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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for predicting sturgeon-vessel interactions in navigable rivers as well as for understanding how fish interact with their habitat in landscapes altered by human activity. PMID:28678798

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.

Control channels in the brain and their influence on brain executive functions

NASA Astrophysics Data System (ADS)

Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

2014-05-01

In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

Pore Helices Play a Dynamic Role as Integrators of Domain Motion during Kv11.1 Channel Inactivation Gating*

PubMed Central

Perry, Matthew D.; Ng, Chai Ann; Vandenberg, Jamie I.

2013-01-01

Proteins that form ion-selective pores in the membrane of cells are integral to many rapid signaling processes, including regulating the rhythm of the heartbeat. In potassium channels, the selectivity filter is critical for both endowing an exquisite selectivity for potassium ions, as well as for controlling the flow of ions through the pore. Subtle rearrangements in the complex hydrogen-bond network that link the selectivity filter to the surrounding pore helices differentiate conducting (open) from nonconducting (inactivated) conformations of the channel. Recent studies suggest that beyond the selectivity filter, inactivation involves widespread rearrangements of the channel protein. Here, we use rate equilibrium free energy relationship analysis to probe the structural changes that occur during selectivity filter gating in Kv11.1 channels, at near atomic resolution. We show that the pore helix plays a crucial dynamic role as a bidirectional interface during selectivity filter gating. We also define the molecular bases of the energetic coupling between the pore helix and outer helix of the pore domain that occurs early in the transition from open to inactivated states, as well as the coupling between the pore helix and inner helix late in the transition. Our data demonstrate that the pore helices are more than just static structural elements supporting the integrity of the selectivity filter; instead they play a crucial dynamic role during selectivity filter gating. PMID:23471968

Electric Field-Controlled Ion Transport In TiO2 Nanochannel.

PubMed

Li, Dan; Jing, Wenheng; Li, Shuaiqiang; Shen, Hao; Xing, Weihong

2015-06-03

On the basis of biological ion channels, we constructed TiO2 membranes with rigid channels of 2.3 nm to mimic biomembranes with flexible channels; an external electric field was employed to regulate ion transport in the confined channels at a high ionic strength in the absence of electrical double layer overlap. Results show that transport rates for both Na+ and Mg2+ were decreased irrespective of the direction of the electric field. Furthermore, a voltage-gated selective ion channel was formed, the Mg2+ channel closed at -2 V, and a reversed relative electric field gradient was at the same order of the concentration gradient, whereas the Na+ with smaller Stokes radius and lower valence was less sensitive to the electric field and thus preferentially occupied and passed the channel. Thus, when an external electric field is applied, membranes with larger nanochannels have promising applications in selective separation of mixture salts at a high concentration.

Isotachophoresis system having larger-diameter channels flowing into channels with reduced diameter and with selectable counter-flow

DOEpatents

Mariella, Jr., Raymond P.

2018-03-06

An isotachophoresis system for separating a sample containing particles into discrete packets including a flow channel, the flow channel having a large diameter section and a small diameter section; a negative electrode operably connected to the flow channel; a positive electrode operably connected to the flow channel; a leading carrier fluid in the flow channel; a trailing carrier fluid in the flow channel; and a control for separating the particles in the sample into discrete packets using the leading carrier fluid, the trailing carrier fluid, the large diameter section, and the small diameter section.

EDMC: An enhanced distributed multi-channel anti-collision algorithm for RFID reader system

NASA Astrophysics Data System (ADS)

Zhang, YuJing; Cui, Yinghua

2017-05-01

In this paper, we proposes an enhanced distributed multi-channel reader anti-collision algorithm for RFID environments which is based on the distributed multi-channel reader anti-collision algorithm for RFID environments (called DiMCA). We proposes a monitor method to decide whether reader receive the latest control news after it selected the data channel. The simulation result shows that it improves interrogation delay.

Voltage gated sodium channels as drug discovery targets

PubMed Central

Bagal, Sharan K; Marron, Brian E; Owen, Robert M; Storer, R Ian; Swain, Nigel A

2015-01-01

Voltage-gated sodium (NaV) channels are a family of transmembrane ion channel proteins. They function by forming a gated, water-filled pore to help establish and control cell membrane potential via control of the flow of ions between the intracellular and the extracellular environments. Blockade of NaVs has been successfully accomplished in the clinic to enable control of pathological firing patterns that occur in a diverse range of conditions such as chronic pain, epilepsy, and cardiac arrhythmias. First generation sodium channel modulator drugs, despite low inherent subtype selectivity, preferentially act on over-excited cells which reduces undesirable side effects in the clinic. However, the limited therapeutic indices observed with the first generation demanded a new generation of sodium channel inhibitors. The structure, function and the state of the art in sodium channel modulator drug discovery are discussed in this chapter. PMID:26646477

Tagging of Endogenous BK Channels with a Fluorogen-Activating Peptide Reveals β4-Mediated Control of Channel Clustering in Cerebellum

PubMed Central

Pratt, Christopher P.; Kuljis, Dika A.; Homanics, Gregg E.; He, Jianjun; Kolodieznyi, Dmytro; Dudem, Srikanth; Hollywood, Mark A.; Barth, Alison L.; Bruchez, Marcel P.

2017-01-01

BK channels are critical regulators of neuronal activity, controlling firing, neurotransmitter release, cerebellar function, and BK channel mutations have been linked to seizure disorders. Modulation of BK channel gating is well characterized, regulated by accessory subunit interactions, intracellular signaling pathways, and membrane potential. In contrast, the role of intracellular trafficking mechanisms in controlling BK channel function, especially in live cells, has been less studied. Fluorogen-activating peptides (FAPs) are well-suited for trafficking and physiological studies due to the binding of malachite green (MG)-based dyes with sub-nanomolar affinity to the FAP, resulting in bright, photostable, far-red fluorescence. Cell-excluded MG dyes enable the selective tagging of surface protein and tracking through endocytic pathways. We used CRISPR to insert the FAP at the extracellular N-terminus of BKα in the first exon of its native locus, enabling regulation by the native promoter elements and tag incorporation into multiple splice isoforms. Motor coordination was found to be normal; however, BK channel expression seems to be reduced in some locations. Alternate start site selection or post-translational proteolytic processing resulted in incomplete FAP tagging of the BKα proteins in brain tissues. In Purkinje cell somata, FAP revealed BK channel clustering previously only observed by electron microscopy. Measurement of these clusters in β4+/- and β4-/- mice showed that puncta number and cluster fluorescence intensity on the soma are reduced in β4-/- knockout animals. This novel mouse line provides a versatile fluorescent platform for studying endogenous BK channels in living and fixed tissues. Future studies could apply this line to ex vivo neuronal cultures to study live-cell channel trafficking. PMID:29163049

Rationale for selection of a flight control system for lift cruise fan V/STOL aircraft

NASA Technical Reports Server (NTRS)

Konsewicz, R. K.

1977-01-01

Various features of the lift cruise fan V/STOL concept are briefly reviewed. The ability to operate from small ships in adverse weather, low visibility, and rough sea conditions is emphasized as is the need for a highly capable, flexible, and reliabile flight control system. A three channel control by wire, digital flight control system is suggested. The requirement for automatic flight control, the advantage of control by wire implementation, the preference for a digital computer, and the need for three channel redundancy are among the factors discussed.

Voltage-gated sodium channels as targets for pyrethroid insecticides.

PubMed

Field, Linda M; Emyr Davies, T G; O'Reilly, Andrias O; Williamson, Martin S; Wallace, B A

2017-10-01

The pyrethroid insecticides are a very successful group of compounds that have been used extensively for the control of arthropod pests of agricultural crops and vectors of animal and human disease. Unfortunately, this has led to the development of resistance to the compounds in many species. The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel. Understanding how binding to the channel is affected by amino acid substitutions that give rise to resistance has helped to elucidate the mode of action of the compounds and the molecular basis of their selectivity for insects vs mammals and between insects and other arthropods. Modelling of the channel/pyrethroid interactions, coupled with the ability to express mutant channels in oocytes and study function, has led to knowledge of both how the channels function and potentially how to design novel insecticides with greater species selectivity.

Experiences with serial and parallel algorithms for channel routing using simulated annealing

NASA Technical Reports Server (NTRS)

Brouwer, Randall Jay

1988-01-01

Two algorithms for channel routing using simulated annealing are presented. Simulated annealing is an optimization methodology which allows the solution process to back up out of local minima that may be encountered by inappropriate selections. By properly controlling the annealing process, it is very likely that the optimal solution to an NP-complete problem such as channel routing may be found. The algorithm presented proposes very relaxed restrictions on the types of allowable transformations, including overlapping nets. By freeing that restriction and controlling overlap situations with an appropriate cost function, the algorithm becomes very flexible and can be applied to many extensions of channel routing. The selection of the transformation utilizes a number of heuristics, still retaining the pseudorandom nature of simulated annealing. The algorithm was implemented as a serial program for a workstation, and a parallel program designed for a hypercube computer. The details of the serial implementation are presented, including many of the heuristics used and some of the resulting solutions.

Fabrication of nanowire channels with unidirectional alignment and controlled length by a simple, gas-blowing-assisted, selective-transfer-printing technique.

PubMed

Kim, Yong-Kwan; Kang, Pil Soo; Kim, Dae-Il; Shin, Gunchul; Kim, Gyu Tae; Ha, Jeong Sook

2009-03-01

A printing-based lithographic technique for the patterning of V(2)O(5) nanowire channels with unidirectional orientation and controlled length is introduced. The simple, directional blowing of a patterned polymer stamp with N(2) gas, inked with randomly distributed V(2)O(5) nanowires, induces alignment of the nanowires perpendicular to the long axis of the line patterns. Subsequent stamping on the amine-terminated surface results in the selective transfer of the aligned nanowires with a controlled length corresponding to the width of the relief region of the polymer stamp. By employing such a gas-blowing-assisted, selective-transfer-printing technique, two kinds of device structures consisting of nanowire channels and two metal electrodes with top contact, whereby the nanowires were aligned either parallel (parallel device) or perpendicular (serial device) to the current flow in the conduction channel, are fabricated. The electrical properties demonstrate a noticeable difference between the two devices, with a large hysteresis in the parallel device but none in the serial device. Systematic analysis of the hysteresis and the electrical stability account for the observed hysteresis in terms of the proton diffusion in the water layer of the V(2)O(5) nanowires, induced by the application of an external bias voltage higher than a certain threshold voltage.

Axial static mixer

DOEpatents

Sandrock, H.E.

1982-05-06

Static axial mixing apparatus includes a plurality of channels, forming flow paths of different dimensions. The axial mixer includes a flow adjusting device for adjustable selective control of flow resistance of various flow paths in order to provide substantially identical flows through the various channels, thereby reducing nonuniform coating of interior surfaces of the channels. The flow adjusting device may include diaphragm valves, and may further include a pressure regulating system therefor.

Wave mixing in coupled phononic crystals via a variable stiffness mechanism

NASA Astrophysics Data System (ADS)

Lee, Gil-Yong; Chong, Christopher; Kevrekidis, Panayotis G.; Yang, Jinkyu

2016-10-01

We investigate wave mixing effects in a phononic crystal that couples the wave dynamics of two channels - primary and control ones - via a variable stiffness mechanism. We demonstrate analytically and numerically that the wave transmission in the primary channel can be manipulated by the control channel's signal. We show that the application of control waves allows the selection of a specific mode through the primary channel. We also demonstrate that the mixing of two wave modes is possible whereby a modulation effect is observed. A detailed study of the design parameters is also carried out to optimize the switching capabilities of the proposed system. Finally, we verify that the system can fulfill both switching and amplification functionalities, potentially enabling the realization of an acoustic transistor.

Optical control of neuronal activity using a light-operated GIRK channel opener (LOGO).

PubMed

Barber, David M; Schönberger, Matthias; Burgstaller, Jessica; Levitz, Joshua; Weaver, C David; Isacoff, Ehud Y; Baier, Herwig; Trauner, Dirk

2016-01-01

G-protein coupled inwardly rectifying potassium channels (GIRKs) are ubiquitously expressed throughout the human body and are an integral part of inhibitory signal transduction pathways. Upon binding of G βγ subunits released from G-protein coupled receptors (GPCRs), GIRK channels open and reduce the activity of excitable cells via hyperpolarization. As such, they play a role in cardiac output, the coordination of movement and cognition. Due to their involvement in a multitude of pathways, the precision control of GIRK channels is an important endeavour. Here, we describe the development of the photoswitchable agonist LOGO (the L ight O perated G IRK-channel O pener), which activates GIRK channels in the dark and is rapidly deactivated upon exposure to long wavelength UV irradiation. LOGO is the first K + channel opener and selectively targets channels that contain the GIRK1 subunit. It can be used to optically silence action potential firing in dissociated hippocampal neurons and LOGO exhibits activity in vivo , controlling the motility of zebrafish larvae in a light dependent fashion. We envisage that LOGO will be a valuable research tool to dissect the function of GIRK channels from other GPCR dependent signalling pathways.

Reduction of the pectoral spine and girdle in domesticated Channel catfish is likely caused by changes in selection pressure.

PubMed

Fine, Michael L; Lahiri, Shweta; Sullivan, Amanda D H; Mayo, Mark; Newton, Scott H; Sismour, Edward N

2014-07-01

Locked pectoral spines of the Channel Catfish Ictalurus punctatus more than double the fish's width and complicate ingestion by gape-limited predators. The spine mates with the pectoral girdle, a robust structure that anchors the spine. This study demonstrates that both spine and girdle exhibit negative allometric growth and that pectoral spines and girdles are lighter in domesticated than in wild Channel Catfish. This finding could be explained by changes in selection pressure for spine growth during domestication or by an epigenetic effect in which exposure to predators in wild fish stimulates pectoral growth. We tested the epigenetic hypothesis by exposing domesticated Channel Catfish fingerlings to Largemouth Bass Micropterus salmoides predators for 13 weeks. Spines and girdles grow isometrically in the fingerlings, and regression analysis indicates no difference in proportional pectoral growth between control and predator-exposed fish. Therefore a change in selection pressure likely accounts for smaller pectoral growth in domesticated Channel Catfish. Decreasing spine growth in older fish suggests anti-predator functions are most important in smaller fish. Additionally, growth of the appendicular and axial skeleton is controlled differentially, and mechanical properties of the spine and not just its length are an important component of this defensive adaptation. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

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

Green Tool

EPA Pesticide Factsheets

The Green Tool represents infiltration-based stormwater control practices. It allows modelers to select a BMP type, channel shape and BMP unit dimensions, outflow control devices, and infiltration method. The program generates an HSPF-formatted FTABLE.

Activation of the mechanosensitive ion channel MscL by mechanical stimulation of supported Droplet-Hydrogel bilayers

PubMed Central

Rosholm, Kadla R.; Baker, Matthew A. B.; Ridone, Pietro; Nakayama, Yoshitaka; Rohde, Paul R.; Cuello, Luis G.; Lee, Lawrence K.; Martinac, Boris

2017-01-01

The droplet on hydrogel bilayer (DHB) is a novel platform for investigating the function of ion channels. Advantages of this setup include tight control of all bilayer components, which is compelling for the investigation of mechanosensitive (MS) ion channels, since they are highly sensitive to their lipid environment. However, the activation of MS ion channels in planar supported lipid bilayers, such as the DHB, has not yet been established. Here we present the activation of the large conductance MS channel of E. coli, (MscL), in DHBs. By selectively stretching the droplet monolayer with nanolitre injections of buffer, we induced quantifiable DHB tension, which could be related to channel activity. The MscL activity response revealed that the droplet monolayer tension equilibrated over time, likely by insertion of lipid from solution. Our study thus establishes a method to controllably activate MS channels in DHBs and thereby advances studies of MS channels in this novel platform. PMID:28345591

Monolithic single mode interband cascade lasers with wide wavelength tunability

NASA Astrophysics Data System (ADS)

von Edlinger, M.; Weih, R.; Scheuermann, J.; Nähle, L.; Fischer, M.; Koeth, J.; Kamp, M.; Höfling, S.

2016-11-01

Monolithic two-section interband cascade lasers offering a wide wavelength tunability in the wavelength range around 3.7 μm are presented. Stable single mode emission in several wavelength channels was realized using the concept of binary superimposed gratings and two-segment Vernier-tuning. The wavelength selective elements in the two segments were based on specially designed lateral metal grating structures defined by electron beam lithography. A dual-step dry etch process provided electrical separation between the segments. Individual current control of the segments allowed wavelength channel selection as well as continuous wavelength tuning within channels. A discontinuous tuning range extending over 158 nm in up to six discrete wavelength channels was achieved. Mode hop free wavelength tuning up to 14 nm was observed within one channel. The devices can be operated in continuous wave mode up to 30 °C with the output powers of 3.5 mW around room temperature.

The Control of Male Fertility by Spermatozoan Ion Channels

PubMed Central

Lishko, Polina V.; Kirichok, Yuriy; Ren, Dejian; Navarro, Betsy; Chung, Jean-Ju

2014-01-01

Ion channels control the sperm ability to fertilize the egg by regulating sperm maturation in the female reproductive tract and by triggering key sperm physiological responses required for successful fertilization such as hyperactivated motility, chemotaxis, and the acrosome reaction. CatSper, a pH-regulated, calcium-selective ion channel, and KSper (Slo3) are core regulators of sperm tail calcium entry and sperm hyperactivated motility. Many other channels had been proposed as regulating sperm activity without direct measurements. With the development of the sperm patch-clamp technique, CatSper and KSper have been confirmed as the primary spermatozoan ion channels. In addition, the voltage-gated proton channel Hv1 has been identified in human sperm tail, and the P2X2 ion channel has been identified in the midpiece of mouse sperm. Mutations and deletions in sperm-specific ion channels affect male fertility in both mice and humans without affecting other physiological functions. The uniqueness of sperm ion channels makes them ideal pharmaceutical targets for contraception. In this review we discuss how ion channels regulate sperm physiology. PMID:22017176

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

Lolicato, Marco; Arrigoni, Cristina; Mori, Takahiro

Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK1 subfamily generate ‘leak’ currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses1, 2, 3. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit4, 5, 6. In contrast to other potassium channels, K2P channels use a selectivity filter ‘C-type’ gate7, 8, 9, 10 as the principal gating site. Despite recent advances3, 11, 12, poor pharmacological profiles of K2P channels limit mechanistic and biological studies. Here we describe a classmore » of small-molecule TREK activators that directly stimulate the C-type gate by acting as molecular wedges that restrict interdomain interface movement behind the selectivity filter. Structures of K2P2.1 (also known as TREK-1) alone and with two selective K2P2.1 (TREK-1) and K2P10.1 (TREK-2) activators—an N-aryl-sulfonamide, ML335, and a thiophene-carboxamide, ML402—define a cryptic binding pocket unlike other ion channel small-molecule binding sites and, together with functional studies, identify a cation–π interaction that controls selectivity. Together, our data reveal a druggable K2P site that stabilizes the C-type gate ‘leak mode’ and provide direct evidence for K2P selectivity filter gating.« less

Selectively-etched nanochannel electrophoretic and electrochemical devices

DOEpatents

Surh, Michael P.; Wilson, William D.; Barbee, Jr., Troy W.; Lane, Stephen M.

2004-11-16

Nanochannel electrophoretic and electrochemical devices having selectively-etched nanolaminates located in the fluid transport channel. The normally flat surfaces of the nanolaminate having exposed conductive (metal) stripes are selectively-etched to form trenches and baffles. The modifications of the prior utilized flat exposed surfaces increase the amount of exposed metal to facilitate electrochemical redox reaction or control the exposure of the metal surfaces to analytes of large size. These etched areas variously increase the sensitivity of electrochemical detection devices to low concentrations of analyte, improve the plug flow characteristic of the channel, and allow additional discrimination of the colloidal particles during cyclic voltammetry.

Selectively-etched nanochannel electrophoretic and electrochemical devices

DOEpatents

Surh, Michael P [Livermore, CA; Wilson, William D [Pleasanton, CA; Barbee, Jr., Troy W.; Lane, Stephen M [Oakland, CA

2006-06-27

Nanochannel electrophoretic and electrochemical devices having selectively-etched nanolaminates located in the fluid transport channel. The normally flat surfaces of the nanolaminate having exposed conductive (metal) stripes are selectively-etched to form trenches and baffles. The modifications of the prior utilized flat exposed surfaces increase the amount of exposed metal to facilitate electrochemical redox reaction or control the exposure of the metal surfaces to analytes of large size. These etched areas variously increase the sensitivity of electrochemical detection devices to low concentrations of analyte, improve the plug flow characteristic of the channel, and allow additional discrimination of the colloidal particles during cyclic voltammetry.

Movement of Potassium Ions inside KcsA in the High Concentration Regime using a Molecular Dynamics Simulation

NASA Astrophysics Data System (ADS)

Kim, Myojeong; Jo, Byeong Chul; Yoon, Hyun Jung; Wu, Sangwook; Thangappan, Jayaraman; Eun, Changsun

2018-05-01

The selectivity and conduction specificity of the KcsA channel toward potassium ions is crucial to the activity of this protein and this channel is intricately associated with several osmotic regulation and neuronal signaling processes. Despite multi-ion characteristics, the selective conduction behavior of KcsA is controlled by the size and distance specific electrostatic interaction between the selected residues and the potassium ions. The mechanism describing the movement of potassium ions in the channel and the conformational changes to KcsA that facilitate ion movement were investigated by a molecular dynamics (MD) simulation. In this study, we analyze the movement of potassium ions and water molecules at various time intervals during a 90 ns molecular dynamics simulation in the high potassium ion concentration regime and in the absence of the voltage. Examination of specific (3.6, 17.3, 43.38 and 43.44 ns) simulation periods revealed that key residues in the selectivity filter of KcsA influence the movement of potassium ions in the channel.

Contrast gain control: a bilinear model for chromatic selectivity.

PubMed

Singer, B; D'Zmura, M

1995-04-01

We report the results of psychophysical experiments on color contrast induction. In earlier work [Vision Res. 34, 3111 (1994)], we showed that modulating the spatial contrast of an annulus in time induces an apparent modulation of the contrast of a central disk, at isoluminance. Here we vary the chromatic properties of disk and annulus systematically in a study of the interactions among the luminance and the color-opponent channels. Results show that induced contrast depends linearly on both disk and annulus contrast, at low and moderate contrast levels. This dependence leads us to propose a bilinear model for color contrast gain control. The model predicts the magnitude and the chromatic properties of induced contrast. In agreement with experimental results, the model displays chromatic selectivity in contrast gain control and a negligible effect of contrast modulation at isoluminance on the appearance of achromatic contrast. We show that the bilinear model for chromatic selectivity may be realized as a feed-forward multiplicative gain control. Data collected at high contrast levels are fit by embellishing the model with saturating nonlinearities in the contrast gain control of each color channel.

Design and Fabrication of a PDMS Microchip Based Immunoassay

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

Shao, Guocheng; Wang, Wanjun; Wang, Jun

2010-07-01

In this paper, we describe the design and fabrication process of a polydimethylsiloxane (PDMS) microchip for on-chip multiplex immunoassay application. The microchip consists of a PDMS microfluidic channel layer and a micro pneumatic valve control layer. By selectively pressurizing the pneumatic microvalves, immuno reagents were controlled to flow and react in certain fluidic channel sites. Cross contamination was prevented by tightly closed valves. Our design was proposed to utilize PDMS micro channel surface as the solid phase immunoassay substrate and simultaneously detect four targets antigens on chip. Experiment result shows that 20psi valve pressure is sufficient to tightly close amore » 200µm wide micro channel with flow rate up to 20µl/min.« less

A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels.

PubMed

Schewe, Marcus; Nematian-Ardestani, Ehsan; Sun, Han; Musinszki, Marianne; Cordeiro, Sönke; Bucci, Giovanna; de Groot, Bert L; Tucker, Stephen J; Rapedius, Markus; Baukrowitz, Thomas

2016-02-25

Two-pore domain (K2P) K(+) channels are major regulators of excitability that endow cells with an outwardly rectifying background "leak" conductance. In some K2P channels, strong voltage-dependent activation has been observed, but the mechanism remains unresolved because they lack a canonical voltage-sensing domain. Here, we show voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of three to four ions into the high electric field of an inactive selectivity filter. Overall, this ion-flux gating mechanism generates a one-way "check valve" within the filter because outward movement of K(+) induces filter opening, whereas inward movement promotes inactivation. Furthermore, many physiological stimuli switch off this flux gating mode to convert K2P channels into a leak conductance. These findings provide insight into the functional plasticity of a K(+)-selective filter and also refine our understanding of K2P channels and the mechanisms by which ion channels can sense voltage. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Inorganic nanotubes and electro-fluidic devices fabricated therefrom

DOEpatents

Yang, Peidong [Kensington, CA; Majumdar, Arunava [Orinda, CA; Fan, Rong [Pasadena, CA; Karnik, Rohit [Cambridge, MA

2011-03-01

Nanofluidic devices incorporating inorganic nanotubes fluidly coupled to channels or nanopores for supplying a fluid containing chemical or bio-chemical species are described. In one aspect, two channels are fluidly interconnected with a nanotube. Electrodes on opposing sides of the nanotube establish electrical contact with the fluid therein. A bias current is passed between the electrodes through the fluid, and current changes are detected to ascertain the passage of select molecules, such as DNA, through the nanotube. In another aspect, a gate electrode is located proximal the nanotube between the two electrodes thus forming a nanofluidic transistor. The voltage applied to the gate controls the passage of ionic species through the nanotube selected as either or both ionic polarities. In either of these aspects the nanotube can be modified, or functionalized, to control the selectivity of detection or passage.

Selective activation of the K(+)(ATP) channel is a mechanism by which sudden death is produced by low-energy chest-wall impact (Commotio cordis).

PubMed

Link, M S; Wang, P J; VanderBrink, B A; Avelar, E; Pandian, N G; Maron, B J; Estes, N A

1999-07-27

Sudden death due to relatively innocent chest-wall impact has been described in young individuals (commotio cordis). In our previously reported swine model of commotio cordis, ventricular fibrillation (with T-wave strikes) and ST-segment elevation (with QRS strikes) were produced by 30-mph baseball impacts to the precordium. Because activation of the K(+)(ATP) channel has been implicated in the pathogenesis of ST elevation and ventricular fibrillation in myocardial ischemia, we hypothesized that this channel could be responsible for the electrophysiologic findings in our experimental model and in victims of commotio cordis. In the initial experiment, 6 juvenile swine were given 0.5 mg/kg IV glibenclamide, a selective inhibitor of the K(+)(ATP) channel, and chest impact was given on the QRS. The results of these strikes were compared with animals in which no glibenclamide was given. In the second phase, 20 swine were randomized to receive glibenclamide or a control vehicle (in a double-blind fashion), with chest impact delivered just before the T-wave peak. With QRS impacts, the maximal ST elevation was significantly less in those animals given glibenclamide (0.16+/-0.10 mV) than in controls (0.35+/-0.20 mV; P=0.004). With T-wave impacts, the animals that received glibenclamide had significantly fewer occurrences of ventricular fibrillation (1 episode in 27 impacts; 4%) than controls (6 episodes in 18 impacts; 33%; P=0.01). In this experimental model of commotio cordis, blockade of the K(+)(ATP) channel reduced the incidence of ventricular fibrillation and the magnitude of ST-segment elevation. Therefore, selective K(+)(ATP) channel activation may be a pivotal mechanism in sudden death resulting from low-energy chest-wall trauma in young people during sporting activities.

Paper-based microfluidic devices by asymmetric calendaring

PubMed Central

Oyola-Reynoso, S.; Frankiewicz, C.; Chang, B.; Chen, J.; Bloch, J.-F.

2017-01-01

We report a simple, efficient, one-step, affordable method to produce open-channel paper-based microfluidic channels. One surface of a sheet of paper is selectively calendared, with concomitant hydrophobization, to create the microfluidic channel. Our method involves asymmetric mechanical modification of a paper surface using a rolling ball (ball-point pen) under a controlled amount of applied stress (σz) to ascertain that only one side is modified. A lubricating solvent (hexane) aids in the selective deformation. The lubricant also serves as a carrier for a perfluoroalkyl trichlorosilane allowing the channel to be made hydrophobic as it is formed. For brevity and clarity, we abbreviated this method as TACH (Targeted Asymmetric Calendaring and Hydrophobization). We demonstrate that TACH can be used to reliably produce channels of variable widths (size of the ball) and depths (number of passes), without affecting the nonworking surface of the paper. Using tomography, we demonstrate that these channels can vary from 10s to 100s of microns in diameter. The created hydrophobic barrier extends around the channel through wicking to ensure no leakages. We demonstrate, through modeling and fabrication, that flow properties of the resulting channels are analogous to conventional devices and are tunable based on associated dimensionless numbers. PMID:28798839

High capacity low delay packet broadcasting multiaccess schemes for satellite repeater systems

NASA Astrophysics Data System (ADS)

Bose, S. K.

1980-12-01

Demand assigned packet radio schemes using satellite repeaters can achieve high capacities but often exhibit relatively large delays under low traffic conditions when compared to random access. Several schemes which improve delay performance at low traffic but which have high capacity are presented and analyzed. These schemes allow random acess attempts by users, who are waiting for channel assignments. The performance of these are considered in the context of a multiple point communication system carrying fixed length messages between geographically distributed (ground) user terminals which are linked via a satellite repeater. Channel assignments are done following a BCC queueing discipline by a (ground) central controller on the basis of requests correctly received over a collision type access channel. In TBACR Scheme A, some of the forward message channels are set aside for random access transmissions; the rest are used in a demand assigned mode. Schemes B and C operate all their forward message channels in a demand assignment mode but, by means of appropriate algorithms for trailer channel selection, allow random access attempts on unassigned channels. The latter scheme also introduces framing and slotting of the time axis to implement a more efficient algorithm for trailer channel selection than the former.

Permeation Mechanisms in the TMEM16B Calcium-Activated Chloride Channels

PubMed Central

2017-01-01

TMEM16A and TMEM16B encode for Ca2+-activated Cl− channels (CaCC) and are expressed in many cell types and play a relevant role in many physiological processes. Here, I performed a site-directed mutagenesis study to understand the molecular mechanisms of ion permeation of TMEM16B. I mutated two positive charged residues R573 and K540, respectively located at the entrance and inside the putative channel pore and I measured the properties of wild-type and mutant TMEM16B channels expressed in HEK-293 cells using whole-cell and excised inside-out patch clamp experiments. I found evidence that R573 and K540 control the ion permeability of TMEM16B depending both on which side of the membrane the ion substitution occurs and on the level of channel activation. Moreover, these residues contribute to control blockage or activation by permeant anions. Finally, R573 mutation abolishes the anomalous mole fraction effect observed in the presence of a permeable anion and it alters the apparent Ca2+-sensitivity of the channel. These findings indicate that residues facing the putative channel pore are responsible both for controlling the ion selectivity and the gating of the channel, providing an initial understanding of molecular mechanism of ion permeation in TMEM16B. PMID:28046119

Contemplating the plasmalemmal control center model

NASA Technical Reports Server (NTRS)

Pickard, B. G.

1994-01-01

An abundant epidermal mechanosensory calcium-selective ion channel appears able not only to detect mechanical stimuli such as those that initiate gravitropism but also to detect thermal, electrical, and various chemical stimuli. Because it responds to multimodal input with a second messenger output, this channel system seems likely to be an integrator that can engage in feedbacks with many other systems of the cell--and feedback is the hallmark of regulation. In general, the mechanical tension required for channel activation is likely transmitted from the relatively rigid cell wall to the plasma membrane system via linkage or adhesion sites that display antigenicities recognized by antibodies to animal beta-1 integrin, vitronectin, and fibronectin and which have mechanical connections to the cytoskeleton. Thus, functionally, leverage exerted against any given adhesion site will tend to control channels within a surrounding domain. Reactions initiated by passage of calcium ions through the channels could presumably be more effectively regulated if channels within the domains were somewhat clustered and if appropriate receptors, kinases, porters, pumps, and some key cytoskeletal anchoring sites were in turn clustered about them. Accumulating evidence suggests not only that activity of clusters of channels may contribute to control of cytoskeletal architecture and of regulatory protein function within their domain, but also that both a variety of regulatory proteins and components of the cortical cytoskeleton may contribute to control of channel activity. The emerging capabilities of electronic optical microscopy are well suited for resolving the spatial distributions of many of these cytoskeletal and regulatory molecules in living cells, and for following some of their behaviors as channels are stimulated to open and cytosolic calcium builds in their vicinity. Such microscopy, coupled with biochemical and physiological probing, should help to establish the nature of the feedback loops putatively controlled by the linkage sites and their channel domains.

A Novel Feature Optimization for Wearable Human-Computer Interfaces Using Surface Electromyography Sensors

PubMed Central

Zhang, Xiong; Zhao, Yacong; Zhang, Yu; Zhong, Xuefei; Fan, Zhaowen

2018-01-01

The novel human-computer interface (HCI) using bioelectrical signals as input is a valuable tool to improve the lives of people with disabilities. In this paper, surface electromyography (sEMG) signals induced by four classes of wrist movements were acquired from four sites on the lower arm with our designed system. Forty-two features were extracted from the time, frequency and time-frequency domains. Optimal channels were determined from single-channel classification performance rank. The optimal-feature selection was according to a modified entropy criteria (EC) and Fisher discrimination (FD) criteria. The feature selection results were evaluated by four different classifiers, and compared with other conventional feature subsets. In online tests, the wearable system acquired real-time sEMG signals. The selected features and trained classifier model were used to control a telecar through four different paradigms in a designed environment with simple obstacles. Performance was evaluated based on travel time (TT) and recognition rate (RR). The results of hardware evaluation verified the feasibility of our acquisition systems, and ensured signal quality. Single-channel analysis results indicated that the channel located on the extensor carpi ulnaris (ECU) performed best with mean classification accuracy of 97.45% for all movement’s pairs. Channels placed on ECU and the extensor carpi radialis (ECR) were selected according to the accuracy rank. Experimental results showed that the proposed FD method was better than other feature selection methods and single-type features. The combination of FD and random forest (RF) performed best in offline analysis, with 96.77% multi-class RR. Online results illustrated that the state-machine paradigm with a 125 ms window had the highest maneuverability and was closest to real-life control. Subjects could accomplish online sessions by three sEMG-based paradigms, with average times of 46.02, 49.06 and 48.08 s, respectively. These experiments validate the feasibility of proposed real-time wearable HCI system and algorithms, providing a potential assistive device interface for persons with disabilities. PMID:29543737

Channels selection using independent component analysis and scalp map projection for EEG-based driver fatigue classification.

PubMed

Rifai Chai; Naik, Ganesh R; Sai Ho Ling; Tran, Yvonne; Craig, Ashley; Nguyen, Hung T

2017-07-01

This paper presents a classification of driver fatigue with electroencephalography (EEG) channels selection analysis. The system employs independent component analysis (ICA) with scalp map back projection to select the dominant of EEG channels. After channel selection, the features of the selected EEG channels were extracted based on power spectral density (PSD), and then classified using a Bayesian neural network. The results of the ICA decomposition with the back-projected scalp map and a threshold showed that the EEG channels can be reduced from 32 channels into 16 dominants channels involved in fatigue assessment as chosen channels, which included AF3, F3, FC1, FC5, T7, CP5, P3, O1, P4, P8, CP6, T8, FC2, F8, AF4, FP2. The result of fatigue vs. alert classification of the selected 16 channels yielded a sensitivity of 76.8%, specificity of 74.3% and an accuracy of 75.5%. Also, the classification results of the selected 16 channels are comparable to those using the original 32 channels. So, the selected 16 channels is preferable for ergonomics improvement of EEG-based fatigue classification system.

Expression Profiling of the Transient Receptor Potential Vanilloid (TRPV) Channels 1, 2, 3 and 4 in Mucosal Epithelium of Human Ulcerative Colitis.

PubMed

Rizopoulos, Theodoros; Papadaki-Petrou, Helen; Assimakopoulou, Martha

2018-06-15

The Transient Receptor Potential (TRP) family of selective and non-selective ion channels is well represented throughout the mammalian gastrointestinal track. Several members of the Transient Receptor Potential Vanilloid (TRPV) subfamily have been identified in contributing to modulation of mobility, secretion and sensitivity of the human intestine. Previous studies have focused on the detection of TRPV mRNA levels in colon tissue of patients with inflammatory bowel disease (IBD) whereas little information exists regarding TRPV channel expression in the colonic epithelium. The aim of this study was to evaluate the expression levels of TRPV1, TRPV2, TRPV3 and TRPV4 in mucosa epithelial cells of colonic biopsies from patients with ulcerative colitis (UC) in comparison to colonic resections from non-IBD patients (control group). Immunohistochemistry, using specific antibodies and quantitative analyses of TRPV-immunostained epithelial cells, was performed in semi-serial sections of the samples. TRPV1 expression was significantly decreased whereas TRPV4 expression was significantly increased in the colonic epithelium of UC patients compared to patients in the control group ( p < 0.05). No significant difference for TRPV2 and TRPV3 expression levels between UC and control specimens was detected ( p > 0.05). There was no correlation between TRPV channel expression and the clinical features of the disease ( p > 0.05). Further investigation is needed to clarify the role of TRPV channels in human bowel inflammatory response.

Structure and selectivity in bestrophin ion channels

DOE PAGES

Yang, Tingting; Liu, Qun; Kloss, Brian; ...

2014-09-25

Human bestrophin 1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where it can suffer mutations associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a subtle control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activationmore » by mutations at the exit restriction. Lastly, a homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.« less

Tunable transmission of quantum Hall edge channels with full degeneracy lifting in split-gated graphene devices.

PubMed

Zimmermann, Katrin; Jordan, Anna; Gay, Frédéric; Watanabe, Kenji; Taniguchi, Takashi; Han, Zheng; Bouchiat, Vincent; Sellier, Hermann; Sacépé, Benjamin

2017-04-13

Charge carriers in the quantum Hall regime propagate via one-dimensional conducting channels that form along the edges of a two-dimensional electron gas. Controlling their transmission through a gate-tunable constriction, also called quantum point contact, is fundamental for many coherent transport experiments. However, in graphene, tailoring a constriction with electrostatic gates remains challenging due to the formation of p-n junctions below gate electrodes along which electron and hole edge channels co-propagate and mix, short circuiting the constriction. Here we show that this electron-hole mixing is drastically reduced in high-mobility graphene van der Waals heterostructures thanks to the full degeneracy lifting of the Landau levels, enabling quantum point contact operation with full channel pinch-off. We demonstrate gate-tunable selective transmission of integer and fractional quantum Hall edge channels through the quantum point contact. This gate control of edge channels opens the door to quantum Hall interferometry and electron quantum optics experiments in the integer and fractional quantum Hall regimes of graphene.

Anisotropic selective etching between SiGe and Si

NASA Astrophysics Data System (ADS)

Ishii, Yohei; Scott-McCabe, Ritchie; Yu, Alex; Okuma, Kazumasa; Maeda, Kenji; Sebastian, Joseph; Manos, Jim

2018-06-01

In Si/SiGe dual-channel FinFETs, it is necessary to simultaneously control the etched amounts of SiGe and Si. However, the SiGe etch rate is higher than the Si etch rate in not only halogen plasmas but also physical sputtering. In this study, we found that hydrogen plasma selectively etches Si over SiGe. The result shows that the selectivity of Si over SiGe can be up to 38 with increasing Ge concentration in SiGe. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) results indicate that hydrogen selectively bonds with Si rather than with Ge in SiGe. During the etching, hydrogen-induced Si surface segregation is also observed. It is also observed that the difference in etched amount between SiGe and Si can be controlled from positive to negative values even in Si/SiGe dual-channel fin patterning while maintaining the vertical profiles. Furthermore, no plasma-induced lattice damage was observed by transmission electron microscopy for both Si and SiGe fin sidewalls.

Sodium and potassium competition in potassium-selective and non-selective channels

NASA Astrophysics Data System (ADS)

Sauer, David B.; Zeng, Weizhong; Canty, John; Lam, Yeeling; Jiang, Youxing

2013-11-01

Potassium channels selectively conduct K+, primarily to the exclusion of Na+, despite the fact that both ions can bind within the selectivity filter. Here we perform crystallographic titration and single-channel electrophysiology to examine the competition of Na+ and K+ binding within the filter of two NaK channel mutants; one is the potassium-selective NaK2K mutant and the other is the non-selective NaK2CNG, a CNG channel pore mimic. With high-resolution structures of these engineered NaK channel constructs, we explicitly describe the changes in K+ occupancy within the filter upon Na+ competition by anomalous diffraction. Our results demonstrate that the non-selective NaK2CNG still retains a K+-selective site at equilibrium, whereas the NaK2K channel filter maintains two high-affinity K+ sites. A double-barrier mechanism is proposed to explain K+ channel selectivity at low K+ concentrations.

Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets

PubMed Central

Humphries, Edward S. A.

2015-01-01

Potassium (K+) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal neuronal activity within the brain. With the exception of drugs that target one particular class, ATP-sensitive K+ (KATP) channels, very few selective K+ channel activators or inhibitors are currently licensed for clinical use in cardiovascular and neurological disease. Here we review what a range of human genetic disorders have told us about the role of specific K+ channel subunits, explore the potential of activators and inhibitors of specific channel populations as a therapeutic strategy, and discuss possible reasons for the difficulty in designing clinically relevant K+ channel modulators. PMID:26303307

Novel on-demand droplet generation for selective fluid sample extraction

PubMed Central

Lin, Robert; Fisher, Jeffery S.; Simon, Melinda G.; Lee, Abraham P.

2012-01-01

A novel microfluidic device enabling selective generation of droplets and encapsulation of targets is presented. Unlike conventional methods, the presented mechanism generates droplets with unique selectivity by utilizing a K-junction design. The K-junction is a modified version of the classic T-junction with an added leg that serves as the exit channel for waste. The dispersed phase fluid enters from one diagonal of the K and exits the other diagonal while the continuous phase travels in the straight leg of the K. The intersection forms an interface that allows the dispersed phase to be controllably injected through actuation of an elastomer membrane located above the inlet channel near the interface. We have characterized two critical components in controlling the droplet size—membrane actuation pressure and timing as well as identified the region of fluid in which the droplet will be formed. This scheme will have applications in fluid sampling processes and selective encapsulation of materials. Selective encapsulation of a single cell from the dispersed phase fluid is demonstrated as an example of functionality of this design. PMID:22655015

TRPP2 ion channels: Critical regulators of organ morphogenesis in health and disease.

PubMed

Busch, Tilman; Köttgen, Michael; Hofherr, Alexis

2017-09-01

Ion channels control the membrane potential and mediate transport of ions across membranes. Archetypical physiological functions of ion channels include processes such as regulation of neuronal excitability, muscle contraction, or transepithelial ion transport. In that regard, transient receptor potential ion channel polycystin 2 (TRPP2) is remarkable, because it controls complex morphogenetic processes such as the establishment of properly shaped epithelial tubules and left-right-asymmetry of organs. The fascinating question of how an ion channel regulates morphogenesis has since captivated the attention of scientists in different disciplines. Four loosely connected key insights on different levels of biological complexity ranging from protein to whole organism have framed our understanding of TRPP2 physiology: 1) TRPP2 is a non-selective cation channel; 2) TRPP2 is part of a receptor-ion channel complex; 3) TRPP2 localizes to primary cilia; and 4) TRPP2 is required for organ morphogenesis. In this review, we will discuss the current knowledge in these key areas and highlight some of the challenges ahead. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Audience Selectivity and Involvement in the Newer Media Environment.

ERIC Educational Resources Information Center

Perse, Elizabeth M.

1990-01-01

Examines cable television viewer selectivity and involvement. Concludes through study of 342 cable subscribers who owned remote control devices that "zapping" (changing television channels during commercials) is an indication of ritualistic television viewing. Suggests that more salient motives are linked to the preexposure activities of…

Peroxisomal Pex11 is a pore-forming protein homologous to TRPM channels.

PubMed

Mindthoff, Sabrina; Grunau, Silke; Steinfort, Laura L; Girzalsky, Wolfgang; Hiltunen, J Kalervo; Erdmann, Ralf; Antonenkov, Vasily D

2016-02-01

More than 30 proteins (Pex proteins) are known to participate in the biogenesis of peroxisomes-ubiquitous oxidative organelles involved in lipid and ROS metabolism. The Pex11 family of homologous proteins is responsible for division and proliferation of peroxisomes. We show that yeast Pex11 is a pore-forming protein sharing sequence similarity with TRPM cation-selective channels. The Pex11 channel with a conductance of Λ=4.1 nS in 1.0M KCl is moderately cation-selective (PK(+)/PCl(-)=1.85) and resistant to voltage-dependent closing. The estimated size of the channel's pore (r~0.6 nm) supports the notion that Pex11 conducts solutes with molecular mass below 300-400 Da. We localized the channel's selectivity determining sequence. Overexpression of Pex11 resulted in acceleration of fatty acids β-oxidation in intact cells but not in the corresponding lysates. The β-oxidation was affected in cells by expression of the Pex11 protein carrying point mutations in the selectivity determining sequence. These data suggest that the Pex11-dependent transmembrane traffic of metabolites may be a rate-limiting step in the β-oxidation of fatty acids. This conclusion was corroborated by analysis of the rate of β-oxidation in yeast strains expressing Pex11 with mutations mimicking constitutively phosphorylated (S165D, S167D) or unphosphorylated (S165A, S167A) protein. The results suggest that phosphorylation of Pex11 is a mechanism that can control the peroxisomal β-oxidation rate. Our results disclose an unexpected function of Pex11 as a non-selective channel responsible for transfer of metabolites across peroxisomal membrane. The data indicate that peroxins may be involved in peroxisomal metabolic processes in addition to their role in peroxisome biogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

A Large Scale Computer Terminal Output Controller.

ERIC Educational Resources Information Center

Tucker, Paul Thomas

This paper describes the design and implementation of a large scale computer terminal output controller which supervises the transfer of information from a Control Data 6400 Computer to a PLATO IV data network. It discusses the cost considerations leading to the selection of educational television channels rather than telephone lines for…

Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels.

PubMed

Cymes, Gisela D; Grosman, Claudio

2016-10-10

Among neurotransmitter-gated ion channels, the superfamily of pentameric ligand-gated ion channels (pLGICs) is unique in that its members display opposite permeant-ion charge selectivities despite sharing the same structural fold. Although much effort has been devoted to the identification of the mechanism underlying the cation-versus-anion selectivity of these channels, a careful analysis of past work reveals that discrepancies exist, that different explanations for the same phenomenon have often been put forth, and that no consensus view has yet been reached. To elucidate the molecular basis of charge selectivity for the superfamily as a whole, we performed extensive mutagenesis and electrophysiological recordings on six different cation-selective and anion-selective homologs from vertebrate, invertebrate, and bacterial origin. We present compelling evidence for the critical involvement of ionized side chains-whether pore-facing or buried-rather than backbone atoms and propose a mechanism whereby not only their charge sign but also their conformation determines charge selectivity. Insertions, deletions, and residue-to-residue mutations involving nonionizable residues in the intracellular end of the pore seem to affect charge selectivity by changing the rotamer preferences of the ionized side chains in the first turn of the M2 α-helices. We also found that, upon neutralization of the charged residues in the first turn of M2, the control of charge selectivity is handed over to the many other ionized side chains that decorate the pore. This explains the long-standing puzzle as to why the neutralization of the intracellular-mouth glutamates affects charge selectivity to markedly different extents in different cation-selective pLGICs.

Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites

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

Derebe, Mehabaw G.; Sauer, David B.; Zeng, Weizhong

2015-11-30

Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K{sup +} channel selectivity filters. Combined with single channel electrophysiology, we show that only themore » channel with four ion binding sites is K{sup +} selective, whereas those with two or three are nonselective and permeate Na{sup +} and K{sup +} equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K{sup +} channels is essential for highly selective and efficient permeation of K{sup +} ions.« less

Predictive 3D modelling of the interactions of pyrethroids with the voltage-gated sodium channels of ticks and mites.

PubMed

O'Reilly, Andrias O; Williamson, Martin S; González-Cabrera, Joel; Turberg, Andreas; Field, Linda M; Wallace, B A; Davies, T G Emyr

2014-03-01

The pyrethroid insecticides are a very successful group of compounds that target invertebrate voltage-gated sodium channels and are widely used in the control of insects, ticks and mites. It is well established that some pyrethroids are good insecticides whereas others are more effective as acaricides. This species specificity is advantageous for controlling particular pest(s) in the presence of another non-target invertebrate, for example controlling the Varroa mite in honeybee colonies. We applied in silico techniques to compare the voltage-gated sodium channels of insects versus ticks and mites and their interactions with a range of pyrethroids and DDT analogues. We identified a single amino acid difference within the pyrethroid binding pocket of ticks/mites that may have significant impact on the effectiveness of pyrethroids as acaricides. Other individual amino acid differences within the binding pocket in distinct tick and mite species may provide a basis for future acaricidal selectivity. Three-dimensional modelling of the pyrethroid/DDT receptor site has led to a new hypothesis to explain the preferential binding of acaricidal pyrethroids to the sodium channels of ticks/mites. This is important for understanding pyrethroid selectivity and the potential effects of mutations that can give rise to resistance to pyrethroids in commercially-important pest species. © 2013 Society of Chemical Industry.

A uniquely adaptable pore is consistent with NALCN being an ion sensor

PubMed Central

Senatore, Adriano; Spafford, J. David

2013-01-01

NALCN is an intriguing, orphan ion channel among the 4x6TM family of related voltage-gated cation channels, sharing a common architecture of four homologous domains consisting of six transmembrane helices, separated by three cytoplasmic linkers and delimited by N and C-terminal ends. NALCN is one of the shortest 4x6TM family members, lacking much of the variation that provides the diverse palate of gating features, and tissue specific adaptations of sodium and calcium channels. NALCN’s most distinctive feature is that that it possesses a highly adaptable pore with a calcium-like EEEE selectivity filter in radially symmetrical animals and a more sodium-like EEKE or EKEE selectivity filter in bilaterally symmetrical animals including vertebrates. Two lineages of animals evolved alternative calcium-like EEEE and sodium-like EEKE / EKEE pores, spliced to regulate NALCN functions in differing cellular environments, such as muscle (heart and skeletal) and secretory tissue (brain and glands), respectively. A highly adaptable pore in an otherwise conserved ion channel in the 4x6TM channel family is not consistent with a role for NALCN in directly gating a significant ion conductance that can be either sodium ions or calcium ions. NALCN was proposed to be an expressible Gd3+-sensitive, NMDG+-impermeant, non-selective and ohmic leak conductance in HEK-293T cells, but we were unable to distinguish these reported currents from leaky patch currents (ILP) in control HEK-293T cells. We suggest that NALCN functions as a sensor for the much larger UNC80/UNC79 complex, in a manner consistent with the coupling mechanism known for other weakly or non-conducting 4x6TM channel sensor proteins such as Nax or Cav1.1. We propose that NALCN serves as a variable sensor that responds to calcium or sodium ion flux, depending on whether the total cellular current density is generated more from calcium-selective or sodium-selective channels. PMID:23442378

A uniquely adaptable pore is consistent with NALCN being an ion sensor.

PubMed

Senatore, Adriano; Spafford, J David

2013-01-01

NALCN is an intriguing, orphan ion channel among the 4x6TM family of related voltage-gated cation channels, sharing a common architecture of four homologous domains consisting of six transmembrane helices, separated by three cytoplasmic linkers and delimited by N and C-terminal ends. NALCN is one of the shortest 4x6TM family members, lacking much of the variation that provides the diverse palate of gating features, and tissue specific adaptations of sodium and calcium channels. NALCN's most distinctive feature is that that it possesses a highly adaptable pore with a calcium-like EEEE selectivity filter in radially symmetrical animals and a more sodium-like EEKE or EKEE selectivity filter in bilaterally symmetrical animals including vertebrates. Two lineages of animals evolved alternative calcium-like EEEE and sodium-like EEKE / EKEE pores, spliced to regulate NALCN functions in differing cellular environments, such as muscle (heart and skeletal) and secretory tissue (brain and glands), respectively. A highly adaptable pore in an otherwise conserved ion channel in the 4x6TM channel family is not consistent with a role for NALCN in directly gating a significant ion conductance that can be either sodium ions or calcium ions. NALCN was proposed to be an expressible Gd ( 3+) -sensitive, NMDG (+) -impermeant, non-selective and ohmic leak conductance in HEK-293T cells, but we were unable to distinguish these reported currents from leaky patch currents (ILP) in control HEK-293T cells. We suggest that NALCN functions as a sensor for the much larger UNC80/UNC79 complex, in a manner consistent with the coupling mechanism known for other weakly or non-conducting 4x6TM channel sensor proteins such as Nax or Cav 1.1. We propose that NALCN serves as a variable sensor that responds to calcium or sodium ion flux, depending on whether the total cellular current density is generated more from calcium-selective or sodium-selective channels.

Review of the If selective channel inhibitor ivabradine in the treatment of chronic stable angina.

PubMed

Prasad, Usha K; Gray, David; Purcell, Henry

2009-02-01

Coronary heart disease is the major cause of morbidity and mortality in industrialized countries, and its prevalence is predicted to grow as the population ages. Current drugs for chronic stable angina (such as beta-blockers, calcium-channel blockers, long- and short-acting nitrates, and potassium-channel activators) are often effective, either as monotherapy or in combination, but side effects and contraindications may limit their use. The "I(f)" (for "funny") channel, discovered in 1979, is expressed mainly in the membrane of pacemaker cells present in the sinus node, the atrioventricular node, the ventricular conduction pathways, and ventricular myocytes. By determining the slope of diastolic depolarization, which in turn controls action potential frequency, it is a key determinant of heart rate and so provides a new therapeutic target for controlling angina symptoms. A new antiangina drug, ivabradine, has been developed and licensed for clinical use. It exclusively reduces the heart rate by selectively blocking the I(f) channel of the sino-atrial node. As clinical trials have shown it to be remarkably well-tolerated, ivabradine offers an alternative for patients who cannot take, or are intolerant of, beta blockade. This review provides an insight into this new agent, its historical background, mechanism of action, and pathophysiologic basis, and provides up-to-date evidence-based information on its optimum use in stable angina.

Projection structure of a ClC-type chloride channel at 6.5Å resolution

NASA Astrophysics Data System (ADS)

Mindell, Joseph A.; Maduke, Merritt; Miller, Christopher; Grigorieff, Nikolaus

2001-01-01

Virtually all cells in all eukaryotic organisms express ion channels of the ClC type, the only known molecular family of chloride-ion-selective channels. The diversity of ClC channels highlights the multitude and range of functions served by gated chloride-ion conduction in biological membranes, such as controlling electrical excitability in skeletal muscle, maintaining systemic blood pressure, acidifying endosomal compartments, and regulating electrical responses of GABA (γ-aminobutyric acid)-containing interneurons in the central nervous system. Previously, we expressed and purified a prokaryotic ClC channel homologue. Here we report the formation of two-dimensional crystals of this ClC channel protein reconstituted into phospholipid bilayer membranes. Cryo-electron microscopic analysis of these crystals yields a projection structure at 6.5Å resolution, which shows off-axis water-filled pores within the dimeric channel complex.

Crystal diffraction lens with variable focal length

DOEpatents

Smither, R.K.

1991-04-02

A method and apparatus for altering the focal length of a focusing element of one of a plurality of pre-determined focal lengths by changing heat transfer within selected portions of the element by controlled quantities is disclosed. Control over heat transfer is accomplished by manipulating one or more of a number of variables, including: the amount of heat or cold applied to surfaces; type of fluids pumped through channels for heating and cooling; temperatures, directions of flow and rates of flow of fluids; and placement of channels. 19 figures.

Ion channels versus ion pumps: the principal difference, in principle.

PubMed

Gadsby, David C

2009-05-01

The incessant traffic of ions across cell membranes is controlled by two kinds of border guards: ion channels and ion pumps. Open channels let selected ions diffuse rapidly down electrical and concentration gradients, whereas ion pumps labour tirelessly to maintain the gradients by consuming energy to slowly move ions thermodynamically uphill. Because of the diametrically opposed tasks and the divergent speeds of channels and pumps, they have traditionally been viewed as completely different entities, as alike as chalk and cheese. But new structural and mechanistic information about both of these classes of molecular machines challenges this comfortable separation and forces its re-evaluation.

Efficient needle plasma actuators for flow control and surface cooling

NASA Astrophysics Data System (ADS)

Zhao, Pengfei; Portugal, Sherlie; Roy, Subrata

2015-07-01

We introduce a milliwatt class needle actuator suitable for plasma channels, vortex generation, and surface cooling. Electrode configurations tested for a channel configuration show 1400% and 300% increase in energy conversion efficiency as compared to conventional surface and channel corona actuators, respectively, generating up to 3.4 m/s air jet across the channel outlet. The positive polarity of the needle is shown to have a beneficial effect on actuator efficiency. Needle-plate configuration is demonstrated for improving cooling of a flat surface with a 57% increase in convective heat transfer coefficient. Vortex generation by selective input signal manipulation is also demonstrated.

A motion-classification strategy based on sEMG-EEG signal combination for upper-limb amputees.

PubMed

Li, Xiangxin; Samuel, Oluwarotimi Williams; Zhang, Xu; Wang, Hui; Fang, Peng; Li, Guanglin

2017-01-07

Most of the modern motorized prostheses are controlled with the surface electromyography (sEMG) recorded on the residual muscles of amputated limbs. However, the residual muscles are usually limited, especially after above-elbow amputations, which would not provide enough sEMG for the control of prostheses with multiple degrees of freedom. Signal fusion is a possible approach to solve the problem of insufficient control commands, where some non-EMG signals are combined with sEMG signals to provide sufficient information for motion intension decoding. In this study, a motion-classification method that combines sEMG and electroencephalography (EEG) signals were proposed and investigated, in order to improve the control performance of upper-limb prostheses. Four transhumeral amputees without any form of neurological disease were recruited in the experiments. Five motion classes including hand-open, hand-close, wrist-pronation, wrist-supination, and no-movement were specified. During the motion performances, sEMG and EEG signals were simultaneously acquired from the skin surface and scalp of the amputees, respectively. The two types of signals were independently preprocessed and then combined as a parallel control input. Four time-domain features were extracted and fed into a classifier trained by the Linear Discriminant Analysis (LDA) algorithm for motion recognition. In addition, channel selections were performed by using the Sequential Forward Selection (SFS) algorithm to optimize the performance of the proposed method. The classification performance achieved by the fusion of sEMG and EEG signals was significantly better than that obtained by single signal source of either sEMG or EEG. An increment of more than 14% in classification accuracy was achieved when using a combination of 32-channel sEMG and 64-channel EEG. Furthermore, based on the SFS algorithm, two optimized electrode arrangements (10-channel sEMG + 10-channel EEG, 10-channel sEMG + 20-channel EEG) were obtained with classification accuracies of 84.2 and 87.0%, respectively, which were about 7.2 and 10% higher than the accuracy by using only 32-channel sEMG input. This study demonstrated the feasibility of fusing sEMG and EEG signals towards improving motion classification accuracy for above-elbow amputees, which might enhance the control performances of multifunctional myoelectric prostheses in clinical application. The study was approved by the ethics committee of Institutional Review Board of Shenzhen Institutes of Advanced Technology, and the reference number is SIAT-IRB-150515-H0077.

The roles of KCa, KATP, and KV channels in regulating cutaneous vasodilation and sweating during exercise in the heat.

PubMed

Louie, Jeffrey C; Fujii, Naoto; Meade, Robert D; McNeely, Brendan D; Kenny, Glen P

2017-05-01

We recently showed the varying roles of Ca 2+ -activated (K Ca ), ATP-sensitive (K ATP ), and voltage-gated (K V ) K + channels in regulating cholinergic cutaneous vasodilation and sweating in normothermic conditions. However, it is unclear whether the respective contributions of these K + channels remain intact during dynamic exercise in the heat. Eleven young (23 ± 4 yr) men completed a 30-min exercise bout at a fixed rate of metabolic heat production (400 W) followed by a 40-min recovery period in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and local sweat rate were assessed at four forearm skin sites perfused via intradermal microdialysis with: 1 ) lactated Ringer solution (control); 2 ) 50 mM tetraethylammonium (nonspecific K Ca channel blocker); 3 ) 5 mM glybenclamide (selective K ATP channel blocker); or 4 ) 10 mM 4-aminopyridine (nonspecific K V channel blocker). Responses were compared at baseline and at 10-min intervals during and following exercise. K Ca channel inhibition resulted in greater CVC versus control at end exercise ( P = 0.04) and 10 and 20 min into recovery (both P < 0.01). K ATP channel blockade attenuated CVC compared with control during baseline ( P = 0.04), exercise (all P ≤ 0.04), and 10 min into recovery ( P = 0.02). No differences in CVC were observed with K V channel inhibition during baseline ( P = 0.15), exercise (all P ≥ 0.06), or recovery (all P ≥ 0.14). With the exception of K V channel inhibition augmenting sweating during baseline ( P = 0.04), responses were similar to control with all K + channel blockers during each time period (all P ≥ 0.07). We demonstrated that K Ca and K ATP channels contribute to the regulation of cutaneous vasodilation during rest and/or exercise and recovery in the heat. Copyright © 2017 the American Physiological Society.

Managing the complexity of communication: regulation of gap junctions by post-translational modification

PubMed Central

Axelsen, Lene N.; Calloe, Kirstine; Holstein-Rathlou, Niels-Henrik; Nielsen, Morten S.

2013-01-01

Gap junctions are comprised of connexins that form cell-to-cell channels which couple neighboring cells to accommodate the exchange of information. The need for communication does, however, change over time and therefore must be tightly controlled. Although the regulation of connexin protein expression by transcription and translation is of great importance, the trafficking, channel activity and degradation are also under tight control. The function of connexins can be regulated by several post translational modifications, which affect numerous parameters; including number of channels, open probability, single channel conductance or selectivity. The most extensively investigated post translational modifications are phosphorylations, which have been documented in all mammalian connexins. Besides phosphorylations, some connexins are known to be ubiquitinated, SUMOylated, nitrosylated, hydroxylated, acetylated, methylated, and γ-carboxyglutamated. The aim of the present review is to summarize our current knowledge of post translational regulation of the connexin family of proteins. PMID:24155720

Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family.

