters illustrated correlations between channel

mTor Regulates Lysosomal ATP-sensitive Two-Pore Na+ Channel to Adapt to Metabolic State

PubMed Central

Navarro, Betsy; Seo, Young-jun; Aranda, Kimberly; Shi, Lucy; Battaglia-Hsu, Shyuefang; Nissim, Itzhak; Clapham, David E.; Ren, Dejian

2014-01-01

SUMMARY Survival in the wild requires organismal adaptations to the availability of nutrients. Endosomes and lysosomes are key intracellular organelles that couple nutrition and metabolic status to cellular responses, but how they detect cytosolic ATP levels is not well understood. Here we identify an endolysosomal ATP-sensitive Na+ channel (lysoNaATP). The channel is a complex formed by Two-Pore Channels (TPC1 and TPC2), ion channels previously thought to be gated by nicotinic acid adenine dinucleotide phosphate (NAADP), and the mammalian target of rapamycin (mTOR). The channel complex detects nutrient status, becomes constitutively open upon nutrient removal and mTOR translocation off the lysosomal membrane, and controls the lysosome's membrane potential, pH stability, and the amino acid homeostasis. Mutant mice lacking lysoNaATP have much reduced exercise endurance after fasting. Thus, TPCs are a new ion channel family that couple the cell's metabolic state to endolysosomal function and are crucial for physical endurance during food restriction. PMID:23394946

Development and flight evaluation of an augmented stability active controls concept with a small horizontal tail

NASA Technical Reports Server (NTRS)

Rising, J. J.; Kairys, A. A.; Maass, C. A.; Siegart, C. D.; Rakness, W. L.; Mijares, R. D.; King, R. W.; Peterson, R. S.; Hurley, S. R.; Wickson, D.

1982-01-01

A limited authority pitch active control system (PACS) was developed for a wide body jet transport (L-1011) with a flying horizontal stabilizer. Two dual channel digital computers and the associated software provide command signals to a dual channel series servo which controls the stabilizer power actuators. Input sensor signals to the computer are pitch rate, column-trim position, and dynamic pressure. Control laws are given for the PACS and the system architecture is defined. The piloted flight simulation and vehicle system simulation tests performed to verify control laws and system operation prior to installation on the aircraft are discussed. Modifications to the basic aircraft are described. Flying qualities of the aircraft with the PACS on and off were evaluated. Handling qualities for cruise and high speed flight conditions with the c.g. at 39% mac ( + 1% stability margin) and PACS operating were judged to be as good as the handling qualities with the c.g. at 25% (+15% stability margin) and PACS off.

The operational stability of a centrifugal compressor and its dependence on the characteristics of the subcomponents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunziker, R.; Gyarmathy, G.

1994-04-01

A centrifugal compressor was tested with three different diffusers with circular-arc vanes. The vane inlet angle was varied from 15 to 30 deg. Detailed static wall pressure measurements show that the pressure field in the diffuser inlet is very sensitive to flow rate. The stability limit regularly occurred at the flow rate giving the maximum pressure rise for the overall stage. Mild surge arises as a dynamic instability of the compression system. The analysis of the pressure rise characteristic of each individual subcomponent (impeller, diffuser inlet, diffuser channel,...) reveals their contribution to the overall pressure rise. The diffuser channels playmore » an inherently destabilizing role while the impeller and the diffuser inlet are typically stabilizing. The stability limit was mainly determined by a change in the characteristic of the diffuser inlet. Further, the stability limit was found to be independent of the development of inducer-tip recirculation.« less

A survey of the role of thermodynamic stability in viscous flow

NASA Technical Reports Server (NTRS)

Horne, W. C.; Smith, C. A.; Karamcheti, K.

1991-01-01

The stability of near-equilibrium states has been studied as a branch of the general field of nonequilibrium thermodynamics. By treating steady viscous flow as an open thermodynamic system, nonequilibrium principles such as the condition of minimum entropy-production rate for steady, near-equilibrium processes can be used to generate flow distributions from variational analyses. Examples considered in this paper are steady heat conduction, channel flow, and unconstrained three-dimensional flow. The entropy-production-rate condition has also been used for hydrodynamic stability criteria, and calculations of the stability of a laminar wall jet support this interpretation.

n-Channel semiconductor materials design for organic complementary circuits.

PubMed

Usta, Hakan; Facchetti, Antonio; Marks, Tobin J

2011-07-19

emphasis on structure-property relationships. We then examine the synthesis and properties of carbonyl-functionalized oligomers, which constitute second-generation n-channel oligothiophenes, in both vacuum- and solution-processed FETs. These materials have high carrier mobilities and good air stability. In parallel, exceptionally electron-deficient cyano-functionalized arylenediimide derivatives are discussed as early examples of thermodynamically air-stable, high-performance n-channel semiconductors; they exhibit record electron mobilities of up to 0.64 cm(2)/V·s. Furthermore, we provide an overview of highly soluble ladder-type macromolecular semiconductors as OFET components, which combine ambient stability with solution processibility. A high electron mobility of 0.16 cm(2)/V·s is obtained under ambient conditions for solution-processed films. Finally, examples of polymeric n-channel semiconductors with electron mobilities as high as 0.85 cm(2)/V·s are discussed; these constitute an important advance toward fully printed polymeric electronic circuitry. Density functional theory (DFT) computations reveal important trends in molecular physicochemical and semiconducting properties, which, when combined with experimental data, shed new light on molecular charge transport characteristics. Our data provide the basis for a fundamental understanding of charge transport in high-performance n-channel organic semiconductors. Moreover, our results provide a road map for developing functional, complementary organic circuitry, which requires combining p- and n-channel transistors.

Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain

PubMed Central

Caires, Rebeca; Luis, Enoch; Taberner, Francisco J.; Fernandez-Ballester, Gregorio; Ferrer-Montiel, Antonio; Balazs, Endre A.; Gomis, Ana; Belmonte, Carlos; de la Peña, Elvira

2015-01-01

Hyaluronan (HA) is present in the extracellular matrix of all body tissues, including synovial fluid in joints, in which it behaves as a filter that buffers transmission of mechanical forces to nociceptor nerve endings thereby reducing pain. Using recombinant systems, mouse-cultured dorsal root ganglia (DRG) neurons and in vivo experiments, we found that HA also modulates polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channels. HA diminishes heat, pH and capsaicin (CAP) responses, thus reducing the opening probability of the channel by stabilizing its closed state. Accordingly, in DRG neurons, HA decreases TRPV1-mediated impulse firing and channel sensitization by bradykinin. Moreover, subcutaneous HA injection in mice reduces heat and capsaicin nocifensive responses, whereas the intra-articular injection of HA in rats decreases capsaicin joint nociceptor fibres discharge. Collectively, these results indicate that extracellular HA reduces the excitability of the ubiquitous TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor endings underlying pain. PMID:26311398

Preliminary assessment of channel stability and bed-material transport in the Tillamook Bay tributaries and Nehalem River basin, northwestern Oregon

USGS Publications Warehouse

Jones, Krista L.; Keith, Mackenzie K.; O'Connor, Jim E.; Mangano, Joseph F.; Wallick, J. Rose

2012-01-01

subject to incision and aggradation as well as lateral shifts in thalweg position and bank deposition and erosion. * In fluvial reaches, unit bar area declined a net 5.3-83.6 percent from 1939 to 2009. The documented reduction in bar area may be attributable to several factors, including vegetation establishment and stabilization of formerly active bar surfaces, lateral channel changes and resulting alterations in sediment deposition and erosion patterns, and streamflow and/or tide differences between photographs. Other factors that may be associated with the observed reduction in bar area but not assessed in this reconnaissance level study include changes in the sediment and hydrology regimes of these rivers over the analysis period. * In tidal reaches, unit bar area increased on the Tillamook and Nehalem Rivers (98.0 and 14.7 percent, respectively), but declined a net 24.2 to 83.1 percent in the other four tidal reaches. Net increases in bar area in the Tidal Tillamook and Nehalem Reaches were possibly attributable to tidal differences between the photographs as well as sediment deposition behind log booms and pile structures on the Tillamook River between 1939 and 1967. * The armoring ratio (ratio of the median grain sizes of a bar's surface and subsurface layers) was 1.6 at Lower Waldron Bar on the Miami River, tentatively indicating a relative balance between transport capacity and sediment supply at this location. Armoring ratios, however, ranged from 2.4 to 5.5 at sites on the Trask, Wilson, Kilchis, and Nehalem Rivers; these coarse armor layers probably reflect limited bed-material supply at these sites. * On the basis of mapping results, measured armoring ratios, and channel cross section surveys, preliminary conclusions are that the fluvial reaches on the Tillamook, Trask, Kilchis, and Nehalem Rivers are currently sediment supply-limited in terms of bed material - that is, the transport capacity of the channel generally exceeds the supply of bed material. The

Tyrosine Residues from the S4-S5 Linker of Kv11.1 Channels Are Critical for Slow Deactivation.

PubMed

Ng, Chai-Ann; Gravel, Andrée E; Perry, Matthew D; Arnold, Alexandre A; Marcotte, Isabelle; Vandenberg, Jamie I

2016-08-12

Slow deactivation of Kv11.1 channels is critical for its function in the heart. The S4-S5 linker, which joins the voltage sensor and pore domains, plays a critical role in this slow deactivation gating. Here, we use NMR spectroscopy to identify the membrane-bound surface of the S4S5 linker, and we show that two highly conserved tyrosine residues within the KCNH subfamily of channels are membrane-associated. Site-directed mutagenesis and electrophysiological analysis indicates that Tyr-542 interacts with both the pore domain and voltage sensor residues to stabilize activated conformations of the channel, whereas Tyr-545 contributes to the slow kinetics of deactivation by primarily stabilizing the transition state between the activated and closed states. Thus, the two tyrosine residues in the Kv11.1 S4S5 linker play critical but distinct roles in the slow deactivation phenotype, which is a hallmark of Kv11.1 channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A MULTIPLE GRID APPROACH FOR OPEN CHANNEL FLOWS WITH STRONG SHOCKS. (R825200)

EPA Science Inventory

Abstract

Explicit finite difference schemes are being widely used for modeling open channel flows accompanied with shocks. A characteristic feature of explicit schemes is the small time step, which is limited by the CFL stability condition. To overcome this limitation,...

Drag reduction in a turbulent channel flow using a passivity-based approach

NASA Astrophysics Data System (ADS)

Heins, Peter; Jones, Bryn; Sharma, Atul

2013-11-01

A new active feedback control strategy for attenuating perturbation energy in a turbulent channel flow is presented. Using a passivity-based approach, a controller synthesis procedure has been devised which is capable of making the linear dynamics of a channel flow as close to passive as is possible given the limitations on sensing and actuation. A controller that is capable of making the linearized flow passive is guaranteed to globally stabilize the true flow. The resulting controller is capable of greatly restricting the amount of turbulent energy that the nonlinearity can feed back into the flow. DNS testing of a controller using wall-sensing of streamwise and spanwise shear stress and actuation via wall transpiration acting upon channel flows with Reτ = 100 - 250 showed significant reductions in skin-friction drag.

The stretch-dependent potassium channel TREK-1 and its function in murine myometrium

PubMed Central

Monaghan, Kevin; Baker, Salah A; Dwyer, Laura; Hatton, William C; Sik Park, Kyung; Sanders, Kenton M; Koh, Sang Don

2011-01-01

Smooth muscle of the uterus stays remarkably quiescent during normal pregnancy to allow sufficient time for development of the fetus. At present the mechanisms leading to uterine quiescence during pregnancy and how the suppression of activity is relieved at term are poorly understood. Myometrial excitability is governed by ion channels, and a major hypothesis regarding the regulation of contractility during pregnancy has been that expression of certain channels is regulated by hormonal influences. We have explored the expression and function of stretch-dependent K+ (SDK) channels, which are likely to be due to TREK channels, in murine myometrial tissues and myocytes using PCR, Western blots, patch clamp, intracellular microelectrode and isometric force measurements. TREK-1 is more highly expressed than TREK-2 in myometrium, and there was no detectable expression of TRAAK. Expression of TREK-1 transcripts and protein was regulated during pregnancy and delivery. SDK channels were activated in response to negative pressure applied to patches. SDK channels were insensitive to a broad-spectrum of K+ channel blockers, including tetraethylammonium and 4-aminopyridine, and insensitive to intracellular Ca2+. SDK channels were activated by stretch and arachidonic acid and inhibited by reagents that block TREK-1 channels, l-methionine and/or methioninol. Our data suggest that uterine excitability and contractility during pregnancy is regulated by the expression of SDK/TREK-1 channels. Up-regulation of these channels stabilizes membrane potential and controls contraction during pregnancy and down-regulation of these channels induces the onset of delivery. PMID:21224218

Structural and Biochemical Consequences of Disease-Causing Mutations in the Ankyrin Repeat Domain of the Human TRPV4 Channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inada, Hitoshi; Procko, Erik; Sotomayor, Marcos

2012-10-23

The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases, including neuropathies and skeletal dysplasias, probably because of the increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD at its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Fingermore » 3 loop) is flexible and may act as a switch to regulate channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics simulations suggest that ATP increases stability in TRPV-ARDs that can bind ATP. Biochemical analyses of a large panel of TRPV4-ARD mutations associated with human inherited diseases showed that some impaired thermal stability while others weakened ATP binding ability, suggesting molecular mechanisms for the diseases.« less

Structure parameters in rotating Couette-Poiseuille channel flow

NASA Technical Reports Server (NTRS)

Knightly, George H.; Sather, D.

1986-01-01

It is well-known that a number of steady state problems in fluid mechanics involving systems of nonlinear partial differential equations can be reduced to the problem of solving a single operator equation of the form: v + lambda Av + lambda B(v) = 0, v is the summation of H, lambda is the summation of one-dimensional Euclid space, where H is an appropriate (real or complex) Hilbert space. Here lambda is a typical load parameter, e.g., the Reynolds number, A is a linear operator, and B is a quadratic operator generated by a bilinear form. In this setting many bifurcation and stability results for problems were obtained. A rotating Couette-Poiseuille channel flow was studied, and it showed that, in general, the superposition of a Poiseuille flow on a rotating Couette channel flow is destabilizing.

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, J.; Chen, M.; Wu, W. Y.

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors, while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize simultaneous coupling of the electron beam and the laser pulse into a second stage. Furthermore, a curved channel with transition segment is used to guide a fresh laser pulse into a subsequent straight channel, while allowing the electrons to propagate in a straight channel. This scheme then benefitsmore » from a shorter coupling distance and continuous guiding of the electrons in plasma, while suppressing transverse beam dispersion. Within moderate laser parameters, particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration, while maintaining high capture efficiency, stability, and beam quality.« less

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channel

DOE PAGES

Luo, J.; Chen, M.; Wu, W. Y.; ...

2018-04-10

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors, while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize simultaneous coupling of the electron beam and the laser pulse into a second stage. Furthermore, a curved channel with transition segment is used to guide a fresh laser pulse into a subsequent straight channel, while allowing the electrons to propagate in a straight channel. This scheme then benefitsmore » from a shorter coupling distance and continuous guiding of the electrons in plasma, while suppressing transverse beam dispersion. Within moderate laser parameters, particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration, while maintaining high capture efficiency, stability, and beam quality.« less

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

PubMed Central

Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

2009-01-01

Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

The role of glycerol and phosphatidylcholine in solubilizing and enhancing insulin stability in reverse hexagonal mesophases.

PubMed

Amar-Yuli, Idit; Azulay, Doron; Mishraki, Tehila; Aserin, Abraham; Garti, Nissim

2011-12-15

The potential of reverse hexagonal mesophases based on monoolein (GMO) and glycerol (as cosolvent) to facilitate the solubilization of proteins, such as insulin was explored. H(II) mesophases composed of GMO/decane/water were compared to GMO/decane/glycerol/water and GMO/phosphatidylcholine (PC)/decane/glycerol/water systems. The stability of insulin was tested, applying external physical modifications such as low pH and heat treatment (up to 70°C), in which insulin is known to form ordered amyloid-like aggregates (that are associated with several neurodegenerative diseases) with a characteristic cross β-pleated sheet structure. The impact of insulin confinement within these carriers on its stability, unfolding, and aggregation pathways was studied by combining SAXS, FTIR, and AFM techniques. These techniques provided a better insight into the molecular level of the "component interplay" in solubilizing and stabilizing insulin and its conformational modifications that dictate its final aggregate morphology. PC enlarged the water channels while glycerol shrank them, yet both facilitated insulin solubilization within the channels. The presence of glycerol within the mesophase water channels led to the formation of stronger hydrogen bonds with the hosting medium that enhanced the thermal stability of the protein and remarkably affected the unfolding process even after heat treatment (at 70°C for 60 min). Copyright © 2011 Elsevier Inc. All rights reserved.

A MULTIPLE GRID ALGORITHM FOR ONE-DIMENSIONAL TRANSIENT OPEN CHANNEL FLOWS. (R825200)

EPA Science Inventory

Numerical modeling of open channel flows with shocks using explicit finite difference schemes is constrained by the choice of time step, which is limited by the CFL stability criteria. To overcome this limitation, in this work we introduce the application of a multiple grid al...

Scorpion Toxins Specific for Potassium (K+) Channels: A Historical Overview of Peptide Bioengineering

PubMed Central

Bergeron, Zachary L.; Bingham, Jon-Paul

2012-01-01

Scorpion toxins have been central to the investigation and understanding of the physiological role of potassium (K+) channels and their expansive function in membrane biophysics. As highly specific probes, toxins have revealed a great deal about channel structure and the correlation between mutations, altered regulation and a number of human pathologies. Radio- and fluorescently-labeled toxin isoforms have contributed to localization studies of channel subtypes in expressing cells, and have been further used in competitive displacement assays for the identification of additional novel ligands for use in research and medicine. Chimeric toxins have been designed from multiple peptide scaffolds to probe channel isoform specificity, while advanced epitope chimerization has aided in the development of novel molecular therapeutics. Peptide backbone cyclization has been utilized to enhance therapeutic efficiency by augmenting serum stability and toxin half-life in vivo as a number of K+-channel isoforms have been identified with essential roles in disease states ranging from HIV, T-cell mediated autoimmune disease and hypertension to various cardiac arrhythmias and Malaria. Bioengineered scorpion toxins have been monumental to the evolution of channel science, and are now serving as templates for the development of invaluable experimental molecular therapeutics. PMID:23202307

Evolutionary Algorithm Based Feature Optimization for Multi-Channel EEG Classification.

PubMed

Wang, Yubo; Veluvolu, Kalyana C

2017-01-01

The most BCI systems that rely on EEG signals employ Fourier based methods for time-frequency decomposition for feature extraction. The band-limited multiple Fourier linear combiner is well-suited for such band-limited signals due to its real-time applicability. Despite the improved performance of these techniques in two channel settings, its application in multiple-channel EEG is not straightforward and challenging. As more channels are available, a spatial filter will be required to eliminate the noise and preserve the required useful information. Moreover, multiple-channel EEG also adds the high dimensionality to the frequency feature space. Feature selection will be required to stabilize the performance of the classifier. In this paper, we develop a new method based on Evolutionary Algorithm (EA) to solve these two problems simultaneously. The real-valued EA encodes both the spatial filter estimates and the feature selection into its solution and optimizes it with respect to the classification error. Three Fourier based designs are tested in this paper. Our results show that the combination of Fourier based method with covariance matrix adaptation evolution strategy (CMA-ES) has the best overall performance.

A three-dimensional dynamical model for channeled lava flow with nonlinear rheology

NASA Astrophysics Data System (ADS)

Filippucci, Marilena; Tallarico, Andrea; Dragoni, Michele

2010-05-01

Recent laboratory studies on the rheology of lava samples from different volcanic areas have highlighted that the apparent viscosity depends on a power of the strain rate. Several authors agree in attributing this dependence to the crystal content of the sample and to temperature. Starting from these results, in this paper we studied the effect of a power law rheology on a gravity-driven lava flow. The equation of motion is nonlinear in the diffusion term, and an analytical solution does not seem to be possible. The finite-volume method has been applied to solve numerically the equation governing the fully developed laminar flow of a power law non-Newtonian fluid in an inclined rectangular channel. The convergence, the stability, and the order of approximation were tested for the Newtonian rheology case, comparing the numerical solution with the available analytical solution. Results indicate that the assumption on the rheology, whether linear or nonlinear, strongly affects the velocity and/or the thickness of the lava channel both for channels with fixed geometry and for channels with constant flow rate. Results on channels with fixed geometry are confirmed by some simulations for real lava channels. Finally, the study of the Reynolds number indicates that gravity-driven lava channel flows are always in laminar regime, except for strongly nonlinear pseudoplastic fluids with low fluid consistency and at high slopes.

An external sodium ion binding site controls allosteric gating in TRPV1 channels

PubMed Central

Jara-Oseguera, Andres; Bae, Chanhyung; Swartz, Kenton J

2016-01-01

TRPV1 channels in sensory neurons are integrators of painful stimuli and heat, yet how they integrate diverse stimuli and sense temperature remains elusive. Here, we show that external sodium ions stabilize the TRPV1 channel in a closed state, such that removing the external ion leads to channel activation. In studying the underlying mechanism, we find that the temperature sensors in TRPV1 activate in two steps to favor opening, and that the binding of sodium to an extracellular site exerts allosteric control over temperature-sensor activation and opening of the pore. The binding of a tarantula toxin to the external pore also exerts control over temperature-sensor activation, whereas binding of vanilloids influences temperature-sensitivity by largely affecting the open/closed equilibrium. Our results reveal a fundamental role of the external pore in the allosteric control of TRPV1 channel gating and provide essential constraints for understanding how these channels can be tuned by diverse stimuli. DOI: http://dx.doi.org/10.7554/eLife.13356.001 PMID:26882503

Interactions of the H5 pore region and hydroxylamine with N-type inactivation in the Shaker K+ channel.

PubMed Central

Yool, A J; Schwarz, T L

1995-01-01

Mutations at sites in the H5 region of the Shaker B K+ channel were used to analyze the influence of the pore on N-type inactivation. Single-channel and two-electrode voltage clamp analyses showed that mutations at residues T441 and T442, which are thought to lie at the internal mouth of the pore, produced opposite effects on inactivation: the inactivated state is stabilized by T441S and destabilized by T442S. In addition, an ammonium derivative, hydroxylamine (OH-(NH3)+), appears to bind in the pore region of T441S and further decreases the rate of recovery from N-type inactivation. This effect relies on the presence of the amino-terminal. The effect of hydroxylamine on the T441S mutation of this K+ channel shows several properties analogous to those of local anesthetics on the Na+ channel. These results can be interpreted to suggest that part of the H5 region contributes to the receptor for the inactivation particle and that a hydroxylamine ion trapped near that site can stabilize their interaction. Images FIGURE 8 PMID:7696498

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)*

PubMed Central

Schmidt, Axel; Löhrer, Daniel; Alsop, Richard J.; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Wirtz, Monika; Rheinstädter, Maikel C.; Gründer, Stefan; Wiemuth, Dominik

2016-01-01

The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na+ channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel. The physiological function of BASIC, however, is unknown. Deg/ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic α-helical structure within its N-terminal domain. This α-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction. PMID:27679529

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC).

PubMed

Schmidt, Axel; Löhrer, Daniel; Alsop, Richard J; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Wirtz, Monika; Rheinstädter, Maikel C; Gründer, Stefan; Wiemuth, Dominik

2016-11-18

The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na + channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel. The physiological function of BASIC, however, is unknown. Deg/ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic α-helical structure within its N-terminal domain. This α-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Multi-channel and porous SiO@N-doped C rods as anodes for high-performance lithium-ion batteries

NASA Astrophysics Data System (ADS)

Huang, Xiao; Li, Mingqi

2018-05-01

To improve the cycling stability and rate capability of SiO electrodes, multi-channel and porous SiO@N-doped C (mp-SiO@N-doped C) rods are fabricated by the combination of electrospinning and heat treatment with the assistance of poly(methyl methacrylate) (PMMA). During annealing, in-situ PMMA degradation and gasification lead to the formation of multi-channel structure and more pores. As anodes for lithium ion batteries, the mp-SiO@N-doped C rods exhibit excellent cycling stability. At a current density of 400 mA g-1, a discharge capacity of 806 mAh g-1 can be kept after 250 cycles, the retention of which is over than 100% versus the initial reversible capacity. Compared with the SiO@N-doped C rods synthesized without the help of PMMA, the mp-SiO@N-doped C rods exhibit more excellent rate capability. The excellent electrochemical performance is attributed to the special structure of the mp-SiO@N-doped C rods. In addition to the conductivity improved by carbon fibers, the multi-channel and porous structures not only make ions/electrons transfer and electrolyte diffusion easier, but also contribute to the structural stability of the electrodes.

Scaling and Predicting the Geotechnical Resistance Provided by Alfalfa in Experimental Studies of Alluvial-Channel Morphology and Planform

NASA Astrophysics Data System (ADS)

Bankhead, N.; Simon, A.

2008-12-01

Several complex interactions occur between riparian vegetation and bank stability processes. Although there are both positive and negative effects of riparian vegetation on streambank stability, a link between increased vegetation density and decreased bank erosion and lateral migration rates of channels has generally been recorded. The ability of vegetation to promote increased bank stability leads to a positive feedback, in which bank stability then allows the growth and establishment of more vegetation. To study interactions between vegetation density and channel planform, past flume studies have used alfalfa sprouts (Medicago sativa), seeded over the entire floodplain in varying densities. Such studies have observed reductions in braiding intensity with increased alfalfa density. It has been assumed in these studies that the alfalfa sprouts increase the resistance of the bank material to lateral erosion. When alfalfa sprouts are scaled up they simulate mature riparian trees well. However, the geotechnical properties of alfalfa roots, and quantification of the increase in resistance provided to the banks under different densities of alfalfa have thus far been ignored. It is therefore unknown if the resistance provided by the alfalfa roots also scales well to real-world root-reinforcement values. To quantify additional bank strength, alfalfa sprouts were grown in sand and the roots tested at regular intervals to measure tensile strength. Results of tensile-strength measurements for alfalfa sprouts displayed the typical non-linear decrease of tensile strength (in MPa) with increasing root diameter. Values for the additional cohesion provided by alfalfa roots were calculated by inputting alfalfa tensile-strength and root density data to the root-reinforcement model, RipRoot, resulting in root-reinforcement values of 0 to 11.8 kPa. These values are similar to those that would be expected under field conditions. The root-cohesion values calculated for alfalfa sprouts

A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs.

PubMed

Mo, Yuanfu; Yu, Dexin; Song, Jun; Zheng, Kun; Guo, Yajuan

2015-01-01

In a vehicular ad hoc network (VANET), the periodic exchange of single-hop status information broadcasts (beacon frames) produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network.

A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs

PubMed Central

Mo, Yuanfu; Yu, Dexin; Song, Jun; Zheng, Kun; Guo, Yajuan

2015-01-01

In a vehicular ad hoc network (VANET), the periodic exchange of single-hop status information broadcasts (beacon frames) produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network. PMID:26571042

Local buckling of composite channel columns

NASA Astrophysics Data System (ADS)

Szymczak, Czesław; Kujawa, Marcin

2018-05-01

The investigation concerns local buckling of compressed flanges of axially compressed composite channel columns. Cooperation of the member flange and web is taken into account here. The buckling mode of the member flange is defined by rotation angle a flange about the line of its connection with the web. The channel column under investigation is made of unidirectional fibre-reinforced laminate. Two approaches to member orthotropic material modelling are performed: the homogenization with the aid of theory of mixture and periodicity cell or homogenization upon the Voigt-Reuss hypothesis. The fundamental differential equation of local buckling is derived with the aid of the stationary total potential energy principle. The critical buckling stress corresponding to a number of buckling half-waves is assumed to be a minimum eigenvalue of the equation. Some numerical examples dealing with columns are given here. The analytical results are compared with the finite element stability analysis carried out by means of ABAQUS software. The paper is focused on a close analytical solution of the critical buckling stress and the associated buckling mode while the web-flange cooperation is assumed.

Electrostatic networks control plug stabilization in the PapC usher.

PubMed

Pham, Thieng; Henderson, Nadine S; Werneburg, Glenn T; Thanassi, David G; Delcour, Anne H

2015-01-01

The PapC usher, a β-barrel pore in the outer membrane of uropathogenic Escherichia coli, is used for assembly of the P pilus, a key virulence factor in bacterial colonization of human kidney cells. Each PapC protein is composed of a 24-stranded β-barrel channel, flanked by N- and C-terminal globular domains protruding into the periplasm, and occluded by a plug domain (PD). The PD is displaced from the channel towards the periplasm during pilus biogenesis, but the molecular mechanism for PD displacement remains unclear. Two structural features within the β-barrel, an α-helix and β5-6 hairpin loop, may play roles in controlling plug stabilization. Here we have tested clusters of residues at the interface of the plug, barrel, α-helix and hairpin, which participate in electrostatic networks. To assess the roles of these residues in plug stabilization, we used patch-clamp electrophysiology to compare the activity of wild-type and mutant PapC channels containing alanine substitutions at these sites. Mutations interrupting each of two salt bridge networks were relatively ineffective in disrupting plug stabilization. However, mutation of two pairs of arginines located at the inner and the outer surfaces of the PD resulted in an enhanced propensity for plug displacement. One arginine pair involved in a repulsive interaction between the linkers that tether the plug to the β-barrel was particularly sensitive to mutation. These results suggest that plug displacement, which is necessary for pilus assembly and translocation, may require a weakening of key electrostatic interactions between the plug linkers, and the plug and the α-helix.

Stability Estimation of ABWR on the Basis of Noise Analysis

NASA Astrophysics Data System (ADS)

Furuya, Masahiro; Fukahori, Takanori; Mizokami, Shinya; Yokoya, Jun

In order to investigate the stability of a nuclear reactor core with an oxide mixture of uranium and plutonium (MOX) fuel installed, channel stability and regional stability tests were conducted with the SIRIUS-F facility. The SIRIUS-F facility was designed and constructed to provide a highly accurate simulation of thermal-hydraulic (channel) instabilities and coupled thermalhydraulics-neutronics instabilities of the Advanced Boiling Water Reactors (ABWRs). A real-time simulation was performed by modal point kinetics of reactor neutronics and fuel-rod thermal conduction on the basis of a measured void fraction in a reactor core section of the facility. A time series analysis was performed to calculate decay ratio and resonance frequency from a dominant pole of a transfer function by applying auto regressive (AR) methods to the time-series of the core inlet flow rate. Experiments were conducted with the SIRIUS-F facility, which simulates ABWR with MOX fuel installed. The variations in the decay ratio and resonance frequency among the five common AR methods are within 0.03 and 0.01 Hz, respectively. In this system, the appropriate decay ratio and resonance frequency can be estimated on the basis of the Yule-Walker method with the model order of 30.