PubMed

Kaufman, I; Luchinsky, D G; Tindjong, R; McClintock, P V E; Eisenberg, R S

2013-11-01

We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Q(f) at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Q(f)=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Q(f) for the sodium-calcium channels family. An increase of Q(f) leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Q(f)(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca(2+)/Na(+) valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.

Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family

NASA Astrophysics Data System (ADS)

Kaufman, I.; Luchinsky, D. G.; Tindjong, R.; McClintock, P. V. E.; Eisenberg, R. S.

2013-11-01

We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Qf at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Qf=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Qf for the sodium-calcium channels family. An increase of Qf leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Qf(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca2+/Na+ valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.

Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model.

PubMed

Hager, Natalie A; Krasowski, Collin J; Mackie, Timothy D; Kolb, Alexander R; Needham, Patrick G; Augustine, Andrew A; Dempsey, Alison; Szent-Gyorgyi, Christopher; Bruchez, Marcel P; Bain, Daniel J; Kwiatkowski, Adam V; O'Donnell, Allyson F; Brodsky, Jeffrey L

2018-05-21

Protein composition at the plasma membrane is tightly regulated, with rapid protein internalization and selective targeting to the cell surface occurring in response to environmental changes. For example, ion channels are dynamically relocalized to or from the plasma membrane in response to physiological alterations, allowing cells and organisms to maintain osmotic and salt homeostasis. To identify additional factors that regulate the selective trafficking of a specific ion channel, we used a yeast model for a mammalian potassium channel, the K+ inwardly rectifying channel Kir2.1. Kir2.1 maintains potassium homeostasis in heart muscle cells, and Kir2.1 defects lead to human disease. By examining the ability of Kir2.1 to rescue the growth of yeast cells lacking endogenous potassium channels, we discovered that specific α-arrestins regulate Kir2.1 localization. Specifically, we found that the Ldb19/Art1, Aly1/Art6, and Aly2/Art3 α-arrestin adaptor proteins promote Kir2.1 trafficking to the cell surface, increase Kir2.1 activity at the plasma membrane, and raise intracellular potassium levels. To better quantify the intracellular and cell-surface populations of Kir2.1, we created fluorescence-activating protein fusions and for the first time used this technique to measure the cell-surface residency of a plasma membrane protein in yeast. Our experiments revealed that two α-arrestin effectors also control Kir2.1 localization. In particular, both the Rsp5 ubiquitin ligase and the protein phosphatase calcineurin facilitated the α-arrestin-mediated trafficking of Kir2.1. Together, our findings implicate α-arrestins in regulating an additional class of plasma membrane proteins and establish a new tool for dissecting the trafficking itinerary of any membrane protein in yeast. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Relationship between grasping force and features of single-channel intramuscular EMG signals.

PubMed

Kamavuako, Ernest Nlandu; Farina, Dario; Yoshida, Ken; Jensen, Winnie

2009-12-15

The surface electromyographic (sEMG) signal can be used for force prediction and control in prosthetic devices. Because of technological advances on implantable sensors, the use of intramuscular EMG (iEMG) is becoming a potential alternative to sEMG for the control of multiple degrees-of-freedom (DOF). An invasive system is not affected by crosstalk, typical of sEMG, and provides more stable and independent control sites. However, intramuscular recordings provide more local information because of their high selectivity, and may thus be less representative of the global muscle activity with respect to sEMG. This study investigates the capacity of selective single-channel iEMG recordings to represent the grasping force with respect to the use of sEMG with the aim of assessing if iEMG can be an effective method for proportional myoelectric control. sEMG and iEMG were recorded concurrently from 10 subjects who exerted six grasping force profiles from 0 to 25/50N. The linear correlation coefficient between features extracted from iEMG and force was approximately 0.9 and was not significantly different from the degree of correlation between sEMG and force. This result indicates that a selective iEMG recording is representative of the applied grasping force and can be used for proportional control.

Magnetoencephalogram blind source separation and component selection procedure to improve the diagnosis of Alzheimer's disease patients.

PubMed

Escudero, Javier; Hornero, Roberto; Abásolo, Daniel; Fernández, Alberto; Poza, Jesús

2007-01-01

The aim of this study was to improve the diagnosis of Alzheimer's disease (AD) patients applying a blind source separation (BSS) and component selection procedure to their magnetoencephalogram (MEG) recordings. MEGs from 18 AD patients and 18 control subjects were decomposed with the algorithm for multiple unknown signals extraction. MEG channels and components were characterized by their mean frequency, spectral entropy, approximate entropy, and Lempel-Ziv complexity. Using Student's t-test, the components which accounted for the most significant differences between groups were selected. Then, these relevant components were used to partially reconstruct the MEG channels. By means of a linear discriminant analysis, we found that the BSS-preprocessed MEGs classified the subjects with an accuracy of 80.6%, whereas 72.2% accuracy was obtained without the BSS and component selection procedure.

Role of different types of Ca2+ channels and a reticulum-like Ca2+ pump in neurotransmitter release.

PubMed

Fossier, P; Baux, G; Tauc, L

1993-01-01

The factors controlling the Ca2+ concentration directly responsible for triggering acetylcholine (ACh) release were investigated at an identified neuro-neuronal synapse of the Aplysia buccal ganglion. The types of presynaptic voltage-gated Ca2+ channels associated with transmitter release were determined by using selective blockers such as nifedipine, omega-conotoxin and a partially purified extract from the venom of a funnel web spider (FTx). L-type, N-type and P-type Ca2+ channels are present in the presynaptic neuron. The influx of Ca2+ through both N- and P-types induces the release of ACh whereas Ca2+ flowing through L-type channels modulates the duration of the presynaptic action potential by controlling the Ca(2+)-dependent K+ current. tBuBHQ, a blocker of the reticulum Ca2+ pump, induces a potentiation of evoked release without modifying the presynaptic Ca2+ influx. This seems to indicate that a part of the Ca2+ entering the presynaptic terminal through N- and P-type Ca2+ channels is sequestered in a presynaptic reticulum-like Ca2+ buffer preventing these ions from contributing to ACh release. To exert its control, this Ca2+ buffer must be located close to both the presynaptic Ca2+ channels and the transmitter release mechanism.

Understanding and improving photo-control of ion channels in nociceptors with azobenzene photo-switches.

PubMed

Mourot, Alexandre; Herold, Christian; Kienzler, Michael A; Kramer, Richard H

2017-06-20

The photo-isomerizable local anaesthetic, quaternary ammonium-azobenzene-quaternary ammonium (QAQ), provides rapid, optical control over pain signalling without involving genetic modification. In darkness or in green light, trans-QAQ blocks voltage-gated K + and Na + channels and silences action potentials in pain-sensing neurons. Upon photo-isomerization to cis with near UV light, QAQ blockade is rapidly relieved, restoring neuronal activity. However, the molecular mechanism of cis and trans QAQ blockade is not known. Moreover, the absorption spectrum of QAQ requires UV light for photo-control, precluding use deep inside neural tissue. Electrophysiology and molecular modelling were used to characterize the binding of cis and trans QAQ to voltage-gated K + channels and to develop quaternary ammonium-ethylamine-azobenzene-quaternary ammonium (QENAQ), a red-shifted QAQ derivative controlled with visible light. trans QAQ was sixfold more potent than cis QAQ, in blocking current through Shaker K + channels. Both isomers were use-dependent, open channel blockers, binding from the cytoplasmic side, but only trans QAQ block was slightly voltage dependent. QENAQ also blocked native K + and Na + channels preferentially in the trans state. QENAQ was photo-isomerized to cis with blue light and spontaneously reverted to trans within seconds in darkness, enabling rapid photo-control of action potentials in sensory neurons. Light-switchable local anaesthetics provide a means to non-invasively photo-control pain signalling with high selectivity and fast kinetics. Understanding the mode of action of QAQ and related compounds will help to design of drugs with improved photo-pharmacological properties. © 2017 The British Pharmacological Society.

Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity

PubMed Central

Ader, Christian; Schneider, Robert; Hornig, Sönke; Velisetty, Phanindra; Vardanyan, Vitya; Giller, Karin; Ohmert, Iris; Becker, Stefan; Pongs, Olaf; Baldus, Marc

2009-01-01

Potassium (K+)-channel gating is choreographed by a complex interplay between external stimuli, K+ concentration and lipidic environment. We combined solid-state NMR and electrophysiological experiments on a chimeric KcsA–Kv1.3 channel to delineate K+, pH and blocker effects on channel structure and function in a membrane setting. Our data show that pH-induced activation is correlated with protonation of glutamate residues at or near the activation gate. Moreover, K+ and channel blockers distinctly affect the open probability of both the inactivation gate comprising the selectivity filter of the channel and the activation gate. The results indicate that the two gates are coupled and that effects of the permeant K+ ion on the inactivation gate modulate activation-gate opening. Our data suggest a mechanism for controlling coordinated and sequential opening and closing of activation and inactivation gates in the K+-channel pore. PMID:19661921

Self-Optimized Biological Channels in Facilitating the Transmembrane Movement of Charged Molecules

PubMed Central

Huyen, V. T. N.; Lap, Vu Cong; Nguyen, V. Lien

2016-01-01

We consider an anisotropically two-dimensional diffusion of a charged molecule (particle) through a large biological channel under an external voltage. The channel is modeled as a cylinder of three structure parameters: radius, length, and surface density of negative charges located at the channel interior-lining. These charges induce inside the channel a potential that plays a key role in controlling the particle current through the channel. It was shown that to facilitate the transmembrane particle movement the channel should be reasonably self-optimized so that its potential coincides with the resonant one, resulting in a large particle current across the channel. Observed facilitation appears to be an intrinsic property of biological channels, regardless of the external voltage or the particle concentration gradient. This facilitation is very selective in the sense that a channel of definite structure parameters can facilitate the transmembrane movement of only particles of proper valence at corresponding temperatures. Calculations also show that the modeled channel is nonohmic with the ion conductance which exhibits a resonance at the same channel potential as that identified in the current. PMID:27022394

Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors

PubMed Central

Moreau, Christophe J.; Revilloud, Jean; Caro, Lydia N.; Dupuis, Julien P.; Trouchet, Amandine; Estrada-Mondragón, Argel; Nieścierowicz, Katarzyna; Sapay, Nicolas; Crouzy, Serge; Vivaudou, Michel

2017-01-01

Ligand-gated ion channels enable intercellular transmission of action potential through synapses by transducing biochemical messengers into electrical signal. We designed artificial ligand-gated ion channels by coupling G protein-coupled receptors to the Kir6.2 potassium channel. These artificial channels called ion channel-coupled receptors offer complementary properties to natural channels by extending the repertoire of ligands to those recognized by the fused receptors, by generating more sustained signals and by conferring potassium selectivity. The first artificial channels based on the muscarinic M2 and the dopaminergic D2L receptors were opened and closed by acetylcholine and dopamine, respectively. We find here that this opposite regulation of the gating is linked to the length of the receptor C-termini, and that C-terminus engineering can precisely control the extent and direction of ligand gating. These findings establish the design rules to produce customized ligand-gated channels for synthetic biology applications. PMID:28145461

Altered Regulation of Airway Epithelial Cell Chloride Channels in Cystic Fibrosis

NASA Astrophysics Data System (ADS)

Frizzell, Raymond A.; Rechkemmer, Gerhard; Shoemaker, Richard L.

1986-08-01

In many epithelial cells the chloride conductance of the apical membrane increases during the stimulation of electrolyte secretion. Single-channel recordings from human airway epithelial cells showed that β -adrenergic stimulation evoked apical membrane chloride channel activity, but this response was absent in cells from patients with cystic fibrosis (CF). However, when membrane patches were excised from CF cells into media containing sufficient free calcium (approximately 180 nanomolar), chloride channels were activated. The chloride channels of CF cells were similar to those of normal cells as judged by their current-voltage relations, ion selectivity, and kinetic behavior. These findings demonstrate the presence of chloride channels in the apical membranes of CF airway cells. Their regulation by calcium appears to be intact, but cyclic adenosine monophosphate (cAMP)-dependent control of their activity is defective.

Independent control of electrical and heat conduction by nanostructure designing for Si-based thermoelectric materials

PubMed Central

Yamasaka, Shuto; Watanabe, Kentaro; Sakane, Shunya; Takeuchi, Shotaro; Sakai, Akira; Sawano, Kentarou; Nakamura, Yoshiaki

2016-01-01

The high electrical and drastically-low thermal conductivities, a vital goal for high performance thermoelectric (TE) materials, are achieved in Si-based nanoarchitecture composed of Si channel layers and epitaxial Ge nanodots (NDs) with ultrahigh areal density (~1012 cm−2). In this nanoarchitecture, the ultrasmall NDs and Si channel layers play roles of phonon scattering sources and electrical conduction channels, respectively. Electron conductivity in n-type nanoacrhitecture shows high values comparable to those of epitaxial Si films despite the existence of epitaxial NDs. This is because Ge NDs mainly scattered not electrons but phonons selectively, which could be attributed to the small conduction band offset at the epitaxially-grown Si/Ge interface and high transmission probability through stacking faults. These results demonstrate an independent control of thermal and electrical conduction for phonon-glass electron-crystal TE materials by nanostructure designing and the energetic and structural interface control. PMID:26973092

A review of channel selection algorithms for EEG signal processing

NASA Astrophysics Data System (ADS)

Alotaiby, Turky; El-Samie, Fathi E. Abd; Alshebeili, Saleh A.; Ahmad, Ishtiaq

2015-12-01

Digital processing of electroencephalography (EEG) signals has now been popularly used in a wide variety of applications such as seizure detection/prediction, motor imagery classification, mental task classification, emotion classification, sleep state classification, and drug effects diagnosis. With the large number of EEG channels acquired, it has become apparent that efficient channel selection algorithms are needed with varying importance from one application to another. The main purpose of the channel selection process is threefold: (i) to reduce the computational complexity of any processing task performed on EEG signals by selecting the relevant channels and hence extracting the features of major importance, (ii) to reduce the amount of overfitting that may arise due to the utilization of unnecessary channels, for the purpose of improving the performance, and (iii) to reduce the setup time in some applications. Signal processing tools such as time-domain analysis, power spectral estimation, and wavelet transform have been used for feature extraction and hence for channel selection in most of channel selection algorithms. In addition, different evaluation approaches such as filtering, wrapper, embedded, hybrid, and human-based techniques have been widely used for the evaluation of the selected subset of channels. In this paper, we survey the recent developments in the field of EEG channel selection methods along with their applications and classify these methods according to the evaluation approach.

Miniaturized Ka-Band Dual-Channel Radar

NASA Technical Reports Server (NTRS)

Hoffman, James P.; Moussessian, Alina; Jenabi, Masud; Custodero, Brian

2011-01-01

Smaller (volume, mass, power) electronics for a Ka-band (36 GHz) radar interferometer were required. To reduce size and achieve better control over RFphase versus temperature, fully hybrid electronics were developed for the RF portion of the radar s two-channel receiver and single-channel transmitter. In this context, fully hybrid means that every active RF device was an open die, and all passives were directly attached to the subcarrier. Attachments were made using wire and ribbon bonding. In this way, every component, even small passives, was selected for the fabrication of the two radar receivers, and the devices were mounted relative to each other in order to make complementary components isothermal and to isolate other components from potential temperature gradients. This is critical for developing receivers that can track each other s phase over temperature, which is a key mission driver for obtaining ocean surface height. Fully hybrid, Ka-band (36 GHz) radar transmitter and dual-channel receiver were developed for spaceborne radar interferometry. The fully hybrid fabrication enables control over every aspect of the component selection, placement, and connection. Since the two receiver channels must track each other to better than 100 millidegrees of RF phase over several minutes, the hardware in the two receivers must be "identical," routed the same (same line lengths), and as isothermal as possible. This level of design freedom is not possible with packaged components, which include many internal passive, unknown internal connection lengths/types, and often a single orientation of inputs and outputs.

High density, multi-range analog output Versa Module Europa board for control system applications

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

Singh, Kundan, E-mail: kundan@iuac.res.in; Das, Ajit Lal

2014-01-15

A new VMEDAC64, 12-bit 64 channel digital-to-analog converter, a Versa Module Europa (VME) module, features 64 analog voltage outputs with user selectable multiple ranges, has been developed for control system applications at Inter University Accelerator Centre. The FPGA (Field Programmable Gate Array) is the module's core, i.e., it implements the DAC control logic and complexity of VMEbus slave interface logic. The VMEbus slave interface and DAC control logic are completely designed and implemented on a single FPGA chip to achieve high density of 64 channels in a single width VME module and will reduce the module count in the controlmore » system applications, and hence will reduce the power consumption and cost of overall system. One of our early design goals was to develop the VME interface such that it can be easily integrated with the peripheral devices and satisfy the timing specifications of VME standard. The modular design of this module reduces the amount of time required to develop other custom modules for control system. The VME slave interface is written as a single component inside FPGA which will be used as a basic building block for any VMEbus interface project. The module offers multiple output voltage ranges depending upon the requirement. The output voltage range can be reduced or expanded by writing range selection bits in the control register. The module has programmable refresh rate and by default hold capacitors in the sample and hold circuit for each channel are charged periodically every 7.040 ms (i.e., update frequency 284 Hz). Each channel has software controlled output switch which disconnects analog output from the field. The modularity in the firmware design on FPGA makes the debugging very easy. On-board DC/DC converters are incorporated for isolated power supply for the analog section of the board.« less

Creating fast flow channels in paper fluidic devices to control timing of sequential reactions.

PubMed

Jahanshahi-Anbuhi, Sana; Chavan, Puneet; Sicard, Clémence; Leung, Vincent; Hossain, S M Zakir; Pelton, Robert; Brennan, John D; Filipe, Carlos D M

2012-12-07

This paper reports the development of a method to control the flow rate of fluids within paper-based microfluidic analytical devices. We demonstrate that by simply sandwiching paper channels between two flexible films, it is possible to accelerate the flow of water through paper by over 10-fold. The dynamics of this process are such that the height of the liquid is dependent on time to the power of 1/3. This dependence was validated using three different flexible films (with markedly different contact angles) and three different fluids (water and two silicon oils with different viscosities). These covered channels provide a low-cost method for controlling the flow rate of fluid in paper channels, and can be added following printing of reagents to control fluid flow in selected fluidic channels. Using this method, we redesigned a previously published bidirectional lateral flow pesticide sensor to allow more rapid detection of pesticides while eliminating the need to run the assay in two stages. The sensor is fabricated with sol-gel entrapped reagents (indoxyl acetate in a substrate zone and acetylcholinesterase, AChE, in a sensing zone) present in an uncovered "slow" flow channel, with a second, covered "fast" channel used to transport pesticide samples to the sensing region through a simple paper-flap valve. In this manner, pesticides reach the sensing region first to allow preincubation, followed by delivery of the substrate to generate a colorimetric signal. This format results in a uni-directional device that detects the presence of pesticides two times faster than the original bidirectional sensors.

Message passing with queues and channels

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

Dozsa, Gabor J; Heidelberger, Philip; Kumar, Sameer

In an embodiment, a send thread receives an identifier that identifies a destination node and a pointer to data. The send thread creates a first send request in response to the receipt of the identifier and the data pointer. The send thread selects a selected channel from among a plurality of channels. The selected channel comprises a selected hand-off queue and an identification of a selected message unit. Each of the channels identifies a different message unit. The selected hand-off queue is randomly accessible. If the selected hand-off queue contains an available entry, the send thread adds the first sendmore » request to the selected hand-off queue. If the selected hand-off queue does not contain an available entry, the send thread removes a second send request from the selected hand-off queue and sends the second send request to the selected message unit.« less

Evaluation of selective control information detection scheme in orthogonal frequency division multiplexing-based radio-over-fiber and visible light communication links

NASA Astrophysics Data System (ADS)

Dalarmelina, Carlos A.; Adegbite, Saheed A.; Pereira, Esequiel da V.; Nunes, Reginaldo B.; Rocha, Helder R. O.; Segatto, Marcelo E. V.; Silva, Jair A. L.

2017-05-01

Block-level detection is required to decode what may be classified as selective control information (SCI) such as control format indicator in 4G-long-term evolution systems. Using optical orthogonal frequency division multiplexing over radio-over-fiber (RoF) links, we report the experimental evaluation of an SCI detection scheme based on a time-domain correlation (TDC) technique in comparison with the conventional maximum likelihood (ML) approach. When compared with the ML method, it is shown that the TDC method improves detection performance over both 20 and 40 km of standard single mode fiber (SSMF) links. We also report a performance analysis of the TDC scheme in noisy visible light communication channel models after propagation through 40 km of SSMF. Experimental and simulation results confirm that the TDC method is attractive for practical orthogonal frequency division multiplexing-based RoF and fiber-wireless systems. Unlike the ML method, another key benefit of the TDC is that it requires no channel estimation.

Ion-binding properties of a K+ channel selectivity filter in different conformations.

PubMed

Liu, Shian; Focke, Paul J; Matulef, Kimberly; Bian, Xuelin; Moënne-Loccoz, Pierre; Valiyaveetil, Francis I; Lockless, Steve W

2015-12-08

K(+) channels are membrane proteins that selectively conduct K(+) ions across lipid bilayers. Many voltage-gated K(+) (KV) channels contain two gates, one at the bundle crossing on the intracellular side of the membrane and another in the selectivity filter. The gate at the bundle crossing is responsible for channel opening in response to a voltage stimulus, whereas the gate at the selectivity filter is responsible for C-type inactivation. Together, these regions determine when the channel conducts ions. The K(+) channel from Streptomyces lividians (KcsA) undergoes an inactivation process that is functionally similar to KV channels, which has led to its use as a practical system to study inactivation. Crystal structures of KcsA channels with an open intracellular gate revealed a selectivity filter in a constricted conformation similar to the structure observed in closed KcsA containing only Na(+) or low [K(+)]. However, recent work using a semisynthetic channel that is unable to adopt a constricted filter but inactivates like WT channels challenges this idea. In this study, we measured the equilibrium ion-binding properties of channels with conductive, inactivated, and constricted filters using isothermal titration calorimetry (ITC). EPR spectroscopy was used to determine the state of the intracellular gate of the channel, which we found can depend on the presence or absence of a lipid bilayer. Overall, we discovered that K(+) ion binding to channels with an inactivated or conductive selectivity filter is different from K(+) ion binding to channels with a constricted filter, suggesting that the structures of these channels are different.

A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.

PubMed

Zhang, Alan H; Sharma, Gagan; Undheim, Eivind A B; Jia, Xinying; Mobli, Mehdi

2018-04-21

Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (Na V s) have attracted particular attention as potential analgesic targets. Na V s, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e.g. Na V 1.7) to controlling electrical signalling in cardiac function (Na V 1.5). Understanding the structural basis of Na V function is therefore of great significance, both to our knowledge of electrical signalling and in development of subtype and state selective drugs. An important tool in this pursuit has been the use of peptides from animal venoms as selective Na V modulators. In this review, we look at peptides, particularly from spider venoms, that inhibit Na V s by binding to the voltage sensing domain (VSD) of this channel, known as gating modifier toxins (GMT). In the first part of the review, we look at the structural determinants of voltage sensing in VGICs, the gating cycle and the conformational changes that accompany VSD movement. Next, the modulation of the analgesic target Na V 1.7 by GMTs is reviewed to develop bioinformatic tools that, based on sequence information alone, can identify toxins that are likely to inhibit this channel. The same approach is also used to define VSD sequences, other than that from Na V 1.7, which are likely to be sensitive to this class of toxins. The final section of the review focuses on the important role of the cellular membrane in channel modulation and also how the lipid composition affects measurements of peptide-channel interactions both in binding kinetics measurements in solution and in cell-based functional assays. Copyright © 2018 Elsevier B.V. All rights reserved.

Tuning the ion selectivity of two-pore channels

PubMed Central

Guo, Jiangtao; Zeng, Weizhong; Jiang, Youxing

2017-01-01

Organellar two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in plants and animals. Interestingly, plant and animal TPCs share high sequence similarity in the filter region, yet exhibit drastically different ion selectivity. Plant TPC1 functions as a nonselective cation channel on the vacuole membrane, whereas mammalian TPC channels have been shown to be endo/lysosomal Na+-selective or Ca2+-release channels. In this study, we performed systematic characterization of the ion selectivity of TPC1 from Arabidopsis thaliana (AtTPC1) and compared its selectivity with the selectivity of human TPC2 (HsTPC2). We demonstrate that AtTPC1 is selective for Ca2+ over Na+, but nonselective among monovalent cations (Li+, Na+, and K+). Our results also confirm that HsTPC2 is a Na+-selective channel activated by phosphatidylinositol 3,5-bisphosphate. Guided by our recent structure of AtTPC1, we converted AtTPC1 to a Na+-selective channel by mimicking the selectivity filter of HsTPC2 and identified key residues in the TPC filters that differentiate the selectivity between AtTPC1 and HsTPC2. Furthermore, the structure of the Na+-selective AtTPC1 mutant elucidates the structural basis for Na+ selectivity in mammalian TPCs. PMID:28096396

Tuning the ion selectivity of two-pore channels

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

Guo, Jiangtao; Zeng, Weizhong; Jiang, Youxing

Organellar two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in plants and animals. Interestingly, plant and animal TPCs share high sequence similarity in the filter region, yet exhibit drastically different ion selectivity. Plant TPC1 functions as a nonselective cation channel on the vacuole membrane, whereas mammalian TPC channels have been shown to be endo/lysosomal Na+-selective or Ca2+-release channels. In this study, we performed systematic characterization of the ion selectivity of TPC1 from Arabidopsis thaliana (AtTPC1) and compared its selectivity with the selectivity of human TPC2 (HsTPC2). We demonstrate thatmore » AtTPC1 is selective for Ca2+ over Na+, but nonselective among monovalent cations (Li+, Na+, and K+). Our results also confirm that HsTPC2 is a Na+-selective channel activated by phosphatidylinositol 3,5-bisphosphate. Guided by our recent structure of AtTPC1, we converted AtTPC1 to a Na+-selective channel by mimicking the selectivity filter of HsTPC2 and identified key residues in the TPC filters that differentiate the selectivity between AtTPC1 and HsTPC2. Furthermore, the structure of the Na+-selective AtTPC1 mutant elucidates the structural basis for Na+ selectivity in mammalian TPCs.« less

Exploring the Structure of the Voltage-gated Na+ Channel by an Engineered Drug Access Pathway to the Receptor Site for Local Anesthetics*

PubMed Central

Lukacs, Peter; Gawali, Vaibhavkumar S.; Cervenka, Rene; Ke, Song; Koenig, Xaver; Rubi, Lena; Zarrabi, Touran; Hilber, Karlheinz; Stary-Weinzinger, Anna; Todt, Hannes

2014-01-01

Despite the availability of several crystal structures of bacterial voltage-gated Na+ channels, the structure of eukaryotic Na+ channels is still undefined. We used predictions from available homology models and crystal structures to modulate an external access pathway for the membrane-impermeant local anesthetic derivative QX-222 into the internal vestibule of the mammalian rNaV1.4 channel. Potassium channel-based homology models predict amino acid Ile-1575 in domain IV segment 6 to be in close proximity to Lys-1237 of the domain III pore-loop selectivity filter. The mutation K1237E has been shown previously to increase the diameter of the selectivity filter. We found that an access pathway for external QX-222 created by mutations of Ile-1575 was abolished by the additional mutation K1237E, supporting the notion of a close spatial relationship between sites 1237 and 1575. Crystal structures of bacterial voltage-gated Na+ channels predict that the side chain of rNaV1.4 Trp-1531 of the domain IV pore-loop projects into the space between domain IV segment 6 and domain III pore-loop and, therefore, should obstruct the putative external access pathway. Indeed, mutations W1531A and W1531G allowed for exceptionally rapid access of QX-222. In addition, W1531G created a second non-selective ion-conducting pore, bypassing the outer vestibule but probably merging into the internal vestibule, allowing for control by the activation gate. These data suggest a strong structural similarity between bacterial and eukaryotic voltage-gated Na+ channels. PMID:24947510

Importance of the Debye Screening Length on Nanowire Field Effect Transistor Sensors

PubMed Central

Stern, Eric; Wagner, Robin; Sigworth, Fred J.; Breaker, Ronald; Fahmy, Tarek M.; Reed, Mark A.

2009-01-01

Nanowire field effect transistors (NW-FETs) can serve as ultrasensitive detectors for label-free reagents. The NW-FET sensing mechanism assumes a controlled modification in the local channel electric field created by the binding of charged molecules to the nanowire surface. Careful control of the solution Debye length is critical for unambiguous selective detection of macromolecules. Here we show the appropriate conditions under which the selective binding of macromolecules is accurately sensed with NW-FET sensors. PMID:17914853

Importance of the Debye screening length on nanowire field effect transistor sensors.

PubMed

Stern, Eric; Wagner, Robin; Sigworth, Fred J; Breaker, Ronald; Fahmy, Tarek M; Reed, Mark A

2007-11-01

Nanowire field effect transistors (NW-FETs) can serve as ultrasensitive detectors for label-free reagents. The NW-FET sensing mechanism assumes a controlled modification in the local channel electric field created by the binding of charged molecules to the nanowire surface. Careful control of the solution Debye length is critical for unambiguous selective detection of macromolecules. Here we show the appropriate conditions under which the selective binding of macromolecules is accurately sensed with NW-FET sensors.

Water Quality Assessment for Deep-water Channel area of Guangzhou Port based on the Comprehensive Water Quality Identification Index Method

NASA Astrophysics Data System (ADS)

Chen, Yi

2018-03-01

The comprehensive water quality identification index method is able to assess the general water quality situation comprehensively and represent the water quality classification; water environment functional zone achieves pollution level and standard objectively and systematically. This paper selects 3 representative zones along deep-water channel of Guangzhou port and applies comprehensive water quality identification index method to calculate sea water quality monitoring data for different selected zones from year 2006 to 2014, in order to investigate the temporal variation of water quality along deep-water channel of Guangzhou port. The comprehensive water quality level from north to south presents an increased trend, and the water quality of the three zones in 2014 is much better than in 2006. This paper puts forward environmental protection measurements and suggestions for Pearl River Estuary, provides data support and theoretical basis for studied sea area pollution prevention and control.

Development of a PC interface board for true color control using an Ar Kr white-light laser

NASA Astrophysics Data System (ADS)

Shin, Yongjin; Park, Sohee; Kim, Youngseop; Lee, Jangwoen

2006-06-01

For the optimal laser display, it is crucial to select and control color signals of proper wavelengths in order to construct a wide range of laser display colors. In traditional laser display schemes, color control has been achieved through the mechanical manipulation of red, green, and blue (RGB) laser beam intensities using color filters. To maximize the effect of a laser display and its color contents, it is desirable to generate laser beams with wide selection of wavelengths. We present an innovative laser display control technique, which generates six channel laser wavelengths from a white-light laser using a RF-controlled polychromatic acousto optical modulator (PCAOM). This technique enables us not only to control the intensity of individual channels, but also to achieve true color signals for the laser beam display including RGB, yellow, cyan, and violet (YCV), and other intermediate colors. For the optimal control of the PCAOM and galvano-mirror, we designed and fabricated a PC interface board. Using this PC control, we separated the white-light from an Ar-Kr mixed gas laser into various wavelengths and reconstructed them into different color schemes. Also we demonstrated the effective control and simultaneous display of reconstructed true color laser beams on a flat screen.

Non-Equilibrium Dynamics Contribute to Ion Selectivity in the KcsA Channel

PubMed Central

Haas, Stephan; Farley, Robert A.

2014-01-01

The ability of biological ion channels to conduct selected ions across cell membranes is critical for the survival of both animal and bacterial cells. Numerous investigations of ion selectivity have been conducted over more than 50 years, yet the mechanisms whereby the channels select certain ions and reject others are not well understood. Here we report a new application of Jarzynski’s Equality to investigate the mechanism of ion selectivity using non-equilibrium molecular dynamics simulations of Na+ and K+ ions moving through the KcsA channel. The simulations show that the selectivity filter of KcsA adapts and responds to the presence of the ions with structural rearrangements that are different for Na+ and K+. These structural rearrangements facilitate entry of K+ ions into the selectivity filter and permeation through the channel, and rejection of Na+ ions. A mechanistic model of ion selectivity by this channel based on the results of the simulations relates the structural rearrangement of the selectivity filter to the differential dehydration of ions and multiple-ion occupancy and describes a mechanism to efficiently select and conduct K+. Estimates of the K+/Na+ selectivity ratio and steady state ion conductance for KcsA from the simulations are in good quantitative agreement with experimental measurements. This model also accurately describes experimental observations of channel block by cytoplasmic Na+ ions, the “punch through” relief of channel block by cytoplasmic positive voltages, and is consistent with the knock-on mechanism of ion permeation. PMID:24465882

Emancipating traditional channel network types: quantification of topology and geometry, and relation to geologic boundary conditions

NASA Astrophysics Data System (ADS)

Temme, A.; Langston, A. L.

2017-12-01

Traditional classification of channel networks is helpful for qualitative geologic and geomorphic inference. For instance, a dendritic network indicates no strong lithological control on where channels flow. However, an approach where channel network structure is quantified, is required to be able to indicate for instance how increasing levels of lithological control lead, gradually or suddenly, to a trellis-type drainage network Our contribution aims to aid this transition to a quantitative analysis of channel networks. First, to establish the range of typically occurring channel network properties, we selected 30 examples of traditional drainage network types from around the world. For each of these, we calculated a set of topological and geometric properties, such as total drainage length, average length of a channel segment and the average angle of intersection of channel segments. A decision tree was used to formalize the relation between these newly quantified properties on the one hand, and traditional network types on the other hand. Then, to explore how variations in lithological and geomorphic boundary conditions affect channel network structure, we ran a set of experiments with landscape evolution model Landlab. For each simulated channel network, the same set of topological and geometric properties was calculated as for the 30 real-world channel networks. The latter were used for a first, visual evaluation to find out whether a simulated network that looked, for instance, rectangular, also had the same set of properties as real-world rectangular channel networks. Ultimately, the relation between these properties and the imposed lithological and geomorphic boundary conditions was explored using simple bivariate statistics.

PAD-MAC: Primary User Activity-Aware Distributed MAC for Multi-Channel Cognitive Radio Networks

PubMed Central

Ali, Amjad; Piran, Md. Jalil; Kim, Hansoo; Yun, Jihyeok; Suh, Doug Young

2015-01-01

Cognitive radio (CR) has emerged as a promising technology to solve problems related to spectrum scarcity and provides a ubiquitous wireless access environment. CR-enabled secondary users (SUs) exploit spectrum white spaces opportunistically and immediately vacate the acquired licensed channels as primary users (PUs) arrive. Accessing the licensed channels without the prior knowledge of PU traffic patterns causes severe throughput degradation due to excessive channel switching and PU-to-SU collisions. Therefore, it is significantly important to design a PU activity-aware medium access control (MAC) protocol for cognitive radio networks (CRNs). In this paper, we first propose a licensed channel usage pattern identification scheme, based on a two-state Markov model, and then estimate the future idle slots using previous observations of the channels. Furthermore, based on these past observations, we compute the rank of each available licensed channel that gives SU transmission success assessment during the estimated idle slot. Secondly, we propose a PU activity-aware distributed MAC (PAD-MAC) protocol for heterogeneous multi-channel CRNs that selects the best channel for each SU to enhance its throughput. PAD-MAC controls SU activities by allowing them to exploit the licensed channels only for the duration of estimated idle slots and enables predictive and fast channel switching. To evaluate the performance of the proposed PAD-MAC, we compare it with the distributed QoS-aware MAC (QC-MAC) and listen-before-talk MAC schemes. Extensive numerical results show the significant improvements of the PAD-MAC in terms of the SU throughput, SU channel switching rate and PU-to-SU collision rate. PMID:25831084

Collisional quenching at ultralow energies: controlling efficiency with internal state selection.

PubMed

Bovino, S; Bodo, E; Gianturco, F A

2007-12-14

Calculations have been carried out for the vibrational quenching of excited H(2) molecules which collide with Li(+) ions at ultralow energies. The dynamics has been treated exactly using the well-known quantum coupled-channel expansions over different initial vibrational levels. The overall interaction potential has been obtained from the calculations carried out earlier by our group using highly correlated ab initio methods. The results indicate that specific features of the scattering observables, e.g., the appearance of Ramsauer-Townsend minima in elastic channel cross sections and the marked increase of the cooling rates from specific initial states, can be linked to potential properties at vanishing energies (sign and size of scattering lengths) and to the presence of either virtual states or bound states. The suggestion is made such that by selecting the initial state preparation of the molecular partners, the ionic interactions would be amenable to controlling quenching efficiency at ultralow energies.

Product selectivity control induced by using liquid-liquid parallel laminar flow in a microreactor.

PubMed

Amemiya, Fumihiro; Matsumoto, Hideyuki; Fuse, Keishi; Kashiwagi, Tsuneo; Kuroda, Chiaki; Fuchigami, Toshio; Atobe, Mahito

2011-06-07

Product selectivity control based on a liquid-liquid parallel laminar flow has been successfully demonstrated by using a microreactor. Our electrochemical microreactor system enables regioselective cross-coupling reaction of aldehyde with allylic chloride via chemoselective cathodic reduction of substrate by the combined use of suitable flow mode and corresponding cathode material. The formation of liquid-liquid parallel laminar flow in the microreactor was supported by the estimation of benzaldehyde diffusion coefficient and computational fluid dynamics simulation. The diffusion coefficient for benzaldehyde in Bu(4)NClO(4)-HMPA medium was determined to be 1.32 × 10(-7) cm(2) s(-1) by electrochemical measurements, and the flow simulation using this value revealed the formation of clear concentration gradient of benzaldehyde in the microreactor channel over a specific channel length. In addition, the necessity of the liquid-liquid parallel laminar flow was confirmed by flow mode experiments.

High-efficient photo-electron transport channel in SiC constructed by depositing cocatalysts selectively on specific surface sites for visible-light H{sub 2} production

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

Wang, Da; Peng, Yuan; Wang, Qi

2016-04-18

Control cocatalyst location on a metal-free semiconductor to promote surface charge transfer for decreasing the electron-hole recombination is crucial for enhancing solar energy conversion. Based on the findings that some metals have an affinity for bonding with the specific atoms of polar semiconductors at a heterostructure interface, we herein control Pt deposition selectively on the Si sites of a micro-SiC photocatalyst surface via in-situ photo-depositing. The Pt-Si bond forming on the interface constructs an excellent channel, which is responsible for accelerating photo-electron transfer from SiC to Pt and then reducing water under visible-light. The hydrogen production is enhanced by twomore » orders of magnitude higher than that of bare SiC, and 2.5 times higher than that of random-depositing nano-Pt with the same loading amount.« less

Slack channels expressed in sensory neurons control neuropathic pain in mice.

PubMed

Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

2015-01-21

Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

Photodissociation of the carbon monoxide dication in the (3)Σ(-) manifold: Quantum control simulation towards the C(2+) + O channel.

PubMed

Vranckx, S; Loreau, J; Vaeck, N; Meier, C; Desouter-Lecomte, M

2015-10-28

The photodissociation and laser assisted dissociation of the carbon monoxide dication X(3)Π CO(2+) into the (3)Σ(-) states are investigated. Ab initio electronic structure calculations of the adiabatic potential energy curves, radial nonadiabatic couplings, and dipole moments for the X (3)Π state are performed for 13 excited (3)Σ(-) states of CO(2+). The photodissociation cross section, calculated by time-dependent methods, shows that the C(+) + O(+) channels dominate the process in the studied energy range. The carbon monoxide dication CO(2+) is an interesting candidate for control because it can be produced in a single, long lived, v = 0 vibrational state due to the instability of all the other excited vibrational states of the ground (3)Π electronic state. In a spectral range of about 25 eV, perpendicular transition dipoles couple this (3)Π state to a manifold of (3)Σ(-) excited states leading to numerous C(+) + O(+) channels and a single C(2+) + O channel. This unique channel is used as target for control calculations using local control theory. We illustrate the efficiency of this method in order to find a tailored electric field driving the photodissociation in a manifold of strongly interacting electronic states. The selected local pulses are then concatenated in a sequence inspired by the "laser distillation" strategy. Finally, the local pulse is compared with optimal control theory.

Development of Energetic Actuators for Shear and Vortex Dominated Flow Control

DTIC Science & Technology

2014-02-19

max-min fairness in data net- works,” Selected Areas in Communications , IEEE Journal on, vol. 9, pp. 1024 –1039, sep 1991. [ 11 ] R. G. Gallager, Poisson...the legitimate messages to route via the communication channel. Unless the secret trigger combination is known and the radio is under physical tests... 11 ]–[15], [17], [18], [29]. Covert channels are mechanisms for communicating information in ways that are difficult to detect. Packet networks are

CALORIC: A readout chip for high granularity calorimeter

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

Royer, L.; Bonnard, J.; Manen, S.

2011-07-01

A very-front-end electronics has been developed to fulfil requirements for the next generation of electromagnetic calorimeters. The compactness of this kind of detector and its large number of channels (up to several millions) impose a drastic limitation of the power consumption and a high level of integration. The electronic channel proposed is first of all composed of a low-noise Charge Sensitive Amplifier (CSA) able to amplify the charge delivered by a silicon diode up to 10 pC. Next, a two-gain shaping, based on a Gated Integration (G.I.), is implemented to cover the 15 bits dynamic range required: a high gainmore » shaper processes signals from 4 fC (charge corresponding to the MIP) up to 1 pC, and a low gain filter handles charges up to 10 pC. The G.I. performs also the analog memorization of the signal until it is digitalized. Hence, the analog-to-digital conversion is carried out through a low-power 12-bit cyclic ADC. If the signal overloads the high-gain channel dynamic range, a comparator selects the low-gain channel instead. Moreover, an auto-trigger channel has been implemented in order to select and store a valid event over the noise. The timing sequence of the channel is managed by a digital IP. It controls the G.I. switches, generates all needed clocks, drives the ADC and delivers the final result over 12 bits. The whole readout channel is power controlled, which permits to reduce the consumption according to the duty cycle of the beam collider. Simulations have been performed with Spectre simulator on the prototype chip designed with the 0.35 {mu}m CMOS technology from Austriamicrosystems. Results show a non-linearity better than 0.1% for the high-gain channel, and a non-linearity limited to 1% for the low-gain channel. The Equivalent Noise Charge referred to the input of the channel is evaluated to 0.4 fC complying with the MIP/10 limit. With the timing sequence of the International Linear Collider, which presents a duty cycle of 1%, the power consumption of the complete channel is limited to 43 {mu}W thanks to the power pulsing. The total area of the channel is 1.2 mm{sup 2} with an analog memory depth of 16. (authors)« less

A K(+)-selective CNG channel orchestrates Ca(2+) signalling in zebrafish sperm.

PubMed

Fechner, Sylvia; Alvarez, Luis; Bönigk, Wolfgang; Müller, Astrid; Berger, Thomas K; Pascal, Rene; Trötschel, Christian; Poetsch, Ansgar; Stölting, Gabriel; Siegfried, Kellee R; Kremmer, Elisabeth; Seifert, Reinhard; Kaupp, U Benjamin

2015-12-09

Calcium in the flagellum controls sperm navigation. In sperm of marine invertebrates and mammals, Ca(2+) signalling has been intensely studied, whereas for fish little is known. In sea urchin sperm, a cyclic nucleotide-gated K(+) channel (CNGK) mediates a cGMP-induced hyperpolarization that evokes Ca(2+) influx. Here, we identify in sperm of the freshwater fish Danio rerio a novel CNGK family member featuring non-canonical properties. It is located in the sperm head rather than the flagellum and is controlled by intracellular pH, but not cyclic nucleotides. Alkalization hyperpolarizes sperm and produces Ca(2+) entry. Ca(2+) induces spinning-like swimming, different from swimming of sperm from other species. The "spinning" mode probably guides sperm into the micropyle, a narrow entrance on the surface of fish eggs. A picture is emerging of sperm channel orthologues that employ different activation mechanisms and serve different functions. The channel inventories probably reflect adaptations to species-specific challenges during fertilization.

Structure of a eukaryotic cyclic nucleotide-gated channel

PubMed Central

Li, Minghui; Zhou, Xiaoyuan; Wang, Shu; Michailidis, Ioannis; Gong, Ye; Su, Deyuan; Li, Huan; Li, Xueming; Yang, Jian

2018-01-01

Summary Cyclic nucleotide-gated (CNG) channels are essential for vision and olfaction. They belong to the voltage-gated ion channel superfamily but their activities are controlled by intracellular cyclic nucleotides instead of transmembrane voltage. Here we report a 3.5 Å-resolution single-particle electron cryomicroscopy structure of a CNG channel from C. elegans in the cGMP-bound open state. The channel has an unusual voltage-sensor-like domain (VSLD), accounting for its deficient voltage dependence. A C-terminal linker connecting S6 and the cyclic nucleotide-binding domain interacts directly with both the VSLD and pore domain, forming a gating ring that couples conformational changes triggered by cyclic nucleotide binding to the gate. The selectivity filter is lined by the carboxylate side chains of a functionally important glutamate and three rings of backbone carbonyls. This structure provides a new framework for understanding mechanisms of ion permeation, gating and channelopathy of CNG channels and cyclic nucleotide modulation of related channels. PMID:28099415

Development of control systems for solar water and solar space heating equipment. Choice of heat conducting fluid. Testing

NASA Astrophysics Data System (ADS)

Meyer, H.

1981-11-01

Flat plate collector systems suitable for hot water supply, swimming pool heating, and auxiliary space heating were developed. A control and ready made packaged pipe assembly, adapted to synthetic fluid, was developed. A heat transfer fluid was selected, pumps, safety devices, armatures and seals were tested for their long term performance. External heat exchangers for simple and cascade arrangement of the hot water tanks were tested. It is found that the channel design of a roll bonded absorber has only limited effect on collector performance if the channel width approximates the space between the plates. Systems already installed work satisfactorily.

NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

PubMed Central

Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

2013-01-01

Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

MULTI-CHANNEL PULSE HEIGHT ANALYZER

DOEpatents

Boyer, K.; Johnstone, C.W.

1958-11-25

An improved multi-channel pulse height analyzer of the type where the device translates the amplitude of each pulse into a time duration electrical quantity which is utilized to control the length of a train of pulses forwarded to a scaler is described. The final state of the scaler for any one train of pulses selects the appropriate channel in a magnetic memory in which an additional count of one is placed. The improvement consists of a storage feature for storing a signal pulse so that in many instances when two signal pulses occur in rapid succession, the second pulse is preserved and processed at a later time.

Channeling in the Use of Nonprescription Paracetamol and Ibuprofen in an Electronic Medical Records Database: Evidence and Implications.

PubMed

Weinstein, Rachel B; Ryan, Patrick; Berlin, Jesse A; Matcho, Amy; Schuemie, Martijn; Swerdel, Joel; Patel, Kayur; Fife, Daniel

2017-12-01

Over-the-counter analgesics such as paracetamol and ibuprofen are among the most widely used, and having a good understanding of their safety profile is important to public health. Prior observational studies estimating the risks associated with paracetamol use acknowledge the inherent limitations of these studies. One threat to the validity of observational studies is channeling bias, i.e. the notion that patients are systematically exposed to one drug or the other, based on current and past comorbidities, in a manner that affects estimated relative risk. The aim of this study was to examine whether evidence of channeling bias exists in observational studies that compare paracetamol with ibuprofen, and, if so, the extent to which confounding adjustment can mitigate this bias. In a cohort of 140,770 patients, we examined whether those who received any paracetamol (including concomitant users) were more likely to have prior diagnoses of gastrointestinal (GI) bleeding, myocardial infarction (MI), stroke, or renal disease than those who received ibuprofen alone. We compared propensity score distributions between drugs, and examined the degree to which channeling bias could be controlled using a combination of negative control disease outcome models and large-scale propensity score matching. Analyses were conducted using the Clinical Practice Research Datalink. The proportions of prior MI, GI bleeding, renal disease, and stroke were significantly higher in those prescribed any paracetamol versus ibuprofen alone, after adjusting for sex and age. We were not able to adequately remove selection bias using a selected set of covariates for propensity score adjustment; however, when we fit the propensity score model using a substantially larger number of covariates, evidence of residual bias was attenuated. Although using selected covariates for propensity score adjustment may not sufficiently reduce bias, large-scale propensity score matching offers a novel approach to consider to mitigate the effects of channeling bias.

Novel ion channel targets in atrial fibrillation.

PubMed

Hancox, Jules C; James, Andrew F; Marrion, Neil V; Zhang, Henggui; Thomas, Dierk

2016-08-01

Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the development of electrical and structural remodeling makes early intervention desirable. Existing antiarrhythmic pharmacological approaches are not always effective and can produce unwanted side effects. Additional atrial-selective antiarrhythmic strategies are therefore desirable. Evidence for three novel ion channel atrial-selective therapeutic targets is evaluated: atrial-selective fast sodium channel current (INa) inhibition; small conductance calcium-activated potassium (SK) channels; and two-pore (K2P) potassium channels. Data from animal models support atrial-ventricular differences in INa kinetics and also suggest atrial-ventricular differences in sodium channel β subunit expression. Further work is required to determine whether intrinsic atrial-ventricular differences in human INa exist or whether functional differences occur due to distinct atrial and ventricular action and resting potentials. SK and K2P channels (particularly K2P 3.1) offer potentially attractive atrial-selective targets. Work is needed to identify the underlying basis of SK current that contributes to (patho)physiological atrial repolarization and settings in which SK inhibition is anti- versus pro-arrhythmic. Although K2P3.1 appears to be a promising target with comparatively selective drugs for experimental use, a lack of selective pharmacology hinders evaluation of other K2P channels as potential atrial-selective targets.

Effects of Levetiracetam, Carbamazepine, Phenytoin, Valproate, Lamotrigine, Oxcarbazepine, Topiramate, Vinpocetine and Sertraline on Presynaptic Hippocampal Na(+) and Ca(2+) Channels Permeability.

PubMed

Sitges, María; Chiu, Luz María; Reed, Ronald C

2016-04-01

Ion channels are targets of various antiepileptic drugs. In cerebral presynaptic nerve endings Na(+) and Ca(2+) channels are particularly abundant, as they control neurotransmitter release, including the release of glutamate (Glu), the most concentrated excitatory amino acid neurotransmitter in the brain. Several pre-synaptic channels are implicated in the mechanism of action of the pro-convulsive agent, 4-aminopyridine (4-AP). In the present study the effects of levetiracetam and other established and newer (vinpocetine) anti-epileptic drugs, as well as of the anti-depressant, sertraline on the increase in Ca(2+) induced by 4-AP in hippocampal isolated nerve endings were investigated. Also the effects of some of the anti-seizure drugs on the selective increase in Ca(2+) induced by high K(+), or on the selective increase in Na(+) induced by veratridine were tested. Sertraline and vinpocetine effectively inhibited the rise in Ca(2+) induced by 4-AP, which was dependent on the out-in Na(+) gradient and tetrodotoxin sensitive. Carbamazepine, phenytoin, lamotrigine and oxcarbazepine inhibited the rise in Ca(2+) induced by 4-AP too, but at higher concentrations than sertraline and vinpocetine, whereas levetiracetam, valproic acid and topiramate did not. The three latter antiepileptic drugs also failed in modifying other responses mediated by the activation of brain presynaptic Na(+) or Ca(2+) channels, including Glu release. This indicates that levetiracetam, valproic acid and topiramate mechanisms of action are unrelated with a decrease in presynaptic Na(+) or Ca(2+) channels permeability. It is concluded that depolarized cerebral isolated nerve endings represent a useful tool to unmask potential antiepileptic drugs targeting presynaptic Na(+) and/or Ca(2+) channels in the brain; such as vinpocetine or the anti-depressant sertraline, which high effectiveness to control seizures in the animal in vivo has been demonstrated.

High-pressure microfluidic control in lab-on-a-chip devices using mobile polymer monoliths.

PubMed

Hasselbrink, Ernest F; Shepodd, Timothy J; Rehm, Jason E

2002-10-01

We have developed a nonstick polymer formulation for creating moving parts inside of microfluidic channels and have applied the technique to create piston-based devices that overcome several microfluidic flow control challenges. The parts were created bycompletely filling the channels of a glass microfluidic chip with the monomer/ solvent/initiator components of a nonstick photopolymer and then selectively exposing the chip to UV light in order to define mobile pistons (or other quasi-two-dimensional shapes) inside the channels. Stops defined in the substrate prevent the part from flushing out of the device but also provide sealing surfaces so that valves and other flow control devices are possible. Sealing against pressures greater than 30 MPa (4,500 psi) and actuation times less than 33 ms are observed. An on-chip check valve, a diverter valve, and a 10-nL pipet are demonstrated. This valving technology, coupled with high-pressure electrokinetic pumps, should make it possible to create a completely integrated HPLC system on a chip.

Protective and control relays as coal-mine power-supply ACS subsystem

NASA Astrophysics Data System (ADS)

Kostin, V. N.; Minakova, T. E.

2017-10-01

The paper presents instantaneous selective short-circuit protection for the cabling of the underground part of a coal mine and central control algorithms as a Coal-Mine Power-Supply ACS Subsystem. In order to improve the reliability of electricity supply and reduce the mining equipment down-time, a dual channel relay protection and central control system is proposed as a subsystem of the coal-mine power-supply automated control system (PS ACS).

The electrostatics of VDAC: implications for selectivity and gating.

PubMed

Choudhary, Om P; Ujwal, Rachna; Kowallis, William; Coalson, Rob; Abramson, Jeff; Grabe, Michael

2010-02-26

The voltage-dependent anion channel (VDAC) is the major pathway mediating the transfer of metabolites and ions across the mitochondrial outer membrane. Two hallmarks of the channel in the open state are high metabolite flux and anion selectivity, while the partially closed state blocks metabolites and is cation selective. Here we report the results from electrostatics calculations carried out on the recently determined high-resolution structure of murine VDAC1 (mVDAC1). Poisson-Boltzmann calculations show that the ion transfer free energy through the channel is favorable for anions, suggesting that mVDAC1 represents the open state. This claim is buttressed by Poisson-Nernst-Planck calculations that predict a high single-channel conductance indicative of the open state and an anion selectivity of 1.75--nearly a twofold selectivity for anions over cations. These calculations were repeated on mutant channels and gave selectivity changes in accord with experimental observations. We were then able to engineer an in silico mutant channel with three point mutations that converted mVDAC1 into a channel with a preference for cations. Finally, we investigated two proposals for how the channel gates between the open and the closed state. Both models involve the movement of the N-terminal helix, but neither motion produced the observed voltage sensitivity, nor did either model result in a cation-selective channel, which is observed experimentally. Thus, we were able to rule out certain models for channel gating, but the true motion has yet to be determined. Copyright (c) 2009. Elsevier Ltd. All rights reserved.

pH-dependent pore-forming activity of OmpATb from Mycobacterium tuberculosis and characterization of the channel by peptidic dissection.

PubMed

Molle, Virginie; Saint, Nathalie; Campagna, Sylvie; Kremer, Laurent; Lea, Edward; Draper, Philip; Molle, Gérard

2006-08-01

Mycobacteria are characterized by an unusual cell wall that controls nutrient and small hydrophilic compound permeability. Porin-like proteins are necessary to ensure the transport of molecules into the cell. Here, we investigated the pore-forming properties of OmpATb, a porin from Mycobacterium tuberculosis, in lipid bilayers. Multi-channel experiments showed an asymmetric behaviour with channel closures at negative critical voltages (Vc) and a strong decrease in Vc at acidic pH. Single-channel experiments gave conductance values of about 850 +/- 80 pS in 1 M KCl and displayed a weak cationic selectivity in 4-8 pH range. The production and characterization of a series of truncated OmpATb proteins, showed that the central domain (OmpATb73-220) was sufficient to induce the ion channel properties of the native protein in lipid bilayers, i.e. asymmetric insertion, pH-dependent voltage closure, cationic selectivity and similar conductance values in 1 M KCl. Western blot analysis suggests that the presence of OmpATb is only restricted to certain pathogenic species. Therefore, the propensity of channels of native OmpATb to close at low pH may represent an intrinsic property allowing pathogenic mycobacteria to adapt and survive to mildly acidic conditions, such as those encountered within the macrophage phagosome.

Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate.

PubMed

Nelson, Michael T; Joksovic, Pavle M; Su, Peihan; Kang, Ho-Won; Van Deusen, Amy; Baumgart, Joel P; David, Laurence S; Snutch, Terrance P; Barrett, Paula Q; Lee, Jung-Ha; Zorumski, Charles F; Perez-Reyes, Edward; Todorovic, Slobodan M

2007-11-14

T-type Ca2+ channels (T-channels) are involved in the control of neuronal excitability and their gating can be modulated by a variety of redox agents. Ascorbate is an endogenous redox agent that can function as both an anti- and pro-oxidant. Here, we show that ascorbate selectively inhibits native Ca(v)3.2 T-channels in peripheral and central neurons, as well as recombinant Ca(v)3.2 channels heterologously expressed in human embryonic kidney 293 cells, by initiating the metal-catalyzed oxidation of a specific, metal-binding histidine residue in domain 1 of the channel. Our biophysical experiments indicate that ascorbate reduces the availability of Ca(v)3.2 channels over a wide range of membrane potentials, and inhibits Ca(v)3.2-dependent low-threshold-Ca2+ spikes as well as burst-firing in reticular thalamic neurons at physiologically relevant concentrations. This study represents the first mechanistic demonstration of ion channel modulation by ascorbate, and suggests that ascorbate may function as an endogenous modulator of neuronal excitability.

Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology.

PubMed

Suchyna, Thomas M

2017-11-01

Discovery of Piezo channels and the reporting of their sensitivity to the inhibitor GsMTx4 were important milestones in the study of non-selective cationic mechanosensitive channels (MSCs) in normal physiology and pathogenesis. GsMTx4 had been used for years to investigate the functional role of cationic MSCs, especially in muscle tissue, but with little understanding of its target or inhibitory mechanism. The sensitivity of Piezo channels to bilayer stress and its robust mechanosensitivity when expressed in heterologous systems were keys to determining GsMTx4's mechanism of action. However, questions remain regarding Piezo's role in muscle function due to the non-selective nature of GsMTx4 inhibition toward membrane mechanoenzymes and the implication of MCS channel types by genetic knockdown. Evidence supporting Piezo like activity, at least in the developmental stages of muscle, is presented. While the MSC targets of GsMTx4 in muscle pathology are unclear, its muscle protective effects are clearly demonstrated in two recent in situ studies on normal cardiomyocytes and dystrophic skeletal muscle. The muscle protective function may be due to the combined effect of GsMTx4's inhibitory action on cationic MSCs like Piezo and TRP, and its potentiation of repolarizing K + selective MSCs like K2P and SAKCa. Paradoxically, the potent in vitro action of GsMTx4 on many physiological functions seems to conflict with its lack of in situ side-effects on normal animal physiology. Future investigations into cytoskeletal control of sarcolemma mechanics and the suspected inclusion of MSCs in membrane micro/nano sized domains with distinct mechanical properties will aide our understanding of this dichotomy. Published by Elsevier Ltd.

Structure-based membrane dome mechanism for Piezo mechanosensitivity

PubMed Central

Guo, Yusong R

2017-01-01

Mechanosensitive ion channels convert external mechanical stimuli into electrochemical signals for critical processes including touch sensation, balance, and cardiovascular regulation. The best understood mechanosensitive channel, MscL, opens a wide pore, which accounts for mechanosensitive gating due to in-plane area expansion. Eukaryotic Piezo channels have a narrow pore and therefore must capture mechanical forces to control gating in another way. We present a cryo-EM structure of mouse Piezo1 in a closed conformation at 3.7Å-resolution. The channel is a triskelion with arms consisting of repeated arrays of 4-TM structural units surrounding a pore. Its shape deforms the membrane locally into a dome. We present a hypothesis in which the membrane deformation changes upon channel opening. Quantitatively, membrane tension will alter gating energetics in proportion to the change in projected area under the dome. This mechanism can account for highly sensitive mechanical gating in the setting of a narrow, cation-selective pore. PMID:29231809

An Adaptive Source-Channel Coding with Feedback for Progressive Transmission of Medical Images

PubMed Central

Lo, Jen-Lung; Sanei, Saeid; Nazarpour, Kianoush

2009-01-01

A novel adaptive source-channel coding with feedback for progressive transmission of medical images is proposed here. In the source coding part, the transmission starts from the region of interest (RoI). The parity length in the channel code varies with respect to both the proximity of the image subblock to the RoI and the channel noise, which is iteratively estimated in the receiver. The overall transmitted data can be controlled by the user (clinician). In the case of medical data transmission, it is vital to keep the distortion level under control as in most of the cases certain clinically important regions have to be transmitted without any visible error. The proposed system significantly reduces the transmission time and error. Moreover, the system is very user friendly since the selection of the RoI, its size, overall code rate, and a number of test features such as noise level can be set by the users in both ends. A MATLAB-based TCP/IP connection has been established to demonstrate the proposed interactive and adaptive progressive transmission system. The proposed system is simulated for both binary symmetric channel (BSC) and Rayleigh channel. The experimental results verify the effectiveness of the design. PMID:19190770

Analysis of channel confined selective area growth in evolutionary growth of GaN on SiO 2

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

Leung, Benjamin; Tsai, Miao-Chan; Song, Jie

2015-09-01

Here, we analyze the chemical vapor deposition of semiconductor crystals by selective area growth in a non-planar geometry. Specifically, the growth process in laterally and vertically confined masks forming single-crystal GaN on SiO2 by metal-organic chemical vapor deposition is considered in detail. A textured AlN seed is used to initiate growth of oriented GaN selectively through the mask, allowing the reduction of degrees of freedom by the evolutionary grain selection process. As shown by measurements of growth rates within the mask, the sub micron length scale of the channel opening is comparable to the mean free path of precursors inmore » the gas phase, resulting in transport characteristics that can be described by an intermediate flow regime between continuum and free-molecular. Mass transport is modeled through kinetic theory to explain the growth rate enhancements of more than a factor of two by changes in reactor pressure. The growth conditions that enable the modification of nucleation density within the channel are then discussed, and are measured by electron-back scatter diffraction of the nucleated grains on the AlN seed. Finally, the selectivity behavior using the low fill factor masks needed in these configurations has been optimized by control of precursor flow rates and the H2 enhanced etching of the polycrystalline GaN nuclei.« less

3D Printed Microtransporters: Compound Micromachines for Spatiotemporally Controlled Delivery of Therapeutic Agents.

PubMed

Huang, Tian-Yun; Sakar, Mahmut Selman; Mao, Angelo; Petruska, Andrew J; Qiu, Famin; Chen, Xue-Bo; Kennedy, Stephen; Mooney, David; Nelson, Bradley J

2015-11-01

Functional compound micromachines are fabricated by a design methodology using 3D direct laser writing and selective physical vapor deposition of magnetic materials. Microtransporters with a wirelessly controlled Archimedes screw pumping mechanism are engineered. Spatiotemporally controlled collection, transport, and delivery of micro particles, as well as magnetic nanohelices inside microfluidic channels are demonstrated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

X-Ray Pulse Selector With 2 ns Lock-in Phase Setting And Stability

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

Lindenau, B.; Raebiger, J.; Polachowski, S.

2004-05-12

Selector devices, which are based on magnetically suspended, high speed triangular shutter rotors, have been designed and built in cooperation with ESRF, APS, and recently Spring-8 for time resolved studies with isolated x-ray pulses at white beam lines. The x-ray pulse selection is accomplished by means of a beam channel along one of the edges of the triangular rotor, which opens once per revolution. Entrance and exit apertures of the channel can be designed wedge shaped for variable tuning of the channel height between 0.1 mm to 0.9 mm. At the 1 kHz maximum operation frequency of a 220 mmmore » diameter disk with 190 mm channel length, the practicable open times of the channel are demonstrated to range down to 200 ns. The selector drive electronics is directly coupled to the storage ring RF clock for rotational phase control. It allows for continuous selector operation in phase locked mode to the temporal pulse structure of the synchrotron at 2 ns RMS stability. The phase angle between the pulse transmission period and the synchrotron bunch sequence can be adjusted with similar precision for X-ray pulse selection according to the experimental needs. ID09, Michael Wulff ; BioCARS 14-BM, Reinhard Pahl; BL40-XU, Shin-ichi Adachi.« less

Variable is better than invariable: sparse VSS-NLMS algorithms with application to adaptive MIMO channel estimation.

PubMed

Gui, Guan; Chen, Zhang-xin; Xu, Li; Wan, Qun; Huang, Jiyan; Adachi, Fumiyuki

2014-01-01

Channel estimation problem is one of the key technical issues in sparse frequency-selective fading multiple-input multiple-output (MIMO) communication systems using orthogonal frequency division multiplexing (OFDM) scheme. To estimate sparse MIMO channels, sparse invariable step-size normalized least mean square (ISS-NLMS) algorithms were applied to adaptive sparse channel estimation (ACSE). It is well known that step-size is a critical parameter which controls three aspects: algorithm stability, estimation performance, and computational cost. However, traditional methods are vulnerable to cause estimation performance loss because ISS cannot balance the three aspects simultaneously. In this paper, we propose two stable sparse variable step-size NLMS (VSS-NLMS) algorithms to improve the accuracy of MIMO channel estimators. First, ASCE is formulated in MIMO-OFDM systems. Second, different sparse penalties are introduced to VSS-NLMS algorithm for ASCE. In addition, difference between sparse ISS-NLMS algorithms and sparse VSS-NLMS ones is explained and their lower bounds are also derived. At last, to verify the effectiveness of the proposed algorithms for ASCE, several selected simulation results are shown to prove that the proposed sparse VSS-NLMS algorithms can achieve better estimation performance than the conventional methods via mean square error (MSE) and bit error rate (BER) metrics.

Variable Is Better Than Invariable: Sparse VSS-NLMS Algorithms with Application to Adaptive MIMO Channel Estimation

PubMed Central

Gui, Guan; Chen, Zhang-xin; Xu, Li; Wan, Qun; Huang, Jiyan; Adachi, Fumiyuki

2014-01-01

Channel estimation problem is one of the key technical issues in sparse frequency-selective fading multiple-input multiple-output (MIMO) communication systems using orthogonal frequency division multiplexing (OFDM) scheme. To estimate sparse MIMO channels, sparse invariable step-size normalized least mean square (ISS-NLMS) algorithms were applied to adaptive sparse channel estimation (ACSE). It is well known that step-size is a critical parameter which controls three aspects: algorithm stability, estimation performance, and computational cost. However, traditional methods are vulnerable to cause estimation performance loss because ISS cannot balance the three aspects simultaneously. In this paper, we propose two stable sparse variable step-size NLMS (VSS-NLMS) algorithms to improve the accuracy of MIMO channel estimators. First, ASCE is formulated in MIMO-OFDM systems. Second, different sparse penalties are introduced to VSS-NLMS algorithm for ASCE. In addition, difference between sparse ISS-NLMS algorithms and sparse VSS-NLMS ones is explained and their lower bounds are also derived. At last, to verify the effectiveness of the proposed algorithms for ASCE, several selected simulation results are shown to prove that the proposed sparse VSS-NLMS algorithms can achieve better estimation performance than the conventional methods via mean square error (MSE) and bit error rate (BER) metrics. PMID:25089286

TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+.

PubMed

Pitt, Samantha J; Funnell, Tim M; Sitsapesan, Mano; Venturi, Elisa; Rietdorf, Katja; Ruas, Margarida; Ganesan, A; Gosain, Rajendra; Churchill, Grant C; Zhu, Michael X; Parrington, John; Galione, Antony; Sitsapesan, Rebecca

2010-11-05

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a molecule capable of initiating the release of intracellular Ca(2+) required for many essential cellular processes. Recent evidence links two-pore channels (TPCs) with NAADP-induced release of Ca(2+) from lysosome-like acidic organelles; however, there has been no direct demonstration that TPCs can act as NAADP-sensitive Ca(2+) release channels. Controversial evidence also proposes ryanodine receptors as the primary target of NAADP. We show that TPC2, the major lysosomal targeted isoform, is a cation channel with selectivity for Ca(2+) that will enable it to act as a Ca(2+) release channel in the cellular environment. NAADP opens TPC2 channels in a concentration-dependent manner, binding to high affinity activation and low affinity inhibition sites. At the core of this process is the luminal environment of the channel. The sensitivity of TPC2 to NAADP is steeply dependent on the luminal [Ca(2+)] allowing extremely low levels of NAADP to open the channel. In parallel, luminal pH controls NAADP affinity for TPC2 by switching from reversible activation of TPC2 at low pH to irreversible activation at neutral pH. Further evidence earmarking TPCs as the likely pathway for NAADP-induced intracellular Ca(2+) release is obtained from the use of Ned-19, the selective blocker of cellular NAADP-induced Ca(2+) release. Ned-19 antagonizes NAADP-activation of TPC2 in a non-competitive manner at 1 μM but potentiates NAADP activation at nanomolar concentrations. This single-channel study provides a long awaited molecular basis for the peculiar mechanistic features of NAADP signaling and a framework for understanding how NAADP can mediate key physiological events.

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

PubMed

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

2014-01-01

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

Utilizing Retinotopic Mapping for a Multi-Target SSVEP BCI With a Single Flicker Frequency.

PubMed

Maye, Alexander; Zhang, Dan; Engel, Andreas K

2017-07-01

In brain-computer interfaces (BCIs) that use the steady-state visual evoked response (SSVEP), the user selects a control command by directing attention overtly or covertly to one out of several flicker stimuli. The different control channels are encoded in the frequency, phase, or time domain of the flicker signals. Here, we present a new type of SSVEP BCI, which uses only a single flicker stimulus and yet affords controlling multiple channels. The approach rests on the observation that the relative position between the stimulus and the foci of overt attention result in distinct topographies of the SSVEP response on the scalp. By classifying these topographies, the computer can determine at which position the user is gazing. Offline data analysis in a study on 12 healthy volunteers revealed that 9 targets can be recognized with about 95±3% accuracy, corresponding to an information transfer rate (ITR) of 40.8 ± 3.3 b/min on average. We explored how the classification accuracy is affected by the number of control channels, the trial length, and the number of EEG channels. Our findings suggest that the EEG data from five channels over parieto-occipital brain areas are sufficient for reliably classifying the topographies and that there is a large potential to improve the ITR by optimizing the trial length. The robust performance and the simple stimulation setup suggest that this approach is a prime candidate for applications on desktop and tablet computers.

Utility of multi-channel surface electromyography in assessment of focal hand dystonia.

PubMed

Sivadasan, Ajith; Sanjay, M; Alexander, Mathew; Devasahayam, Suresh R; Srinivasa, Babu K

2013-09-01

Surface electromyography (SEMG) allows objective assessment and guides selection of appropriate treatment in focal hand dystonia (FHD). Sixteen-channel SEMG obtained during different phases of a writing task was used to study timing, activation patterns, and spread of muscle contractions in FHD compared with normal controls. Customized software was developed to acquire and analyze EMG signals. SEMG of FHD subjects (20) showed "early onset" during motor imagery, rapid proximal muscle recruitment, agonist-antagonist co-contraction involving proximal muscle groups, "delayed offset" after stopping writing, higher rectified mean amplitudes, and mirror activity in contralateral limb compared with controls (16). Muscle activation latencies were heterogenous in FHD. Anticipation, delayed relaxation, and mirror EMG activation were noted in FHD. A clear pattern of muscle activation cannot be ascertained. Multi-channel SEMG can aid in objective assessment of temporal-spatial distribution of activity and can refine targeted therapies like chemodenervation and biofeedback. Copyright © 2013 Wiley Periodicals, Inc.

Bargaining and the MISO Interference Channel

NASA Astrophysics Data System (ADS)

Nokleby, Matthew; Swindlehurst, A. Lee

2009-12-01

We examine the MISO interference channel under cooperative bargaining theory. Bargaining approaches such as the Nash and Kalai-Smorodinsky solutions have previously been used in wireless networks to strike a balance between max-sum efficiency and max-min equity in users' rates. However, cooperative bargaining for the MISO interference channel has only been studied extensively for the two-user case. We present an algorithm that finds the optimal Kalai-Smorodinsky beamformers for an arbitrary number of users. We also consider joint scheduling and beamformer selection, using gradient ascent to find a stationary point of the Kalai-Smorodinsky objective function. When interference is strong, the flexibility allowed by scheduling compensates for the performance loss due to local optimization. Finally, we explore the benefits of power control, showing that power control provides nontrivial throughput gains when the number of transmitter/receiver pairs is greater than the number of transmit antennas.

Photodissociation of the carbon monoxide dication in the {sup 3}Σ{sup −} manifold: Quantum control simulation towards the C{sup 2+} + O channel

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

Vranckx, S.; Laboratoire de Chimie Physique; Loreau, J.

The photodissociation and laser assisted dissociation of the carbon monoxide dication X{sup 3}Π CO{sup 2+} into the {sup 3}Σ{sup −} states are investigated. Ab initio electronic structure calculations of the adiabatic potential energy curves, radial nonadiabatic couplings, and dipole moments for the X {sup 3}Π state are performed for 13 excited {sup 3}Σ{sup −} states of CO{sup 2+}. The photodissociation cross section, calculated by time-dependent methods, shows that the C{sup +} + O{sup +} channels dominate the process in the studied energy range. The carbon monoxide dication CO{sup 2+} is an interesting candidate for control because it can be producedmore » in a single, long lived, v = 0 vibrational state due to the instability of all the other excited vibrational states of the ground {sup 3}Π electronic state. In a spectral range of about 25 eV, perpendicular transition dipoles couple this {sup 3}Π state to a manifold of {sup 3}Σ{sup −} excited states leading to numerous C{sup +} + O{sup +} channels and a single C{sup 2+} + O channel. This unique channel is used as target for control calculations using local control theory. We illustrate the efficiency of this method in order to find a tailored electric field driving the photodissociation in a manifold of strongly interacting electronic states. The selected local pulses are then concatenated in a sequence inspired by the “laser distillation” strategy. Finally, the local pulse is compared with optimal control theory.« less

Mechanism of activation at the selectivity filter of the KcsA K+ channel

PubMed Central

Heer, Florian T; Posson, David J; Wojtas-Niziurski, Wojciech

2017-01-01

Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary. PMID:28994652

Molecular Dynamics Simulations of Orai Reveal How the Third Transmembrane Segment Contributes to Hydration and Ca2+ Selectivity in Calcium Release-Activated Calcium Channels.

PubMed

Alavizargar, Azadeh; Berti, Claudio; Ejtehadi, Mohammad Reza; Furini, Simone

2018-04-26

Calcium release-activated calcium (CRAC) channels open upon depletion of Ca 2+ from the endoplasmic reticulum, and when open, they are permeable to a selective flux of calcium ions. The atomic structure of Orai, the pore domain of CRAC channels, from Drosophila melanogaster has revealed many details about conduction and selectivity in this family of ion channels. However, it is still unclear how residues on the third transmembrane helix can affect the conduction properties of the channel. Here, molecular dynamics and Brownian dynamics simulations were employed to analyze how a conserved glutamate residue on the third transmembrane helix (E262) contributes to selectivity. The comparison between the wild-type and mutated channels revealed a severe impact of the mutation on the hydration pattern of the pore domain and on the dynamics of residues K270, and Brownian dynamics simulations proved that the altered configuration of residues K270 in the mutated channel impairs selectivity to Ca 2+ over Na + . The crevices of water molecules, revealed by molecular dynamics simulations, are perfectly located to contribute to the dynamics of the hydrophobic gate and the basic gate, suggesting a possible role in channel opening and in selectivity function.

Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice.

PubMed

Gulati, Puja; Muthuraman, Arunachalam; Kaur, Parneet

2015-04-01

The present study was designed to investigate the role of flunarizine (a non-selective calcium channel blocker) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice. Bilateral carotid artery occlusion of 12min followed by reperfusion for 24h was given to induce cerebral injury in male Swiss mice. The assessment of learning & memory was performed by Morris water maze test; motor in-coordination was evaluated by rota rod, lateral push and inclined beam walking tests; cerebral infarct size was quantified by triphenyltetrazolium chloride staining. In addition, reduced glutathione (GSH), total calcium and acetylcholinesterase (AChE) activity were also estimated in aged brain tissue. Donepezil treated group served as a positive control in this study. Ischemia reperfusion (I/R) injury produced significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Further, I/R injury also produced significant increase in levels of total calcium, AChE activity and decrease in GSH levels. Pretreatment of flunarizine significantly attenuated I/R induced infarct size, behavioral and biochemical changes. Hence, it may be concluded that, a non-selective calcium channel blocker can be useful in I/R associated cognitive dysfunction due to its anti-oxidant, anti-infarct and modulatory actions of neurotransmitters & calcium channels. Copyright © 2015 Elsevier Inc. All rights reserved.

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

PubMed

Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

2015-01-01

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

Sodium channel selectivity and conduction: Prokaryotes have devised their own molecular strategy

PubMed Central

Finol-Urdaneta, Rocio K.; Wang, Yibo; Al-Sabi, Ahmed; Zhao, Chunfeng

2014-01-01

Striking structural differences between voltage-gated sodium (Nav) channels from prokaryotes (homotetramers) and eukaryotes (asymmetric, four-domain proteins) suggest the likelihood of different molecular mechanisms for common functions. For these two channel families, our data show similar selectivity sequences among alkali cations (relative permeability, Pion/PNa) and asymmetric, bi-ionic reversal potentials when the Na/K gradient is reversed. We performed coordinated experimental and computational studies, respectively, on the prokaryotic Nav channels NaChBac and NavAb. NaChBac shows an “anomalous,” nonmonotonic mole-fraction dependence in the presence of certain sodium–potassium mixtures; to our knowledge, no comparable observation has been reported for eukaryotic Nav channels. NaChBac’s preferential selectivity for sodium is reduced either by partial titration of its highly charged selectivity filter, when extracellular pH is lowered from 7.4 to 5.8, or by perturbation—likely steric—associated with a nominally electro-neutral substitution in the selectivity filter (E191D). Although no single molecular feature or energetic parameter appears to dominate, our atomistic simulations, based on the published NavAb crystal structure, revealed factors that may contribute to the normally observed selectivity for Na over K. These include: (a) a thermodynamic penalty to exchange one K+ for one Na+ in the wild-type (WT) channel, increasing the relative likelihood of Na+ occupying the binding site; (b) a small tendency toward weaker ion binding to the selectivity filter in Na–K mixtures, consistent with the higher conductance observed with both sodium and potassium present; and (c) integrated 1-D potentials of mean force for sodium or potassium movement that show less separation for the less selective E/D mutant than for WT. Overall, tight binding of a single favored ion to the selectivity filter, together with crucial inter-ion interactions within the pore, suggests that prokaryotic Nav channels use a selective strategy more akin to those of eukaryotic calcium and potassium channels than that of eukaryotic Nav channels. PMID:24420772

Control of glutamate release by calcium channels and κ-opioid receptors in rodent and primate striatum

PubMed Central

Hill, M P; Brotchie, J M

1999-01-01

The modulation of depolarization (4-aminopyridine, 2 mM)-evoked endogenous glutamate release by κ-opioid receptor activation and blockade of voltage-dependent Ca2+-channels has been investigated in synaptosomes prepared from rat and marmoset striatum.4-Aminopyridine (4-AP)-stimulated, Ca2+-dependent glutamate release was inhibited by enadoline, a selective κ-opioid receptor agonist, in a concentration-dependent and nor-binaltorphimine (nor-BNI, selective κ-opioid receptor antagonist)-sensitive manner in rat (IC50=4.4±0.4 μM) and marmoset (IC50=2.9±0.7 μM) striatal synaptosomes. However, in the marmoset, there was a significant (≈23%) nor-BNI-insensitive component.In rat striatal synaptosomes, the Ca2+-channel antagonists ω-agatoxin-IVA (P/Q-type blocker), ω-conotoxin-MVIIC (N/P/Q-type blocker) and ω-conotoxin-GVIA (N-type blocker) reduced 4-AP-stimulated, Ca2+-dependent glutamate release in a concentration-dependent manner with IC50 values of 6.5±0.9 nM, 75.5±5.9 nM and 106.5±8.7 nM, respectively. In marmoset striatal synaptosomes, 4-AP-stimulated, Ca2+-dependent glutamate release was significantly inhibited by ω-agatoxin-IVA (30 nM, 57.6±2.3%, inhibition), ω-conotoxin-MVIIC (300 nM, 57.8±3.1%) and ω-conotoxin-GVIA (1 μM, 56.7±2%).Studies utilizing combinations of Ca2+-channel antagonists suggests that in the rat striatum, two relatively distinct pools of glutamate, released by activation of either P or Q-type Ca2+-channels, exist. In contrast, in the primate there is much overlap between the glutamate released by P and Q-type Ca2+-channel activation.Studies using combinations of enadoline and the Ca2+-channel antagonists suggest that enadoline-induced inhibition of glutamate release occurs primarily via reduction of Ca2+-influx through P-type Ca2+-channels in the rat but via N-type Ca2+-channels in the marmoset.In conclusion, the results presented suggest that there are species differences in the control of glutamate release by κ-opioid receptors and Ca2+-channels. PMID:10369483

Transport mechanisms in nanopores and nanochannels: Can we mimic nature?

DOE PAGES

Tagliazucchi, Mario; Szleifer, Igal

2014-11-03

The last few years have witnessed major advancements in the synthesis, modification, characterization and modeling of nanometer-size solid-state channels and pores. Future applications in sensing, energy conversion and purification technologies will critically rely on qualitative improvements in the control over the selectivity, directionality and responsiveness of these nanochannels and nanopores. It is not surprising, therefore, that researchers in the field seek inspiration in biological ion channels and ion pumps, paradigmatic examples of transport selectivity. This work reviews our current fundamental understanding of the mechanisms of transport of ions and larger cargoes through nanopores and nanochannels by examining recent experimental andmore » theoretical work. It is argued that that structure and transport in biological channels and polyelectrolyte-modified synthetic nanopores are strongly coupled: the structure dictates transport and transport affects the structure. We compare synthetic and biological systems throughout this review to conclude that while they present interesting similarities, they also have striking differences.« less

Distinct modes of perimembrane TRP channel turnover revealed by TIR-FRAP.

PubMed

Ghosh, Debapriya; Segal, Andrei; Voets, Thomas

2014-11-19

Transient Receptor Potential (TRP) channels form a broadly expressed and functionally diverse family of cation channels involved in various (patho)physiological processes. Whereas the mechanisms that control opening of TRP channels have been extensively studied, little is known about the transport processes of TRP channels to and within the plasma membrane. Here we used Total Internal Reflection--Fluorescence Recovery after Photobleaching (TIR-FRAP) to selectively visualize and bleach the fluorescently labeled TRP channels TRPV2 and TRPM4 in close proximity of the glass-plasma membrane interface, allowing detailed analysis of their perimembrane dynamics. We show that recovery of TRPM4 occurs via 200-nm diameter transport vesicles, and demonstrate the full fusion of such vesicles with the plasma membrane. In contrast, TRPV2 recovery proceeded mainly via lateral diffusion from non-bleached areas of the plasma membrane. Analysis of the two-dimensional channel diffusion kinetics yielded 2D diffusion coefficients ranging between 0.1 and 0.3 μm(2)/s, suggesting that these TRP channels move relatively unrestricted within the plasma membrane. These data demonstrate distinct modes of TRP channel turnover at the plasma membrane and illustrate the usefulness of TIR-FRAP to monitor these processes with high resolution.

Multi-channel detector readout method and integrated circuit

DOEpatents

Moses, William W.; Beuville, Eric; Pedrali-Noy, Marzio

2006-12-12

An integrated circuit which provides multi-channel detector readout from a detector array. The circuit receives multiple signals from the elements of a detector array and compares the sampled amplitudes of these signals against a noise-floor threshold and against one another. A digital signal is generated which corresponds to the location of the highest of these signal amplitudes which exceeds the noise floor threshold. The digital signal is received by a multiplexing circuit which outputs an analog signal corresponding the highest of the input signal amplitudes. In addition a digital control section provides for programmatic control of the multiplexer circuit, amplifier gain, amplifier reset, masking selection, and test circuit functionality on each input thereof.

Multi-channel detector readout method and integrated circuit

DOEpatents

Moses, William W.; Beuville, Eric; Pedrali-Noy, Marzio

2004-05-18

An integrated circuit which provides multi-channel detector readout from a detector array. The circuit receives multiple signals from the elements of a detector array and compares the sampled amplitudes of these signals against a noise-floor threshold and against one another. A digital signal is generated which corresponds to the location of the highest of these signal amplitudes which exceeds the noise floor threshold. The digital signal is received by a multiplexing circuit which outputs an analog signal corresponding the highest of the input signal amplitudes. In addition a digital control section provides for programmatic control of the multiplexer circuit, amplifier gain, amplifier reset, masking selection, and test circuit functionality on each input thereof.

A Novel Piggyback Selection Scheme in IEEE 802.11e HCCA

NASA Astrophysics Data System (ADS)

Lee, Hyun-Jin; Kim, Jae-Hyun

A control frame can be piggybacked onto a data frame to increase channel efficiency in wireless communication. However, if the control frame including global control information is piggybacked, the delay of the data frame from a access point will be increased even though there is only one station with low physical transmission rate. It is similar to the anomaly phenomenon in a network which supports multi-rate transmission. In this letter, we define this phenomenon as “the piggyback problem at low physical transmission rate” and evaluate the effect of this problem with respect to physical transmission rate and normalized traffic load. Then, we propose a delay-based piggyback scheme. Simulations show that the proposed scheme reduces average frame transmission delay and improves channel utilization about 24% and 25%, respectively.

Multiparameter cell affinity chromatography: separation and analysis in a single microfluidic channel.

PubMed

Li, Peng; Gao, Yan; Pappas, Dimitri

2012-10-02

The ability to sort and capture more than one cell type from a complex sample will enable a wide variety of studies of cell proliferation and death and the analysis of disease states. In this work, we integrated a pneumatic actuated control layer to an affinity separation layer to create different antibody-coating regions on the same fluidic channel. The comparison of different antibody capture capabilities to the same cell line was demonstrated by flowing Ramos cells through anti-CD19- and anti-CD71-coated regions in the same channel. It was determined that the cell capture density on the anti-CD19 region was 2.44 ± 0.13 times higher than that on the anti-CD71-coated region. This approach can be used to test different affinity molecules for selectivity and capture efficiency using a single cell line in one separation. Selective capture of Ramos and HuT 78 cells from a mixture was also demonstrated using two antibody regions in the same channel. Greater than 90% purity was obtained on both capture areas in both continuous flow and stop flow separation modes. A four-region antibody-coated device was then fabricated to study the simultaneous, serial capture of three different cell lines. In this case the device showed effective capture of cells in a single separation channel, opening up the possibility of multiple cell sorting. Multiparameter sequential blood sample analysis was also demonstrated with high capture specificity (>97% for both CD19+ and CD4+ leukocytes). The chip can also be used to selectively treat cells after affinity separation.

Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

PubMed

Haidar, Yarah M; Sahyouni, Ronald; Moshtaghi, Omid; Wang, Beverly Y; Djalilian, Hamid R; Middlebrooks, John C; Verma, Sunil P; Lin, Harrison W

2017-10-31

Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses. Acute experiments in cats. The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement. Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments. We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management. NA Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium.

PubMed

Shabir, Saqib; Cross, William; Kirkwood, Lisa A; Pearson, Joanna F; Appleby, Peter A; Walker, Dawn; Eardley, Ian; Southgate, Jennifer

2013-08-01

In addition to its role as a physical barrier, the urothelium is considered to play an active role in mechanosensation. A key mechanism is the release of transient mediators that activate purinergic P2 receptors and transient receptor potential (TRP) channels to effect changes in intracellular Ca²⁺. Despite the implied importance of these receptors and channels in urothelial tissue homeostasis and dysfunctional bladder disease, little is known about their functional expression by the human urothelium. To evaluate the expression and function of P2X and P2Y receptors and TRP channels, the human ureter and bladder were used to separate urothelial and stromal tissues for RNA isolation and cell culture. RT-PCR using stringently designed primer sets was used to establish which P2 and TRP species were expressed at the transcript level, and selective agonists/antagonists were used to confirm functional expression by monitoring changes in intracellular Ca²⁺ and in a scratch repair assay. The results confirmed the functional expression of P2Y₄ receptors and excluded nonexpressed receptors/channels (P2X₁, P2X₃, P2X₆, P2Y₆, P2Y₁₁, TRPV5, and TRPM8), while a dearth of specific agonists confounded the functional validation of expressed P2X₂, P2X₄, P2Y₁, P2Y₂, TRPV2, TRPV3, TRPV6 and TRPM7 receptors/channels. Although a conventional response was elicited in control stromal-derived cells, the urothelial cell response to well-characterized TRPV1 and TRPV4 agonists/antagonists revealed unexpected anomalies. In addition, agonists that invoked an increase in intracellular Ca²⁺ promoted urothelial scratch repair, presumably through the release of ATP. The study raises important questions about the ligand selectivity of receptor/channel targets expressed by the urothelium. These pathways are important in urothelial tissue homeostasis, and this opens the possibility of selective drug targeting.

Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium

PubMed Central

Shabir, Saqib; Cross, William; Kirkwood, Lisa A.; Pearson, Joanna F.; Appleby, Peter A.; Walker, Dawn; Eardley, Ian

2013-01-01

In addition to its role as a physical barrier, the urothelium is considered to play an active role in mechanosensation. A key mechanism is the release of transient mediators that activate purinergic P2 receptors and transient receptor potential (TRP) channels to effect changes in intracellular Ca2+. Despite the implied importance of these receptors and channels in urothelial tissue homeostasis and dysfunctional bladder disease, little is known about their functional expression by the human urothelium. To evaluate the expression and function of P2X and P2Y receptors and TRP channels, the human ureter and bladder were used to separate urothelial and stromal tissues for RNA isolation and cell culture. RT-PCR using stringently designed primer sets was used to establish which P2 and TRP species were expressed at the transcript level, and selective agonists/antagonists were used to confirm functional expression by monitoring changes in intracellular Ca2+ and in a scratch repair assay. The results confirmed the functional expression of P2Y4 receptors and excluded nonexpressed receptors/channels (P2X1, P2X3, P2X6, P2Y6, P2Y11, TRPV5, and TRPM8), while a dearth of specific agonists confounded the functional validation of expressed P2X2, P2X4, P2Y1, P2Y2, TRPV2, TRPV3, TRPV6 and TRPM7 receptors/channels. Although a conventional response was elicited in control stromal-derived cells, the urothelial cell response to well-characterized TRPV1 and TRPV4 agonists/antagonists revealed unexpected anomalies. In addition, agonists that invoked an increase in intracellular Ca2+ promoted urothelial scratch repair, presumably through the release of ATP. The study raises important questions about the ligand selectivity of receptor/channel targets expressed by the urothelium. These pathways are important in urothelial tissue homeostasis, and this opens the possibility of selective drug targeting. PMID:23720349

High-Assurance System Support through 3-D Integration

DTIC Science & Technology

2007-11-09

algorithms ), tagging, and in selected systems, offensive mecha- nisms. For example, we can exploit the control plane to tag all traffic traveling...October 2005. [35] D. Page. Theoretical use of cache memory as a cryptanalytic side-channel. Technical Report CSTR - 02-003, Department of Computer

Fluidic Grooves on Doped-Ice Surface as Size-Tunable Channels

PubMed Central

Inagawa, Arinori; Harada, Makoto; Okada, Tetsuo

2015-01-01

We propose a new principle for fabrication of size-tunable fluidic nano- and microchannels with a ubiquitous green material, water. Grooves filled with a solution are spontaneously formed on the surface of ice when an appropriate dopant is incorporated. Sucrose doping allows the development of grooves with lengths of 300 μm along the boundaries of ice crystal grains. This paper focuses on controlling the size of the liquid-filled groove and reveals its applicability to size-selective differentiation of nano- and micromaterials. The width of this groove can be varied in a range of 200 nm to 4 μm by adjusting the working temperature of the frozen platform. The channel dimension is reproducible as long as the same frozen condition is employed. We demonstrate the size-selective entrapment of particles as well as the state evaluation of DNA by controlling the physical interference of the ice wall with the electrophoretic migration of particles. PMID:26601703

Fluidic Grooves on Doped-Ice Surface as Size-Tunable Channels

NASA Astrophysics Data System (ADS)

Inagawa, Arinori; Harada, Makoto; Okada, Tetsuo

2015-11-01

We propose a new principle for fabrication of size-tunable fluidic nano- and microchannels with a ubiquitous green material, water. Grooves filled with a solution are spontaneously formed on the surface of ice when an appropriate dopant is incorporated. Sucrose doping allows the development of grooves with lengths of 300 μm along the boundaries of ice crystal grains. This paper focuses on controlling the size of the liquid-filled groove and reveals its applicability to size-selective differentiation of nano- and micromaterials. The width of this groove can be varied in a range of 200 nm to 4 μm by adjusting the working temperature of the frozen platform. The channel dimension is reproducible as long as the same frozen condition is employed. We demonstrate the size-selective entrapment of particles as well as the state evaluation of DNA by controlling the physical interference of the ice wall with the electrophoretic migration of particles.

Training site statistics from Landsat and Seasat satellite imagery registered to a common map base

NASA Technical Reports Server (NTRS)

Clark, J.

1981-01-01

Landsat and Seasat satellite imagery and training site boundary coordinates were registered to a common Universal Transverse Mercator map base in the Newport Beach area of Orange County, California. The purpose was to establish a spatially-registered, multi-sensor data base which would test the use of Seasat synthetic aperture radar imagery to improve spectral separability of channels used for land use classification of an urban area. Digital image processing techniques originally developed for the digital mosaics of the California Desert and the State of Arizona were adapted to spatially register multispectral and radar data. Techniques included control point selection from imagery and USGS topographic quadrangle maps, control point cataloguing with the Image Based Information System, and spatial and spectral rectifications of the imagery. The radar imagery was pre-processed to reduce its tendency toward uniform data distributions, so that training site statistics for selected Landsat and pre-processed Seasat imagery indicated good spectral separation between channels.

Sperm Patch-Clamp

PubMed Central

Lishko, Polina; Clapham, David E.; Navarro, Betsy; Kirichok, Yuriy

2014-01-01

Sperm intracellular pH and calcium concentration ([Ca2+]i) are two central factors that control sperm activity within the female reproductive tract. As such, the ion channels of the sperm plasma membrane that alter intracellular sperm [Ca2+] and pH play important roles in sperm physiology and the process of fertilization. Indeed, sperm ion channels regulate sperm motility, control sperm chemotaxis toward the egg in some species, and may trigger the acrosome reaction. Until recently, our understanding of these important molecules was rudimentary due to the inability to patch-clamp spermatozoa and directly record the activity of these ion channels under voltage clamp. Recently, we overcame this technical barrier and developed a method for reproducible application of the patch-clamp technique to mouse and human spermatozoa. This chapter covers important aspects of application of the patch-clamp technique to spermatozoa, such as selection of the electrophysiological equipment, isolation of spermatozoa for patch-clamp experiments, formation of the gigaohm seal with spermatozoa, and transition into the whole-cell mode of recording. We also discuss potential pitfalls in application of the patch-clamp technique to flagellar ion channels. PMID:23522465

Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide–gated channels

PubMed Central

Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun

2015-01-01

Calcium permeability and the concomitant calcium block of monovalent ion current (“Ca2+ block”) are properties of cyclic nucleotide–gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca2+ block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca2+ block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca2+ block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca2+ block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca2+ block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca2+ block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca2+ block. PMID:26283200

Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide-gated channels.

PubMed

Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun; Jiang, Youxing

2015-09-01

Calcium permeability and the concomitant calcium block of monovalent ion current ("Ca(2+) block") are properties of cyclic nucleotide-gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca(2+) block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca(2+) block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca(2+) block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca(2+) block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca(2+) block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca(2+) block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca(2+) block. © 2015 Lam et al.

Choice: 36 band feature selection software with applications to multispectral pattern recognition

NASA Technical Reports Server (NTRS)

Jones, W. C.

1973-01-01

Feature selection software was developed at the Earth Resources Laboratory that is capable of inputting up to 36 channels and selecting channel subsets according to several criteria based on divergence. One of the criterion used is compatible with the table look-up classifier requirements. The software indicates which channel subset best separates (based on average divergence) each class from all other classes. The software employs an exhaustive search technique, and computer time is not prohibitive. A typical task to select the best 4 of 22 channels for 12 classes takes 9 minutes on a Univac 1108 computer.

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

PubMed Central

Finnerty, Justin John

2015-01-01

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

Insulin and IGF-1 activate Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage.

PubMed

Zaika, Oleg; Palygin, Oleg; Tomilin, Viktor; Mamenko, Mykola; Staruschenko, Alexander; Pochynyuk, Oleh

2016-02-15

Potassium Kir4.1/5.1 channels are abundantly expressed at the basolateral membrane of principal cells in the cortical collecting duct (CCD), where they are thought to modulate transport rates by controlling transepithelial voltage. Insulin and insulin-like growth factor-1 (IGF-1) stimulate apically localized epithelial sodium channels (ENaC) to augment sodium reabsorption in the CCD. However, little is known about their actions on potassium channels localized at the basolateral membrane. In this study, we implemented patch-clamp analysis in freshly isolated murine CCD to assess the effect of these hormones on Kir4.1/5.1 at both single channel and cellular levels. We demonstrated that K(+)-selective conductance via Kir4.1/5.1 is the major contributor to the macroscopic current recorded from the basolateral side in principal cells. Acute treatment with 10 μM amiloride (ENaC blocker), 100 nM tertiapin-Q (TPNQ; ROMK inhibitor), and 100 μM ouabain (Na(+)-K(+)-ATPase blocker) failed to produce a measurable effect on the macroscopic current. In contrast, Kir4.1 inhibitor nortriptyline (100 μM), but not fluoxetine (100 μM), virtually abolished whole cell K(+)-selective conductance. Insulin (100 nM) markedly increased the open probability of Kir4.1/5.1 and nortriptyline-sensitive whole cell current, leading to significant hyperpolarization of the basolateral membrane. Inhibition of the phosphatidylinositol 3-kinase cascade with LY294002 (20 μM) abolished action of insulin on Kir4.1/5.1. IGF-1 had similar stimulatory actions on Kir4.1/5.1-mediated conductance only when applied at a higher (500 nM) concentration and was ineffective at 100 nM. We concluded that both insulin and, to a lesser extent, IGF-1 activate Kir4.1/5.1 channel activity and open probability to hyperpolarize the basolateral membrane, thereby facilitating Na(+) reabsorption in the CCD. Copyright © 2016 the American Physiological Society.

An evolutionarily conserved gene family encodes proton-selective ion channels.

PubMed

Tu, Yu-Hsiang; Cooper, Alexander J; Teng, Bochuan; Chang, Rui B; Artiga, Daniel J; Turner, Heather N; Mulhall, Eric M; Ye, Wenlei; Smith, Andrew D; Liman, Emily R

2018-03-02

Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3 , and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A novel type of ATP block on a Ca(2+)-activated K(+) channel from bullfrog erythrocytes.

PubMed

Shindo, M; Imai, Y; Sohma, Y

2000-07-01

Using the patch-clamp technique, we have identified an intermediate conductance Ca(2+)-activated K(+) channel from bullfrog (Rana catesbeiana) erythrocytes and have investigated the regulation of channel activity by cytosolic ATP. The channel was highly selective for K(+) over Na(+), gave a linear I-V relationship with symmetrical 117.5 mM K(+) solutions and had a single-channel conductance of 60 pS. Channel activity was dependent on Ca(2+) concentration (K(1/2) = 600 nM) but voltage-independent. These basic characteristics are similar to those of human and frog erythrocyte Ca(2+)-activated K(+) (Gardos) channels previously reported. However, cytoplasmic application of ATP reduced channel activity with block exhibiting a novel bell-shaped concentration dependence. The channel was inhibited most by approximately 10 microM ATP (P(0) reduced to 5% of control) but less blocked by lower and higher concentrations of ATP. Moreover, the novel type of ATP block did not require Mg(2+), was independent of PKA or PKC, and was mimicked by a nonhydrolyzable ATP analog, AMP-PNP. This suggests that ATP exerts its effect by direct binding to sites on the channel or associated regulatory proteins, but not by phosphorylation of either of these components.

Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine.

PubMed

Zhang, Fan; Cheng, Yanxin; Li, Hong; Jia, Qingzhong; Zhang, Hailin; Zhao, Senming

2015-01-01

Chloroprocaine is a local ester anesthetic, producing excellent sensory block in clinical use. The Kv7/M potassium channel plays an important role in the control of neuronal excitability. In this study, we investigated the effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the effect of retigabine on chloroprocaine-induced seizures. A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from rat dorsal root ganglion (DRG) neurons. Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a lowering of current amplitudes, a rightward shift in the voltage-dependent activation curves, and a slowing of channel activation. Chloroprocaine had a more selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3 channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited native M channel currents and induced a depolarization of the DRG neuron membrane potential. Taken together, the findings indicate that chloroprocaine concentration dependently inhibited Kv7/M channel currents. © 2015 S. Karger AG, Basel.

Persistent enhancement of bacterial motility increases tumor penetration.

PubMed

Thornlow, Dana N; Brackett, Emily L; Gigas, Jonathan M; Van Dessel, Nele; Forbes, Neil S

2015-11-01

Motile bacteria can overcome the transport limitations that hinder many cancer therapies. Active bacteria can penetrate through tissue to deliver treatment to resistant tumor regions. Bacterial therapy has had limited success, however, because this motility is heterogeneous, and within a population many individuals are non-motile. In human trials, heterogeneity led to poor dispersion and incomplete tumor colonization. To address these problems, a swarm-plate selection method was developed to increase swimming velocity. Video microscopy was used to measure the velocity distribution of selected bacteria and a microfluidic tumor-on-a-chip device was used to measure penetration through tumor cell masses. Selection on swarm plates increased average velocity fourfold, from 4.9 to 18.7 μm/s (P < 0.05) and decreased the number of non-motile individuals from 51% to 3% (P < 0.05). The selected phenotype was both robust and stable. Repeating the selection process consistently increased velocity and eliminated non-motile individuals. When selected strains were cryopreserved and subcultured for 30.1 doublings, the high-motility phenotype was preserved. In the microfluidic device, selected Salmonella penetrated deeper into cell masses than unselected controls. By 10 h after inoculation, control bacteria accumulated in the front 30% of cell masses, closest to the flow channel. In contrast, selected Salmonella accumulated in the back 30% of cell masses, farthest from the channel. Selection increased the average penetration distance from 150 to 400 μm (P < 0.05). This technique provides a simple and rapid method to generate high-motility Salmonella that has increased penetration and potential for greater tumor dispersion and clinical efficacy. © 2015 Wiley Periodicals, Inc.

Locating the route of entry and binding sites of benzocaine and phenytoin in a bacterial voltage gated sodium channel.

PubMed

Martin, Lewis J; Corry, Ben

2014-07-01

Sodium channel blockers are used to control electrical excitability in cells as a treatment for epileptic seizures and cardiac arrhythmia, and to provide short term control of pain. Development of the next generation of drugs that can selectively target one of the nine types of voltage-gated sodium channel expressed in the body requires a much better understanding of how current channel blockers work. Here we make use of the recently determined crystal structure of the bacterial voltage gated sodium channel NavAb in molecular dynamics simulations to elucidate the position at which the sodium channel blocking drugs benzocaine and phenytoin bind to the protein as well as to understand how these drugs find their way into resting channels. We show that both drugs have two likely binding sites in the pore characterised by nonspecific, hydrophobic interactions: one just above the activation gate, and one at the entrance to the the lateral lipid filled fenestrations. Three independent methods find the same sites and all suggest that binding to the activation gate is slightly more favourable than at the fenestration. Both drugs are found to be able to pass through the fenestrations into the lipid with only small energy barriers, suggesting that this can represent the long posited hydrophobic entrance route for neutral drugs. Our simulations highlight the importance of a number of residues in directing drugs into and through the fenestration, and in forming the drug binding sites.

Locating the Route of Entry and Binding Sites of Benzocaine and Phenytoin in a Bacterial Voltage Gated Sodium Channel

PubMed Central

Martin, Lewis J.; Corry, Ben

2014-01-01

Sodium channel blockers are used to control electrical excitability in cells as a treatment for epileptic seizures and cardiac arrhythmia, and to provide short term control of pain. Development of the next generation of drugs that can selectively target one of the nine types of voltage-gated sodium channel expressed in the body requires a much better understanding of how current channel blockers work. Here we make use of the recently determined crystal structure of the bacterial voltage gated sodium channel NavAb in molecular dynamics simulations to elucidate the position at which the sodium channel blocking drugs benzocaine and phenytoin bind to the protein as well as to understand how these drugs find their way into resting channels. We show that both drugs have two likely binding sites in the pore characterised by nonspecific, hydrophobic interactions: one just above the activation gate, and one at the entrance to the the lateral lipid filled fenestrations. Three independent methods find the same sites and all suggest that binding to the activation gate is slightly more favourable than at the fenestration. Both drugs are found to be able to pass through the fenestrations into the lipid with only small energy barriers, suggesting that this can represent the long posited hydrophobic entrance route for neutral drugs. Our simulations highlight the importance of a number of residues in directing drugs into and through the fenestration, and in forming the drug binding sites. PMID:24992293

Historical Channel Adjustment and Estimates of Selected Hydraulic Values in the Lower Sabine River and Lower Brazos River Basins, Texas and Louisiana

USGS Publications Warehouse

Heitmuller, Franklin T.; Greene, Lauren E.

2009-01-01

The U.S. Geological Survey, in cooperation with the Texas Water Development Board, evaluated historical channel adjustment and estimated selected hydraulic values at U.S. Geological Survey streamflow-gaging stations in the lower Sabine River Basin in Texas and Louisiana and lower Brazos River Basin in Texas to support geomorphic assessments of the Texas Instream Flow Program. Channel attributes including cross-section geometry, slope, and planform change were evaluated to learn how each river's morphology changed over the years in response to natural and anthropogenic disturbances. Historical and contemporary cross-sectional channel geometries at several gaging stations on each river were compared, planform changes were assessed, and hydraulic values were estimated including mean flow velocity, bed shear stress, Froude numbers, and hydraulic depth. The primary sources of historical channel morphology information were U.S. Geological Survey hard-copy discharge-measurement field notes. Additional analyses were done using computations of selected flow hydraulics, comparisons of historical and contemporary aerial photographs, comparisons of historical and contemporary ground photographs, evaluations of how frequently stage-discharge rating curves were updated, reviews of stage-discharge relations for field measurements, and considerations of bridge and reservoir construction activities. Based on historical cross sections at three gaging stations downstream from Toledo Bend Reservoir, the lower Sabine River is relatively stable, but is subject to substantial temporary scour-and-fill processes during floods. Exceptions to this characterization of relative stability include an episode of channel aggradation at the Sabine River near Bon Wier, Texas, during the 1930s, and about 2 to 3 feet of channel incision at the Sabine River near Burkeville, Texas, since the late 1950s. The Brazos River, at gaging stations downstream from Waco, Texas, has adjusted to a combination of hydrologic, sedimentary, and anthropogenic controls. Since the 1960s, numerous point bars have vertically accreted and vegetation has encroached along the channel margins, which probably promotes channel-bed incision to compensate for a reduction in cross-sectional area. Channel incision was detected at all gaging stations along the Brazos River, and the depth of incision is greatest in the lowermost gaging stations, exemplified by about 5 feet of channel-bed incision between 1993 and 2004 at Richmond, Texas. One notable exception to this pattern of incision was a period of aggradation at U.S. Geological Survey gaging station 08096500 Brazos River at Waco, Texas, during the late 1920s and 1930s, probably associated with upstream dam construction. Lateral channel migration rates along the Brazos River determined from aerial photographs are greatest between Waco and Hempstead, Texas, with numerous bends moving an average of more than 10 feet per year. Migration rates at selected bends downstream from Hempstead were measured as less than 10 feet per year, on average. Two tributaries of the Brazos River, the Little and Navasota Rivers, also were investigated for historical channel adjustment. The Little River near Cameron, Texas (08106500) has incised its channel bed about 12 feet since 1949, and the lower Navasota River shows complex adjustment to bridge construction activities and a channel avulsion.

Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

PubMed

Li, Yang; Liu, Huihui; Xia, Mengdie; Gong, Haipeng

2016-01-01

Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group.

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

Design of a mobile brain computer interface-based smart multimedia controller.

PubMed

Tseng, Kevin C; Lin, Bor-Shing; Wong, Alice May-Kuen; Lin, Bor-Shyh

2015-03-06

Music is a way of expressing our feelings and emotions. Suitable music can positively affect people. However, current multimedia control methods, such as manual selection or automatic random mechanisms, which are now applied broadly in MP3 and CD players, cannot adaptively select suitable music according to the user's physiological state. In this study, a brain computer interface-based smart multimedia controller was proposed to select music in different situations according to the user's physiological state. Here, a commercial mobile tablet was used as the multimedia platform, and a wireless multi-channel electroencephalograph (EEG) acquisition module was designed for real-time EEG monitoring. A smart multimedia control program built in the multimedia platform was developed to analyze the user's EEG feature and select music according his/her state. The relationship between the user's state and music sorted by listener's preference was also examined in this study. The experimental results show that real-time music biofeedback according a user's EEG feature may positively improve the user's attention state.

Focus on Kir7.1: physiology and channelopathy

PubMed Central

Kumar, Mohit; Pattnaik, Bikash R

2014-01-01

Genetic studies have linked alterations in Kir7.1 channel to diverse pathologies. We summarize functional relevance of Kir7.1 channel in retinal pigment epithelium (RPE), regulation of channel function by various cytoplasmic metabolites, and mutations that cause channelopathies. At the apical membrane of RPE, K+ channels contribute to subretinal K+ homeostasis and support Na+/K+ pump and Na+-K+-2Cl− cotransporter function by providing a pathway for K+ secretion. Electrophysiological studies have established that barium- and cesium-sensitive inwardly rectifying K+ (Kir) channels make up a major component of the RPE apical membrane K+ conductance. Native human RPE expresses transcripts for Kir1.1, Kir2.1, Kir2.2, Kir3.1, Kir3.4, Kir4.2, and Kir6.1, albeit at levels at least 50-fold lower than Kir7.1. Kir7.1 is structurally similar to other Kir channels, consisting of 2 trans-membrane domains, a pore-forming loop that contains the selectivity filter, and 2 cytoplasmic polar tails. Within the cytoplasmic structure, clusters of amino acid sequences form regulatory domains that interact with cellular metabolites and control the opening and closing of the channel. Recent evidence indicated that intrinsic sequence motifs present in Kir7.1 control surface expression. Mutant Kir7.1 channels are associated with inherited eye pathologies such as Snowflake Vitreoretinal Degeneration (SVD) and Lebers Congenital Amaurosis (LCA16). Based on the current evidence, mutations implicated in channelopathies have the potential to be used for genetic testing to diagnose blindness due to Kir7.1. PMID:25558901

Effects of ginger and its pungent constituents on transient receptor potential channels.

PubMed

Kim, Young-Soo; Hong, Chan Sik; Lee, Sang Weon; Nam, Joo Hyun; Kim, Byung Joo

2016-12-01

Ginger extract is used as an analeptic in herbal medicine and has been reported to exert antioxidant effects. Transient receptor potential (TRP) canonical 5 (TRPC5), TRP cation channel, subfamily M, member 7 (TRPM7; melastatin 7), and TRP cation channel, subfamily A, member 1 (TRPA1; ankyrin 1) are non-selective cation channels that are modulated by reactive oxygen/nitrogen species (ROS/RNS) and subsequently control various cellular processes. The aim of this study was to evaluate whether ginger and its pungent constituents modulate these channels and exert antioxidant effects. It was found that TRPC5 and TRPA1 currents were modulated by ginger extract and by its pungent constituents, [6]-gingerol, zingerone and [6]-shogaol. In particular, [6]-shogaol markedly and dose-dependently inhibited TRPC5 currents with an IC50 of value of ~18.3 µM. Furthermore, the strong dose-dependent activation of TRPA1 currents by [6]-shogaol was abolished by A‑967079 (a selective TRPA1 inhibitor). However, ginger extract and its pungent constituents had no effect on TRPM7 currents. These results suggest the antioxidant effects of ginger extract and its pungent constituents are mediated through TRPC5 and TRPA1, and that [6]-shogaol is predominantly responsible for the regulation of TRPC5 and TRPA1 currents by ginger extract.

Selectivity filters and cysteine-rich extracellular loops in voltage-gated sodium, calcium, and NALCN channels

PubMed Central

Stephens, Robert F.; Guan, W.; Zhorov, Boris S.; Spafford, J. David

2015-01-01

How nature discriminates sodium from calcium ions in eukaryotic channels has been difficult to resolve because they contain four homologous, but markedly different repeat domains. We glean clues from analyzing the changing pore region in sodium, calcium and NALCN channels, from single-cell eukaryotes to mammals. Alternative splicing in invertebrate homologs provides insights into different structural features underlying calcium and sodium selectivity. NALCN generates alternative ion selectivity with splicing that changes the high field strength (HFS) site at the narrowest level of the hourglass shaped pore where the selectivity filter is located. Alternative splicing creates NALCN isoforms, in which the HFS site has a ring of glutamates contributed by all four repeat domains (EEEE), or three glutamates and a lysine residue in the third (EEKE) or second (EKEE) position. Alternative splicing provides sodium and/or calcium selectivity in T-type channels with extracellular loops between S5 and P-helices (S5P) of different lengths that contain three or five cysteines. All eukaryotic channels have a set of eight core cysteines in extracellular regions, but the T-type channels have an infusion of 4–12 extra cysteines in extracellular regions. The pattern of conservation suggests a possible pairing of long loops in Domains I and III, which are bridged with core cysteines in NALCN, Cav, and Nav channels, and pairing of shorter loops in Domains II and IV in T-type channel through disulfide bonds involving T-type specific cysteines. Extracellular turrets of increasing lengths in potassium channels (Kir2.2, hERG, and K2P1) contribute to a changing landscape above the pore selectivity filter that can limit drug access and serve as an ion pre-filter before ions reach the pore selectivity filter below. Pairing of extended loops likely contributes to the large extracellular appendage as seen in single particle electron cryo-microscopy images of the eel Nav1 channel. PMID:26042044

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.

Dual-channel microreactor for gas-liquid syntheses.

PubMed

Park, Chan Pil; Kim, Dong-Pyo

2010-07-28

A microreactor consisting of two microfluidic channels that are separated by a thin membrane is devised for intimate contact between gas and liquid phases. Gas flowing in one microchannel can diffuse into the liquid flowing in the other microchannel through the thin membrane. An oxidative Heck reaction carried out in the dual-channel (DC) microreactor, in which gaseous oxygen plays a key role in the catalytic reaction, shows the significant improvement that can be made over the traditional batch reactor and the conventional segmental microreactor in terms of yield, selectivity, and reaction time. It also allows independent control of the flow of the gaseous reagent. The proposed DC microreactor should prove to be a powerful tool for fully exploring gas-liquid microchemistry.

Adiabatic Edge Channel Transport in a Nanowire Quantum Point Contact Register.

PubMed

Heedt, S; Manolescu, A; Nemnes, G A; Prost, W; Schubert, J; Grützmacher, D; Schäpers, Th

2016-07-13

We report on a prototype device geometry where a number of quantum point contacts are connected in series in a single quasi-ballistic InAs nanowire. At finite magnetic field the backscattering length is increased up to the micron-scale and the quantum point contacts are connected adiabatically. Hence, several input gates can control the outcome of a ballistic logic operation. The absence of backscattering is explained in terms of selective population of spatially separated edge channels. Evidence is provided by regular Aharonov-Bohm-type conductance oscillations in transverse magnetic fields, in agreement with magnetoconductance calculations. The observation of the Shubnikov-de Haas effect at large magnetic fields corroborates the existence of spatially separated edge channels and provides a new means for nanowire characterization.

Warpage optimisation on the moulded part with straight-drilled and conformal cooling channels using response surface methodology (RSM) and glowworm swarm optimisation (GSO)

NASA Astrophysics Data System (ADS)

Hazwan, M. H. M.; Shayfull, Z.; Sharif, S.; Nasir, S. M.; Zainal, N.

2017-09-01

In injection moulding process, quality and productivity are notably important and must be controlled for each product type produced. Quality is measured as the extent of warpage of moulded parts while productivity is measured as a duration of moulding cycle time. To control the quality, many researchers have introduced various of optimisation approaches which have been proven enhanced the quality of the moulded part produced. In order to improve the productivity of injection moulding process, some of researches have proposed the application of conformal cooling channels which have been proven reduced the duration of moulding cycle time. Therefore, this paper presents an application of alternative optimisation approach which is Response Surface Methodology (RSM) with Glowworm Swarm Optimisation (GSO) on the moulded part with straight-drilled and conformal cooling channels mould. This study examined the warpage condition of the moulded parts before and after optimisation work applied for both cooling channels. A front panel housing have been selected as a specimen and the performance of proposed optimisation approach have been analysed on the conventional straight-drilled cooling channels compared to the Milled Groove Square Shape (MGSS) conformal cooling channels by simulation analysis using Autodesk Moldflow Insight (AMI) 2013. Based on the results, melt temperature is the most significant factor contribute to the warpage condition and warpage have optimised by 39.1% after optimisation for straight-drilled cooling channels and cooling time is the most significant factor contribute to the warpage condition and warpage have optimised by 38.7% after optimisation for MGSS conformal cooling channels. In addition, the finding shows that the application of optimisation work on the conformal cooling channels offers the better quality and productivity of the moulded part produced.

Application of a taste evaluation system to the monitoring of Kimchi fermentation.

PubMed

Kim, Namsoo; Park, Kyung-Rim; Park, In-Seon; Cho, Yong-Jin; Bae, Young Min

2005-05-15

As an objective method, taste evaluation with an instrument is able to supplement the subjective sensory evaluation and to be applied to the optimization of food processing. Kimchi, a Korean traditional pickle fermented with lactic acid bacteria, is expanding its consumption worldwide. The fermentation control of it has been routinely done by measuring titratable acidity and pH. In this study, an eight-channel taste evaluation system was prepared, followed by an application to the monitoring of Kimchi fermentation. Eight polymer membranes which individually responded to cationic or anionic substances were prepared by mixing electroactive materials such as tri-n-octylmethylammonium chloride, bis(2-ethylhexyl)sebacate as the plasticizer and polyvinyl chloride in the ratio of 1:66:33. Each membrane prepared was separately installed onto the sensitive area of an ion-selective electrode to produce the respective taste sensor. The eight-channel sensor array and a double junction reference electrode were connected to a 16-channel high input impedance amplifier. The amplified sensor signals were stored to a personal computer via a multi-channel A/D converter. Two sensor groups composed of the cation-selective and anion-selective polymer membrane electrodes showed characteristic concentration-dependency to various artificial taste substances. As a whole, the response potentials of the sensor array increased during the fermentation period at 4, 10 and 25 degrees C. Even the response potentials of the anion-selective taste sensors slightly increased possibly due to the protonation of anions by liberated H+ ions, thereby leading to a decrease in the anion concentration. When the signal data were interpreted by principal component analysis (PCA), the first PC at 4 degrees C explained most of the total data variance. A close correlation was found between the values of titratable acidity and the first PC, which indicated a possible applicability of the multi-channel taste sensor of this study to the process monitoring of various pickle.

System for concentrating and analyzing particles suspended in a fluid

DOEpatents

Fiechtner, Gregory J [Bethesda, MD; Cummings, Eric B [Livermore, CA; Singh, Anup K [Danville, CA

2011-04-26

Disclosed is a device for separating and concentrating particles suspended in a fluid stream by using dielectrophoresis (DEP) to trap and/or deflect those particles as they migrate through a fluid channel. The method uses fluid channels designed to constrain a liquid flowing through it to uniform electrokinetic flow velocities. This behavior is achieved by connecting deep and shallow sections of channels, with the channel depth varying abruptly along an interface. By careful design of abrupt changes in specific permeability at the interface, an abrupt and spatially uniform change in electrokinetic force can be selected. Because these abrupt interfaces also cause a sharp gradient in applied electric fields, a DEP force also can be established along the interface. Depending on the complex conductivity of the suspended particles and the immersion liquid, the DEP force can controllably complement or oppose the local electrokinetic force transporting the fluid through the channel allowing for manipulation of particles suspended in the transporting liquid.

Apparatus and method for concentrating and filtering particles suspended in a fluid

DOEpatents

Fiechtner, Gregory J [Bethesda, MD; Cummings, Eric B [Livermore, CA; Singh, Anup K [Danville, CA

2009-05-19

Disclosed is a device for separating and concentrating particles suspended in a fluid stream by using dielectrophoresis (DEP) to trap and/or deflect those particles as they migrate through a fluid channel. The method uses fluid channels designed to constrain a liquid flowing through it to uniform electrokinetic flow velocities. This behavior is achieved by connecting deep and shallow sections of channels, with the channel depth varying abruptly along an interface. By careful design of abrupt changes in specific permeability at the interface, an abrupt and spatially uniform change in electrokinetic force can be selected. Because these abrupt interfaces also cause a sharp gradient in applied electric fields, a DEP force also can be established along the interface. Depending on the complex conductivity of the suspended particles and the immersion liquid, the DEP force can controllably complement or oppose the local electrokinetic force transporting the fluid through the channel allowing for manipulation of particles suspended in the transporting liquid.

Structure-based membrane dome mechanism for Piezo mechanosensitivity.

PubMed

Guo, Yusong R; MacKinnon, Roderick

2017-12-12

Mechanosensitive ion channels convert external mechanical stimuli into electrochemical signals for critical processes including touch sensation, balance, and cardiovascular regulation. The best understood mechanosensitive channel, MscL, opens a wide pore, which accounts for mechanosensitive gating due to in-plane area expansion. Eukaryotic Piezo channels have a narrow pore and therefore must capture mechanical forces to control gating in another way. We present a cryo-EM structure of mouse Piezo1 in a closed conformation at 3.7Å-resolution. The channel is a triskelion with arms consisting of repeated arrays of 4-TM structural units surrounding a pore. Its shape deforms the membrane locally into a dome. We present a hypothesis in which the membrane deformation changes upon channel opening. Quantitatively, membrane tension will alter gating energetics in proportion to the change in projected area under the dome. This mechanism can account for highly sensitive mechanical gating in the setting of a narrow, cation-selective pore. © 2017, Guo et al.

Protective effects of phosphodiesterase-1 (PDE1) and ATP sensitive potassium (KATP) channel modulators against 3-nitropropionic acid induced behavioral and biochemical toxicities in experimental Huntington׳s disease.

PubMed

Gupta, Surbhi; Sharma, Bhupesh

2014-06-05

Huntington׳s disease (HD), a devastating neurodegenerative disorder, is characterized by weight loss, impairment of motor function, cognitive dysfunction, neuropsychiatric disturbances and striatal damage. Phosphodiesterase-1 (PDE1) has been implicated in various neurological diseases. Mitochondrial potassium channels in the brain take part in neuroprotection. This study has been structured to investigate the role of vinpocetine, a selective PDE1 inhibitor as well as nicorandil, selective ATP sensitive potassium (KATP) channel opener in 3-nitropropionic acid (3-NP) induced HD symptoms in rats. Systemic administration of 3-NP significantly, reduced body weight, impaired locomotion, grip strength and impaired cognition. 3-NP elicited marked oxidative stress in the brain (enhanced malondialdehyde-MDA, reduced glutathione-GSH content, superoxide dismutase-SOD and catalase-CAT), elevated brain acetylcholinesterase activity and inflammation (myeloperoxidase-MPO), with marked nitrosative stress (nitrite/nitrate) in the brain. 3-NP has also induced mitochondrial dysfunction (impaired mitochondrial NADH dehydrogenase-complex I, succinate dehydrogenase-complex II and cytochrome oxidase-complex IV) activities in the striatum of the rat. Tetrabenazine was used as a positive control. Treatment with vinpocetine, nicorandil and tetrabenazine ameliorated 3-NP induced reduction in body weight, impaired locomotion, grip strength and impaired cognition. Treatment with these drugs reduced brain striatum oxidative (MDA, GSH, SOD and CAT) and nitrosative (nitrite/nitrate) stress, acetylcholinesterase activity, inflammation and mitochondrial dysfunctions. These results indicate that vinpocetine, a selective PDE1 inhibitor and nicorandil, a KATP channel opener have attenuated 3-NP induced experimental HD. Hence, pharmacological modulation of PDE1 as well as KATP channels may be considered as potential research targets for mitigation of HD. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

Ozkan, Melike Hacer; Uma, Serdar

2018-06-01

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

Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

PubMed Central

Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

2015-01-01

K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

ReliefF-Based EEG Sensor Selection Methods for Emotion Recognition.