Mechanics of flow and sediment transport in delta distributary channels

USGS Publications Warehouse

Nelson, Jonathan M.; Kinzel, Paul J.; Duc Toan, Duong; Shimizu, Yasuyuki; McDonald, Richard R.

2011-01-01

boundary conditions. Over time, the pattern of erosion and deposition in the distributary channels gives rise to variations in the amount of water and sediment routed into them. In the simplest case, this results in channel switching on deltas, but in a more general sense these dynamics produce a rich suite of interesting morphologic change contributing both to the evolution of the channel distributary network and the overall evolution of the delta. As part of a study to develop a better understanding of these processes, we conducted a field study measuring the detailed morphology of the Hong-Luoc junction on the Red River downstream of Hanoi, Vietnam. This junction was selected for such a study because it has a 1,000-year history, modern observations suggest that it is currently switching (changing the proportion of sediment and streamflow provided to each of the distributary channels), and hydrologic configuration of the junction allows for the study of two bifurcations and one confluence in a single junction complex. In this paper, our morphologic observations are used in computational flow models to show how flow and sediment transport changes as a function of total discharge upstream of the junction. This is a key component of understanding how the junction attains stability over a range of flows or how imbalances in the distribution of flow and sediment transport lead to destabilization of the channel bifurcation.

Effect of palladium doping on the stability and fragmentation patterns of cationic gold clusters

NASA Astrophysics Data System (ADS)

Ferrari, P.; Hussein, H. A.; Heard, C. J.; Vanbuel, J.; Johnston, R. L.; Lievens, P.; Janssens, E.

2018-05-01

We analyze in detail how the interplay between electronic structure and cluster geometry determines the stability and the fragmentation channels of single Pd-doped cationic Au clusters, PdA uN-1+ (N =2 -20 ). For this purpose, a combination of photofragmentation experiments and density functional theory calculations was employed. A remarkable agreement between the experiment and the calculations is obtained. Pd doping is found to modify the structure of the Au clusters, in particular altering the two-dimensional to three-dimensional transition size, with direct consequences on the stability of the clusters. Analysis of the electronic density of states of the clusters shows that depending on cluster size, Pd delocalizes one 4 d electron, giving an enhanced stability to PdA u6 + , or remains with all 4 d10 electrons localized, closing an electronic shell in PdA u9 + . Furthermore, it is observed that for most clusters, Au evaporation is the lowest-energy decay channel, although for some sizes Pd evaporation competes. In particular, PdA u7 + and PdA u9 + decay by Pd evaporation due to the high stability of the A u7 + and A u9 + fragmentation products.

Riparian vegetation controls on channels formed in non-cohesive sediment

NASA Astrophysics Data System (ADS)

Gran, K.; Tal, M.; Paola, C.

2002-05-01

Riparian vegetation can significantly influence the morphology of a river, affecting channel geometry and flow dynamics. In channels formed in non-cohesive material, vegetation is the main source of bank cohesion and could affect the overall behavior of the river, potentially constraining the flow from a multi-thread channel to a single-thread channel. To examine the effects of riparian vegetation on streams formed in non-cohesive material, we conducted a series of physical experiments at the St. Anthony Falls Laboratory. The first set of experiments examines the effects of varying densities of vegetation on braided stream dynamics. Water discharge, sediment discharge, and grain size were held constant. For each run, we allowed a braided system to develop, then halved the discharge, and seeded the flume with alfalfa (Medicago sativa). After ten to fourteen days of growth, we returned the discharge to its original value and continued the run for 30-36 hours. Our results show that the influence of vegetation on the overall river pattern varied systematically with the spatial density of plant stems. The vegetation reduced the number of active channels and increased bank stability, leading to lower lateral migration rates, narrower and deeper channels, and an increase in channel relief. All these effects increased with vegetation density. Vegetation also influenced flow dynamics, increasing the variance of flow direction in the vegetated runs, and increasing scour depths through strong downwelling where the flow collided with relatively resistant banks. This oblique bank collision provides a new mechanism for producing secondary flows. We found these bank collision driven secondary flows to be more important than the classical curvature-driven mechanism in the vegetated runs. The next set of experiments examines more closely how the channel pattern evolves through time, allowing for both channel migration and successive vegetation growth. In these on-going experiments

The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility*

PubMed Central

Ding, Xi-Qin; Thapa, Arjun; Ma, Hongwei; Xu, Jianhua; Elliott, Michael H.; Rodgers, Karla K.; Smith, Marci L.; Wang, Jin-Shan; Pittler, Steven J.; Kefalov, Vladimir J.

2016-01-01

Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2–3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3−/−/Nrl−/− mice with CNGB3 deficiency on a cone-dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3−/−/Nrl−/− mice compared with Nrl−/− mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. PMID:26893377

Two Salt Bridges Differentially Contribute to the Maintenance of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel Function*

PubMed Central

Cui, Guiying; Freeman, Cody S.; Knotts, Taylor; Prince, Chengyu Z.; Kuang, Christopher; McCarty, Nael A.

2013-01-01

Previous studies have identified two salt bridges in human CFTR chloride ion channels, Arg352-Asp993 and Arg347-Asp924, that are required for normal channel function. In the present study, we determined how the two salt bridges cooperate to maintain the open pore architecture of CFTR. Our data suggest that Arg347 not only interacts with Asp924 but also interacts with Asp993. The tripartite interaction Arg347-Asp924-Asp993 mainly contributes to maintaining a stable s2 open subconductance state. The Arg352-Asp993 salt bridge, in contrast, is involved in stabilizing both the s2 and full (f) open conductance states, with the main contribution being to the f state. The s1 subconductance state does not require either salt bridge. In confirmation of the role of Arg352 and Asp993, channels bearing cysteines at these sites could be latched into a full open state using the bifunctional cross-linker 1,2-ethanediyl bismethanethiosulfonate, but only when applied in the open state. Channels remained latched open even after washout of ATP. The results suggest that these interacting residues contribute differently to stabilizing the open pore in different phases of the gating cycle. PMID:23709221

Analysis of four connexin26 mutant gap junctions and hemichannels reveals variations in hexamer stability.

PubMed

Ambrosi, Cinzia; Boassa, Daniela; Pranskevich, Jennifer; Smock, Amy; Oshima, Atsunori; Xu, Ji; Nicholson, Bruce J; Sosinsky, Gina E

2010-05-19

Connexin26 is a ubiquitous gap junction protein that serves critical homeostatic functions. Four single-site mutations found in the transmembrane helices (M1-M4) cause different types of dysfunctional channels: 1), Cx26T135A in M3 produces a closed channel; 2), Cx26M34A in M1 severely decreases channel activity; 3), Cx26P87L in M2 has been implicated in defective channel gating; and 4), Cx26V84L in M2, a nonsyndromic deafness mutant, retains normal dye coupling and electrophysiological properties but is deficient in IP(3) transfer. These mutations do not affect Cx26 trafficking in mammalian cells, and make normal-appearing channels in baculovirus-infected Sf9 membranes when imaged by negative stain electron microscopy. Upon dodecylmaltoside solubilization of the membrane fraction, Cx26M34A and Cx26V84L are stable as hexamers or dodecamers, but Cx26T135A and Cx26P87L oligomers are not. This instability is also found in Cx26T135A and Cx26P87L hemichannels isolated from mammalian cells. In this work, coexpression of both wild-type Cx26 and Cx26P87L in Sf9 cells rescued P87L hexamer stability. Similarly, in paired Xenopus oocytes, coexpression with wild-type restored function. In contrast, the stability of Cx26T135A hemichannels could not be rescued by coexpression with WT. Thus, T135 and P87 residues are in positions that are important for oligomer stability and can affect gap junction gating. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Probing the effect of electron channelling on atomic resolution energy dispersive X-ray quantification.

PubMed

MacArthur, Katherine E; Brown, Hamish G; Findlay, Scott D; Allen, Leslie J

2017-11-01

Advances in microscope stability, aberration correction and detector design now make it readily possible to achieve atomic resolution energy dispersive X-ray mapping for dose resilient samples. These maps show impressive atomic-scale qualitative detail as to where the elements reside within a given sample. Unfortunately, while electron channelling is exploited to provide atomic resolution data, this very process makes the images rather more complex to interpret quantitatively than if no electron channelling occurred. Here we propose small sample tilt as a means for suppressing channelling and improving quantification of composition, whilst maintaining atomic-scale resolution. Only by knowing composition and thickness of the sample is it possible to determine the atomic configuration within each column. The effects of neighbouring atomic columns with differing composition and of residual channelling on our ability to extract exact column-by-column composition are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

High-power AlGaAs channeled substrate planar diode lasers for spaceborne communications

NASA Technical Reports Server (NTRS)

Connolly, J. C.; Goldstein, B.; Pultz, G. N.; Slavin, S. E.; Carlin, D. B.; Ettenberg, M.

1988-01-01

A high power channeled substrate planar AlGaAs diode laser with an emission wavelength of 8600 to 8800 A was developed. The optoelectronic behavior (power current, single spatial and spectral behavior, far field characteristics, modulation, and astigmatism properties) and results of computer modeling studies on the performance of the laser are discussed. Lifetest data on these devices at high output power levels is also included. In addition, a new type of channeled substrate planar laser utilizing a Bragg grating to stabilize the longitudinal mode was demonstrated. The fabrication procedures and optoelectronic properties of this new diode laser are described.

Interaction of 4.1G and cGMP-gated channels in rod photoreceptor outer segments.

PubMed

Cheng, Christiana L; Molday, Robert S

2013-12-15

In photoreceptors, the assembly of signaling molecules into macromolecular complexes is important for phototransduction and maintaining the structural integrity of rod outer segments (ROSs). However, the molecular composition and formation of these complexes are poorly understood. Using immunoprecipitation and mass spectrometry, 4.1G was identified as a new interacting partner for the cyclic-nucleotide gated (CNG) channels in ROSs. 4.1G is a widely expressed multifunctional protein that plays a role in the assembly and stability of membrane protein complexes. Multiple splice variants of 4.1G were cloned from bovine retina. A smaller splice variant of 4.1G selectively interacted with CNG channels not associated with peripherin-2-CNG channel complex. A combination of truncation studies and domain-binding assays demonstrated that CNG channels selectively interacted with 4.1G through their FERM and CTD domains. Using immunofluorescence, labeling of 4.1G was seen to be punctate and partially colocalized with CNG channels in the ROS. Our studies indicate that 4.1G interacts with a subset of CNG channels in the ROS and implicate this protein-protein interaction in organizing the spatial arrangement of CNG channels in the plasma membrane of outer segments.

Sodium channel blockers as therapeutic target for treating epilepsy: recent updates.

PubMed

Zuliani, Valentina; Fantini, Marco; Rivara, Mirko

2012-01-01

The voltage-gated sodium channels (VGSCs) are a family of membrane proteins forming a pore, through which they selectively conduct sodium ions inward and outward cell's plasma membranes in response to variations of membrane potentials, playing a fundamental role in controlling cellular excitability. Growing evidences suggest that abnormal VGSCs are involved in the pathophysiology of both acquired and inherited epilepsy. Approximately two dozen drugs are currently marketed for the treatment of epilepsy and most of them act as sodium channel blockers, preventing the return of the channels to the active state by stabilizing the inactive form. Despite the many drugs on the market, 30% of patients continue to experience seizures even in the presence of optimal doses of AEDs, while others continue to suffer from medication induced side effects. Thus, there is a great need to continue the search for new AEDs that are not only more effective, but also have a better side effects profile. For this reason, many efforts have been made in the recent years to identify new sodium channel blockers for the treatment of epilepsy. These studies have led to different classes of compounds, characterized by a great structural diversity. The aim of this review is to provide an introduction on the structure and function of the sodium channels, followed by a brief historical perspective on the sodium channel blockers in use as anticonvulsant drugs. Moreover, it will focus on the medicinal chemistry of the sodium channel blockers recently published (2008-2011) and the drug design/molecular modeling studies related to the receptor.

Stability analysis of confined V-shaped flames in high-velocity streams.

PubMed

El-Rabii, Hazem; Joulin, Guy; Kazakov, Kirill A

2010-06-01

The problem of linear stability of confined V-shaped flames with arbitrary gas expansion is addressed. Using the on-shell description of flame dynamics, a general equation governing propagation of disturbances of an anchored flame is obtained. This equation is solved analytically for V-flames anchored in high-velocity channel streams. It is demonstrated that dynamics of the flame disturbances in this case is controlled by the memory effects associated with vorticity generated by the perturbed flame. The perturbation growth rate spectrum is determined, and explicit analytical expressions for the eigenfunctions are given. It is found that the piecewise linear V structure is unstable for all values of the gas expansion coefficient. Despite the linearity of the basic pattern, however, evolutions of the V-flame disturbances are completely different from those found for freely propagating planar flames or open anchored flames. The obtained results reveal strong influence of the basic flow and the channel walls on the stability properties of confined V-flames.

Voltage-dependent conformational changes in connexin channels.

PubMed

Bargiello, Thaddeus A; Tang, Qingxiu; Oh, Seunghoon; Kwon, Taekyung

2012-08-01

Channels formed by connexins display two distinct types of voltage-dependent gating, termed V(j)- or fast-gating and loop- or slow-gating. Recent studies, using metal bridge formation and chemical cross-linking have identified a region within the channel pore that contributes to the formation of the loop-gate permeability barrier. The conformational changes are remarkably large, reducing the channel pore diameter from 15 to 20Å to less than 4Å. Surprisingly, the largest conformational change occurs in the most stable region of the channel pore, the 3(10) or parahelix formed by amino acids in the 42-51 segment. The data provide a set of positional constraints that can be used to model the structure of the loop-gate closed state. Less is known about the conformation of the V(j)-gate closed state. There appear to be two different mechanisms; one in which conformational changes in channel structure are linked to a voltage sensor contained in the N-terminus of Cx26 and Cx32 and a second in which the C-terminus of Cx43 and Cx40 may act either as a gating particle to block the channel pore or alternatively to stabilize the closed state. The later mechanism utilizes the same domains as implicated in effecting pH gating of Cx43 channels. It is unclear if the two V(j)-gating mechanisms are related or if they represent different gating mechanisms that operate separately in different subsets of connexin channels. A model of the V(j)-closed state of Cx26 hemichannel that is based on the X-ray structure of Cx26 and electron crystallographic structures of a Cx26 mutation suggests that the permeability barrier for V(j)-gating is formed exclusively by the N-terminus, but recent information suggests that this conformation may not represent a voltage-closed state. Closed state models are considered from a thermodynamic perspective based on information from the 3.5Å Cx26 crystal structure and molecular dynamics (MD) simulations. The applications of computational and experimental

Control of Ambipolar Transport in SnO Thin-Film Transistors by Back-Channel Surface Passivation for High Performance Complementary-like Inverters.

PubMed

Luo, Hao; Liang, Lingyan; Cao, Hongtao; Dai, Mingzhi; Lu, Yicheng; Wang, Mei

2015-08-12

For ultrathin semiconductor channels, the surface and interface nature are vital and often dominate the bulk properties to govern the field-effect behaviors. High-performance thin-film transistors (TFTs) rely on the well-defined interface between the channel and gate dielectric, featuring negligible charge trap states and high-speed carrier transport with minimum carrier scattering characters. The passivation process on the back-channel surface of the bottom-gate TFTs is indispensable for suppressing the surface states and blocking the interactions between the semiconductor channel and the surrounding atmosphere. We report a dielectric layer for passivation of the back-channel surface of 20 nm thick tin monoxide (SnO) TFTs to achieve ambipolar operation and complementary metal oxide semiconductor (CMOS) like logic devices. This chemical passivation reduces the subgap states of the ultrathin channel, which offers an opportunity to facilitate the Fermi level shifting upward upon changing the polarity of the gate voltage. With the advent of n-type inversion along with the pristine p-type conduction, it is now possible to realize ambipolar operation using only one channel layer. The CMOS-like logic inverters based on ambipolar SnO TFTs were also demonstrated. Large inverter voltage gains (>100) in combination with wide noise margins are achieved due to high and balanced electron and hole mobilities. The passivation also improves the long-term stability of the devices. The ability to simultaneously achieve field-effect inversion, electrical stability, and logic function in those devices can open up possibilities for the conventional back-channel surface passivation in the CMOS-like electronics.

Variation of alluvial-channel width with discharge and character of sediment

USGS Publications Warehouse

Osterkamp, W.R.

1979-01-01

Use of channel measurements to estimate discharge characteristics of alluvial streams has shown that little agreement exists for the exponent of the width-discharge relation. For the equation Q = aWAb, where Q is mean discharge and WA is active-channel width, it is proposed that the exponent, b, should be of fixed value for most natural, perennial, alluvial stream channels and that the coefficient, a, varies with the characteristics of the bed and bank material.Three groups of perennial stream channels with differing characteristics were selected for study using consistent procedures of data collection. A common feature of the groups was general channel stability, that is, absence of excessive widening by erosive discharges. Group 1 consisted of 32 channels of gradient exceeding 0.0080, low suspended-sediment discharge, high channel roughness, and low discharge variability. Group 2 consisted of 13 streams in Kansas having at least 70 percent silt and clay in the bed material and having similar discharge variability, climate, gradient, and riparian vegetation. Group 3, in southern Missouri, consisted of discharge channels of 18 springs having similar conditions of very low discharge variability, climate and vegetation, but variable bed and bank material. Values for the exponent for the three groups of data are 1.98, 1.97, and 1.97, respectively, whereas values of the coefficients are 0.017, 0.042, and 0.011 when discharge is expressed in cubic meters per second and width is in meters. The relation for high-gradient channels (group 1) is supported by published data from laboratory flumes.The similarity of the three values of the exponent demonstrates that a standard exponent of 2.0, significant to two figures, is reasonable for the width-mean discharge relation of perennial, alluvial stream channels, and that the exponent is independent of other variables. Using a fixed exponent of 2.0, a family of simple power-function equations was developed expressing the manner

TRP Channels

NASA Astrophysics Data System (ADS)

Voets, Thomas; Owsianik, Grzegorz; Nilius, Bernd

The TRP superfamily represents a highly diverse group of cation-permeable ion channels related to the product of the Drosophila trp (transient receptor potential) gene. The cloning and characterization of members of this cation channel family has experienced a remarkable growth during the last decade, uncovering a wealth of information concerning the role of TRP channels in a variety of cell types, tissues, and species. Initially, TRP channels were mainly considered as phospholipase C (PLC)-dependent and/or store-operated Ca2+-permeable cation channels. More recent research has highlighted the sensitivity of TRP channels to a broad array of chemical and physical stimuli, allowing them to function as dedicated biological sensors involved in processes ranging from vision to taste, tactile sensation, and hearing. Moreover, the tailored selectivity of certain TRP channels enables them to play key roles in the cellular uptake and/or transepithelial transport of Ca2+, Mg2+, and trace metal ions. In this chapter we give a brief overview of the TRP channel superfamily followed by a survey of current knowledge concerning their structure and activation mechanisms.

Channelized melting drives thinning under Dotson ice shelf, Western Antarctic Ice Sheet

NASA Astrophysics Data System (ADS)

Gourmelen, N.; Goldberg, D.; Snow, K.; Henley, S. F.; Bingham, R. G.; Kimura, S.; Hogg, A.; Shepherd, A.; Mouginot, J.; Lenaerts, J.; Ligtenberg, S.; Van De Berg, W. J.

2017-12-01

The majority of meteoric ice that forms in West Antarctica leaves the ice sheet through floating ice shelves, many of which have been thinning substantially over the last 25 years. A significant proportion of ice-shelf thinning has been driven by submarine melting facilitated by increased access of relatively warm (>0.6oC) modified Circumpolar Deep Water to sub-shelf cavities. Ice shelves play a significant role in stabilising the ice sheet from runaway retreat and regulating its contribution to sea level change. Ice-shelf melting has also been implicated in sustaining high primary productivity in Antarctica's coastal seas. However, these processes vary regionally and are not fully understood. Under some ice shelves, concentrated melting leads to the formation of inverted channels. These channels guide buoyant melt-laden outflow, which can lead to localised melting of the sea ice cover. The channels may also potentially lead to heightened crevassing, which in turn affects ice-shelf stability. Meanwhile, numerical studies suggest that buttressing loss is sensitive to the location of ice removal within an ice-shelf. Thus it is important that we observe spatial patterns, as well as magnitudes, of ice-shelf thinning, in order to improve understanding of the ocean drivers of thinning and of their impacts on ice-shelf stability. Here we show from high-resolution altimetry measurements acquired between 2010 to 2016 that Dotson Ice Shelf, West Antarctica, thins in response to basal melting focussed along a single 5 km-wide and 60 km-long channel extending from the ice shelf's grounding zone to its calving front. The coupled effect of geostrophic circulation and ice-shelf topography leads to the observed concentration of basal melting. Analysis of previous datasets suggests that this process has been ongoing for at least the last 25 years. If focused thinning continues at present rates, the channel would melt through within 40-50 years, almost two centuries before it is

Analytical study of magnetohydrodynamic propulsion stability

NASA Astrophysics Data System (ADS)

Abdollahzadeh Jamalabadi, M. Y.

2014-09-01

In this paper an analytical solution for the stability of the fully developed flow drive in a magneto-hydro-dynamic pump with pulsating transverse Eletro-magnetic fields is presented. To do this, a theoretical model of the flow is developed and the analytical results are obtained for both the cylindrical and Cartesian configurations that are proper to use in the propulsion of marine vessels. The governing parabolic momentum PDEs are transformed into an ordinary differential equation using approximate velocity distribution. The numerical results are obtained and asymptotic analyses are built to discover the mathematical behavior of the solutions. The maximum velocity in a magneto-hydro-dynamic pump versus time for various values of the Stuart number, electro-magnetic interaction number, Reynolds number, aspect ratio, as well as the magnetic and electrical angular frequency and the shift of the phase angle is presented. Results show that for a high Stuart number there is a frequency limit for stability of the fluid flow in a certain direction of the flow. This stability frequency is dependent on the geometric parameters of a channel.

Information Flow in Interaction Networks II: Channels, Path Lengths, and Potentials

PubMed Central

Stojmirović, Aleksandar

2012-01-01

Abstract In our previous publication, a framework for information flow in interaction networks based on random walks with damping was formulated with two fundamental modes: emitting and absorbing. While many other network analysis methods based on random walks or equivalent notions have been developed before and after our earlier work, one can show that they can all be mapped to one of the two modes. In addition to these two fundamental modes, a major strength of our earlier formalism was its accommodation of context-specific directed information flow that yielded plausible and meaningful biological interpretation of protein functions and pathways. However, the directed flow from origins to destinations was induced via a potential function that was heuristic. Here, with a theoretically sound approach called the channel mode, we extend our earlier work for directed information flow. This is achieved by constructing a potential function facilitating a purely probabilistic interpretation of the channel mode. For each network node, the channel mode combines the solutions of emitting and absorbing modes in the same context, producing what we call a channel tensor. The entries of the channel tensor at each node can be interpreted as the amount of flow passing through that node from an origin to a destination. Similarly to our earlier model, the channel mode encompasses damping as a free parameter that controls the locality of information flow. Through examples involving the yeast pheromone response pathway, we illustrate the versatility and stability of our new framework. PMID:22409812

Peptides and genes coding for scorpion toxins that affect ion-channels.

PubMed

Possani, L D; Merino, E; Corona, M; Bolivar, F; Becerril, B

2000-01-01

Most scorpion toxins are ligand peptides that recognize and bind to integral membrane proteins known as ion-channels. To date there are at least 202 distinct sequences described, obtained from 30 different species of scorpions, 27 from the family Buthidae and three from the family Scorpionidae. Toxins that recognize potassium and chloride channels are usually from 29 to 41 amino acids long, stabilized by three or four disulfide bridges, whereas those that recognize sodium channels are longer, 60 to 76 amino acid residues, compacted by four disulfide bridges. Toxins specific for calcium channels are scarcely known and have variable amino acid lengths. The entire repertoire of toxins, independently of their specificity, was analyzed together by computational programs and a phylogenetic tree was built showing two separate branches. The K(+) and Cl(-) channel specific toxins are clustered into 14 subfamilies, whereas those of Na(+) and Ca(2+) specific toxins comprise at least 12 subfamilies. There are clear similarities among them, both in terms of primary sequence and the main three-dimensional folding pattern. A dense core formed by a short alpha helix segment and several antiparallel beta-sheet stretches, maintained by disulfide pairing, seems to be a common structural feature present in all toxins. The physiological function of these peptides is manifested by a blockage of ion passage through the channels or by a modification of the gating mechanism that controls opening and closing of the ion pore.

KCNE1 constrains the voltage sensor of Kv7.1 K+ channels.

PubMed

Shamgar, Liora; Haitin, Yoni; Yisharel, Ilanit; Malka, Eti; Schottelndreier, Hella; Peretz, Asher; Paas, Yoav; Attali, Bernard

2008-04-09

Kv7 potassium channels whose mutations cause cardiovascular and neurological disorders are members of the superfamily of voltage-gated K(+) channels, comprising a central pore enclosed by four voltage-sensing domains (VSDs) and sharing a homologous S4 sensor sequence. The Kv7.1 pore-forming subunit can interact with various KCNE auxiliary subunits to form K(+) channels with very different gating behaviors. In an attempt to characterize the nature of the promiscuous gating of Kv7.1 channels, we performed a tryptophan-scanning mutagenesis of the S4 sensor and analyzed the mutation-induced perturbations in gating free energy. Perturbing the gating energetics of Kv7.1 bias most of the mutant channels towards the closed state, while fewer mutations stabilize the open state or the inactivated state. In the absence of auxiliary subunits, mutations of specific S4 residues mimic the gating phenotypes produced by co-assembly of Kv7.1 with either KCNE1 or KCNE3. Many S4 perturbations compromise the ability of KCNE1 to properly regulate Kv7.1 channel gating. The tryptophan-induced packing perturbations and cysteine engineering studies in S4 suggest that KCNE1 lodges at the inter-VSD S4-S1 interface between two adjacent subunits, a strategic location to exert its striking action on Kv7.1 gating functions.

KCNE1 Constrains the Voltage Sensor of Kv7.1 K+ Channels

PubMed Central

Yisharel, Ilanit; Malka, Eti; Schottelndreier, Hella; Peretz, Asher; Paas, Yoav; Attali, Bernard

2008-01-01

Kv7 potassium channels whose mutations cause cardiovascular and neurological disorders are members of the superfamily of voltage-gated K+ channels, comprising a central pore enclosed by four voltage-sensing domains (VSDs) and sharing a homologous S4 sensor sequence. The Kv7.1 pore-forming subunit can interact with various KCNE auxiliary subunits to form K+ channels with very different gating behaviors. In an attempt to characterize the nature of the promiscuous gating of Kv7.1 channels, we performed a tryptophan-scanning mutagenesis of the S4 sensor and analyzed the mutation-induced perturbations in gating free energy. Perturbing the gating energetics of Kv7.1 bias most of the mutant channels towards the closed state, while fewer mutations stabilize the open state or the inactivated state. In the absence of auxiliary subunits, mutations of specific S4 residues mimic the gating phenotypes produced by co-assembly of Kv7.1 with either KCNE1 or KCNE3. Many S4 perturbations compromise the ability of KCNE1 to properly regulate Kv7.1 channel gating. The tryptophan-induced packing perturbations and cysteine engineering studies in S4 suggest that KCNE1 lodges at the inter-VSD S4-S1 interface between two adjacent subunits, a strategic location to exert its striking action on Kv7.1 gating functions. PMID:18398469

Automatic bad channel detection in intracranial electroencephalographic recordings using ensemble machine learning.

PubMed

Tuyisenge, Viateur; Trebaul, Lena; Bhattacharjee, Manik; Chanteloup-Forêt, Blandine; Saubat-Guigui, Carole; Mîndruţă, Ioana; Rheims, Sylvain; Maillard, Louis; Kahane, Philippe; Taussig, Delphine; David, Olivier

2018-03-01

Intracranial electroencephalographic (iEEG) recordings contain "bad channels", which show non-neuronal signals. Here, we developed a new method that automatically detects iEEG bad channels using machine learning of seven signal features. The features quantified signals' variance, spatial-temporal correlation and nonlinear properties. Because the number of bad channels is usually much lower than the number of good channels, we implemented an ensemble bagging classifier known to be optimal in terms of stability and predictive accuracy for datasets with imbalanced class distributions. This method was applied on stereo-electroencephalographic (SEEG) signals recording during low frequency stimulations performed in 206 patients from 5 clinical centers. We found that the classification accuracy was extremely good: It increased with the number of subjects used to train the classifier and reached a plateau at 99.77% for 110 subjects. The classification performance was thus not impacted by the multicentric nature of data. The proposed method to automatically detect bad channels demonstrated convincing results and can be envisaged to be used on larger datasets for automatic quality control of iEEG data. This is the first method proposed to classify bad channels in iEEG and should allow to improve the data selection when reviewing iEEG signals. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Mathematical simulation of sound propagation in a flow channel with impedance walls

NASA Astrophysics Data System (ADS)

Osipov, A. A.; Reent, K. S.

2012-07-01

The paper considers the specifics of calculating tonal sound propagating in a flow channel with an installed sound-absorbing device. The calculation is performed on the basis of numerical integrating on linearized nonstationary Euler equations using a code developed by the authors based on the so-called discontinuous Galerkin method. Using the linear theory of small perturbations, the effect of the sound-absorbing lining of the channel walls is described with the modified value of acoustic impedance proposed by the authors, for which, under flow channel conditions, the traditional classification of the active and reactive types of lining in terms of the real and imaginary impedance values, respectively, remains valid. To stabilize the computation process, a generalized impedance boundary condition is proposed in which, in addition to the impedance value itself, some additional parameters are introduced characterizing certain fictitious properties of inertia and elasticity of the impedance surface.

Single-channel kinetics of BK (Slo1) channels

PubMed Central

Geng, Yanyan; Magleby, Karl L.

2014-01-01

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 five closed states on the upper tier and five 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. PMID:25653620

Progress in Development of Improved Ion-Channel Biosensors

NASA Technical Reports Server (NTRS)

Nadeau, Jay L.; White, Victor E.; Maurer, Joshua A.; Dougherty, Dennis A.