PubMed

Zhang, Jianhai; Chen, Ming; Zhao, Shaokai; Hu, Sanqing; Shi, Zhiguo; Cao, Yu

2016-09-22

Electroencephalogram (EEG) signals recorded from sensor electrodes on the scalp can directly detect the brain dynamics in response to different emotional states. Emotion recognition from EEG signals has attracted broad attention, partly due to the rapid development of wearable computing and the needs of a more immersive human-computer interface (HCI) environment. To improve the recognition performance, multi-channel EEG signals are usually used. A large set of EEG sensor channels will add to the computational complexity and cause users inconvenience. ReliefF-based channel selection methods were systematically investigated for EEG-based emotion recognition on a database for emotion analysis using physiological signals (DEAP). Three strategies were employed to select the best channels in classifying four emotional states (joy, fear, sadness and relaxation). Furthermore, support vector machine (SVM) was used as a classifier to validate the performance of the channel selection results. The experimental results showed the effectiveness of our methods and the comparison with the similar strategies, based on the F-score, was given. Strategies to evaluate a channel as a unity gave better performance in channel reduction with an acceptable loss of accuracy. In the third strategy, after adjusting channels' weights according to their contribution to the classification accuracy, the number of channels was reduced to eight with a slight loss of accuracy (58.51% ± 10.05% versus the best classification accuracy 59.13% ± 11.00% using 19 channels). In addition, the study of selecting subject-independent channels, related to emotion processing, was also implemented. The sensors, selected subject-independently from frontal, parietal lobes, have been identified to provide more discriminative information associated with emotion processing, and are distributed symmetrically over the scalp, which is consistent with the existing literature. The results will make a contribution to the realization of a practical EEG-based emotion recognition system.

Current State of Theoretical and Experimental Studies of the Voltage-Dependent Anion Channel (VDAC)

PubMed Central

Noskov, Sergei Yu.; Rostovtseva, Tatiana K.; Chamberlin, Adam C.; Teijido, Oscar; Jiang, Wei; Bezrukov, Sergey M.

2016-01-01

Voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane provides a controlled pathway for respiratory metabolites in and out of the mitochondria. In spite of the wealth of experimental data from structural, biochemical, and biophysical investigations, the exact mechanisms governing selective ion and metabolite transport, especially the role of titratable charged residues and interactions with soluble cytosolic proteins, remain hotly debated in the field. The computational advances hold a promise to provide a much sought-after solution to many of the scientific disputes around solute and ion transport through VDAC and hence, across the mitochondrial outer membrane. In this review, we examine how Molecular Dynamics, Free Energy, and Brownian Dynamics simulations of the large β-barrel channel, VDAC, advanced our understanding. We will provide a short overview of non-conventional techniques and also discuss examples of how the modeling excursions into VDAC biophysics prospectively aid experimental efforts. PMID:26940625

Noise-Riding Video Signal Threshold Generation Scheme for a Plurality of Video Signal Channels

DTIC Science & Technology

2007-02-12

on the selected one signal channel to generate a new video signal threshold . The processing resource has an output to provide the new video signal threshold to the comparator circuit corresponding to the selected signal channel.

Homologue Structure of the SLAC1 Anion Channel for Closing Stomata in Leaves

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

Y Chen; L Hu; M Punta

2011-12-31

The plant SLAC1 anion channel controls turgor pressure in the aperture-defining guard cells of plant stomata, thereby regulating the exchange of water vapour and photosynthetic gases in response to environmental signals such as drought or high levels of carbon dioxide. Here we determine the crystal structure of a bacterial homologue (Haemophilus influenzae) of SLAC1 at 1.20 {angstrom} resolution, and use structure-inspired mutagenesis to analyse the conductance properties of SLAC1 channels. SLAC1 is a symmetrical trimer composed from quasi-symmetrical subunits, each having ten transmembrane helices arranged from helical hairpin pairs to form a central five-helix transmembrane pore that is gated bymore » an extremely conserved phenylalanine residue. Conformational features indicate a mechanism for control of gating by kinase activation, and electrostatic features of the pore coupled with electrophysiological characteristics indicate that selectivity among different anions is largely a function of the energetic cost of ion dehydration.« less

The hitchhiker’s guide to the voltage-gated sodium channel galaxy

PubMed Central

2016-01-01

Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure–function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na+ selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts. PMID:26712848

Mobility-Resolved Ion Selection in Uniform Drift Field Ion Mobility Spectrometry/Mass Spectrometry: Dynamic Switching in Structures for Lossless Ion Manipulations

DOE PAGES

Webb, Ian K.; Garimella, Sandilya V. B.; Tolmachev, Aleksey V.; ...

2014-09-15

A Structures for Lossless Ion Manipulations (SLIM) module that allows ion mobility separations and the switching of ions between alternative drift paths is described. The SLIM switch component has a “Tee” configuration and allows switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be deflected to an alternative channel as a function of their mobilities. In the initial evaluation the switch is used in a static mode and shown compatible with high performance ion mobility separations at 4 torr. In the “dynamic mode” we show that mobility-selected ions can be switched intomore » the alternative channel, and that various ion species can be independently selected based on their mobilities for time-of-flight mass spectrometer (TOF MS) IMS detection and mass analysis. Ultimately, this development also provides the basis for e.g. the selection of specific mobilities for storage and accumulation, and key modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations.« less

Novel role for the transient potential receptor melastatin 4 channel in guinea pig detrusor smooth muscle physiology

PubMed Central

Smith, Amy C.; Hristov, Kiril L.; Cheng, Qiuping; Xin, Wenkuan; Parajuli, Shankar P.; Earley, Scott; Malysz, John

2013-01-01

Members of the transient receptor potential (TRP) channel superfamily, including the Ca2+-activated monovalent cation-selective TRP melastatin 4 (TRPM4) channel, have been recently identified in the urinary bladder. However, their expression and function at the level of detrusor smooth muscle (DSM) remain largely unexplored. In this study, for the first time we investigated the role of TRPM4 channels in guinea pig DSM excitation-contraction coupling using a multidisciplinary approach encompassing protein detection, electrophysiology, live-cell Ca2+ imaging, DSM contractility, and 9-phenanthrol, a recently characterized selective inhibitor of the TRPM4 channel. Western blot and immunocytochemistry experiments demonstrated the expression of the TRPM4 channel in whole DSM tissue and freshly isolated DSM cells with specific localization on the plasma membrane. Perforated whole cell patch-clamp recordings and real-time Ca2+ imaging experiments with fura 2-AM, both using freshly isolated DSM cells, revealed that 9-phenanthrol (30 μM) significantly reduced the cation current and decreased intracellular Ca2+ levels. 9-Phenanthrol (0.1–30 μM) significantly inhibited spontaneous, 0.1 μM carbachol-induced, 20 mM KCl-induced, and nerve-evoked contractions in guinea pig DSM-isolated strips with IC50 values of 1–7 μM and 70–80% maximum inhibition. 9-Phenanthrol also reduced nerve-evoked contraction amplitude induced by continuous repetitive electrical field stimulation of 10-Hz frequency and shifted the frequency-response curve (0.5–50 Hz) relative to the control. Collectively, our data demonstrate the novel finding that TRPM4 channels are expressed in guinea pig DSM and reveal their critical role in the regulation of guinea pig DSM excitation-contraction coupling. PMID:23302778

Theory of Alike Selectivity in Biological Channels

NASA Technical Reports Server (NTRS)

Luchinsky, Dmitry G.; Gibby, Will A. T.; Kaufman, Igor Kh.; Eisenberg, Robert S.; McClintock, Peter V. E.

2016-01-01

We introduce a statistical mechanical model of the selectivity filter that accounts for the interaction between ions within the channel and derive Eisenman equation of the filter selectivity directly from the condition of barrier-less conduction.

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

PubMed Central

Zamponi, Gerald W.; Striessnig, Joerg; Koschak, Alexandra

2015-01-01

Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type CaV1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (CaV3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (CaV2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., CaV1.2 and CaV1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective CaV1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson’s disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and anxiety. Use-dependent N-type calcium channel blockers are likely to be of therapeutic use in chronic pain conditions. Thus, more selective calcium channel blockers hold promise for therapeutic intervention. PMID:26362469

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

Webb, Ian K.; Garimella, Sandilya V. B.; Tolmachev, Aleksey V.

A Structures for Lossless Ion Manipulations (SLIM) module that allows ion mobility separations and the switching of ions between alternative drift paths is described. The SLIM switch component has a “Tee” configuration and allows switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be deflected to an alternative channel as a function of their mobilities. In the initial evaluation the switch is used in a static mode and shown compatible with high performance ion mobility separations at 4 torr. In the “dynamic mode” we show that mobility-selected ions can be switched intomore » the alternative channel, and that various ion species can be independently selected based on their mobilities for time-of-flight mass spectrometer (TOF MS) IMS detection and mass analysis. Ultimately, this development also provides the basis for e.g. the selection of specific mobilities for storage and accumulation, and key modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations.« less

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

P/Q-type calcium channel modulators

PubMed Central

Nimmrich, V; Gross, G

2012-01-01

P/Q-type calcium channels are high-voltage-gated calcium channels contributing to vesicle release at synaptic terminals. A number of neurological diseases have been attributed to malfunctioning of P/Q channels, including ataxia, migraine and Alzheimer's disease. To date, only two specific P/Q-type blockers are known: both are peptides deriving from the spider venom of Agelenopsis aperta, ω-agatoxins. Other peptidic calcium channel blockers with activity at P/Q channels are available, albeit with less selectivity. A number of low molecular weight compounds modulate P/Q-type currents with different characteristics, and some exhibit a peculiar bidirectional pattern of modulation. Interestingly, there are a number of therapeutics in clinical use, which also show P/Q channel activity. Because selectivity as well as the exact mode of action is different between all P/Q-type channel modulators, the interpretation of clinical and experimental data is complicated and needs a comprehensive understanding of their target profile. The situation is further complicated by the fact that information on potency varies vastly in the literature, which may be the result of different experimental systems, conditions or the splice variants of the P/Q channel. This review attempts to provide a comprehensive overview of the compounds available that affect the P/Q-type channel and should help with the interpretation of results of in vitro experiments and animal models. It also aims to explain some clinical observations by implementing current knowledge about P/Q channel modulation of therapeutically used non-selective drugs. Chances and challenges of the development of P/Q channel-selective molecules are discussed. PMID:22670568

Robust Control for the Mercury Laser Altimeter

NASA Technical Reports Server (NTRS)

Rosenberg, Jacob S.

2006-01-01

Mercury Laser Altimeter Science Algorithms is a software system for controlling the laser altimeter aboard the Messenger spacecraft, which is to enter into orbit about Mercury in 2011. The software will control the altimeter by dynamically modifying hardware inputs for gain, threshold, channel-disable flags, range-window start location, and range-window width, by using ranging information provided by the spacecraft and noise counts from instrument hardware. In addition, because of severe bandwidth restrictions, the software also selects returns for downlink.

Identification of Intracellular β-Barrel Residues Involved in Ion Selectivity in the Mechanosensitive Channel of Thermoanaerobacter tengcongensis

PubMed Central

Song, Yingcai; Zhang, Bing; Guo, Fei; Yang, Maojun; Li, Yang; Liu, Zhi-Qiang

2017-01-01

The mechanosensitive channel of small conductance (MscS) is a bacterial membrane pore that senses membrane tension and protects cells from lysis by releasing osmolytes. MscS is a homoheptameric channel with a cytoplasmic domain with seven portals and a β-barrel opening to the cytoplasm. TtMscS, an MscS channel from Thermoanaerobacter tengcongensis, is an anion-selective channel. A previous study from our laboratory has defined the crucial role of β-barrel in the anion selectivity of TtMscS (Zhang et al., 2012). However, the mechanistic details by which the β-barrel determines anion selectivity remain unclear. Here, using mutagenesis and patch-clamp recordings, we investigated the function and structural correlations between β-barrels and the anion selectivity of TtMscS at the atomic level. Our results indicated that mutation of V274, a residue at the center of the inner wall of the β-barrel in TtMscS, caused the anion selectivity of TtMscS reverse to cation selectivity. Moreover, the electrostatic potential (T272) and physical size (L276) of residues in the inner wall of β-barrel also determine the anion selectivity of TtMscS. In summary, the present study confirmed that the β-barrel region of TtMscS acts as a “selective filter” that renders TtMscS anion selectivity. PMID:29118717

Gating of a pH-sensitive K(2P) potassium channel by an electrostatic effect of basic sensor residues on the selectivity filter.

PubMed

Zúñiga, Leandro; Márquez, Valeria; González-Nilo, Fernando D; Chipot, Christophe; Cid, L Pablo; Sepúlveda, Francisco V; Niemeyer, María Isabel

2011-01-25

K(+) channels share common selectivity characteristics but exhibit a wide diversity in how they are gated open. Leak K(2P) K(+) channels TASK-2, TALK-1 and TALK-2 are gated open by extracellular alkalinization. The mechanism for this alkalinization-dependent gating has been proposed to be the neutralization of the side chain of a single arginine (lysine in TALK-2) residue near the pore of TASK-2, which occurs with the unusual pK(a) of 8.0. We now corroborate this hypothesis by transplanting the TASK-2 extracellular pH (pH(o)) sensor in the background of a pH(o)-insensitive TASK-3 channel, which leads to the restitution of pH(o)-gating. Using a concatenated channel approach, we also demonstrate that for TASK-2 to open, pH(o) sensors must be neutralized in each of the two subunits forming these dimeric channels with no apparent cross-talk between the sensors. These results are consistent with adaptive biasing force analysis of K(+) permeation using a model selectivity filter in wild-type and mutated channels. The underlying free-energy profiles confirm that either a doubly or a singly charged pH(o) sensor is sufficient to abolish ion flow. Atomic detail of the associated mechanism reveals that, rather than a collapse of the pore, as proposed for other K(2P) channels gated at the selectivity filter, an increased height of the energetic barriers for ion translocation accounts for channel blockade at acid pH(o). Our data, therefore, strongly suggest that a cycle of protonation/deprotonation of pH(o)-sensing arginine 224 side chain gates the TASK-2 channel by electrostatically tuning the conformational stability of its selectivity filter.

Gating of a pH-Sensitive K2P Potassium Channel by an Electrostatic Effect of Basic Sensor Residues on the Selectivity Filter

PubMed Central

Zúñiga, Leandro; Márquez, Valeria; González-Nilo, Fernando D.; Chipot, Christophe; Cid, L. Pablo; Sepúlveda, Francisco V.; Niemeyer, María Isabel

2011-01-01

K+ channels share common selectivity characteristics but exhibit a wide diversity in how they are gated open. Leak K2P K+ channels TASK-2, TALK-1 and TALK-2 are gated open by extracellular alkalinization. The mechanism for this alkalinization-dependent gating has been proposed to be the neutralization of the side chain of a single arginine (lysine in TALK-2) residue near the pore of TASK-2, which occurs with the unusual pKa of 8.0. We now corroborate this hypothesis by transplanting the TASK-2 extracellular pH (pHo) sensor in the background of a pHo-insensitive TASK-3 channel, which leads to the restitution of pHo-gating. Using a concatenated channel approach, we also demonstrate that for TASK-2 to open, pHo sensors must be neutralized in each of the two subunits forming these dimeric channels with no apparent cross-talk between the sensors. These results are consistent with adaptive biasing force analysis of K+ permeation using a model selectivity filter in wild-type and mutated channels. The underlying free-energy profiles confirm that either a doubly or a singly charged pHo sensor is sufficient to abolish ion flow. Atomic detail of the associated mechanism reveals that, rather than a collapse of the pore, as proposed for other K2P channels gated at the selectivity filter, an increased height of the energetic barriers for ion translocation accounts for channel blockade at acid pHo. Our data, therefore, strongly suggest that a cycle of protonation/deprotonation of pHo-sensing arginine 224 side chain gates the TASK-2 channel by electrostatically tuning the conformational stability of its selectivity filter. PMID:21283586

Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue

PubMed Central

Smith, Carolyn L.; Abdallah, Salsabil; Le, Phuong; Harracksingh, Alicia N.; Artinian, Liana; Tamvacakis, Arianna N.; Rehder, Vincent; Reese, Thomas S.

2017-01-01

Four-domain voltage-gated Ca2+ (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells. Here, we characterize the single T-type calcium channel from Trichoplax adhaerens (TCav3), an early diverging animal that lacks muscle, neurons, and synapses. Co-immunolocalization using antibodies against TCav3 and neurosecretory cell marker complexin labeled gland cells, which are hypothesized to play roles in paracrine signaling. Cloning and in vitro expression of TCav3 reveals that, despite roughly 600 million years of divergence from other T-type channels, it bears the defining structural and biophysical features of the Cav3 family. We also characterize the channel’s cation permeation properties and find that its pore is less selective for Ca2+ over Na+ compared with the human homologue Cav3.1, yet it exhibits a similar potent block of inward Na+ current by low external Ca2+ concentrations (i.e., the Ca2+ block effect). A comparison of the permeability features of TCav3 with other cloned channels suggests that Ca2+ block is a locus of evolutionary change in T-type channel cation permeation properties and that mammalian channels distinguish themselves from invertebrate ones by bearing both stronger Ca2+ block and higher Ca2+ selectivity. TCav3 is the most divergent metazoan T-type calcium channel and thus provides an evolutionary perspective on Cav3 channel structure–function properties, ion selectivity, and cellular physiology. PMID:28330839

No moving parts safe & arm apparatus and method with monitoring and built-in-test for optical firing of explosive systems

DOEpatents

Hendrix, J.L.

1995-04-11

A laser initiated ordnance controller apparatus which provides a safe and arm scheme with no moving parts. The safe & arm apparatus provides isolation of firing energy to explosive devices using a combination of polarization isolation and control through acousto-optical deviation of laser energy pulses. The apparatus provides constant monitoring of the systems status and performs 100% built-in-test at any time prior to ordnance ignition without the risk of premature ignition or detonation. The apparatus has a computer controller, a solid state laser, an acousto-optic deflector and RF drive circuitry, built-in-test optics and electronics, and system monitoring capabilities. The optical system is completed from the laser beam power source to the pyrotechnic ordnance through fiber optic cabling, optical splitters and optical connectors. During operation of the apparatus, a command is provided by the computer controller and, simultaneous with laser flashlamp fire, the safe & arm device is opened for approximately 200 microseconds which allows the laser pulse to transmit through the device. The arm signal also energizes the laser power supply and activates the acousto-optical deflector. When the correct fire format command is received, the acousto-optic deflector moves to the selected event channel, and the channel is verified to ensure the system is pointing to the correct position. Laser energy is transmitted through the fiber where an ignitor or detonator designed to be sensitive to optical pulses is fired at the end of the fiber channel. Simultaneous event channels may also be utilized by optically splitting a single event channel. The built-in-test may be performed anytime prior to ordnance ignition. 6 figures.

No moving parts safe & arm apparatus and method with monitoring and built-in-test for optical firing of explosive systems

DOEpatents

Hendrix, James L.

1995-01-01

A laser initiated ordnance controller apparatus which provides a safe and m scheme with no moving parts. The safe & arm apparatus provides isolation of firing energy to explosive devices using a combination of polarization isolation and control through acousto-optical deviation of laser energy pulses. The apparatus provides constant monitoring of the systems status and performs 100% built-in-test at any time prior to ordnance ignition without the risk of premature ignition or detonation. The apparatus has a computer controller, a solid state laser, an acousto-optic deflector and RF drive circuitry, built-in-test optics and electronics, and system monitoring capabilities. The optical system is completed from the laser beam power source to the pyrotechnic ordnance through fiber optic cabling, optical splitters and optical connectors. During operation of the apparatus, a command is provided by the computer controller and, simultaneous with laser flashlamp fire, the safe & arm device is opened for approximately 200 microseconds which allows the laser pulse to transmit through the device. The arm signal also energizes the laser power supply and activates the acousto-optical deflector. When the correct fire format command is received, the acousto-optic deflector moves to the selected event channel, and the channel is verified to ensure the system is pointing to the correct position. Laser energy is transmitted through the fiber where an ignitor or detonator designed to be sensitive to optical pulses is fired at the end of the fiber channel. Simultaneous event channels may also be utilized by optically splitting a single event channel. The built-in-test may be performed anytime prior to ordnance ignition.

[Portable multi-purpose device for monitoring of physiological informations].

PubMed

Tamura, T; Togawa, T

1983-05-01

Unconstrained system that measures physiological information as skin temperatures and heart rate per unit time of a human subject was developed. The system contained portable device included memory control unit, instrumentation unit, timer and batteries, read-out unit, test unit and verify unit. Total number of data and channels, and interval were selected by switches in the memory control unit. The data from the instrumentation unit were transferred to memory control unit and stored in the Erasable Programmable ROM (EPROM). After measurement, EPROM chip was taken off the memory control unit and put on the read-out unit which transferred the data to the microcomputer. The data were directly calculated and analyzed by microcomputer. In application of the instrumentation unit, 8-channel skin thermometer was developed and tested. After amplification, 8 analog signals were multiplexed and converted into the binary codes. The digital signals were sequentially transferred to memory control unit and stored in the EPROM under controlled signal. The accuracy of the system is determined primarily by the accuracy of the sensor of instrumentation unit. The overall accuracy of 8-channel skin thermometer is conservatively stated within 0.1 degree C. This may prove to be useful in providing an objective measurement of human subjects, and can be used in studying environmental effect for human body and sport activities in a large population setting.

Electromechanical flight control actuator, volume 3

NASA Technical Reports Server (NTRS)

1978-01-01

The design verification tests which were conducted on the electromechanical actuator are described. A description is also given of the power components tests which were conducted to aid in selecting the power transistors for use in the single-channel power electronics breadboard and the results of tests which were conducted on the power electronics breadboard.

Recent applications of liquid metals featuring nanoscale surface oxides

NASA Astrophysics Data System (ADS)

Neumann, Taylor V.; Dickey, Michael D.

2016-05-01

This proceeding describes recent efforts from our group to control the shape and actuation of liquid metal. The liquid metal is an alloy of gallium and indium which is non-toxic, has negligible vapor pressure, and develops a thin, passivating surface oxide layer. The surface oxide allows the liquid metal to be patterned and shaped into structures that do not minimize interfacial energy. The surface oxide can be selectively removed by changes in pH or by applying a voltage. The surface oxide allows the liquid metal to be 3D printed to form free-standing structures. It also allows for the liquid metal to be injected into microfluidic channels and to maintain its shape within the channels. The selective removal of the oxide results in drastic changes in surface tension that can be used to control the flow behavior of the liquid metal. The metal can also wet thin, solid films of metal that accelerates droplets of the liquid along the metal traces .Here we discuss the properties and applications of liquid metal to make soft, reconfigurable electronics.

A modern ionotropic glutamate receptor with a K(+) selectivity signature sequence.

PubMed

Janovjak, H; Sandoz, G; Isacoff, E Y

2011-01-01

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K(+) channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.

Type-controlled nanodevices based on encapsulated few-layer black phosphorus for quantum transport

NASA Astrophysics Data System (ADS)

Long, Gen; Xu, Shuigang; Shen, Junying; Hou, Jianqiang; Wu, Zefei; Han, Tianyi; Lin, Jiangxiazi; Wong, Wing Ki; Cai, Yuan; Lortz, Rolf; Wang, Ning

2016-09-01

We demonstrate that encapsulation of atomically thin black phosphorus (BP) by hexagonal boron nitride (h-BN) sheets is very effective for minimizing the interface impurities induced during fabrication of BP channel material for quantum transport nanodevices. Highly stable BP nanodevices with ultrahigh mobility and controllable types are realized through depositing appropriate metal electrodes after conducting a selective etching to the BP encapsulation structure. Chromium and titanium are suitable metal electrodes for BP channels to control the transition from a p-type unipolar property to ambipolar characteristic because of different work functions. Record-high mobilities of 6000 cm2 V-1 s-1 and 8400 cm2 V-1 s-1 are respectively obtained for electrons and holes at cryogenic temperatures. High-mobility BP devices enable the investigation of quantum oscillations with an indistinguishable Zeeman effect in laboratory magnetic field.

Electrode channel selection based on backtracking search optimization in motor imagery brain-computer interfaces.

PubMed

Dai, Shengfa; Wei, Qingguo

2017-01-01

Common spatial pattern algorithm is widely used to estimate spatial filters in motor imagery based brain-computer interfaces. However, use of a large number of channels will make common spatial pattern tend to over-fitting and the classification of electroencephalographic signals time-consuming. To overcome these problems, it is necessary to choose an optimal subset of the whole channels to save computational time and improve the classification accuracy. In this paper, a novel method named backtracking search optimization algorithm is proposed to automatically select the optimal channel set for common spatial pattern. Each individual in the population is a N-dimensional vector, with each component representing one channel. A population of binary codes generate randomly in the beginning, and then channels are selected according to the evolution of these codes. The number and positions of 1's in the code denote the number and positions of chosen channels. The objective function of backtracking search optimization algorithm is defined as the combination of classification error rate and relative number of channels. Experimental results suggest that higher classification accuracy can be achieved with much fewer channels compared to standard common spatial pattern with whole channels.

A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels

PubMed Central

Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

2015-01-01

Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K+ channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na+, Cs+, and dimethylammonium (DMA+), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels. PMID:26100907

A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels.

PubMed

Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

2015-07-07

Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K(+) channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na(+), Cs(+), and dimethylammonium (DMA(+)), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels.

Use of color-coded sleeve shutters accelerates oscillograph channel selection

NASA Technical Reports Server (NTRS)

Bouchlas, T.; Bowden, F. W.

1967-01-01

Sleeve-type shutters mechanically adjust individual galvanometer light beams onto or away from selected channels on oscillograph papers. In complex test setups, the sleeve-type shutters are color coded to separately identify each oscillograph channel. This technique could be used on any equipment using tubular galvanometer light sources.

Plasma polar lipid profiles of channel catfish with different growth rates

USDA-ARS?s Scientific Manuscript database

Increased growth in channel catfish is an economically important trait and has been used as a criterion for the selection and development of brood fish. Selection of channel catfish toward increased growth usually results in the accumulation of large amounts of fats in their abdomen rather than incr...

Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels.

PubMed

Mizuno, Masaki; Kamiya, Atsunori; Kawada, Toru; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Sugimachi, Masaru

2008-12-01

Although muscarinic K(+) (K(ACh)) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the K(ACh)channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K(ACh) channel blocker, decreased the dynamic gain (to 2.3+/- 0.9 beats.min(-1).Hz(-1), from 4.6+/- 1.1, P < 0.01, mean+/- SD) and the corner frequency (to 0.05+/- 0.01 Hz, from 0.26+/- 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6+/- 1.0 beats.min(-1).Hz(-1), from 7.3+/- 1.1, P < 0.01) and the corner frequency (to 0.06+/- 0.02 Hz, from 0.23+/- 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the K(ACh) channels. The rapidity of the HR response obtained by the K(ACh) channel pathway was robust during the accentuated antagonism.

Aromatic–aromatic interactions between residues in KCa3.1 pore helix and S5 transmembrane segment control the channel gating process

PubMed Central

Garneau, Line; Klein, Hélène; Lavoie, Marie-France; Brochiero, Emmanuelle; Parent, Lucie

2014-01-01

The Ca2+-activated potassium channel KCa3.1 is emerging as a therapeutic target for a large variety of health disorders. One distinguishing feature of KCa3.1 is that the channel open probability at saturating Ca2+ concentrations (Pomax) is low, typically 0.1–0.2 for KCa3.1 wild type. This observation argues for the binding of Ca2+ to the calmodulin (CaM)–KCa3.1 complex, promoting the formation of a preopen closed-state configuration leading to channel opening. We have previously shown that the KCa3.1 active gate is most likely located at the level of the selectivity filter. As Ca2+-dependent gating of KCa3.1 originates from the binding of Ca2+ to CaM in the C terminus, the hypothesis of a gate located at the level of the selectivity filter requires that the conformational change initiated in the C terminus be transmitted to the S5 and S6 transmembrane helices, with a resulting effect on the channel pore helix directly connected to the selectivity filter. A study was thus undertaken to determine to what extent the interactions between the channel pore helix with the S5 and S6 transmembrane segments contribute to KCa3.1 gating. Molecular dynamics simulations first revealed that the largest contact area between the pore helix and the S5 plus S6 transmembrane helices involves residue F248 at the C-terminal end of the pore helix. Unitary current recordings next confirmed that modulating aromatic–aromatic interactions between F248 and W216 of the S5 transmembrane helical segment and/or perturbing the interactions between F248 and residues in S6 surrounding the glycine hinge G274 cause important changes in Pomax. This work thus provides the first evidence for a key contribution of the pore helix in setting Pomax by stabilizing the channel closed configuration through aromatic–aromatic interactions involving F248 of the pore helix. We propose that the interface pore helix/S5 constitutes a promising site for designing KCa3.1 potentiators. PMID:24470490

Winter habitat use by cutthroat trout in the Snake River near Jackson, Wyoming

USGS Publications Warehouse

Harper, D.D.; Farag, A.M.

2004-01-01

Winter habitat use by Yellowstone cutthroat trout Oncorhynchus clarki bouvieri was monitored with radiotelemetry during November-March 1998-2001 in channelized and unaltered sections of the Snake River near Jackson, Wyoming. The use of run and off-channel pool habitat was significantly correlated to water temperature; run use was most frequent when mean water temperature exceeded 1.0°C, and off-channel pool use was greatest when mean water temperature was below 1.0°C. Available habitat was surveyed during winter 1999-2000 and was compared with actual habitat use. This comparison indicated that cutthroat trout avoided riffle habitat, selected deep runs, and strongly selected off-channel pool habitat. Large, deep, off-channel pools with groundwater influence were uncommon in the study area but were frequently selected as over-wintering habitat in the channelized section during all three study years. During 2000-2001, mainstem water temperatures were significantly colder than in 1998-1999 or 1999-2000, and anchor ice was observed more frequently in 2000-2001 than in 1998-1999 or 1999-2000 (on 18 d versus 5 d and 3 d, respectively). Mean water temperatures in off-channel pools were not significantly different among years. Depth and shelf ice were most frequently identified as cover elements in the channelized section. Run habitat was more common and used more frequently upstream of the channelized section. Large woody debris was more common and selected more frequently as cover in the unaltered section than in the channelized section.

Directional acceleration vector-driven displacement of fluids (DAVD-DOF)

NASA Technical Reports Server (NTRS)

Clarke, Mark S. F. (Inventor); Feeback, Daniel L. (Inventor)

2004-01-01

Centrifugal analyzer and method for staining biological or non-biological samples in microgravity, wherein the method utilizes an increase in weight of a fluid sample as a function of g-load, to overcome cohesive and frictional forces from preventing its movement in a preselected direction. Apparatus is characterized by plural specimen reservoirs and channels in a slide, each channel being of differing cross-section, wherein respective samples are selectively dispensed, from the reservoirs in response to an imposed g-factor, precedent to sample staining. Within the method, one thus employs microscope slides which define channels, each being of a differing cross-section dimension relative to others. In combination therewith, centrifugal slide mounting apparatus controllably imposes g-vectors of differing magnitudes within a defined structure of the centrifuge such as a chip array.

Pharmacological Modulation of Diacylglycerol-Sensitive TRPC3/6/7 Channels

PubMed Central

Harteneck, Christian; Gollasch, Maik

2011-01-01

Members of the classic type of transient receptor potential channels (TRPC) represent important molecules involved in hormonal signal transduction. TRPC3/6/7 channels are of particular interest as they are components of phospholipase C driven signalling pathways. Upon receptor-activation, G-protein-mediated stimulation of phospholipase C results in breakdown of phosphatidylinositides leading to increased intracellular diacylglycerol and inositol-trisphosphate levels. Diacylglycerol activates protein kinase C, but more interestingly diacylglycerol directly activates TRPC2/3/6/7 channels. Molecular cloning, expression and characterization of TRP channels enabled reassignment of traditional inhibitors of receptor-dependent calcium entry such as SKF-96365 and 2-APB as blockers of TRPC3/6/7 and several members of non-classic TRP channels. Furthermore, several enzyme inhibitors have also been identified as TRP channel blockers, such as ACA, a phospholipase A2 inhibitor, and W-7, a calmodulin antagonist. Finally, the naturally occurring secondary plant compound hyperforin has been identified as TRPC6-selective drug, providing an exciting proof of concept that it is possible to generate TRPC-selective channel modulators. The description of Pyr3 as the first TRPC3-selective inhibitor shows that not only nature but also man is able to generate TRP-selective modulators. The review sheds lights on the current knowledge and historical development of pharmacological modulators of TRPC3/6/7. Our analysis indicates that Pyr3 and hyperforin provide promising core structures for the development of new, selective and more potent modulators of TRPC3/6/7 activity. PMID:20932261

Sandhill crane roost selection, human disturbance, and forage resources

USGS Publications Warehouse

Pearse, Aaron T.; Krapu, Gary; Brandt, David

2017-01-01

Sites used for roosting represent a key habitat requirement for many species of birds because availability and quality of roost sites can influence individual fitness. Birds select roost sites based on numerous factors, requirements, and motivations, and selection of roosts can be dynamic in time and space because of various ecological and environmental influences. For sandhill cranes (Antigone canadensis) at their main spring-staging area along the Platte River in south-central Nebraska, USA, past investigations of roosting cranes focused on physical channel characteristics related to perceived security as motivating roost distribution. We used 6,310 roost sites selected by 313 sandhill cranes over 5 spring migration seasons (2003–2007) to quantify resource selection functions of roost sites on the central Platte River using a discrete choice analysis. Sandhill cranes generally showed stronger selection for wider channels with shorter bank vegetation situated farther from potential human disturbance features such as roads, bridges, and dwellings. Furthermore, selection for roost sites with preferable physical characteristics (wide channels with short bank vegetation) was more resilient to nearby disturbance features than more narrow channels with taller bank vegetation. The amount of cornfields surrounding sandhill crane roost sites positively influenced relative probability of use but only for more narrow channels < 100 m and those with shorter bank vegetation. We confirmed key resource features that sandhill cranes selected at river channels along the Platte River, and after incorporating spatial variation due to human disturbance, our understanding of roost site selection was more robust, providing insights on how disturbance may interact with physical habitat features. Managers can use information on roost-site selection when developing plans to increase probability of crane use at existing roost sites and to identify new areas for potential use if existing sites become limited.

RNAi-mediated knockdown of the voltage gated sodium ion channel TcNav causes mortality in Tribolium castaneum.

PubMed

Abd El Halim, Hesham M; Alshukri, Baida M H; Ahmad, Munawar S; Nakasu, Erich Y T; Awwad, Mohammed H; Salama, Elham M; Gatehouse, Angharad M R; Edwards, Martin G

2016-07-14

The voltage-gated sodium ion channel (VGSC) belongs to the largest superfamily of ion channels. Since VGSCs play key roles in physiological processes they are major targets for effective insecticides. RNA interference (RNAi) is widely used to analyse gene function, but recently, it has shown potential to contribute to novel strategies for selectively controlling agricultural insect pests. The current study evaluates the delivery of dsRNA targeted to the sodium ion channel paralytic A (TcNav) gene in Tribolium castaneum as a viable means of controlling this insect pest. Delivery of TcNav dsRNA caused severe developmental arrest with larval mortalities up to 73% post injection of dsRNA. Injected larvae showed significant (p < 0.05) knockdown in gene expression between 30-60%. Expression was also significantly (p < 0.05) reduced in pupae following injection causing 30% and 42% knockdown for early and late pupal stages, respectively. Oral delivery of dsRNA caused dose-dependant mortalities of between 19 and 51.34%; this was accompanied by significant (p < 0.05) knockdown in gene expression following 3 days of continuous feeding. The majority of larvae injected with, or fed, dsRNA died during the final larval stage prior to pupation. This work provides evidence of a viable RNAi-based strategy for insect control.

Solid state television camera (CCD-buried channel)

NASA Technical Reports Server (NTRS)

1976-01-01

The development of an all solid state television camera, which uses a buried channel charge coupled device (CCD) as the image sensor, was undertaken. A 380 x 488 element CCD array is utilized to ensure compatibility with 525 line transmission and display monitor equipment. Specific camera design approaches selected for study and analysis included (a) optional clocking modes for either fast (1/60 second) or normal (1/30 second) frame readout, (b) techniques for the elimination or suppression of CCD blemish effects, and (c) automatic light control and video gain control (i.e., ALC and AGC) techniques to eliminate or minimize sensor overload due to bright objects in the scene. Preferred approaches were determined and integrated into a deliverable solid state TV camera which addressed the program requirements for a prototype qualifiable to space environment conditions.

Solid state television camera (CCD-buried channel), revision 1

NASA Technical Reports Server (NTRS)

1977-01-01

An all solid state television camera was designed which uses a buried channel charge coupled device (CCD) as the image sensor. A 380 x 488 element CCD array is utilized to ensure compatibility with 525-line transmission and display monitor equipment. Specific camera design approaches selected for study and analysis included (1) optional clocking modes for either fast (1/60 second) or normal (1/30 second) frame readout, (2) techniques for the elimination or suppression of CCD blemish effects, and (3) automatic light control and video gain control techniques to eliminate or minimize sensor overload due to bright objects in the scene. Preferred approaches were determined and integrated into a deliverable solid state TV camera which addressed the program requirements for a prototype qualifiable to space environment conditions.

Solid state, CCD-buried channel, television camera study and design

NASA Technical Reports Server (NTRS)

Hoagland, K. A.; Balopole, H.

1976-01-01

An investigation of an all solid state television camera design, which uses a buried channel charge-coupled device (CCD) as the image sensor, was undertaken. A 380 x 488 element CCD array was utilized to ensure compatibility with 525 line transmission and display monitor equipment. Specific camera design approaches selected for study and analysis included (a) optional clocking modes for either fast (1/60 second) or normal (1/30 second) frame readout, (b) techniques for the elimination or suppression of CCD blemish effects, and (c) automatic light control and video gain control techniques to eliminate or minimize sensor overload due to bright objects in the scene. Preferred approaches were determined and integrated into a design which addresses the program requirements for a deliverable solid state TV camera.

Habitat associations of three crayfish endemic to the Ouachita Mountain Ecoregion

USGS Publications Warehouse

Dyer, Joseph J.; Brewer, Shannon K.

2018-01-01

Many crayfish are of conservation concern because of their use of unique habitats and often narrow ranges. In this study, we determined fine-scale habitat use by 3 crayfishes that are endemic to the Ouachita Mountains, in Oklahoma and Arkansas. We sampled Faxonius menae (Mena Crayfish), F. leptogonopodus (Little River Creek Crayfish), and Fallicambarus tenuis (Ouachita Mountain Crayfish) from wet and dry erosional channel units of 29 reaches within the Little River catchment. We compared channel-unit and microhabitat selection for each species. Crayfish of all species and life stages selected erosional channel units more often than depositional units, even though these sites were often dry. Accordingly, crayfish at all life stages typically selected the shallowest available microhabitats. Adult crayfish of all species and juvenile Little River Creek Crayfish selected patches of coarse substrate, and all crayfish tended to use the lowest amount of bedrock available. In general, we showed that these endemic crayfish used erosional channel units of streams, even when the channel units were dry. Conservation efforts that protect erosional channel units and mitigate actions that cause channel downcutting to bedrock would benefit these crayfish, particularly during harsh, summer drying periods.

Role of antispasmodics in the treatment of irritable bowel syndrome

PubMed Central

Annaházi, Anita; Róka, Richárd; Rosztóczy, András; Wittmann, Tibor

2014-01-01

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS. PMID:24876726

Neurological perspectives on voltage-gated sodium channels

PubMed Central

Linley, John E.; Baker, Mark D.; Minett, Michael S.; Cregg, Roman; Werdehausen, Robert; Rugiero, François

2012-01-01

The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain. Recent genetic studies have now expanded the role of sodium channels in health and disease, to include autism, migraine, multiple sclerosis, cancer as well as muscle and immune system disorders. Transgenic mouse models have proved useful in understanding the physiological role of individual sodium channels, and there has been significant progress in the development of subtype selective inhibitors of sodium channels. This review will outline the functions and roles of specific sodium channels in electrical signalling and disease, focusing on neurological aspects. We also discuss recent advances in the development of selective sodium channel inhibitors. PMID:22961543

Functional reconstitution of the voltage-regulated sodium channel purified from electroplax of Electrophorus electricus

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

Rosenberg, R.L.

1985-01-01

The voltage-regulated NA channel is responsible for the depolarization of the excitable cell membrane during the normal action potential. This research has focused on the functional properties of the Na channel, purified from detergent extracts of electroplax membranes of the electric eel, and reconstituted into vesicles of defined phospholipid. These properties were assessed by measuring neurotoxin-modulated ion flux into the reconstituted membrane vesicles and by recording the single-channel currents of the purified channel by the patch-clamp method. The binding of tritiated tetrodotoxin (TTX) was employed as a marker for the purification of the channel. Two high-resolution fractionation steps, based onmore » molecular charge and protein size, were used to obtain a preparation that is 80% homogeneous for a large peptide of 270,000 daltons. Radiotracer /sup 22/Na/sup +/ influx into the vesicles was stimulated by veratridine and by batrachotoxin (BTX) at concentrations of 100 ..mu..M and 5 ..mu..M, respectively. The stimulation by BTX was greater than that by veratridine, and can be as much as 16-fold over control influx levels. The stimulated influx is blocked by TTX with a K/sub i/ of 35 nM, and by local anesthetics in the normal pharmacological range. Large multilamellar vesicles prepared with a freeze-thaw step are suitable for single-channel recording techniques. When excised patches of the reconstituted membranes were voltage-clamped in the absence of activating neurotoxins, voltage-dependent single-channel currents were recorded. These displayed properties similar to those from native membranes of nerve and muscle. These results indicate that the protein purified on the basis of TTX binding is a functional Na channel possessing these functional domains: the ion-selective channel, the voltage sensors controlling activation and inactivation, and the sites of action of TTX, alkaloid neurotoxins, and local anesthetics.« less

Electrophysiological channel interactions using focused multipolar stimulation for cochlear implants

NASA Astrophysics Data System (ADS)

George, Shefin S.; Shivdasani, Mohit N.; Wise, Andrew K.; Shepherd, Robert K.; Fallon, James B.

2015-12-01

Objective. Speech intelligibility with existing multichannel cochlear implants (CIs) is thought to be limited by poor spatial selectivity and interactions between CI channels caused by overlapping activation with monopolar (MP) stimulation. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation in the inferior colliculus (IC), compared to MP stimulation. Approach. This study explored interactions in the IC produced by simultaneous stimulation of two CI channels. We recorded multi-unit neural activity in the IC of anaesthetized cats with normal and severely degenerated spiral ganglion neuron populations in response to FMP, TP and MP stimulation from a 14 channel CI. Stimuli were applied to a ‘fixed’ CI channel, chosen toward the middle of the cochlear electrode array, and the effects of simultaneously stimulating a more apical ‘test’ CI channel were measured as a function of spatial separation between the two stimulation channels and stimulus level of the fixed channel. Channel interactions were quantified by changes in neural responses and IC threshold (i.e., threshold shift) elicited by simultaneous stimulation of two CI channels, compared to stimulation of the test channel alone. Main results. Channel interactions were significantly lower for FMP and TP than for MP stimulation (p < 0.001), whereas no significant difference was observed between FMP and TP stimulation. With MP stimulation, threshold shifts increased with decreased inter-electrode spacing and increased stimulus levels of the fixed channel. For FMP and TP stimulation, channel interactions were found to be similar for different inter-electrode spacing and stimulus levels of the fixed channel. Significance. The present study demonstrates how the degree of channel interactions in a CI can be controlled using stimulation configurations such as FMP and TP; such knowledge is essential in enhancing CI function in complex acoustic environments.

Mus musculus-microRNA-449a ameliorates neuropathic pain by decreasing the level of KCNMA1 and TRPA1, and increasing the level of TPTE.

PubMed

Lu, Shan; Ma, Sichao; Wang, Yunyun; Huang, Tao; Zhu, Zhihua; Zhao, Guoqing

2017-07-01

Neuropathic pain is a nerve disorder characterized by the dysregulation of ion channels in dorsal root ganglion (DRG) neurons. MicroRNAs (miRs) may be associated with the molecular mechanisms underlying the altered levels of ion channels; however, the molecular mechanisms remain widely unknown. To investigate these mechanisms, the present study conducted a genomic analysis of miR between a unilateral spared nerve injury (SNI) model and sham control. Differentially expressed miRs between the SNI and sham groups were selected for transfection of DRG cells, a polymerase chain reaction (PCR) array analysis was subsequently performed. A total of three significantly differently expressed genes were selected from the results of the PCR array and further analyzed by reverse transcription‑quantitative PCR. Genomic analysis revealed that Mus musculus miR‑449a (mmu‑miR‑449a) was reduced in the SNI groups compared with the sham controls. The PCR array indicated that mmu‑miR‑449a‑transfection reduced the mRNA expression levels of transient receptor potential cation channel subfamily A member 1 (TRPA1), and calcium‑activated potassium channel subunit α‑1 (KCNMA1) and increased the level of transmembrane phosphatase with tension homology (TPTE) in the DRG cells (P<0.05). qRT‑PCR analysis further indicated that mmu‑miR‑449a transfection caused similar alterations in the mRNA expression levels of TRPA1, KCNMA1 and TPTE in DRG cells, respectively (P<0.05). Therefore, mmu‑miR‑449a may ameliorate neuropathic pain by decreasing the activity of the channel proteins TRPA1 and KCNMA1 and increasing the levels of TPTE. mmu‑miR‑449a may be a potential therapeutic molecule for the alleviation of neuropathic pain.

PyFLOWGO: An open-source platform for simulation of channelized lava thermo-rheological properties

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

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.

Purification and Characterization of Two Voltage-Dependent Anion Channel Isoforms from Plant Seeds1

PubMed Central

Abrecht, Helge; Wattiez, Ruddy; Ruysschaert, Jean-Marie; Homblé, Fabrice

2000-01-01

Mitochondria were isolated from imbibed seeds of lentil (Lens culinaris) and Phaseolus vulgaris. We copurified two voltage-dependent anion channel from detergent solubilized mitochondria in a single purification step using hydroxyapatite. The two isoforms from P. vulgaris were separated by chromatofocusing chromatography in 4 m urea without any loss of channel activity. Channel activity of each isoform was characterized upon reconstitution into diphytanoyl phosphatidylcholine planar lipid bilayers. Both isoforms form large conductance channels that are slightly anion selective and display cation selective substates. PMID:11080295

Lipid microdomains and the regulation of ion channel function

PubMed Central

Dart, Caroline

2010-01-01

Many types of ion channel localize to cholesterol and sphingolipid-enriched regions of the plasma membrane known as lipid microdomains or ‘rafts’. The precise physiological role of these unique lipid microenvironments remains elusive due largely to difficulties associated with studying these potentially extremely small and dynamic domains. Nevertheless, increasing evidence suggests that membrane rafts regulate channel function in a number of different ways. Raft-enriched lipids such as cholesterol and sphingolipids exert effects on channel activity either through direct protein–lipid interactions or by influencing the physical properties of the bilayer. Rafts also appear to selectively recruit interacting signalling molecules to generate subcellular compartments that may be important for efficient and selective signal transduction. Direct interaction with raft-associated scaffold proteins such as caveolin can also influence channel function by altering gating kinetics or by affecting trafficking and surface expression. Selective association of ion channels with specific lipid microenvironments within the membrane is thus likely to be an important and fundamental regulatory aspect of channel physiology. This brief review highlights some of the existing evidence for raft modulation of channel function. PMID:20519314

Design of a Mobile Brain Computer Interface-Based Smart Multimedia Controller

PubMed Central

Tseng, Kevin C.; Lin, Bor-Shing; Wong, Alice May-Kuen; Lin, Bor-Shyh

2015-01-01

Music is a way of expressing our feelings and emotions. Suitable music can positively affect people. However, current multimedia control methods, such as manual selection or automatic random mechanisms, which are now applied broadly in MP3 and CD players, cannot adaptively select suitable music according to the user’s physiological state. In this study, a brain computer interface-based smart multimedia controller was proposed to select music in different situations according to the user’s physiological state. Here, a commercial mobile tablet was used as the multimedia platform, and a wireless multi-channel electroencephalograph (EEG) acquisition module was designed for real-time EEG monitoring. A smart multimedia control program built in the multimedia platform was developed to analyze the user’s EEG feature and select music according his/her state. The relationship between the user’s state and music sorted by listener’s preference was also examined in this study. The experimental results show that real-time music biofeedback according a user’s EEG feature may positively improve the user’s attention state. PMID:25756862

Performance comparison between packet and continuous data transmission using two adaptive equalizers in shallow water

NASA Astrophysics Data System (ADS)

Yoon, Jong Rak; Park, Kyu-Chil; Park, Jihyun

2015-07-01

Transmitted signals are markedly affected by sea surface and bottom boundaries in shallow water. The time variant reflection signals from such boundaries characterize the channel as a frequency-selective fading channel and cause intersymbol interference (ISI) in underwater acoustic communication. A channel-estimate-based equalizer is usually adopted to compensate for the reflected signals under this kind of acoustic channel. In this study, we apply two approaches for packet and continuous data transmission of the quadrature phase shift keying (QPSK) system. One is the use of a two-dimensional (2D) rotation matrix in a non-frequency-selective channel. The other is the use of two equalizers of types — the feed forward equalizer (FFE) and decision-directed equalizer (DDE) — with a normalized least mean square (NLMS) algorithm in a frequency-selective channel. The percentage improvement of packet transmission is notably better than that of continuous transmission.

Enzyme-like specificity in zeolites: a unique site position in mordenite for selective carbonylation of methanol and dimethyl ether with CO.

PubMed

Boronat, Mercedes; Martínez-Sánchez, Cristina; Law, David; Corma, Avelino

2008-12-03

The mechanism of methanol carbonylation at different positions of zeolite MOR is investigated by quantum-chemical methods in order to discover which are the active sites that can selectively catalyze the desired reaction. It is shown that when methanol carbonylation competes with hydrocarbon formation, the first reaction occurs preferentially within 8MR channels. However, the unique selectivity for the carbonylation of methanol and dimethyl ether in mordenite is not only due to the size of the 8MR channel: neither process occurs equally at the two T3-O31 and T3-O33 positions. We show that only the T3-O33 positions are selective and that this selectivity is due to the unusual orientation of the methoxy group in relation to the 8MR channel (parallel to the cylinder axis). Only in this situation does the transition state for the attack of CO fit perfectly in the 8MR channel, while the reaction with methanol or DME is sterically impeded. This result explains why T3-O31, while also located in the 8MR channel of mordenite, is not as selective as the T3-O33 position and why ferrierite, although it contains 8MR channels, is less selective than mordenite. The competing effect of water is explained at the molecular level, and the molecular microkinetic reaction model has been established.

Viking 1975 Orbiter Development Test Model/Lander Dynamic Test Model dynamic environmental testing - An overview

NASA Technical Reports Server (NTRS)

Milder, G.

1975-01-01

The current work presents an overview of the Viking 1975 environmental testing from an engineering standpoint. An extremely large vibration test fixture had to be designed, analyzed, and integrated into a test setup that employed hydrostatic bearings in a new fashion. A vibration control system was also required that would allow for thirty-six channels of sine-wave peak select control from acceleration, force-of-strain transducers. In addition, some 68 channels of peak limiting shutdown capability were needed for backup and monitoring of other data during the forced vibration test. Pretesting included analyses of the fixture design, overturning moment, control system capabilities, and response of the entire spacecraft/fixture/exciter system to the test environment. Closed-loop control for acoustic testing was a necessity due to the fact that the Viking spacecraft took up a major portion of the volume of the 10,000 cu ft chamber. The spacecraft emerged from testing undamaged.

Critical band masking reveals the effects of optical distortions on the channel mediating letter identification.

PubMed

Young, Laura K; Smithson, Hannah E

2014-01-01

There is evidence that letter identification is mediated by only a narrow band of spatial frequencies and that the center frequency of the neural channel thought to underlie this selectivity is related to the size of the letters. When letters are spatially filtered (at a fixed size) the channel tuning characteristics change according to the properties of the spatial filter (Majaj et al., 2002). Optical aberrations in the eye act to spatially filter the image formed on the retina-their effect is generally to attenuate high frequencies more than low frequencies but often in a non-monotonic way. We might expect the change in the spatial frequency spectrum caused by the aberration to predict the shift in channel tuning observed for aberrated letters. We show that this is not the case. We used critical-band masking to estimate channel-tuning in the presence of three types of aberration-defocus, coma and secondary astigmatism. We found that the maximum masking was shifted to lower frequencies in the presence of an aberration and that this result was not simply predicted by the spatial-frequency-dependent degradation in image quality, assessed via metrics that have previously been shown to correlate well with performance loss in the presence of an aberration. We show that if image quality effects are taken into account (using visual Strehl metrics), the neural channel required to model the data is shifted to lower frequencies compared to the control (no-aberration) condition. Additionally, we show that when spurious resolution (caused by π phase shifts in the optical transfer function) in the image is masked, the channel tuning properties for aberrated letters are affected, suggesting that there may be interference between visual channels. Even in the presence of simulated aberrations, whose properties change from trial-to-trial, observers exhibit flexibility in selecting the spatial frequencies that support letter identification.

Energy efficient window and skylight assemblies

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

Howe, W.C. Jr.

1986-03-25

A totally self-contained apparatus is described for use as a window or skylight assembly, and adapted for simultaneously controlling the amount of both sunlight and air admitted into a building. The apparatus consists of: a head member and a sill member; a first sheet of material through which sunlight can pass, the first sheet of material forming a major portion of the exterior surface of the apparatus and being mounted between the head and sill members; a second sheet of material through which sunlight can pass, the second sheet of material being spaced from the first sheet of material themore » second sheet of material forming a major portion of the interior surface of the window apparatus and being mounted between the head and sill members; first and second window jams positioned between the first and second sheets of material and extending from the head member to the sill member so as to form an essentially enclosed air flow channel; means, positioned in the air flow channel, for regulating the amount of sunlight passing through the apparatus; and ventilation means for directing air through the air flow channel, and comprising a motor-driven fan mounted within the air flow channel at one end thereof so as to circulate air through the air flow channel together with a plurality of apertures disposed in the head and sill members for placing the air flow channel in communication with the interior and exterior of the building and means for selectively opening and closing the apertures whereby air may selectively flow from one of (a) the outside to the inside of the building, (b) from the inside to the outside of the building, (c) from the inside of the building through the air flow channel and back to the inside of the building and (d) from the outside of the building through the air flow channel and back to the outside of the building.« less

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

Evaluation of Dynamic Channel and Power Assignment for Cognitive Networks

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

Syed A. Ahmad; Umesh Shukla; Ryan E. Irwin

2011-03-01

In this paper, we develop a unifying optimization formulation to describe the Dynamic Channel and Power Assignment (DCPA) problem and evaluation method for comparing DCPA algorithms. DCPA refers to the allocation of transmit power and frequency channels to links in a cognitive network so as to maximize the total number of feasible links while minimizing the aggregate transmit power. We apply our evaluation method to five algorithms representative of DCPA used in literature. This comparison illustrates the tradeoffs between control modes (centralized versus distributed) and channel/power assignment techniques. We estimate the complexity of each algorithm. Through simulations, we evaluate themore » effectiveness of the algorithms in achieving feasible link allocations in the network, as well as their power efficiency. Our results indicate that, when few channels are available, the effectiveness of all algorithms is comparable and thus the one with smallest complexity should be selected. The Least Interfering Channel and Iterative Power Assignment (LICIPA) algorithm does not require cross-link gain information, has the overall lowest run time, and highest feasibility ratio of all the distributed algorithms; however, this comes at a cost of higher average power per link.« less

Solvent-programmed microchip open-channel electrochromatography.

PubMed

Kutter, J P; Jacobson, S C; Matsubara, N; Ramsey, J M

1998-08-01

Open-channel electrochromatography in combination with solvent programming is demonstrated using a microchip device. Channel walls were coated with octadecylsilanes at ambient temperatures, yielding stationary phases for chromatographic separations of neutral dyes. The electroosmotic flow after coating was sufficient to ensure transport of all species and on-chip mixing of isocratic and gradient elution conditions with acetonitrile-buffer mixtures. Chips having different channel depths between 10.2 and 2.9 μm were evaluated for performance, and van Deemter plots were established. Channel depths of about 5 μm were found to be a good compromise between efficiency and ease of operation. Isocratic and gradient elution conditions were easily established and manipulated by computer-controlled application of voltages to the terminals of the microchip. Linear gradients with different slopes, start times, duration times, and start percentages of organic modifier proved to be powerful tools to tune selectivity and analysis time for the separation of a test mixture. Even very steep gradients still produced excellent efficiencies. Together with fast reconditioning times, complete runs could be finished in under 60 s.

Schottky barrier MOSFET systems and fabrication thereof

DOEpatents

Welch, James D.

1997-01-01

(MOS) device systems-utilizing Schottky barrier source and drain to channel region junctions are disclosed. Experimentally derived results which demonstrate operation of fabricated N-channel and P-channel Schottky barrier (MOSFET) devices, and of fabricated single devices with operational characteristics similar to (CMOS) and to a non-latching (SRC) are reported. Use of essentially non-rectifying Schottky barriers in (MOS) structures involving highly doped and the like and intrinsic semiconductor to allow non-rectifying interconnection of, and electrical accessing of device regions is also disclosed. Insulator effected low leakage current device geometries and fabrication procedures therefore are taught. Selective electrical interconnection of drain to drain, source to drain, or source to source, of N-channel and/or P-channel Schottky barrier (MOSFET) devices formed on P-type, N-type and Intrinsic semiconductor allows realization of Schottky Barrier (CMOS), (MOSFET) with (MOSFET) load, balanced differential (MOSFET) device systems and inverting and non-inverting single devices with operating characteristics similar to (CMOS), which devices can be utilized in modulation, as well as in voltage controled switching and effecting a direction of rectification.

Schottky barrier MOSFET systems and fabrication thereof

DOEpatents

Welch, J.D.

1997-09-02

(MOS) device systems-utilizing Schottky barrier source and drain to channel region junctions are disclosed. Experimentally derived results which demonstrate operation of fabricated N-channel and P-channel Schottky barrier (MOSFET) devices, and of fabricated single devices with operational characteristics similar to (CMOS) and to a non-latching (SRC) are reported. Use of essentially non-rectifying Schottky barriers in (MOS) structures involving highly doped and the like and intrinsic semiconductor to allow non-rectifying interconnection of, and electrical accessing of device regions is also disclosed. Insulator effected low leakage current device geometries and fabrication procedures therefore are taught. Selective electrical interconnection of drain to drain, source to drain, or source to source, of N-channel and/or P-channel Schottky barrier (MOSFET) devices formed on P-type, N-type and Intrinsic semiconductor allows realization of Schottky Barrier (CMOS), (MOSFET) with (MOSFET) load, balanced differential (MOSFET) device systems and inverting and non-inverting single devices with operating characteristics similar to (CMOS), which devices can be utilized in modulation, as well as in voltage controlled switching and effecting a direction of rectification. 89 figs.

Introduction of the ASGARD code (Automated Selection and Grouping of events in AIA Regional Data)

NASA Astrophysics Data System (ADS)

Bethge, Christian; Winebarger, Amy; Tiwari, Sanjiv K.; Fayock, Brian

2017-08-01

We have developed the ASGARD code to automatically detect and group brightenings ("events") in AIA data. The event selection and grouping can be optimized to the respective dataset with a multitude of control parameters. The code was initially written for IRIS data, but has since been optimized for AIA. However, the underlying algorithm is not limited to either and could be used for other data as well.Results from datasets in various AIA channels show that brightenings are reliably detected and that coherent coronal structures can be isolated by using the obtained information about the start, peak, and end times of events. We are presently working on a follow-up algorithm to automatically determine the heating and cooling timescales of coronal structures. This will be done by correlating the information from different AIA channels with different temperature responses. We will present the code and preliminary results.

Centrifugal sedimentation for selectively packing channels with silica microbeads in three-dimensional micro/nanofluidic devices.

PubMed

Gong, Maojun; Bohn, Paul W; Sweedler, Jonathan V

2009-03-01

Incorporation of nanofluidic elements into microfluidic channels is one approach for adding filtration and partition functionality to planar microfluidic devices, as well as providing enhanced biomolecular separations. Here we introduce a strategy to pack microfluidic channels with silica nanoparticles and microbeads, thereby indirectly producing functional nanostructures; the method allows selected channels to be packed, here demonstrated so that a separation channel is packed while keeping an injection channel unpacked. A nanocapillary array membrane is integrated between two patterned microfluidic channels that cross each other in vertically separated layers. The membrane serves both as a frit for bead packing and as a fluid communication conduit between microfluidic channels. Centrifugal force-assisted sedimentation is then used to selectively pack the microfluidic channels using an aqueous silica bead suspension loaded into the appropriate inlet reservoirs. This packing approach may be used to simultaneously pack multiple channels with silica microbeads having different sizes and surface properties. The chip design and packing method introduced here are suitable for packing silica particles in sizes ranging from nanometers to micrometers and allow rapid (approximately 10 min) packing with high quality. The liquid/analyte transport characteristics of these packed micro/nanofluidic devices have potential utility in a wide range of applications, including electroosmotic pumping, liquid chromatographic separations, and electrochromatography.

Inhibitors of voltage-gated sodium channel Nav1.7: patent applications since 2010.

PubMed

Sun, Shaoyi; Cohen, Charles J; Dehnhardt, Christoph M

2014-09-01

There has been intense interest in developing inhibitors of the sodium channel Nav1.7 because genetic studies have established very strong validation for the efficacy to alleviate both inflammatory and neuropathic pain. This review summarizes patent applications targeting Nav1.7 since 2010 until May, 2014. We have classified the patents into three categories as follows: small molecules with well-defined molecular selectivity among sodium channel isoforms; biologicals with well-defined molecular selectivity; and, small molecules that inhibit Nav1.7 with unknown molecular selectivity. Most of the review is dedicated to small molecule selective compounds.