2008-01-01

Further improvements have recently been made in the development of the devices described in Improved Ion-Channel Biosensors (NPO-30710), NASA Tech Briefs, Vol. 28, No. 10 (October 2004), page 30. As discussed in more detail in that article, these sensors offer advantages of greater stability, greater lifetime, and individual electrical addressability, relative to prior ion-channel biosensors. In order to give meaning to a brief description of the recent improvements, it is necessary to recapitulate a substantial portion of the text of the cited previous article. The figure depicts one sensor that incorporates the recent improvements, and can be helpful in understanding the recapitulated text, which follows: These sensors are microfabricated from silicon and other materials compatible with silicon. Typically, the sensors are fabricated in arrays in silicon wafers on glass plates. Each sensor in the array can be individually electrically addressed, without interference with its neighbors. Each sensor includes a well covered by a thin layer of silicon nitride, in which is made a pinhole for the formation of a lipid bilayer membrane. In one stage of fabrication, the lower half of the well is filled with agarose, which is allowed to harden. Then the upper half of the well is filled with a liquid electrolyte (which thereafter remains liquid) and a lipid bilayer is painted over the pinhole. The liquid contains a protein that forms an ion channel on top of the hardened agarose. The combination of enclosure in the well and support by the hardened agarose provides the stability needed to keep the membrane functional for times as long as days or even weeks. An electrode above the well, another electrode below the well, and all the materials between the electrodes together constitute a capacitor. What is measured is the capacitive transient current in response to an applied voltage pulse. One notable feature of this sensor, in comparison with prior such sensors, is a

Structure of the TRPA1 ion channel suggests regulatory mechanisms.

PubMed

Paulsen, Candice E; Armache, Jean-Paul; Gao, Yuan; Cheng, Yifan; Julius, David

2015-04-23

The TRPA1 ion channel (also known as the wasabi receptor) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here we use single-particle electron cryo- microscopy to determine the structure of full-length human TRPA1 to ∼4 Å resolution in the presence of pharmacophores, including a potent antagonist. Several unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted transient receptor potential (TRP)-like allosteric domain. These findings provide new insights into the mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents.

Structure of the TRPA1 ion channel suggests regulatory mechanisms

PubMed Central

Paulsen, Candice E.; Armache, Jean-Paul; Gao, Yuan; Cheng, Yifan; Julius, David

2015-01-01

The TRPA1 ion channel (a.k.a the ‘wasabi receptor’) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here, we use single-particle electron cryo-microscopy to determine the structure of full-length human TRPA1 to ~4Å resolution in the presence of pharmacophores, including a potent antagonist. A number of unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted TRP-like allosteric domain. These findings provide novel insights into mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents. PMID:25855297

The gating cycle of a K+ channel at atomic resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuello, Luis G.; Cortes, D. Marien; Perozo, Eduardo

C-type inactivation in potassium channels helps fine-tune long-term channel activity through conformational changes at the selectivity filter. Here, through the use of cross-linked constitutively open constructs, we determined the structures of KcsA’s mutants that stabilize the selectivity filter in its conductive (E71A, at 2.25 Å) and deep C-type inactivated (Y82A at 2.4 Å) conformations. These structural snapshots represent KcsA’s transient open-conductive (O/O) and the stable open deep C-type inactivated states (O/I), respectively. The present structures provide an unprecedented view of the selectivity filter backbone in its collapsed deep C-type inactivated conformation, highlighting the close interactions with structural waters and themore » local allosteric interactions that couple activation and inactivation gating. Together with the structures associated with the closed-inactivated state (C/I) and in the well-known closed conductive state (C/O), this work recapitulates, at atomic resolution, the key conformational changes of a potassium channel pore domain as it progresses along its gating cycle.« less

Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel

PubMed Central

Sauguet, Ludovic; Howard, Rebecca J.; Malherbe, Laurie; Lee, Ui S.; Corringer, Pierre-Jean; Harris, R. Adron; Delarue, Marc

2014-01-01

Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. A recent series of mutagenesis experiments on Gloeobacter violaceus ligand-gated ion channel, a prokaryotic member of this family, identified a single-site variant that is potentiated by pharmacologically relevant concentrations of ethanol. Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. Structural and mutagenesis studies defined overlapping mechanisms of potentiation by alcohols and anaesthetics via the inter-subunit cavity. Furthermore, homology modelling show this cavity to be conserved in human ethanol-sensitive glycine and GABA(A) receptors, and to involve residues previously shown to influence alcohol and anaesthetic action on these proteins. These results suggest a common structural basis for ethanol potentiation of an important class of targets for neurological actions of ethanol. PMID:23591864

Bi-layer channel structure-based oxide thin-film transistors consisting of ZnO and Al-doped ZnO with different Al compositions and stacking sequences

NASA Astrophysics Data System (ADS)

Cho, Sung Woon; Yun, Myeong Gu; Ahn, Cheol Hyoun; Kim, So Hee; Cho, Hyung Koun

2015-03-01

Zinc oxide (ZnO)-based bi-layers, consisting of ZnO and Al-doped ZnO (AZO) layers grown by atomic layer deposition, were utilized as the channels of oxide thin-film transistors (TFTs). Thin AZO layers (5 nm) with different Al compositions (5 and 14 at. %) were deposited on top of and beneath the ZnO layers in a bi-layer channel structure. All of the bi-layer channel TFTs that included the AZO layers showed enhanced stability (Δ V Th ≤ 3.2 V) under a positive bias stress compared to the ZnO single-layer channel TFT (Δ V Th = 4.0 V). However, the AZO/ZnO bi-layer channel TFTs with an AZO interlayer between the gate dielectric and the ZnO showed a degraded field effect mobility (0.3 cm2/V·s for 5 at. % and 1.8 cm2/V·s for 14 at. %) compared to the ZnO single-layer channel TFT (5.5 cm2/V·s) due to increased scattering caused by Al-related impurities near the gate dielectric/channel interface. In contrast, the ZnO/AZO bi-layer channel TFTs with an AZO layer on top of the ZnO layer exhibited an improved field effect mobility (7.8 cm2/V·s for 14 at. %) and better stability. [Figure not available: see fulltext.

A Secondary Structural Transition in the C-helix Promotes Gating of Cyclic Nucleotide-regulated Ion Channels*

PubMed Central

Puljung, Michael C.; Zagotta, William N.

2013-01-01

Cyclic nucleotide-regulated ion channels bind second messengers like cAMP to a C-terminal domain, consisting of a β-roll, followed by two α-helices (B- and C-helices). We monitored the cAMP-dependent changes in the structure of the C-helix of a C-terminal fragment of HCN2 channels using transition metal ion FRET between fluorophores on the C-helix and metal ions bound between histidine pairs on the same helix. cAMP induced a change in the dimensions of the C-helix and an increase in the metal binding affinity of the histidine pair. cAMP also caused an increase in the distance between a fluorophore on the C-helix and metal ions bound to the B-helix. Stabilizing the C-helix of intact CNGA1 channels by metal binding to a pair of histidines promoted channel opening. These data suggest that ordering of the C-helix is part of the gating conformational change in cyclic nucleotide-regulated channels. PMID:23525108

The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability.

PubMed

Meng, Xin; Clews, Jack; Kargas, Vasileios; Wang, Xiaomeng; Ford, Robert C

2017-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body. There are over 1500 mutations that have been characterised as CF-causing; the most common of these, accounting for ~70 % of CF cases, is the deletion of a phenylalanine at position 508. This leads to instability of the nascent protein and the modified structure is recognised and then degraded by the ER quality control mechanism. However, even pharmacologically 'rescued' F508del CFTR displays instability at the cell's surface, losing its channel function rapidly and it is rapidly removed from the plasma membrane for lysosomal degradation. This review will, therefore, explore the link between stability and structure/function relationships of membrane proteins and CFTR in particular and how approaches to study CFTR structure depend on its stability. We will also review the application of a fluorescence labelling method for the assessment of the thermostability and the tertiary structure of CFTR.

Antagonism of Lidocaine Inhibition by Open-Channel Blockers That Generate Resurgent Na Current

PubMed Central

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

2013-01-01

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

Results From a Channel Restoration Project: Hydraulic Design Considerations

USGS Publications Warehouse

Karle, K.F.; Densmore, R.V.; ,

2001-01-01

Techniques for the hydraulic restoration of placer-mined streams and floodplains were developed in Denali National Park and Preserve, Alaska. The two-year study at Glen Creek focused on a design of stream and floodplain geometry using hydraulic capacity and shear stress equations. Slope and sinuosity values were based on regional relationships. Design requirements included a channel capacity for a bankfull discharge and a floodplain capacity for a 1.5- to 100-year discharge. Several bio-engineering techniques using alder and willow, including anchored brush bars, streambank hedge layering, seedlings, and cuttings, were tested to dissipate floodwater energy and encourage sediment deposition until natural revegetation stabilized the new floodplains. Permanently monumented cross-sections installed throughout the project site were surveyed every one to three years. Nine years after the project began, a summer flood caused substantial damage to the channel form, including a change in width/depth ratio, slope, and thalweg location. Many of the alder brush bars were heavily damaged or destroyed, resulting in significant bank erosion. This paper reviews the original hydraulic design process, and describes changes to the channel and floodplain geometry over time, based on nine years of cross-section surveys.

Roles of somatic A-type K(+) channels in the synaptic plasticity of hippocampal neurons.

PubMed

Yang, Yoon-Sil; Kim, Kyeong-Deok; Eun, Su-Yong; Jung, Sung-Cherl

2014-06-01

In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hippocampus and the cerebral cortices. The modulatory mechanisms of synaptic excitability that are correlated with neuronal tasks are fundamental factors for synaptic plasticity, and they are dependent on intracellular Ca(2+)-mediated signaling. In the present review, the A-type K(+) (IA) channel, one of the voltage-dependent cation channels, is considered as a key player in the modulation of Ca(2+) influx through synaptic NMDA receptors and their correlated signaling pathways. The cellular functions of IA channels indicate that they possibly play as integral parts of synaptic and somatic complexes, completing the initiation and stabilization of memory.

Streambed stability and scour potential at selected bridge sites in Michigan

USGS Publications Warehouse

Holtschlag, D.J.; Miller, R.L.

1998-01-01

Contraction scour in the main stream channel at a bridge and local scour near piers and abutments can result in bridge failure. Estimates of contraction-scour and local-scour potentials associated with the 100-year flood were computed for 13 bridge sites in Michigan by use of semi-theoretical equations and procedures recommended by the Federal Highway Administration. These potentials were compared with measures of Streambed stability obtained by use of data from 773 historical streamflow measurements, documenting 20,741 individual Streambed soundings between 1959 and 1995. Analysis of these data indicate small, but statistically significant, monotonic trends in Streambed elevation at 10 sites. No consistent patterns in relations between changes in Streambed elevations and streamflow, flow velocity, or flow depth were evident. Also, estimates of contraction-scour potential were not correlated with measures of Streambed stability, and no differences were detected between measures of Streambed stability in the main channel and stability adjacent to piers. Despite the inconsistencies between measures of Streambed stability and scour potential, data from a single, large flood (greater than a 100-year event) provided field evidence that the relation between scour and streamflow is highly nonlinear. This nonlinearity and the limited availability of measurements of extreme flood events may have reduced the utility of the empirical measures for confirming the nonlinear scour-potential equations and procedures. Results of field surveys using ground-penetrating radar and tuned transducers showed limited ability to aid interpretation of historical scour conditions at four bridge sites. Additional research is needed to confirm the applicability of scour-potential equations for hydrogeologic conditions in Michigan.

Application of ELJ to create and maintain side channels in a dynamic gravel bed river

NASA Astrophysics Data System (ADS)

Crabbe, E.; Crowe Curran, J.; Ockelford, A.

2017-12-01

Braided and anastomosing rivers create and maintain a large amount of side channel habitat. Unfortunately, many rivers that were once multi-channel rivers have been constrained to single thread channels as a consequence of land use changes that occurred in the 19th and 20th centuries or earlier. An increasingly common management goal today is the re-creation of self-maintaining side and tributary habitat through as natural means as possible. This work examines the geomorphic history of one such channel and the success of recent rehabilitation efforts. Our case study comes from the South Fork Nooksack River in the Cascades Range in Washington State. The Nooksack River is a gravel and sand bed channel with a snowmelt dominated hydrograph. Engineered log jams (ELJ) have been employed to direct flow into side and chute channels with the larger goals of increasing overall channel complexity and salmon spawning opportunities. ELJs have been constructed on the channel since the 2000s, and the ELJs in the study reaches range in age up to 10 years. The size and design of individual jams within the reach vary, enabling a comparison between jam types. ELJs are evaluated for their ability to maintain gravel bar locations and open tributary channels through the snowmelt season over the reach scale. Additional goals of trapping wood onto the jams and existing bars, stabilizing channel banks, and allowing for the growth of bar vegetation are also examined.

Fading channel simulator

DOEpatents

Argo, Paul E.; Fitzgerald, T. Joseph

1993-01-01

Fading channel effects on a transmitted communication signal are simulated with both frequency and time variations using a channel scattering function to affect the transmitted signal. A conventional channel scattering function is converted to a series of channel realizations by multiplying the square root of the channel scattering function by a complex number of which the real and imaginary parts are each independent variables. The two-dimensional inverse-FFT of this complex-valued channel realization yields a matrix of channel coefficients that provide a complete frequency-time description of the channel. The transmitted radio signal is segmented to provide a series of transmitted signal and each segment is subject to FFT to generate a series of signal coefficient matrices. The channel coefficient matrices and signal coefficient matrices are then multiplied and subjected to inverse-FFT to output a signal representing the received affected radio signal. A variety of channel scattering functions can be used to characterize the response of a transmitter-receiver system to such atmospheric effects.

Amazon floodplain channels regulate channel-floodplain water exchange

NASA Astrophysics Data System (ADS)

Bates, P. D.; Baugh, C.; Trigg, M.

2017-12-01

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

Structural stability of purified human CFTR is systematically improved by mutations in nucleotide binding domain 1.

PubMed

Yang, Zhengrong; Hildebrandt, Ellen; Jiang, Fan; Aleksandrov, Andrei A; Khazanov, Netaly; Zhou, Qingxian; An, Jianli; Mezzell, Andrew T; Xavier, Bala M; Ding, Haitao; Riordan, John R; Senderowitz, Hanoch; Kappes, John C; Brouillette, Christie G; Urbatsch, Ina L

2018-05-01

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is an ABC transporter containing two transmembrane domains forming a chloride ion channel, and two nucleotide binding domains (NBD1 and NBD2). CFTR has presented a formidable challenge to obtain monodisperse, biophysically stable protein. Here we report a comprehensive study comparing effects of single and multiple NBD1 mutations on stability of both the NBD1 domain alone and on purified full length human CFTR. Single mutations S492P, A534P, I539T acted additively, and when combined with M470V, S495P, and R555K cumulatively yielded an NBD1 with highly improved structural stability. Strategic combinations of these mutations strongly stabilized the domain to attain a calorimetric T m  > 70 °C. Replica exchange molecular dynamics simulations on the most stable 6SS-NBD1 variant implicated fluctuations, electrostatic interactions and side chain packing as potential contributors to improved stability. Progressive stabilization of NBD1 directly correlated with enhanced structural stability of full-length CFTR protein. Thermal unfolding of the stabilized CFTR mutants, monitored by changes in intrinsic fluorescence, demonstrated that Tm could be shifted as high as 67.4 °C in 6SS-CFTR, more than 20 °C higher than wild-type. H1402S, an NBD2 mutation, conferred CFTR with additional thermal stability, possibly by stabilizing an NBD-dimerized conformation. CFTR variants with NBD1-stabilizing mutations were expressed at the cell surface in mammalian cells, exhibited ATPase and channel activity, and retained these functions to higher temperatures. The capability to produce enzymatically active CFTR with improved structural stability amenable to biophysical and structural studies will advance mechanistic investigations and future cystic fibrosis drug development. Copyright © 2018 Elsevier B.V. All rights reserved.

Interaction of Gortler vortices and Tollmien-Schlichting waves in curved channel flow

NASA Technical Reports Server (NTRS)

Daudpota, Q. Isa; Zang, Thomas A.; Hall, Philip

1987-01-01

The flow in a two-dimensional curved channel driven by an azimuthal pressure gradient can become linearly unstable due to axisymmetric perturbations and/or nonaxisymmetric perturbations depending on the curvature of the channel and the Reynolds number. For a particular small value of curvature, the critical Reynolds number for both these perturbations becomes identical. In the neighborhood of this curvature value and critical Reynolds number, nonlinear interactions occur between these perturbations. The Stuart-Watson approach is used to derive two coupled Landau equations for the amplitudes of these perturbations. The stability of the various possible states of these perturbations is shown through bifurcation diagrams. Emphasis is given to those cases which have relevance to external flows.

Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel

PubMed Central

Boiteux, Céline; Vorobyov, Igor; French, Robert J.; French, Christopher; Yarov-Yarovoy, Vladimir; Allen, Toby W.

2014-01-01

Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the “hinged lid”-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water–protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID:25136136

Suspended-sediment yields and stream-channel processes on Judy's Branch watershed in the St. Louis Metro East region in Illinois

USGS Publications Warehouse

Straub, Timothy D.; Johnson, Gary P.; Roseboom, Donald P.; Sierra, Carlos R.

2006-01-01

Judy's Branch watershed, a small basin (8.64 square miles) in the St. Louis Metro East region in Illinois, was selected as a pilot site to determine suspended-sediment yields and stream-channel processes in the bluffs and American Bottoms (expansive low-lying valley floor in the region). Suspended-sediment and stream-chan-nel data collected and analyzed for Judy's Branch watershed are presented in this report to establish a baseline of data for water-resource managers to evaluate future stream rehabilitation and manage-ment alternatives. The sediment yield analysis determines the amount of sediment being delivered from the watershed and two subwatersheds: an urban tributary and an undeveloped headwater (pri-marily agricultural). The analysis of the subwater-sheds is used to compare the effects of urbanization on sediment yield to the river. The stream-channel contribution to sediment yield was determined by evaluation of the stream-channel processes operat-ing on the streambed and banks of Judy's Branch watershed. Bank stability was related to hydrologic events, bank stratigraphy, and channel geometry through model development and simulation. The average suspended-sediment yield from two upland subwatersheds (drainage areas of 0.23 and 0.40 sq.mi. was 1,163 tons per square mile per year (tons/sq.mi.-year) between July 2000 and June 2004. The suspended-sediment yield at the Route 157 station was 2,523 tons/sq.mi.-year, near the outlet of Judy's Branch watershed (drainage area = 8.33 sq.mi.). This is approximately 1,360 tons/sq.mi.-year greater than the average at the upland stations for the same time period. This result is unexpected in that, generally, the suspended-sediment yield decreases as the watershed area increases because of sediment stored in the channel and flood plain. The difference indicates a possible increase in yield from a source, such as bank retreat, and supports the concept that land-use changes increase stream-flows that may in turn result in

Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baconguis, Isabelle; Gouaux, Eric

2012-07-29

Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na +-selective currents in chicken ASIC1a at pH7.25 and 5.5, respectively. Crystal structures of ASIC1a–psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH7.25 the pore is approximately 10Å in diameter, whereas at pH5.5 the poremore » is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7Å, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.« less

Fluvial processes and passive rehabilitation of the Lisbon Bottom side-channel chute, Lower Missouri River

USGS Publications Warehouse

Jacobson, Robert B.; Laustrup, Mark S.; Chapman, Michael D.

2001-01-01

Multiple large floods in 1993-1997 on the Lower Missouri River carved a side-channel chute through the river bottom at Lisbon, Missouri. Although similar in some respects to engineered side-channel chutes designed for habitat rehabilitation projects, the Lisbon Bottom chute has been unique in that it was allowed to evolve for more than four years with minimal stabilization. During the wet years, 1996-1999, the chute was subjected to abnormally high discharges and passed as much as 20% of the total discharge of the Missouri River. Relatively unrestrained fluvial processes during this time created a wide channel with highly diverse habitats. The upper one-half of the chute established a shallow, braided channel morphology similar to the pre-managed Missouri River. The lower half established a dynamically migrating, single-thread channel, and an incipient flood plain. Compared to the adjacent navigation channel, the chute established substantial areas of shallow, slow-velocity aquatic habitat that is considered to be in short supply in the present-day Lower Missouri River. The shortterm biological benefits have been mixed: the chute has fewer waterbird and benthic macroinvertebrate taxa than adjacent riverine habitats, but greater numbers of fish species compared to the navigation channel.

Stability of multiloop LQ regulators with nonlinearities. I - Regions of attraction. II - Regions of ultimate boundedness

NASA Technical Reports Server (NTRS)

Joshi, S. M.

1986-01-01

An investigation is conducted for the closed loop stability of linear time-invariant systems controlled by linear quadratic (LQ) regulators, in cases where nonlinearities exist in the control channels lying outside the stability sector in regions away from the origin. The estimate of the region of attraction thus obtained furnishes methods for the selection of performance function weights for more robust LQ designs. Attention is then given to the closed loop stability of linear time-invariant systems controlled by the LQ regulators when the nonlinearities in the loops escape the stability sector in a bounded region containing the origin.

Simulating bank erosion over an extended natural sinuous river reach using a universal slope stability algorithm coupled with a morphodynamic model

NASA Astrophysics Data System (ADS)

Rousseau, Yannick Y.; Van de Wiel, Marco J.; Biron, Pascale M.

2017-10-01

Meandering river channels are often associated with cohesive banks. Yet only a few river modelling packages include geotechnical and plant effects. Existing packages are solely compatible with single-threaded channels, require a specific mesh structure, derive lateral migration rates from hydraulic properties, determine stability based on friction angle, rely on nonphysical assumptions to describe cutoffs, or exclude floodplain processes and vegetation. In this paper, we evaluate the accuracy of a new geotechnical module that was developed and coupled with Telemac-Mascaret to address these limitations. Innovatively, the newly developed module relies on a fully configurable, universal genetic algorithm with tournament selection that permits it (1) to assess geotechnical stability along potentially unstable slope profiles intersecting liquid-solid boundaries, and (2) to predict the shape and extent of slump blocks while considering mechanical plant effects, bank hydrology, and the hydrostatic pressure caused by flow. The profiles of unstable banks are altered while ensuring mass conservation. Importantly, the new stability module is independent of mesh structure and can operate efficiently along multithreaded channels, cutoffs, and islands. Data collected along a 1.5-km-long reach of the semialluvial Medway Creek, Canada, over a period of 3.5 years are used to evaluate the capacity of the coupled model to accurately predict bank retreat in meandering river channels and to evaluate the extent to which the new model can be applied to a natural river reach located in a complex environment. Our results indicate that key geotechnical parameters can indeed be adjusted to fit observations, even with a minimal calibration effort, and that the model correctly identifies the location of the most severely eroded bank regions. The combined use of genetic and spatial analysis algorithms, in particular for the evaluation of geotechnical stability independently of the hydrodynamic

Conformational heterogeneity in closed and open states of the KcsA potassium channel in lipid bicelles

PubMed Central

Kim, Dorothy M.; Dikiy, Igor; Upadhyay, Vikrant; Posson, David J.

2016-01-01

The process of ion channel gating—opening and closing—involves local and global structural changes in the channel in response to external stimuli. Conformational changes depend on the energetic landscape that underlies the transition between closed and open states, which plays a key role in ion channel gating. For the prokaryotic, pH-gated potassium channel KcsA, closed and open states have been extensively studied using structural and functional methods, but the dynamics within each of these functional states as well as the transition between them is not as well understood. In this study, we used solution nuclear magnetic resonance (NMR) spectroscopy to investigate the conformational transitions within specific functional states of KcsA. We incorporated KcsA channels into lipid bicelles and stabilized them into a closed state by using either phosphatidylcholine lipids, known to favor the closed channel, or mutations designed to trap the channel shut by disulfide cross-linking. A distinct state, consistent with an open channel, was uncovered by the addition of cardiolipin lipids. Using selective amino acid labeling at locations within the channel that are known to move during gating, we observed at least two different slowly interconverting conformational states for both closed and open channels. The pH dependence of these conformations and the predictable disruptions to this dependence observed in mutant channels with altered pH sensing highlight the importance of conformational heterogeneity for KcsA gating. PMID:27432996

Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats.

PubMed

Nassoiy, Sean P; Byron, Kenneth L; Majetschak, Matthias

2017-01-17

Recent evidence suggests that drugs targeting Kv7 channels could be used to modulate vascular function and blood pressure. Here, we studied whether Kv7 channel inhibitors can be utilized to stabilize hemodynamics and reduce resuscitation fluid requirements after hemorrhagic shock. Anesthetized male Sprague-Dawley rats were instrumented with arterial and venous catheters for blood pressure monitoring, hemorrhage and fluid resuscitation. Series 1: Linopirdine (Kv7 channel blocker, 0.1-6 mg/kg) or retigabine (Kv7 channel activator, 0.1-12 mg/kg) were administered to normal animals. Series 2: Animals were hemorrhaged to a MAP of 25 mmHg for 30 min, followed by fluid resuscitation with normal saline (NS) to a MAP of 70 mmHg until t = 75 min. Animals were treated with single bolus injections of vehicle, linopirdine (1-6 mg/kg), XE-991 (structural analogue of linopirdine with higher potency for channel blockade, 1 mg/kg) prior to fluid resuscitation. Series 3: Animals were resuscitated with NS alone or NS supplemented with linopirdine (1.25-200 μg/mL). Data were analyzed with 2-way ANOVA/Bonferroni post-hoc testing. Series 1: Linopirdine transiently (10-15 min) and dose-dependently increased MAP by up to 15%. Retigabine dose-dependently reduced MAP by up to 60%, which could be reverted with linopirdine. Series 2: Fluid requirements to maintain MAP at 70 mmHg were 65 ± 34 mL/kg with vehicle, and 57 ± 13 mL/kg, 22 ± 8 mL/kg and 22 ± 11 mL/kg with intravenous bolus injection of 1, 3 and 6 mg/kg linopirdine, respectively. XE-991 (1 mg/kg), reduced resuscitation requirements comparable to 3 mg/kg linopirdine. Series 3: When resuscitation was performed with linopirdine-supplemented normal saline (NS), fluid requirements to stabilize MAP were 73 ± 12 mL/kg with NS alone and 72 ± 24, 61 ± 20, 36 ± 9 and 31 ± 9 mL/kg with NS supplemented with 1.25, 6.25, 12.5 and 200 μg/mL linopirdine, respectively. Our data suggest that Kv7

Instruments at the Lowell Observatory Discovery Channel Telescope (DCT)

NASA Astrophysics Data System (ADS)

Jacoby, George H.; Bida, Thomas A.; Fischer, Debra; Horch, Elliott; Kutyrev, Alexander; Mace, Gregory N.; Massey, Philip; Roe, Henry G.; Prato, Lisa A.

2017-01-01

The Lowell Observatory Discovery Channel Telescope (DCT) has been in full science operation for 2 years (2015 and 2016). Five instruments have been commissioned during that period, and two additional instruments are planned for 2017. These include:+ Large Monolithic Imager (LMI) - a CCD imager (12.6 arcmin FoV)+ DeVeny - a general purpose optical spectrograph (2 arcmin slit length, 10 grating choices)+ NIHTS - a low resolution (R=160) YJHK spectrograph (1.3 arcmin slit)+ DSSI - a two-channel optical speckle imager (5 arcsec FoV)+ IGRINS - a high resolution (45,000) HK spectrograph, on loan from the University of Texas.In the upcoming year, instruments will be delivered from the University of Maryland (RIMAS - a YJHK imager/spectrograph) and from Yale University (EXPRES - a very high resolution stabilized optical echelle for PRV).Each of these instruments will be described, along with their primary science goals.

XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction

DOE PAGES

Thomaston, Jessica L.; Woldeyes, Rahel A.; Nakane, Takanori; ...

2017-08-23

The M2 proton channel of influenza A is a drug target that is essential for the reproduction of the flu virus. It is also a model system for the study of selective, unidirectional proton transport across a membrane. Ordered water molecules arranged in “wires” inside the channel pore have been proposed to play a role in both the conduction of protons to the four gating His37 residues and the stabilization of multiple positive charges within the channel. To visualize the solvent in the pore of the channel at room temperature while minimizing the effects of radiation damage, data were collectedmore » to a resolution of 1.4 Å using an X-ray free-electron laser (XFEL) at three different pH conditions: pH 5.5, pH 6.5, and pH 8.0. Data were collected on the Inward open state, which is an intermediate that accumulates at high protonation of the His37 tetrad. At pH 5.5, a continuous hydrogen-bonded network of water molecules spans the vertical length of the channel, consistent with a Grotthuss mechanism model for proton transport to the His37 tetrad. This ordered solvent at pH 5.5 could act to stabilize the positive charges that build up on the gating His37 tetrad during the proton conduction cycle. The number of ordered pore waters decreases at pH 6.5 and 8.0, where the Inward open state is less stable. Furthermore, these studies provide a graphical view of the response of water to a change in charge within a restricted channel environment.« less

XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomaston, Jessica L.; Woldeyes, Rahel A.; Nakane, Takanori

The M2 proton channel of influenza A is a drug target that is essential for the reproduction of the flu virus. It is also a model system for the study of selective, unidirectional proton transport across a membrane. Ordered water molecules arranged in “wires” inside the channel pore have been proposed to play a role in both the conduction of protons to the four gating His37 residues and the stabilization of multiple positive charges within the channel. To visualize the solvent in the pore of the channel at room temperature while minimizing the effects of radiation damage, data were collectedmore » to a resolution of 1.4 Å using an X-ray free-electron laser (XFEL) at three different pH conditions: pH 5.5, pH 6.5, and pH 8.0. Data were collected on the Inward open state, which is an intermediate that accumulates at high protonation of the His37 tetrad. At pH 5.5, a continuous hydrogen-bonded network of water molecules spans the vertical length of the channel, consistent with a Grotthuss mechanism model for proton transport to the His37 tetrad. This ordered solvent at pH 5.5 could act to stabilize the positive charges that build up on the gating His37 tetrad during the proton conduction cycle. The number of ordered pore waters decreases at pH 6.5 and 8.0, where the Inward open state is less stable. Furthermore, these studies provide a graphical view of the response of water to a change in charge within a restricted channel environment.« less

The Earliest Ion Channels in Protocellular Membranes

NASA Technical Reports Server (NTRS)

Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

2010-01-01

Cellular membranes with their hydrophobic interior are virtually impermeable to ions. Bulk of ion transport through them is enabled through ion channels. Ion channels of contemporary cells are complex protein molecules which span the membrane creating a cylindrical pore filled with water. Protocells, which are widely regarded as precursors to modern cells, had similarly impermeable membranes, but the set of proteins in their disposal was much simpler and more limited. We have been, therefore, exploring an idea that the first ion channels in protocellular membranes were formed by much smaller peptide molecules that could spontaneously selfassemble into short-lived cylindrical bundles in a membrane. Earlier studies have shown that a group of peptides known as peptaibols is capable of forming ion channels in lipid bilayers when they are exposed to an electric field. Peptaibols are small, non-genetically encoded peptides produced by some fungi as a part of their system of defense against bacteria. They are usually only 14-20 residues long, which is just enough to span the membrane. Their sequence is characterized by the presence of non-standard amino acids which, interestingly, are also expected to have existed on the early earth. In particular, the presence of 2-aminoisobutyric acid (AIB) gives peptaibols strong helix forming propensities. Association of the helices inside membranes leads to the formation of cylindrical bundles, typically containing 4 to 10 monomers. Although peptaibols are excellent candidates for models of the earliest ion channels their structures, which are stabilized only by van der Waals forces and occasional hydrogen bonds between neighboring helices, are not very stable. Although it might properly reflect protobiological reality, it is also a major obstacle in studying channel behavior. For this reason we focused on two members of the peptaibol family, trichotoxin and antiamoebin, which are characterized by a single conductance level. This

The earliest ion channels in protocellular membranes

NASA Astrophysics Data System (ADS)

Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

Cellular membranes with their hydrophobic interior are virtually impermeable to ions. Bulk of ion transport through them is enabled through ion channels. Ion channels of contemporary cells are complex protein molecules which span the membrane creating a cylindrical pore filled with water. Protocells, which are widely regarded as precursors to modern cells, had similarly impermeable membranes, but the set of proteins in their disposal was much simpler and more limited. We have been, therefore, exploring an idea that the first ion channels in protocellular membranes were formed by much smaller peptide molecules that could spontaneously self-assemble into short-lived cylindrical bundles in a membrane. Earlier studies have shown that a group of peptides known as peptaibols is capable of forming ion channels in lipid bilayers when they are exposed to an electric field. Peptaibols are small, non-genetically encoded peptides produced by some fungi as a part of their system of defense against bacteria. They are usually only 14-20 residues long, which is just enough to span the membrane. Their sequence is characterized by the presence of non-standard amino acids which, interestingly, are also expected to have existed on the early earth. In particular, the presence of 2-aminoisobutyric acid (AIB) gives peptaibols strong helix forming propensities. Association of the helices inside membranes leads to the formation of cylindrical bundles, typically containing 4 to 10 monomers. Although peptaibols are excellent candidates for models of the earliest ion channels their struc-tures, which are stabilized only by van der Waals forces and occasional hydrogen bonds between neighboring helices, are not very stable. Although it might properly reflect protobiological real-ity, it is also a major obstacle in studying channel behavior. For this reason we focused on two members of the peptaibol family, trichotoxin and antiamoebin, which are characterized by a single conductance level. This

Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution.