Stability of Reference Genes for Real-Time PCR Analyses in Channel Catfish (Ictalurus punctatus) Tissues Under Varying Physiological Conditions

USDA-ARS?s Scientific Manuscript database

Real-time PCR is a highly sensitive, relatively easy to perform assay for quantifying mRNA abundance. However, there are several complexities built into the assay that can affect data interpretation. Most notably, the selection of an appropriate internal control for normalization is essential for ...

Effects of data selection on the assimilation of AIRS data

NASA Technical Reports Server (NTRS)

Joiner, Joanna; Brin, E.; Treadon, R.; Derber, J.; VanDelst, P.; DeSilva, A.; Marshall, J. Le; Poli, P.; Atlas, R.; Cruz, C.;

Fractographic Investigation of Micromechanisms of Fracture in Alumina Ceramics

DTIC Science & Technology

1981-11-30

mechanisms flaw linking work of fracture electron channeling crack branching environmental effects 20. A07 ACT (Continue an reverse side Of necessary and...CLASSIFICATION OF THIS PAGE(I hm Date "ftn.,a environments using multiple techniques such as SEM, TEM, selected area electron channeling , and...94 Selected area electron channeling (SAEC) .. .... ........ 99 V. CONCLUSIONS. .. ............................ 100 VI. REFERENCES

Mechanisms for Rapid Adaptive Control of Motion Processing in Macaque Visual Cortex.

PubMed

McLelland, Douglas; Baker, Pamela M; Ahmed, Bashir; Kohn, Adam; Bair, Wyeth

2015-07-15

A key feature of neural networks is their ability to rapidly adjust their function, including signal gain and temporal dynamics, in response to changes in sensory inputs. These adjustments are thought to be important for optimizing the sensitivity of the system, yet their mechanisms remain poorly understood. We studied adaptive changes in temporal integration in direction-selective cells in macaque primary visual cortex, where specific hypotheses have been proposed to account for rapid adaptation. By independently stimulating direction-specific channels, we found that the control of temporal integration of motion at one direction was independent of motion signals driven at the orthogonal direction. We also found that individual neurons can simultaneously support two different profiles of temporal integration for motion in orthogonal directions. These findings rule out a broad range of adaptive mechanisms as being key to the control of temporal integration, including untuned normalization and nonlinearities of spike generation and somatic adaptation in the recorded direction-selective cells. Such mechanisms are too broadly tuned, or occur too far downstream, to explain the channel-specific and multiplexed temporal integration that we observe in single neurons. Instead, we are compelled to conclude that parallel processing pathways are involved, and we demonstrate one such circuit using a computer model. This solution allows processing in different direction/orientation channels to be separately optimized and is sensible given that, under typical motion conditions (e.g., translation or looming), speed on the retina is a function of the orientation of image components. Many neurons in visual cortex are understood in terms of their spatial and temporal receptive fields. It is now known that the spatiotemporal integration underlying visual responses is not fixed but depends on the visual input. For example, neurons that respond selectively to motion direction integrate signals over a shorter time window when visual motion is fast and a longer window when motion is slow. We investigated the mechanisms underlying this useful adaptation by recording from neurons as they responded to stimuli moving in two different directions at different speeds. Computer simulations of our results enabled us to rule out several candidate theories in favor of a model that integrates across multiple parallel channels that operate at different time scales. Copyright © 2015 the authors 0270-6474/15/3510268-13$15.00/0.

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers.

PubMed

Camilleri, Michael; Bharucha, Adil E; Ueno, Ryuji; Burton, Duane; Thomforde, George M; Baxter, Kari; McKinzie, Sanna; Zinsmeister, Alan R

2006-05-01

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.

KATP Channel Expression and Genetic Polymorphisms Associated with Progression and Survival in Amyotrophic Lateral Sclerosis.

PubMed

Vidal-Taboada, José M; Pugliese, Marco; Salvadó, Maria; Gámez, Josep; Mahy, Nicole; Rodríguez, Manuel J

2018-02-28

The ATP-sensitive potassium (K ATP ) channel directly regulates the microglia-mediated inflammatory response following CNS injury. To determine the putative role of the K ATP channel in amyotrophic lateral sclerosis (ALS) pathology, we investigated whether ALS induces changes in K ATP channel expression in the spinal cord and motor cortex. We also characterized new functional variants of human ABCC8, ABCC9, KCNJ8, and KCNJ11 genes encoding for the K ATP channel and analyzed their association with ALS risk, rate of progression, and survival in a Spanish ALS cohort. The expression of ABCC8 and KCNJ8 genes was enhanced in the spinal cord of ALS samples, and KCNJ11 increased in motor cortex of ALS samples, as determined by real-time polymerase chain reaction. We then sequenced the exons and regulatory regions of K ATP channel genes from a subset of 28 ALS patients and identified 50 new genetic variants. For the case-control association analysis, we genotyped five selected polymorphisms with predicted functional relevance in 185 Spanish ALS (134 spinal ALS and 51 bulbar ALS) patients and 493 controls. We found that bulbar ALS patients presenting the G/G genotype of the rs4148646 variant of ABCC8 and the T/T genotype of the rs5219 variant of KCNJ11 survived longer than other ALS patients presenting other genotypes. Also, the C/C genotype of the rs4148642 variant of ABCC8 and the T/C genotype of the rs148416760 variant of ABCC9 modified the progression rate in spinal ALS patients. Our results suggest that the K ATP channel plays a role in the pathophysiological mechanisms of ALS.

Glutamate transporter-associated anion channels adjust intracellular chloride concentrations during glial maturation.

PubMed

Untiet, Verena; Kovermann, Peter; Gerkau, Niklas J; Gensch, Thomas; Rose, Christine R; Fahlke, Christoph

2017-02-01

Astrocytic volume regulation and neurotransmitter uptake are critically dependent on the intracellular anion concentration, but little is known about the mechanisms controlling internal anion homeostasis in these cells. Here we used fluorescence lifetime imaging microscopy (FLIM) with the chloride-sensitive dye MQAE to measure intracellular chloride concentrations in murine Bergmann glial cells in acute cerebellar slices. We found Bergmann glial [Cl - ] int to be controlled by two opposing transport processes: chloride is actively accumulated by the Na + -K + -2Cl - cotransporter NKCC1, and chloride efflux through anion channels associated with excitatory amino acid transporters (EAATs) reduces [Cl - ] int to values that vary upon changes in expression levels or activity of these channels. EAATs transiently form anion-selective channels during glutamate transport, and thus represent a class of ligand-gated anion channels. Age-dependent upregulation of EAATs results in a developmental chloride switch from high internal chloride concentrations (51.6 ± 2.2 mM, mean ± 95% confidence interval) during early development to adult levels (35.3 ± 0.3 mM). Simultaneous blockade of EAAT1/GLAST and EAAT2/GLT-1 increased [Cl - ] int in adult glia to neonatal values. Moreover, EAAT activation by synaptic stimulations rapidly decreased [Cl - ] int . Other tested chloride channels or chloride transporters do not contribute to [Cl - ] int under our experimental conditions. Neither genetic removal of ClC-2 nor pharmacological block of K + -Cl - cotransporter change resting Bergmann glial [Cl - ] int in acute cerebellar slices. We conclude that EAAT anion channels play an important and unexpected role in adjusting glial intracellular anion concentration during maturation and in response to cerebellar activity. GLIA 2017;65:388-400. © 2016 Wiley Periodicals, Inc.

Identification of ML204, a Novel Potent Antagonist That Selectively Modulates Native TRPC4/C5 Ion Channels*

PubMed Central

Miller, Melissa; Shi, Jie; Zhu, Yingmin; Kustov, Maksym; Tian, Jin-bin; Stevens, Amy; Wu, Meng; Xu, Jia; Long, Shunyou; Yang, Pu; Zholos, Alexander V.; Salovich, James M.; Weaver, C. David; Hopkins, Corey R.; Lindsley, Craig W.; McManus, Owen; Li, Min; Zhu, Michael X.

2011-01-01

Transient receptor potential canonical (TRPC) channels are Ca2+-permeable nonselective cation channels implicated in diverse physiological functions, including smooth muscle contractility and synaptic transmission. However, lack of potent selective pharmacological inhibitors for TRPC channels has limited delineation of the roles of these channels in physiological systems. Here we report the identification and characterization of ML204 as a novel, potent, and selective TRPC4 channel inhibitor. A high throughput fluorescent screen of 305,000 compounds of the Molecular Libraries Small Molecule Repository was performed for inhibitors that blocked intracellular Ca2+ rise in response to stimulation of mouse TRPC4β by μ-opioid receptors. ML204 inhibited TRPC4β-mediated intracellular Ca2+ rise with an IC50 value of 0.96 μm and exhibited 19-fold selectivity against muscarinic receptor-coupled TRPC6 channel activation. In whole-cell patch clamp recordings, ML204 blocked TRPC4β currents activated through either μ-opioid receptor stimulation or intracellular dialysis of guanosine 5′-3-O-(thio)triphosphate (GTPγS), suggesting a direct interaction of ML204 with TRPC4 channels rather than any interference with the signal transduction pathways. Selectivity studies showed no appreciable block by 10–20 μm ML204 of TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and native voltage-gated sodium, potassium, and calcium channels in mouse dorsal root ganglion neurons. In isolated guinea pig ileal myocytes, ML204 blocked muscarinic cation currents activated by bath application of carbachol or intracellular infusion of GTPγS, demonstrating its effectiveness on native TRPC4 currents. Therefore, ML204 represents an excellent novel tool for investigation of TRPC4 channel function and may facilitate the development of therapeutics targeted to TRPC4. PMID:21795696

Dehalogenation of arenes via SN2 reactions at bromine: competition with nucleophilic aromatic substitution.

PubMed

Gronert, Scott; Garver, John M; Nichols, Charles M; Worker, Benjamin B; Bierbaum, Veronica M

2014-11-21

The gas-phase reactions of carbon- and nitrogen-centered nucleophiles with polyfluorobromobenzenes were examined in a selected-ion flow tube (SIFT) and modeled computationally at the MP2/6-31+G(d,p)//MP2/6-31+G(d) level. In the gas-phase experiments, rate constants and branching ratios were determined. The carbon nucleophiles produce expected nucleophilic aromatic substitution (SNAr) and proton transfer products along with unexpected products that result from SN2 reactions at the bromine center (polyfluorophenide leaving group). With nitrogen nucleophiles, the SN2 at bromine channel is suppressed. In the SNAr channels, the "element effect" is observed, and fluoride loss competes with bromide loss. The computational modeling indicates that all the substitution barriers are well below the entrance channel and that entropy and dynamics effects control the product distributions.

Controlled transport of latex beads through vertically aligned carbon nanofiber membranes

NASA Astrophysics Data System (ADS)

Zhang, L.; Melechko, A. V.; Merkulov, V. I.; Guillorn, M. A.; Simpson, M. L.; Lowndes, D. H.; Doktycz, M. J.

2002-07-01

Stripes of vertically aligned carbon nanofibers (VACNFs) have been used to form membranes for size selectively controlling the transport of latex beads. Fluidic structures were created in poly(dimethylsiloxane) (PDMS) and interfaced to the VACNF structures for characterization of the membrane pore size. Solutions of fluorescently labeled latex beads were introduced into the PDMS channels and characterized by fluorescence and scanning electron microscopy. Results show that the beads size selectively pass through the nanofiber barriers and the size restriction limit correlates with the interfiber spacing. The results suggest that altering VACNF array density can alter fractionation properties of the membrane. Such membranes may be useful for molecular sorting and for mimicking the properties of natural membranes.

A Wearable Channel Selection-Based Brain-Computer Interface for Motor Imagery Detection.

PubMed

Lo, Chi-Chun; Chien, Tsung-Yi; Chen, Yu-Chun; Tsai, Shang-Ho; Fang, Wai-Chi; Lin, Bor-Shyh

2016-02-06

Motor imagery-based brain-computer interface (BCI) is a communication interface between an external machine and the brain. Many kinds of spatial filters are used in BCIs to enhance the electroencephalography (EEG) features related to motor imagery. The approach of channel selection, developed to reserve meaningful EEG channels, is also an important technique for the development of BCIs. However, current BCI systems require a conventional EEG machine and EEG electrodes with conductive gel to acquire multi-channel EEG signals and then transmit these EEG signals to the back-end computer to perform the approach of channel selection. This reduces the convenience of use in daily life and increases the limitations of BCI applications. In order to improve the above issues, a novel wearable channel selection-based brain-computer interface is proposed. Here, retractable comb-shaped active dry electrodes are designed to measure the EEG signals on a hairy site, without conductive gel. By the design of analog CAR spatial filters and the firmware of EEG acquisition module, the function of spatial filters could be performed without any calculation, and channel selection could be performed in the front-end device to improve the practicability of detecting motor imagery in the wearable EEG device directly or in commercial mobile phones or tablets, which may have relatively low system specifications. Finally, the performance of the proposed BCI is investigated, and the experimental results show that the proposed system is a good wearable BCI system prototype.

Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.

PubMed

Findeisen, Felix; Campiglio, Marta; Jo, Hyunil; Abderemane-Ali, Fayal; Rumpf, Christine H; Pope, Lianne; Rossen, Nathan D; Flucher, Bernhard E; DeGrado, William F; Minor, Daniel L

2017-06-21

For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein-protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (Ca V ) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (Ca V β). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:Ca V β interactions and reduce the entropic penalty associated with AID binding to Ca V β. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the Ca V α 1 :Ca V β interaction that modulate Ca V function in an Ca V β isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein-protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based Ca V modulator design.

Sub-micron resolution selected area electron channeling patterns.

PubMed

Guyon, J; Mansour, H; Gey, N; Crimp, M A; Chalal, S; Maloufi, N

2015-02-01

Collection of selected area channeling patterns (SACPs) on a high resolution FEG-SEM is essential to carry out quantitative electron channeling contrast imaging (ECCI) studies, as it facilitates accurate determination of the crystal plane normal with respect to the incident beam direction and thus allows control the electron channeling conditions. Unfortunately commercial SACP modes developed in the past were limited in spatial resolution and are often no longer offered. In this contribution we present a novel approach for collecting high resolution SACPs (HR-SACPs) developed on a Gemini column. This HR-SACP technique combines the first demonstrated sub-micron spatial resolution with high angular accuracy of about 0.1°, at a convenient working distance of 10mm. This innovative approach integrates the use of aperture alignment coils to rock the beam with a digitally calibrated beam shift procedure to ensure the rocking beam is maintained on a point of interest. Moreover a new methodology to accurately measure SACP spatial resolution is proposed. While column considerations limit the rocking angle to 4°, this range is adequate to index the HR-SACP in conjunction with the pattern simulated from the approximate orientation deduced by EBSD. This new technique facilitates Accurate ECCI (A-ECCI) studies from very fine grained and/or highly strained materials. It offers also new insights for developing HR-SACP modes on new generation high-resolution electron columns. Copyright © 2014 Elsevier B.V. All rights reserved.

Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein–Protein Interaction Inhibitors of CaV Function

PubMed Central

2017-01-01

For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein–protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein–protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein–protein interaction, the interaction between the voltage-gated calcium channel (CaV) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (CaVβ). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:CaVβ interactions and reduce the entropic penalty associated with AID binding to CaVβ. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the CaVα1:CaVβ interaction that modulate CaV function in an CaVβ isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein–protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based CaV modulator design. PMID:28278376

Revision of XLM-2013-1129 as invited by the Action Editor, Rebekah Smith

PubMed Central

Naveh-Benjamin, Moshe; Kilb, Angela; Maddox, Geoff; Thomas, Jenna; Fine, Hope; Chen, Tina; Cowan, Nelson

2014-01-01

Although older adults have lower working memory spans on average than young adults, we demonstrate in five experiments one way in which older adults paradoxically resemble higher-capacity young adults. Specifically, in a selective-listening task, older adults almost always failed to notice their names presented in an unattended channel. This is an exaggeration of what high-span young adults show, and the opposite of what low spans show. This striking finding in older adults remained significant after controlling for working memory span and for noticing their names in an attended channel. The findings were replicated when presentation rate was made slower and when the ear in which the unattended name was presented was controlled. These results point to an account of older adults’ performance involving not only an inhibition factor, which allows high-span young adults to suppress the channel to be ignored, but also an attentional capacity factor, with more unallocated capacity allowing low-span young adults to notice their names much more often than older adults with comparably low spans. PMID:24820668

Spectral bandwidth-efficient four-wave mixing minimization scheme for C-band dense wavelength division multiplexed system

NASA Astrophysics Data System (ADS)

Singh, Gurpreet; Singh, Maninder Lal

2017-07-01

A hybrid suboptimum channel separation (S-CS) scheme is presented. The distinct feature of the scheme is that it selectively minimizes the four-wave mixing (FWM) effect on the worst-affected channels and enhances the performance and spectral bandwidth efficiency in a controlled way. The scheme is helpful in the precise adjustment of tradeoff between immunity from FWM and spectral bandwidth requirement. The simulative comparison of the S-CS with optimum unequal channel separation (OUCS) and equal channel separation (ECS) schemes is performed to show its effectiveness. A dense wavelength division multiplexed system having a total capacity of 1.64 Tb/s in C band is implemented using the presented scheme. A maximum of 82 channels spaced at minimum CS of 50 GHz operating at a data rate of 20 Gb/s for each of the channels is realized using a S-CS (n=12) hybrid scheme. The simulations are performed in the presence of all the linear and nonlinear impairments and noises. A maximum of 480- and 300-km distances using SSMF and ITUT.G655 fibers, respectively, is realized using dispersion-compensating fibers for 82 channels. The ECS and hybrid OUCS can be realized to cover the same distances but with 73 and 79 channels, respectively, due to the realization problem and bandwidth inefficiency.

P300 Chinese input system based on Bayesian LDA.

PubMed

Jin, Jing; Allison, Brendan Z; Brunner, Clemens; Wang, Bei; Wang, Xingyu; Zhang, Jianhua; Neuper, Christa; Pfurtscheller, Gert

2010-02-01

A brain-computer interface (BCI) is a new communication channel between humans and computers that translates brain activity into recognizable command and control signals. Attended events can evoke P300 potentials in the electroencephalogram. Hence, the P300 has been used in BCI systems to spell, control cursors or robotic devices, and other tasks. This paper introduces a novel P300 BCI to communicate Chinese characters. To improve classification accuracy, an optimization algorithm (particle swarm optimization, PSO) is used for channel selection (i.e., identifying the best electrode configuration). The effects of different electrode configurations on classification accuracy were tested by Bayesian linear discriminant analysis offline. The offline results from 11 subjects show that this new P300 BCI can effectively communicate Chinese characters and that the features extracted from the electrodes obtained by PSO yield good performance.

SVANET: A smart vehicular ad hoc network for efficient data transmission with wireless sensors.

PubMed

Sahoo, Prasan Kumar; Chiang, Ming-Jer; Wu, Shih-Lin

2014-11-25

Wireless sensors can sense any event, such as accidents, as well as icy roads, and can forward the rescue/warning messages through intermediate vehicles for any necessary help. In this paper, we propose a smart vehicular ad hoc network (SVANET) architecture that uses wireless sensors to detect events and vehicles to transmit the safety and non-safety messages efficiently by using different service channels and one control channel with different priorities. We have developed a data transmission protocol for the vehicles in the highway, in which data can be forwarded with the help of vehicles if they are connected with each other or data can be forwarded with the help of nearby wireless sensors. Our data transmission protocol is designed to increase the driving safety, to prevent accidents and to utilize channels efficiently by adjusting the control and service channel time intervals dynamically. Besides, our protocol can transmit information to vehicles in advance, so that drivers can decide an alternate route in case of traffic congestion. For various data sharing, we design a method that can select a few leader nodes among vehicles running along a highway to broadcast data efficiently. Simulation results show that our protocol can outperform the existing standard in terms of the end to end packet delivery ratio and latency.

SVANET: A Smart Vehicular Ad Hoc Network for Efficient Data Transmission with Wireless Sensors

PubMed Central

Sahoo, Prasan Kumar; Chiang, Ming-Jer; Wu, Shih-Lin

2014-01-01

Wireless sensors can sense any event, such as accidents, as well as icy roads, and can forward the rescue/warning messages through intermediate vehicles for any necessary help. In this paper, we propose a smart vehicular ad hoc network (SVANET) architecture that uses wireless sensors to detect events and vehicles to transmit the safety and non-safety messages efficiently by using different service channels and one control channel with different priorities. We have developed a data transmission protocol for the vehicles in the highway, in which data can be forwarded with the help of vehicles if they are connected with each other or data can be forwarded with the help of nearby wireless sensors. Our data transmission protocol is designed to increase the driving safety, to prevent accidents and to utilize channels efficiently by adjusting the control and service channel time intervals dynamically. Besides, our protocol can transmit information to vehicles in advance, so that drivers can decide an alternate route in case of traffic congestion. For various data sharing, we design a method that can select a few leader nodes among vehicles running along a highway to broadcast data efficiently. Simulation results show that our protocol can outperform the existing standard in terms of the end to end packet delivery ratio and latency. PMID:25429409

47 CFR 90.723 - Selection and assignment of frequencies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Selection and assignment of frequencies. 90.723... 220-222 MHz Band § 90.723 Selection and assignment of frequencies. (a) Phase II applications for... systems, 10-channel EA systems, 15-channel Regional systems, public safety/mutual aid use, or emergency...

Multichannel Networked Phasemeter Readout and Analysis

NASA Technical Reports Server (NTRS)

Edmonds, Karina

2008-01-01

Netmeter software reads a data stream from up to 250 networked phasemeters, synchronizes the data, saves the reduced data to disk (after applying a low-pass filter), and provides a Web server interface for remote control. Unlike older phasemeter software that requires a special, real-time operating system, this program can run on any general-purpose computer. It needs about five percent of the CPU (central processing unit) to process 20 channels because it adds built-in data logging and network-based GUIs (graphical user interfaces) that are implemented in Scalable Vector Graphics (SVG). Netmeter runs on Linux and Windows. It displays the instantaneous displacements measured by several phasemeters at a user-selectable rate, up to 1 kHz. The program monitors the measure and reference channel frequencies. For ease of use, levels of status in Netmeter are color coded: green for normal operation, yellow for network errors, and red for optical misalignment problems. Netmeter includes user-selectable filters up to 4 k samples, and user-selectable averaging windows (after filtering). Before filtering, the program saves raw data to disk using a burst-write technique.

Enhancement of the NMSU Channel Error Simulator to Provide User-Selectable Link Delays

NASA Technical Reports Server (NTRS)

Horan, Stephen; Wang, Ru-Hai

2000-01-01

This is the third in a continuing series of reports describing the development of the Space-to-Ground Link Simulator (SGLS) to be used for testing data transfers under simulated space channel conditions. The SGLS is based upon Virtual Instrument (VI) software techniques for managing the error generation, link data rate configuration, and, now, selection of the link delay value. In this report we detail the changes that needed to be made to the SGLS VI configuration to permit link delays to be added to the basic error generation and link data rate control capabilities. This was accomplished by modifying the rate-splitting VIs to include a buffer the hold the incoming data for the duration selected by the user to emulate the channel link delay. In sample tests of this configuration, the TCP/IP(sub ftp) service and the SCPS(sub fp) service were used to transmit 10-KB data files using both symmetric (both forward and return links set to 115200 bps) and unsymmetric (forward link set at 2400 bps and a return link set at 115200 bps) link configurations. Transmission times were recorded at bit error rates of 0 through 10(exp -5) to give an indication of the link performance. In these tests. we noted separate timings for the protocol setup time to initiate the file transfer and the variation in the actual file transfer time caused by channel errors. Both protocols showed similar performance to that seen earlier for the symmetric and unsymmetric channels. This time, the delays in establishing the file protocol also showed that these delays could double the transmission time and need to be accounted for in mission planning. Both protocols also showed a difficulty in transmitting large data files over large link delays. In these tests, there was no clear favorite between the TCP/IP(sub ftp) and the SCPS(sub fp). Based upon these tests, further testing is recommended to extend the results to different file transfer configurations.

Tight junctions of the proximal tubule and their channel proteins.

PubMed

Fromm, Michael; Piontek, Jörg; Rosenthal, Rita; Günzel, Dorothee; Krug, Susanne M

2017-08-01

The renal proximal tubule achieves the majority of renal water and solute reabsorption with the help of paracellular channels which lead through the tight junction. The proteins forming such channels in the proximal tubule are claudin-2, claudin-10a, and possibly claudin-17. Claudin-2 forms paracellular channels selective for small cations like Na + and K + . Independently of each other, claudin-10a and claudin-17 form anion-selective channels. The claudins form the paracellular "pore pathway" and are integrated, together with purely sealing claudins and other tight junction proteins, in the belt of tight junction strands surrounding the tubular epithelial cells. In most species, the proximal tubular tight junction consists of only 1-2 (pars convoluta) to 3-5 (pars recta) horizontal strands. Even so, they seal the tubule very effectively against leak passage of nutrients and larger molecules. Remarkably, claudin-2 channels are also permeable to water so that 20-25% of proximal water absorption may occur paracellularly. Although the exact structure of the claudin-2 channel is still unknown, it is clear that Na + and water share the same pore. Already solved claudin crystal structures reveal a characteristic β-sheet, comprising β-strands from both extracellular loops, which is anchored to a left-handed four-transmembrane helix bundle. This allowed homology modeling of channel-forming claudins present in the proximal tubule. The surface of cation- and anion-selective claudins differ in electrostatic potentials in the area of the proposed ion channel, resulting in the opposite charge selectivity of these claudins. Presently, while models of the molecular structure of the claudin-based oligomeric channels have been proposed, its full understanding has only started.

Mechanism of resveratrol-induced relaxation in the human gallbladder.

PubMed

Tsai, Ching-Chung; Lee, Ming-Che; Tey, Shu-Leei; Liu, Ching-Wen; Huang, Shih-Che

2017-05-08

Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips. We studied the relaxant effects of resveratrol in human gallbladder. In addition, we also investigated mechanism of resveratrol-induced relaxation in human gallbladder by tetraethylammonium (a non-selective potassium channels blocker), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channel), glibenclamide (an ATP-sensitive potassium channel blocker), charybdotoxin (an inhibitor of large conductance calcium-activated potassium channels and slowly inactivating voltage-gated potassium channels), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-Nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), and ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker). The present study showed that resveratrol has relaxant effects in human gallbladder muscle strips. In addition, we found that resveratrol-induced relaxation in human gallbladder is associated with nitric oxide, ATP-sensitive potassium channel, and large conductance calcium-activated potassium channel pathways. This study provides the first evidence concerning the relaxant effects of resveratrol in human gallbladder muscle strips. Furthermore, these results demonstrate that resveratrol is a potential new drug or health supplement in the treatment of biliary colic.

Ion-binding properties of the ClC chloride selectivity filter

PubMed Central

Lobet, Séverine; Dutzler, Raimund

2006-01-01

The ClC channels are members of a large protein family of chloride (Cl−) channels and secondary active Cl− transporters. Despite their diverse functions, the transmembrane architecture within the family is conserved. Here we present a crystallographic study on the ion-binding properties of the ClC selectivity filter in the close homolog from Escherichia coli (EcClC). The ClC selectivity filter contains three ion-binding sites that bridge the extra- and intracellular solutions. The sites bind Cl− ions with mM affinity. Despite their close proximity within the filter, the three sites can be occupied simultaneously. The ion-binding properties are found conserved from the bacterial transporter EcClC to the human Cl− channel ClC-1, suggesting a close functional link between ion permeation in the channels and active transport in the transporters. In resemblance to K+ channels, ions permeate the ClC channel in a single file, with mutual repulsion between the ions fostering rapid conduction. PMID:16341087

Image Discrimination Models With Stochastic Channel Selection

NASA Technical Reports Server (NTRS)

Ahumada, Albert J., Jr.; Beard, Bettina L.; Null, Cynthia H. (Technical Monitor)

1995-01-01

Many models of human image processing feature a large fixed number of channels representing cortical units varying in spatial position (visual field direction and eccentricity) and spatial frequency (radial frequency and orientation). The values of these parameters are usually sampled at fixed values selected to ensure adequate overlap considering the bandwidth and/or spread parameters, which are usually fixed. Even high levels of overlap does not always ensure that the performance of the model will vary smoothly with image translation or scale changes. Physiological measurements of bandwidth and/or spread parameters result in a broad distribution of estimated parameter values and the prediction of some psychophysical results are facilitated by the assumption that these parameters also take on a range of values. Selecting a sample of channels from a continuum of channels rather than using a fixed set can make model performance vary smoothly with changes in image position, scale, and orientation. It also facilitates the addition of spatial inhomogeneity, nonlinear feature channels, and focus of attention to channel models.

Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock.

PubMed

Collin, Solène; Sennoun, Nacira; Dron, Anne-Gaëlle; de la Bourdonnaye, Mathilde; Montemont, Chantal; Asfar, Pierre; Lacolley, Patrick; Meziani, Ferhat; Levy, Bruno

2011-05-01

To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular K(ATP) (PNU-37883A) or BK(Ca) [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular K(ATP) channels, while expression of vascular BK(Ca) channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular K(ATP) channel expression. Vascular K(ATP) but not BK(Ca) channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular K(ATP) channel inhibitors offer potential therapeutic perspectives for septic shock.

Fundoplication for laryngopharyngeal reflux despite preoperative dysphagia.

PubMed

Falk, G L; Van der Wall, H; Burton, L; Falk, M G; O'Donnell, H; Vivian, S J

2017-03-01

INTRODUCTION Fundoplication for laryngopharyngeal disease with oesophageal dysmotility has led to mixed outcomes. In the presence of preoperative dysphagia and oesophageal dysmotility, this procedure has engendered concern in certain regards. METHODS This paper describes a consecutive series of laryngopharyngeal reflux (LPR) patients with a high frequency of dysmotility. Patients were selected for surgery with 24-hour dual channel pH monitoring, oesophageal manometry and standardised reflux scintigraphy. RESULTS Following careful patient selection, 33 patients underwent fundoplication by laparoscopy. Surgery had high efficacy in symptom control and there was no adverse dysphagia. CONCLUSIONS Evidence of proximal reflux can select a group of patients for good results of fundoplication for atypical symptoms.

Determinants of cation transport selectivity: Equilibrium binding and transport kinetics

PubMed Central

2015-01-01

The crystal structures of channels and transporters reveal the chemical nature of ion-binding sites and, thereby, constrain mechanistic models for their transport processes. However, these structures, in and of themselves, do not reveal equilibrium selectivity or transport preferences, which can be discerned only from various functional assays. In this Review, I explore the relationship between cation transport protein structures, equilibrium binding measurements, and ion transport selectivity. The primary focus is on K+-selective channels and nonselective cation channels because they have been extensively studied both functionally and structurally, but the principles discussed are relevant to other transport proteins and molecules. PMID:26078056

X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel.

PubMed

Baconguis, Isabelle; Bohlen, Christopher J; Goehring, April; Julius, David; Gouaux, Eric

2014-02-13

Acid-sensing ion channels (ASICs) detect extracellular protons produced during inflammation or ischemic injury and belong to the superfamily of degenerin/epithelial sodium channels. Here, we determine the cocrystal structure of chicken ASIC1a with MitTx, a pain-inducing toxin from the Texas coral snake, to define the structure of the open state of ASIC1a. In the MitTx-bound open state and in the previously determined low-pH desensitized state, TM2 is a discontinuous α helix in which the Gly-Ala-Ser selectivity filter adopts an extended, belt-like conformation, swapping the cytoplasmic one-third of TM2 with an adjacent subunit. Gly 443 residues of the selectivity filter provide a ring of three carbonyl oxygen atoms with a radius of ∼3.6 Å, presenting an energetic barrier for hydrated ions. The ASIC1a-MitTx complex illuminates the mechanism of MitTx action, defines the structure of the selectivity filter of voltage-independent, sodium-selective ion channels, and captures the open state of an ASIC. Copyright © 2014 Elsevier Inc. All rights reserved.

Cl- channels of the gastric parietal cell that are active at low pH.

PubMed

Cuppoletti, J; Baker, A M; Malinowska, D H

1993-06-01

HCl secretion across mammalian gastric parietal cell apical membrane may involve Cl- channels. H(+)-K(+)-ATPase-containing membranes isolated from gastric mucosa of histamine-stimulated rabbits were fused to planar lipid bilayers. Channels were recorded with symmetric 800 mM CsCl solutions, pH 7.4. A linear current-voltage (I-V) relationship was obtained, and conductance was 28 +/- 1 pS at 800 mM CsCl. Conductance was 6.9 +/- 2 pS at 150 mM CsCl. Reversal potential was +22 mV with a fivefold cis-trans CsCl concentration gradient, indicating that the channel was anion selective with a discrimination ratio of 6:1 for Cl- over Cs+. Anion selectivity of the channel was I- > Cl- > or = Br- > NO3-, and gluconate was impermeant. Channels obtained at pH 7.4 persisted when pH of medium bathing the trans side of the bilayer (pHtrans) was reduced to pH 3, without a change in conductance, linearity of I-V relationship, or ion selectivity. In contrast, asymmetric reduction of pH of medium bathing the cis side of the bilayer from 7.4 to 3 always resulted in loss of channel activity. At pH 7.4, open probability (Po) of the channel was voltage dependent, i.e., predominantly open at +80 mV but mainly closed at -80 mV. In contrast, with low pHtrans, channel Po at -80 mV was increased 3.5-fold. The Cl- channel was Ca2+ indifferent. In absence of ionophores, ion selectivity for support of H(+)-K(+)-ATPase activity and H+ transport was consistent with that exhibited by the channel and could be limited by substitution with NO3-, whereas maximal H(+)-K(+)-ATPase activity was indifferent to anion present, demonstrating that anion transport can be rate limiting. Cl- channels with similar characteristics (conductance, linear I-V relationship, and ion selectivity) were also present in H(+)-K(+)-ATPase-containing vesicles isolated from resting (cimetidine-treated) gastric mucosa, exhibiting at -80 mV a pH-independent approximately 3.5-fold lower Po than stimulated vesicle channels. At -80 mV, reduction of pHtrans increased Po of both resting and stimulated Cl- channels by five- to sixfold. Changing membrane potential from 0 to -80 mV across stimulated vesicles increased Cl- channel activity an additional 10-fold.(ABSTRACT TRUNCATED AT 400 WORDS)

Transduction channels' gating can control friction on vibrating hair-cell bundles in the ear.

PubMed

Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

2014-05-20

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force-displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell's characteristic frequency of responsiveness.

Pore dilatation increases the bicarbonate permeability of CFTR, ANO1 and glycine receptor anion channels

PubMed Central

Jun, Ikhyun; Cheng, Mary Hongying; Sim, Eunji; Jung, Jinsei; Suh, Bong Lim; Kim, Yonjung; Son, Hankil; Park, Kyungsoo; Kim, Chul Hoon; Yoon, Joo‐Heon; Whitcomb, David C.; Bahar, Ivet

2016-01-01

Key points Cellular stimuli can modulate the ion selectivity of some anion channels, such as CFTR, ANO1 and the glycine receptor (GlyR), by changing pore size.Ion selectivity of CFTR, ANO1 and GlyR is critically affected by the electric permittivity and diameter of the channel pore.Pore size change affects the energy barriers of ion dehydration as well as that of size‐exclusion of anion permeation.Pore dilatation increases the bicarbonate permeability (P HC O3/ Cl ) of CFTR, ANO1 and GlyR.Dynamic change in P HC O3/ Cl may mediate many physiological and pathological processes. Abstract Chloride (Cl−) and bicarbonate (HCO3 −) are two major anions and their permeation through anion channels plays essential roles in our body. However, the mechanism of ion selection by the anion channels is largely unknown. Here, we provide evidence that pore dilatation increases the bicarbonate permeability (P HC O3/ Cl ) of anion channels by reducing energy barriers of size‐exclusion and ion dehydration of HCO3 − permeation. Molecular, physiological and computational analyses of major anion channels, such as cystic fibrosis transmembrane conductance regulator (CFTR), anoctamin‐1(ANO1/TMEM16A) and the glycine receptor (GlyR), revealed that the ion selectivity of anion channels is basically determined by the electric permittivity and diameter of the pore. Importantly, cellular stimuli dynamically modulate the anion selectivity of CFTR and ANO1 by changing the pore size. In addition, pore dilatation by a mutation in the pore‐lining region alters the anion selectivity of GlyR. Changes in pore size affected not only the energy barriers of size exclusion but that of ion dehydration by altering the electric permittivity of water‐filled cavity in the pore. The dynamic increase in P HC O3/ Cl by pore dilatation may have many physiological and pathophysiological implications ranging from epithelial HCO3 − secretion to neuronal excitation. PMID:26663196

Locating the Anion-selectivity Filter of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel

PubMed Central

Cheung, Min; Akabas, Myles H.

1997-01-01

The cystic fibrosis transmembrane conductance regulator forms an anion-selective channel; the site and mechanism of charge selectivity is unknown. We previously reported that cysteines substituted, one at a time, for Ile331, Leu333, Arg334, Lys335, Phe337, Ser341, Ile344, Arg347, Thr351, Arg352, and Gln353, in and flanking the sixth membrane-spanning segment (M6), reacted with charged, sulfhydryl-specific, methanethiosulfonate (MTS) reagents. We inferred that these residues are on the water-accessible surface of the protein and may line the ion channel. We have now measured the voltage-dependence of the reaction rates of the MTS reagents with the accessible, engineered cysteines. By comparing the reaction rates of negatively and positively charged MTS reagents with these cysteines, we measured the extent of anion selectivity from the extracellular end of the channel to eight of the accessible residues. We show that the major site determining anion vs. cation selectivity is near the cytoplasmic end of the channel; it favors anions by ∼25-fold and may involve the residues Arg347 and Arg352. From the voltage dependence of the reaction rates, we calculated the electrical distance to the accessible residues. For the residues from Leu333 to Ser341 the electrical distance is not significantly different than zero; it is significantly different than zero for the residues Thr351 to Gln353. The maximum electrical distance measured was 0.6 suggesting that the channel extends more cytoplasmically and may include residues flanking the cytoplasmic end of the M6 segment. Furthermore, the electrical distance calculations indicate that R352C is closer to the extracellular end of the channel than either of the adjacent residues. We speculate that the cytoplasmic end of the M6 segment may loop back into the channel narrowing the lumen and thereby forming both the major resistance to current flow and the anion-selectivity filter. PMID:9089437

Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents.

PubMed

Andrè, E; Gatti, R; Trevisani, M; Preti, D; Baraldi, P G; Patacchini, R; Geppetti, P

2009-11-01

The transient receptor potential ankyrin receptor 1 (TRPA1) is a cation channel, co-expressed with the pro-tussive transient receptor potential vanilloid type 1 (TRPV1) channel in primary sensory neurons. TRPA1 is activated by a series of irritant exogenous and endogenous alpha,beta-unsaturated aldehydes which seem to play a role in airway diseases. We investigated whether TRPA1 agonists provoke cough in guinea pigs and whether TRPA1 antagonists inhibit this response. Animals were placed in a Perspex box, and cough sounds were recorded and counted by observers unaware of the treatment used. Inhalation of two selective TRPA1 agonists, allyl isothiocyanate and cinnamaldehyde, dose-dependently caused cough in control guinea pigs, but not in those with airway sensory nerves desensitized by capsaicin. Coughs elicited by TRPA1 agonists were reduced by non-selective (camphor and gentamicin) and selective (HC-030031) TRPA1 antagonists, whereas they were unaffected by the TRPV1 antagonist, capsazepine. Acrolein and crotonaldehyde, two alpha,beta-unsaturated aldehydes recently identified as TRPA1 stimulants and contained in cigarette smoke, air pollution or produced endogenously by oxidative stress, caused a remarkable tussive effect, a response that was selectively inhibited by HC-030031. Part of the cough response induced by cigarette smoke inhalation was inhibited by HC-030031, suggesting the involvement of TRPA1. A novel pro-tussive pathway involves the TRPA1 channel, expressed by capsaicin-sensitive airway sensory nerves and is activated by a series of exogenous (cigarette smoke) and endogenous irritants. These results suggest TRPA1 may be a novel target for anti-tussive medicines.

Open-top selective plane illumination microscope for conventionally mounted specimens.

PubMed

McGorty, Ryan; Liu, Harrison; Kamiyama, Daichi; Dong, Zhiqiang; Guo, Su; Huang, Bo

2015-06-15

We have developed a new open-top selective plane illumination microscope (SPIM) compatible with microfluidic devices, multi-well plates, and other sample formats used in conventional inverted microscopy. Its key element is a water prism that compensates for the aberrations introduced when imaging at 45 degrees through a coverglass. We have demonstrated its unique high-content imaging capability by recording Drosophila embryo development in environmentally-controlled microfluidic channels and imaging zebrafish embryos in 96-well plates. We have also shown the imaging of C. elegans and moving Drosophila larvae on coverslips.

RLS Channel Estimation with Adaptive Forgetting Factor for DS-CDMA Frequency-Domain Equalization

NASA Astrophysics Data System (ADS)

Kojima, Yohei; Tomeba, Hiromichi; Takeda, Kazuaki; Adachi, Fumiyuki

Frequency-domain equalization (FDE) based on the minimum mean square error (MMSE) criterion can increase the downlink bit error rate (BER) performance of DS-CDMA beyond that possible with conventional rake combining in a frequency-selective fading channel. FDE requires accurate channel estimation. Recently, we proposed a pilot-assisted channel estimation (CE) based on the MMSE criterion. Using MMSE-CE, the channel estimation accuracy is almost insensitive to the pilot chip sequence, and a good BER performance is achieved. In this paper, we propose a channel estimation scheme using one-tap recursive least square (RLS) algorithm, where the forgetting factor is adapted to the changing channel condition by the least mean square (LMS)algorithm, for DS-CDMA with FDE. We evaluate the BER performance using RLS-CE with adaptive forgetting factor in a frequency-selective fast Rayleigh fading channel by computer simulation.

Voltage activation and hysteresis of the non-selective voltage-dependent channel in the intact human red cell.

PubMed

Bennekou, Poul; Barksmann, Trine L; Jensen, Lars R; Kristensen, Berit I; Christophersen, Palle

2004-05-01

Suspension of intact human red cells in media with low chloride and sodium concentrations (isotonic sucrose substitution) results in strongly inside positive membrane potentials, which activate the voltage-dependent non-selective cation (NSVDC) channel. By systematic variation of the initial Nernst potentials for chloride (degree of ion substitution) as well as the chloride conductance (block by NS1652), and by exploiting the interplay between the Ca(2+)-permeable NSVDC channel, the Ca(2+)-activated K+ channel (the Gárdos channel) and the Ca(2+)-pump, a graded activation of the NSVDC channel was achieved. Under these conditions, it was shown that the NSVDC channels exist in two states of activation depending on the initial conditions for the activation. The hysteretic behaviour, which in patch clamp experiments has been found for the individual channel unit, is thus retained at the cellular level and can be demonstrated with red cells in suspension.

Rotary Joints With Electrical Connections

NASA Technical Reports Server (NTRS)

Osborn, F. W.

1986-01-01

Power and data transmitted on many channels. Two different rotary joints equipped with electrical connections between rotating and stationary parts. One joint transmits axial thrust and serves as interface between spinning and nonspinning parts of Galileo spacecraft. Other is scanning (limitedrotation) joint that aims scientific instruments from nonspinning part. Selected features of both useful to designers of robots, advanced production equipment, and remotely controlled instruments.

Space-Time Joint Interference Cancellation Using Fuzzy-Inference-Based Adaptive Filtering Techniques in Frequency-Selective Multipath Channels

NASA Astrophysics Data System (ADS)

Hu, Chia-Chang; Lin, Hsuan-Yu; Chen, Yu-Fan; Wen, Jyh-Horng

2006-12-01

An adaptive minimum mean-square error (MMSE) array receiver based on the fuzzy-logic recursive least-squares (RLS) algorithm is developed for asynchronous DS-CDMA interference suppression in the presence of frequency-selective multipath fading. This receiver employs a fuzzy-logic control mechanism to perform the nonlinear mapping of the squared error and squared error variation, denoted by ([InlineEquation not available: see fulltext.],[InlineEquation not available: see fulltext.]), into a forgetting factor[InlineEquation not available: see fulltext.]. For the real-time applicability, a computationally efficient version of the proposed receiver is derived based on the least-mean-square (LMS) algorithm using the fuzzy-inference-controlled step-size[InlineEquation not available: see fulltext.]. This receiver is capable of providing both fast convergence/tracking capability as well as small steady-state misadjustment as compared with conventional LMS- and RLS-based MMSE DS-CDMA receivers. Simulations show that the fuzzy-logic LMS and RLS algorithms outperform, respectively, other variable step-size LMS (VSS-LMS) and variable forgetting factor RLS (VFF-RLS) algorithms at least 3 dB and 1.5 dB in bit-error-rate (BER) for multipath fading channels.

Bovine chromaffin cells possess FTX-sensitive calcium channels.

PubMed

Gandía, L; Albillos, A; García, A G

1993-07-30

The effects of the synthetic analogue of the toxin from the venom of the funnel-web spider Agenelopsis aperta (sFTX) on whole-cell Ba2+ currents through Ca2+ channels were studied in cultured bovine chromaffin cells. sFTX selectively and reversibly blocked a significant component (55 +/- 3%) of the whole-cell IBa. Effects of sFTX were additive to those of omega-conotoxin GVIA, a selective blocker of N-type Ca2+ channels, and those of furnidipine, a novel dihydropyridine L-type Ca2+ channel blocker. We conclude that the cultured bovine chromaffin cells, in addition to N- and L-type Ca2+ channels, possess a P-type component in their whole-cell currents through their Ca2+ channels.

Characterization of a C-type natriuretic peptide (CNP-39)-formed cation-selective channel from platypus (Ornithorhynchus anatinus) venom

PubMed Central

Kourie, Joseph I

1999-01-01

The lipid bilayer technique is used to characterize the biophysical and pharmacological properties of a novel, fast, cation-selective channel formed by incorporating platypus (Ornithorhynchus anatinus) venom (OaV) into lipid membranes.A synthetic C-type natriuretic peptide OaCNP-39, which is identical to that present in platypus venom, mimics the conductance, kinetics, selectivity and pharmacological properties of the OaV-formed fast cation-selective channel. The N-terminal fragment containing residues 1-17, i.e. OaCNP-39(1-17), induces the channel activity.The current amplitude of the TEACl-insensitive fast cation-selective channel is dependent on cytoplasmic K+, [K+]cis. The increase in the current amplitude, as a function of increasing [K+]cis, is non-linear and can be described by the Michaelis-Menten equation. At +140 mV, the values of γmax and KS are 63·1 pS and 169 mM, respectively, whereas at 0 mV the values of γmax and KS are 21·1 pS and 307 mM, respectively. γmax and KS are maximal single channel conductance and concentration for half-maximal γ, respectively. The calculated permeability ratios, PK:PRb:PNa: PCs:PLi, were 1:0·76:0·21:0·09:0·03, respectively.The probability of the fast channel being open, Po, increases from 0·15 at 0 mV to 0·75 at +140 mV. In contrast, the channel frequency, Fo, decreases from 400 to 180 events per second for voltages between 0 mV and +140. The mean open time, To, increases as the bilayer is made more positive, between 0 and +140 mV. The mean values of the voltage-dependent kinetic parameters, Po, Fo, To and mean closed time (Tc), are independent of [KCl]cis between 50 and 750 mM (P > 0·05).It is proposed that some of the symptoms of envenomation by platypus venom may be caused partly by changes in cellular functions mediated via the OaCNP-39-formed fast cation-selective channel, which affects signal transduction. PMID:10381585

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

Increases in intracellular pH facilitate endocytosis and decrease availability of voltage-gated proton channels in osteoclasts and microglia

PubMed Central

Sakai, Hiromu; Li, Guangshuai; Hino, Yoshiko; Moriura, Yoshie; Kawawaki, Junko; Sawada, Makoto; Kuno, Miyuki

2013-01-01

Voltage-gated proton channels (H+ channels) are highly proton-selective transmembrane pathways. Although the primary determinants for activation are the pH and voltage gradients across the membrane, the current amplitudes fluctuate often when these gradients are constant. The aim of this study was to investigate the role of the intracellular pH (pHi) in regulating the availability of H+ channels in osteoclasts and microglia. In whole-cell clamp recordings, the pHi was elevated after exposure to NH4Cl and returned to the control level after washout. However, the H+ channel conductance did not recover fully when the exposure was prolonged (>5 min). Similar results were observed in osteoclasts and microglia, but not in COS7 cells expressing a murine H+ channel gene (mVSOP). As other electrophysiological properties, like the gating kinetics and voltage dependence for activation, were unchanged, the decreases in the H+ channel conductance were probably due to the decreases in H+ channels available at the plasma membrane. The decreases in the H+ channel conductances were accompanied by reductions in the cell capacitance. Exposure to NH4Cl increased the uptake of the endocytosis marker FM1-43, substantiating the idea that pHi increases facilitated endocytosis. In osteoclasts, whose plasma membrane expresses V-ATPases and H+ channels, pHi increases by these H+-transferring molecules in part facilitated endocytosis. The endocytosis and decreases in the H+ channel conductance were reduced by dynasore, a dynamin blocker. These results suggest that pHi increases in osteoclasts and microglia decrease the numbers of H+ channels available at the plasma membrane through facilitation of dynamin-dependent endocytosis. PMID:24081153

Electrostatics of aquaporin and aquaglyceroporin channels correlates with their transport selectivity

PubMed Central

Oliva, Romina; Calamita, Giuseppe; Thornton, Janet M.; Pellegrini-Calace, Marialuisa

2010-01-01

Aquaporins are homotetrameric channel proteins, which allow the diffusion of water and small solutes across biological membranes. According to their transport function, aquaporins can be divided into “orthodox aquaporins”, which allow the flux of water molecules only, and “aquaglyceroporins”, which facilitate the diffusion of glycerol and other small solutes in addition to water. The contribution of individual residues in the pore to the selectivity of orthodox aquaporins and aquaglyceroporins is not yet fully understood. To gain insights into aquaporin selectivity, we focused on the sequence variation and electrostatics of their channels. The continuum Poisson-Boltzmann electrostatic potential along the channel was calculated and compared for ten three-dimensional-structures which are representatives of different aquaporin subfamilies, and a panel of functionally characterized mutants, for which high-accuracy three-dimensional-models could be derived. Interestingly, specific electrostatic profiles associated with the main selectivity to water or glycerol could be identified. In particular: (i) orthodox aquaporins showed a distinctive electrostatic potential maximum at the periplasmic side of the channel around the aromatic/Arg (ar/R) constriction site; (ii) aquaporin-0 (AQP0), a mammalian aquaporin with considerably low water permeability, had an additional deep minimum at the cytoplasmic side; (iii) aquaglyceroporins showed a rather flat potential all along the channel; and (iv) the bifunctional protozoan PfAQP had an unusual all negative profile. Evaluation of electrostatics of the mutants, along with a thorough sequence analysis of the aquaporin pore-lining residues, illuminated the contribution of specific residues to the electrostatics of the channels and possibly to their selectivity. PMID:20147624

Streaming potentials in gramicidin channels measured with ion-selective microelectrodes.

PubMed Central

Tripathi, S; Hladky, S B

1998-01-01

Streaming potentials have been measured for gramicidin channels with a new method employing ion-selective microelectrodes. It is shown that ideally ion-selective electrodes placed at the membrane surface record the true streaming potential. Using this method for ion concentrations below 100 mM, approximately seven water molecules are transported whenever a sodium, potassium, or cesium ion, passes through the channel. This new method confirms earlier measurements (Rosenberg, P.A., and A. Finkelstein. 1978. Interaction of ions and water in gramicidin A channels. J. Gen. Physiol. 72:327-340) in which the streaming potentials were calculated as the difference between electrical potentials measured in the presence of gramicidin and in the presence of the ion carriers valinomycin and nonactin. PMID:9635745

The external pore loop interacts with S6 and S3-S4 linker in domain 4 to assume an essential role in gating control and anticonvulsant action in the Na+ channel

PubMed Central

Yang, Ya-Chin; Hsieh, Jui-Yi

2009-01-01

Carbamazepine, phenytoin, and lamotrigine are widely prescribed anticonvulsants in neurological clinics. These drugs bind to the same receptor site, probably with the diphenyl motif in their structure, to inhibit the Na+ channel. However, the location of the drug receptor remains controversial. In this study, we demonstrate close proximity and potential interaction between an external aromatic residue (W1716 in the external pore loop) and an internal aromatic residue (F1764 in the pore-lining part of the sixth transmembrane segment, S6) of domain 4 (D4), both being closely related to anticonvulsant and/or local anesthetic binding to the Na+ channel. Double-mutant cycle analysis reveals significant cooperativity between the two phenyl residues for anticonvulsant binding. Concomitant F1764C mutation evidently decreases the susceptibility of W1716C to external Cd2+ and membrane-impermeable methanethiosulfonate reagents. Also, the W1716E/F1764R and G1715E/F1764R double mutations significantly alter the selectivity for Na+ over K+ and markedly shift the activation curve, respectively. W1716 and F1764 therefore very likely form a link connecting the outer and inner compartments of the Na+ channel pore (in addition to the selectivity filter). Anticonvulsants and local anesthetics may well traverse this “S6 recess” without trespassing on the selectivity filter. Furthermore, we found that Y1618K, a point mutation in the S3-4 linker (the extracellular extension of D4S4), significantly alters the consequences of carbamazepine binding to the Na+ channel. The effect of Y1618K mutation, however, is abolished by concomitant point mutations in the vicinity of Y1618, but not by those in the internally located inactivation machinery, supporting a direct local rather than a long-range allosteric action. Moreover, Y1618 could interact with D4 pore residues W1716 and L1719 to have a profound effect on both channel gating and anticonvulsant action. We conclude that there are direct interactions among the external S3-4 linker, the external pore loop, and the internal S6 segment in D4, making the external pore loop a pivotal point critically coordinating ion permeation, gating, and anticonvulsant binding in the Na+ channel. PMID:19635852

The external pore loop interacts with S6 and S3-S4 linker in domain 4 to assume an essential role in gating control and anticonvulsant action in the Na(+) channel.

PubMed

Yang, Ya-Chin; Hsieh, Jui-Yi; Kuo, Chung-Chin

2009-08-01

Carbamazepine, phenytoin, and lamotrigine are widely prescribed anticonvulsants in neurological clinics. These drugs bind to the same receptor site, probably with the diphenyl motif in their structure, to inhibit the Na(+) channel. However, the location of the drug receptor remains controversial. In this study, we demonstrate close proximity and potential interaction between an external aromatic residue (W1716 in the external pore loop) and an internal aromatic residue (F1764 in the pore-lining part of the sixth transmembrane segment, S6) of domain 4 (D4), both being closely related to anticonvulsant and/or local anesthetic binding to the Na(+) channel. Double-mutant cycle analysis reveals significant cooperativity between the two phenyl residues for anticonvulsant binding. Concomitant F1764C mutation evidently decreases the susceptibility of W1716C to external Cd(2+) and membrane-impermeable methanethiosulfonate reagents. Also, the W1716E/F1764R and G1715E/F1764R double mutations significantly alter the selectivity for Na(+) over K(+) and markedly shift the activation curve, respectively. W1716 and F1764 therefore very likely form a link connecting the outer and inner compartments of the Na(+) channel pore (in addition to the selectivity filter). Anticonvulsants and local anesthetics may well traverse this "S6 recess" without trespassing on the selectivity filter. Furthermore, we found that Y1618K, a point mutation in the S3-4 linker (the extracellular extension of D4S4), significantly alters the consequences of carbamazepine binding to the Na(+) channel. The effect of Y1618K mutation, however, is abolished by concomitant point mutations in the vicinity of Y1618, but not by those in the internally located inactivation machinery, supporting a direct local rather than a long-range allosteric action. Moreover, Y1618 could interact with D4 pore residues W1716 and L1719 to have a profound effect on both channel gating and anticonvulsant action. We conclude that there are direct interactions among the external S3-4 linker, the external pore loop, and the internal S6 segment in D4, making the external pore loop a pivotal point critically coordinating ion permeation, gating, and anticonvulsant binding in the Na(+) channel.

Angle Performance on Optima XE

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

David, Jonathan; Satoh, Shu

2011-01-07

Angle control on high energy implanters is important due to shrinking device dimensions, and sensitivity to channeling at high beam energies. On Optima XE, beam-to-wafer angles are controlled in both the horizontal and vertical directions. In the horizontal direction, the beam angle is measured through a series of narrow slits, and any angle adjustment is made by steering the beam with the corrector magnet. In the vertical direction, the beam angle is measured through a high aspect ratio mask, and any angle adjustment is made by slightly tilting the wafer platen during implant.Using a sensitive channeling condition, we were ablemore » to quantify the angle repeatability of Optima XE. By quantifying the sheet resistance sensitivity to both horizontal and vertical angle variation, the total angle variation was calculated as 0.04 deg. (1{sigma}). Implants were run over a five week period, with all of the wafers selected from a single boule, in order to control for any crystal cut variation.« less

Evaluation of CAESAR-Lisflood as a tool for modelling river channel change and floodplain sediment residence times.

NASA Astrophysics Data System (ADS)

Feeney, Christopher; Smith, Hugh; Chiverrell, Richard; Hooke, Janet; Cooper, James

2017-04-01

Sediment residence time represents the duration of particle storage, from initial deposition to remobilisation, within reservoirs such as floodplains. Residence time influences rates of downstream redistribution of sediment and associated contaminants and is a useful indicator of landform stability and hence, preservation potential of alluvial archives of environmental change. River channel change controls residence times, reworking sediments via lateral migration, avulsion and incision through floodplain deposits. As reworking progresses, the floodplain age distribution is 'updated', reflecting the time since 'older' sediments were removed and replaced with 'younger' ones. The relationship between ages and the spatial extents they occupy can be used to estimate the average floodplain sediment residence times. While dating techniques, historic maps and remote sensing can reconstruct age distributions from historic reworking, modelling provides advantages, including: i) capturing detailed river channel changes and resulting floodplain ages over longer timescales and higher resolutions than from historic mapping, and ii) control over inputs to simulate hypothetical scenarios to investigate the effects of different environmental drivers on residence times. CAESAR-Lisflood is a landform evolution model capable of simulating variable channel width, divergent flow, and both braided and meandering planforms. However, the model's ability to accurately simulate channel changes requires evaluation if it is to be useful for quantitative evaluation of floodplain sediment residence times. This study aims to simulate recent historic river channel changes along ten 1 km reaches in northern England. Simulation periods were defined by available overlapping historic map and mean daily flow datasets, ranging 27-39 years. LiDAR-derived 2 m DEMs were modified to smooth out present-day channels and burn in historic channel locations. To reduce run times, DEMs were resampled to coarser resolutions based on the size of the channel and historic rate of lateral channel migration. Separate pre-defined coarse and finer channel bed and floodplain grain size distributions were used, respectively, in combination with constructed reach DEMs for model simulations. Calibration was performed by modifying selected parameters to obtain best fits between observed and modelled channel planforms. Initial simulations suggest the model can broadly reproduce observed planform change and is comparable in terms of channel sinuosities and the mean radius of curvature. As such, CAESAR-Lisflood may provide a useful tool for evaluating floodplain sediment residence times under environmental change scenarios.

Manipulation of micro-objects using acoustically oscillating bubbles based on the gas permeability of PDMS.

PubMed

Liu, Bendong; Tian, Baohua; Yang, Xu; Li, Mohan; Yang, Jiahui; Li, Desheng; Oh, Kwang W

2018-05-01

This paper presents a novel manipulation method for micro-objects using acoustically oscillating bubbles with a controllable position based on the gas permeability of polydimethylsiloxane. The oscillating bubble trapped within the side channel attracts the neighboring micro-objects, and the position of the air-liquid interface is controlled by generating temporary pressure difference between the side channel and the air channel. To demonstrate the feasibility of the method in technological applications, polystyrene microparticles of 10  μ m in diameter were successfully captured, transported, and released. The influence of pressure difference on the movement speed of the air-liquid interface was demonstrated in our experiments, and the manipulation performance was also characterized by varying the frequency of the acoustic excitation and the pressure difference. Since the bubble generation and the air-liquid interface movement in our manipulation method do not need any electrochemical reaction and any high temperature, this on-chip manipulation method provides a controllable, efficient, and noninvasive tool for handling micro-objects such as particles, cells, and other entities. The whole manipulation process, including capturing, transporting, and releasing of particles, spent less than 1 min. It can be used to select the cells and particles in the microfluidic device or change the cell culture medium.

A low noise remotely controllable wireless telemetry system for single-unit recording in rats navigating in a vertical maze.

PubMed

Chen, Hsin-Yung; Wu, Jin-Shang; Hyland, Brian; Lu, Xiao-Dong; Chen, Jia Jin Jason

2008-08-01

The use of cables for recording neural activity limits the scope of behavioral tests used in conscious free-moving animals. Particularly, cable attachments make it impossible to record in three-dimensional (3D) mazes where levels are vertically stacked or in enclosed spaces. Such environments are of particular interest in investigations of hippocampal place cells, in which neural activity is correlated with spatial position in the environment. We developed a flexible miniaturized Bluetooth-based wireless data acquisition system. The wireless module included an 8-channel analogue front end, digital controller, and Bluetooth transceiver mounted on a backpack. Our bidirectional wireless design allowed all data channels to be previewed at 1 kHz sample rate, and one channel, selected by remote control, to be sampled at 10 kHz. Extracellular recordings of neuronal activity are highly susceptible to ambient electrical noise due to the high electrode impedance. Through careful design of appropriate shielding and hardware configuration to avoid ground loops, mains power and Bluetooth hopping frequency noise were reduced sufficiently to yield signal quality comparable to those recorded by wired systems. With this system we were able to obtain single-unit recordings of hippocampal place cells in rats running an enclosed vertical maze, over a range of 5 m.

Pore size matters for potassium channel conductance

PubMed Central

Moldenhauer, Hans; Pincuntureo, Matías

2016-01-01

Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance. PMID:27619418

Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating

PubMed Central

Kim, Dorothy M.; Nimigean, Crina M.

2016-01-01

Voltage-gated potassium channels play a fundamental role in the generation and propagation of the action potential. The discovery of these channels began with predictions made by early pioneers, and has culminated in their extensive functional and structural characterization by electrophysiological, spectroscopic, and crystallographic studies. With the aid of a variety of crystal structures of these channels, a highly detailed picture emerges of how the voltage-sensing domain reports changes in the membrane electric field and couples this to conformational changes in the activation gate. In addition, high-resolution structural and functional studies of K+ channel pores, such as KcsA and MthK, offer a comprehensive picture on how selectivity is achieved in K+ channels. Here, we illustrate the remarkable features of voltage-gated potassium channels and explain the mechanisms used by these machines with experimental data. PMID:27141052

NS6180, a new KCa3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease

PubMed Central

Strøbæk, D; Brown, DT; Jenkins, DP; Chen, Y-J; Coleman, N; Ando, Y; Chiu, P; Jørgensen, S; Demnitz, J; Wulff, H; Christophersen, P

2013-01-01

Background and Purpose The KCa3.1 channel is a potential target for therapy of immune disease. We identified a compound from a new chemical class of KCa3.1 inhibitors and assessed in vitro and in vivo inhibition of immune responses. Experimental Approach We characterized the benzothiazinone NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one) with respect to potency and molecular site of action on KCa3.1 channels, selectivity towards other targets, effects on T-cell activation as well as pharmacokinetics and inflammation control in colitis induced by 2,4-dinitrobenzene sulfonic acid, a rat model of inflammatory bowel disease (IBD). Key Results NS6180 inhibited cloned human KCa3.1 channels (IC50 = 9 nM) via T250 and V275, the same amino acid residues conferring sensitivity to triarylmethanes such as like TRAM-34. NS6180 inhibited endogenously expressed KCa3.1 channels in human, mouse and rat erythrocytes, with similar potencies (15–20 nM). NS6180 suppressed rat and mouse splenocyte proliferation at submicrolar concentrations and potently inhibited IL-2 and IFN-γ production, while exerting smaller effects on IL-4 and TNF-α and no effect on IL-17 production. Antibody staining showed KCa3.1 channels in healthy colon and strong up-regulation in association with infiltrating immune cells after induction of colitis. Despite poor plasma exposure, NS6180 (3 and 10 mg·kg−1 b.i.d.) dampened colon inflammation and improved body weight gain as effectively as the standard IBD drug sulfasalazine (300 mg·kg−1 q.d.). Conclusions and Implications NS6180 represents a novel class of KCa3.1 channel inhibitors which inhibited experimental colitis, suggesting KCa3.1 channels as targets for pharmacological control of intestinal inflammation. PMID:22891655

Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

PubMed

Ghazizadeh, Vahid; Nazıroğlu, Mustafa

2014-09-01

Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

Unraveling the mechanism of selective ion transport in hydrophobic subnanometer channels.

PubMed

Li, Hui; Francisco, Joseph S; Zeng, Xiao Cheng

2015-09-01

Recently reported synthetic organic nanopore (SONP) can mimic a key feature of natural ion channels, i.e., selective ion transport. However, the physical mechanism underlying the K(+)/Na(+) selectivity for the SONPs is dramatically different from that of natural ion channels. To achieve a better understanding of the selective ion transport in hydrophobic subnanometer channels in general and SONPs in particular, we perform a series of ab initio molecular dynamics simulations to investigate the diffusivity of aqua Na(+) and K(+) ions in two prototype hydrophobic nanochannels: (i) an SONP with radius of 3.2 Å, and (ii) single-walled carbon nanotubes (CNTs) with radii of 3-5 Å (these radii are comparable to those of the biological potassium K(+) channels). We find that the hydration shell of aqua Na(+) ion is smaller than that of aqua K(+) ion but notably more structured and less yielding. The aqua ions do not lower the diffusivity of water molecules in CNTs, but in SONP the diffusivity of aqua ions (Na(+) in particular) is strongly suppressed due to the rugged inner surface. Moreover, the aqua Na(+) ion requires higher formation energy than aqua K(+) ion in the hydrophobic nanochannels. As such, we find that the ion (K(+) vs. Na(+)) selectivity of the (8, 8) CNT is ∼20× higher than that of SONP. Hence, the (8, 8) CNT is likely the most efficient artificial K(+) channel due in part to its special interior environment in which Na(+) can be fully solvated, whereas K(+) cannot. This work provides deeper insights into the physical chemistry behind selective ion transport in nanochannels.

KV7 channels in the human detrusor: channel modulator effects and gene and protein expression.

PubMed

Bientinesi, Riccardo; Mancuso, Cesare; Martire, Maria; Bassi, Pier Francesco; Sacco, Emilio; Currò, Diego

2017-02-01

Voltage-gated type 7 K + (K V 7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of K V 7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of K V 7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective K V 7 channel blocker, concentration-dependently contracted the human detrusor; mean EC 50 and E max of XE-991-induced concentration-response curve were 14.1 μM and 28.8 % of the maximal bethanechol-induced contraction, respectively. Flupirtine and retigabine, selective K V 7.2-7.5 channel activators, induced concentration-dependent relaxations of bethanechol-precontracted strips, with maximal relaxations of 51.6 and 51.8 % of the precontraction, respectively. XE-991 blocked the relaxations induced by flupirtine and retigabine. All five KCNQ genes were found to be expressed in the detrusor with KCNQ4 being the most expressed among them. Different bands, having sizes similar to some of reported K V 7.1, 7.4, and 7.5 channel subunit isoforms, were detected in the detrusor by Western blot with the K V 7.4 band being the most intense among them. In conclusion, K V 7 channels contribute to set the basal tone of the human detrusor. In addition, K V 7 channel activators significantly relax the detrusor. The K V 7.4 channels are probably the most important K V 7 channels expressed in the human detrusor. These data suggest that selective K V 7.4 channel activators might represent new pharmacological tools for inducing therapeutic relaxation of the detrusor.

Multi-channel temperature measurement system for automotive battery stack

NASA Astrophysics Data System (ADS)

Lewczuk, Radoslaw; Wojtkowski, Wojciech

2017-08-01

A multi-channel temperature measurement system for monitoring of automotive battery stack is presented in the paper. The presented system is a complete battery temperature measuring system for hybrid / electric vehicles that incorporates multi-channel temperature measurements with digital temperature sensors communicating through 1-Wire buses, individual 1-Wire bus for each sensor for parallel computing (parallel measurements instead of sequential), FPGA device which collects data from sensors and translates it for CAN bus frames. CAN bus is incorporated for communication with car Battery Management System and uses additional CAN bus controller which communicates with FPGA device through SPI bus. The described system can parallel measure up to 12 temperatures but can be easily extended in the future in case of additional needs. The structure of the system as well as particular devices are described in the paper. Selected results of experimental investigations which show proper operation of the system are presented as well.

Superhydrophobic nanofluidic channels for enhanced electrokinetic conversion

NASA Astrophysics Data System (ADS)

Checco, Antonio; Al Hossain, Aktaruzzaman; Rahmani, Amir; Black, Charles; Doerk, Gregory; Colosqui, Carlos

2017-11-01

We present current efforts in the development of novel slit nanofluidic channels with superhydrophobic nanostructured surfaces designed to enhance hydrodynamic conductivity and improve selective transport and electrokinetic energy conversion efficiencies (mechanical-electrical energy conversion). The nanochannels are fabricated on silicon wafers using UV lithography, and their internal surface is patterned with conical nanostructures (feature size and spacing 30 nm) defined by block copolymer self-assembly and plasma etching. These nanostructures are rendered superhydrophobic by passivation with a hydrophobic silane monolayer. We experimentally characterize hydrodynamic conductivity, effective zeta potentials, and eletrokinetic flows for the patterned nanochannels, comparing against control channels with bare surfaces. Experimental observations are rationalized using both continuum-based modeling and molecular dynamics simulations. Scientific and technical knowledge produced by this work is particularly relevant for sustainable energy conversion and storage, separation processes and water treatment using nanoporous materials. The ONR Contract # N000141613178 and NSF-CBET award# 1605809.

The N-terminal domain of GluR6-subtype glutamate receptor ion channels

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

Kumar, Janesh; Schuck, Peter; Jin, Rongsheng

2009-09-25

The amino-terminal domain (ATD) of glutamate receptor ion channels, which controls their selective assembly into AMPA, kainate and NMDA receptor subtypes, is also the site of action of NMDA receptor allosteric modulators. Here we report the crystal structure of the ATD from the kainate receptor GluR6. The ATD forms dimers in solution at micromolar protein concentrations and crystallizes as a dimer. Unexpectedly, each subunit adopts an intermediate extent of domain closure compared to the apo and ligand-bound complexes of LIVBP and G protein-coupled glutamate receptors (mGluRs), and the dimer assembly has a markedly different conformation from that found in mGluRs.more » This conformation is stabilized by contacts between large hydrophobic patches in the R2 domain that are absent in NMDA receptors, suggesting that the ATDs of individual glutamate receptor ion channels have evolved into functionally distinct families.« less

Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice.

PubMed

Ardiles, Alvaro O; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M; Palacios, Adrian G; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C; Martínez, Agustín D

2014-01-01

The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca(2+) concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory.

Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice

PubMed Central

Ardiles, Alvaro O.; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M.; Palacios, Adrian G.; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C.; Martínez, Agustín D.

2014-01-01

The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory. PMID:25360084

Independent and cooperative motions of the Kv1.2 channel: voltage sensing and gating.

PubMed

Yeheskel, Adva; Haliloglu, Turkan; Ben-Tal, Nir

2010-05-19

Voltage-gated potassium (Kv) channels, such as Kv1.2, are involved in the generation and propagation of action potentials. The Kv channel is a homotetramer, and each monomer is composed of a voltage-sensing domain (VSD) and a pore domain (PD). We analyzed the fluctuations of a model structure of Kv1.2 using elastic network models. The analysis suggested a network of coupled fluctuations of eight rigid structural units and seven hinges that may control the transition between the active and inactive states of the channel. For the most part, the network is composed of amino acids that are known to affect channel activity. The results suggested allosteric interactions and cooperativity between the subunits in the coupling between the motion of the VSD and the selectivity filter of the PD, in accordance with recent empirical data. There are no direct contacts between the VSDs of the four subunits, and the contacts between these and the PDs are loose, suggesting that the VSDs are capable of functioning independently. Indeed, they manifest many inherent fluctuations that are decoupled from the rest of the structure. In general, the analysis suggests that the two domains contribute to the channel function both individually and cooperatively. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

An atypical CNG channel activated by a single cGMP molecule controls sperm chemotaxis.

PubMed

Bönigk, Wolfgang; Loogen, Astrid; Seifert, Reinhard; Kashikar, Nachiket; Klemm, Clementine; Krause, Eberhard; Hagen, Volker; Kremmer, Elisabeth; Strünker, Timo; Kaupp, U Benjamin

2009-10-27

Sperm of the sea urchin Arbacia punctulata can respond to a single molecule of chemoattractant released by an egg. The mechanism underlying this extreme sensitivity is unknown. Crucial signaling events in the response of A. punctulata sperm to chemoattractant include the rapid synthesis of the intracellular messenger guanosine 3',5'-monophosphate (cGMP) and the ensuing membrane hyperpolarization that results from the opening of potassium-selective cyclic nucleotide-gated (CNGK) channels. Here, we use calibrated photolysis of caged cGMP to show that approximately 45 cGMP molecules are generated during the response to a single molecule of chemoattractant. The CNGK channel can respond to such small cGMP changes because it is exquisitely sensitive to cGMP and activated in a noncooperative fashion. Like voltage-activated Ca(v) and Na(v) channels, the CNGK polypeptide consists of four homologous repeat sequences. Disabling each of the four cyclic nucleotide-binding sites through mutagenesis revealed that binding of a single cGMP molecule to repeat 3 is necessary and sufficient to activate the CNGK channel. Thus, CNGK has developed a mechanism of activation that is different from the activation of other CNG channels, which requires the cooperative binding of several ligands and operates in the micromolar rather than the nanomolar range.

TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

PubMed Central

Raphaël, Maylis; Lehen’kyi, V’yacheslav; Vandenberghe, Matthieu; Beck, Benjamin; Khalimonchyk, Sergiy; Vanden Abeele, Fabien; Farsetti, Leonardo; Germain, Emmanuelle; Bokhobza, Alexandre; Mihalache, Adriana; Gosset, Pierre; Romanin, Christoph; Clézardin, Philippe; Skryma, Roman; Prevarskaya, Natalia

2014-01-01

Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca2+/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca2+/Annexin I/S100A11 pathway. PMID:25172921

Selective ion accumulation in an ICP/ITMS using a filtered noise field

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

Eiden, G.C.; Barinaga, C.J.; Koppenaal, D.W.

1995-12-31

Selective accumulation of ions in an ion trap mass spectrometer (ITMS) has been characterized using both single frequency and broadband resonant excitation. The goal of this work is to enhance selective accumulation of ions from plasmas and other external ion sources. The charge capacity of the ITMS is 10{sup 6} to 10{sup 7} ions, although the mass spectrum is distorted at much lower space charge. Detection of trace ions necessitates selective detection schemes such as selective trapping or optical detection. The authors report results of selective trapping studies for Sr, Y, and Zr solutions (100 ppb Y and 1 ppbmore » each Sr, Zr). {open_quotes}Background{close_quotes} ions in mass channels adjacent to the channel of interest is a worst case situation with respect to selective ejection and abundance sensitivity. Real samples will often have matrix ion m/z values much further removed from the m/z of the ions of interest. Thus, the authors also give results for a multielement solution. Ions from an inductively coupled plasma ion source are endcap injected into the ITMS. Broadband waveforms were generated by an HST-1000 (Teledyne MEC) instrument, using the filtered noise field (FNF) method. The experiment is controlled by the ITMS electronics and ICMS software. The sequence of experimental events is: ion injection at q{sub z} = 0.4 (typical), collisionally cool ions, set trapping potential for resonant excitation (q{sub z} = 0.2 to 0.6), analysis rf ramp.« less

Channel-forming activity in the venom of the cockroach-hunting wasp, Ampulex compressa.

PubMed

Gincel, Dan; Haspel, Gal; Libersat, Frederic

2004-05-01

The parasitoid solitary wasp Ampulex compressa uses the cockroach Periplaneta americana as a food supply for its larvae. To subdue its prey, the wasp injects a venom cocktail into the brain of the cockroach. We investigated channel activity of A. compressa venom by collecting venom and incorporating it into a planar lipid bilayer. The venom, reconstituted into the bilayer, showed ion channel activity, forming a fast-fluctuating channel with a small conductance of 20+/-0.1pS, with no voltage sensitivity. These channels were not observed when the venom was digested with proteases before application to the bilayer, but were not affected by exposure to protease after their incorporation into the bilayer, indicating that the active venom component is a peptide. The channels were found to be cation selective with similar selectivity for the monovalent cations K(+), Li(+) and Na(+), but showed high selectivity against anions (Cl(-)) and divalent cations (Ca(2+) and Mg(2+)). This study is the first demonstration and biophysical characterization of channel activity in the venom of A. compressa. The possible functional significance of this channel activity is discussed in light of the unusual nature of the effects of this wasp venom on the behavior of its prey.

The OGO attitude control subsystem redesign as a result of OGO 3 experience. Volume 1: System analysis and design studies

NASA Technical Reports Server (NTRS)

Mckenna, K. J.

1967-01-01

An oscillation in the OGO-3 roll control channel, resulting from the EP-5 and EP-6 boom motion coupling into the control channel and causing loss of attitude control, is investigated. The study includes (1) an analysis of the OGO-3 and OGO-2 flight data to determine the nature and extent of the roll oscillation phenomena, (2) design analysis of the complete attitude control subsystem (ACS) to evolve changes which would prevent recurrences of the coupled ACS boom oscillation observed on OGO-3, and (3) analog simulations to verify the performance of the design changes selected. Portions of OGO-3 and OGO-2 flight data are illustrated and the major flexible body oscillation are identified. A model of the major flexible appendage dynamics is developed and is shown analytically and through analog simulations to reproduce the OGO-3 oscillation phenomena. The design changes which were found necessary are: a reversal delay logic for the roll reaction wheels, widening of the solar array dead zone from 0.5 to 1.0 deg, and modification of the OPEP control loop to include a filter and stabilizing feedback loops.

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.

Region based Brain Computer Interface for a home control application.

PubMed

Akman Aydin, Eda; Bay, Omer Faruk; Guler, Inan

2015-08-01

Environment control is one of the important challenges for disabled people who suffer from neuromuscular diseases. Brain Computer Interface (BCI) provides a communication channel between the human brain and the environment without requiring any muscular activation. The most important expectation for a home control application is high accuracy and reliable control. Region-based paradigm is a stimulus paradigm based on oddball principle and requires selection of a target at two levels. This paper presents an application of region based paradigm for a smart home control application for people with neuromuscular diseases. In this study, a region based stimulus interface containing 49 commands was designed. Five non-disabled subjects were attended to the experiments. Offline analysis results of the experiments yielded 95% accuracy for five flashes. This result showed that region based paradigm can be used to select commands of a smart home control application with high accuracy in the low number of repetitions successfully. Furthermore, a statistically significant difference was not observed between the level accuracies.

A Study of the Effects of Electrode Number and Decoding Algorithm on Online EEG-Based BCI Behavioral Performance

PubMed Central

Meng, Jianjun; Edelman, Bradley J.; Olsoe, Jaron; Jacobs, Gabriel; Zhang, Shuying; Beyko, Angeliki; He, Bin

2018-01-01

Motor imagery–based brain–computer interface (BCI) using electroencephalography (EEG) has demonstrated promising applications by directly decoding users' movement related mental intention. The selection of control signals, e.g., the channel configuration and decoding algorithm, plays a vital role in the online performance and progressing of BCI control. While several offline analyses report the effect of these factors on BCI accuracy for a single session—performance increases asymptotically by increasing the number of channels, saturates, and then decreases—no online study, to the best of our knowledge, has yet been performed to compare for a single session or across training. The purpose of the current study is to assess, in a group of forty-five subjects, the effect of channel number and decoding method on the progression of BCI performance across multiple training sessions and the corresponding neurophysiological changes. The 45 subjects were divided into three groups using Laplacian Filtering (LAP/S) with nine channels, Common Spatial Pattern (CSP/L) with 40 channels and CSP (CSP/S) with nine channels for online decoding. At the first training session, subjects using CSP/L displayed no significant difference compared to CSP/S but a higher average BCI performance over those using LAP/S. Despite the average performance when using the LAP/S method was initially lower, but LAP/S displayed improvement over first three sessions, whereas the other two groups did not. Additionally, analysis of the recorded EEG during BCI control indicates that the LAP/S produces control signals that are more strongly correlated with the target location and a higher R-square value was shown at the fifth session. In the present study, we found that subjects' average online BCI performance using a large EEG montage does not show significantly better performance after the first session than a smaller montage comprised of a common subset of these electrodes. The LAP/S method with a small EEG montage allowed the subjects to improve their skills across sessions, but no improvement was shown for the CSP method. PMID:29681792

A Study of the Effects of Electrode Number and Decoding Algorithm on Online EEG-Based BCI Behavioral Performance.

PubMed

Meng, Jianjun; Edelman, Bradley J; Olsoe, Jaron; Jacobs, Gabriel; Zhang, Shuying; Beyko, Angeliki; He, Bin

2018-01-01

Motor imagery-based brain-computer interface (BCI) using electroencephalography (EEG) has demonstrated promising applications by directly decoding users' movement related mental intention. The selection of control signals, e.g., the channel configuration and decoding algorithm, plays a vital role in the online performance and progressing of BCI control. While several offline analyses report the effect of these factors on BCI accuracy for a single session-performance increases asymptotically by increasing the number of channels, saturates, and then decreases-no online study, to the best of our knowledge, has yet been performed to compare for a single session or across training. The purpose of the current study is to assess, in a group of forty-five subjects, the effect of channel number and decoding method on the progression of BCI performance across multiple training sessions and the corresponding neurophysiological changes. The 45 subjects were divided into three groups using Laplacian Filtering (LAP/S) with nine channels, Common Spatial Pattern (CSP/L) with 40 channels and CSP (CSP/S) with nine channels for online decoding. At the first training session, subjects using CSP/L displayed no significant difference compared to CSP/S but a higher average BCI performance over those using LAP/S. Despite the average performance when using the LAP/S method was initially lower, but LAP/S displayed improvement over first three sessions, whereas the other two groups did not. Additionally, analysis of the recorded EEG during BCI control indicates that the LAP/S produces control signals that are more strongly correlated with the target location and a higher R-square value was shown at the fifth session. In the present study, we found that subjects' average online BCI performance using a large EEG montage does not show significantly better performance after the first session than a smaller montage comprised of a common subset of these electrodes. The LAP/S method with a small EEG montage allowed the subjects to improve their skills across sessions, but no improvement was shown for the CSP method.

Ion Trapping with Fast-Response Ion-Selective Microelectrodes Enhances Detection of Extracellular Ion Channel Gradients

PubMed Central

Messerli, Mark A.; Collis, Leon P.; Smith, Peter J.S.

2009-01-01

Previously, functional mapping of channels has been achieved by measuring the passage of net charge and of specific ions with electrophysiological and intracellular fluorescence imaging techniques. However, functional mapping of ion channels using extracellular ion-selective microelectrodes has distinct advantages over the former methods. We have developed this method through measurement of extracellular K+ gradients caused by efflux through Ca2+-activated K+ channels expressed in Chinese hamster ovary cells. We report that electrodes constructed with short columns of a mechanically stable K+-selective liquid membrane respond quickly and measure changes in local [K+] consistent with a diffusion model. When used in close proximity to the plasma membrane (<4 μm), the ISMs pose a barrier to simple diffusion, creating an ion trap. The ion trap amplifies the local change in [K+] without dramatically changing the rise or fall time of the [K+] profile. Measurement of extracellular K+ gradients from activated rSlo channels shows that rapid events, 10–55 ms, can be characterized. This method provides a noninvasive means for functional mapping of channel location and density as well as for characterizing the properties of ion channels in the plasma membrane. PMID:19217875

Elucidating the mechanism of protein water channels by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Grubmuller, Helmut

2004-03-01

Aquaporins are highly selective water channels. Molecular dynamics simulations of multiple water permeation events correctly predict the measured rate and explain at the atomic level why these membrane channels are so efficient, while blocking other small molecules, ions, and even protons. High efficiency is achieved through a carefully tailored balance of hydrogen bonds that the protein substitutes for the bulk interactions; selectivity is achieved mainly by electrostatic barriers.

The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential.

PubMed

Antonenkov, Vasily D; Isomursu, Antti; Mennerich, Daniela; Vapola, Miia H; Weiher, Hans; Kietzmann, Thomas; Hiltunen, J Kalervo

2015-05-29

The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel's selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17(-/-) mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential*

PubMed Central

Antonenkov, Vasily D.; Isomursu, Antti; Mennerich, Daniela; Vapola, Miia H.; Weiher, Hans; Kietzmann, Thomas; Hiltunen, J. Kalervo

2015-01-01

The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel's selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17−/− mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions. PMID:25861990

TRPC3 channels play a critical role in the theta component of pilocarpine-induced Status Epilepticus in mice

PubMed Central

Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang

2016-01-01

Summary Objective Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the BDNF/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced Status Epilepticus (SE). Methods The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and EEG recording of pilocarpine-induced seizures were performed. Results We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity which dominates both the pre-ictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anti-convulsive drugs. PMID:28012173

Optical Addressing of Multi-Colour Photochromic Material Mixture for Volumetric Display.

PubMed

Hirayama, Ryuji; Shiraki, Atsushi; Naruse, Makoto; Nakamura, Shinichiro; Nakayama, Hirotaka; Kakue, Takashi; Shimobaba, Tomoyoshi; Ito, Tomoyoshi

2016-08-16

This is the first study to demonstrate that colour transformations in the volume of a photochromic material (PM) are induced at the intersections of two control light channels, one controlling PM colouration and the other controlling decolouration. Thus, PM colouration is induced by position selectivity, and therefore, a dynamic volumetric display may be realised using these two control lights. Moreover, a mixture of multiple PM types with different absorption properties exhibits different colours depending on the control light spectrum. Particularly, the spectrum management of the control light allows colour-selective colouration besides position selectivity. Therefore, a PM-based, full-colour volumetric display is realised. We experimentally construct a mixture of two PM types and validate the operating principles of such a volumetric display system. Our system is constructed simply by mixing multiple PM types; therefore, the display hardware structure is extremely simple, and the minimum size of a volume element can be as small as the size of a molecule. Volumetric displays can provide natural three-dimensional (3D) perception; therefore, the potential uses of our system include high-definition 3D visualisation for medical applications, architectural design, human-computer interactions, advertising, and entertainment.

Optical Addressing of Multi-Colour Photochromic Material Mixture for Volumetric Display

NASA Astrophysics Data System (ADS)

Hirayama, Ryuji; Shiraki, Atsushi; Naruse, Makoto; Nakamura, Shinichiro; Nakayama, Hirotaka; Kakue, Takashi; Shimobaba, Tomoyoshi; Ito, Tomoyoshi

2016-08-01

This is the first study to demonstrate that colour transformations in the volume of a photochromic material (PM) are induced at the intersections of two control light channels, one controlling PM colouration and the other controlling decolouration. Thus, PM colouration is induced by position selectivity, and therefore, a dynamic volumetric display may be realised using these two control lights. Moreover, a mixture of multiple PM types with different absorption properties exhibits different colours depending on the control light spectrum. Particularly, the spectrum management of the control light allows colour-selective colouration besides position selectivity. Therefore, a PM-based, full-colour volumetric display is realised. We experimentally construct a mixture of two PM types and validate the operating principles of such a volumetric display system. Our system is constructed simply by mixing multiple PM types; therefore, the display hardware structure is extremely simple, and the minimum size of a volume element can be as small as the size of a molecule. Volumetric displays can provide natural three-dimensional (3D) perception; therefore, the potential uses of our system include high-definition 3D visualisation for medical applications, architectural design, human-computer interactions, advertising, and entertainment.

Delineation of soil temperature regimes from HCMM data

NASA Technical Reports Server (NTRS)

Day, R. L.; Petersen, G. W. (Principal Investigator)

1982-01-01

The subsetting of HCMM data into ORSER format was completed for four dates using a modified SUBSET program. Large areas (approximately 2500 scan lines, 1680 elements) were selected to increase the occurrence of suitable control points for registration. Average daily temperatures (ADT) were calculated for each date. The MERGE program combined registered daytime temperature (DAY-IR) with nighttime temperature (NIGHT-IR) to form a separate two-channel data set. The SUBTRAN program averaged the DAY-IR and NIGHT-IR creating a third ADT channel. Registration equations for the four ADT data sets were generated. A one dimensional soil heat flow equation was modified to allow for mean annual soil temperature predictions using merged ADT data sets.

Intrathecal resiniferatoxin in a dog model: Efficacy in bone cancer pain

PubMed Central

Brown, Dorothy Cimino; Agnello, Kimberly; Iadarola, Michael J.

2015-01-01

Resiniferatoxin (RTX) is the most potent amongst all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium permeable non-selective cation channel, expressed on the peripheral and central terminals of small diameter sensory neurons. [11,32] Prolonged calcium influx induced by RTX causes cytotoxicity and death of only those sensory neurons that express the TRPV1 ion channel leading to selective targeting and permanent deletion of the TRPV1-expressing C-fiber neuronal cell bodies in the dorsal root ganglia. [10,17] The goal of this project was to provide pre-clinical efficacy data, that intrathecal RTX could provide effective pain relief and improve function in dogs with bone cancer without significant long-term side effects. In a single blind, controlled study, 72 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n=36) or 1.2 mcg/kg intrathecal RTX in addition to standard of care analgesic therapy (treated, n=36). Significantly more dogs in the control group (78%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with RTX (50%; p<0.03); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with RTX (p<0.02). The analgesic effect was documented in these dogs without any evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies. PMID:25659068

Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

PubMed Central

2010-01-01

Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS), considered a neuropathic orofacial pain disorder. Methods Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5) and controls (n = 12), and the other patients with BMS (n = 7) and controls (n = 10). BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS). Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Nav1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results There was a significantly increased visual intensity score for Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS. PMID:20529324

Voltage-gated Proton Channels

PubMed Central

DeCoursey, Thomas E.

2014-01-01

Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance ~103 smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn2+ (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H+ for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens. PMID:23798303

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

PubMed Central

Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

2014-01-01

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force–displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell’s characteristic frequency of responsiveness. PMID:24799674

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

PubMed Central

Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

2013-01-01

The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

Modeling the human Nav1.5 sodium channel: structural and mechanistic insights of ion permeation and drug blockade

PubMed Central

Ahmed, Marawan; Jalily Hasani, Horia; Ganesan, Aravindhan; Houghton, Michael; Barakat, Khaled

2017-01-01

Abnormalities in the human Nav1.5 (hNav1.5) voltage-gated sodium ion channel (VGSC) are associated with a wide range of cardiac problems and diseases in humans. Current structural models of hNav1.5 are still far from complete and, consequently, their ability to study atomistic interactions of this channel is very limited. Here, we report a comprehensive atomistic model of the hNav1.5 ion channel, constructed using homology modeling technique and refined through long molecular dynamics simulations (680 ns) in the lipid membrane bilayer. Our model was comprehensively validated by using reported mutagenesis data, comparisons with previous models, and binding to a panel of known hNav1.5 blockers. The relatively long classical MD simulation was sufficient to observe a natural sodium permeation event across the channel’s selectivity filters to reach the channel’s central cavity, together with the identification of a unique role of the lysine residue. Electrostatic potential calculations revealed the existence of two potential binding sites for the sodium ion at the outer selectivity filters. To obtain further mechanistic insight into the permeation event from the central cavity to the intracellular region of the channel, we further employed “state-of-the-art” steered molecular dynamics (SMD) simulations. Our SMD simulations revealed two different pathways through which a sodium ion can be expelled from the channel. Further, the SMD simulations identified the key residues that are likely to control these processes. Finally, we discuss the potential binding modes of a panel of known hNav1.5 blockers to our structural model of hNav1.5. We believe that the data presented here will enhance our understanding of the structure–property relationships of the hNav1.5 ion channel and the underlying molecular mechanisms in sodium ion permeation and drug interactions. The results presented here could be useful for designing safer drugs that do not block the hNav1.5 channel. PMID:28831242

Fabrication and Analysis of a Selectively Contacted Dual Channel High Electron Mobility Field-Effect Transistor

NASA Astrophysics Data System (ADS)

Khanna, Ravi

1992-01-01

A selectively contacted dual-channel high electron mobility transistor (SCD-CHEMT) has been designed, fabricated, and electrically characterized, in order to better understand the properties of two layers of two-dimensional electron gases (2DEGs) confined within a quantum well. The 2DEGs are placed under a Schottky barrier control gate which modulates their sheet charge densities, and by use of auxiliary Schottky barrier gates and two levels of ohmic contacts, electrical contacts to the individual channels in which each 2DEG resides is achieved. The design of the dual channel FET structure, and its practical realization by recourse to process development and fabrication are described, as are the techniques, results, and interpretations of electrical characterizations used to analyze the completed device. Critical fabrication procedures involving photolithography, etching, deposition, shallow and deep ohmic contact formation, and gate formation are developed, and a simple technique to reduce gate leakage by photo-oxidation is demonstrated. Analysis of the completed device is performed using one-dimensional band diagram simulations, magnetotransport and electrical measurements. Magnetotransport studies establish the existence of two 2DEGs within the quantum well at 4K. Drain current vs. drain voltage, and transconductance vs. gate voltage characteristics at room temperature confirm the presence of two 2DEGs and show that current flow between them occurs easily at room temperature. Carrier electron mobility profiles are taken of the 2DEGs and show that the lower 2DEG has a mobility comparable to that of a 2DEG formed at a normal interface, indicating that the "inverted interface problem" has been overcome. Capacitance vs. gate voltage measurements are taken, which are consistent with a simple device model consisting of gate depletion and interelectrode parasitic capacitances. It is concluded from the analysis that the dual channel system resides in three basic states: (1) Both channels are occupied by 2DEGs or (2) The upper channel is depleted, or (3) Both channels depleted. Finally, increase in isolation between the two 2DEGs is dramatically demonstrated at 77K by the drain current vs. drain voltage, and transconductance vs. gate voltage characteristics.

Reconstitution and functional comparison of purified GlpF and AqpZ, the glycerol and water channels from Escherichia coli.

PubMed

Borgnia, M J; Agre, P

2001-02-27

A large family of membrane channel proteins selective for transport of water (aquaporins) or water plus glycerol (aquaglyceroporins) has been found in diverse life forms. Escherichia coli has two members of this family-a water channel, AqpZ, and a glycerol facilitator, GlpF. Despite having similar primary amino acid sequences and predicted structures, the oligomeric state and solute selectivity of AqpZ and GlpF are disputed. Here we report biochemical and functional characterizations of affinity-purified GlpF and compare it to AqpZ. Histidine-tagged (His-GlpF) and hemagglutinin-tagged (HA-GlpF) polypeptides encoded by a bicistronic construct were expressed in bacteria. HA-GlpF and His-GlpF appear to form oligomers during Ni-nitrilotriacetate affinity purification. Sucrose gradient sedimentation analyses showed that the oligomeric state of octyl glucoside-solubilized GlpF varies: low ionic strength favors subunit dissociation, whereas Mg(2+) stabilizes tetrameric assembly. Reconstitution of affinity-purified GlpF into proteoliposomes increases glycerol permeability more than 100-fold and water permeability up to 10-fold compared with control liposomes. Glycerol and water permeability of GlpF both occur with low Arrhenius activation energies and are reversibly inhibited by HgCl(2). Our studies demonstrate that, unlike AqpZ, a water-selective stable tetramer, purified GlpF exists in multiple oligomeric forms under nondenaturing conditions and is highly permeable to glycerol but less well permeated by water.

Anion channels in the sea urchin sperm plasma membrane.

PubMed

Morales, E; de la Torre, L; Moy, G W; Vacquier, V D; Darszon, A

1993-10-01

Ionic fluxes in sea urchin sperm plasma membrane regulate cell motility and the acrosome reaction (AR). Although cationic channels mediate some of the ionic movements, little is known about anion channels in these cells. The fusion of sperm plasma membranes into lipid bilayers allowed identification of a 150 pS anion channel. This anion channel was enriched from detergent-solubilized sperm plasma membranes using a wheat germ agglutinin Sepharose column. Vesicles formed from this preparation were fused into black lipid membranes (BLM), yielding single channel anion-selective activity with the properties of those found in the sperm membranes. The following anion selectivity sequence was found: NO3- > CNS- > Br- > Cl-. This anion channel has a high open probability at the holding potentials tested, it is partially blocked by 4,4'-diisothiocyano-2,2'-stilbendisulfonic acid (DIDS), and it often displays substates. The sperm AR was also inhibited by DIDS.

Altered ion channel conductance and ionic selectivity induced by large imposed membrane potential pulse.

PubMed Central

Chen, W; Lee, R C

1994-01-01

The effects of large magnitude transmembrane potential pulses on voltage-gated Na and K channel behavior in frog skeletal muscle membrane were studied using a modified double vaseline-gap voltage clamp. The effects of electroconformational damage to ionic channels were separated from damage to lipid bilayer (electroporation). A 4 ms transmembrane potential pulse of -600 mV resulted in a reduction of both Na and K channel conductivities. The supraphysiologic pulses also reduced ionic selectivity of the K channels against Na+ ions, resulting in a depolarization of the membrane resting potential. However, TTX and TEA binding effects were unaltered. The kinetics of spontaneous reversal of the electroconformational damage of channel proteins was found to be dependent on the magnitude of imposed membrane potential pulse. These results suggest that muscle and nerve dysfunction after electrical shock may be in part caused by electroconformational damage to voltage-gated ion channels. PMID:7948676

Role of the Local Anesthetic Receptor in the State-Dependent Inhibition of Voltage-Gated Sodium Channels by the Insecticide Metaflumizone

PubMed Central

von Stein, Richard T.

2012-01-01

Sodium channel inhibitor (SCI) insecticides selectively target voltage-gated sodium (Nav) channels in the slow-inactivated state by binding at or near the local anesthetic receptor within the sodium channel pore. Metaflumizone is a new insecticide for the treatment of fleas on domesticated pets and has recently been reported to block insect sodium channels in the slow-inactivated state, thereby implying that it is also a member of the SCI class. Using the two-electrode voltage-clamp technique, we examined metaflumizone inhibition of rat Nav1.4 sodium channels expressed in Xenopus laevis oocytes. Metaflumizone selectively inhibited Nav1.4 channels at potentials that promoted slow inactivation and shifted the voltage dependence of slow inactivation in the direction of hyperpolarization. Metaflumizone perfusion at a hyperpolarized holding potential also shifted the conductance-voltage curve for activation in the direction of depolarization and antagonized use-dependent lidocaine inhibition of fast-inactivated sodium channels, actions not previously observed with other SCI insecticides. We expressed mutated Nav1.4/F1579A and Nav1.4/Y1586A channels to investigate whether metaflumizone shares the domain IV segment S6 (DIV-S6) binding determinants identified for other SCI insecticides. Consistent with previous investigations of SCI insecticides on rat Nav1.4 channels, the F1579A mutation reduced sensitivity to block by metaflumizone, whereas the Y1586A mutation paradoxically increased the sensitivity to metaflumizone. We conclude that metaflumizone selectively inhibits slow-inactivated Nav1.4 channels and shares DIV-S6 binding determinants with other SCI insecticides and therapeutic drugs. However, our results suggest that metaflumizone interacts with resting and fast-inactivated channels in a manner that is distinct from other compounds in this insecticide class. PMID:22127519

47 CFR 90.627 - Limitation on the number of frequency pairs that may be assignable for trunked systems and on the...

Code of Federal Regulations, 2010 CFR

2010-10-01

... MOBILE RADIO SERVICES Regulations Governing Licensing and Use of Frequencies in the 806-824, 851-869, 896-901, and 935-940 MHz Bands Policies Governing the Processing of Applications and the Selection and... 70 mobile and control stations per channel. [47 FR 41032, Sept. 16, 1982, as amended at 48 FR 44559...

Communications circuit including a linear quadratic estimator

DOEpatents

Ferguson, Dennis D.

2015-07-07

A circuit includes a linear quadratic estimator (LQE) configured to receive a plurality of measurements a signal. The LQE is configured to weight the measurements based on their respective uncertainties to produce weighted averages. The circuit further includes a controller coupled to the LQE and configured to selectively adjust at least one data link parameter associated with a communication channel in response to receiving the weighted averages.

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

Ngo, Van; Wang, Yibo; Haas, Stephan

Crystal structures of several bacterial Na v channels have been recently published and molecular dynamics simulations of ion permeation through these channels are consistent with many electrophysiological properties of eukaryotic channels. Bacterial Na v channels have been characterized as functionally asymmetric, and the mechanism of this asymmetry has not been clearly understood. To address this question, we combined non-equilibrium simulation data with two-dimensional equilibrium unperturbed landscapes generated by umbrella sampling and Weighted Histogram Analysis Methods for multiple ions traversing the selectivity filter of bacterial Na vAb channel. This approach provided new insight into the mechanism of selective ion permeation inmore » bacterial Nav channels. The non-equilibrium simulations indicate that two or three extracellular K + ions can block the entrance to the selectivity filter of Na vAb in the presence of applied forces in the inward direction, but not in the outward direction. The block state occurs in an unstable local minimum of the equilibrium unperturbed free-energy landscape of two K+ ions that can be ‘locked’ in place bymodest applied forces. In contrast to K +, three Na + ions move favorably through the selectivity filter together as a unit in a loose “knock-on” mechanism of permeation in both inward and outward directions, and there is no similar local minimum in the two-dimensional free-energy landscape of two Na + ions for a block state. The useful work predicted by the non-equilibrium simulations that is required to break the K + block is equivalent to large applied potentials experimentally measured for two bacterial Na v channels to induce inward currents of K + ions. Here, these results illustrate how inclusion of non-equilibrium factors in the simulations can provide detailed information about mechanisms of ion selectivity that is missing from mechanisms derived from either crystal structures or equilibrium unperturbed free-energy landscapes.« less

Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.

PubMed

Capes, Deborah L; Arcisio-Miranda, Manoel; Jarecki, Brian W; French, Robert J; Chanda, Baron

2012-02-14

Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.

Efficient control-channel multifailure management mechanism in GMPLS-based optical networks

NASA Astrophysics Data System (ADS)

Muñoz, Raül; Martínez, Ricardo; Junyent, Gabriel

2006-12-01

In generalized multiprotocol label switching (GMPLS) architecture, the control channels between each pair of optical nodes are not forced to use the same physical link as the data/transport channels. The problem arises when, due to the fact of allowing the control channels to be physically diverse from the associated data links, there may not be any active control channels available while data channels are still in use. Control-channel faults should not have a service impact on the existing connections; that is, a link that is carrying data traffic must not be torn down because the control channel is no longer available. But, due to the lack of the control channel, the active traffic that is using the data link may no longer be guaranteed with the same level of recovery service (protection or restoration). Under these circumstances the link must be considered to be in a degraded state. This means that routing and signaling should be notified that new connections are not accepted and the link is advertised with no unreserved resources. For this purpose, here we propose a control-channel multifailure management mechanism involving routing, signaling, and link management with extended GMPLS-based protocol extensions to keep the same level of service (in terms of provisioning and recovery) when a link is in the degraded state.

Longitudinal-control design approach for high-angle-of-attack aircraft

NASA Technical Reports Server (NTRS)

Ostroff, Aaron J.; Proffitt, Melissa S.

1993-01-01

This paper describes a control synthesis methodology that emphasizes a variable-gain output feedback technique that is applied to the longitudinal channel of a high-angle-of-attack aircraft. The aircraft is a modified F/A-18 aircraft with thrust-vectored controls. The flight regime covers a range up to a Mach number of 0.7; an altitude range from 15,000 to 35,000 ft; and an angle-of-attack (alpha) range up to 70 deg, which is deep into the poststall region. A brief overview is given of the variable-gain mathematical formulation as well as a description of the discrete control structure used for the feedback controller. This paper also presents an approximate design procedure with relationships for the optimal weights for the selected feedback control structure. These weights are selected to meet control design guidelines for high-alpha flight controls. Those guidelines that apply to the longitudinal-control design are also summarized. A unique approach is presented for the feed-forward command generator to obtain smooth transitions between load factor and alpha commands. Finally, representative linear analysis results and nonlinear batch simulation results are provided.

Overexpressed TRPV3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2

PubMed Central

Huang, Susan M.; Lee, Hyosang; Chung, Man-Kyo; Park, Una; Yu, Yin Yin; Bradshaw, Heather B.; Coulombe, Pierre A.; Walker, J. Michael; Caterina, Michael J.

2009-01-01

The ability to sense changes in the environment is essential for survival because it permits responses such as withdrawal from noxious stimuli and regulation of body temperature. Keratinocytes, which occupy much of the skin epidermis, are situated at the interface between the external environment and the body's internal milieu, and have long been appreciated for their barrier function against external insults. The recent discovery of temperature-sensitive TRPV ion channels in keratinocytes has raised the possibility that these cells also actively participate in acute temperature and pain sensation. To address this notion, we generated and characterized transgenic mice that overexpress TRPV3 in epidermal keratinocytes under the control of the keratin 14 promoter. Compared to wild-type controls, keratinocytes overexpressing TRPV3 exhibited larger currents as well as augmented prostaglandin E2 (PGE2) release in response to two TRPV3 agonists, 2-aminoethoxydiphenyl borate (2APB) and heat. Thermal selection behavior and heat-evoked withdrawal behavior of naïve mice overexpressing TRPV3 were not consistently altered. Upon selective pharmacological inhibition of TRPV1 with JNJ-7203212, however, the keratinocyte-specific TRPV3 transgenic mice showed increased escape responses to noxious heat relative to their wild-type littermates. Co-administration of the cyclooxygenase inhibitor, ibuprofen, with the TRPV1 antagonist decreased inflammatory thermal hyperalgesia in transgenic but not wild-type animals. Our results reveal a previously undescribed mechanism for keratinocyte participation in thermal pain transduction through keratinocyte TRPV3 ion channels and the intercellular messenger PGE2. PMID:19091963

The Physiology of Mechanoelectrical Transduction Channels in Hearing

PubMed Central

Fettiplace, Robert; Kim, Kyunghee X.

2014-01-01

Much is known about the mechanotransducer (MT) channels mediating transduction in hair cells of the vertrbrate inner ear. With the use of isolated preparations, it is experimentally feasible to deliver precise mechanical stimuli to individual cells and record the ensuing transducer currents. This approach has shown that small (1–100 nm) deflections of the hair-cell stereociliary bundle are transmitted via interciliary tip links to open MT channels at the tops of the stereocilia. These channels are cation-permeable with a high selectivity for Ca2+; two channels are thought to be localized at the lower end of the tip link, each with a large single-channel conductance that increases from the low- to high-frequency end of the cochlea. Ca2+ influx through open channels regulates their resting open probability, which may contribute to setting the hair cell resting potential in vivo. Ca2+ also controls transducer fast adaptation and force generation by the hair bundle, the two coupled processes increasing in speed from cochlear apex to base. The molecular intricacy of the stereocilary bundle and the transduction apparatus is reflected by the large number of single-gene mutations that are linked to sensorineural deafness, especially those in Usher syndrome. Studies of such mutants have led to the discovery of many of the molecules of the transduction complex, including the tip link and its attachments to the stereociliary core. However, the MT channel protein is still not firmly identified, nor is it known whether the channel is activated by force delivered through accessory proteins or by deformation of the lipid bilayer. PMID:24987009

Evaluation of criteria for selecting the spectral attributes of digital LANDSAT MSS imagery for discriminating lithological units in the lower Curaca River Valley, Bahia. [Brazil

NASA Technical Reports Server (NTRS)

Paradella, W. R. (Principal Investigator)

1984-01-01

The use of spectral attributes criteria was investigated, based on measures of statistical distance of separability between thematic classes in MSS digital LANDSAT imagery, in order to select the best subsets of channels in composite colors for the detection and discrimination of lithological units in the lower valley of Curaca River, State of Bahia, Brazil. Three situations were investigated: (1) selection of the three best channels, considering all of the original bands (channels 4, 5, 6, and 7); (2) selection of the three best bands, considering the six MSS band-ratios (channels 4/5, 4/6. 4/7, 5/6, 5/7, and 6/7); and (3) selection of the three best bands in a hybrid approach (the four original bands and the six ratios). A visual analysis was done on color composite images using the selected sets. Results show that the hybrid product (bands 4, 5/7, and 7 with green, blue, and red respectively) and the Normal Color Composite (bands 4, 5, and 7 with blue, green, and red colors respectively) had the best performance.

Reflectance of vegetation, soil, and water

NASA Technical Reports Server (NTRS)

Wiegand, C. L. (Principal Investigator)

1973-01-01

There are no author-identified significant results in this report. This report deals with the selection of the best channels from the 24-channel aircraft data to represent crop and soil conditions. A three-step procedure has been developed that involves using univariate statistics and an F-ratio test to indicate the best 14 channels. From the 14, the 10 best channels are selected by a multivariate stochastic process. The third step involves the pattern recognition procedures developed in the data analysis plan. Indications are that the procedures in use are satsifactory and will extract the desired information from the data.

Habitat selection by tundra swans on Northern Alaska breeding grounds

USGS Publications Warehouse

Earnst, Susan L.; Rothe, T.

2004-01-01

Habitat selection by the Tundra Swan (Cygnus columbianus columbianus) was evaluated on the Colville River Delta prior to oil field development (1982-1989). Tundra Swan territories comprised a lake, used for refuge and foraging, and terrestrial habitats and ponds near the lakea??s perimeter used for foraging and nesting. Tundra swan sightings from early and late summer aerial surveys were used to investigate habitat selection at the territory and within-territory scale. At the territory or lake scale, swan sightings/lake increased with lake size, and increased from discrete to tapped (i.e., connected to a river channel) to drained lakes within size categories. Overall, 49% of the variation in swan sightings/lake was explained by lake size and type, a size-x-type interaction term, and the proportion of lake perimeter comprised of Halophytic Ponds and Halophytic Wet Meadows. At the within-territory or within-lake scale, foraging swans significantly selected Halophytic Ponds, Halophytic Wet Meadows, and Fresh Ponds relative to Uplands; nesting swans significantly selected Halophytic Ponds and significantly avoided Fresh Wet Meadows relative to Uplands. Vegetation sampling indicated that sites used by Tundra Swans on river channels and tapped lakes were significantly more likely to have Sheathed Pondweed (Potamogeton vaginatus) than control sites. The three major components of Tundra Swan diet were Carex sedges, Sheathed Pondweed, and algae, together comprising 85% of identifiable plant fragments in feces.

Fluoride resistance and transport by riboswitch-controlled CLC antiporters

PubMed Central

Stockbridge, Randy B.; Lim, Hyun-Ho; Otten, Renee; Williams, Carole; Shane, Tania; Weinberg, Zasha; Miller, Christopher

2012-01-01

A subclass of bacterial CLC anion-transporting proteins, phylogenetically distant from long-studied CLCs, was recently shown to be specifically up-regulated by F-. We establish here that a set of randomly selected representatives from this “CLCF” clade protect Escherichia coli from F- toxicity, and that the purified proteins catalyze transport of F- in liposomes. Sequence alignments and membrane transport experiments using 19F NMR, osmotic response assays, and planar lipid bilayer recordings reveal four mechanistic traits that set CLCF proteins apart from all other known CLCs. First, CLCFs lack conserved residues that form the anion binding site in canonical CLCs. Second, CLCFs exhibit high anion selectivity for F- over Cl-. Third, at a residue thought to distinguish CLC channels and transporters, CLCFs bear a channel-like valine rather than a transporter-like glutamate, and yet are F-/H+ antiporters. Finally, F-/H+ exchange occurs with 1∶1 stoichiometry, in contrast to the usual value of 2∶1. PMID:22949689

Fluoride resistance and transport by riboswitch-controlled CLC antiporters.

PubMed

Stockbridge, Randy B; Lim, Hyun-Ho; Otten, Renee; Williams, Carole; Shane, Tania; Weinberg, Zasha; Miller, Christopher

2012-09-18

A subclass of bacterial CLC anion-transporting proteins, phylogenetically distant from long-studied CLCs, was recently shown to be specifically up-regulated by F(-). We establish here that a set of randomly selected representatives from this "CLC(F)" clade protect Escherichia coli from F(-) toxicity, and that the purified proteins catalyze transport of F(-) in liposomes. Sequence alignments and membrane transport experiments using (19)F NMR, osmotic response assays, and planar lipid bilayer recordings reveal four mechanistic traits that set CLC(F) proteins apart from all other known CLCs. First, CLC(F)s lack conserved residues that form the anion binding site in canonical CLCs. Second, CLC(F)s exhibit high anion selectivity for F(-) over Cl(-). Third, at a residue thought to distinguish CLC channels and transporters, CLC(F)s bear a channel-like valine rather than a transporter-like glutamate, and yet are F(-)/H(+) antiporters. Finally, F(-)/H(+) exchange occurs with 1:1 stoichiometry, in contrast to the usual value of 2:1.

Selective activation of vascular Kv7.4/Kv7.5 K+ channels by fasudil contributes to its vasorelaxant effect

PubMed Central

Zhang, Xuan; An, Hailong; Li, Junwei; Zhang, Yuanyuan; Liu, Yang; Jia, Zhanfeng; Zhang, Wei

2016-01-01

Background and Purpose Kv7 (Kv7.1–7.5) channels play an important role in the regulation of neuronal excitability and the cardiac action potential. Growing evidence suggests Kv7.4/Kv7.5 channels play a crucial role in regulating vascular smooth muscle contractility. Most of the reported Kv7 openers have shown poor selectivity across these five subtypes. In this study, fasudil – a drug used for cerebral vasospasm – has been found to be a selective opener of Kv7.4/Kv7.5 channels. Experimental Approach A perforated whole‐cell patch technique was used to record the currents and membrane potential. Homology modelling and a docking technique were used to investigate the interaction between fasudil and the Kv7.4 channel. An isometric tension recording technique was used to assess the vascular tension. Key Results Fasudil selectively and potently enhanced Kv7.4 and Kv7.4/Kv7.5 currents expressed in HEK293 cells, and shifted the voltage‐dependent activation curve in a more negative direction. Fasudil did not affect either Kv7.2 and Kv7.2/Kv7.3 currents expressed in HEK293 cells, the native neuronal M‐type K+ currents, or the resting membrane potential in small rat dorsal root ganglia neurons. The Val248 in S5 and Ile308 in S6 segment of Kv7.4 were critical for this activating effect of fasudil. Fasudil relaxed precontracted rat small arteries in a concentration‐dependent fashion; this effect was antagonized by the Kv7 channel blocker XE991. Conclusions and Implications These results suggest that fasudil is a selective Kv7.4/Kv7.5 channel opener and provide a new dimension for developing selective Kv7 modulators and a new prospective for the use, action and mechanism of fasudil. PMID:27677924

Multi-channels coupling-induced pattern transition in a tri-layer neuronal network

NASA Astrophysics Data System (ADS)

Wu, Fuqiang; Wang, Ya; Ma, Jun; Jin, Wuyin; Hobiny, Aatef

2018-03-01

Neurons in nerve system show complex electrical behaviors due to complex connection types and diversity in excitability. A tri-layer network is constructed to investigate the signal propagation and pattern formation by selecting different coupling channels between layers. Each layer is set as different states, and the local kinetics is described by Hindmarsh-Rose neuron model. By changing the number of coupling channels between layers and the state of the first layer, the collective behaviors of each layer and synchronization pattern of network are investigated. A statistical factor of synchronization on each layer is calculated. It is found that quiescent state in the second layer can be excited and disordered state in the third layer is suppressed when the first layer is controlled by a pacemaker, and the developed state is dependent on the number of coupling channels. Furthermore, the collapse in the first layer can cause breakdown of other layers in the network, and the mechanism is that disordered state in the third layer is enhanced when sampled signals from the collapsed layer can impose continuous disturbance on the next layer.

A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief

PubMed Central

Lee, Jun-Ho; Park, Chul-Kyu; Chen, Gang; Han, Qingjian; Xie, Rou-Gang; Liu, Tong; Ji, Ru-Rong; Lee, Seok-Yong

2014-01-01

Summary Voltage-gated sodium (NaV) channels control the upstroke of the action potentials in excitable cells. Multiple studies have shown distinct roles of NaV channel subtypes in human physiology and diseases, but subtype-specific therapeutics are lacking and the current efforts have been limited to small molecules. Here we present a monoclonal antibody that targets the voltage-sensor paddle of NaV1.7, the subtype critical for pain sensation. This antibody not only inhibits NaV1.7 with high selectivity but also effectively suppresses inflammatory and neuropathic pain in mice. Interestingly, the antibody inhibits acute and chronic itch, despite well-documented differences in pain and itch modulation. Using this antibody, we discovered that NaV1.7 plays a key role in spinal cord nociceptive and pruriceptive synaptic transmission. Our studies reveal that NaV1.7 is a target for itch management and the antibody has therapeutic potential for suppressing pain and itch. Our antibody strategy may have broad applications for voltage-gated cation channels. PMID:24856969

Flexible ambipolar organic field-effect transistors with reverse-offset-printed silver electrodes for a complementary inverter.

PubMed

Park, Junsu; Kim, Minseok; Yeom, Seung-Won; Ha, Hyeon Jun; Song, Hyenggun; Min Jhon, Young; Kim, Yun-Hi; Ju, Byeong-Kwon

2016-06-03

We report ambipolar organic field-effect transistors and complementary inverter circuits with reverse-offset-printed (ROP) Ag electrodes fabricated on a flexible substrate. A diketopyrrolopyrrole-based co-polymer (PDPP-TAT) was used as the semiconductor and poly(methyl methacrylate) was used as the gate insulator. Considerable improvement is observed in the n-channel electrical characteristics by inserting a cesium carbonate (Cs2CO3) as the electron-injection/hole-blocking layer at the interface between the semiconductors and the electrodes. The saturation mobility values are 0.35 cm(2) V(-1) s(-1) for the p-channel and 0.027 cm(2) V(-1) s(-1) for the n-channel. A complementary inverter is demonstrated based on the ROP process, and it is selectively controlled by the insertion of Cs2CO3 onto the n-channel region via thermal evaporation. Moreover, the devices show stable operation during the mechanical bending test using tensile strains ranging from 0.05% to 0.5%. The results confirm that these devices have great potential for use in flexible and inexpensive integrated circuits over a large area.

Inhibitors of ATP-sensitive potassium channels in guinea pig isolated ischemic hearts.

PubMed

Weyermann, A; Vollert, H; Busch, A E; Bleich, M; Gögelein, H

2004-04-01

During heart ischemia, ATP-sensitive potassium channels in the sarcolemmal membrane (sarcK(ATP)) open and cause shortening of the action potential duration. This creates heterogeneity of repolarization, being responsible for the development of re-entry arrhythmias and sudden cardiac death. Therefore, the aim is to develop selective blockers of the cardiac sarcK(ATP) channel. In the present study we established an in vitro model and classified 5 K(ATP) channel inhibitors with respect to their potency and selectivity between cardiomyocytes and the coronary vasculature and compared the results with inhibition of Kir6.2/SUR2A channels expressed in HEK293 cells, recorded with the Rb(+)-efflux methods. We used Langendorff-perfused guinea pig hearts, where low-flow ischemia plus hypoxia was performed by reducing the coronary flow (CF) to 1.2 ml/min and by gassing the perfusion solution with N(2) instead of O(2). Throughout the experiment, the monophasic action potential duration at 90% repolarization (MAPD(90)) was recorded. In separate experiments, high-flow hypoxia was produced by oxygen reduction in the perfusate from 95% to 20%, which caused an increase in the coronary flow. Under normoxic conditions, the substances glibenclamide, repaglinide, meglitinide, HMR 1402 and HMR 1098 (1 microM each) reduced the CF by 34%, 38%, 19%, 12% and 5%, respectively. The hypoxia-induced increase in CF was inhibited by the compounds half-maximally at 25 nM, approximately 200 nM, 600 nM, approximately 9 microM and >100 microM, respectively. In control experiments after 5 min low-flow ischemia plus hypoxia, the MAPD(90) shortened from 121+/-2 to 99+/-2 ms ( n=29). This shortening was half-maximally inhibited by the substances at concentrations of 95 nM, 74 nM, 400 nM, 110 nM and 550 nM, respectively. In HEK293 cells the Rb(+)-efflux through KIR6.2/SUR2A channels was inhibited by the compounds with IC(50) values of 21 nM, 67 nM, 205 nM, 60 nM and 181 nM, respectively. In summary, the present data demonstrate that the sulfonylurea glibenclamide, and the carbamoylbenzoic acid derivatives repaglinide and meglitinide are unselective blockers of K(ATP) channels in cardiac cells and in the cardiac vascular system, whereas the sulfonylthioureas HMR 1402, and especially HMR 1098 selectively blocked the cardiac sarcK(ATP) channel. Blockade of Kir6.2/SUR2A channels in HEK293 cells occurred with comparable efficacy as in the cardiac tissue, indicating that the expression system is suited for screening for novel inhibitors.

Chemical substitutions in the selectivity filter of potassium channels do not rule out constricted-like conformations for C-type inactivation

PubMed Central

Li, Jing; Boulanger, Eliot; Rui, Huan; Perozo, Eduardo; Roux, Benoît

2017-01-01

In many K+ channels, prolonged activating stimuli lead to a time-dependent reduction in ion conduction, a phenomenon known as C-type inactivation. X-ray structures of the KcsA channel suggest that this inactivated state corresponds to a “constricted” conformation of the selectivity filter. However, the functional significance of the constricted conformation has become a matter of debate. Functional and structural studies based on chemically modified semisynthetic KcsA channels along the selectivity filter led to the conclusion that the constricted conformation does not correspond to the C-type inactivated state. The main results supporting this view include the observation that C-type inactivation is not suppressed by a substitution of D-alanine at Gly77, even though this modification is believed to lock the selectivity filter into its conductive conformation, whereas it is suppressed following amide-to-ester backbone substitutions at Gly77 and Tyr78, even though these structure-conserving modifications are not believed to prevent the selectivity filter from adopting the constricted conformation. However, several untested assumptions about the structural and functional impact of these chemical modifications underlie these arguments. To make progress, molecular dynamics simulations based on atomic models of the KcsA channel were performed. The computational results support the notion that the constricted conformation of the selectivity filter corresponds to the functional C-type inactivated state of the KcsA. Importantly, MD simulations reveal that the semisynthetic KcsAD-ala77 channel can adopt an asymmetrical constricted-like nonconductive conformation and that the amide-to-ester backbone substitutions at Gly77 and Tyr78 perturb the hydrogen bonding involving the buried water molecules stabilizing the constricted conformation. PMID:28973956

Targeting of sodium channel blockers into nociceptors to produce long-duration analgesia: a systematic study and review

PubMed Central

Roberson, DP; Binshtok, AM; Blasl, F; Bean, BP; Woolf, CJ

2011-01-01

BACKGROUND AND PURPOSE We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves co-administration of QX-314 and a TRPV1 agonist to produce a long-lasting local analgesia. For potential clinical use we propose using lidocaine as the TRPV1 agonist, because it activates TRPV1 at clinical doses. EXPERIMENTAL APPROACH We conducted experiments in rats to determine optimal concentrations and ratios of lidocaine and QX-314 that produce the greatest degree and duration of pain-selective block when administered nearby the sciatic nerve: reduction in the response to noxious mechanical (pinch) and to radiant heat stimuli, with minimal disruption in motor function (grip strength). KEY RESULTS A combination of 0.5% QX-314 and 2% lidocaine produced 1 h of non-selective sensory and motor block followed by >9 h of pain-selective block, where grip strength was unimpaired. QX-314 at this concentration had no effect by itself, while 2% lidocaine by itself produced 1 h of non-selective block. The combination of 0.5% QX-314 and 2% lidocaine was the best of the many tested, in terms of the duration and selectivity of local analgesia. CONCLUSIONS AND IMPLICATIONS Targeting charged sodium channel blockers into specific sets of axons via activation of differentially expressed large-pore channels provides an opportunity to produce prolonged local analgesia, and represents an example of how exploiting ion channels as a drug delivery port can be used to increase the specificity and efficacy of therapeutics. PMID:21457220

Unraveling the mechanism of selective ion transport in hydrophobic subnanometer channels

PubMed Central

Li, Hui; Francisco, Joseph S.; Zeng, Xiao Cheng

2015-01-01

Recently reported synthetic organic nanopore (SONP) can mimic a key feature of natural ion channels, i.e., selective ion transport. However, the physical mechanism underlying the K+/Na+ selectivity for the SONPs is dramatically different from that of natural ion channels. To achieve a better understanding of the selective ion transport in hydrophobic subnanometer channels in general and SONPs in particular, we perform a series of ab initio molecular dynamics simulations to investigate the diffusivity of aqua Na+ and K+ ions in two prototype hydrophobic nanochannels: (i) an SONP with radius of 3.2 Å, and (ii) single-walled carbon nanotubes (CNTs) with radii of 3–5 Å (these radii are comparable to those of the biological potassium K+ channels). We find that the hydration shell of aqua Na+ ion is smaller than that of aqua K+ ion but notably more structured and less yielding. The aqua ions do not lower the diffusivity of water molecules in CNTs, but in SONP the diffusivity of aqua ions (Na+ in particular) is strongly suppressed due to the rugged inner surface. Moreover, the aqua Na+ ion requires higher formation energy than aqua K+ ion in the hydrophobic nanochannels. As such, we find that the ion (K+ vs. Na+) selectivity of the (8, 8) CNT is ∼20× higher than that of SONP. Hence, the (8, 8) CNT is likely the most efficient artificial K+ channel due in part to its special interior environment in which Na+ can be fully solvated, whereas K+ cannot. This work provides deeper insights into the physical chemistry behind selective ion transport in nanochannels. PMID:26283377

Fine-scale pathways used by adult sea lampreys during riverine spawning migrations

USGS Publications Warehouse

Holbrook, Christopher; Bergstedt, Roger A.; Adams, Noah S.; Hatton, Tyson; McLaughlin, Robert L.