PubMed

Shen, Huaizong; Zhou, Qiang; Pan, Xiaojing; Li, Zhangqiang; Wu, Jianping; Yan, Nieng

2017-03-03

Voltage-gated sodium (Na v ) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Na v channel from American cockroach (designated Na v PaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSD I , and a carboxy-terminal domain binds to the III-IV linker. The structure of Na v PaS establishes an important foundation for understanding function and disease mechanism of Na v and related voltage-gated calcium channels. Copyright © 2017, American Association for the Advancement of Science.

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis.

PubMed

De Franceschi, Lucia; Rivera, Alicia; Fleming, Mark D; Honczarenko, Marek; Peters, Luanne L; Gascard, Philippe; Mohandas, Narla; Brugnara, Carlo

2005-08-15

It has been shown that mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis) and decreased membrane stability. Here, we characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75 +/- 1.06 vs 6.08 +/- 0.09 mM cell x minute; P < .04) and a decrease in Km (1.01 +/- 0.06 vs 1.47 +/- 1.02 microM; P < .03), indicating an increased sensitivity to activation by intracellular calcium. In vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker. Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival and increased numbers of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, potassium and water loss through the Gardos channel may play an important protective role in compensating for the reduced surface-membrane area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments.

Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains

PubMed Central

Garcia-Olivares, Jennie; Alekov, Alexi; Boroumand, Mohammad Reza; Begemann, Birgit; Hidalgo, Patricia; Fahlke, Christoph

2008-01-01

Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability PMID:18801843

Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains.

PubMed

Garcia-Olivares, Jennie; Alekov, Alexi; Boroumand, Mohammad Reza; Begemann, Birgit; Hidalgo, Patricia; Fahlke, Christoph

2008-11-15

Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability.

Phase stabilization of multidimensional amplification architectures for ultrashort pulses

NASA Astrophysics Data System (ADS)

Müller, M.; Kienel, M.; Klenke, A.; Eidam, T.; Limpert, J.; Tünnermann, A.

2015-03-01

The active phase stabilization of spatially and temporally combined ultrashort pulses is investigated theoretically and experimentally. Particularly, considering a combining scheme applying 2 amplifier channels and 4 divided-pulse replicas a bistable behavior is observed. The reason is mutual influence of the optical error signals that is intrinsic to temporal polarization beam combining. A successful mitigation strategy is proposed and is analyzed theoretically and experimentally.

Extracellular blockade of K(+) channels by TEA: results from molecular dynamics simulations of the KcsA channel.

PubMed

Crouzy, S; Bernèche, S; Roux, B

2001-08-01

mutant channel. The enhanced stability conferred by the tyrosine residues does not arise from Pi-cation interactions, but appears to be due to differences in the hydration structure of the TEA. Finally, it is shown that the experimentally observed voltage dependence of TEA block, which is traditionally interpreted in terms of the physical position of the TEA along the axis of the pore, must arise indirectly via coupling with the ions in the pore.

The role of entropic potential in voltage activation and K+ transport through Kv 1.2 channels

NASA Astrophysics Data System (ADS)

Wawrzkiewicz-Jałowiecka, Agata; Grzywna, Zbigniew J.

2018-03-01

We analyze the entropic effects of inner pore geometry changes of Kv 1.2 channel during membrane depolarization and their implications for the rate of transmembrane transport of potassium ions. We base this on the idea that spatial confinements within the channel pore give rise to entropic barriers which can both effectively affect the stability of open macroconformation and influence channel's ability to conduct the potassium ions through the membrane. First, we calculate the differences in entropy between voltage-activated and resting states of the channel. As a template, we take a set of structures of channel pore in an open state at different membrane potentials generated in our previous research. The obtained results indicate that tendency to occupy open states at membrane depolarization is entropy facilitated. Second, we describe the differences in rates of K+ transport through the channel pore at different voltages based on the results of appropriate random walk simulations in entropic and electric potentials. The simulated single channel currents (I) suggest that the geometry changes during membrane depolarization are an important factor contributing to the observed flow of potassium ions through the channel. Nevertheless, the charge distribution within the channel pore (especially at the extracellular entrance) seems most prominent for the observed I/Imax relation at a qualitative level at analyzed voltages.

A Fast, Open EEG Classification Framework Based on Feature Compression and Channel Ranking

PubMed Central

Han, Jiuqi; Zhao, Yuwei; Sun, Hongji; Chen, Jiayun; Ke, Ang; Xu, Gesen; Zhang, Hualiang; Zhou, Jin; Wang, Changyong

2018-01-01

Superior feature extraction, channel selection and classification methods are essential for designing electroencephalography (EEG) classification frameworks. However, the performance of most frameworks is limited by their improper channel selection methods and too specifical design, leading to high computational complexity, non-convergent procedure and narrow expansibility. In this paper, to remedy these drawbacks, we propose a fast, open EEG classification framework centralized by EEG feature compression, low-dimensional representation, and convergent iterative channel ranking. First, to reduce the complexity, we use data clustering to compress the EEG features channel-wise, packing the high-dimensional EEG signal, and endowing them with numerical signatures. Second, to provide easy access to alternative superior methods, we structurally represent each EEG trial in a feature vector with its corresponding numerical signature. Thus, the recorded signals of many trials shrink to a low-dimensional structural matrix compatible with most pattern recognition methods. Third, a series of effective iterative feature selection approaches with theoretical convergence is introduced to rank the EEG channels and remove redundant ones, further accelerating the EEG classification process and ensuring its stability. Finally, a classical linear discriminant analysis (LDA) model is employed to classify a single EEG trial with selected channels. Experimental results on two real world brain-computer interface (BCI) competition datasets demonstrate the promising performance of the proposed framework over state-of-the-art methods. PMID:29713262

Structure of Voltage-gated Two-pore Channel TPC1 from Arabidopsis thaliana

PubMed Central

Guo, Jiangtao; Zeng, Weizhong; Chen, Qingfeng; Lee, Changkeun; Chen, Liping; Yang, Yi; Cang, Chunlei; Ren, Dejian; Jiang, Youxing

2015-01-01

Two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in both animals and plants as organellar cation channels. Here, we present the first crystal structure of a vacuolar two-pore channel from Arabidopsis thaliana, AtTPC1, which functions as a homodimer. AtTPC1 activation requires both voltage and cytosolic Ca2+. Ca2+ binding to the cytosolic EF-hand domain triggers conformational changes coupled to the pair of pore-lining inner helices (IS6 helices) from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain (VSD2) whose conformational changes are coupled to the pair of inner helices (IIS6 helices) from the second 6-TM domains. Luminal Ca2+ or Ba2+ can modulate voltage activation by stabilizing VSD2 in the resting state and shifts voltage activation towards more positive potentials. Our Ba2+ bound AtTPC1 structure reveals a voltage sensor in the resting state, providing hitherto unseen structural insight into the general voltage-gating mechanism among voltage-gated channels. PMID:26689363

Allosteric modulation balances thermodynamic stability and restores function of ΔF508 CFTR

PubMed Central

Aleksandrov, Andrei A.; Kota, Pradeep; Cui, Liying; Jensen, Tim; Alekseev, Alexey E.; Reyes, Santiago; He, Lihua; Gentzsch, Martina; Aleksandrov, Luba A.; Dokholyan, Nikolay V.; Riordan, John R.

2013-01-01

Most cystic fibrosis is caused by a deletion of a single residue (F508) in CFTR that disrupts the folding and biosynthetic maturation of the ion channel protein. Progress towards understanding the underlying mechanisms and overcoming the defect remain incomplete. Here we show that the thermal instability of human ΔF508 CFTR channel activity evident in both cell-attached membrane patches and planar phospholipid bilayers is not observed in corresponding mutant CFTRs of several non-mammalian species. These more stable orthologs are distinguished from their mammalian counterparts by the substitution of proline residues at several key dynamic locations in the first nucleotide domain (NBD1), including the structurally diverse region (SDR), the gamma phosphate switch loop and the Regulatory Insertion (RI). Molecular Dynamic analyses revealed that addition of the prolines could reduce flexibility at these locations and increase the temperatures of unfolding transitions of ΔF508 NBD1 to that of the wild-type. Introduction of these prolines experimentally into full-length human ΔF508 CFTR together with the already recognized I539T suppressor mutation, also in the SDR, restored channel function and thermodynamic stability as well as its trafficking to and lifetime at the cell surface. Thus, while cellular manipulations that circumvent its culling by quality control systems leave ΔF508 CFTR dysfunctional at physiological temperature, restoration of the delicate balance between the dynamic protein’s inherent stability and channel activity returns a near-normal state. PMID:22406676

Identification of potential novel interaction partners of the sodium-activated potassium channels Slick and Slack in mouse brain.

PubMed

Rizzi, Sandra; Schwarzer, Christoph; Kremser, Leopold; Lindner, Herbert H; Knaus, Hans-Günther

2015-12-01

The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are paralogous channels of the Slo family of high-conductance potassium channels. Slick and Slack channels are widely distributed in the mammalian CNS and they play a role in slow afterhyperpolarization, generation of depolarizing afterpotentials and in setting and stabilizing the resting potential. In the present study we used a combined approach of (co)-immunoprecipitation studies, Western blot analysis, double immunofluorescence and mass spectrometric sequencing in order to investigate protein-protein interactions of the Slick and Slack channels. The data strongly suggest that Slick and Slack channels co-assemble into identical cellular complexes. Double immunofluorescence experiments revealed that Slick and Slack channels co-localize in distinct mouse brain regions. Moreover, we identified the small cytoplasmic protein beta-synuclein and the transmembrane protein 263 (TMEM 263) as novel interaction partners of both, native Slick and Slack channels. In addition, the inactive dipeptidyl-peptidase (DPP 10) and the synapse associated protein 102 (SAP 102) were identified as constituents of the native Slick and Slack channel complexes in the mouse brain. This study presents new insights into protein-protein interactions of native Slick and Slack channels in the mouse brain.

Channel characteristics and coordination in three-echelon dual-channel supply chain

NASA Astrophysics Data System (ADS)

Saha, Subrata

2016-02-01

We explore the impact of channel structure on the manufacturer, the distributer, the retailer and the entire supply chain by considering three different channel structures in radiance of with and without coordination. These structures include a traditional retail channel and two manufacturer direct channels with and without consistent pricing. By comparing the performance of the manufacturer, the distributer and the retailer, and the entire supply chain in three different supply chain structures, it is established analytically that, under some conditions, a dual channel can outperform a single retail channel; as a consequence, a coordination mechanism is developed that not only coordinates the dual channel but also outperforms the non-cooperative single retail channel. All the analytical results are further analysed through numerical examples.

Differential distribution of the sodium-activated potassium channels slick and slack in mouse brain.

PubMed

Rizzi, Sandra; Knaus, Hans-Günther; Schwarzer, Christoph

2016-07-01

The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high-conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093-2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Differential distribution of the sodium‐activated potassium channels slick and slack in mouse brain

PubMed Central

Knaus, Hans‐Günther; Schwarzer, Christoph

2015-01-01

ABSTRACT The sodium‐activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high‐conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093–2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26587966

B-52 stability augmentation system reliability

NASA Technical Reports Server (NTRS)

Bowling, T. C.; Key, L. W.

1976-01-01

The B-52 SAS (Stability Augmentation System) was developed and retrofitted to nearly 300 aircraft. It actively controls B-52 structural bending, provides improved yaw and pitch damping through sensors and electronic control channels, and puts complete reliance on hydraulic control power for rudder and elevators. The system has experienced over 300,000 flight hours and has exhibited service reliability comparable to the results of the reliability test program. Development experience points out numerous lessons with potential application in the mechanization and development of advanced technology control systems of high reliability.

Therapeutic targeting of two-pore-domain potassium (K(2P)) channels in the cardiovascular system.

PubMed

Wiedmann, Felix; Schmidt, Constanze; Lugenbiel, Patrick; Staudacher, Ingo; Rahm, Ann-Kathrin; Seyler, Claudia; Schweizer, Patrick A; Katus, Hugo A; Thomas, Dierk

2016-05-01

The improvement of treatment strategies in cardiovascular medicine is an ongoing process that requires constant optimization. The ability of a therapeutic intervention to prevent cardiovascular pathology largely depends on its capacity to suppress the underlying mechanisms. Attenuation or reversal of disease-specific pathways has emerged as a promising paradigm, providing a mechanistic rationale for patient-tailored therapy. Two-pore-domain K(+) (K(2P)) channels conduct outward K(+) currents that stabilize the resting membrane potential and facilitate action potential repolarization. K(2P) expression in the cardiovascular system and polymodal K2P current regulation suggest functional significance and potential therapeutic roles of the channels. Recent work has focused primarily on K(2P)1.1 [tandem of pore domains in a weak inwardly rectifying K(+) channel (TWIK)-1], K(2P)2.1 [TWIK-related K(+) channel (TREK)-1], and K(2P)3.1 [TWIK-related acid-sensitive K(+) channel (TASK)-1] channels and their role in heart and vessels. K(2P) currents have been implicated in atrial and ventricular arrhythmogenesis and in setting the vascular tone. Furthermore, the association of genetic alterations in K(2P)3.1 channels with atrial fibrillation, cardiac conduction disorders and pulmonary arterial hypertension demonstrates the relevance of the channels in cardiovascular disease. The function, regulation and clinical significance of cardiovascular K(2P) channels are summarized in the present review, and therapeutic options are emphasized. © 2016 Authors; published by Portland Press Limited.

Field gamma-ray spectrometer GS256: measurements stability

NASA Astrophysics Data System (ADS)

Mojzeš, Andrej

2009-01-01

The stability of in situ readings of the portable gamma-ray spectrometer GS256 during the field season of 2006 was studied. The instrument is an impulse detector of gamma rays based on NaI(Tl) 3" × 3" scintillation unit and 256-channel spectral analyzer which allows simultaneous assessment of up to 8 radioisotopes in rocks. It is commonly used in surface geophysical survey for the measurement of natural 40K, 238U and 232Th but also artificial 137Cs quantities. The statistical evaluation is given of both repeated measurements - in the laboratory and at several field control points in different survey areas. The variability of values shows both the instrument stability and also the relative influence of some meteorological factors, mainly rainfalls. The analysis shows an acceptable level of instrument measurements stability, the necessity to avoid measurement under unfavourable meteorological conditions and to keep detailed field book information about time, position and work conditions.

Changes in vegetation and biological soil crust communities on sand dunes stabilizing after a century of grazing on San Miguel Island, Channel Island National Park, California

USGS Publications Warehouse

Zellman, Kristine L.

2014-01-01

San Miguel Island is the westernmost of the California Channel Islands and one of the windiest areas on the west coast of North America. The majority of the island is covered by coastal sand dunes, which were stripped of vegetation and subsequently mobilized due to droughts and sheep ranching during the late 19th century and early 20th century. Since the removal of grazing animals, vegetation and biological soil crusts have once again stabilized many of the island's dunes. In this study, historical aerial photographs and field surveys were used to develop a chronosequence of the pattern of change in vegetation communities and biological soil crust levels of development (LOD) along a gradient of dune stabilization. Historical aerial photographs from 1929, 1954, 1977, and 2009 were georeferenced and used to delineate changes in vegetation canopy cover and active (unvegetated) dune extent among 5 historical periods (pre-1929, 1929–1954, 1954–1977, 1977–2009, and 2009–2011). During fieldwork, vegetation and biological soil crust communities were mapped along transects distributed throughout San Miguel Island's central dune field on land forms that had stabilized during the 5 time periods of interest. Analyses in a geographic information system (GIS) quantified the pattern of changes that vegetation and biological soil crust communities have exhibited on the San Miguel Island dunes over the past 80 years. Results revealed that a continuing increase in total vegetation cover and a complex pattern of change in vegetation communities have taken place on the San Miguel Island dunes since the removal of grazing animals. The highly specialized native vascular vegetation (sea rocket, dunedelion, beach-bur, and locoweed) are the pioneer stabilizers of the dunes. This pioneer community is replaced in later stages by communities that are dominated by native shrubs (coastal goldenbush, silver lupine, coyote-brush, and giant coreopsis), with apparently overlapping or

The Interaction between Logjams, Channel Evolution, and Sports Fisheries on a Dam Regulated Low Gradient River.

NASA Astrophysics Data System (ADS)

Schenk, E.; Hupp, C. R.; Moulin, B.

2014-12-01

The purpose of our study was to determine the interaction between in-stream large wood (LW), bank erosion, and sports fisheries in the 210 river kilometer (km) Coastal Plain segment of the dam-regulated Roanoke River, North Carolina. Methods included collecting background geomorphic data including a 200 km channel geometry survey and measurements from 701 bank erosion pins at 36 cross-sections over 132 km. LW concentrations were evaluated over a 177 km reach using georeferenced aerial video taken during regulated low flow (56 m3/s). LW transport was measured using 290 radio tagged LW pieces (mean diameter = 35.0 cm, length = 9.3 m) installed between 2008 and 2010. Largemouth bass (Micropterus salmoides) were surveyed in 2010 at 29 sites using a boat mounted electroshock unit. The abundance of LW in logjams was 59 pieces/km and these were concentrated (21.5 logjams/km) in an actively eroding reach with relatively high sinuosity, high local LW production rates, and narrow channel widths. Most jams (70%) are available nearly year round as aquatic habitat, positioned either on the lower bank or submerged at low-water flows. The actively eroding reach is adjusting to upstream dam regulation by channel widening. The channel upstream of this reach has widened and stabilized while the channel downstream of the eroding reach is still relatively narrow but with lower bank erosion rates. Repeat surveys of radio tagged LW determined that transport was common throughout the study area despite dam regulation and a low channel gradient (0.0016). The mean distance travelled by a radio tagged piece of LW was 11.9 km with a maximum of 101 km (84 tags moved, 96 stationary, 110 not found). Radio tagged LW that moved during the study was found at low flow either in logjams (44%), as individual LW (43%), or submerged mid-channel (14%). Largemouth bass biomass density (g/hr effort) was highest in the actively eroding reach where logjams were most common. Our results support the

Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line.

PubMed

Drews, R; Pattyn, F; Hewitt, I J; Ng, F S L; Berger, S; Matsuoka, K; Helm, V; Bergeot, N; Favier, L; Neckel, N

2017-05-09

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers' size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability.

Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line

PubMed Central

Drews, R.; Pattyn, F.; Hewitt, I. J.; Ng, F. S. L.; Berger, S.; Matsuoka, K.; Helm, V.; Bergeot, N.; Favier, L.; Neckel, N.

2017-01-01

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers' size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability. PMID:28485400

Stability of miscible core?annular flows with viscosity stratification

NASA Astrophysics Data System (ADS)

Selvam, B.; Merk, S.; Govindarajan, Rama; Meiburg, E.

The linear stability of variable viscosity, miscible core-annular flows is investigated. Consistent with pipe flow of a single fluid, the flow is stable at any Reynolds number when the magnitude of the viscosity ratio is less than a critical value. This is in contrast to the immiscible case without interfacial tension, which is unstable at any viscosity ratio. Beyond the critical value of the viscosity ratio, the flow can be unstable even when the more viscous fluid is in the core. This is in contrast to plane channel flows with finite interface thickness, which are always stabilized relative to single fluid flow when the less viscous fluid is in contact with the wall. If the more viscous fluid occupies the core, the axisymmetric mode usually dominates over the corkscrew mode. It is demonstrated that, for a less viscous core, the corkscrew mode is inviscidly unstable, whereas the axisymmetric mode is unstable for small Reynolds numbers at high Schmidt numbers. For the parameters under consideration, the switchover occurs at an intermediate Schmidt number of about 500. The occurrence of inviscid instability for the corkscrew mode is shown to be consistent with the Rayleigh criterion for pipe flows. In some parameter ranges, the miscible flow is seen to be more unstable than its immiscible counterpart, and the physical reasons for this behaviour are discussed.A detailed parametric study shows that increasing the interface thickness has a uniformly stabilizing effect. The flow is least stable when the interface between the two fluids is located at approximately 0.6 times the tube radius. Unlike for channel flow, there is no sudden change in the stability with radial location of the interface. The instability originates mainly in the less viscous fluid, close to the interface.

Stream Channel Stability. Appendix E. Geomorphic Controls of Channel Stability,

DTIC Science & Technology

1981-04-01

first from late-Eocene to middle- Oligocene and the second from middle-Miocene to Pleistocene. These two times of cooling were separated by a warming ...Starkel, 1966). It was warm but rather dry with pronounced fluctuations in humidity. For the North American continent, however, climatic conditions were...post-glacial warming continued until 3500 to 4000 yr BP (Zumberge and Potzer, 1956). This was the warmest and driest period during the Holocene for

Development and application of hydraulic geometry equations for tidal channel restoration in Atlantic Canada

NASA Astrophysics Data System (ADS)

Graham, J.; van Proosdij, D.; Bowron, T.

2017-12-01

Tidal wetlands play a key role in our environment, particularly in the face of climate change and rising sea levels. Successful restoration of these coastal habitats requires a good understanding of the hydrology and morphology of the site. In Atlantic Canada, restoration design must consider significant variation in tidal range (1 to 16 m), sediment supply (50-70,000 mg/L) and winter conditions. In 2012 ground surveys, aerial photos and digital terrain data were used to conduct a morphometric analysis of representative tidal channels and to establish regional hydraulic geometry relationships to aid in restoration design. Channel morphology was strongly related to freshwater discharge and channel order while drainage density, channel length, and sinuosity were related to site history and maturity. Five years after the initial study, two restored salt marshes have been analyzed to assess the validity of the equations. At both marshes, tidal channels were excavated and erosion/accretion tracked for five years following restoration. Channels were found to experience rapid erosion in the first 2 years following restoration but to stabilize with dimensions on par with those predicted. Furthermore, both sites rapidly developed hybrid creek networks beyond the primary excavated channels when allowed to self design. The methodology has been used to design tidal channels for 2 additional sites. Although these sites have not been restored at present, hydrodynamic modeling supported channel dimension predictions, with acceptable in-channel velocities and flood extents simulated in the model. The authors conclude that the use of regional hydraulic geometry equations have been effective in salt marsh restoration design in Atlantic Canada, particularly when used in conjunction with other techniques such as hydrodynamic modeling and analysis of historic conditions.

Stability of isolated Barchan dunes

NASA Astrophysics Data System (ADS)

Fourrière, Antoine; Charru, François

2010-11-01

When sand grains are entrained by an air flow over a non-erodible ground, or with limited sediment supply from the bed, they form isolated dunes showing a remarkable crescentic shape with horns pointing downstream. These dunes, known as Barchan dunes, are commonly observed in deserts, with height of a few meters and velocity of a few meters per year (Bagnold 1941). These dunes also exist under water, at a much smaller, centimetric size (Franklin & Charru 2010). Their striking stability properties are not well understood yet. Two phenomena are likely to be involved in this stability: (i) relaxation effects of the sand flux which increases from the dune foot up to the crest, related to grain inertia or deposition, and (ii) a small transverse sand flux due to slope effects and the divergence of the streamlines of the fluid flow. We reproduced aqueous Barchan dunes in a channel, and studied their geometrical and dynamic properties (in particular their shape, velocity, minimum size, and rate of erosion). Using coloured glass beads (see the figure), we were then able to measure the particle flux over the whole dune surface. We will discuss the stability of these dunes in the light of our measurements.

Growth, Failure, and Erosion of Submarine Channel Levees on the Upper Mississippi Fan, Gulf of Mexico

NASA Astrophysics Data System (ADS)

Sawyer, D. E.; Flemings, P. B.; Nikolinakou, M. A.

2011-12-01

Late Pleistocene channel levees on the Mississippi Fan failed repeatedly along deep-seated listric faults. These growth faults begin at the top of the levee, as much as a kilometer away from the channel axis. They plunge 150-200 meters downward reaching their deepest point halfway towards the channel axis (0.5 km) along the base of a regional sand unit. They then rise toward the channel axis where they emerge. The erosion of toe-thrust material coupled with levee growth, promoted a dynamic equilibrium: turbidity currents flushed the channel axis and deposited new levee on the margins, which induced further displacement into the channel. With a geomechanical model we show that deep-seated failure occurred by undrained loading of an underlying low permeability mudstone. Excess pore pressure formed a low-strength layer that localized the detachment at the base of a regional sand. Our results show that deep-seated failure is expected when levee systems form above regional sand bodies that were deposited rapidly above low permeability mudstone. Furthermore, the presence of this failure style in channel-levee systems is a strong indicator that overpressures and low effective stresses were present during formation and thus record paleo-pressures. Understanding these systems is critical for the design of safe well penetrations, predicting hydraulic connectivity of deepwater channel sands, and the growth of submarine channel-levee systems. This study illuminates the linkages between sedimentation, erosion, and the mechanical stability of levees in submarine channel systems.

Multiple Interactions between Cytoplasmic Domains Regulate Slow Deactivation of Kv11.1 Channels*

PubMed Central

Ng, Chai Ann; Phan, Kevin; Hill, Adam P.; Vandenberg, Jamie I.; Perry, Matthew D.

2014-01-01

The intracellular domains of many ion channels are important for fine-tuning their gating kinetics. In Kv11.1 channels, the slow kinetics of channel deactivation, which are critical for their function in the heart, are largely regulated by the N-terminal N-Cap and Per-Arnt-Sim (PAS) domains, as well as the C-terminal cyclic nucleotide-binding homology (cNBH) domain. Here, we use mutant cycle analysis to probe for functional interactions between the N-Cap/PAS domains and the cNBH domain. We identified a specific and stable charge-charge interaction between Arg56 of the PAS domain and Asp803 of the cNBH domain, as well an additional interaction between the cNBH domain and the N-Cap, both of which are critical for maintaining slow deactivation kinetics. Furthermore, we found that positively charged arginine residues within the disordered region of the N-Cap interact with negatively charged residues of the C-linker domain. Although this interaction is likely more transient than the PAS-cNBD interaction, it is strong enough to stabilize the open conformation of the channel and thus slow deactivation. These findings provide novel insights into the slow deactivation mechanism of Kv11.1 channels. PMID:25074935

Heat transfer in the coolant channel of a heat-exchanger system based on fluctuation theories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz-Guilera, A.; Rodriguez, M.A.; Rubi, J.M.

1988-11-01

We present a model to study the heat transfer in the coolant channel of a heat-exchanger system. Such a model introduces thermal fluctuations as well as external noises due to different mechanisms of heat interchange. A unified treatment of both kinds of noise is carried out. The stationary mean value of the channel temperature is studied, obtaining effective transport coefficients which affect the stability of the system. The effects of the different noises are visualized in a correlation length obtained from the temperature correlation function. The model has practical implications in the field of nuclear-reactor noise theory.

Evaluation of stress stabilities in amorphous In-Ga-Zn-O thin-film transistors: Effect of passivation with Si-based resin

NASA Astrophysics Data System (ADS)

Ochi, Mototaka; Hino, Aya; Goto, Hiroshi; Hayashi, Kazushi; Fujii, Mami N.; Uraoka, Yukiharu; Kugimiya, Toshihiro

2018-02-01

Fabrication process conditions of a passivation (PV) layer correlated with stress stabilities of amorphous In-Ga-Zn-O (a-IGZO) thin-film transistors (TFTs). In etch-stop layer (ESL)-TFTs, by inserting a Si-based resin between SiN x and SiO x PV layers, the peak intensity in the photoinduced transient spectroscopy (PITS) spectrum was notably reduced. This suggested the suppression of hydrogen incorporation into a-IGZO, which led to the improvement of stability under negative bias thermal illumination stress (NBTIS). In contrast, the hydrogen-related defects in the a-IGZO were easily formed by the back-channel etch (BCE) process. Furthermore, it was found that, under NBTIS, the transfer curves of the BCE-TFTs shifted in parallel owing to the positive fixed charge located in the back channel of the a-IGZO TFTs. The hump-shaped shift increased with stress time. This is because hydrogen atoms located at the back-channel surfaces of the a-IGZO and/or PV layers were incorporated into the channel region of the BCE-TFTs and induced the hydrogen-related defects.

Channel nut tool

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, Marvin

A method, system, and apparatus for installing channel nuts includes a shank, a handle formed on a first end of a shank, and an end piece with a threaded shaft configured to receive a channel nut formed on the second end of the shaft. The tool can be used to insert or remove a channel nut in a channel framing system and then removed from the channel nut.

Microstructure stability of ultra-fine grained magnesium alloy AZ31 processed by extrusion and equal-channel angular pressing (EX–ECAP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stráská, Jitka, E-mail: straska.jitka@gmail.com; Janeček, Miloš, E-mail: janecek@met.mff.cuni.cz; Čížek, Jakub, E-mail: jcizek@mbox.troja.mff.cuni.cz

Thermal stability of the ultra-fine grained (UFG) microstructure of magnesium AZ31 alloy was investigated. UFG microstructure was achieved by a combined two-step severe plastic deformation process: the extrusion (EX) and subsequent equal-channel angular pressing (ECAP). This combined process leads to refined microstructure and enhanced microhardness. Specimens with UFG microstructure were annealed isochronally at temperatures 150–500 °C for 1 h. The evolution of microstructure, mechanical properties and dislocation density was studied by electron backscatter diffraction (EBSD), microhardness measurements and positron annihilation spectroscopy (PAS). The coarsening of the fine-grained structure at higher temperatures was accompanied by a gradual decrease of the microhardnessmore » and decrease of dislocation density. Mechanism of grain growth was studied by general equation for grain growth and Arrhenius equation. Activation energies for grain growth were calculated to be 115, 33 and 164 kJ/mol in temperature ranges of 170–210 °C, 210–400 °C and 400–500 °C (443–483 K, 483–673 K and 673–773 K), respectively. - Highlights: • Microhardness of UFG AZ31 alloy decreases with increasing annealing temperature. • This fact has two reasons: dislocation annihilations and/or grain growth. • The activation energies for grain growth were calculated for all temperature ranges.« less

The Role of Conjoining (Tie) Channels in Lowland Floodplain Development and Lake Infilling

NASA Astrophysics Data System (ADS)

Rowland, J. C.; Dietrich, W. E.; Day, G.; Lepper, K.; Wilson, C. J.

2003-12-01

, grain size characteristics, water levels and geochronological sampling using optically stimulated luminescence (OSL). Across all systems channel morphology is similar and exhibit scale independence, however, channel size and rates of progradation are directly related to the size of the main stem river. Through these studies and ongoing scaled modeling we are examining the morphodynamics that lead to the formation, advancement and stability of these unique self formed channels.

Identification of a Cholesterol-Binding Pocket in Inward Rectifier K+ (Kir) Channels

PubMed Central

Fürst, Oliver; Nichols, Colin G.; Lamoureux, Guillaume; D’Avanzo, Nazzareno

2014-01-01

Cholesterol is the major sterol component of all mammalian plasma membranes. Recent studies have shown that cholesterol inhibits both bacterial (KirBac1.1 and KirBac3.1) and eukaryotic (Kir2.1) inward rectifier K+ (Kir) channels. Lipid-sterol interactions are not enantioselective, and the enantiomer of cholesterol (ent-cholesterol) does not inhibit Kir channel activity, suggesting that inhibition results from direct enantiospecific binding to the channel, and not indirect effects of changes to the bilayer. Furthermore, conservation of the effect of cholesterol among prokaryotic and eukaryotic Kir channels suggests an evolutionary conserved cholesterol-binding pocket, which we aimed to identify. Computational experiments were performed by docking cholesterol to the atomic structures of Kir2.2 (PDB: 3SPI) and KirBac1.1 (PDB: 2WLL) using Autodock 4.2. Poses were assessed to ensure biologically relevant orientation and then clustered according to location and orientation. The stability of cholesterol in each of these poses was then confirmed by molecular dynamics simulations. Finally, mutation of key residues (S95H and I171L) in this putative binding pocket found within the transmembrane domain of Kir2.1 channels were shown to lead to a loss of inhibition by cholesterol. Together, these data provide support for this location as a biologically relevant pocket. PMID:25517146

Specific stabilization of CFTR by phosphatidylserine.

PubMed

Hildebrandt, Ellen; Khazanov, Netaly; Kappes, John C; Dai, Qun; Senderowitz, Hanoch; Urbatsch, Ina L

2017-02-01

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR, ABCC7) is a plasma membrane chloride ion channel in the ABC transporter superfamily. CFTR is a key target for cystic fibrosis drug development, and its structural elucidation would advance those efforts. However, the limited in vivo and in vitro stability of the protein, particularly its nucleotide binding domains, has made structural studies challenging. Here we demonstrate that phosphatidylserine uniquely stimulates and thermally stabilizes the ATP hydrolysis function of purified human CFTR. Among several lipids tested, the greatest stabilization was observed with brain phosphatidylserine, which shifted the Tm for ATPase activity from 22.7±0.8°C to 35.0±0.2°C in wild-type CFTR, and from 26.6±0.7°C to 42.1±0.2°C in a more stable mutant CFTR having deleted regulatory insertion and S492P/A534P/I539T mutations. When ATPase activity was measured at 37°C in the presence of brain phosphatidylserine, Vmax for wild-type CFTR was 240±60nmol/min/mg, a rate higher than previously reported and consistent with rates for other purified ABC transporters. The significant thermal stabilization of CFTR by phosphatidylserine may be advantageous in future structural and biophysical studies of CFTR. Copyright © 2016. Published by Elsevier B.V.

River channel patterns: Braided, meandering, and straight

USGS Publications Warehouse

Leopold, Luna Bergere; Wolman, M. Gordon

1957-01-01

Channel pattern is used to describe the plan view of a reach of river as seen from an airplane, and includes meandering, braiding, or relatively straight channels.Natural channels characteristically exhibit alternating pools or deep reaches and riffles or shallow reaches, regardless of the type of pattern. The length of the pool or distance between riffles in a straight channel equals the straight line distance between successive points of inflection in the wave pattern of a meandering river of the same width. The points of inflection are also shallow points and correspond to riffles in the straight channel. This distance, which is half the wavelength of the meander, varies approximately as a linear function of channel width. In the data we analysed the meander wavelength, or twice the distance between successive riffles, is from 7 to 12 times the channel width. It is concluded that the mechanics which may lead to meandering operate in straight channels.River braiding is characterized by channel division around alluvial islands. The growth of an island begins as the deposition of a central bar which results from sorting and deposition of the coarser fractions of the load which locally cannot be transported. The bar grows downstream and in height by continued deposition on its surface, forcing the water into the flanking channels, which, to carry the flow, deepen and cut laterally into the original banks. Such deepening locally lowers the water surface and the central bar emerges as an island which becomes stabilized by vegetation. Braiding was observed in a small river in a laboratory. Measurements of the adjustments of velocity, depth, width, and slope associated with island development lead to the conclusion that braiding is one of the many patterns which can maintain quasi-equilibrium among discharge, load, and transporting ability. Braiding does not necessarily indicate an excess of total load.Channel cross section and pattern are ultimately controlled by the

The channels of Mars

NASA Technical Reports Server (NTRS)

Baker, Victor R.

1988-01-01

The geomorphology of Mars is discussed, focusing on the Martian channels. The great flood channels of Mars, the processes of channel erosion, and dendritic channel networks, are examined. The topography of the Channeled Scabland region of the northwestern U.S. is described and compared to the Martian channels. The importance of water in the evolution of the channel systems is considered.

Conductive Channel for Energy Transmission

NASA Astrophysics Data System (ADS)

Apollonov, Victor V.

2011-11-01

For many years the attempts to create conductive channels of big length were taken in order to study the upper atmosphere and to settle special tasks, related to energy transmission. There upon the program of creation of "Impulsar" represents a great interest, as this program in a combination with high-voltage high repetition rate electrical source can be useful to solve the above mentioned problems (N. Tesla ideas for the days of high power lasers). The principle of conductive channel production can be shortly described as follows. The "Impulsar"—laser jet engine vehicle—propulsion take place under the influence of powerful high repetition rate pulse-periodic laser radiation. In the experiments the CO2—laser and solid state Nd:YAG laser systems had been used. Active impulse appears thanks to air breakdown (<30 km) or to the breakdown of ablated material on the board (>30 km), placed in the vicinity of the focusing mirror-acceptor of the breakdown waves. With each pulse of powerful laser the device rises up, leaving a bright and dense trace of products with high degree of ionization and metallization by conductive nano-particles due to ablation. Conductive dust plasma properties investigation in our experiments was produced by two very effective approaches: high power laser controlled ablation and by explosion of wire. Experimental and theoretical results of conductive canal modeling will be presented. The estimations show that with already experimentally demonstrated figures of specific thrust impulse the lower layers of the Ionosphere can be reached in several ten seconds that is enough to keep the high level of channel conductivity and stability with the help of high repetition rate high voltage generator. Some possible applications for new technology are highlighted.

Phosphatidic acid modulation of Kv channel voltage sensor function.

PubMed

Hite, Richard K; Butterwick, Joel A; MacKinnon, Roderick

2014-10-06

Membrane phospholipids can function as potent regulators of ion channel function. This study uncovers and investigates the effect of phosphatidic acid on Kv channel gating. Using the method of reconstitution into planar lipid bilayers, in which protein and lipid components are defined and controlled, we characterize two effects of phosphatidic acid. The first is a non-specific electrostatic influence on activation mediated by electric charge density on the extracellular and intracellular membrane surfaces. The second is specific to the presence of a primary phosphate group, acts only through the intracellular membrane leaflet and depends on the presence of a particular arginine residue in the voltage sensor. Intracellular phosphatidic acid accounts for a nearly 50 mV shift in the midpoint of the activation curve in a direction consistent with stabilization of the voltage sensor's closed conformation. These findings support a novel mechanism of voltage sensor regulation by the signaling lipid phosphatidic acid.

Phosphatidic acid modulation of Kv channel voltage sensor function

PubMed Central

Hite, Richard K; Butterwick, Joel A; MacKinnon, Roderick

2014-01-01

Membrane phospholipids can function as potent regulators of ion channel function. This study uncovers and investigates the effect of phosphatidic acid on Kv channel gating. Using the method of reconstitution into planar lipid bilayers, in which protein and lipid components are defined and controlled, we characterize two effects of phosphatidic acid. The first is a non-specific electrostatic influence on activation mediated by electric charge density on the extracellular and intracellular membrane surfaces. The second is specific to the presence of a primary phosphate group, acts only through the intracellular membrane leaflet and depends on the presence of a particular arginine residue in the voltage sensor. Intracellular phosphatidic acid accounts for a nearly 50 mV shift in the midpoint of the activation curve in a direction consistent with stabilization of the voltage sensor's closed conformation. These findings support a novel mechanism of voltage sensor regulation by the signaling lipid phosphatidic acid. DOI: http://dx.doi.org/10.7554/eLife.04366.001 PMID:25285449

Mechanism of the Pseudoirreversible Binding of Amantadine to the M2 Proton Channel.

PubMed

Llabrés, Salomé; Juárez-Jiménez, Jordi; Masetti, Matteo; Leiva, Rosana; Vázquez, Santiago; Gazzarrini, Sabrina; Moroni, Anna; Cavalli, Andrea; Luque, F Javier

2016-11-30

The M2 proton channel of influenza A virus is an integral membrane protein involved in the acidification of the viral interior, a step necessary for the release of the viral genetic material and replication of new virions. The aim of this study is to explore the mechanism of drug (un)binding to the M2 channel in order to gain insight into the structural and energetic features relevant for the development of novel inhibitors. To this end, we have investigated the binding of amantadine (Amt) to the wild type (wt) M2 channel and its V27A variant using multiple independent molecular dynamics simulations, exploratory conventional metadynamics, and multiple-walkers well-tempered metadynamics calculations. The results allow us to propose a sequential mechanism for the (un)binding of Amt to the wt M2 channel, which involves the adoption of a transiently populated intermediate (up state) leading to the thermodynamically favored down binding mode in the channel pore. Furthermore, they suggest that chloride anions play a relevant role in stabilizing the down binding mode of Amt to the wt channel, giving rise to a kinetic trapping that explains the experimentally observed pseudoirreversible inhibition of the wt channel by Amt. We propose that this trapping mechanism underlies the inhibitory activity of potent M2 channel blockers, as supported by the experimental confirmation of the irreversible binding of a pyrrolidine analogue from electrophysiological current assays. Finally, the results reveal that the thermodynamics and kinetics of Amt (un)binding is very sensitive to the V27A mutation, providing a quantitative rationale to the drastic decrease in inhibitory potency against the V27A variant. Overall, these findings pave the way to explore the inhibitory activity of Amt-related analogues in mutated M2 channel variants, providing guidelines for the design of novel inhibitors against resistant virus strains.

Influence of tidal range on the stability of coastal marshland

USGS Publications Warehouse

Kirwan, Matthew L.; Guntenspergen, Glenn R.

2010-01-01

Early comparisons between rates of vertical accretion and sea level rise across marshes in different tidal ranges inspired a paradigm that marshes in high tidal range environments are more resilient to sea level rise than marshes in low tidal range environments. We use field-based observations to propose a relationship between vegetation growth and tidal range and to adapt two numerical models of marsh evolution to explicitly consider the effect of tidal range on the response of the marsh platform channel network system to accelerating rates of sea level rise. We find that the stability of both the channel network and vegetated platform increases with increasing tidal range. Our results support earlier hypotheses that suggest enhanced stability can be directly attributable to a vegetation growth range that expands with tidal range. Accretion rates equilibrate to the rate of sea level rise in all experiments regardless of tidal range, suggesting that comparisons between accretion rate and tidal range will not likely produce a significant relationship. Therefore, our model results offer an explanation to widely inconsistent field-based attempts to quantify this relationship while still supporting the long-held paradigm that high tidal range marshes are indeed more stable.

Instability of a cantilevered flexible plate in viscous channel flow

NASA Astrophysics Data System (ADS)

Balint, T. S.; Lucey, A. D.

2005-10-01

The stability of a flexible cantilevered plate in viscous channel flow is studied as a representation of the dynamics of the human upper airway. The focus is on instability mechanisms of the soft palate (flexible plate) that cause airway blockage during sleep. We solve the Navier Stokes equations for flow with Reynolds numbers up to 1500 fully coupled with the dynamics of the plate motion solved using finite-differences. The study is 2-D and based upon linearized plate mechanics. When both upper and lower airways are open, the plate is found to lose its stability through a flutter mechanism and a critical Reynolds number exists. When one airway is closed, the plate principally loses its stability through a divergence mechanism and a critical flow speed exists. However, below the divergence-onset flow speed, flutter can exist for low levels of structural damping in the flexible plate. Our results serve to extend understanding of flow-induced instability of cantilevered flexible plates and will ultimately improve the diagnosis and treatment of upper-airway disorders.

Linking long-term gully and river channel dynamics to environmental change using repeat photography (Northern Ethiopia)

NASA Astrophysics Data System (ADS)

Frankl, Amaury; Nyssen, Jan; De Dapper, Morgan; Haile, Mitiku; Billi, Paolo; Munro, R. Neil; Deckers, Jozef; Poesen, Jean

2011-06-01

In the Highlands of Northern Ethiopia gully occurrence is linked to poverty-driven unsustainable use of the land in a vulnerable semi-arid and mountainous environment, where intensive rainfall challenges the physical integrity of the landscape. Trends in gully and river channel erosion, and their relation to triggering environmental changes can proffer valuable insights into sustainable development in Northern Ethiopia. In order to assess the region-wide change in gully and river channel morphology over 140 years, a set of 57 historical photographs taken in Tigray, and, clearly displaying gully cross-sections, were precisely repeated from 2006 till 2009. Ninety-two percent of the gully and river sections (n = 38) increased in cross-sectional area during the studied period, especially after 1975. Two repeatedly photographed catchments of Lake Ashenge and Atsela allowed a detailed study of gully development from 1936 until 2009. A conceptual hydrogeomorphic model was devised for these catchments and validated for the Northern Ethiopian Highlands. Three major phases can be distinguished in the hydrological regime of the catchments. In the first phase, between 1868 (or earlier) and ca. 1965, the relatively stable channels showed an oversized morphology inherited from a previous period when external forcing in environmental conditions had caused the channels to shape. In the second phase (ca. 1965 - ca. 2000), increased aridity and continued vegetation clearance accelerated the channel dynamics of the gully and river system. The third phase (ca. 2000 - present) started after the large-scale implementation of soil and water conservation measures. In 2009, 23% of the gully and river sections were stabilizing. This paper validates previous research indicating severe land degradation in the second half of the 20th century. Additionally, it demonstrates that the recent erosive cycle started around 1965 and, that at the present time, improved land management stabilizes

The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

PubMed Central

Marsakova, Lenka; Barvik, Ivan; Zima, Vlastimil; Zimova, Lucie; Vlachova, Viktorie

2017-01-01

Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate. We show that, upon opening, the upper part of the sensor module approaches the pore domain of an adjacent subunit and the conformational dynamics of the first extracellular flexible loop may govern the voltage-dependence of multimodal gating, thereby serving to stabilize the open state of the channel. These results are generally important in understanding the structure and function of TRPA1 and offer new insights into the gating mechanism of TRPA1 and related channels. PMID:28197074

Amortized entanglement of a quantum channel and approximately teleportation-simulable channels

NASA Astrophysics Data System (ADS)

Kaur, Eneet; Wilde, Mark M.

2018-01-01

This paper defines the amortized entanglement of a quantum channel as the largest difference in entanglement between the output and the input of the channel, where entanglement is quantified by an arbitrary entanglement measure. We prove that the amortized entanglement of a channel obeys several desirable properties, and we also consider special cases such as the amortized relative entropy of entanglement and the amortized Rains relative entropy. These latter quantities are shown to be single-letter upper bounds on the secret-key-agreement and PPT-assisted quantum capacities of a quantum channel, respectively. Of especial interest is a uniform continuity bound for these latter two special cases of amortized entanglement, in which the deviation between the amortized entanglement of two channels is bounded from above by a simple function of the diamond norm of their difference and the output dimension of the channels. We then define approximately teleportation- and positive-partial-transpose-simulable (PPT-simulable) channels as those that are close in diamond norm to a channel which is either exactly teleportation- or PPT-simulable, respectively. These results then lead to single-letter upper bounds on the secret-key-agreement and PPT-assisted quantum capacities of channels that are approximately teleportation- or PPT-simulable, respectively. Finally, we generalize many of the concepts in the paper to the setting of general resource theories, defining the amortized resourcefulness of a channel and the notion of ν-freely-simulable channels, connecting these concepts in an operational way as well.

Connexin Type and Fluorescent Protein Fusion Tag Determine Structural Stability of Gap Junction Plaques.

PubMed

Stout, Randy F; Snapp, Erik Lee; Spray, David C

2015-09-25

Gap junctions (GJs) are made up of plaques of laterally clustered intercellular channels and the membranes in which the channels are embedded. Arrangement of channels within a plaque determines subcellular distribution of connexin binding partners and sites of intercellular signaling. Here, we report the discovery that some connexin types form plaque structures with strikingly different degrees of fluidity in the arrangement of the GJ channel subcomponents of the GJ plaque. We uncovered this property of GJs by applying fluorescence recovery after photobleaching to GJs formed from connexins fused with fluorescent protein tags. We found that connexin 26 (Cx26) and Cx30 GJs readily diffuse within the plaque structures, whereas Cx43 GJs remain persistently immobile for more than 2 min after bleaching. The cytoplasmic C terminus of Cx43 was required for stability of Cx43 plaque arrangement. We provide evidence that these qualitative differences in GJ arrangement stability reflect endogenous characteristics, with the caveat that the sizes of the GJs examined were necessarily large for these measurements. We also uncovered an unrecognized effect of non-monomerized fluorescent protein on the dynamically arranged GJs and the organization of plaques composed of multiple connexin types. Together, these findings redefine our understanding of the GJ plaque structure and should be considered in future studies using fluorescent protein tags to probe dynamics of highly ordered protein complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Functional relationships between vegetation, channel morphology, and flow efficiency in an alluvial (anabranching) river

NASA Astrophysics Data System (ADS)

Jansen, John D.; Nanson, Gerald C.

2010-12-01

Water and sediment flux interactions are examined in Magela Creek, an alluvial (anabranching) sand bed river in the northern Australian tropics. Dense riparian vegetation stabilizes the channels and floodplains thereby preventing erosional instability at flow depths up to 6.2 times bankfull and discharges up to 15 times bankfull. Narrow anabranching channels characterize >92% of the alluvial reach and transport bed load more efficiently than short reaches of wide single-channels, yet overall 29 ± 12% of the bed load is sequestered and the average vertical accretion rate is 0.41 ± 0.17 mm yr-1 along the 12 km study reach. The most effective discharge for transporting sediment (40-45 m3 s-1) is consistent at all 5 stations (10 channels) examined and is equivalent to the channel-forming discharge. It has an average recurrence interval of 1.01 years, occurs for an exceptionally long portion (13-15%) of the annual flow duration, and averages a remarkable 2.1 times bankfull. The high flow efficiency (i.e., bed load transport rate to stream power ratio) of the anabranches is facilitated by low width/depth channels with banks reinforced by vegetation. Colonnades of bank top trees confine high-velocity flows overbed (i.e., over the channel bed) at stages well above bankfull. At even larger overbank flows, momentum exchange between the channels and forested floodplains restrains overbed velocities, in some cases causing them to decline, thereby limiting erosion. Magela Creek exhibits a complicated set of planform, cross-sectional and vegetative adjustments that boost overbed velocities and enhance bed load yield in multiple channels while restraining velocities and erosion at the largest discharges.

Stream Bank Stability in Eastern Nebraska

USGS Publications Warehouse

Soenksen, Phillip J.; Turner, Mary J.; Dietsch, Benjamin J.; Simon, Andrew

2003-01-01

Dredged and straightened channels in eastern Nebraska have experienced degradation leading to channel widening by bank failure. Degradation has progressed headward and affected the drainage systems upstream from the modified reaches. This report describes a study that was undertaken to analyze bank stability at selected sites in eastern Nebraska and develop a simplified method for estimating the stability of banks at future study sites. Bank cross sections along straight reaches of channel and geotechnical data were collected at approximately 150 sites in 26 counties of eastern Nebraska. The sites were categorized into three groups based on mapped soil permeability. With increasing permeability of the soil groups, the median cohesion values decreased and the median friction angles increased. Three analytical methods were used to determine if banks were stable (should not fail even when saturated), at risk (should not fail unless saturated), or unstable (should have already failed). The Culmann and Agricultural Research Service methods were based on the Coulomb equation and planar failure; an indirect method was developed that was based on Bishop's simplified method of slices and rotational failure. The maximum angle from horizontal at which the bank would be stable for the given soil and bank height conditions also was computed with the indirect method. Because of few soil shear-strength data, all analyses were based on the assumption of homogeneous banks, which was later shown to be atypical, at least for some banks. Using the Culmann method and assuming no soil tension cracks, 67 percent of all 908 bank sections were identified as stable, 32 percent were at risk, and 1 percent were unstable; when tension cracks were assumed, the results changed to 58 percent stable, 40 percent at risk, and 1 percent unstable. Using the Agricultural Research Service method, 67 percent of all bank sections were identified as stable and 33 percent were at risk. Using the indirect

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

PubMed Central

De Franceschi, Lucia; Rivera, Alicia; Fleming, Mark D.; Honczarenko, Marek; Peters, Luanne L.; Gascard, Philippe; Mohandas, Narla; Brugnara, Carlo

2005-01-01

It has been shown that mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis) and decreased membrane stability. Here, we characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75 ± 1.06 vs 6.08 ± 0.09 mM cell × minute; P < .04) and a decrease in Km (1.01 ± 0.06 vs 1.47 ± 1.02 μM; P < .03), indicating an increased sensitivity to activation by intracellular calcium. In vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker. Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival and increased numbers of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, potassium and water loss through the Gardos channel may play an important protective role in compensating for the reduced surface-membrane area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments. (Blood. 2005;106:1454-1459) PMID:15855279

Stability analysis of Eulerian-Lagrangian methods for the one-dimensional shallow-water equations

USGS Publications Warehouse

Casulli, V.; Cheng, R.T.

1990-01-01

In this paper stability and error analyses are discussed for some finite difference methods when applied to the one-dimensional shallow-water equations. Two finite difference formulations, which are based on a combined Eulerian-Lagrangian approach, are discussed. In the first part of this paper the results of numerical analyses for an explicit Eulerian-Lagrangian method (ELM) have shown that the method is unconditionally stable. This method, which is a generalized fixed grid method of characteristics, covers the Courant-Isaacson-Rees method as a special case. Some artificial viscosity is introduced by this scheme. However, because the method is unconditionally stable, the artificial viscosity can be brought under control either by reducing the spatial increment or by increasing the size of time step. The second part of the paper discusses a class of semi-implicit finite difference methods for the one-dimensional shallow-water equations. This method, when the Eulerian-Lagrangian approach is used for the convective terms, is also unconditionally stable and highly accurate for small space increments or large time steps. The semi-implicit methods seem to be more computationally efficient than the explicit ELM; at each time step a single tridiagonal system of linear equations is solved. The combined explicit and implicit ELM is best used in formulating a solution strategy for solving a network of interconnected channels. The explicit ELM is used at channel junctions for each time step. The semi-implicit method is then applied to the interior points in each channel segment. Following this solution strategy, the channel network problem can be reduced to a set of independent one-dimensional open-channel flow problems. Numerical results support properties given by the stability and error analyses. ?? 1990.

Anesthetic sites and allosteric mechanisms of action on Cys-loop ligand-gated ion channels.

PubMed

Forman, Stuart A; Miller, Keith W

2011-02-01

The Cys-loop ligand-gated ion channel superfamily is a major group of neurotransmitter-activated receptors in the central and peripheral nervous system. The superfamily includes inhibitory receptors stimulated by γ-aminobutyric acid (GABA) and glycine and excitatory receptors stimulated by acetylcholine and serotonin. The first part of this review presents current evidence on the location of the anesthetic binding sites on these channels and the mechanism by which binding to these sites alters their function. The second part of the review addresses the basis for this selectivity, and the third part describes the predictive power of a quantitative allosteric model showing the actions of etomidate on γ-aminobutyric acid type A receptors (GABA(A)Rs). General anesthetics at clinical concentrations inhibit the excitatory receptors and enhance the inhibitory receptors. The location of general anesthetic binding sites on these receptors is being defined by photoactivable analogues of general anesthetics. The receptor studied most extensively is the muscle-type nicotinic acetylcholine receptor (nAChR), and progress is now being made with GABA(A)Rs. There are three categories of sites that are all in the transmembrane domain: 1) within a single subunit's four-helix bundle (intrasubunit site; halothane and etomidate on the δ subunit of AChRs); 2) between five subunits in the transmembrane conduction pore (channel lumen sites; etomidate and alcohols on nAChR); and 3) between two subunits (subunit interface sites; etomidate between the α1 and β2/3 subunits of the GABA(A)R). These binding sites function allosterically. Certain conformations of a receptor bind the anesthetic with greater affinity than others. Time-resolved photolabelling of some sites occurs within milliseconds of channel opening on the nAChR but not before. In GABA(A)Rs, electrophysiological data fit an allosteric model in which etomidate binds to and stabilizes the open state, increasing both the fraction

Development of a Radiolabeled Amlodipine Analog for L-type Calcium Channel Imaging.

PubMed

Firouzyar, Tahereh; Jalilian, Amir Reza; Aboudzadeh, Mohammad Reza; Sadeghpour, Hossein; Pooladi, Mehrban; Shafiee-Ardestani, Mahdi; Khalaj, Ali

2017-01-01

The non-invasive imaging and quantification of L-type calcium channels (also known as dihydropyridine channels) in living tissues is of great interest in diagnosis of congestive heart failure, myocardial hypertrophy, irritable bowel syndrome etc. Technetium-99m labeled amlodipine conjugate ([99mTc]-DTPA-AMLO) was prepared starting freshly eluted (<1 h) 99mTechnetium pertechnetate (86.5 MBq) and conjugated DTPAAMLO at pH 5 in 30 min at room temperature in high radiochemical purity (>99%, RTLC; specific activity: 55-60 GBq/mmol). The calcium channel blockade activity (CCBA) and apoptosis/necrosis assay of DTPA-amlodipine conjugate evaluations were performed for the conjugate. Log P, stability, bio-distribution and imaging studies were performed for the tracer followed by biodistribution studies as well as imaging. The conjugate demonstrated low toxicity on MCF-7 cells and CCBA (at µm level) compared to the amlodipine. The tracer was stable up to 4 h in final production and presence of human serum and log P (-0.49) was consistent with a water soluble complex. The tracer was excreted through kidneys and liver as expected for dihydropyridines; excluding excretory organs, calcium channel rich smooth muscle cells; including colon, intestine and lungs which demonstrated significant uptake. SPECT images supported the bio-distribution data up to 4 h. significant uptake of [99mTc]-DTPA-AMLO was obtained in calcium channel rich organs. The complex can be a candidate for further SPECT imaging for L-type calcium channels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization.

PubMed

Forst, Anna-Lena; Olteanu, Vlad Sorin; Mollet, Géraldine; Wlodkowski, Tanja; Schaefer, Franz; Dietrich, Alexander; Reiser, Jochen; Gudermann, Thomas; Mederos y Schnitzler, Michael; Storch, Ursula

2016-03-01

Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X4) blocker 5-BDBD. Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X4 channels as mechanotransducers in podocytes. Copyright © 2016 by the American Society of Nephrology.

Chasing the open-state structure of pentameric ligand-gated ion channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonzalez-Gutierrez, Giovanni; Wang, Yuhang; Cymes, Gisela D.

Remarkable advances have been made toward the structural characterization of ion channels in the last two decades. However, the unambiguous assignment of well-defined functional states to the obtained structural models has proved challenging. In the case of the superfamily of nicotinic-receptor channels (also referred to as pentameric ligand-gated ion channels [pLGICs]), for example, two different types of model of the open-channel conformation have been proposed on the basis of structures solved to resolutions better than 4.0 Å. At the level of the transmembrane pore, the open-state models of the proton-gated pLGIC fromGloeobacter violaceus(GLIC) and the invertebrate glutamate-gated Cl –channel (GluCl)more » are very similar to each other, but that of the glycine receptor (GlyR) is considerably wider. Indeed, the mean distances between the axis of ion permeation and the Cα atoms at the narrowest constriction of the pore (position -2') differ by ~2 Å in these two classes of model, a large difference when it comes to understanding the physicochemical bases of ion conduction and charge selectivity. Here, we take advantage of the extreme open-channel stabilizing effect of mutations at pore-facing position 9'. We find that the I9'A mutation slows down entry into desensitization of GLIC to the extent that macroscopic currents decay only slightly by the end of pH 4.5 solution applications to the extracellular side for several minutes. We crystallize (at pH 4.5) two variants of GLIC carrying this mutation and solve their structures to resolutions of 3.12 Å and 3.36 Å. Furthermore, we perform all-atom molecular dynamics simulations of ion permeation and picrotoxinin block, using the different open-channel structural models. On the basis of these results, we favor the notion that the open-channel structure of pLGICs from animals is much closer to that of the narrow models (of GLIC and GluCl) than it is to that of the GlyR.« less

Effect of structural modification on the gastrointestinal stability and hepatic metabolism of α-aminoxy peptides.