2015-01-01

Better knowledge of upstream migratory patterns of spawning Sea Lampreys Petromyzon marinus, an invasive species in the Great Lakes, is needed to improve trapping for population control and assessment. Although trapping of adult Sea Lampreys provides the basis for estimates of lake-wide abundance that are used to evaluate the Sea Lamprey control program, traps have only been operated at dams due to insufficient knowledge of Sea Lamprey behavior in unobstructed channels. Acoustic telemetry and radiotelemetry were used to obtain movement tracks for 23 Sea Lampreys in 2008 and 18 Sea Lampreys in 2009 at two locations in the Mississagi River, Ontario. Cabled hydrophone arrays provided two-dimensional geographic positions from acoustic transmitters at 3-s intervals; depth-encoded radio tag detections provided depths. Upstream movements occurred at dusk or during the night (2015–0318 hours). Sea Lampreys were closely associated with the river bottom and showed some preference to move near banks in shallow glide habitats, suggesting that bottom-oriented gears could selectively target adult Sea Lampreys in some habitats. However, Sea Lampreys were broadly distributed across the river channel, suggesting that the capture efficiency of nets and traps in open channels would depend heavily on the proportion of the channel width covered. Lack of vertical movements into the water column may have reflected lamprey preference for low water velocities, suggesting that energy conservation was more beneficial for lampreys than was vertical searching in rivers. Improved understanding of Sea Lamprey movement will assist in the development of improved capture strategies for their assessment and control in the Great Lakes.

K + block is the mechanism of functional asymmetry in bacterial Na v channels

DOE PAGES

Ngo, Van; Wang, Yibo; Haas, Stephan; ...

2016-01-04

Crystal structures of several bacterial Na v channels have been recently published and molecular dynamics simulations of ion permeation through these channels are consistent with many electrophysiological properties of eukaryotic channels. Bacterial Na v channels have been characterized as functionally asymmetric, and the mechanism of this asymmetry has not been clearly understood. To address this question, we combined non-equilibrium simulation data with two-dimensional equilibrium unperturbed landscapes generated by umbrella sampling and Weighted Histogram Analysis Methods for multiple ions traversing the selectivity filter of bacterial Na vAb channel. This approach provided new insight into the mechanism of selective ion permeation inmore » bacterial Nav channels. The non-equilibrium simulations indicate that two or three extracellular K + ions can block the entrance to the selectivity filter of Na vAb in the presence of applied forces in the inward direction, but not in the outward direction. The block state occurs in an unstable local minimum of the equilibrium unperturbed free-energy landscape of two K+ ions that can be ‘locked’ in place bymodest applied forces. In contrast to K +, three Na + ions move favorably through the selectivity filter together as a unit in a loose “knock-on” mechanism of permeation in both inward and outward directions, and there is no similar local minimum in the two-dimensional free-energy landscape of two Na + ions for a block state. The useful work predicted by the non-equilibrium simulations that is required to break the K + block is equivalent to large applied potentials experimentally measured for two bacterial Na v channels to induce inward currents of K + ions. Here, these results illustrate how inclusion of non-equilibrium factors in the simulations can provide detailed information about mechanisms of ion selectivity that is missing from mechanisms derived from either crystal structures or equilibrium unperturbed free-energy landscapes.« less

The food dye FD&C Blue No. 1 is a selective inhibitor of the ATP release channel Panx1.

PubMed

Wang, Junjie; Jackson, David George; Dahl, Gerhard

2013-05-01

The food dye FD&C Blue No. 1 (Brilliant Blue FCF [BB FCF]) is structurally similar to the purinergic receptor antagonist Brilliant Blue G (BBG), which is a well-known inhibitor of the ionotropic P2X7 receptor (P2X7R). The P2X7R functionally interacts with the membrane channel protein pannexin 1 (Panx1) in inflammasome signaling. Intriguingly, ligands to the P2X7R, regardless of whether they are acting as agonists or antagonists at the receptor, inhibit Panx1 channels. Thus, because both P2X7R and Panx1 are inhibited by BBG, the diagnostic value of the drug is limited. Here, we show that the food dye BB FCF is a selective inhibitor of Panx1 channels, with an IC50 of 0.27 µM. No significant effect was observed with concentrations as high as 100 µM of BB FCF on P2X7R. Differing by just one hydroxyl group from BB FCF, the food dye FD&C Green No. 3 exhibited similar selective inhibition of Panx1 channels. A reverse selectivity was observed for the P2X7R antagonist, oxidized ATP, which in contrast to other P2X7R antagonists had no significant inhibitory effect on Panx1 channels. Based on its selective action, BB FCF can be added to the repertoire of drugs to study the physiology of Panx1 channels. Furthermore, because Panx1 channels appear to be involved directly or indirectly through P2X7Rs in several disorders, BB FCF and derivatives of this "safe" food dye should be given serious consideration for pharmacological intervention of conditions such as acute Crohn's disease, stroke, and injuries to the central nervous system.

K+ Block Is the Mechanism of Functional Asymmetry in Bacterial Nav Channels

PubMed Central

Ngo, Van; Wang, Yibo; Haas, Stephan; Noskov, Sergei Y.; Farley, Robert A.

2016-01-01

Crystal structures of several bacterial Nav channels have been recently published and molecular dynamics simulations of ion permeation through these channels are consistent with many electrophysiological properties of eukaryotic channels. Bacterial Nav channels have been characterized as functionally asymmetric, and the mechanism of this asymmetry has not been clearly understood. To address this question, we combined non-equilibrium simulation data with two-dimensional equilibrium unperturbed landscapes generated by umbrella sampling and Weighted Histogram Analysis Methods for multiple ions traversing the selectivity filter of bacterial NavAb channel. This approach provided new insight into the mechanism of selective ion permeation in bacterial Nav channels. The non-equilibrium simulations indicate that two or three extracellular K+ ions can block the entrance to the selectivity filter of NavAb in the presence of applied forces in the inward direction, but not in the outward direction. The block state occurs in an unstable local minimum of the equilibrium unperturbed free-energy landscape of two K+ ions that can be ‘locked’ in place by modest applied forces. In contrast to K+, three Na+ ions move favorably through the selectivity filter together as a unit in a loose “knock-on” mechanism of permeation in both inward and outward directions, and there is no similar local minimum in the two-dimensional free-energy landscape of two Na+ ions for a block state. The useful work predicted by the non-equilibrium simulations that is required to break the K+ block is equivalent to large applied potentials experimentally measured for two bacterial Nav channels to induce inward currents of K+ ions. These results illustrate how inclusion of non-equilibrium factors in the simulations can provide detailed information about mechanisms of ion selectivity that is missing from mechanisms derived from either crystal structures or equilibrium unperturbed free-energy landscapes. PMID:26727271

47 CFR 90.621 - Selection and assignment of frequencies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... channel(s) for which authorization for commercial use is sought that operate within 25 kHz of the center...-channel station that has been granted channel exclusivity and authorized 1 kW ERP on any of the following... been granted channel exclusivity and authorized 1 kW ERP on any of the following mountaintop sites...

47 CFR 90.621 - Selection and assignment of frequencies.

Code of Federal Regulations, 2013 CFR

2013-10-01

... channel(s) for which authorization for commercial use is sought that operate within 25 kHz of the center...-channel station that has been granted channel exclusivity and authorized 1 kW ERP on any of the following... been granted channel exclusivity and authorized 1 kW ERP on any of the following mountaintop sites...

Image analysis for maintenance of coating quality in nickel electroplating baths--real time control.

PubMed

Vidal, M; Amigo, J M; Bro, R; van den Berg, F; Ostra, M; Ubide, C

2011-11-07

The aim of this paper is to show how it is possible to extract analytical information from images acquired with a flatbed scanner and make use of this information for real time control of a nickel plating process. Digital images of plated steel sheets in a nickel bath are used to follow the process under degradation of specific additives. Dedicated software has been developed for making the obtained results accessible to process operators. This includes obtaining the RGB image, to select the red channel data exclusively, to calculate the histogram of the red channel data and to calculate the mean colour value (MCV) and the standard deviation of the red channel data. MCV is then used by the software to determine the concentration of the additives Supreme Plus Brightner (SPB) and SA-1 (for confidentiality reasons, the chemical contents cannot be further detailed) present in the bath (these two additives degrade and their concentration changes during the process). Finally, the software informs the operator when the bath is generating unsuitable quality plating and suggests the amount of SPB and SA-1 to be added in order to recover the original plating quality. Copyright © 2011 Elsevier B.V. All rights reserved.

Older adults do not notice their names: a new twist to a classic attention task.

PubMed

Naveh-Benjamin, Moshe; Kilb, Angela; Maddox, Geoffrey B; Thomas, Jenna; Fine, Hope C; Chen, Tina; Cowan, Nelson

2014-11-01

Although working memory spans are, on average, lower for older adults than young adults, we demonstrate in 5 experiments a way in which older adults paradoxically resemble higher capacity young adults. Specifically, in a selective-listening task, older adults almost always failed to notice their names presented in an unattended channel. This is an exaggeration of what high-span young adults show and the opposite of what low-span young adults show. This striking finding in older adults remained significant after controlling for working memory span and for noticing their names in an attended channel. The findings were replicated when presentation rate was slowed and when the ear in which the unattended name was presented was controlled. These results point to an account of older adults' performance involving not only an inhibition factor, which allows high-span young adults to suppress the channel to be ignored, but also an attentional capacity factor, with more unallocated capacity. This capacity allows low-span young adults to notice their names much more often than older adults with comparably low working memory spans do. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Quantification of gap junction selectivity.

PubMed

Ek-Vitorín, Jose F; Burt, Janis M

2005-12-01

Gap junctions, which are essential for functional coordination and homeostasis within tissues, permit the direct intercellular exchange of small molecules. The abundance and diversity of this exchange depends on the number and selectivity of the comprising channels and on the transjunctional gradient for and chemical character of the permeant molecules. Limited knowledge of functionally significant permeants and poor detectability of those few that are known have made it difficult to define channel selectivity. Presented herein is a multifaceted approach to the quantification of gap junction selectivity that includes determination of the rate constant for intercellular diffusion of a fluorescent probe (k2-DYE) and junctional conductance (gj) for each junction studied, such that the selective permeability (k2-DYE/gj) for dyes with differing chemical characteristics or junctions with differing connexin (Cx) compositions (or treatment conditions) can be compared. In addition, selective permeability can be correlated using single-channel conductance when this parameter is also measured. Our measurement strategy is capable of detecting 1) rate constants and selective permeabilities that differ across three orders of magnitude and 2) acute changes in that rate constant. Using this strategy, we have shown that 1) the selective permeability of Cx43 junctions to a small cationic dye varied across two orders of magnitude, consistent with the hypothesis that the various channel configurations adopted by Cx43 display different selective permeabilities; and 2) the selective permeability of Cx37 vs. Cx43 junctions was consistently and significantly lower.

Surface-Chemistry-Mediated Control of Individual Magnetic Helical Microswimmers in a Swarm.

PubMed

Wang, Xiaopu; Hu, Chengzhi; Schurz, Lukas; De Marco, Carmela; Chen, Xiangzhong; Pané, Salvador; Nelson, Bradley J

2018-05-31

Magnetic helical microswimmers, also known as artificial bacterial flagella (ABFs), perform 3D navigation in various liquids under low-strength rotating magnetic fields by converting rotational motion to translational motion. ABFs have been widely studied as carriers for targeted delivery and release of drugs and cells. For in vivo/ in vitro therapeutic applications, control over individual groups of swimmers within a swarm is necessary for several biomedical applications such as drug delivery or small-scale surgery. In this work, we present the selective control of individual swimmers in a swarm of geometrically and magnetically identical ABFs by modifying their surface chemistry. We confirm experimentally and analytically that the forward/rotational velocity ratio of ABFs is independent of their surface coatings when the swimmers are operated below their step-out frequency (the frequency requiring the entire available magnetic torque to maintain synchronous rotation). We also show that ABFs with hydrophobic surfaces exhibit larger step-out frequencies and higher maximum forward velocities compared to their hydrophilic counterparts. Thus, selective control of a group of swimmers within a swarm of ABFs can be achieved by operating the selected ABFs at a frequency that is below their step-out frequencies but higher than the step-out frequencies of unselected ABFs. The feasibility of this method is investigated in water and in biologically relevant solutions. Selective control is also demonstrated inside a Y-shaped microfluidic channel. Our results present a systematic approach for realizing selective control within a swarm of magnetic helical microswimmers.

Method and apparatus for signal processing in a sensor system for use in spectroscopy

DOEpatents

O'Connor, Paul [Bellport, NY; DeGeronimo, Gianluigi [Nesconset, NY; Grosholz, Joseph [Natrona Heights, PA

2008-05-27

A method for processing pulses arriving randomly in time on at least one channel using multiple peak detectors includes asynchronously selecting a non-busy peak detector (PD) in response to a pulse-generated trigger signal, connecting the channel to the selected PD in response to the trigger signal, and detecting a pulse peak amplitude. Amplitude and time of arrival data are output in first-in first-out (FIFO) sequence. An apparatus includes trigger comparators to generate the trigger signal for the pulse-receiving channel, PDs, a switch for connecting the channel to the selected PD, and logic circuitry which maintains the write pointer. Also included, time-to-amplitude converters (TACs) convert time of arrival to analog voltage and an analog multiplexer provides FIFO output. A multi-element sensor system for spectroscopy includes detector elements, channels, trigger comparators, PDs, a switch, and a logic circuit with asynchronous write pointer. The system includes TACs, a multiplexer and analog-to-digital converter.

Crystal structure of the epithelial calcium channel TRPV6.

PubMed

Saotome, Kei; Singh, Appu K; Yelshanskaya, Maria V; Sobolevsky, Alexander I

2016-06-23

Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels. Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K(+) channel-like transmembrane domain, Ca(2+) selectivity is determined by direct coordination of Ca(2+) by a ring of aspartate side chains in the selectivity filter. On the basis of crystallographically identified cation-binding sites at the pore axis and extracellular vestibule, we propose a Ca(2+) permeation mechanism. Our results provide a structural foundation for understanding the regulation of epithelial Ca(2+) uptake and its role in pathophysiology.

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.

Research on imaging spectrometer using LC-based tunable filter

NASA Astrophysics Data System (ADS)

Shen, Zhixue; Li, Jianfeng; Huang, Lixian; Luo, Fei; Luo, Yongquan; Zhang, Dayong; Long, Yan

2012-09-01

A liquid crystal tunable filter (LCTF) with large aperture is developed using PDLC liquid crystal. A small scale imaging spectrometer is established based on this tunable filter. This spectrometer can continuously tuning, or random-access selection of any wavelength in the visible and near infrared (VNIR) band synchronized with the imaging processes. Notable characteristics of this spectrometer include the high flexibility control of its operating channels, the image cubes with high spatial resolution and spectral resolution and the strong ability of acclimation to environmental temperature. The image spatial resolution of each tuning channel is almost near the one of the same camera without the LCTF. The spectral resolution is about 20 nm at 550 nm. This spectrometer works normally under 0-50°C with a maximum power consumption of 10 Watts (with exclusion of the storage module). Due to the optimization of the electrode structure and the driving mode of the Liquid Crystal cell, the switch time between adjacent selected channels can be reduced to 20 ms or even shorter. Spectral imaging experiments in laboratory are accomplished to verify the performance of this spectrometer, which indicate that this compact imaging spectrometer works reliably, and functionally. Possible applications of this imaging spectrometer include medical science, protection of historical relics, criminal investigation, disaster monitoring and mineral detection by remote sensing.

Music-induced positive mood broadens the scope of auditory attention

PubMed Central

Makkonen, Tommi; Eerola, Tuomas

2017-01-01

Abstract Previous studies indicate that positive mood broadens the scope of visual attention, which can manifest as heightened distractibility. We used event-related potentials (ERP) to investigate whether music-induced positive mood has comparable effects on selective attention in the auditory domain. Subjects listened to experimenter-selected happy, neutral or sad instrumental music and afterwards participated in a dichotic listening task. Distractor sounds in the unattended channel elicited responses related to early sound encoding (N1/MMN) and bottom-up attention capture (P3a) while target sounds in the attended channel elicited a response related to top-down-controlled processing of task-relevant stimuli (P3b). For the subjects in a happy mood, the N1/MMN responses to the distractor sounds were enlarged while the P3b elicited by the target sounds was diminished. Behaviorally, these subjects tended to show heightened error rates on target trials following the distractor sounds. Thus, the ERP and behavioral results indicate that the subjects in a happy mood allocated their attentional resources more diffusely across the attended and the to-be-ignored channels. Therefore, the current study extends previous research on the effects of mood on visual attention and indicates that even unfamiliar instrumental music can broaden the scope of auditory attention via its effects on mood. PMID:28460035

Data collected to support monitoring of constructed emergent sandbar habitat on the Missouri River downstream from Gavins Point Dam, South Dakota and Nebraska, 2004-06

USGS Publications Warehouse

Thompson, Ryan F.; Johnson, Michaela R.; Andersen, Michael J.

2007-01-01

The U.S. Army Corps of Engineers has constructed emergent sandbar habitat on sections of the Missouri River bordering South Dakota and Nebraska downstream from Gavins Point Dam to create and enhance habitat for threatened and endangered bird species. Two areas near river miles 761.3 and 769.8 were selected for construction of emergent sandbar habitat. Pre- and postconstruction data were collected by the U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, to evaluate the success of the habitat management techniques. Data collected include pre- and postconstruction channel-geometry data (bathymetric and topographic) for areas upstream from, downstream from, and within each construction site. Water-velocity data were collected for selected parts of the site near river mile 769.8. Instruments and methods used in data collection, as well as quality-assurance and quality-control measures, are described. Geospatial channel-geometry data are presented for transects of the river channel as cross sections and as geographical information system shapefiles. Geospatial land-surface elevation data are provided for part of each site in the form of a color-shaded relief map. Geospatial water-velocity data also are provided as color-shaded maps and geographical information system shapefiles.

Bladder contractility is modulated by Kv7 channels in pig detrusor.

PubMed

Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja; Sheykhzade, Majid; Nordling, Jørgen; Bouchelouche, Pierre

2013-09-05

Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view to determining the effects of the following potassium channel activators: ML213 (Kv7.2/Kv7.4 channels) and retigabine (Kv7.2-7.5 channels). Retigabine produced a concentration-dependent relaxation of carbachol- and electric field-induced contractions. The potency was similar in magnitude to that of ML213-induced relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P<0.05), which in turn confirmed Kv7 channel selectivity. Subtype-selective effects were further investigated by incubating the detrusor with 10µM chromanol 293B (Kv7.1 channel blocker). Regardless of the experimental protocol, this did not cause a further increase in the evoked contraction. In contrast, the addition of XE991 potentiated the KCl-induced contractions, but not those induced by carbachol or electric field, indicating the presence of a phosphatidyl-inositol-4,5-biphosphate-dependent mechanism amongst the Kv7 channels in detrusor. qRT-PCR studies of the mRNA transcript level of Kv7.3-7.5 channels displayed a higher level of Kv7.4 transcript in detrusor compared to that present in brain cortex and heart tissues. Thus, we have shown that Kv7.4 channels are expressed and functionally active in pig detrusor, and that the use of selective Kv7.4 channel modulators in the treatment of detrusor overactivity seems promising. © 2013 Elsevier B.V. All rights reserved.

Pilot-Assisted Channel Estimation for Orthogonal Multi-Carrier DS-CDMA with Frequency-Domain Equalization

NASA Astrophysics Data System (ADS)

Shima, Tomoyuki; Tomeba, Hiromichi; Adachi, Fumiyuki

Orthogonal multi-carrier direct sequence code division multiple access (orthogonal MC DS-CDMA) is a combination of time-domain spreading and orthogonal frequency division multiplexing (OFDM). In orthogonal MC DS-CDMA, the frequency diversity gain can be obtained by applying frequency-domain equalization (FDE) based on minimum mean square error (MMSE) criterion to a block of OFDM symbols and can improve the bit error rate (BER) performance in a severe frequency-selective fading channel. FDE requires an accurate estimate of the channel gain. The channel gain can be estimated by removing the pilot modulation in the frequency domain. In this paper, we propose a pilot-assisted channel estimation suitable for orthogonal MC DS-CDMA with FDE and evaluate, by computer simulation, the BER performance in a frequency-selective Rayleigh fading channel.

Identification of an HV 1 voltage-gated proton channel in insects.

PubMed

Chaves, Gustavo; Derst, Christian; Franzen, Arne; Mashimo, Yuta; Machida, Ryuichiro; Musset, Boris

2016-04-01

The voltage-gated proton channel 1 (HV 1) is an important component of the cellular proton extrusion machinery and is essential for charge compensation during the respiratory burst of phagocytes. HV 1 has been identified in a wide range of eukaryotes throughout the animal kingdom, with the exception of insects. Therefore, it has been proposed that insects do not possess an HV 1 channel. In the present study, we report the existence of an HV 1-type proton channel in insects. We searched insect transcriptome shotgun assembly (TSA) sequence databases and found putative HV 1 orthologues in various polyneopteran insects. To confirm that these putative HV 1 orthologues were functional channels, we studied the HV 1 channel of Nicoletia phytophila (NpHV 1), an insect of the Zygentoma order, in more detail. NpHV 1 comprises 239 amino acids and is 33% identical to the human voltage-gated proton channel 1. Patch clamp measurements in a heterologous expression system showed proton selectivity, as well as pH- and voltage-dependent gating. Interestingly, NpHV 1 shows slightly enhanced pH-dependent gating compared to the human channel. Mutations in the first transmembrane segment at position 66 (Asp66), the presumed selectivity filter, lead to a loss of proton-selective conduction, confirming the importance of this aspartate residue in voltage-gated proton channels. Nucleotide sequence data have been deposited in the GenBank database under accession number KT780722. © 2016 Federation of European Biochemical Societies.

Main-channel slopes of selected streams in Iowa for estimation of flood-frequency discharges.

DOT National Transportation Integrated Search

2003-01-01

This report describes a statewide study : conducted to develop main-channel slope (MCS) : curves for 138 selected streams in Iowa with : drainage areas greater than 100 square miles. : MCS values determined from the curves can be : used in regression...

Apparent phosphorus availabilities of selected traditional and alternative feedstuffs for channel catfish

USDA-ARS?s Scientific Manuscript database

A digestibility trial with channel catfish Ictalurus punctatus was conducted to determine apparent availability coefficients (AACs) of phosphorus for selected common feedstuffs: soybean meal, cottonseed meal, wheat middlings, corn gluten feed (CGF), and corn distillers dried grains with solubles (DD...

Evaluation of entropy and JM-distance criterions as features selection methods using spectral and spatial features derived from LANDSAT images

NASA Technical Reports Server (NTRS)

Parada, N. D. J. (Principal Investigator); Dutra, L. V.; Mascarenhas, N. D. A.; Mitsuo, Fernando Augusta, II

1984-01-01

A study area near Ribeirao Preto in Sao Paulo state was selected, with predominance in sugar cane. Eight features were extracted from the 4 original bands of LANDSAT image, using low-pass and high-pass filtering to obtain spatial features. There were 5 training sites in order to acquire the necessary parameters. Two groups of four channels were selected from 12 channels using JM-distance and entropy criterions. The number of selected channels was defined by physical restrictions of the image analyzer and computacional costs. The evaluation was performed by extracting the confusion matrix for training and tests areas, with a maximum likelihood classifier, and by defining performance indexes based on those matrixes for each group of channels. Results show that in spatial features and supervised classification, the entropy criterion is better in the sense that allows a more accurate and generalized definition of class signature. On the other hand, JM-distance criterion strongly reduces the misclassification within training areas.

A double tyrosine motif in the cardiac sodium channel domain III-IV linker couples calcium-dependent calmodulin binding to inactivation gating.

PubMed

Sarhan, Maen F; Van Petegem, Filip; Ahern, Christopher A

2009-11-27

Voltage-gated sodium channels maintain the electrical cadence and stability of neurons and muscle cells by selectively controlling the transmembrane passage of their namesake ion. The degree to which these channels contribute to cellular excitability can be managed therapeutically or fine-tuned by endogenous ligands. Intracellular calcium, for instance, modulates sodium channel inactivation, the process by which sodium conductance is negatively regulated. We explored the molecular basis for this effect by investigating the interaction between the ubiquitous calcium binding protein calmodulin (CaM) and the putative sodium channel inactivation gate composed of the cytosolic linker between homologous channel domains III and IV (DIII-IV). Experiments using isothermal titration calorimetry show that CaM binds to a novel double tyrosine motif in the center of the DIII-IV linker in a calcium-dependent manner, N-terminal to a region previously reported to be a CaM binding site. An alanine scan of aromatic residues in recombinant DIII-DIV linker peptides shows that whereas multiple side chains contribute to CaM binding, two tyrosines (Tyr(1494) and Tyr(1495)) play a crucial role in binding the CaM C-lobe. The functional relevance of these observations was then ascertained through electrophysiological measurement of sodium channel inactivation gating in the presence and absence of calcium. Experiments on patch-clamped transfected tsA201 cells show that only the Y1494A mutation of the five sites tested renders sodium channel steady-state inactivation insensitive to cytosolic calcium. The results demonstrate that calcium-dependent calmodulin binding to the sodium channel inactivation gate double tyrosine motif is required for calcium regulation of the cardiac sodium channel.

Novel regulatory mechanism in human urinary bladder: central role of transient receptor potential melastatin 4 channels in detrusor smooth muscle function

PubMed Central

Hristov, Kiril L.; Smith, Amy C.; Parajuli, Shankar P.; Malysz, John; Rovner, Eric S.

2016-01-01

Transient receptor potential melastatin 4 (TRPM4) channels are Ca2+-activated nonselective cation channels that have been recently identified as regulators of detrusor smooth muscle (DSM) function in rodents. However, their expression and function in human DSM remain unexplored. We provide insights into the functional role of TRPM4 channels in human DSM under physiological conditions. We used a multidisciplinary experimental approach, including RT-PCR, Western blotting, immunohistochemistry and immunocytochemistry, patch-clamp electrophysiology, and functional studies of DSM contractility. DSM samples were obtained from patients without preoperative overactive bladder symptoms. RT-PCR detected mRNA transcripts for TRPM4 channels in human DSM whole tissue and freshly isolated single cells. Western blotting and immunohistochemistry with confocal microscopy revealed TRPM4 protein expression in human DSM. Immunocytochemistry further detected TRPM4 protein expression in DSM single cells. Patch-clamp experiments showed that 9-phenanthrol, a selective TRPM4 channel inhibitor, significantly decreased the transient inward cation currents and voltage step-induced whole cell currents in freshly isolated human DSM cells. In current-clamp mode, 9-phenanthrol hyperpolarized the human DSM cell membrane potential. Furthermore, 9-phenanthrol attenuated the spontaneous phasic, carbachol-induced and nerve-evoked contractions in human DSM isolated strips. Significant species-related differences in TRPM4 channel activity between human, rat, and guinea pig DSM were revealed, suggesting a more prominent physiological role for the TRPM4 channel in the regulation of DSM function in humans than in rodents. In conclusion, TRPM4 channels regulate human DSM excitability and contractility and are critical determinants of human urinary bladder function. Thus, TRPM4 channels could represent promising novel targets for the pharmacological or genetic control of overactive bladder. PMID:26791488

Kainate receptor pore‐forming and auxiliary subunits regulate channel block by a novel mechanism

PubMed Central

Brown, Patricia M. G. E.; Aurousseau, Mark R. P.; Musgaard, Maria; Biggin, Philip C.

2016-01-01

Key points Kainate receptor heteromerization and auxiliary subunits, Neto1 and Neto2, attenuate polyamine ion‐channel block by facilitating blocker permeation.Relief of polyamine block in GluK2/GluK5 heteromers results from a key proline residue that produces architectural changes in the channel pore α‐helical region.Auxiliary subunits exert an additive effect to heteromerization, and thus relief of polyamine block is due to a different mechanism.Our findings have broad implications for work on polyamine block of other cation‐selective ion channels. Abstract Channel block and permeation by cytoplasmic polyamines is a common feature of many cation‐selective ion channels. Although the channel block mechanism has been studied extensively, polyamine permeation has been considered less significant as it occurs at extreme positive membrane potentials. Here, we show that kainate receptor (KAR) heteromerization and association with auxiliary proteins, Neto1 and Neto2, attenuate polyamine block by enhancing blocker permeation. Consequently, polyamine permeation and unblock occur at more negative and physiologically relevant membrane potentials. In GluK2/GluK5 heteromers, enhanced permeation is due to a single proline residue in GluK5 that alters the dynamics of the α‐helical region of the selectivity filter. The effect of auxiliary proteins is additive, and therefore the structural basis of polyamine permeation and unblock is through a different mechanism. As native receptors are thought to assemble as heteromers in complex with auxiliary proteins, our data identify an unappreciated impact of polyamine permeation in shaping the signalling properties of neuronal KARs and point to a structural mechanism that may be shared amongst other cation‐selective ion channels. PMID:26682513

Grain size indicators of sedimentary coupling between hillslopes and channels in a dryland basin

NASA Astrophysics Data System (ADS)

Hollings, Rory; Michealides, Katerina; Bliss Singer, Michael

2017-04-01

In dryland landscapes, heterogeneous and short-lived rainstorms generate runoff on slopes and streamflow in channels, which drive sediment movement from hillslope surfaces to channels and the transport of bed material sediment within channels. Long-term topographic evolution of drainage basins is partly determined by the relative balance of hillslope sediment supply to channels and the evacuation of channel sediment. However, it is not clear whether supply or evacuation is dominant over longer timescales (>>100 y) within dryland basins. One important indicator of local cumulative sediment transport is grain size (GS). On dryland hillslopes, grain size is governed over long timescales by weathering, but on short time scales (events to decades), is controlled by event-driven transport of the debris mantle. In the channel, GS reflects the input of hillslope sediment and the selective transport of particles along the bed. It is currently unknown how these two processes are expressed systematically within GS distributions on slopes and in channels within drylands, but this information could be useful to explain the history of the relative balance between hillslope sediment supply to channels and net sediment transport in the channel. We investigate this problem by combining field measurements of surface sediment grain size distributions in channels and on hillslopes with 1m LiDAR topography, >60 years of rainfall and channel discharge data from the Walnut Gulch Experimental Watershed (WGEW) in Arizona, and simple calculations of grain-sized based local stress distributions for various rainfall and discharge events. Hydrological scenarios of overland flow on hillslopes and channel flow conditions were derived from distributions of historic data at WGEW and were selected to reflect the wide range of storm intensities and durations, and channel discharges. 1) We used three quartiles of the entire distribution of measured discharge values for 80 locations throughout the channel network to represent low, medium and high flows. 2) For rainfall we used three quartiles of the entire distribution of measured rainfall intensity and duration from 85 rain gauges spanning the basin, to derive low, medium and high rainfall durations. We then calculated the corresponding rainfall intensities based on four intensity-duration curves that were characteristic of different parts of the phase space of the measured data-points. 3) The derived rainfall intensities and durations were converted into hillslope overland flow using Coup2D (a hillslope rainfall-runoff model) for 44 hillslopes within WGEW for which we have GS and topographic data. We employ the median grain size (D50) to compare stress metrics on hillslopes and in channel for each location. Typically, low-order streams experience greater influxes of hillslope derived sediment than is evacuated by the channel. However, the main channel stem is characterised by sediment removal in most scenarios including low discharge, long duration rainfall, suggesting most hillslope supplied sediment is balanced by channel evacuation. Near tributary junctions, and close to the mouth of the basin there are fluctuations in net balance of sediment transport from evacuation- to supply-dominance for different scenarios. These fluctuations could influence channel bed GS distribution and longitudinal profile development.

Ultrafast nuclear dynamics in halomethanes studied with time-resolved Coulomb explosion imaging and channel-selective Fourier spectroscopy

NASA Astrophysics Data System (ADS)

Malakar, Y.; Kaderiya, B.; Pearson, W. L.; Ziaee, F.; Kanaka Raju, P.; Zohrabi, M.; Jensen, K.; Rajput, J.; Ben-Itzhak, I.; Rolles, D.; Rudenko, A.

2016-05-01

Halomethanes have recently attracted considerable attention since they often serve as prototype systems for laser-controlled chemistry (e.g., selective bond breaking or concerted elimination reactions), and are important molecules in atmospheric chemistry. Here we combine a femtosecond laser pump-probe setup with coincident 3D ion momentum imaging apparatus to study strong-field induced nuclear dynamics in methane and several of its halogenated derivatives (CH3 I, CH2 I2, CH2 ICl). We apply a time-resolved Coulomb explosion imaging technique to map the nuclear motion on both, bound and continuum potential surfaces, disentangle different fragmentation pathways and, for halogenated molecules, observe clear signatures of vibrational wave packets in neutral or ionized states. Channel-selective and kinetic-energy resolved Fourier analysis of these data allows for unique identification of different electronic states and vibrational modes responsible for a particular structure. Supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. DOE. K. R. P. and W. L. P. supported by NSF Award No. IIA-143049. K.J. supported by the NSF-REU Grant No. PHYS-1461251.

Large scale rearrangement of protein domains is associated with voltage gating of the VDAC channel.

PubMed Central

Peng, S; Blachly-Dyson, E; Forte, M; Colombini, M

1992-01-01

The VDAC channel of the mitochondrial outer membrane is voltage-gated like the larger, more complex voltage-gated channels of the plasma membrane. However, VDAC is a low molecular weight (30 kDa), abundant protein, which is readily purified and reconstituted, making it an ideal system for analyzing the molecular basis for ion selectivity and voltage-gating. We have probed the VDAC channel by subjecting the cloned yeast (S. cerevisiae) VDAC gene to site-directed mutagenesis and introducing the resulting mutant channels into planar bilayers to detect the effects of specific sequence changes on channel properties. This approach has allowed us to formulate and test a model of the open state structure of the VDAC channel. Now we have applied the same approach to analyzing the structure of the channel's low-conducting "closed state" (essentially closed to important metabolites). We have identified protein domains forming the wall of the closed conformation and domains that seem to be removed from the wall of the pore during channel closure. The latter can explain the reduction in pore diameter and volume and the dramatically altered channel selectivity resulting from the channel closure. This process would make a natural coupling between motion of the sensor and channel gating. PMID:1376163

ATP transport through VDAC and the VDAC-tubulin complex probed by equilibrium and nonequilibrium MD simulations.

PubMed

Noskov, Sergei Yu; Rostovtseva, Tatiana K; Bezrukov, Sergey M

2013-12-23

Voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane, serves as a principal pathway for ATP, ADP, and other respiratory substrates across this membrane. Using umbrella-sampling simulations, we established the thermodynamic and kinetic components governing ATP transport across the VDAC1 channel. We found that there are several low-affinity binding sites for ATP along the translocation pathway and that the main barrier for ATP transport is located around the center of the channel and is formed predominantly by residues in the N-terminus. The binding affinity of ATP to an open channel was found to be in the millimolar to micromolar range. However, we show that this weak binding increases the ATP translocation probability by about 10-fold compared with the VDAC pore in which attractive interactions were artificially removed. Recently, it was found that free dimeric tubulin induces a highly efficient, reversible blockage of VDAC reconstituted into planar lipid membranes. It was proposed that by blocking VDAC permeability for ATP/ADP and other mitochondrial respiratory substrates tubulin controls mitochondrial respiration. Using the Rosetta protein-protein docking algorithm, we established a tentative structure of the VDAC-tubulin complex. An extensive set of equilibrium and nonequilibrium (under applied electric field) molecular dynamics (MD) simulations was used to establish the conductance of the open and blocked channel. It was found that the presence of the unstructured C-terminal tail of tubulin in the VDAC pore decreases its conductance by more than 40% and switches its selectivity from anionic to cationic. The subsequent 1D potential of mean force (PMF) computations for the VDAC-tubulin complex show that the state renders ATP transport virtually impossible. A number of residues pivotal for tubulin binding to the channel were identified that help to clarify the molecular details of VDAC-tubulin interaction and to provide new insight into the mechanism of the control of mitochondria respiration by VDAC.

Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

PubMed

Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

2012-09-01

What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in ATP-sensitive potassium channels. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

Massively parallel processor networks with optical express channels

DOEpatents

Deri, R.J.; Brooks, E.D. III; Haigh, R.E.; DeGroot, A.J.

1999-08-24

An optical method for separating and routing local and express channel data comprises interconnecting the nodes in a network with fiber optic cables. A single fiber optic cable carries both express channel traffic and local channel traffic, e.g., in a massively parallel processor (MPP) network. Express channel traffic is placed on, or filtered from, the fiber optic cable at a light frequency or a color different from that of the local channel traffic. The express channel traffic is thus placed on a light carrier that skips over the local intermediate nodes one-by-one by reflecting off of selective mirrors placed at each local node. The local-channel-traffic light carriers pass through the selective mirrors and are not reflected. A single fiber optic cable can thus be threaded throughout a three-dimensional matrix of nodes with the x,y,z directions of propagation encoded by the color of the respective light carriers for both local and express channel traffic. Thus frequency division multiple access is used to hierarchically separate the local and express channels to eliminate the bucket brigade latencies that would otherwise result if the express traffic had to hop between every local node to reach its ultimate destination. 3 figs.

Massively parallel processor networks with optical express channels

DOEpatents

Deri, Robert J.; Brooks, III, Eugene D.; Haigh, Ronald E.; DeGroot, Anthony J.

1999-01-01

An optical method for separating and routing local and express channel data comprises interconnecting the nodes in a network with fiber optic cables. A single fiber optic cable carries both express channel traffic and local channel traffic, e.g., in a massively parallel processor (MPP) network. Express channel traffic is placed on, or filtered from, the fiber optic cable at a light frequency or a color different from that of the local channel traffic. The express channel traffic is thus placed on a light carrier that skips over the local intermediate nodes one-by-one by reflecting off of selective mirrors placed at each local node. The local-channel-traffic light carriers pass through the selective mirrors and are not reflected. A single fiber optic cable can thus be threaded throughout a three-dimensional matrix of nodes with the x,y,z directions of propagation encoded by the color of the respective light carriers for both local and express channel traffic. Thus frequency division multiple access is used to hierarchically separate the local and express channels to eliminate the bucket brigade latencies that would otherwise result if the express traffic had to hop between every local node to reach its ultimate destination.

CLAG3 Self-Associates in Malaria Parasites and Quantitatively Determines Nutrient Uptake Channels at the Host Membrane.

PubMed

Gupta, Ankit; Balabaskaran-Nina, Praveen; Nguitragool, Wang; Saggu, Gagandeep S; Schureck, Marc A; Desai, Sanjay A

2018-05-08

Malaria parasites increase host erythrocyte permeability to ions and nutrients via a broad-selectivity channel known as the plasmodial surface anion channel (PSAC), linked to parasite-encoded CLAG3 and two associated proteins. These proteins lack the multiple transmembrane domains typically present in channel-forming proteins, raising doubts about their precise roles. Using the virulent human Plasmodium falciparum parasite, we report that CLAG3 undergoes self-association and that this protein's expression determines channel phenotype quantitatively. We overcame epigenetic silencing of clag3 paralogs and engineered parasites that express two CLAG3 isoforms simultaneously. Stoichiometric expression of these isoforms yielded intermediate channel phenotypes, in agreement with observed trafficking of both proteins to the host membrane. Coimmunoprecipitation and surface labeling revealed formation of CLAG3 oligomers. In vitro selections applied to these transfectant lines yielded distinct mutants with correlated changes in channel activity. These findings support involvement of the identified oligomers in PSAC formation and parasite nutrient acquisition. IMPORTANCE Malaria parasites are globally important pathogens that evade host immunity by replicating within circulating erythrocytes. To facilitate intracellular growth, these parasites increase erythrocyte nutrient uptake through an unusual ion channel. The parasite CLAG3 protein is a key determinant of this channel, but its lack of homology to known ion channels has raised questions about possible mechanisms. Using a new method that allows simultaneous expression of two different CLAG3 proteins, we identify self-association of CLAG3. The two expressed isoforms faithfully traffic to and insert in the host membrane, while remaining associated with two unrelated parasite proteins. Both the channel phenotypes and molecular changes produced upon selections with a highly specific channel inhibitor are consistent with a multiprotein complex that forms the nutrient pore. These studies support direct involvement of the CLAG3 protein in channel formation and are relevant to antimalarial drug discovery projects targeting parasite nutrient acquisition.

Gating modifier toxins isolated from spider venom: modulation of voltage-gated sodium channels and the role of lipid membranes.

PubMed

Agwa, Akello J; Peigneur, Steve; Chow, Chun Yuen; Lawrence, Nicole; Craik, David J; Tytgat, Jan; King, Glenn F; Henriques, Sonia Troeira; Schroeder, Christina I

2018-04-27

Gating modifier toxins (GMTs) are venom-derived peptides isolated from spiders and other venomous creatures that modulate activity of disease-relevant voltage-gated ion channels and are therefore being pursued as therapeutic leads. The amphipathic surface profile of GMTs has prompted the proposal that some GMTs simultaneously bind to the cell membrane and voltage-gated ion channels in a trimolecular complex. Here we examined whether there is a relationship among spider GMT amphipathicity, membrane binding and potency or selectivity for voltage-gated sodium (NaV) channels. We used NMR spectroscopy and in silico calculations to examine the structures and physicochemical properties of a panel of nine GMTs and deployed surface plasmon resonance to measure GMT affinity for lipids putatively found in proximity to NaV channels. Electrophysiology was used to quantify GMT activity on NaV1.7, an ion channel linked to chronic pain. Selectivity of the peptides was further examined against a panel of NaV channel subtypes. We show that GMTs adsorb to the outer leaflet of anionic lipid bilayers through electrostatic interactions. We did not observe a direct correlation between GMT amphipathicity and affinity for lipid bilayers. Furthermore, GMT-lipid bilayer interactions did not correlate with potency or selectivity for NaVs. We therefore propose that increased membrane binding is unlikely to improve subtype selectivity and that the conserved amphipathic GMT surface profile is an adaptation that facilitates simultaneous modulation of multiple NaVs. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

An energy-efficient rate adaptive media access protocol (RA-MAC) for long-lived sensor networks.

PubMed

Hu, Wen; Chen, Quanjun; Corke, Peter; O'Rourke, Damien

2010-01-01

We introduce an energy-efficient Rate Adaptive Media Access Control (RA-MAC) algorithm for long-lived Wireless Sensor Networks (WSNs). Previous research shows that the dynamic and lossy nature of wireless communications is one of the major challenges to reliable data delivery in WSNs. RA-MAC achieves high link reliability in such situations by dynamically trading off data rate for channel gain. The extra gain that can be achieved reduces the packet loss rate which contributes to reduced energy expenditure through a reduced numbers of retransmissions. We achieve this at the expense of raw bit rate which generally far exceeds the application's link requirement. To minimize communication energy consumption, RA-MAC selects the optimal data rate based on the estimated link quality at each data rate and an analytical model of the energy consumption. Our model shows how the selected data rate depends on different channel conditions in order to minimize energy consumption. We have implemented RA-MAC in TinyOS for an off-the-shelf sensor platform (the TinyNode) on top of a state-of-the-art WSN Media Access Control Protocol, SCP-MAC, and evaluated its performance by comparing our implementation with the original SCP-MAC using both simulation and experiment.

Considerations of Scale and Processes in Stream Restoration and Ecological Response

NASA Astrophysics Data System (ADS)

Simon, A.; Shields, D.; Kuhnle, R.; Knight, S.

2005-12-01

Stream restoration as a means of controlling accelerated channel erosion and improving biological function in streams has become pervasive in the United States over the past twenty years. A broad range of practices often involving direct modifications to stream channels and adjacent floodplains, including alterations to morphology and pattern have been used for stream restoration. Because alluvial-channel processes and biological functioning operate as linked, open systems, any restoration project must be placed in the context of existing watershed and channel processes with a quantitative understanding of the rates of transfer of flow energy and materials. This is particularly true of reach-scale projects where local stabilization and habitat improvements may be completely overwhelmed by watershed or channel-system scale instabilities. In this regard, it is unlikely that a reach-scale project will be successful in an unstable alluvial system. This is analogous to constructing bank-stabilization measures in an actively incising channel. A conceptual model of channel response and evolution that marks systematic shifts in channel processes over time and space has been linked to fish-community structure in Mississippi streams. This link reflects changing habitat conditions and sediment-transport regimes over the course of fluvial adjustment. Suspended-sediment concentrations that can increase by orders of magnitude for a given discharge during the incision and mass-wasting phases abrade fish gills and reduce the ability of fish to hunt for food due to reduced water clarity. Similarly, durations of high suspended-sediment concentrations are shown to be inversely related to numbers of benthic macro invertebrates. Streambeds experiencing active incision (Stage III) may be too mobile for benthic macro invertebrate communities to thrive. Channels dominated by mass-wasting processes (Stages IV and V) lose riparian vegetative cover and shading which may result in higher stream temperatures. Aggradation processes typical of Stage V result in loss of interstitial spaces for spawning, de-oxygenation of substrate and may suffocate organisms. Perhaps most importantly, channel widening produces shallower depths at base flow and renders streams less retentive of large wood. Ecological characteristics recover in advanced stages of channel evolution as baseflow channels are narrowed and berms re-vegetate (Stage VI), but full recovery to pre-incision (Stage I) conditions has not been observed for both ecologic and sediment-transport systems. The processes reflected by stages of evolution can operate over entire fluvial networks and over time scales in the order of 100 years. Issues regarding effectiveness or benefit of stream restoration practices, therefore, must address scale. Furthermore, site and approach selection for reach-scale restoration projects should be guided by knowledge of watershed-scale processes. As an example, a grade control structure installed on Hotophia Creek, Mississippi successfully eliminated upstream-progressing incision and resulted in locally improved aquatic populations in the stilling basin. However, the trapping of hydraulically-controlled sediment on the upstream side of the structure resulted in streambed incision, de-stabilization of streambanks and degraded aquatic habitat in downstream reaches not protected by other grade-control structures.

Using lidocaine and benzocaine to link sodium channel molecular conformations to state-dependent antiarrhythmic drug affinity.

PubMed

Hanck, Dorothy A; Nikitina, Elena; McNulty, Megan M; Fozzard, Harry A; Lipkind, Gregory M; Sheets, Michael F

2009-08-28

Lidocaine and other antiarrhythmic drugs bind in the inner pore of voltage-gated Na channels and affect gating use-dependently. A phenylalanine in domain IV, S6 (Phe1759 in Na(V)1.5), modeled to face the inner pore just below the selectivity filter, is critical in use-dependent drug block. Measurement of gating currents and concentration-dependent availability curves to determine the role of Phe1759 in coupling of drug binding to the gating changes. The measurements showed that replacement of Phe1759 with a nonaromatic residue permits clear separation of action of lidocaine and benzocaine into 2 components that can be related to channel conformations. One component represents the drug acting as a voltage-independent, low-affinity blocker of closed channels (designated as lipophilic block), and the second represents high-affinity, voltage-dependent block of open/inactivated channels linked to stabilization of the S4s in domains III and IV (designated as voltage-sensor inhibition) by Phe1759. A homology model for how lidocaine and benzocaine bind in the closed and open/inactivated channel conformation is proposed. These 2 components, lipophilic block and voltage-sensor inhibition, can explain the differences in estimates between tonic and open-state/inactivated-state affinities, and they identify how differences in affinity for the 2 binding conformations can control use-dependence, the hallmark of successful antiarrhythmic drugs.

Role for the TRPV1 channel in insulin secretion from pancreatic beta cells.

PubMed

Diaz-Garcia, Carlos Manlio; Morales-Lázaro, Sara L; Sánchez-Soto, Carmen; Velasco, Myrian; Rosenbaum, Tamara; Hiriart, Marcia

2014-06-01

Transient receptor potential channels have been put forward as regulators of insulin secretion. A role for the TRPV1 ion channel in insulin secretion has been suggested in pancreatic beta cell lines. We explored whether TRPV1 is functionally expressed in RINm5F and primary beta cells from neonate and adult rats. We examined if capsaicin could activate cationic non-selective currents. Our results show that TRPV1 channels are not functional in insulin-secreting cells, since capsaicin did not produce current activation, not even under culture conditions known to induce the expression of other ion channels in these cells. Although TRPV1 channels seem to be irrelevant for the physiology of isolated beta cells, they may play a role in glucose homeostasis acting through the nerve fibers that regulate islet function. At the physiological level, we observed that Trpv1 (-/-) mice presented lower fasting insulin levels than their wild-type littermates, however, we did not find differences between these experimental groups nor in the glucose tolerance test or in the insulin secretion. However, we did find that the Trpv1 (-/-) mice exhibited a higher insulin sensitivity compared to their wild-type counterparts. Our results demonstrate that TRPV1 does not contribute to glucose-induced insulin secretion in beta cells as was previously thought, but it is possible that it may control insulin sensitivity.

Molecular and functional characterization of Anopheles gambiae inward rectifier potassium (Kir1) channels: a novel role in egg production.

PubMed

Raphemot, Rene; Estévez-Lao, Tania Y; Rouhier, Matthew F; Piermarini, Peter M; Denton, Jerod S; Hillyer, Julián F

2014-08-01

Inward rectifier potassium (Kir) channels play essential roles in regulating diverse physiological processes. Although Kir channels are encoded in mosquito genomes, their functions remain largely unknown. In this study, we identified the members of the Anopheles gambiae Kir gene family and began to investigate their function. Notably, we sequenced the A. gambiae Kir1 (AgKir1) gene and showed that it encodes all the canonical features of a Kir channel: an ion pore that is composed of a pore helix and a selectivity filter, two transmembrane domains that flank the ion pore, and the so-called G-loop. Heterologous expression of AgKir1 in Xenopus oocytes revealed that this gene encodes a functional, barium-sensitive Kir channel. Quantitative RT-PCR experiments then showed that relative AgKir1 mRNA levels are highest in the pupal stage, and that AgKir1 mRNA is enriched in the adult ovaries. Gene silencing of AgKir1 by RNA interference did not affect the survival of female mosquitoes following a blood meal, but decreased their egg output. These data provide evidence for a new role of Kir channels in mosquito fecundity, and further validates them as promising molecular targets for the development of a new class of mosquitocides to be used in vector control. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Potent and Site-Selective Agonist of TRPA1.

PubMed

Takaya, Junichiro; Mio, Kazuhiro; Shiraishi, Takuya; Kurokawa, Tatsuki; Otsuka, Shinya; Mori, Yasuo; Uesugi, Motonari

2015-12-23

TRPA1 is a member of the transient receptor potential (TRP) cation channel family that is expressed primarily on sensory neurons. This chemosensor is activated through covalent modification of multiple cysteine residues with a wide range of reactive compounds including allyl isothiocyanate (AITC), a spicy component of wasabi. The present study reports on potent and selective agonists of TRPA1, discovered through screening 1657 electrophilic molecules. In an effort to validate the mode of action of hit molecules, we noted a new TRPA1-selective agonist, JT010 (molecule 1), which opens the TRPA1 channel by covalently and site-selectively binding to Cys621 (EC50 = 0.65 nM). The results suggest that a single modification of Cys621 is sufficient to open the TRPA1 channel. The TRPA1-selective probe described herein might be useful for further mechanistic studies of TRPA1 activation.

Management of Communication Channels for Health Information in the Community

ERIC Educational Resources Information Center

Tanvatanakul, Vasuton; Amado, Joao; Saowakontha, Sastri

2007-01-01

Object: To investigate channels for communication of health information to various groups in the community. Design: An exploratory cross sectional design was used, followed by focus groups of selected participants to confirm and clarify the findings. Setting: Five levels of sub-district administration organizations were selected from different…

Enhancement of time images for photointerpretation

NASA Technical Reports Server (NTRS)

Gillespie, A. R.

1986-01-01

The Thermal Infrared Multispectral Scanner (TIMS) images consist of six channels of data acquired in bands between 8 and 12 microns, thus they contain information about both temperature and emittance. Scene temperatures are controlled by reflectivity of the surface, but also by its geometry with respect to the Sun, time of day, and other factors unrelated to composition. Emittance is dependent upon composition alone. Thus the photointerpreter may wish to enhance emittance information selectively. Because thermal emittances in real scenes vary but little, image data tend to be highly correlated along channels. Special image processing is required to make this information available for the photointerpreter. Processing includes noise removal, construction of model emittance images, and construction of false-color pictures enhanced by decorrelation techniques.

Selective Dirac voltage engineering of individual graphene field-effect transistors for digital inverter and frequency multiplier integrations

NASA Astrophysics Data System (ADS)

Sul, Onejae; Kim, Kyumin; Jung, Yungwoo; Choi, Eunsuk; Lee, Seung-Beck

2017-09-01

The ambipolar band structure of graphene presents unique opportunities for novel electronic device applications. A cycle of gate voltage sweep in a conventional graphene transistor produces a frequency-doubled output current. To increase the frequency further, we used various graphene doping control techniques to produce Dirac voltage engineered graphene channels. The various surface treatments and substrate conditions produced differently doped graphene channels that were integrated on a single substrate and multiple Dirac voltages were observed by applying a single gate voltage sweep. We applied the Dirac voltage engineering techniques to graphene field-effect transistors on a single chip for the fabrication of a frequency multiplier and a logic inverter demonstrating analog and digital circuit application possibilities.

Coding/decoding and reversibility of droplet trains in microfluidic networks.

PubMed

Fuerstman, Michael J; Garstecki, Piotr; Whitesides, George M

2007-02-09

Droplets of one liquid suspended in a second, immiscible liquid move through a microfluidic device in which a channel splits into two branches that reconnect downstream. The droplets choose a path based on the number of droplets that occupy each branch. The interaction among droplets in the channels results in complex sequences of path selection. The linearity of the flow through the microchannels, however, ensures that the behavior of the system can be reversed. This reversibility makes it possible to encrypt and decrypt signals coded in the intervals between droplets. The encoding/decoding device is a functional microfluidic system that requires droplets to navigate a network in a precise manner without the use of valves, switches, or other means of external control.

Selective Dirac voltage engineering of individual graphene field-effect transistors for digital inverter and frequency multiplier integrations.

PubMed

Sul, Onejae; Kim, Kyumin; Jung, Yungwoo; Choi, Eunsuk; Lee, Seung-Beck

2017-09-15

The ambipolar band structure of graphene presents unique opportunities for novel electronic device applications. A cycle of gate voltage sweep in a conventional graphene transistor produces a frequency-doubled output current. To increase the frequency further, we used various graphene doping control techniques to produce Dirac voltage engineered graphene channels. The various surface treatments and substrate conditions produced differently doped graphene channels that were integrated on a single substrate and multiple Dirac voltages were observed by applying a single gate voltage sweep. We applied the Dirac voltage engineering techniques to graphene field-effect transistors on a single chip for the fabrication of a frequency multiplier and a logic inverter demonstrating analog and digital circuit application possibilities.

Mapping of Residues Forming the Voltage Sensor of the Voltage-Dependent Anion-Selective Channel

NASA Astrophysics Data System (ADS)

Thomas, Lorie; Blachly-Dyson, Elizabeth; Colombini, Marco; Forte, Michael

1993-06-01

Voltage-gated ion-channel proteins contain "voltage-sensing" domains that drive the conformational transitions between open and closed states in response to changes in transmembrane voltage. We have used site-directed mutagenesis to identify residues affecting the voltage sensitivity of a mitochondrial channel, the voltage-dependent anion-selective channel (VDAC). Although charge changes at many sites had no effect, at other sites substitutions that increased positive charge also increased the steepness of voltage dependance and substitutions that decreased positive charge decreased voltage dependance by an appropriate amount. In contrast to the plasma membrane K^+ and Na^+ channels, these residues are distributed over large parts of the VDAC protein. These results have been used to define the conformational transitions that accompany voltage gating of an ion channel. This gating mechanism requires the movement of large portions of the VDAC protein through the membrane.

Electron cryo-microscopy structure of the canonical TRPC4 ion channel

PubMed Central

Vinayagam, Deivanayagabarathy; Mager, Thomas; Apelbaum, Amir; Bothe, Arne; Merino, Felipe; Hofnagel, Oliver; Gatsogiannis, Christos

2018-01-01

Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3.6 Å. The structure reveals the molecular architecture of the cation conducting pore, including the selectivity filter and lower gate. The cytoplasmic domain contains two key hubs that have been shown to interact with modulating proteins. Structural comparisons with other TRP channels give novel insights into the general architecture and domain organization of this superfamily of channels and help to understand their function and pharmacology. PMID:29717981

Evoked potential correlates of selective attention with multi-channel auditory inputs

NASA Technical Reports Server (NTRS)

Schwent, V. L.; Hillyard, S. A.

1975-01-01

Ten subjects were presented with random, rapid sequences of four auditory tones which were separated in pitch and apparent spatial position. The N1 component of the auditory vertex evoked potential (EP) measured relative to a baseline was observed to increase with attention. It was concluded that the N1 enhancement reflects a finely tuned selective attention to one stimulus channel among several concurrent, competing channels. This EP enhancement probably increases with increased information load on the subject.

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.

CLAG3 Self-Associates in Malaria Parasites and Quantitatively Determines Nutrient Uptake Channels at the Host Membrane

PubMed Central

Gupta, Ankit; Balabaskaran-Nina, Praveen; Nguitragool, Wang; Saggu, Gagandeep S.; Schureck, Marc A.

2018-01-01

ABSTRACT Malaria parasites increase host erythrocyte permeability to ions and nutrients via a broad-selectivity channel known as the plasmodial surface anion channel (PSAC), linked to parasite-encoded CLAG3 and two associated proteins. These proteins lack the multiple transmembrane domains typically present in channel-forming proteins, raising doubts about their precise roles. Using the virulent human Plasmodium falciparum parasite, we report that CLAG3 undergoes self-association and that this protein’s expression determines channel phenotype quantitatively. We overcame epigenetic silencing of clag3 paralogs and engineered parasites that express two CLAG3 isoforms simultaneously. Stoichiometric expression of these isoforms yielded intermediate channel phenotypes, in agreement with observed trafficking of both proteins to the host membrane. Coimmunoprecipitation and surface labeling revealed formation of CLAG3 oligomers. In vitro selections applied to these transfectant lines yielded distinct mutants with correlated changes in channel activity. These findings support involvement of the identified oligomers in PSAC formation and parasite nutrient acquisition. PMID:29739907

Study of Internal Channel Surface Roughnesses Manufactured by Selective Laser Melting in Aluminum and Titanium Alloys

NASA Astrophysics Data System (ADS)

Pakkanen, Jukka; Calignano, Flaviana; Trevisan, Francesco; Lorusso, Massimo; Ambrosio, Elisa Paola; Manfredi, Diego; Fino, Paolo

2016-08-01

Interest in additive manufacturing (AM) has gained considerable impetus over the past decade. One of the driving factors for AM success is the ability to create unique designs with intrinsic characteristics as, e.g., internal channels used for hydraulic components, cooling channels, and heat exchangers. However, a couple of the main problems in internal channels manufactured by AM technologies are the high surface roughness obtained and the distortion of the channel shape. There is still much to understand in these design aspects. In this study, a cylindrical geometry for internal channels to be built with different angles with respect to the building plane in AlSi10Mg and Ti6Al4V alloys by selective laser melting was considered. The internal surfaces of the channels produced in both materials were analyzed by means of a surface roughness tester and by optical and electron microscopy to evaluate the effects of the material and design choices.

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.

Language Planning, Channel Management, and ESP.

ERIC Educational Resources Information Center

Kennedy, Chris

Channel management, a concept developed in marketing to refer to the process by which a product is moved from production to consumption, uses a channel of distribution operating at several levels, each responsible for one or more of the activities of moving the product forward to the consumer. The function of channel management is to select the…

Ion channel gene expression predicts survival in glioma patients

PubMed Central

Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

2015-01-01

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. PMID:26235283

Channel geometry and hydrologic data for six eruption-affected tributaries of the Lewis River, Mount St. Helens, Washington, water years 1983-84

USGS Publications Warehouse

Martinson, H.A.; Hammond, H.E.; Mast, W.W.; Mango, P.D.