PubMed

Ma, Bin; Yin, Chun; Yang, Dan; Lin, Ge

2012-11-01

α-Aminoxy peptide AxyP1 has been reported to form synthetic chloride channel in living cells, thus it may have therapeutic potential for the treatment of diseases associated with chloride channel dysfunction. However, this study revealed significant gastrointestinal (GI) instability and extensive hepatic metabolism of AxyP1. To improve its GI and metabolic stability, structural modifications were conducted by replacing the isobutyl side chains of AxyP1 with methyl group (AxyP2), hydroxymethyl group (AxyP3), 4-aminobutyl group (AxyP4) and 3-carboxyl propyl group (AxyP5). Compared with AxyP1 (41 and 47 % degradation), GI stability of the modified peptides was significantly improved by 8-fold (AxyP2), 9-fold (AxyP3) and 12-fold (AxyP5) with no degradation for AxyP4 in simulated gastric fluid within 1 h, and by 12-fold (AxyP2) and 9-fold (AxyP3) with no degradation for AxyP4 and AxyP5 in simulated intestinal fluid within 3 h, respectively. The hepatic metabolic stability of the four modified peptides within 30 min in rat liver S9 preparation was also improved significantly with no metabolism of AxyP5 and threefold (AxyP2 and AxyP4) and eightfold (AxyP3) less metabolism compared with AxyP1 (39 % metabolism). Unlike hydrolysis as the major metabolism of peptides of natural α-amino acids, oxidation mediated by the cytochrome P450 enzymes, especially CYP3A subfamily, to form the corresponding mono-hydroxyl metabolites was the predominant hepatic metabolism of the five α-aminoxy peptides tested. The present findings demonstrate that structural modification can significantly improve the GI and metabolic stability of α-aminoxy peptides and thus increase their potential for therapeutic use in the treatment of chloride channel related diseases.

The influence of channel anion identity on the high-pressure crystal structure, compressibility, and stability of apatite

NASA Astrophysics Data System (ADS)

Skelton, Richard; Walker, Andrew M.

2018-03-01

The material properties of the common phosphate mineral apatite are influenced by the identity of the channel anion, which is usually F-, Cl-, or (OH)-. Density functional theory calculations have been used to determine the effect of channel anion identity on the compressibility and structure of apatite. Hydroxyapatite and fluorapatite are found to have similar zero pressure bulk moduli, of 79.2 and 82.1 GPa, respectively, while chlorapatite is considerably more compressible, with K 0 = 55.0 GPa. While the space groups of hydroxyapatite and fluorapatite do not change between 0 and 25 GPa, symmetrization of the Cl- site in chlorapatite at 7.5 GPa causes the space group to change from P2 1 /b to P6 3 /m. Examination of the valence electron density distribution in chlorapatite reveals that this symmetry change is associated with a change in the coordination of the Cl- anion from threefold to sixfold coordinated by Ca. We also calculate the pressure at which apatite decomposes to form tuite, a calcium orthophosphate mineral, and find that the transition pressure is sensitive to the identity of the channel anion, being lowest for fluorapatite (13.8 GPa) and highest for chlorapatite (26.9 GPa). Calculations are also performed within the DFT-D2 framework to investigate the influence of dispersion forces on the compressibility of apatite minerals.

Interactions of Pannexin1 channels with purinergic and NMDA receptor channels.

PubMed

Li, Shuo; Bjelobaba, Ivana; Stojilkovic, Stanko S

2018-01-01

Pannexins are a three-member family of vertebrate plasma membrane spanning molecules that have homology to the invertebrate gap junction forming proteins, the innexins. However, pannexins do not form gap junctions but operate as plasma membrane channels. The best-characterized member of these proteins, Pannexin1 (Panx1) was suggested to be functionally associated with purinergic P2X and N-methyl-D-aspartate (NMDA) receptor channels. Activation of these receptor channels by their endogenous ligands leads to cross-activation of Panx1 channels. This in turn potentiates P2X and NMDA receptor channel signaling. Two potentiation concepts have been suggested: enhancement of the current responses and/or sustained receptor channel activation by ATP released through Panx1 pore and adenosine generated by ectonucleotidase-dependent dephosphorylation of ATP. Here we summarize the current knowledge and hypotheses about interactions of Panx1 channels with P2X and NMDA receptor channels. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Published by Elsevier B.V.

Creating self-formed meandering channels in laboratory flumes (Invited)

NASA Astrophysics Data System (ADS)

Braudrick, C. A.

2009-12-01

Our ability to construct predictive numerical models for meandering rivers is hampered by the inability to create meandering channels in the laboratory where individual variables can be isolated and controlled. Typically, experimental channels braid, straighten, or cease migration once they develop curvature. By using alfalfa sprouts to provide bank strength and fine sediment to attach point bars to the floodplain, we have successfully created and maintained meandering morphology in a laboratory flume. The 6.1 by 17 m flume has a floodplain slope of approximately 0.005 with a sandy bed and banks that scales as a gravel bed river. The alfalfa sprouts slow bank erosion allowing time for the bars to create new floodplain deposits. The sprouts also increase floodplain roughness, armor new bar deposits, and promote deposition of overbank sediment. The fine sediment, a lightweight plastic that scaled as sand, was crucial for blocking chutes formed between the bar and the floodplain, isolating cut-off channels from the main flow, and creating levees. During this 136-hour long experiment, the channel width stabilized as the channel migrated across the floodplain, and the curvature was recreated following cutoffs. Although the sinuosity (about 1.2) was low relative to meandering channels observed in the field, the spacing of bends was within the upper bounds of field examples. Subsequent experiments with higher bank strength had more limited chute development were able to generate a sinuosity of about 1.4. Scaling analysis indicates that the bank migration rates in the lower sinuosity experiment were approximately 10 times faster than migration rates in the field. A particular challenge in these experiments is maintaining a healthy alfalfa crop. After 15-20 hours of flood flows, the alfalfa begins to die off and new emergent bars need to be seeded. It then takes about 7 days for the alfalfa to grow to the size used in these experiments. The 15-20 hours scale to about one

Preliminary assessment of channel stability and bed-material transport in the Coquille River basin, southwestern Oregon

USGS Publications Warehouse

Jones, Krista L.; O'Connor, Jim E.; Keith, Mackenzie K.; Mangano, Joseph F.; Wallick, J. Rose

2012-01-01

This report summarizes a preliminary study of bed-material transport, vertical and lateral channel changes, and existing datasets for the Coquille River basin, which encompasses 2,745 km2 (square kilometers) of the southwestern Oregon coast. This study, conducted to inform permitting decisions regarding instream gravel mining, revealed that:

Demonstration and Field Evaluation of Streambank Stabilization with Submerged Vanes

USGS Publications Warehouse

Whitman, H.; Hoopes, J.; Poggi, D.; Fitzpatrick, F.; Walz, K.; ,

2001-01-01

The effectiveness of submerged vanes for reducing bank erosion and improving aquatic habitat is being evaluated at a site on North Fish Creek, a Lake Superior tributary. Increased runoff from agricultural areas with clayey soils has increased flood magnitudes and the erosion potential/transport capacity of the stream. Most of the creek's sediment load originates from the erosion of 17 large bluffs. This creek contains important recreational fisheries that are potentially limited by the loss of aquatic habitat from deposition of sediment on spawning beds. Submerged vanes are a cost effective and environmentally less intrusive alternative to traditional structural stabilization measures. Submerged vanes protrude from a channel bed, are oriented at an angle to the local velocity, and are distributed along a portion of channel. They induce a transverse force and torque on the flow along with longitudinal vortexes that alter the cross sectional shape and alignment of the channel. Submerged vanes were installed at a bluff/bend site in summer and fall 2000. The number, size, and layout of the vanes were based upon the channel morphology under estimated bankfull conditions. The effectiveness of the vanes will be evaluated by comparing surveys of the bluff face, streamflow, and channel conditions for several years after installation of the submerged vanes with surveys before and immediately after their installation.

Inception of supraglacial channelization under turbulent flow conditions

NASA Astrophysics Data System (ADS)

Mantelli, E.; Camporeale, C.; Ridolfi, L.

2013-12-01

Glacier surfaces exhibit an amazing variety of meltwater-induced morphologies, ranging from small scale ripples and dunes on the bed of supraglacial channels to meandering patterns, till to large scale drainage networks. Even though the structure and geometry of these morphologies play a key role in the glacier melting processes, the physical-based modeling of such spatial patterns have attracted less attention than englacial and subglacial channels. In order to partially fill this gap, our work concerns the large scale channelization occurring on the ice slopes and focuses on the role of turbulence on the wavelength selection processes during the channelization inception. In a recent study[1], two of us showed that the morphological instability induced by a laminar film flowing over an ice bed is characterized by transversal length scales of order of centimeters. Being these scales much smaller than the spacing observed in the channelization of supraglacial drainage networks (that are of order of meters) and considering that the water films flowing on glaciers can exhibit Reynolds numbers larger than 104, we investigated the role of turbulence in the inception of channelization. The flow-field is modeled by means of two-dimensional shallow water equations, where Reynolds stresses are also considered. In the depth-averaged heat balance equation an incoming heat flux from air is assumed and forced convection heat exchange with the wall is taken into account, in addition to convection and diffusion in the liquid. The temperature profile in the ice is finally coupled to the liquid through Stefan equation. We then perform a linear stability analysis and, under the assumption of small Stefan number, we solve the differential eigenvalue problem analytically. As main outcome of such an analysis, the morphological instability of the ice-water interface is detected and investigated in a wide range of the independent parameters: longitudinal and transversal wavenumbers

A Froude-scaled model of a bedrock-alluvial channel reach: 2. Sediment cover

NASA Astrophysics Data System (ADS)

Hodge, Rebecca A.; Hoey, Trevor B.

2016-09-01

Previous research into sediment cover in bedrock-alluvial channels has focussed on total sediment cover, rather than the spatial distribution of cover within the channel. The latter is important because it determines the bedrock areas that are protected from erosion and the start and end of sediment transport pathways. We use a 1:10 Froude-scaled model of an 18 by 9 m reach of a bedrock-alluvial channel to study the production and erosion of sediment patches and hence the spatial relationships between flow, bed topography, and sediment dynamics. The hydraulic data from this bed are presented in the companion paper. In these experiments specified volumes of sediment were supplied at the upstream edge of the model reach as single inputs, at each of a range of discharges. This sediment formed patches, and once these stabilized, flow was steadily increased to erode the patches. In summary: (1) patches tend to initiate in the lowest areas of the bed, but areas of topographically induced high flow velocity can inhibit patch development; (2) at low sediment inputs the extent of sediment patches is determined by the bed topography and can be insensitive to the exact volume of sediment supplied; and (3) at higher sediment inputs more extensive patches are produced, stabilized by grain-grain and grain-flow interactions and less influenced by the bed topography. Bedrock topography can therefore be an important constraint on sediment patch dynamics, and topographic metrics are required that incorporate its within-reach variability. The magnitude and timing of sediment input events controls reach-scale sediment cover.

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

PubMed Central

Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 Å resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were confirmed by systematic site-specific functional tests. We observed that the bound capsaicin takes “tail-up, head-down” configurations. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes the open state by “pull-and-contact” interactions between the vanillyl group and the S4-S5 linker. Our study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures. PMID:26053297

Field Investigation of Flow Structure and Channel Morphology at Confluent-Meander Bends

NASA Astrophysics Data System (ADS)

Riley, J. D.; Rhoads, B. L.

2007-12-01

and channel morphology were also surveyed with a digital fathometer to document geomorphic change. Preliminary analysis of the velocity data reveals the presence of a well-defined shear layer between the converging flows and secondary circulation in the main channel. The tributary channel appears to oppose high velocity flow directed toward the outer bank by centrifugal acceleration through the meander bend of the main channel, thereby diminishing erosion along the cut bank and possibly stabilizing the meander bend channel. The flow structure and channel morphology of the study sites are compared to consider the effect of spatial scale and geometric characteristics on confluent-meander bend dynamics.

Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

PubMed Central

Yan, Meng; Zhang, Kaiping; Shi, Yanhui; Feng, Lifang; Lv, Lin; Li, Baoxin

2015-01-01

Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. PMID:26543354

Temporal and voltage stress stability of high performance indium-zinc-oxide thin film transistors

NASA Astrophysics Data System (ADS)

Song, Yang; Katsman, Alexander; Butcher, Amy L.; Paine, David C.; Zaslavsky, Alexander

2017-10-01

Thin film transistors (TFTs) based on transparent oxide semiconductors, such as indium zinc oxide (IZO), are of interest due to their improved characteristics compared to traditional a-Si TFTs. Previously, we reported on top-gated IZO TFTs with an in-situ formed HfO2 gate insulator and IZO active channel, showing high performance: on/off ratio of ∼107, threshold voltage VT near zero, extracted low-field mobility μ0 = 95 cm2/V·s, and near-perfect subthreshold slope at 62 mV/decade. Since device stability is essential for technological applications, in this paper we report on the temporal and voltage stress stability of IZO TFTs. Our devices exhibit a small negative VT shift as they age, consistent with an increasing carrier density resulting from an increasing oxygen vacancy concentration in the channel. Under gate bias stress, freshly annealed TFTs show a negative VT shift during negative VG gate bias stress, while aged (>1 week) TFTs show a positive VT shift during negative VG stress. This indicates two competing mechanisms, which we identify as the field-enhanced generation of oxygen vacancies and the field-assisted migration of oxygen vacancies, respectively. A simplified kinetic model of the vacancy concentration evolution in the IZO channel under electrical stress is provided.

CNG channel subunit glycosylation regulates MMP-dependent changes in channel gating

PubMed Central

Meighan, Starla E.; Meighan, Peter C.; Rich, Elizabeth D.; Brown, R. Lane; Varnum, Michael D.

2013-01-01

Cyclic-nucleotide gated (CNG) channels are essential for phototransduction within retinal photoreceptors. We have demonstrated previously that enzymatic activity of matrix metalloproteinase-2 and -9, members of the MMP family of extracellular, Ca+2- and Zn+2-dependent proteases, enhances the ligand sensitivity of both rod (CNGA1 + CNGB1) and cone CNGA3 + CNGB3) CNG channels. Additionally, we have observed a decrease in maximal CNG channel current (IMAX) that begins late during MMP-directed gating changes. Here we demonstrate that CNG channels become non-conductive after prolonged MMP exposure. Concurrent with the loss of conductive channels is the increased relative contribution of channels exhibiting non-modified gating properties, suggesting the presence of a subpopulation of channels that are protected from MMP-induced gating effects. CNGA subunits are known to possess one extracellular core glycosylation site, located at one of two possible positions within the turret loop near the pore-forming region. Our results indicate that CNGA glycosylation can impede MMP-dependent modification of CNG channels. Furthermore, the relative position of the glycosylation site within the pore turret influences the extent of MMP-dependent proteolysis. Glycosylation at the site found in CNGA3 subunits was found to be protective, while glycosylation at the bovine CNGA1 site was not. Relocating the glycosylation site in CNGA1 to the position found in CNGA3 recapitulated CNGA3-like protection from MMP-dependent processing. Taken together, these data indicate that CNGA glycosylation may protect CNG channels from MMP-dependent proteolysis, consistent with MMP modification of channel function having a requirement for physical access to the extracellular face of the channel. PMID:24164424

Monitoring Changes in Channel Morphology in Las Vegas Wash with Global Fiducials Program Imagery

NASA Astrophysics Data System (ADS)

Wheeler, D. J.

2012-12-01

To borrow from a popular adage, "What happens in Las Vegas [Wash], stays in Las Vegas [Wash]"—but only with a lot of help. This past decade has seen a concerted effort to curb erosion and sediment transport along the 12 mile long channel between East Las Vegas and Lake Mead. Las Vegas Wash is prototypical of an urban river in an arid environment that is being impacted by increasing urban development and impervious surface runoff within its drainage area. Rapid urbanization since the 1970s has increased the flow of water into Las Vegas Wash, causing severe channel destabilization. Within two decades millions of cubic yards of rocks and sediment were scoured out of the wash and transported downstream to Lake Mead. The wetlands that once covered over 2,000 acres within Las Vegas Wash dwindled to 200 acres in the 1990s as the channel became as much as 40 feet deeper and 300 feet wider at some points. In 1999 the Las Vegas Wash Coordination Committee (LVWCC) initiated a 20-year plan to construct erosion control structures (weirs) for channel stabilization and rock riprap for stream bank protection. The hope is to design structures that will slow down the water flow, trap sediments, and to eventually restore much of the wetland environment. Using high-resolution satellite imagery from the Global Fiducials Program Library housed at the U. S. Geological Survey, this transition is being tracked from 1999 to the present. From November 1999 to July 2008 new residential and commercial development has claimed an additional 12 square kilometers (3000 acres) of land in Henderson, NV, along the south side of Las Vegas Wash. Even with the increased volume of surface and groundwater runoff entering the wash, current sediment yields are much lower than the 1999 totals. The imagery documents the construction of 14 of the 22 LVWCC planned weirs by the year 2011. It also shows many miles of stream bank stabilization by riprap, planting of riparian vegetation and placing of

Restoration of Kv7 Channel-Mediated Inhibition Reduces Cued-Reinstatement of Cocaine Seeking.

PubMed

Parrilla-Carrero, Jeffrey; Buchta, William C; Goswamee, Priyodarshan; Culver, Oliver; McKendrick, Greer; Harlan, Benjamin; Moutal, Aubin; Penrod, Rachel; Lauer, Abigail; Ramakrishnan, Viswanathan; Khanna, Rajesh; Kalivas, Peter; Riegel, Arthur C

2018-04-25

Cocaine addicts display increased sensitivity to drug-associated cues, due in part to changes in the prelimbic prefrontal cortex (PL-PFC). The cellular mechanisms underlying cue-induced reinstatement of cocaine seeking remain unknown. Reinforcement learning for addictive drugs may produce persistent maladaptations in intrinsic excitability within sparse subsets of PFC pyramidal neurons. Using a model of relapse in male rats, we sampled >600 neurons to examine spike frequency adaptation (SFA) and afterhyperpolarizations (AHPs), two systems that attenuate low-frequency inputs to regulate neuronal synchronization. We observed that training to self-administer cocaine or nondrug (sucrose) reinforcers decreased SFA and AHPs in a subpopulation of PL-PFC neurons. Only with cocaine did the resulting hyperexcitability persist through extinction training and increase during reinstatement. In neurons with intact SFA, dopamine enhanced excitability by inhibiting Kv7 potassium channels that mediate SFA. However, dopamine effects were occluded in neurons from cocaine-experienced rats, where SFA and AHPs were reduced. Pharmacological stabilization of Kv7 channels with retigabine restored SFA and Kv7 channel function in neuroadapted cells. When microinjected bilaterally into the PL-PFC 10 min before reinstatement testing, retigabine reduced cue-induced reinstatement of cocaine seeking. Last, using cFos-GFP transgenic rats, we found that the loss of SFA correlated with the expression of cFos-GFP following both extinction and re-exposure to drug-associated cues. Together, these data suggest that cocaine self-administration desensitizes inhibitory Kv7 channels in a subpopulation of PL-PFC neurons. This subpopulation of neurons may represent a persistent neural ensemble responsible for driving drug seeking in response to cues. SIGNIFICANCE STATEMENT Long after the cessation of drug use, cues associated with cocaine still elicit drug-seeking behavior, in part by activation of the

Communication Channel Estimation and Waveform Design: Time Delay Estimation on Parallel, Flat Fading Channels

DTIC Science & Technology

2010-02-01

channels, so the channel gain is known on each realization and used in a coherent matched filter; and (c) Rayleigh channels with noncoherent matched...gain is known on each realization and used in a coherent matched filter (channel model 1A); and (c) Rayleigh channels with noncoherent matched filters...filters, averaged over Rayleigh channel realizations (channel model 1A). (b) Noncoherent matched filters with Rayleigh fading (channel model 3). MSEs are

Improved Mobility and Bias Stability of Thin Film Transistors Using the Double-Layer a-InGaZnO/a-InGaZnO:N Channel.

PubMed

Yu, H; Zhang, L; Li, X H; Xu, H Y; Liu, Y C

2016-04-01

The amorphous indium-gallium-zinc oxide (a-IGZO) thin film transistors (TFTs) were demonstrated based on a double-layer channel structure, where the channel is composed of an ultrathin nitro-genated a-IGZO (a-IGZO:N) layer and an undoped a-IGZO layer. The double-layer channel device showed higher saturation mobility and lower threshold-voltage shift (5.74 cm2/Vs, 2.6 V) compared to its single-layer counterpart (0.17 cm2/Vs, 7.23 V). The improvement can be attributed to three aspects: (1) improved carrier transport properties of the channel by the a-IGZO:N layer with high carrier mobility and the a-IGZO layer with high carrier concentration, (2) reduced interfacial trap density between the active channel and the gate insulator, and (3) higher surface flatness of the double-layer channel. Our study reveals key insights into double-layer channel, involving selecting more suitable electrical property for back-channel layer and more suitable interface modification for active layer. Meanwhile, room temperature fabrication amorphous TFTs offer certain advantages on better flexibility and higher uniformity over a large area.

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Interactive communication channel

NASA Astrophysics Data System (ADS)

Chan, R. H.; Mann, M. R.; Ciarrocchi, J. A.

1985-10-01

Discussed is an interactive communications channel (ICC) for providing a digital computer with high-performance multi-channel interfaces. Sixteen full duplex channels can be serviced in the ICC with the sequence or scan pattern being programmable and dependent upon the number or channels and their speed. A channel buffer system is used for line interface, and character exchange. The channel buffer system is on a byte basis. The ICC performs frame start and frame end functions, bit stripping and bit stuffing. Data is stored in a memory in block format (256 bytes maximum) by a program control and the ICC maintains byte address information and a block byte count. Data exchange with a memory is made by cycle steals. Error detection is also provided for using a cyclic redundancy check technique.

Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age

PubMed Central

Oiki, Shigetoshi

2015-01-01

The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the ‘frozen’ crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. PMID:25833254

Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age.

PubMed

Oiki, Shigetoshi

2015-06-15

The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Computer Simulation Studies of Ion Channel Gating: Characteristics of the M2 Channel of Influenza-A Virus in a Phospholipid Bilayer

NASA Technical Reports Server (NTRS)

Schweighofer, Karl J.; Pohorille, Andrew; DeVincenzi, D. (Technical Monitor)

1999-01-01

The 25 amino acids long, transmembrane fragment of the Influenza virus M2 protein forms a homotetrameric channel that transports protons across lipid bilayers. It has been postulated that high efficiency and selectivity of this process is due to gating by four histidine residues that occlude the channel lumen in the closed state. Two mechanisms of gating have been postulated. In one mechanism, the proton is "shuttled" through the gate by attaching to the delta nitrogen atom on the extracellular side of the imidazole ring, followed by the release of the proton attached to the epsilon nitrogen atom on the opposite side. In the second mechanism, the four histidines move away from each other due to electrostatic repulsion upon protonation, thus opening the gate sufficiently that a wire of water molecules can penetrate the gate. Then, protons are transported by "hopping" along the wire. In this paper, both mechanisms are evaluated in a series of molecular dynamics simulations by investigating stability of different protonation states of the channel that are involved in these mechanisms. For the shuttle mechanism, these are states with all epsilon protonated histidines, one biprotonated residue or one histidine protonated in the delta position. For the gate opening mechanism, this is the state in which all four histidines are biprotonated. In addition, a state with two biprotonated histidines is considered. For each system, composed of the protein channel embedded in phospholipid bilayer located between two water lamellae, a molecular dynamics trajectory of approximately 1.3 ns (after equilibration) was obtained. It is found that the states involved in the shuttle mechanism are stable during the simulations. Furthermore, the orientations and dynamics of water molecules near the gate are conducive to proton transfers involved in the shuttle. In contract, the fully biprotonated state, implicated in the gate opening mechanism, is not stable and the channel looses its

Nimbus-7 Earth radiation budget calibration history. Part 1: The solar channels

NASA Technical Reports Server (NTRS)

Kyle, H. Lee; Hoyt, Douglas V.; Hickey, John R.; Maschhoff, Robert H.; Vallette, Brenda J.

1993-01-01

The Earth Radiation Budget (ERB) experiment on the Nimbus-7 satellite measured the total solar irradiance plus broadband spectral components on a nearly daily basis from 16 Nov. 1978, until 16 June 1992. Months of additional observations were taken in late 1992 and in 1993. The emphasis is on the electrically self calibrating cavity radiometer, channel 10c, which recorded accurate total solar irradiance measurements over the whole period. The spectral channels did not have inflight calibration adjustment capabilities. These channels can, with some additional corrections, be used for short-term studies (one or two solar rotations - 27 to 60 days), but not for long-term trend analysis. For channel 10c, changing radiometer pointing, the zero offsets, the stability of the gain, the temperature sensitivity, and the influences of other platform instruments are all examined and their effects on the measurements considered. Only the question of relative accuracy (not absolute) is examined. The final channel 10c product is also compared with solar measurements made by independent experiments on other satellites. The Nimbus experiment showed that the mean solar energy was about 0.1 percent (1.4 W/sqm) higher in the excited Sun years of 1979 and 1991 than in the quiet Sun years of 1985 and 1986. The error analysis indicated that the measured long-term trends may be as accurate as +/- 0.005 percent. The worse-case error estimate is +/- 0.03 percent.

Preparation and preclinical evaluation of 68Ga-DOTA-amlodipine for L-type calcium channel imaging.

PubMed

Firuzyar, Tahereh; Jalilian, Amir Reza; Aboudzadeh, Mohammad Reza; Sadeghpour, Hossein; Shafiee-Ardestani, Mahdi; Khalaj, Ali

2016-01-01

In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging. Amlodipine DOTA conjugate was synthesized, characterized and went through calcium channel blockade, toxicity, apoptosis/necrosis tests. [ 68 Ga] DOTA AMLO was prepared at optimized conditions followed by stability tests, partition coefficient determination and biodistribution studies using tissue counting and co incidence imaging up to 2 h. [ 68 Ga] DOTA AMLO was prepared at pH 4-5 in 7-10 min at 95°C in high radiochemical purity (>99%, radio thin layer chromatography; specific activity: 1.9-2.1 GBq/mmol) and was stable up to 4 h with a log P of -0.94. Calcium channel rich tissues including myocardium, and tissues with smooth muscle cells such as colon, intestine, and lungs demonstrated significant uptake. Co incidence images supported the biodistribution data up to 2 h. The complex can be a candidate for further positron emission tomography imaging for L type calcium channels.

Microfluidic channel fabrication method

DOEpatents

Arnold, Don W.; Schoeniger, Joseph S.; Cardinale, Gregory F.

2001-01-01

A new channel structure for microfluidic systems and process for fabricating this structure. In contrast to the conventional practice of fabricating fluid channels as trenches or grooves in a substrate, fluid channels are fabricated as thin walled raised structures on a substrate. Microfluidic devices produced in accordance with the invention are a hybrid assembly generally consisting of three layers: 1) a substrate that can or cannot be an electrical insulator; 2) a middle layer, that is an electrically conducting material and preferably silicon, forms the channel walls whose height defines the channel height, joined to and extending from the substrate; and 3) a top layer, joined to the top of the channels, that forms a cover for the channels. The channels can be defined by photolithographic techniques and are produced by etching away the material around the channel walls.

Factors controlling the size and shape of stream channels in coarse noncohesive sands

USGS Publications Warehouse

Wolman, M. Gordon; Brush, Lucien M.

1961-01-01

The size and shape of equilibrium channels in uniform, noncohesive sands, 0.67 mm and 2.0 mm in diameter, were studied experimentally in a laboratory flume 52 feet long in which discharge, slope, sediment load, and bed and bank material could be varied independently. For each run a straight trapezoidal channel was molded in the sand and the flume set at a predetermined slope. Introduction of the discharge was accompanied by widening and aggradation until a stable channel was established. By definition a stable equilibrium existed when channel width, water surface slope, and rate of transport became constant. The duration of individual runs ranged from 2 to 52 hours depending upon the time required for establishing equilibrium. Stability of the banks determined channel shape. In the 2.0 mm sand at a given slope and discharge, only one depth was stable. At this depth the flow was just competent to move particles along the bed of the channel. An increase in discharge produced a wider channel of the same depth and thus transport per unit width remained at a minimum. Channels in the 0.67 mm sand were somewhat more stable and permitted a 1.5 fold increase in depth above that required to start movement of the bed material. An increased transport was associated with the increase in depth. The rate of transport is adequately described in terms of the total shear or in terms of the difference between the total shear and the critical shear required to begin movement. In these experiments the finer, or 0.67 mm, sand, began to move along the bed of the channel at a constant shear stress. Incipient movement of the coarser, or 2.0 mm, sand, varied with the shear stress as well as the mean velocity. At the initiation of movement a lower shear was associated with a higher velocity and vice versa. Anabranches of braided rivers and some natural river channels formed in relatively noncohesive materials resemble the essential characteristics of the flume channels. For a given slope and

Molecular dynamics of alamethicin transmembrane channels from open-channel current noise analysis.

PubMed

Mak, D O; Webb, W W

1995-12-01

Conductance noise measurement of the open states of alamethicin transmembrane channels reveals excess noise attributable to cooperative low-frequency molecular dynamics that can generate fluctuations approximately 1 A rms in the effective channel pore radius. Single-channel currents through both persistent and nonpersistent channels with multiple conductance states formed by purified polypeptide alamethicin in artificial phospholipid bilayers isolated onto micropipettes with gigaohm seals were recorded using a voltage-clamp technique with low background noise (rms noise < 3 pA up to 20 kHz). Current noise power spectra between 100 Hz and 20 kHz of each open channel state showed little frequency dependence. Noise from undetected conductance state transitions was insignificant. Johnson and shot noises were evaluated. Current noise caused by electrolyte concentration fluctuation via diffusion was isolated by its dependence on buffer concentration. After removing these contributions, significant current noise remains in all persistent channel states and increases in higher conductance states. In nonpersistent channels, remaining noise occurs primarily in the lowest two states. These fluctuations of channel conductance are attributed to thermal oscillations of the channel molecular conformation and are modeled as a Langevin translational oscillation of alamethicin molecules moving radially from the channel pore, damped mostly by lipid bilayer viscosity.

Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations in the voltage-sensing domain.

PubMed

Miceli, Francesco; Vargas, Ernesto; Bezanilla, Francisco; Taglialatela, Maurizio

2012-03-21

Changes in voltage-dependent gating represent a common pathogenetic mechanism for genetically inherited channelopathies, such as benign familial neonatal seizures or peripheral nerve hyperexcitability caused by mutations in neuronal K(v)7.2 channels. Mutation-induced changes in channel voltage dependence are most often inferred from macroscopic current measurements, a technique unable to provide a detailed assessment of the structural rearrangements underlying channel gating behavior; by contrast, gating currents directly measure voltage-sensor displacement during voltage-dependent gating. In this work, we describe macroscopic and gating current measurements, together with molecular modeling and molecular-dynamics simulations, from channels carrying mutations responsible for benign familial neonatal seizures and/or peripheral nerve hyperexcitability; K(v)7.4 channels, highly related to K(v)7.2 channels both functionally and structurally, were used for these experiments. The data obtained showed that mutations affecting charged residues located in the more distal portion of S(4) decrease the stability of the open state and the active voltage-sensing domain configuration but do not directly participate in voltage sensing, whereas mutations affecting a residue (R4) located more proximally in S(4) caused activation of gating-pore currents at depolarized potentials. These results reveal that distinct molecular mechanisms underlie the altered gating behavior of channels carrying disease-causing mutations at different voltage-sensing domain locations, thereby expanding our current view of the pathogenesis of neuronal hyperexcitability diseases. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Tubular Unimolecular Transmembrane Channels: Construction Strategy and Transport Activities.

PubMed

Si, Wen; Xin, Pengyang; Li, Zhan-Ting; Hou, Jun-Li

2015-06-16

Lipid bilayer membranes separate living cells from their environment. Membrane proteins are responsible for the processing of ion and molecular inputs and exports, sensing stimuli and signals across the bilayers, which may operate in a channel or carrier mechanism. Inspired by these wide-ranging functions of membrane proteins, chemists have made great efforts in constructing synthetic mimics in order to understand the transport mechanisms, create materials for separation, and develop therapeutic agents. Since the report of an alkylated cyclodextrin for transporting Cu(2+) and Co(2+) by Tabushi and co-workers in 1982, chemists have constructed a variety of artificial transmembrane channels by making use of either the multimolecular self-assembly or unimolecular strategy. In the context of the design of unimolecular channels, important advances have been made, including, among others, the tethering of natural gramicidin A or alamethicin and the modification of various macrocycles such as crown ethers, cyclodextrins, calixarenes, and cucurbiturils. Many of these unimolecular channels exhibit high transport ability for metal ions, particularly K(+) and Na(+). Concerning the development of artificial channels based on macrocyclic frameworks, one straightforward and efficient approach is to introduce discrete chains to reinforce their capability to insert into bilayers. Currently, this approach has found the widest applications in the systems of crown ethers and calixarenes. We envisioned that for macrocycle-based unimolecular channels, control of the arrangement of the appended chains in the upward and/or downward direction would favor the insertion of the molecular systems into bilayers, while the introduction of additional interactions among the chains would further stabilize a tubular conformation. Both factors should be helpful for the formation of new efficient channels. In this Account, we discuss our efforts in designing new unimolecular artificial channels from

Groundwater exchanges near a channelized versus unmodified stream mouth discharging to a subalpine lake

USGS Publications Warehouse

Constantz, James; Naranjo, Ramon C.; Niswonger, Richard G.; Allander, Kip K.; Neilson, B.; Rosenberry, Donald O.; Smith, David W.; Rosecrans, C.; Stonestrom, David A.

2016-01-01

The terminus of a stream flowing into a larger river, pond, lake, or reservoir is referred to as the stream-mouth reach or simply the stream mouth. The terminus is often characterized by rapidly changing thermal and hydraulic conditions that result in abrupt shifts in surface water/groundwater (sw/gw) exchange patterns, creating the potential for unique biogeochemical processes and ecosystems. Worldwide shoreline development is changing stream-lake interfaces through channelization of stream mouths, i.e., channel straightening and bank stabilization to prevent natural meandering at the shoreline. In the central Sierra Nevada (USA), Lake Tahoe's shoreline has an abundance of both “unmodified” (i.e., not engineered though potentially impacted by broader watershed engineering) and channelized stream mouths. Two representative stream mouths along the lake's north shore, one channelized and one unmodified, were selected to compare and contrast water and heat exchanges. Hydraulic and thermal properties were monitored during separate campaigns in September 2012 and 2013 and sw/gw exchanges were estimated within the stream mouth-shoreline continuum. Heat-flow and water-flow patterns indicated clear differences in the channelized versus the unmodified stream mouth. For the channelized stream mouth, relatively modulated, cool-temperature, low-velocity longitudinal streambed flows discharged offshore beneath warmer buoyant lakeshore water. In contrast, a seasonal barrier bar formed across the unmodified stream mouth, creating higher-velocity subsurface flow paths and higher diurnal temperature variations relative to shoreline water. As a consequence, channelization altered sw/gw exchanges potentially altering biogeochemical processing and ecological systems in and near the stream mouth.

WHIRLIN INCREASES TRPV1 CHANNEL EXPRESSION AND CELLULAR STABILITY

PubMed Central

Ciardo, Maria Grazia; Andrés-Bordería, Amparo; Cuesta, Natalia; Valente, Pierluigi; Camprubí-Robles, María; Yang, Jun; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

2017-01-01

The expression and function of TRPV1 is influenced by its interaction with cellular proteins. Here, we identify whirlin, a cytoskeletal PDZ-scaffold protein implicated in hearing, vision and mechanosensory transduction, as an interacting partner of TRPV1. Whirlin associates with TRPV1 in cell lines and in primary cultures of rat nociceptors. Whirlin is expressed in 55% of mouse sensory C-fibers, including peptidergic and non-peptidergic nociceptors, and co-localizes with TRPV1 in 70% of them. Heterologous expression of Whirlin increased TRPV1 protein expression and trafficking to the plasma membrane, and promoted receptor clustering. Silencing Whirlin expression with siRNA or blocking protein translation resulted in a concomitant degradation of TRPV1 that could be prevented by inhibiting the proteasome. The degradation kinetics of TRPV1 upon arresting protein translation mirrored that of Whirlin in cells co-expressing both proteins, suggesting a parallel degradation mechanism. Noteworthy, Whirlin expression significantly reduced TRPV1 degradation induced by prolonged exposure to capsaicin. Thus, our findings indicate that Whirlin and TRPV1 are associated in a subset of nociceptors and that TRPV1 protein stability is increased through the interaction with the cytoskeletal scaffold protein. Our results suggest that the Whirlin-TRPV1 complex may represent a novel molecular target and its pharmacological disruption might be a therapeutic strategy for the treatment of peripheral TRPV1-mediated disorders. PMID:26516054

Helicity, membrane incorporation, orientation and thermal stability of the large conductance mechanosensitive ion channel from E. coli

NASA Technical Reports Server (NTRS)

Arkin, I. T.; Sukharev, S. I.; Blount, P.; Kung, C.; Brunger, A. T.

1998-01-01

In this report, we present structural studies on the large conductance mechanosensitive ion channel (MscL) from E. coli in detergent micelles and lipid vesicles. Both transmission Fourier transform infrared spectroscopy and circular dichroism (CD) spectra indicate that the protein is highly helical in detergents as well as liposomes. The secondary structure of the proteins was shown to be highly resistant towards denaturation (25-95 degrees C) based on an ellipticity thermal profile. Amide H+/D+ exchange was shown to be extensive (ca. 66%), implying that two thirds of the protein are water accessible. MscL, reconstituted in oriented lipid bilayers, was shown to possess a net bilayer orientation using dichroic ratios measured by attenuated total-reflection Fourier transform infrared spectroscopy. Here, we present and discuss this initial set of structural data on this new family of ion-channel proteins.

Absence of ion-binding affinity in the putatively inactivated low-[K+] structure of the KcsA potassium channel.

PubMed

Boiteux, Céline; Bernèche, Simon

2011-01-12

Potassium channels are membrane proteins that selectively conduct K(+) across cellular membranes. The narrowest part of their pore, the selectivity filter, is responsible for distinguishing K(+) from Na(+), and can also act as a gate through a mechanism known as C-type inactivation. It has been proposed that a conformation of the KcsA channel obtained by crystallization in presence of low concentration of K(+) (PDB 1K4D) could correspond to the C-type inactivated state. Here, we show using molecular mechanics simulations that such conformation has little ion-binding affinity and that ions do not contribute to its stability. The simulations suggest that, in this conformation, the selectivity filter is mostly occupied by water molecules. Whether such ion-free state of the KcsA channel is physiologically accessible and representative of the inactivated state of eukaryotic channels remains unclear. Copyright © 2011 Elsevier Ltd. All rights reserved.

A large iris-like expansion of a mechanosensitive channel protein induced by membrane tension

NASA Technical Reports Server (NTRS)

Betanzos, Monica; Chiang, Chien-Sung; Guy, H. Robert; Sukharev, Sergei

2002-01-01

MscL, a bacterial mechanosensitive channel of large conductance, is the first structurally characterized mechanosensor protein. Molecular models of its gating mechanisms are tested here. Disulfide crosslinking shows that M1 transmembrane alpha-helices in MscL of resting Escherichia coli are arranged similarly to those in the crystal structure of MscL from Mycobacterium tuberculosis. An expanded conformation was trapped in osmotically shocked cells by the specific bridging between Cys 20 and Cys 36 of adjacent M1 helices. These bridges stabilized the open channel. Disulfide bonds engineered between the M1 and M2 helices of adjacent subunits (Cys 32-Cys 81) do not prevent channel gating. These findings support gating models in which interactions between M1 and M2 of adjacent subunits remain unaltered while their tilts simultaneously increase. The MscL barrel, therefore, undergoes a large concerted iris-like expansion and flattening when perturbed by membrane tension.

Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel

PubMed Central

Niemeyer, María Isabel; González-Nilo, Fernando D.; Zúñiga, Leandro; González, Wendy; Cid, L. Pablo; Sepúlveda, Francisco V.

2007-01-01

Potassium channels share a common selectivity filter that determines the conduction characteristics of the pore. Diversity in K+ channels is given by how they are gated open. TASK-2, TALK-1, and TALK-2 are two-pore region (2P) KCNK K+ channels gated open by extracellular alkalinization. We have explored the mechanism for this alkalinization-dependent gating using molecular simulation and site-directed mutagenesis followed by functional assay. We show that the side chain of a single arginine residue (R224) near the pore senses pH in TASK-2 with an unusual pKa of 8.0, a shift likely due to its hydrophobic environment. R224 would block the channel through an electrostatic effect on the pore, a situation relieved by its deprotonation by alkalinization. A lysine residue in TALK-2 fulfills the same role but with a largely unchanged pKa, which correlates with an environment that stabilizes its positive charge. In addition to suggesting unified alkaline pH-gating mechanisms within the TALK subfamily of channels, our results illustrate in a physiological context the principle that hydrophobic environment can drastically modulate the pKa of charged amino acids within a protein. PMID:17197424

Thermal Stability of RP-2 for Hydrocarbon Boost Regenerative Cooling

NASA Technical Reports Server (NTRS)

Kleinhenz, Julie E.; Deans, Matthew C.; Stiegemeier, Benjamin R.; Psaras, Peter M.

2013-01-01

A series of tests were performed in the NASA Glenn Research Centers Heated Tube Facility to study the heat transfer and thermal stability behavior of RP-2 under conditions similar to those found in rocket engine cooling channels. It has long been known that hydrocarbon fuels, such as RP-2, can decompose at high temperature to form deposits (coke) which can adversely impact rocket engine cooling channel performance. The heated tube facility provides a simple means to study these effects. Using resistively heated copper tubes in a vacuum chamber, flowing RP-2 was heated to explore thermal effects at a range of test conditions. Wall temperature (850-1050F) and bulk fluid temperature (300-500F) were varied to define thermal decomposition and stability at each condition. Flow velocity and pressure were fixed at 75 fts and 1000 psia, respectively. Additionally, five different batches of RP-2 were tested at identical conditions to examine any thermal stability differences resulting from batch to batch compositional variation. Among these tests was one with a potential coke reducing additive known as 1,2,3,4-Tetrahydroquinoline (THQ). While copper tubes were used for the majority of tests, two exploratory tests were performed with a copper alloy known as GRCop-42. Each tube was instrumented with 15 thermocouples to examine the temperature profile, and carbon deposition at each thermocouple location was determined post-test in an oxidation furnace. In many tests, intermittent local temperature increases were observed visually and in the thermocouple data. These hot spots did not appear to correspond with a higher carbon deposition.

Two different types of channels exhibiting distinct proton transport behavior in an open-framework aluminophosphate

NASA Astrophysics Data System (ADS)

Xue, Chen; Zou, Yang; Liu, Shao-Xian; Ren, Xiao-Ming; Tian, Zheng-Fang

2018-02-01

A three-dimensional open-framework aluminophosphate, (NH4)2Al4(PO4)4(HPO4)·H2O (1), shows two types of eight-membered polyhedral ring channels. The lattice water molecules occupy within the channel with (HO)PO3 tetrahedra (channel-I), whilst the ammonium ions reside in another type of channel (channel-II). This aluminophosphate shows superior stability to water and NaOH aqueous solution, but unstable to H2SO4 aqueous solution. The proton conductance of 1 has been investigated under anhydrous condition and various relative humidity, indicating rather low conductivity under anhydrous condition even at elevated temperature (σdc = 9.05 × 10-13 S cm-1 at 343 K and 4.25 × 10-10 S cm-1 even at 473 K), and this situation demonstrates that both the ammonium ions and the protons in (HO)PO3 tetrahedra have quite low mobility. The conductivity of 1 reaches to 4.0 × 10-5 S cm-1 at 299 K, 2.57 × 10-4 S cm-1 at 343 K under 99%RH, respectively. The greatly enhancement of proton conductivity at 99%RH is due to the formation of H-bond between H2O molecules and (HO)PO3 tetrahedra in the channel-I to assist proton hopping process, while the ammonium ions show negligible contribution to enhancement of proton conductivity.

Neurotransmitter Release Can Be Stabilized by a Mechanism That Prevents Voltage Changes Near the End of Action Potentials from Affecting Calcium Currents

PubMed Central

Clarke, Stephen G.; Scarnati, Matthew S.

2016-01-01

At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating. In support of this, presynaptic calcium entry is affected by afterpotentials after standard instant voltage jumps. Here, we used the mouse calyx of Held synapse, which allows simultaneous presynaptic and postsynaptic patch-clamp recording, to show that the postsynaptic response is affected significantly by presynaptic afterpotentials after voltage jumps. We therefore tested the effects of presynaptic afterpotentials using simultaneous presynaptic and postsynaptic recordings and AP waveforms or real APs. Surprisingly, presynaptic afterpotentials after AP stimuli did not alter calcium channel responses or neurotransmitter release appreciably. We show that the AP repolarization time course causes afterpotential-induced changes in calcium driving force and changes in calcium channel gating to effectively cancel each other out. This mechanism, in which electrical driving force is balanced by channel gating, prevents changes in calcium influx from occurring at the end of the AP and therefore acts to stabilize synaptic transmission. In addition, this mechanism can act to stabilize neurotransmitter release when the presynaptic resting potential changes. SIGNIFICANCE STATEMENT The shape of presynaptic action potentials (APs), particularly the falling phase, affects calcium entry and small changes in calcium influx can produce large

[Single channel analysis of aconitine blockade of calcium channels in rat myocardiocytes].

PubMed

Chen, L; Ma, C; Cai, B C; Lu, Y M; Wu, H

1995-01-01

Ventricular myocardiocytes from neonatal Wistar rats were isolated and cultured. Aconitine, Ca2+ channel blocker verapamil or Ca2+ channel activator BAY K8644 were added to the bath solution separately. Using the cell-attached configuration of the patch clamp technique, the single channel activities of L type Ca2+ channel were recorded before and after addition of all three drugs. The results showed the blocking effect of aconitine (50 micrograms.ml-1) on L type Ca2+ channels. Its mechanism may be relevant to the decrease in both open state probability and the mean open time of Ca2+ channel. The difference was statistically significant compared with control group (P < 0.01). The amplitude of Ba2+ currents, which flow through open L type Ca2+ channel was unchanged.

Plasma-deposited amorphous silicon carbide films for micromachined fluidic channels

NASA Astrophysics Data System (ADS)

Wuu, Dong-Sing; Horng, Ray-Hua; Chan, Chia-Chi; Lee, Yih-Shing

1999-04-01

The stress properties of the a-SiC:H films on Si by plasma-enhanced chemical vapor deposition (PECVD) are investigated. It is found that the stability of the a-SiC:H films relates to Si-H bonds breaking and changes the stress toward tensile. No evident reduction in the content of Si-H bonds after thermal cycles was found in the carbon-rich samples. Moreover, a new method to fabricate microchannels by through-hole etching with subsequent planarization is proposed. The process is based on etching out the deep grooves through a perforated a-SiC:H membrane, where poly-Si is used as a sacrificial layer to define the channel structure, followed by PECVD sealing the SiC:H membrane. In order to improve the etching performance, the agitated KOH etch is performed at low temperatures (<50°C). The process technology is demonstrated on the fabrication of microfluidic channels with the low-stress (<0.1 GPa) a-SiC:H membranes.

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channels.

PubMed

Luo, J; Chen, M; Wu, W Y; Weng, S M; Sheng, Z M; Schroeder, C B; Jaroszynski, D A; Esarey, E; Leemans, W P; Mori, W B; Zhang, J

2018-04-13

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV-level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize the simultaneous coupling of the electron beam and the laser pulse into a second stage. A partly curved channel, integrating a straight acceleration stage with a curved transition segment, is used to guide a fresh laser pulse into a subsequent straight channel, while the electrons continue straight. This scheme benefits from a shorter coupling distance and continuous guiding of the electrons in plasma while suppressing transverse beam dispersion. Particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration while maintaining high capture efficiency, stability, and beam quality.

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channels

NASA Astrophysics Data System (ADS)

Luo, J.; Chen, M.; Wu, W. Y.; Weng, S. M.; Sheng, Z. M.; Schroeder, C. B.; Jaroszynski, D. A.; Esarey, E.; Leemans, W. P.; Mori, W. B.; Zhang, J.

2018-04-01

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV-level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize the simultaneous coupling of the electron beam and the laser pulse into a second stage. A partly curved channel, integrating a straight acceleration stage with a curved transition segment, is used to guide a fresh laser pulse into a subsequent straight channel, while the electrons continue straight. This scheme benefits from a shorter coupling distance and continuous guiding of the electrons in plasma while suppressing transverse beam dispersion. Particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration while maintaining high capture efficiency, stability, and beam quality.

TRPC5 channels participate in pressure-sensing in aortic baroreceptors

PubMed Central

Lau, On-Chai; Shen, Bing; Wong, Ching-On; Tjong, Yung-Wui; Lo, Chun-Yin; Wang, Hui-Chuan; Huang, Yu; Yung, Wing-Ho; Chen, Yang-Chao; Fung, Man-Lung; Rudd, John Anthony; Yao, Xiaoqiang

2016-01-01

Blood pressure is maintained within a normal physiological range by a sophisticated regulatory mechanism. Baroreceptors serve as a frontline sensor to detect the change in blood pressure. Nerve signals are then sent to the cardiovascular control centre in the brain in order to stimulate baroreflex responses. Here, we identify TRPC5 channels as a mechanical sensor in aortic baroreceptors. In Trpc5 knockout mice, the pressure-induced action potential firings in the afferent nerve and the baroreflex-mediated heart rate reduction are attenuated. Telemetric measurements of blood pressure demonstrate that Trpc5 knockout mice display severe daily blood pressure fluctuation. Our results suggest that TRPC5 channels represent a key pressure transducer in the baroreceptors and play an important role in maintaining blood pressure stability. Because baroreceptor dysfunction contributes to a variety of cardiovascular diseases including hypertension, heart failure and myocardial infarction, our findings may have important future clinical implications. PMID:27411851

Reconstructive techniques for creation of catheterizable channels: tunneled and nipple valve channels

PubMed Central

Levy, Mya E.

2016-01-01

Cutaneous catheterizable channels allow for continent bladder emptying when an alternate route is desired. The goals of channel creation in the neurogenic bladder population are successful urine elimination, renal preservation, continence and lastly cosmesis. In addition to a particular surgeon’s comfort and experience with a given procedure, individual patient factors such as medical comorbidities, anatomic factors, and occupational function should be central to the selection of a surgical approach. An ideal channel is one that is short, straight, and well supported by associated blood supply and surrounding adventitia, so as to minimize difficulty with catheterization. Two types of channel continence mechanisms are discussed at length in this review—the tunneled channel, and the nipple valve. The appendicovesicostomy (Mitrofanoff), and reconfigured ileum (Yang-Monti) are both tunneled channels. The ileocecal valve is a commonly used nipple valve and provides continence when reinforced. The continent catheterizable ileal cecocystoplasty (CCIC) is an example of this channel technique. This method couples a tapered ileal limb as a catheterizable channel, the ileocecal valve as the continence mechanism, and the cecum and ascending colon as a bladder augmentation. While this procedure has higher perioperative complications relative to a simple tunneled channel, it has increased channel length flexibility and is also coupled with a bladder augment, which is completely performed using one bowel segment. Continent channel creation in adults can improve quality of life and minimize morbidity associated with neurogenic bladder. However, the decision to proceed with creation of a catheterizable channel should be made only after careful consideration of the patient’s medical comorbidities, physical abilities social support, and surgeon experience. PMID:26904419

Resilience and stability of a pelagic marine ecosystem

PubMed Central

Lindegren, Martin; Checkley, David M.; Ohman, Mark D.; Koslow, J. Anthony; Goericke, Ralf

2016-01-01

The accelerating loss of biodiversity and ecosystem services worldwide has accentuated a long-standing debate on the role of diversity in stabilizing ecological communities and has given rise to a field of research on biodiversity and ecosystem functioning (BEF). Although broad consensus has been reached regarding the positive BEF relationship, a number of important challenges remain unanswered. These primarily concern the underlying mechanisms by which diversity increases resilience and community stability, particularly the relative importance of statistical averaging and functional complementarity. Our understanding of these mechanisms relies heavily on theoretical and experimental studies, yet the degree to which theory adequately explains the dynamics and stability of natural ecosystems is largely unknown, especially in marine ecosystems. Using modelling and a unique 60-year dataset covering multiple trophic levels, we show that the pronounced multi-decadal variability of the Southern California Current System (SCCS) does not represent fundamental changes in ecosystem functioning, but a linear response to key environmental drivers channelled through bottom-up and physical control. Furthermore, we show strong temporal asynchrony between key species or functional groups within multiple trophic levels caused by opposite responses to these drivers. We argue that functional complementarity is the primary mechanism reducing community variability and promoting resilience and stability in the SCCS. PMID:26763697

Multiple Channel Bridges for Spinal Cord Injury: Cellular Characterization of Host Response

PubMed Central

Yang, Yang; Laporte, Laura De; Zelivyanskaya, Marina L.; Whittlesey, Kevin J.; Anderson, Aileen J.; Cummings, Brian J.

2009-01-01

Bridges for treatment of the injured spinal cord must stabilize the injury site to prevent secondary damage and create a permissive environment that promotes regeneration. The host response to the bridge is central to creating a permissive environment, as the cell types that respond to the injury have the potential to secrete both stimulatory and inhibitory factors. We investigated multiple channel bridges for spinal cord regeneration and correlated the bridge structure to cell infiltration and axonal elongation. Poly(lactide-co-glycolide) bridges were fabricated by a gas foaming/particulate leaching process. Channels within the bridge had diameters of 150 or 250 μm, and the main body of the bridge was highly porous with a controllable pore size. Upon implantation in a rat spinal cord hemisection site, cells infiltrated into the bridge pores and channels, with the pore size influencing the rate of infiltration. The pores had significant cell infiltration, including fibroblasts, macrophages, S-100β-positive cells, and endothelial cells. The channels of the bridge were completely infiltrated with cells, which had aligned axially, and consisted primarily of fibroblasts, S-100β-positive cells, and endothelial cells. Reactive astrocytes were observed primarily outside of the bridge, and staining for chondroitin sulfate proteoglycans was decreased in the region surrounding the bridge relative to studies without bridges. Neurofilament staining revealed a preferential growth of the neural fibers within the bridge channels relative to the pores. Multiple channel bridges capable of supporting cellular infiltration, creating a permissive environment, and directing the growth of neural fibers have potential for promoting and directing spinal cord regeneration. PMID:19382871

Hemoglobin crystals immersed in liquid oxygen reveal diffusion channels.

PubMed

Terrell, James Ross; Gumpper, Ryan H; Luo, Ming

2018-01-08

Human hemoglobin (HbA) transports molecular oxygen (O 2 ) from the lung to tissues where the partial pressure of O 2 is lower. O 2 binds to HbA at the heme cofactor and is stabilized by a distal histidine (HisE7). HisE7 has been observed to occupy opened and closed conformations, and is postulated to act as a gate controlling the binding/release of O 2 . However, it has been suggested that HbA also contains intraprotein oxygen channels for entrances/exits far from the heme. In this study, we developed a novel method of crystal immersion in liquid oxygen prior to X-ray data collection. In the crystals immersed in liquid oxygen, the heme center was oxidized to generate aquomethemoglobin. Increases of structural flexibility were also observed in regions that are synonymous with previously postulated oxygen channels. These regions also correspond to medically relevant mutations which affect O 2 affinity. The way HbA utilizes these O 2 channels could have a profound impact on understanding the relationship of HbA O 2 transport within these disease conditions. Finally, the liquid oxygen immersion technique can be utilized as a new tool to crystallographically examine proteins and protein complexes which utilize O 2 for enzyme catalysis or transport. Copyright © 2017 Elsevier Inc. All rights reserved.

Adaptive channel estimation for soft decision decoding over non-Gaussian optical channel

NASA Astrophysics Data System (ADS)

Xiang, Jing-song; Miao, Tao-tao; Huang, Sheng; Liu, Huan-lin

2016-10-01

An adaptive priori likelihood ratio (LLR) estimation method is proposed over non-Gaussian channel in the intensity modulation/direct detection (IM/DD) optical communication systems. Using the nonparametric histogram and the weighted least square linear fitting in the tail regions, the LLR is estimated and used for the soft decision decoding of the low-density parity-check (LDPC) codes. This method can adapt well to the three main kinds of intensity modulation/direct detection (IM/DD) optical channel, i.e., the chi-square channel, the Webb-Gaussian channel and the additive white Gaussian noise (AWGN) channel. The performance penalty of channel estimation is neglected.

Ion channels in plants.

PubMed

Hedrich, Rainer

2012-10-01

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K(+)-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K(+) channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

Thin walled channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crowther, R.L.; Johansson, E.B.

1988-06-07

A fuel assembly is described comprising fuel rods positioned in a spaced array by upper and lower tie-plates, an open ended flow channel surrounding the array for conducting coolant upward about the fuel rods, the open ended channel having a polygon shaped cross section with flat side sections connected between the corner sections; means separate from the channel connecting the upper and lower tie-plates together and maintaining the fuel rods in spaced array independent of the flow channel, improvement in the flow channel comprising: four corners having a first thickness; four sides having a second and reduced thickness from themore » corner thickness, the sides welded to the corner sections.« less

Stabilization of a gravel channel by large streamside obstructions and bedrock bends, Jacoby Creek, northwestern California

Treesearch

Thomas E. Lisle

1996-01-01

Abstract - Jacoby Creek (bed width =12 m; bankfull discharge = 32.6 m 3 /s) contains stationary gravel bars that have forms and positions controlled by numerous large streamside obstructions (bedrock outcrops, large woody debris, and rooted bank projections) and bedrock bends. Bank-projection width and bar volume measured in 104 channel segments 1 bed-width long are...

Channel and Timeslot Co-Scheduling with Minimal Channel Switching for Data Aggregation in MWSNs

PubMed Central

Yeoum, Sanggil; Kang, Byungseok; Lee, Jinkyu; Choo, Hyunseung

2017-01-01

Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs). While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources) optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel and time slot scheduling for minimal channel switching in MWSNs, while achieving efficient and collision-free transmission between nodes. The proposed scheme constructs a duty-cycled tree while reducing the amount of channel switching. As a next step, collision-free time slots are assigned to every node based on the minimal data collection delay. The experimental results demonstrate that the validity of our scheme reduces the amount of channel switching by 17.5%, reduces energy consumption for channel switching by 28%, and reduces the schedule length by 46%, as compared to the existing schemes. PMID:28471416

Channel and Timeslot Co-Scheduling with Minimal Channel Switching for Data Aggregation in MWSNs.

PubMed

Yeoum, Sanggil; Kang, Byungseok; Lee, Jinkyu; Choo, Hyunseung

2017-05-04

Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs). While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources) optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel and time slot scheduling for minimal channel switching in MWSNs, while achieving efficient and collision-free transmission between nodes. The proposed scheme constructs a duty-cycled tree while reducing the amount of channel switching. As a next step, collision-free time slots are assigned to every node based on the minimal data collection delay. The experimental results demonstrate that the validity of our scheme reduces the amount of channel switching by 17.5%, reduces energy consumption for channel switching by 28%, and reduces the schedule length by 46%, as compared to the existing schemes.

Reliable video transmission over fading channels via channel state estimation

NASA Astrophysics Data System (ADS)

Kumwilaisak, Wuttipong; Kim, JongWon; Kuo, C.-C. Jay

2000-04-01

Transmission of continuous media such as video over time- varying wireless communication channels can benefit from the use of adaptation techniques in both source and channel coding. An adaptive feedback-based wireless video transmission scheme is investigated in this research with special emphasis on feedback-based adaptation. To be more specific, an interactive adaptive transmission scheme is developed by letting the receiver estimate the channel state information and send it back to the transmitter. By utilizing the feedback information, the transmitter is capable of adapting the level of protection by changing the flexible RCPC (rate-compatible punctured convolutional) code ratio depending on the instantaneous channel condition. The wireless channel is modeled as a fading channel, where the long-term and short- term fading effects are modeled as the log-normal fading and the Rayleigh flat fading, respectively. Then, its state (mainly the long term fading portion) is tracked and predicted by using an adaptive LMS (least mean squares) algorithm. By utilizing the delayed feedback on the channel condition, the adaptation performance of the proposed scheme is first evaluated in terms of the error probability and the throughput. It is then extended to incorporate variable size packets of ITU-T H.263+ video with the error resilience option. Finally, the end-to-end performance of wireless video transmission is compared against several non-adaptive protection schemes.

Ferritin ion channel disorder inhibits Fe(II)/O2 reactivity at distant sites.

PubMed

Tosha, Takehiko; Behera, Rabindra K; Theil, Elizabeth C

2012-11-05

Ferritins, a complex, mineralized, protein nanocage family essential for life, provide iron concentrates and oxidant protection. Protein-based ion channels and Fe(II)/O(2) catalysis initiate conversion of thousands of Fe atoms to caged, ferritin Fe(2)O(3)·H(2)O minerals. The ion channels consist of six helical segments, contributed by 3 of 12 or 24 polypeptide subunits, around the 3-fold cage axes. The channel structure guides entering Fe(II) ions toward multiple, catalytic, diiron sites buried inside ferritin protein helices, ~20 Å away from channel internal exits. The catalytic product, Fe(III)-O(H)-Fe(III), is a mineral precursor; mineral nucleation begins inside the protein cage with mineral growth in the central protein cavity (5-8 nm diameter). Amino acid substitutions that changed ionic or hydrophobic channel interactions R72D, D122R, and L134P increased ion channel structural disorder (protein crystallographic analyses) and increased Fe(II) exit [chelated Fe(II) after ferric mineral reduction/dissolution]. Since substitutions of some channel carboxylate residues diminished ferritin catalysis with no effect on Fe(II) exit, such as E130A and D127A, we investigated catalysis in ferritins with altered Fe(II) exit, R72D, D122R and L134P. The results indicate that simply changing the ionic properties of the channels, as in the R72D variant, need not change the forward catalytic rate. However, both D122R and L134P, which had dramatic effects on ferritin catalysis, also caused larger effects on channel structure and order, contrasting with R72D. All three amino acid substitutions, however, decreased the stability of the catalytic intermediate, diferric peroxo, even though overall ferritin cage structure is very stable, resisting 80 °C and 6 M urea. The localized structural changes in ferritin subdomains that affect ferritin function over long distances illustrate new properties of the protein cage in natural ferritin function and for applied ferritin uses.

Symmetrization for redundant channels

NASA Technical Reports Server (NTRS)

Tulplue, Bhalchandra R. (Inventor); Collins, Robert E. (Inventor)

1988-01-01

A plurality of redundant channels in a system each contain a global image of all the configuration data bases in each of the channels in the system. Each global image is updated periodically from each of the other channels via cross channel data links. The global images of the local configuration data bases in each channel are separately symmetrized using a voting process to generate a system signal configuration data base which is not written into by any other routine and is available for indicating the status of the system within each channel. Equalization may be imposed on a suspect signal and a number of chances for that signal to heal itself are provided before excluding it from future votes. Reconfiguration is accomplished upon detecting a channel which is deemed invalid. A reset function is provided which permits an externally generated reset signal to permit a previously excluded channel to be reincluded within the system. The updating of global images and/or the symmetrization process may be accomplished at substantially the same time within a synchronized time frame common to all channels.

Development of a Flow Injection Based High Frequency Dual Channel Quartz Crystal Microbalance

PubMed Central

Liang, Jinxing; Zhang, Jing; Zhou, Wenxiang; Ueda, Toshitsugu

2017-01-01

When the quartz crystal microbalance (QCM) is used in liquid for adsorption or desorption monitoring based bio- or chemical sensing applications, the frequency shift is not only determined by the surface mass change, but also by the change of liquid characteristics, such as density and viscosity, which are greatly affected by the liquid environmental temperature. A monolithic dual-channel QCM is designed and fabricated by arranging two QCM resonators on one single chip for cancelling the fluctuation induced by environmental factors. In actual applications, one QCM works as a specific sensor by modifying with functional membranes and the other acts as a reference, only measuring the liquid property. The dual-channel QCM is designed with an inverted-mesa structure, aiming to realize a high frequency miniaturized chip and suppress the frequency interference between the neighbored QCM resonators. The key problem of dual-channel QCMs is the interference between two channels, which is influenced by the distance of adjacent resonators. The diameter of the reference electrode has been designed into several values in order to find the optimal parameter. Experimental results demonstrated that the two QCMs could vibrate individually and the output frequency stability and drift can be greatly improved with the aid of the reference QCM. PMID:28509851

Interacting tilt and kink instabilities in repelling current channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keppens, R.; Porth, O.; Xia, C., E-mail: rony.keppens@wis.kuleuven.be

2014-11-01

We present a numerical study in resistive magnetohydrodynamics (MHD) where the initial equilibrium configuration contains adjacent, oppositely directed, parallel current channels. Since oppositely directed current channels repel, the equilibrium is liable to an ideal magnetohydrodynamic tilt instability. This tilt evolution, previously studied in planar settings, involves two magnetic islands or flux ropes, which on Alfvénic timescales undergo a combined rotation and separation. This in turn leads to the creation of (near) singular current layers, posing severe challenges to numerical approaches. Using our open-source grid-adaptive MPI-AMRVAC software, we revisit the planar evolution case in compressible MHD, as well as its extensionmore » to two-and-a-half-dimensional (2.5D) and full three-dimensional (3D) scenarios. As long as the third dimension can be ignored, pure tilt evolutions result that are hardly affected by out of plane magnetic field components. In all 2.5D runs, our simulations do show secondary tearing type disruptions throughout the near singular current sheets in the far nonlinear saturation regime. In full 3D runs, both current channels can be liable to additional ideal kink deformations. We discuss the effects of having both tilt and kink instabilities acting simultaneously in the violent, reconnection-dominated evolution. In 3D, both the tilt and the kink instabilities can be stabilized by tension forces. As a concrete space plasma application, we argue that interacting tilt-kink instabilities in repelling current channels provide a novel route to initiate solar coronal mass ejections, distinctly different from the currently favored pure kink or torus instability routes.« less

Artificial semiconductor/insulator superlattice channel structure for high-performance oxide thin-film transistors

PubMed Central

Ahn, Cheol Hyoun; Senthil, Karuppanan; Cho, Hyung Koun; Lee, Sang Yeol

2013-01-01

High-performance thin-film transistors (TFTs) are the fundamental building blocks in realizing the potential applications of the next-generation displays. Atomically controlled superlattice structures are expected to induce advanced electric and optical performance due to two-dimensional electron gas system, resulting in high-electron mobility transistors. Here, we have utilized a semiconductor/insulator superlattice channel structure comprising of ZnO/Al2O3 layers to realize high-performance TFTs. The TFT with ZnO (5 nm)/Al2O3 (3.6 nm) superlattice channel structure exhibited high field effect mobility of 27.8 cm2/Vs, and threshold voltage shift of only < 0.5 V under positive/negative gate bias stress test during 2 hours. These properties showed extremely improved TFT performance, compared to ZnO TFTs. The enhanced field effect mobility and stability obtained for the superlattice TFT devices were explained on the basis of layer-by-layer growth mode, improved crystalline nature of the channel layers, and passivation effect of Al2O3 layers. PMID:24061388

Micromolar-Affinity Benzodiazepine Receptors Regulate Voltage-Sensitive Calcium Channels in Nerve Terminal Preparations

NASA Astrophysics Data System (ADS)

Taft, William C.; Delorenzo, Robert J.

1984-05-01

Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance.

Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations.

PubMed Central

Taft, W C; DeLorenzo, R J

1984-01-01

Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance. PMID:6328498

The Psychology of Channeling.

ERIC Educational Resources Information Center

Corey, Michael A.

1988-01-01

Theoretically analyzes phenomenon of channeling from perspective of C. G. Jung's analytic psychology. Hypothesizes that contact with otherworldly spiritual beings claimed by channelers is actually projected contact with contents of channeler's own unconscious mind. Suggests that channelers seek more constructive ways of contacting their…

Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

PubMed Central

Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M.T.; Wasmuth, Hermann E.; Gründer, Stefan

2013-01-01

Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA. PMID:23064163

Charged and Neutral Particles Channeling Phenomena Channeling 2008

NASA Astrophysics Data System (ADS)

Dabagov, Sultan B.; Palumbo, Luigi

2010-04-01

On the discovery of coherent Bremsstrahlung in a single crystal at the Frascati National Laboratories / C. Barbiellini, G. P. Murtas and S. B. Dabagov -- Advances in coherent Bremsstrahlung and LPM-effect studies (to the lOOth anniversary from the birth of L. D. Landau) / N. F. Shul'ga -- Spectra of radiation and created particles at intermediate energy in oriented crystal taking into account energy loss / V. N. Baier and V. M. Katkov -- The coherent Bremsstrahlung beam at MAX-lab facility / K. Fissum ... [et al.] -- Radiation from thin, structured targets (CERN NA63) / A. Dizdar -- Hard incoherent radiation in thick crystals / N. F. Shul'ga, V. V. Syshchenko and A. I. Tarnovsky -- Coherent Bremsstrahlung in periodically deformed crystals with a complex base / A. R. Mkrtchyan, A. A. Saharian and V. V. Parazian -- Induction of coherent x-ray Bremsstrahlung in crystals under the influence of acoustic waves / A. R. Mkrtchyan and V. V. Parazian -- Coherent processes in bent single crystals / V. A. Maisheev -- Experimental and theoretical investigation of complete transfer phenomenon for media with various heat exchange coefficients / A. R. Mkrtchyan, A. E. Movsisyan and V. R. Kocharyan -- Coherent pair production in crystals / A. R. Mkrtchyan, A. A. Saharian and V. V. Parazian -- Negative particle planar and axial channeling and channeling collimation / R. A. Carrigan, Jr. -- CERN crystal-based collimation in modern hadron colliders / W. Scandale -- Studies and application of bent crystals for beam steering at 70 GeV IHEP accelerator / A. G. Afonin ... [et al.] -- Crystal collimation studies at the Tevatron (T-980) / N. V. Mokhov ... [et al.] -- Fabrication of crystals for channeling of particles in accellerators / A. Mazzolari ... [et al.] -- New possibilities to facilitate collimation of both positively and negatively charged particle beams by crystals / V. Guidi, A. Mazzolari and V. V. Tikhomirov -- Increase of probability of particle capture into the channeling

Bayesian sparse channel estimation

NASA Astrophysics Data System (ADS)

Chen, Chulong; Zoltowski, Michael D.

2012-05-01

In Orthogonal Frequency Division Multiplexing (OFDM) systems, the technique used to estimate and track the time-varying multipath channel is critical to ensure reliable, high data rate communications. It is recognized that wireless channels often exhibit a sparse structure, especially for wideband and ultra-wideband systems. In order to exploit this sparse structure to reduce the number of pilot tones and increase the channel estimation quality, the application of compressed sensing to channel estimation is proposed. In this article, to make the compressed channel estimation more feasible for practical applications, it is investigated from a perspective of Bayesian learning. Under the Bayesian learning framework, the large-scale compressed sensing problem, as well as large time delay for the estimation of the doubly selective channel over multiple consecutive OFDM symbols, can be avoided. Simulation studies show a significant improvement in channel estimation MSE and less computing time compared to the conventional compressed channel estimation techniques.

Potassium channels in brain mitochondria.

PubMed

Bednarczyk, Piotr

2009-01-01

Potassium channels are the most widely distributed class of ion channels. These channels are transmembrane proteins known to play important roles in both normal and pathophysiological functions in all cell types. Various potassium channels are recognised as potential therapeutic targets in the treatment of Parkinson's disease, Alzheimer's disease, brain/spinal cord ischaemia and sepsis. In addition to their importance as therapeutic targets, certain potassium channels are known for their beneficial roles in anaesthesia, cardioprotection and neuroprotection. Some types of potassium channels present in the plasma membrane of various cells have been found in the inner mitochondrial membrane as well. Potassium channels have been proposed to regulate mitochondrial membrane potential, respiration, matrix volume and Ca(+) ion homeostasis. It has been proposed that mitochondrial potassium channels mediate ischaemic preconditioning in various tissues. However, the specificity of a pharmacological agents and the mechanisms underlying their effects on ischaemic preconditioning remain controversial. The following potassium channels from various tissues have been identified in the inner mitochondrial membrane: ATP-regulated (mitoK(ATP)) channel, large conductance Ca(2+)-regulated (mitoBK(Ca)) channel, intermediate conductance Ca(2+)-regulated (mitoIK(Ca)) channel, voltage-gated (mitoKv1.3 type) channel, and twin-pore domain (mitoTASK-3) channel. It has been shown that increased potassium flux into brain mitochondria induced by either the mitoK(ATP) channel or mitoBK(Ca) channel affects the beneficial effects on neuronal cell survival under pathological conditions. Recently, differential distribution of mitoBK(Ca) channels has been observed in neuronal mitochondria. These findings may suggest a neuroprotective role for the mitoBK(Ca) channel in specific brain structures. This minireview summarises current data on brain mitochondrial potassium channels and the efforts to identify

Lightning-channel conditioning

NASA Astrophysics Data System (ADS)

Sonnenfeld, R.; da Silva, C. L.; Eack, K.; Edens, H. E.; Harley, J.; McHarg, M.; Contreras Vidal, L.

2017-12-01

The concept of "conditioning" has several distinct applications in understanding lightning. It is commonly associated to the greater speed of dart-leaders vs. stepped leaders and the retrace of a cloud-to-ground channel by later return strokes. We will showadditional examples of conditioning: (A) High-speed videos of triggered flashes show "dark" periods of up to 50 ms between rebrightenings of an existing channel. (B) Interferometer (INTF) images of intra-cloud (IC) flashes demonstrate that electric-field "K-changes" correspond to rapid propagation of RF impulses along a previously formed channel separated by up to 20 ms with little RF emission on that channel. (C) Further, INTF images (like the one below) frequently show that the initial IC channel is more branched and "fuzzier'' than its later incarnations. Also, we contrast high-speed video, INTF observations, and spectroscopic measurements with possible physical mechanisms that can explain how channel conditioning guides and facilitates dart leader propagation. These mechanisms include: (1) a plasmochemical effect where electrons are stored in negative ions and released during the dart leader propagation via field-induced detachment; (2) small-amplitude residual currents that can maintain electrical conductivity; and (3) slow heat conduction cooling of plasma owing to channel expansion dynamics.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

PubMed

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis

PubMed Central

Patten, Shunmoogum A.; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary A.B.; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J. Alexander

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease. PMID:29202456

Meandering channels without vegetation: Examples from Nevada and Chile

NASA Astrophysics Data System (ADS)

Matsubara, Y.; Howard, A. D.; Burr, D. M.; Williams, R. M.; Moore, J. M.

2012-12-01

We report on a study motivated by the occurrence of highly sinuous, actively migrating paleochannels on Mars. Highly sinuous, unconfined meanders require small aspect ratios, which in turn require cohesive channel banks. This cohesion is obtained most commonly by vegetation cover coupled with high suspended sediment loading. The dominant role of vegetation in meandering is reflected in the difficulty in creating highly sinuous channels in flume experiment without introduction of vegetation. The occurrence of strongly meandering channels on Mars suggests meanders can develop in the absence of vegetation. The main objective of our study is to understand the processes of meander evolution in non-vegetated surfaces. We have studied two terrestrial sites in which meandering channels form where vegetation is sparse and has little influence on bank erodibility or point-bar deposition, indicating that there must be other mechanisms creating bank cohesion. One mechanism is stabilization of point-bar deposits by mud drapes. The Quinn River in Nevada is a sinuous channel that flows through fine lacustrine sediments on the floor of paleolake Lahontan resulting in the river having both bed and bank composed of sediment containing least 40% silt/clay. In addition to abundant mud, high salt content of the river water encourages flocculation and settling of fine sediment; thus both high clay/silt content and salt work together at the Quinn River to maintain a small aspect ratio. In contrast to the Quinn River, meandering channels on alluvial fans in the Atacama Desert in northern Chile are deposited by flows originating from the foothills of the Andes Mountains where sediments are coarser and more variable in size. Like Quinn River both fine sediments and salts contribute to meandering. The bank cohesion is provided by mudflows or hyperconcentrated flows creating bank drapes as well as extensive overbank levees which harden to adobe-like consistency. The Atacama Desert is rich in

Method and apparatus for stabilizing pulsed microwave amplifiers

DOEpatents

Hopkins, Donald B.

1993-01-01

Phase and amplitude variations at the output of a high power pulsed microwave amplifier arising from instabilities of the driving electron beam are suppressed with a feed-forward system that can stabilize pulses which are too brief for regulation by conventional feedback techniques. Such variations tend to be similar during successive pulses. The variations are detected during each pulse by comparing the amplifier output with the low power input signal to obtain phase and amplitude error signals. This enables storage of phase and amplitude correction signals which are used to make compensating changes in the low power input signal during the following amplifier output pulse which suppress the variations. In the preferred form of the invention, successive increments of the correction signals for each pulse are stored in separate channels of a multi-channel storage. Sequential readout of the increments during the next pulse provides variable control voltages to a voltage controlled phase shifter and voltage controlled amplitude modulator in the amplifier input signal path.

Method and apparatus for stabilizing pulsed microwave amplifiers

DOEpatents

Hopkins, D.B.

1993-01-26

Phase and amplitude variations at the output of a high power pulsed microwave amplifier arising from instabilities of the driving electron beam are suppressed with a feed-forward system that can stabilize pulses which are too brief for regulation by conventional feedback techniques. Such variations tend to be similar during successive pulses. The variations are detected during each pulse by comparing the amplifier output with the low power input signal to obtain phase and amplitude error signals. This enables storage of phase and amplitude correction signals which are used to make compensating changes in the low power input signal during the following amplifier output pulse which suppress the variations. In the preferred form of the invention, successive increments of the correction signals for each pulse are stored in separate channels of a multi-channel storage. Sequential readout of the increments during the next pulse provides variable control voltages to a voltage controlled phase shifter and voltage controlled amplitude modulator in the amplifier input signal path.

Stability limits of superhydrophobic longitudinal microgrooves in high Reynolds number turbulent flows

NASA Astrophysics Data System (ADS)

Rastegari, Amirreza; Akhavan, Rayhaneh

2017-11-01

The stability of the liquid/gas interfaces on SuperHydrophobic (SH) Longitudinal MicroGrooves (LMGs) in high Reynolds number turbulent flows of practical interest is investigated by analytical extrapolation of DNS results in turbulent channel flow at Reτ0 222 and 442 with SH LMGs at protrusion angle of θ = -30o . Given that the magnitude of pressure fluctuations in turbulent channel flow scales as prms+ √{ ln(Reτ) } , it is found that the stability limits of SH LMGs diminishes by factors of 4 when the Reynolds number of the base flow increases from Reτ0 200 of DNS to Reτ0 105 -106 of practical applications. For SH LMGs operating at Weber numbers of We+0 ≡ μuτ0 / σ 3 ×10-3 - 1.5 ×10-2 , corresponding to friction velocities of uτ0 0.2 - 1 m/s, this limits the size of stable LMGs to g+0 5 - 30 at Reτ0 105 and g+0 4 - 20 at Reτ0 106 , and the maximum drag reductions to DRmax 20 - 30 % at Reτ0 105 and DRmax 10 - 20 % at Reτ0 106 .

CFTR Cl- channel and CFTR-associated ATP channel: distinct pores regulated by common gates.

PubMed Central

Sugita, M; Yue, Y; Foskett, J K

1998-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is regulated by phosphorylation of the R domain and ATP hydrolysis at two nucleotide-binding domains (NBDs). It is controversial whether CFTR conducts ATP or whether CFTR might be closely associated with a separate ATP conductance. To characterize ATP channels associated with CFTR, we analyzed Cl- and ATP single channel-currents in excised inside-out membrane patches from MDCK epithelial cells transiently expressing CFTR. With 100 mM ATP in the pipette and 140 mM Cl- in the bath, ATP channels were associated with CFTR Cl- channels in two-thirds of patches that included CFTR. CFTR Cl- channels and CFTR-associated ATP channels had slope conductances of 7.4 pS and 5.2 pS, respectively, and had distinct reversal potentials and sensitivities to channel blockers. CFTR-associated ATP channels exhibited slow gating kinetics that depended on the presence of protein kinase A and cytoplasmic ATP, similar to CFTR Cl- channels. Gating kinetics of the ATP channels as well as the CFTR Cl- channels were similarly affected by non-hydrolyzable ATP analogues and mutations in the CFTR R domain and NBDs. Our results indicate that phosphorylation- and nucleotide-hydrolysis-dependent gating of CFTR is directly involved in gating of an associated ATP channel. However, the permeation pathways for Cl- and ATP are distinct and the ATP conduction pathway is not obligatorily associated with the expression of CFTR. PMID:9463368

Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639

PubMed Central

2015-01-01

The discovery of a novel peripherally acting and selective Cav3.2 T-type calcium channel blocker, ABT-639, is described. HTS hits 1 and 2, which have poor metabolic stability, were optimized to obtain 4, which has improved stability and oral bioavailability. Modification of 4 to further improve ADME properties led to the discovery of ABT-639. Following oral administration, ABT-639 produces robust antinociceptive activity in experimental pain models at doses that do not significantly alter psychomotor or hemodynamic function in the rat. PMID:26101566

Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639.

PubMed

Zhang, Qingwei; Xia, Zhiren; Joshi, Shailen; Scott, Victoria E; Jarvis, Michael F

2015-06-11

The discovery of a novel peripherally acting and selective Cav3.2 T-type calcium channel blocker, ABT-639, is described. HTS hits 1 and 2, which have poor metabolic stability, were optimized to obtain 4, which has improved stability and oral bioavailability. Modification of 4 to further improve ADME properties led to the discovery of ABT-639. Following oral administration, ABT-639 produces robust antinociceptive activity in experimental pain models at doses that do not significantly alter psychomotor or hemodynamic function in the rat.

Preparation and preclinical evaluation of 68Ga-DOTA-amlodipine for L-type calcium channel imaging

PubMed Central

Firuzyar, Tahereh; Jalilian, Amir Reza; Aboudzadeh, Mohammad Reza; Sadeghpour, Hossein; Shafiee-Ardestani, Mahdi; Khalaj, Ali

2016-01-01

Aim: In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging. Materials and Methods: Amlodipine DOTA conjugate was synthesized, characterized and went through calcium channel blockade, toxicity, apoptosis/necrosis tests. [68Ga] DOTA AMLO was prepared at optimized conditions followed by stability tests, partition coefficient determination and biodistribution studies using tissue counting and co incidence imaging up to 2 h. Results: [68Ga] DOTA AMLO was prepared at pH 4–5 in 7–10 min at 95°C in high radiochemical purity (>99%, radio thin layer chromatography; specific activity: 1.9–2.1 GBq/mmol) and was stable up to 4 h with a log P of −0.94. Calcium channel rich tissues including myocardium, and tissues with smooth muscle cells such as colon, intestine, and lungs demonstrated significant uptake. Co incidence images supported the biodistribution data up to 2 h. Conclusions: The complex can be a candidate for further positron emission tomography imaging for L type calcium channels. PMID:27833311

Enhancement-mode two-channel triple quantum dot from an undoped Si/Si 0.8Ge 0.2 quantum well hetero-structure

DOE PAGES

Studenikin, S. A.; Gaudreau, L.; Kataoka, K.; ...

2018-06-04

Here, we demonstrate coupled triple dot operation and charge sensing capability for the recently introduced quantum dot technology employing undoped Si/Si 0.8Ge 0.2 hetero-structures which also incorporate a single metal-gate layer to simplify fabrication. Si/SiGe hetero-structures with a Ge concentration of 20% rather than the more usual 30% typically encountered offer higher electron mobility. The devices consist of two in-plane parallel electron channels that host a double dot in one channel and a single dot in the other channel. In a device where the channels are sufficiently close a triple dot in a triangular configuration is induced leading to regionsmore » in the charge stability diagram where three charge-addition lines of different slope approach each other and anti-cross. In a device where the channels are further apart, the single dot charge-senses the double dot with relative change of ~2% in the sensor current.« less

Enhancement-mode two-channel triple quantum dot from an undoped Si/Si 0.8Ge 0.2 quantum well hetero-structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Studenikin, S. A.; Gaudreau, L.; Kataoka, K.

Here, we demonstrate coupled triple dot operation and charge sensing capability for the recently introduced quantum dot technology employing undoped Si/Si 0.8Ge 0.2 hetero-structures which also incorporate a single metal-gate layer to simplify fabrication. Si/SiGe hetero-structures with a Ge concentration of 20% rather than the more usual 30% typically encountered offer higher electron mobility. The devices consist of two in-plane parallel electron channels that host a double dot in one channel and a single dot in the other channel. In a device where the channels are sufficiently close a triple dot in a triangular configuration is induced leading to regionsmore » in the charge stability diagram where three charge-addition lines of different slope approach each other and anti-cross. In a device where the channels are further apart, the single dot charge-senses the double dot with relative change of ~2% in the sensor current.« less

Affinity purification of the voltage-sensitive sodium channel from electroplax with resins selective for sialic acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, W.M.; Emerick, M.C.; Agnew, W.S.

1989-07-11

The voltage-sensitive sodium channel present in the eel (Electrophorus electricus) has an unusually high content of sialic acid, including {alpha}-(2{yields}8)-linked polysialic acid, not found in other electroplax membrane glycopeptides. Lectins from Limax flavus (LFA) and wheat germ (WGA) proved the most effective of 11 lectin resins tried. The most selective resin was prepared from IgM antibodies against Neisseria meningitidis {alpha}-(2{yields}8)-polysialic acid which were affinity purified and coupled to Sepharose 4B. The sodium channel was found to bind to WGA, LFA, and IgM resins and was readily eluted with the appropriate soluble carbohydrates. Experiments with LFA and IgM resins demonstrated bindingmore » and unbinding rates and displacement kinetics, which suggest highly specific binding at multiple sites on the sodium channel protein. In preparative-scale purification of protein previously fractionated by anion-exchange chromatography, without stabilizing TTX, high yields were reproducibly obtained. Further, when detergent extracts were prepared from electroplax membranes fractionated by low-speed sedimentation, a single step over the IgM resin provided a 70-fold purification, yielding specific activities of 3,200 pmol of ({sup 3}H)TTX-binding sites/mg of protein and a single polypeptide of {approximately}285,000 Da on SDS-acrylamide gels. No small peptides were observed after this 5-h isolation. The authors describe a cation-dependent stabilization with millimolar levels of monovalent and micromolar levels of divalent species.« less

Bio-fabrication of nanomesh channels of single-walled carbon nanotubes for locally gated field-effect transistors

NASA Astrophysics Data System (ADS)

Byeon, Hye-Hyeon; Lee, Woo Chul; Kim, Wonbin; Kim, Seong Keun; Kim, Woong; Yi, Hyunjung

2017-01-01

Single-walled carbon nanotubes (SWNTs) are one of the promising electronic components for nanoscale electronic devices such as field-effect transistors (FETs) owing to their excellent device characteristics such as high conductivity, high carrier mobility and mechanical flexibility. Localized gating gemometry of FETs enables individual addressing of active channels and allows for better electrostatics via thinner dielectric layer of high k-value. For localized gating of SWNTs, it becomes critical to define SWNTs of controlled nanostructures and functionality onto desired locations in high precision. Here, we demonstrate that a biologically templated approach in combination of microfabrication processes can successfully produce a nanostructured channels of SWNTs for localized active devices such as local bottom-gated FETs. A large-scale nanostructured network, nanomesh, of SWNTs were assembled in solution using an M13 phage with strong binding affinity toward SWNTs and micrometer-scale nanomesh channels were defined using negative photolithography and plasma-etching processes. The bio-fabrication approach produced local bottom-gated FETs with remarkably controllable nanostructures and successfully enabled semiconducting behavior out of unsorted SWNTs. In addition, the localized gating scheme enhanced the device performances such as operation voltage and I on/I off ratio. We believe that our approach provides a useful and integrative method for fabricating electronic devices out of nanoscale electronic materials for applications in which tunable electrical properties, mechanical flexibility, ambient stability, and chemical stability are of crucial importance.

Regulation of Kv7.2/Kv7.3 channels by cholesterol: Relevance of an optimum plasma membrane cholesterol content.

PubMed

Delgado-Ramírez, Mayra; Sánchez-Armass, Sergio; Meza, Ulises; Rodríguez-Menchaca, Aldo A

2018-05-01

Kv7.2/Kv7.3 channels are the molecular correlate of the M-current, which stabilizes the membrane potential and controls neuronal excitability. Previous studies have shown the relevance of plasma membrane lipids on both M-currents and Kv7.2/Kv7.3 channels. Here, we report the sensitive modulation of Kv7.2/Kv7.3 channels by membrane cholesterol level. Kv7.2/Kv7.3 channels transiently expressed in HEK-293 cells were significantly inhibited by decreasing the cholesterol level in the plasma membrane by three different pharmacological strategies: methyl-β-cyclodextrin (MβCD), Filipin III, and cholesterol oxidase treatment. Surprisingly, Kv7.2/Kv7.3 channels were also inhibited by membrane cholesterol loading with the MβCD/cholesterol complex. Depletion or enrichment of plasma membrane cholesterol differentially affected the biophysical parameters of the macroscopic Kv7.2/Kv7.3 currents. These results indicate a complex mechanism of Kv7.2/Kv7.3 channels modulation by membrane cholesterol. We propose that inhibition of Kv7.2/Kv7.3 channels by membrane cholesterol depletion involves a loss of a direct cholesterol-channel interaction. However, the inhibition of Kv7.2/Kv7.3 channels by membrane cholesterol enrichment could include an additional direct cholesterol-channel interaction, or changes in the physical properties of the plasma membrane. In summary, our results indicate that an optimum cholesterol level in the plasma membrane is required for the proper functioning of Kv7.2/Kv7.3 channels. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous protection of organic p- and n-channels in complementary inverter from aging and bias-stress by DNA-base guanine/Al2O3 double layer.

PubMed

Lee, Junyeong; Hwang, Hyuncheol; Min, Sung-Wook; Shin, Jae Min; Kim, Jin Sung; Jeon, Pyo Jin; Lee, Hee Sung; Im, Seongil

2015-01-28

Although organic field-effect transistors (OFETs) have various advantages of lightweight, low-cost, mechanical flexibility, and nowadays even higher mobility than amorphous Si-based FET, stability issue under bias and ambient condition critically hinder its practical application. One of the most detrimental effects on organic layer comes from penetrated atmospheric species such as oxygen and water. To solve such degradation problems, several molecular engineering tactics are introduced: forming a kinetic barrier, lowering the level of molecule orbitals, and increasing the band gap. However, direct passivation of organic channels, the most promising strategy, has not been reported as often as other methods. Here, we resolved the ambient stability issues of p-type (heptazole)/or n-type (PTCDI-C13) OFETs and their bias-stability issues at once, using DNA-base small molecule guanine (C5H5N5O)/Al2O3 bilayer. The guanine protects the organic channels as buffer/and H getter layer between the channels and capping Al2O3, whereas the oxide capping resists ambient molecules. As a result, both p-type and n-type OFETs are simultaneously protected from gate-bias stress and 30 days-long ambient aging, finally demonstrating a highly stable, high-gain complementary-type logic inverter.