1986-01-01

The May 18, 1980, eruption of Mount St. Helens generated a lateral blast, lahars, and tephra deposits that altered stream channels in the Lewis River drainage basin. In order to assess potential flood hazards, monitor channel adjustments, and construct a sediment budget for disturbed drainages on the east and southeast flanks of the volcano, channel cross sections were monumented and surveyed on Pine Creek, Muddy River, and Smith Creek during September and October of 1980. Additional cross sections were monumented and surveyed on Swift Creek, Bean Creek , and Clearwater Creek during 1981. This network of channel cross sections has been resurveyed annually. Selected cross sections have been surveyed more frequently, following periods of higher flow. Longitudinal stream profiles of the low-water thalweg and (or) water surfaces were surveyed periodically for selected short reaches of channel. Corresponding map views for these reaches were constructed using the survey data and aerial photographs. This report presents plots of channel cross-section profiles, longitudinal stream profiles, and channel maps constructed from survey data collected during water years 1983-84. (USGS)

Bandwidth efficient channel estimation method for airborne hyperspectral data transmission in sparse doubly selective communication channels

NASA Astrophysics Data System (ADS)

Vahidi, Vahid; Saberinia, Ebrahim; Regentova, Emma E.

2017-10-01

A channel estimation (CE) method based on compressed sensing (CS) is proposed to estimate the sparse and doubly selective (DS) channel for hyperspectral image transmission from unmanned aircraft vehicles to ground stations. The proposed method contains three steps: (1) the priori estimate of the channel by orthogonal matching pursuit (OMP), (2) calculation of the linear minimum mean square error (LMMSE) estimate of the received pilots given the estimated channel, and (3) estimate of the complex amplitudes and Doppler shifts of the channel using the enhanced received pilot data applying a second round of a CS algorithm. The proposed method is named DS-LMMSE-OMP, and its performance is evaluated by simulating transmission of AVIRIS hyperspectral data via the communication channel and assessing their fidelity for the automated analysis after demodulation. The performance of the DS-LMMSE-OMP approach is compared with that of two other state-of-the-art CE methods. The simulation results exhibit up to 8-dB figure of merit in the bit error rate and 50% improvement in the hyperspectral image classification accuracy.

Purified ryanodine receptor from rabbit skeletal muscle is the calcium- release channel of sarcoplasmic reticulum

PubMed Central

1988-01-01

The ryanodine receptor of rabbit skeletal muscle sarcoplasmic reticulum was purified as a single 450,000-dalton polypeptide from CHAPS- solubilized triads using immunoaffinity chromatography. The purified receptor had a [3H]ryanodine-binding capacity (Bmax) of 490 pmol/mg and a binding affinity (Kd) of 7.0 nM. Using planar bilayer recording techniques, we show that the purified receptor forms cationic channels selective for divalent ions. Ryanodine receptor channels were identical to the Ca-release channels described in native sarcoplasmic reticulum using the same techniques. In the present work, four criteria were used to establish this identity: (a) activation of channels by micromolar Ca and millimolar ATP and inhibition by micromolar ruthenium red, (b) a main channel conductance of 110 +/- 10 pS in 54 mM trans Ca, (c) a long- term open state of lower unitary conductance induced by ryanodine concentrations as low as 20 nM, and (d) a permeability ratio PCa/PTris approximately equal to 14. In addition, we show that the purified ryanodine receptor channel displays a saturable conductance in both monovalent and divalent cation solutions (gamma max for K and Ca = 1 nS and 172 pS, respectively). In the absence of Ca, channels had a broad selectivity for monovalent cations, but in the presence of Ca, they were selectively permeable to Ca against K by a permeability ratio PCa/PK approximately equal to 6. Receptor channels displayed several equivalent conductance levels, which suggest an oligomeric pore structure. We conclude that the 450,000-dalton polypeptide ryanodine receptor is the Ca-release channel of the sarcoplasmic reticulum and is the target site of ruthenium red and ryanodine. PMID:2459298

TRPM4 channel: a new player in urinary bladder smooth muscle function in rats

PubMed Central

Smith, Amy C.; Parajuli, Shankar P.; Hristov, Kiril L.; Cheng, Qiuping; Soder, Rupal P.; Afeli, Serge A. Y.; Earley, Scott; Xin, Wenkuan; Malysz, John

2013-01-01

The TRPM4 channel is a Ca2+-activated, monovalent cation-selective channel of the melastatin transient receptor potential (TRPM) family. The TRPM4 channel is implicated in the regulation of many cellular processes including the immune response, insulin secretion, and pressure-induced vasoconstriction of cerebral arteries. However, the expression and function of the TRPM4 channels in detrusor smooth muscle (DSM) have not yet been explored. Here, we provide the first molecular, electrophysiological, and functional evidence for the presence of TRPM4 channels in rat DSM. We detected the expression of TRPM4 channels at mRNA and protein levels in freshly isolated DSM single cells and DSM tissue using RT-PCR, Western blotting, immunohistochemistry, and immunocytochemistry. 9-Hydroxyphenanthrene (9-phenanthrol), a novel selective inhibitor of TRPM4 channels, was used to examine their role in DSM function. In perforated patch-clamp recordings using freshly isolated rat DSM cells, 9-phenanthrol (30 μM) decreased the spontaneous inward current activity at −70 mV. Real-time DSM live-cell Ca2+ imaging showed that selective inhibition of TRPM4 channels with 9-phenanthrol (30 μM) significantly reduced the intracellular Ca2+ levels. Isometric DSM tension recordings revealed that 9-phenanthrol (0.1–30 μM) significantly inhibited the amplitude, muscle force integral, and frequency of the spontaneous phasic and pharmacologically induced contractions of rat DSM isolated strips. 9-Phenanthrol also decreased the amplitude and muscle force integral of electrical field stimulation-induced contractions. In conclusion, this is the first study to examine the expression and provide evidence for TRPM4 channels as critical regulators of rat DSM excitability and contractility. PMID:23283997

Fingerprint recognition of alien invasive weeds based on the texture character and machine learning

NASA Astrophysics Data System (ADS)

Yu, Jia-Jia; Li, Xiao-Li; He, Yong; Xu, Zheng-Hao

2008-11-01

Multi-spectral imaging technique based on texture analysis and machine learning was proposed to discriminate alien invasive weeds with similar outline but different categories. The objectives of this study were to investigate the feasibility of using Multi-spectral imaging, especially the near-infrared (NIR) channel (800 nm+/-10 nm) to find the weeds' fingerprints, and validate the performance with specific eigenvalues by co-occurrence matrix. Veronica polita Pries, Veronica persica Poir, longtube ground ivy, Laminum amplexicaule Linn. were selected in this study, which perform different effect in field, and are alien invasive species in China. 307 weed leaves' images were randomly selected for the calibration set, while the remaining 207 samples for the prediction set. All images were pretreated by Wallis filter to adjust the noise by uneven lighting. Gray level co-occurrence matrix was applied to extract the texture character, which shows density, randomness correlation, contrast and homogeneity of texture with different algorithms. Three channels (green channel by 550 nm+/-10 nm, red channel by 650 nm+/-10 nm and NIR channel by 800 nm+/-10 nm) were respectively calculated to get the eigenvalues.Least-squares support vector machines (LS-SVM) was applied to discriminate the categories of weeds by the eigenvalues from co-occurrence matrix. Finally, recognition ratio of 83.35% by NIR channel was obtained, better than the results by green channel (76.67%) and red channel (69.46%). The prediction results of 81.35% indicated that the selected eigenvalues reflected the main characteristics of weeds' fingerprint based on multi-spectral (especially by NIR channel) and LS-SVM model.

Low-Complexity User Selection for Rate Maximization in MIMO Broadcast Channels with Downlink Beamforming

PubMed Central

Silva, Adão; Gameiro, Atílio

2014-01-01

We present in this work a low-complexity algorithm to solve the sum rate maximization problem in multiuser MIMO broadcast channels with downlink beamforming. Our approach decouples the user selection problem from the resource allocation problem and its main goal is to create a set of quasiorthogonal users. The proposed algorithm exploits physical metrics of the wireless channels that can be easily computed in such a way that a null space projection power can be approximated efficiently. Based on the derived metrics we present a mathematical model that describes the dynamics of the user selection process which renders the user selection problem into an integer linear program. Numerical results show that our approach is highly efficient to form groups of quasiorthogonal users when compared to previously proposed algorithms in the literature. Our user selection algorithm achieves a large portion of the optimum user selection sum rate (90%) for a moderate number of active users. PMID:24574928

In situ control of synchronous germanide/silicide reactions with Ge/Si core/shell nanowires to monitor formation and strain evolution in abrupt 2.7 nm channel length

DOE PAGES

Chen, Renjie; Nguyen, Binh-Minh; Tang, Wei; ...

2017-05-22

The metal-semiconductor interface in self-aligned contact formation can determine the overall performance of nanoscale devices. This interfacial morphology is predicted and well researched in homogenous semiconductor nanowires (NWs) but was not pursued in heterostructured core/shell nanowires. Here, we found here that the solid-state reactions between Ni and Ge/Si core/shell nanowires resulted in a protruded and a leading NiSiy segment into the channel. A single Ni 2Ge/NiSi y to Ge/Si core/shell interface was achieved by the selective shell removal near the Ni source/drain contact areas. In using in situ transmission electron microscopy, we measured the growth rate and anisotropic strain evolutionmore » in ultra-short channels. We also found elevated compressive strains near the interface between the compound contact and the NW and relatively lower strains near the center of the channel which increased exponentially below the 10 nm channel length to exceed 10% strain at ~3 nm lengths. These compressive strains are expected to result in a non-homogeneous energy band structure in Ge/Si core/shell NWs below 10 nm and potentially benefit their transistor performance.« less

An insecticide resistance-breaking mosquitocide targeting inward rectifier potassium channels in vectors of Zika virus and malaria.

PubMed

Swale, Daniel R; Engers, Darren W; Bollinger, Sean R; Gross, Aaron; Inocente, Edna Alfaro; Days, Emily; Kanga, Fariba; Johnson, Reed M; Yang, Liu; Bloomquist, Jeffrey R; Hopkins, Corey R; Piermarini, Peter M; Denton, Jerod S

2016-11-16

Insecticide resistance is a growing threat to mosquito control programs around the world, thus creating the need to discover novel target sites and target-specific compounds for insecticide development. Emerging evidence suggests that mosquito inward rectifier potassium (Kir) channels represent viable molecular targets for developing insecticides with new mechanisms of action. Here we describe the discovery and characterization of VU041, a submicromolar-affinity inhibitor of Anopheles (An.) gambiae and Aedes (Ae.) aegypti Kir1 channels that incapacitates adult female mosquitoes from representative insecticide-susceptible and -resistant strains of An. gambiae (G3 and Akron, respectively) and Ae. aegypti (Liverpool and Puerto Rico, respectively) following topical application. VU041 is selective for mosquito Kir channels over several mammalian orthologs, with the exception of Kir2.1, and is not lethal to honey bees. Medicinal chemistry was used to develop an analog, termed VU730, which retains activity toward mosquito Kir1 but is not active against Kir2.1 or other mammalian Kir channels. Thus, VU041 and VU730 are promising chemical scaffolds for developing new classes of insecticides to combat insecticide-resistant mosquitoes and the transmission of mosquito-borne diseases, such as Zika virus, without harmful effects on humans and beneficial insects.

Optimum Adaptive Modulation and Channel Coding Scheme for Frequency Domain Channel-Dependent Scheduling in OFDM Based Evolved UTRA Downlink

NASA Astrophysics Data System (ADS)

Miki, Nobuhiko; Kishiyama, Yoshihisa; Higuchi, Kenichi; Sawahashi, Mamoru; Nakagawa, Masao

In the Evolved UTRA (UMTS Terrestrial Radio Access) downlink, Orthogonal Frequency Division Multiplexing (OFDM) based radio access was adopted because of its inherent immunity to multipath interference and flexible accommodation of different spectrum arrangements. This paper presents the optimum adaptive modulation and channel coding (AMC) scheme when resource blocks (RBs) is simultaneously assigned to the same user when frequency and time domain channel-dependent scheduling is assumed in the downlink OFDMA radio access with single-antenna transmission. We start by presenting selection methods for the modulation and coding scheme (MCS) employing mutual information both for RB-common and RB-dependent modulation schemes. Simulation results show that, irrespective of the application of power adaptation to RB-dependent modulation, the improvement in the achievable throughput of the RB-dependent modulation scheme compared to that for the RB-common modulation scheme is slight, i.e., 4 to 5%. In addition, the number of required control signaling bits in the RB-dependent modulation scheme becomes greater than that for the RB-common modulation scheme. Therefore, we conclude that the RB-common modulation and channel coding rate scheme is preferred, when multiple RBs of the same coded stream are assigned to one user in the case of single-antenna transmission.

The Upregulation of α2δ-1 Subunit Modulates Activity-Dependent Ca2+ Signals in Sensory Neurons

PubMed Central

Margas, Wojciech; Cassidy, John S.

2015-01-01

As auxiliary subunits of voltage-gated Ca2+ channels, the α2δ proteins modulate membrane trafficking of the channels and their localization to specific presynaptic sites. Following nerve injury, upregulation of the α2δ-1 subunit in sensory dorsal root ganglion neurons contributes to the generation of chronic pain states; however, very little is known about the underlying molecular mechanisms. Here we show that the increased expression of α2δ-1 in rat sensory neurons leads to prolonged Ca2+ responses evoked by membrane depolarization. This mechanism is coupled to CaV2.2 channel-mediated responses, as it is blocked by a ω-conotoxin GVIA application. Once initiated, the prolonged Ca2+ transients are not dependent on extracellular Ca2+ and do not require Ca2+ release from the endoplasmic reticulum. The selective inhibition of mitochondrial Ca2+ uptake demonstrates that α2δ-1-mediated prolonged Ca2+ signals are buffered by mitochondria, preferentially activated by Ca2+ influx through CaV2.2 channels. Thus, by controlling channel abundance at the plasma membrane, the α2δ-1 subunit has a major impact on the organization of depolarization-induced intracellular Ca2+ signaling in dorsal root ganglion neurons. PMID:25878262

In situ control of synchronous germanide/silicide reactions with Ge/Si core/shell nanowires to monitor formation and strain evolution in abrupt 2.7 nm channel length

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

Chen, Renjie; Nguyen, Binh-Minh; Tang, Wei

The metal-semiconductor interface in self-aligned contact formation can determine the overall performance of nanoscale devices. This interfacial morphology is predicted and well researched in homogenous semiconductor nanowires (NWs) but was not pursued in heterostructured core/shell nanowires. Here, we found here that the solid-state reactions between Ni and Ge/Si core/shell nanowires resulted in a protruded and a leading NiSiy segment into the channel. A single Ni 2Ge/NiSi y to Ge/Si core/shell interface was achieved by the selective shell removal near the Ni source/drain contact areas. In using in situ transmission electron microscopy, we measured the growth rate and anisotropic strain evolutionmore » in ultra-short channels. We also found elevated compressive strains near the interface between the compound contact and the NW and relatively lower strains near the center of the channel which increased exponentially below the 10 nm channel length to exceed 10% strain at ~3 nm lengths. These compressive strains are expected to result in a non-homogeneous energy band structure in Ge/Si core/shell NWs below 10 nm and potentially benefit their transistor performance.« less

Ion channel-mediated uptake of cationic vital dyes into live cells: a potential source of error when assessing cell viability.

PubMed

Bukhari, Maurish; Burm, Hayley; Samways, Damien S K

2016-10-01

Ionic "vital dyes" are commonly used to assess cell viability based on the idea that their permeation is contingent on a loss of membrane integrity. However, the possibility that dye entry is conducted into live cells by endogenous membrane transporters must be recognized and controlled for. Several cation-selective plasma membrane-localized ion channels, including the adenosine 5'-triphosphate (ATP)-gated P2X receptors, have been reported to conduct entry of the DNA-binding fluorescence dye, YO-PRO-1, into live cells. Extracellular ATP often becomes elevated as a result of release from dying cells, and so it is possible that activation of P2X channels on neighboring live cells could lead to exaggerated estimation of cytotoxicity. Here, we screened a number of fluorescent vital dyes for ion channel-mediated uptake in HEK293 cells expressing recombinant P2X2, P2X7, or TRPV1 channels. Our data shows that activation of all three channels caused substantial uptake and nuclear accumulation of YO-PRO-1, 4',6-diamidino-2-phenylindole (DAPI), and Hoechst 33258 into transfected cells and did so well within the time period usually used for incubation of cells with vital dyes. In contrast, channel activation in the presence of propidium iodide and SYTOX Green caused no measurable uptake and accumulation during a 20-min exposure, suggesting that these dyes are not likely to exhibit measurable uptake through these particular ion channels during a conventional cell viability assay. Caution is encouraged when choosing and employing cationic dyes for the purpose of cell viability assessment, particularly when there is a likelihood of cells expressing ion channels permeable to large ions.

Drosophila KCNQ Channel Displays Evolutionarily Conserved Electrophysiology and Pharmacology with Mammalian KCNQ Channels

PubMed Central

Cavaliere, Sonia; Hodge, James J. L.

2011-01-01

Of the five human KCNQ (Kv7) channels, KCNQ1 with auxiliary subunit KCNE1 mediates the native cardiac IKs current with mutations causing short and long QT cardiac arrhythmias. KCNQ4 mutations cause deafness. KCNQ2/3 channels form the native M-current controlling excitability of most neurons, with mutations causing benign neonatal febrile convulsions. Drosophila contains a single KCNQ (dKCNQ) that appears to serve alone the functions of all the duplicated mammalian neuronal and cardiac KCNQ channels sharing roughly 50–60% amino acid identity therefore offering a route to investigate these channels. Current information about the functional properties of dKCNQ is lacking therefore we have investigated these properties here. Using whole cell patch clamp electrophysiology we compare the biophysical and pharmacological properties of dKCNQ with the mammalian neuronal and cardiac KCNQ channels expressed in HEK cells. We show that Drosophila KCNQ (dKCNQ) is a slowly activating and slowly-deactivating K+ current open at sub-threshold potentials that has similar properties to neuronal KCNQ2/3 with some features of the cardiac KCNQ1/KCNE1 accompanied by conserved sensitivity to a number of clinically relevant KCNQ blockers (chromanol 293B, XE991, linopirdine) and opener (zinc pyrithione). We also investigate the molecular basis of the differential selectivity of KCNQ channels to the opener retigabine and show a single amino acid substitution (M217W) can confer sensitivity to dKCNQ. We show dKCNQ has similar electrophysiological and pharmacological properties as the mammalian KCNQ channels, allowing future study of physiological and pathological roles of KCNQ in Drosophila and whole organism screening for new modulators of KCNQ channelopathies. PMID:21915266

Proof-of-principle test of coherent-state continuous variable quantum key distribution through turbulent atmosphere (Conference Presentation)

NASA Astrophysics Data System (ADS)

Derkach, Ivan D.; Peuntinger, Christian; Ruppert, László; Heim, Bettina; Gunthner, Kevin; Usenko, Vladyslav C.; Elser, Dominique; Marquardt, Christoph; Filip, Radim; Leuchs, Gerd

2016-10-01

Continuous-variable quantum key distribution is a practical application of quantum information theory that is aimed at generation of secret cryptographic key between two remote trusted parties and that uses multi-photon quantum states as carriers of key bits. Remote parties share the secret key via a quantum channel, that presumably is under control of of an eavesdropper, and which properties must be taken into account in the security analysis. Well-studied fiber-optical quantum channels commonly possess stable transmittance and low noise levels, while free-space channels represent a simpler, less demanding and more flexible alternative, but suffer from atmospheric effects such as turbulence that in particular causes a non-uniform transmittance distribution referred to as fading. Nonetheless free-space channels, providing an unobstructed line-of-sight, are more apt for short, mid-range and potentially long-range (using satellites) communication and will play an important role in the future development and implementation of QKD networks. It was previously theoretically shown that coherent-state CV QKD should be in principle possible to implement over a free-space fading channel, but strong transmittance fluctuations result in the significant modulation-dependent channel excess noise. In this regime the post-selection of highly transmitting sub-channels may be needed, which can even restore the security of the protocol in the strongly turbulent channels. We now report the first proof-of-principle experimental test of coherent state CV QKD protocol using different levels Gaussian modulation over a mid-range (1.6-kilometer long) free-space atmospheric quantum channel. The transmittance of the link was characterized using intensity measurements for the reference but channel estimation using the modulated coherent states was also studied. We consider security against Gaussian collective attacks, that were shown to be optimal against CV QKD protocols . We assumed a general entangling cloner collective attack (modeled using data obtained from the state measurement results on both trusted sides of the protocol), that allows to purify the noise added in the quantum channel . Our security analysis of coherent-state protocol also took into account the effect of imperfect channel estimation, limited post-processing efficiency and finite data ensemble size on the performance of the protocol. In this regime we observe the positive key rate even without the need of applying post-selection. We show the positive improvement of the key rate with increase of the modulation variance, still remaining low enough to tolerate the transmittance fluctuations. The obtained results show that coherent-state CV QKD protocol that uses real free-space atmospheric channel can withstand negative influence of transmittance fluctuations, limited post-processing efficiency, imperfect channel estimation and other finite-size effects, and be successfully implemented. Our result paves the way to the full-scale implementation of the CV QKD in real free-space channels at mid-range distances.

Distributed Fair Auto Rate Medium Access Control for IEEE 802.11 Based WLANs

NASA Astrophysics Data System (ADS)

Zhu, Yanfeng; Niu, Zhisheng

Much research has shown that a carefully designed auto rate medium access control can utilize the underlying physical multi-rate capability to exploit the time-variation of the channel. In this paper, we develop a simple analytical model to elucidate the rule that maximizes the throughput of RTS/CTS based multi-rate wireless local area networks. Based on the discovered rule, we propose two distributed fair auto rate medium access control schemes called FARM and FARM+ from the view-point of throughput fairness and time-share fairness, respectively. With the proposed schemes, after receiving a RTS frame, the receiver selectively returns the CTS frame to inform the transmitter the maximum feasible rate probed by the signal-to-noise ratio of the received RTS frame. The key feature of the proposed schemes is that they are capable of maintaining throughput/time-share fairness in asymmetric situation where the distribution of SNR varies with stations. Extensive simulation results show that the proposed schemes outperform the existing throughput/time-share fair auto rate schemes in time-varying channel conditions.

Communications protocol

NASA Technical Reports Server (NTRS)

Zhou, Xiaoming (Inventor); Baras, John S. (Inventor)

2010-01-01

The present invention relates to an improved communications protocol which increases the efficiency of transmission in return channels on a multi-channel slotted Alohas system by incorporating advanced error correction algorithms, selective retransmission protocols and the use of reserved channels to satisfy the retransmission requests.

Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity.

PubMed

Valente, Pierluigi; Fernández-Carvajal, Asia; Camprubí-Robles, María; Gomis, Ana; Quirce, Susana; Viana, Félix; Fernández-Ballester, Gregorio; González-Ros, José M; Belmonte, Carlos; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

2011-05-01

The transient receptor potential vanilloid 1 (TRPV1) channel is a thermosensory receptor implicated in diverse physiological and pathological processes. The TRP domain, a highly conserved region in the C terminus adjacent to the internal channel gate, is critical for subunit tetramerization and channel gating. Here, we show that cell-penetrating, membrane-anchored peptides patterned after this protein domain are moderate and selective TRPV1 antagonists both in vitro and in vivo, blocking receptor activity in intact rat primary sensory neurons and their peripheral axons with mean decline time of 30 min. The most potent lipopeptide, TRP-p5, blocked all modes of TRPV1 gating with micromolar efficacy (IC(50)<10 μM), without significantly affecting other thermoTRP channels. In contrast, its retrosequence or the corresponding sequences of other TRPV channels did not alter TRPV1 channel activity (IC(50)>100 μM). TRP-p5 did not affect the capsaicin sensitivity of the vanilloid receptor. Our data suggest that TRP-p5 interferes with protein-protein interactions at the level of the TRP domain that are essential for the "conformational" change that leads to gate opening. Therefore, these palmitoylated peptides, which we termed TRPducins, are noncompetitive, voltage-independent, sequence-specific TRPV1 blockers. Our findings indicate that TRPducin-like peptides may embody a novel molecular strategy that can be exploited to generate a selective pharmacological arsenal for the TRP superfamily of ion channels.

LED lamp power management system and method

DOEpatents

Gaines, James; Clauberg, Bernd; Van Erp, Josephus A. M.

2013-03-19

An LED lamp power management system and method including an LED lamp having an LED controller 58; a plurality of LED channels 60 operably connected to the LED controller 58, each of the plurality of LED channels 60 having a channel switch 62 in series with at least one shunted LED circuit 83, the shunted LED circuit 83 having a shunt switch 68 in parallel with an LED source 80. The LED controller 58 reduces power loss in one of the channel switch 62 and the shunt switch 68 when LED lamp electronics power loss (P.sub.loss) exceeds an LED lamp electronics power loss limit (P.sub.lim); and each of the channel switches 62 receives a channel switch control signal 63 from the LED controller 58 and each of the shunt switches 68 receives a shunt switch control signal 69 from the LED controller 58.

System for routing messages in a vertex symmetric network by using addresses formed from permutations of the transmission line indicees

DOEpatents

Faber, Vance; Moore, James W.

1992-01-01

A network of interconnected processors is formed from a vertex symmetric graph selected from graphs .GAMMA..sub.d (k) with degree d, diameter k, and (d+1)!/(d-k+1)! processors for each d.gtoreq.k and .GAMMA..sub.d (k,-1) with degree 3-1, diameter k+1, and (d+1)!/(d-k+1)! processors for each d.gtoreq.k.gtoreq.4. Each processor has an address formed by one of the permutations from a predetermined sequence of letters chosen a selected number of letters at a time, and an extended address formed by appending to the address the remaining ones of the predetermined sequence of letters. A plurality of transmission channels is provided from each of the processors, where each processor has one less channel than the selected number of letters forming the sequence. Where a network .GAMMA..sub.d (k,-1) is provided, no processor has a channel connected to form an edge in a direction .delta..sub.1. Each of the channels has an identification number selected from the sequence of letters and connected from a first processor having a first extended address to a second processor having a second address formed from a second extended address defined by moving to the front of the first extended address the letter found in the position within the first extended address defined by the channel identification number. The second address is then formed by selecting the first elements of the second extended address corresponding to the selected number used to form the address permutations.

Developing a geomorphic approach for ranking watersheds for rehabilitation, Zuni Indian Reservation, New Mexico

USGS Publications Warehouse

Gellis, A.C.; Cheama, A.; Lalio, S.M.

2001-01-01

As a result of past erosion problems on the Zuni Indian Reservation in western New Mexico, the US Congress in 1990 authorized the Zuni Tribe to begin a program for watershed rehabilitation. This paper describes an approach to rank the most appropriate watersheds for rehabilitation for the Zuni Reservation. The approach was based on data collected during a 3-year study on geomorphic and anthropogenic characteristics of the Rio Nutria Watershed, including data on (i) arroyo cross-sectional changes, (ii) erosion-control structures, and (iii) sheetwash erosion. Results of this 3-year study indicated that 61 of 85 channel cross-sections aggraded and channels with lower width-to-depth ratios eroded. Results on assessment of erosion-control structures, some dating back to the 1930's, indicated that 60% of earthen dams and 22% of rock-and-brush structures were breached or flanked in the Rio Nutria Watershed. Sheetwash erosion measured on five land-cover sites (sagebrush, pasture, chained pin??on and juniper, unchained pin??on and juniper, and ponderosa pine) indicated chained pin??on and juniper sites and pasture sites had the highest volume-weighted sediment concentrations of 13,000 and 9970 ppm, respectively. Based on interpretations of the 3-year study in the Rio Nutria Watershed, a two-stage approach was developed to rank the most appropriate watersheds for rehabilitation on the Zuni Reservation. In the first stage, the reservation was divided into eight major watersheds, which were ranked according to the most potential for erosion. In the second stage, the watershed with the most potential for erosion was divided into sub-basins, which were ranked according to the most potential for erosion. Quantitative and qualitative information on physical and anthropogenic factors were used at each stage to rank the watersheds. Quantitative physical data included headcut density, percentage of bare ground, percentage of chained area, channel width-to-depth ratio, change in channel density from 1934 to 1988, and sheetwash erosion rates. Qualitative physical data included erosion rankings on the main channels, tributaries, and entire basins. Anthropogenic data included density of dirt roads and condition of erosion-control structures. A community survey and agricultural acreage were also used in the selection process. The first stage analysis resulted in the selection of the Rio Nutria Watershed as the most appropriate major watershed for rehabilitation. In the second stage, the Rio Nutria Watershed was divided into 15 sub-basins; the analysis indicated the highest priority sub-basins for rehabilitation were Benny Draw, Coal Mine Canyon Draw, and Garcia Draw.

Distinguishing between tectonic and lithologic controls on bedrock channel longitudinal profiles using cosmogenic 10Be erosion rates and channel steepness index

USGS Publications Warehouse

Cyr, Andrew J.; Granger, Darryl E.; Olivetti, Valerio; Molin, Paola

2014-01-01

Knickpoints in fluvial channel longitudinal profiles and channel steepness index values derived from digital elevation data can be used to detect tectonic structures and infer spatial patterns of uplift. However, changes in lithologic resistance to channel incision can also influence the morphology of longitudinal profiles. We compare the spatial patterns of both channel steepness index and cosmogenic 10Be-determined erosion rates from four landscapes in Italy, where the geology and tectonics are well constrained, to four theoretical predictions of channel morphologies, which can be interpreted as the result of primarily tectonic or lithologic controls. These data indicate that longitudinal profile forms controlled by unsteady or nonuniform tectonics can be distinguished from those controlled by nonuniform lithologic resistance. In each landscape the distribution of channel steepness index and erosion rates is consistent with model predictions and demonstrates that cosmogenic nuclide methods can be applied to distinguish between these two controlling factors.

Polarization-Engineered Ga-Face GaN-Based Heterostructures for Normally-Off Heterostructure Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Kim, Hyeongnam; Nath, Digbijoy; Rajan, Siddharth; Lu, Wu

2013-01-01

Polarization-engineered Ga-face GaN-based heterostructures with a GaN cap layer and an AlGaN/ p-GaN back barrier have been designed for normally-off field-effect transistors (FETs). The simulation results show that an unintentionally doped GaN cap and p-GaN layer in the buffer primarily deplete electrons in the channel and the Al0.2Ga0.8N back barrier helps to pinch off the channel. Experimentally, we have demonstrated a normally-off GaN-based field-effect transistor on the designed GaN cap/Al0.3Ga0.7N/GaN channel/Al0.2Ga0.8N/ p-GaN/GaN heterostructure. A positive threshold voltage of 0.2 V and maximum transconductance of 2.6 mS/mm were achieved for 80- μm-long gate devices. The device fabrication process does not require a dry etching process for gate recessing, while highly selective etching of the GaN cap against a very thin Al0.3GaN0.7N top barrier has to be performed to create a two-dimensional electron gas for both the ohmic and access regions. A self-aligned, selective etch of the GaN cap in the access region is introduced, using the gate metal as an etch mask. The absence of gate recess etching is promising for uniform and repeatable threshold voltage control in normally-off AlGaN/GaN heterostructure FETs for power switching applications.

Tadalafil attenuates hypotonicity-induced Ca2+ influx via TRPV2 and TRPV4 in primary rat bladder urothelial cell cultures.

PubMed

Dong, Xiao; Nakagomi, Hiroshi; Miyamoto, Tatsuya; Ihara, Tatsuya; Kira, Satoru; Sawada, Norifumi; Mitsui, Takahiko; Takeda, Masayuki

2018-03-22

To investigate the localization of phosphodiesterase 5 (PDE5) and the molecular mechanism underlying the effect of the PDE5 inhibitor tadalafil in signal transduction in the bladder urothelium. PDE5 expression in rat bladder tissues and cultured primary rat bladder urothelial cells was evaluated using immunochemistry and western blot assays. Ca 2+ influx in cells exposed to isotonic solution, hypotonic solution, a selective transient receptor potential vanilloid 2 (TRPV2) channel agonist (cannabidiol), a selective TRPV4 channel agonist (GSK1016790A), a TRP cation channel melastatin 7 (TRPM7) channel agonist (PIP2), or a purinergic receptor agonist (ATP) in the presence or absence of 10 µM tadalafil was evaluated using calcium imaging techniques. We also evaluated stretch-induced changes in ATP concentration in the mouse bladder in the presence or absence of 100 µM tadalafil. Immunochemistry and western blot analyses demonstrated that PDE5 is abundantly expressed in the bladder urothelium and in primary rat urothelial cells. Ca 2+ influx induced by hypotonic stimulation, GSK1016790A, or cannabidiol was significantly inhibited by tadalafil, whereas ATP-induced Ca 2+ influx was unaffected by tadalafil. PIP2 did not induce Ca2+ influx. ATP release in tadalafil-pretreated bladders significantly decreased compared to control bladders. Tadalafil attenuates Ca 2+ influx via TRPV4 and TRPV2, and inhibits ATP release in the bladder urothelium. These findings indicate that tadalafil functions as an inhibitor of urothelial signal transduction. © 2018 Wiley Periodicals, Inc.

An Elevation in Physical Coupling of Type 1 IP3 Receptors to TRPC3 Channels Constricts Mesenteric Arteries in Genetic Hypertension

PubMed Central

Adebiyi, Adebowale; Thomas-Gatewood, Candice M.; Leo, M. Dennis; Kidd, Michael W.; Neeb, Zachary P.; Jaggar, Jonathan H.

2013-01-01

Hypertension is associated with an elevation in agonist-induced vasoconstriction, but mechanisms involved require further investigation. Many vasoconstrictors bind to phospholipase C-coupled receptors, leading to an elevation in inositol 1,4,5-trisphosphate (IP3) that activates sarcoplasmic reticulum (SR) IP3 receptors (IP3Rs). In cerebral artery myocytes, IP3Rs release SR Ca2+ and can physically couple to canonical transient receptor potential 3 (TRPC3) channels in a caveolin-1-containing macromolecular complex, leading to cation current (ICat) activation that stimulates vasoconstriction. Here, we investigated mechanisms by which IP3Rs control vascular contractility in systemic arteries and IP3R involvement in elevated agonist-induced vasoconstriction during hypertension. Total and plasma membrane-localized TRPC3 protein was ~2.7- and 2-fold higher in mesenteric arteries of hypertensive spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rat controls, respectively. In contrast, IP3R1, TRPC1, TRPC6, and caveolin-1 expression was similar. TRPC3 expression was also similar in arteries of pre-hypertensive SHR and WKY rats. Control, IP3- and endothelin-1 (ET-1)-induced FRET between IP3R1 and TRPC3 was higher in hypertensive SHR than WKY myocytes. IP3-induced ICat was ~3-fold larger in SHR myocytes. Pyr3, a selective TRPC3 channel blocker, and CIRBP-TAT, an IP3R-TRP physical coupling inhibitor, reduced IP3-induced ICat and ET-1-induced vasoconstriction more in SHR than WKY myocytes and arteries. Thapsigargin, a SR Ca2+-ATPase blocker, did not alter ET-1-stimulated vasoconstriction in SHR or WKY arteries. These data indicate that ET-1 stimulates physical coupling of IP3R1 to TRPC3 channels in mesenteric artery myocytes, leading to vasoconstriction. Furthermore, an elevation in IP3R1 to TRPC3 channel molecular coupling augments ET-1-induced vasoconstriction during hypertension. PMID:23045459

HCN Channels Modulators: The Need for Selectivity

PubMed Central

Romanelli, Maria Novella; Sartiani, Laura; Masi, Alessio; Mannaioni, Guido; Manetti, Dina; Mugelli, Alessandro; Cerbai, Elisabetta

2016-01-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (If/Ih), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks If. Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects. HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators. PMID:26975509

Logic design and implementation of FPGA for a high frame rate ultrasound imaging system

NASA Astrophysics Data System (ADS)

Liu, Anjun; Wang, Jing; Lu, Jian-Yu

2002-05-01

Recently, a method has been developed for high frame rate medical imaging [Jian-yu Lu, ``2D and 3D high frame rate imaging with limited diffraction beams,'' IEEE Trans. Ultrason. Ferroelectr. Freq. Control 44(4), 839-856 (1997)]. To realize this method, a complicated system [multiple-channel simultaneous data acquisition, large memory in each channel for storing up to 16 seconds of data at 40 MHz and 12-bit resolution, time-variable-gain (TGC) control, Doppler imaging, harmonic imaging, as well as coded transmissions] is designed. Due to the complexity of the system, field programmable gate array (FPGA) (Xilinx Spartn II) is used. In this presentation, the design and implementation of the FPGA for the system will be reported. This includes the synchronous dynamic random access memory (SDRAM) controller and other system controllers, time sharing for auto-refresh of SDRAMs to reduce peak power, transmission and imaging modality selections, ECG data acquisition and synchronization, 160 MHz delay locked loop (DLL) for accurate timing, and data transfer via either a parallel port or a PCI bus for post image processing. [Work supported in part by Grant 5RO1 HL60301 from NIH.

Frequency of technical complications in fixed implant prosthesis: the effect of prosthesis screw emergence correction by CAD-CAM.

PubMed

Anitua, Eduardo; Flores, Carlos; Piñas, Laura; Alkhraisat, Mohammad

2018-06-05

CAD-CAM technology permits the angular correction of screw emergence into the prosthesis, however there is lack of controlled clinical studies that assess the frequency of technical complications in angled screw channel restorations. This controlled clinical study was designed to assess technical incidences in angled screw channel restorations. Patients having implant prosthesis placed between November, 2014 and December, 2015 were screened. The patients were selected if they received prosthesis with up to 30º correction of the prosthesis screw emergence and had at least one non-angulated prosthesis (screw-retained). All the prostheses were located completely/partially in the posterior region. The frequency of technical complications was the principal variable. A total of 52 patients with a mean age of 62 ± 10 years participated with a total 110 prostheses (55 in the test group and 55 in the control group). A total of 11 technical complications occurred (7 in the test group and 4 in the control group). These differences were not statistically significant. All the prostheses in both groups survived the follow-up. The correction of the screw emergence into the prosthesis has not increased the risk of technical complications in CAD-CAM implant prostheses.

Selective filling for patterning in microfluidic channels and integration of chromatography in "lab-on-a-chip" devices using sol-gel technology

NASA Astrophysics Data System (ADS)

Jindal, Rohit

The last decade has seen tremendous advancement in the development of miniaturized chemical analysis system also known as "lab-on-a-chip". It is believed that the true potential of these devices will be achieved by integrating various functions such as separation, reaction, sensing, mixing, pumping, injection and detection onto a single chip. The ability to pattern different functionalities is indispensable for the development of highly integrated devices. In this work, a simple method based on the concept of selective filling is described for patterning in the microfluidic channels. It is based on the difference in the free energy of filling between an open and a covered part of the channel. This method was used for the integration of chromatography in the microfluidic devices. A chromatographic column was realized by utilizing sol-gel as an immobilization matrix for entrapping reversed phase chromatographic particles. Localization of the stationary phase was achieved using the selective filling technique. Channels were fabricated in quartz using photolithography and wet etching. Electroosmotic flow was used for manipulating fluid movement in the channels. Cross channel design was used for making a pulse injection of the solutes in the separation channel. An optical fiber setup was developed for carrying out on-chip UV absorbance detection. Stationary phase was created under different sol-gel synthesis conditions. It was established that the sol-gel synthesis carried out under acidic conditions provides the optimum synthesis conditions for creating separation column. Chromatographic performance of the stationary phase material was demonstrated by separating peptides present in a mixture. The sol-gel immobilization method was extended for the integration of micropump in the chip. The micropump enables pumping of the fluid in field free channels. Preliminary results, demonstrating the potential of carbon nanotubes as a support material in the microfluidic channels, were obtained using CVD (chemical vapor deposition) grown tubes in the channel. Results obtained in this work demonstrate the potential of selective filling technique along with sol-gel technology as a useful tool for the fabrication of multifunctional "lab-on-a-chip" devices.

Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells.

PubMed

Chimote, Ameet A; Hajdu, Peter; Kucher, Vladimir; Boiko, Nina; Kuras, Zerrin; Szilagyi, Orsolya; Yun, Yeo-Heung; Conforti, Laura

2013-12-15

Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels. The activity of T lymphocytes relies on ion channels. KCa3.1 and Kv1.3 channels control cytokine release and, together with TRPM7, regulate T cell motility. Adenosine selectively inhibited KCa3.1, but not Kv1.3 and TRPM7, in activated human T cells. This effect of adenosine was mainly mediated by A2A receptors, as KCa3.1 inhibition was reversed by SCH58261 (selective A2A receptor antagonist), but not by MRS1754 (A2B receptor antagonist), and it was mimicked by the A2A receptor agonist CGS21680. Furthermore, it was mediated by the cAMP/protein kinase A isoform (PKAI) signaling pathway, as adenylyl-cyclase and PKAI inhibition prevented adenosine effect on KCa3.1. The functional implication of the effect of adenosine on KCa3.1 was determined by measuring T cell motility on ICAM-1 surfaces. Adenosine and CGS21680 inhibited T cell migration. Comparable effects were obtained by KCa3.1 blockade with TRAM-34. Furthermore, the effect of adenosine on cell migration was abolished by pre-exposure to TRAM-34. Additionally, adenosine suppresses IL-2 secretion via KCa3.1 inhibition. Our data indicate that adenosine inhibits KCa3.1 in human T cells via A2A receptor and PKAI, thereby resulting in decreased T cell motility and cytokine release. This mechanism is likely to contribute to decreased immune surveillance in solid tumors.

Novel TASK channels inhibitors derived from dihydropyrrolo[2,1-a]isoquinoline.

PubMed

Noriega-Navarro, R; Lopez-Charcas, O; Hernández-Enríquez, B; Reyes-Gutiérrez, P E; Martínez, R; Landa, A; Morán, J; Gomora, J C; Garcia-Valdes, J

2014-04-01

TASK channels belong to the family of K(+) channels with 4 transmembrane segments and 2 pore domains (4TM/2P) per subunit. These channels have been related to apoptosis in cerebellar granule neurons (CGN), as well as cancer in other tissues. TASK current is regulated by hormones, neurotransmitters, anesthetics and divalent cations, which are not selective. Recently, there has been found some organic compounds that inhibit TASK current selectively. In order to find other modulators, we report here a group of five dihydropyrrolo[2,1-a]isoquinolines (DPIs), four of them with putative anticancer activity, that were evaluated on TASK-1 and TASK-3 channels. The compounds 1, 2 and 3 showed IC50 < 320 μM on TASK-1 and TASK-3, intermediate activity on TASK-1/TASK-3 heterodimer, moderate effect over hslo and TREK-1 (500 μM), and practically not inhibition on Shaker-IR, herg and IRK2.1 potassium channels, when they were expressed heterologously in Xenopus laevis oocytes. In rat CGN, 500 μM of these three compounds induced a decrement by >39% of the TASK-carried leak current. Finally, only compound 1 showed significant protection (∼36%) against apoptotic death of CGN induced by K(+) deprivation. These results suggest that DPI compounds could be potential candidates for designing new selective inhibitors of TASK channels. Copyright © 2013 Elsevier Ltd. 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 tubular pillar[n]arenes by extending their lengths with various ester, hydrazide, and short peptide chains. We have utilized well-defined pillar[5]arene and pillar[6]arene as rigid frameworks that allow the appended chains to afford extended tubular structures. We demonstrate that the hydrazide and peptide chains form intramolecular N-H···O═C hydrogen bonds that enhance the tubular conformation of the whole molecule. The new pillar[n]arene derivatives have been successfully applied as unimolecular channels for the selective transport of protons, water, and amino acids and the voltage-gated transport of K(+). We also show that aromatic hydrazide helices and macrocycles appended with peptide chains are able to mediate the selective transport of NH4(+).

Biological and economic impact of stream alteration in the Virginia Piedmont

USGS Publications Warehouse

Whelan, James B.

1981-01-01

A 31 month (September 1974 - March 1977) study was conducted on warmwater streams located in the Roanoke Creek watershed of the Piedmont Region of Virginia. The purpose of the study was to determine the effects of stream channelization on the aquatic/riparian wildlife resource and agricultural land-use patterns associated with the altered streams. Three streams, which were channelized 3, 6, and 10 years prior to initiation of the study, and teo unaltered streams, were selected as representative streams for the study. Recently channelized streams lacked overstory cover but has an abundance of herbaceous and small woody plany cover, Conversely, control streams had significantly larger percentages of trees over 46 m tall. Plant species diversity, foliage height diversity, and evenness diversity increased as age since channelization increased. No major differences in water quality parameters were found for either channelized or control streams, although channelized streams had greater deposits of sand and lesser amount of rock, rubble, and gravel. These changes in substrate composition did not significantly modify actual stream flow rates. Fish species composition and species diversity among channelized and unchannelized streams were only slightly different, with most of the differences probably attributable to strays from adjacent habitats, However, evenness diversity for fish communities was lower in channelized streams. The benthic population showed greater changes than did the fish populations with an increase in Chironominae tolerant of unstable sand substrates in channelized streams. Evenness diversity of benthic populations was also higher and showed more consistency in the control stream than in channelized streams. Evenness diversity of benthic communities in control stream averaged between 0.5 to 0.6 and was quite consistent; whereas, the average in the two youngest channelized streams was 0.3 to 0.4. These data seem to indicate decreased stability of the biota in altered streams. In general, benthic macroinvertabrate and fish community parameters collected from channelized streams located 1200 m below a reservoir were either comparable to, or intermediate between, upstream (unchannelized) and reservoir tailwater values. The shallow surface discharge impoundments associated with channelized streams appeared to have a highly localized impact on the downstream benthic marcoinvertabrate and fish communities. During winter, bird species diversity (BSD) among channelized stream sites was not significantly different. During the breeding season, species richness (number of breeding species) and BSD increased with age since channelization. Breeding bird densities were 6.2 pairs/ha in the most recent (3 yr) channelized site and 13.3 pairs/ha on the control streams. Bird diversity and density, particularly for Parulids (warblers), during the breeding season were reduced significantly by removal of tree and shrub layers along channelized streams. No significant differences were found among study sites for either total number of small mammals or their species diversity indices; although, there was a trend toward increasing diversity as age since channelization increased. Smaller differences in species diversity values for small mammals on channelized sites than for birds suggests that small mammal populations require less time for recovery following channelization than avian communities. When streams are channelized: 1) vegetation should be removed from only one side of the stream, with minimal disturbance of top-soil; followed by plantings of herbaceous and woody vegetation, 2) hedgrow plantings should be maintained between agricultural fields and the stream for bank stabilization, 3) dead snags and large trees should be left for birds, 4) all channelization projects should be designed according to the most recent guidelines recommended by the SCS and other resources agencies. In 1958, the Roanoke County Watershed Work Plan projected annual costs of the structured measures (mainly reservoirs and downstream channelization) to be $79,897 and the average annual monetary benefits to be $111,103. With this favorable benefit/cost ration of 1.4, work began in 1960. In 1970, the annual capital cost was 60,780 and operations/maintenance costs were 10,402, or a total annual project cost of $71, 182. High and low values of annual benefits from agricultural income, water supply, recreation, and non-agricultural flood damage were determined for 1970 and compared to annual project cost. The benefit/cost ratio obtained was between 0.25 and 0.58, considerably lower than the 1.4 estimate of the 1958. work plan. This unsatisfactory ratio for the project was due mainly to the failure of the project to encourage large scale cropping of bottomland area. Future projects should be planned with 1) a greater recognition of constraints on farm operator behavior which affect land use change, 2) conservative projection for land use changes in area where agriculture ids in overall decline, 3) increased use of sensitivity analysis to examine the consequences for project economic justification of alternative land use change projections.

Role of voltage-gated L-type Ca2+ channel isoforms for brain function.

PubMed

Striessnig, J; Koschak, A; Sinnegger-Brauns, M J; Hetzenauer, A; Nguyen, N K; Busquet, P; Pelster, G; Singewald, N

2006-11-01

Voltage-gated LTCCs (L-type Ca2+ channels) are established drug targets for the treatment of cardiovascular diseases. LTCCs are also expressed outside the cardiovascular system. In the brain, LTCCs control synaptic plasticity in neurons, and DHP (dihydropyridine) LTCC blockers such as nifedipine modulate brain function (such as fear memory extinction and depression-like behaviour). Voltage-sensitive Ca2+ channels Cav1 .2 and Cav1.3 are the predominant brain LTCCs. As DHPs and other classes of organic LTCC blockers inhibit both isoforms, their pharmacological distinction is impossible and their individual contributions to defined brain functions remain largely unknown. Here, we summarize our recent experiments with two genetically modified mouse strains, which we generated to explore the individual biophysical features of Cav1.2 and Cav1.3 LTCCs and to determine their relative contributions to various physiological peripheral and neuronal functions. The results described here also allow predictions about the pharmacotherapeutic potential of isoform-selective LTCC modulators.

Grafting of antibodies inside integrated microfluidic-microoptic devices by means of automated microcontact printing

PubMed Central

Bou Chakra, Elie; Hannes, Benjamin; Vieillard, Julien; Mansfield, Colin D.; Mazurczyk, Radoslav; Bouchard, Aude; Potempa, Jan; Krawczyk, Stanislas; Cabrera, Michel

2009-01-01

A novel approach to integrating biochip and microfluidic devices is reported in which microcontact printing is a key fabrication technique. The process is performed using an automated microcontact printer that has been developed as an application-specific tool. As proof-of-concept the instrument is used to consecutively and selectively graft patterns of antibodies at the bottom of a glass channel for use in microfluidic immunoassays. Importantly, feature collapse due to over compression of the PDMS stamp is avoided by fine control of the stamp’s compression during contact. The precise alignment of biomolecules at the intersection of microfluidic channel and integrated optical waveguides has been achieved, with antigen detection performed via fluorescence excitation. Thus, it has been demonstrated that this technology permits sequential microcontact printing of isolated features consisting of functional biomolecules at any position along a microfluidic channel and also that it is possible to precisely align these features with existing components. PMID:20161128

Ion channels of the mammalian urethra

PubMed Central

Kyle, Barry D

2014-01-01

The mammalian urethra is a muscular tube responsible for ensuring that urine remains in the urinary bladder until urination. In order to prevent involuntary urine leakage, the urethral musculature must be capable of constricting the urethral lumen to an extent that exceeds bladder intravesicular pressure during the urine-filling phase. The main challenge in anti-incontinence treatments involves selectively-controlling the excitability of the smooth muscles in the lower urinary tract. Almost all strategies to battle urinary incontinence involve targeting the bladder and as a result, this tissue has been the focus for the majority of research and development efforts. There is now increasing recognition of the value of targeting the urethral musculature in the treatment and management of urinary incontinence. Newly-identified and characterized ion channels and pathways in the smooth muscle of the urethra provides a range of potential therapeutic targets for the treatment of urinary incontinence. This review provides a summary of the current state of knowledge of the ion channels discovered in urethral smooth muscle cells that regulate their excitability. PMID:25483582

Bubble gate for in-plane flow control.

PubMed

Oskooei, Ali; Abolhasani, Milad; Günther, Axel

2013-07-07

We introduce a miniature gate valve as a readily implementable strategy for actively controlling the flow of liquids on-chip, within a footprint of less than one square millimetre. Bubble gates provide for simple, consistent and scalable control of liquid flow in microchannel networks, are compatible with different bulk microfabrication processes and substrate materials, and require neither electrodes nor moving parts. A bubble gate consists of two microchannel sections: a liquid-filled channel and a gas channel that intercepts the liquid channel to form a T-junction. The open or closed state of a bubble gate is determined by selecting between two distinct gas pressure levels: the lower level corresponds to the "open" state while the higher level corresponds to the "closed" state. During closure, a gas bubble penetrates from the gas channel into the liquid, flanked by a column of equidistantly spaced micropillars on each side, until the flow of liquid is completely obstructed. We fabricated bubble gates using single-layer soft lithographic and bulk silicon micromachining procedures and evaluated their performance with a combination of theory and experimentation. We assessed the dynamic behaviour during more than 300 open-and-close cycles and report the operating pressure envelope for different bubble gate configurations and for the working fluids: de-ionized water, ethanol and a biological buffer. We obtained excellent agreement between the experimentally determined bubble gate operational envelope and a theoretical prediction based on static wetting behaviour. We report case studies that serve to illustrate the utility of bubble gates for liquid sampling in single and multi-layer microfluidic devices. Scalability of our strategy was demonstrated by simultaneously addressing 128 bubble gates.

Adaptive evolution of insect selective excitatory β-type sodium channel neurotoxins from scorpion venom.

PubMed

Wu, Wenlan; Li, Zhongjie; Ma, Yibao

2017-06-01

Insect selective excitatory β-type sodium channel neurotoxins from scorpion venom (β-NaScTxs) are composed of about 70-76 amino acid residues and share a common scaffold stabilized by four unique disulfide bonds. The phylogenetic analysis of these toxins was hindered by limited sequence data. In our recent study, two new insect selective excitatory β-NaScTxs, LmIT and ImIT, were isolated from Lychas mucronatus and Isometrus maculatus, respectively. With the sequences previously reported, we examined the adaptive molecular evolution of insect selective excitatory β-NaScTxs by estimating the nonsynonymous-to-synonymous rate ratio (ω=d N /d S ). The results revealed 12 positively selected sites in the genes of insect selective excitatory β-NaScTxs. Moreover, these positively selected sites match well with the sites important for interacting with sodium channels, as demonstrated in previous mutagenesis study. These results reveal that adaptive evolution after gene duplication is one of the most important genetic mechanisms of scorpion neurotoxin diversification. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficient Terahertz detection in black-phosphorus nano-transistors with selective and controllable plasma-wave, bolometric and thermoelectric response

PubMed Central

Viti, Leonardo; Hu, Jin; Coquillat, Dominique; Politano, Antonio; Knap, Wojciech; Vitiello, Miriam S.

2016-01-01

The ability to convert light into an electrical signal with high efficiencies and controllable dynamics, is a major need in photonics and optoelectronics. In the Terahertz (THz) frequency range, with its exceptional application possibilities in high data rate wireless communications, security, night-vision, biomedical or video-imaging and gas sensing, detection technologies providing efficiency and sensitivity performances that can be “engineered” from scratch, remain elusive. Here, by exploiting the inherent electrical and thermal in-plane anisotropy of a flexible thin flake of black-phosphorus (BP), we devise plasma-wave, thermoelectric and bolometric nano-detectors with a selective, switchable and controllable operating mechanism. All devices operates at room-temperature and are integrated on-chip with planar nanoantennas, which provide remarkable efficiencies through light-harvesting in the strongly sub-wavelength device channel. The achieved selective detection (∼5–8 V/W responsivity) and sensitivity performances (signal-to-noise ratio of 500), are here exploited to demonstrate the first concrete application of a phosphorus-based active THz device, for pharmaceutical and quality control imaging of macroscopic samples, in real-time and in a realistic setting. PMID:26847823

Automatic sequential fluid handling with multilayer microfluidic sample isolated pumping

PubMed Central

Liu, Jixiao; Fu, Hai; Yang, Tianhang; Li, Songjing

2015-01-01

To sequentially handle fluids is of great significance in quantitative biology, analytical chemistry, and bioassays. However, the technological options are limited when building such microfluidic sequential processing systems, and one of the encountered challenges is the need for reliable, efficient, and mass-production available microfluidic pumping methods. Herein, we present a bubble-free and pumping-control unified liquid handling method that is compatible with large-scale manufacture, termed multilayer microfluidic sample isolated pumping (mμSIP). The core part of the mμSIP is the selective permeable membrane that isolates the fluidic layer from the pneumatic layer. The air diffusion from the fluidic channel network into the degassing pneumatic channel network leads to fluidic channel pressure variation, which further results in consistent bubble-free liquid pumping into the channels and the dead-end chambers. We characterize the mμSIP by comparing the fluidic actuation processes with different parameters and a flow rate range of 0.013 μl/s to 0.097 μl/s is observed in the experiments. As the proof of concept, we demonstrate an automatic sequential fluid handling system aiming at digital assays and immunoassays, which further proves the unified pumping-control and suggests that the mμSIP is suitable for functional microfluidic assays with minimal operations. We believe that the mμSIP technology and demonstrated automatic sequential fluid handling system would enrich the microfluidic toolbox and benefit further inventions. PMID:26487904

S-acylation dependent post-translational cross-talk regulates large conductance calcium- and voltage- activated potassium (BK) channels

PubMed Central

Shipston, Michael J.

2014-01-01

Mechanisms that control surface expression and/or activity of large conductance calcium-activated potassium (BK) channels are important determinants of their (patho)physiological function. Indeed, BK channel dysfunction is associated with major human disorders ranging from epilepsy to hypertension and obesity. S-acylation (S-palmitoylation) represents a major reversible, post-translational modification controlling the properties and function of many proteins including ion channels. Recent evidence reveals that both pore-forming and regulatory subunits of BK channels are S-acylated and control channel trafficking and regulation by AGC-family protein kinases. The pore-forming α-subunit is S-acylated at two distinct sites within the N- and C-terminus, each site being regulated by different palmitoyl acyl transferases (zDHHCs) and acyl thioesterases (APTs). S-acylation of the N-terminus controls channel trafficking and surface expression whereas S-acylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. S-acylation of the regulatory β4-subunit controls ER exit and surface expression of BK channels but does not affect ion channel kinetics at the plasma membrane. Furthermore, a significant number of previously identified BK-channel interacting proteins have been shown, or are predicted to be, S-acylated. Thus, the BK channel multi-molecular signaling complex may be dynamically regulated by this fundamental post-translational modification and thus S-acylation likely represents an important determinant of BK channel physiology in health and disease. PMID:25140154

Implementation Strategies for a Universal Acquisition and Tracking Channel Applied to Real GNSS Signals.

PubMed

Fortin, Marc-Antoine; Landry, René

2016-05-02

This paper presents a universal GNSS receiver channel capable of tracking any civil GNSS signal. This fundamentally differs from dedicated channels, each customized for a given signal. A mobile device could integrate fewer universal channels to harvest all available signals. This would allow securing signal availability, while minimizing power consumption and chip size, thus maximizing battery lifetime. In fact, the universal channel allows sequential acquisition and tracking of any chipping rate, carrier frequency, FDMA channel, modulation, or constellation, and is totally configurable (any integration time, any discriminator, etc.). It can switch from one signal to another in 1.07 ms, making it possible for the receiver to rapidly adapt to its sensed environment. All this would consume 3.5 mW/channel in an ASIC implementation, i.e., with a slight overhead compared to the original GPS L1 C/A dedicated channel from which it was derived. After extensive surveys on GNSS signals and tracking channels, this paper details the implementation strategies that led to the proposed universal channel architecture. Validation is achieved using GNSS signals issued from different constellations, frequency bands, modulations and spreading code schemes. A discussion on acquisition approaches and conclusive remarks follow, which open up a new signal selection challenge, rather than satellite selection.

Implementation Strategies for a Universal Acquisition and Tracking Channel Applied to Real GNSS Signals

PubMed Central

Fortin, Marc-Antoine; Landry, René

2016-01-01

This paper presents a universal GNSS receiver channel capable of tracking any civil GNSS signal. This fundamentally differs from dedicated channels, each customized for a given signal. A mobile device could integrate fewer universal channels to harvest all available signals. This would allow securing signal availability, while minimizing power consumption and chip size, thus maximizing battery lifetime. In fact, the universal channel allows sequential acquisition and tracking of any chipping rate, carrier frequency, FDMA channel, modulation, or constellation, and is totally configurable (any integration time, any discriminator, etc.). It can switch from one signal to another in 1.07 ms, making it possible for the receiver to rapidly adapt to its sensed environment. All this would consume 3.5 mW/channel in an ASIC implementation, i.e., with a slight overhead compared to the original GPS L1 C/A dedicated channel from which it was derived. After extensive surveys on GNSS signals and tracking channels, this paper details the implementation strategies that led to the proposed universal channel architecture. Validation is achieved using GNSS signals issued from different constellations, frequency bands, modulations and spreading code schemes. A discussion on acquisition approaches and conclusive remarks follow, which open up a new signal selection challenge, rather than satellite selection. PMID:27144569

Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.

PubMed

Chen, Jun; Joshi, Shailen K; DiDomenico, Stanley; Perner, Richard J; Mikusa, Joe P; Gauvin, Donna M; Segreti, Jason A; Han, Ping; Zhang, Xu-Feng; Niforatos, Wende; Bianchi, Bruce R; Baker, Scott J; Zhong, Chengmin; Simler, Gricelda H; McDonald, Heath A; Schmidt, Robert G; McGaraughty, Steve P; Chu, Katharine L; Faltynek, Connie R; Kort, Michael E; Reilly, Regina M; Kym, Philip R

2011-05-01

Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). It is >1000-fold selective over other TRP channels, and is >150-fold selective over 75 other ion channels, enzymes, and G-protein-coupled receptors. Oral dosing of A-967079 produces robust drug exposure in rodents, and exhibits analgesic efficacy in allyl isothiocyanate-induced nocifensive response and osteoarthritic pain in rats (ED(50): 23.2 mg/kg, p.o.). A-967079 attenuates cold allodynia produced by nerve injury but does not alter noxious cold sensation in naive animals, suggesting distinct roles of TRPA1 in physiological and pathological states. Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Activation of a Ca2+-dependent cation conductance with properties of TRPM2 by reactive oxygen species in lens epithelial cells.

PubMed

Keckeis, Susanne; Wernecke, Laura; Salchow, Daniel J; Reichhart, Nadine; Strauß, Olaf

2017-08-01

Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca 2+ -dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca 2+ - and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca 2+ -activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells. Using whole-cell patch-clamp technique, ionomycin evoked non-selective cation currents with linear current-voltage relationship in both cell types. The current was decreased by flufenamic acid (FFA), 2-APB, 9-phenanthrol and miconazole, but insensitive to DIDS, ruthenium red, and intracellularly applied spermine. H 2 O 2 evoked a comparable current, abolished by FFA. TRPM2 protein expression in HLE-B3 cells was confirmed by means of immunocytochemistry and western blot. In summary, we conclude that lens epithelial cells functionally express Ca 2+ - and H 2 O 2 -activated non-selective cation channels with properties of TRPM2. Copyright © 2017. Published by Elsevier Ltd.

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

Sancho Pitarch, Jose Carlos; Kerbyson, Darren; Lang, Mike

Increasing the core-count on current and future processors is posing critical challenges to the memory subsystem to efficiently handle concurrent memory requests. The current trend to cope with this challenge is to increase the number of memory channels available to the processor's memory controller. In this paper we investigate the effectiveness of this approach on the performance of parallel scientific applications. Specifically, we explore the trade-off between employing multiple memory channels per memory controller and the use of multiple memory controllers. Experiments conducted on two current state-of-the-art multicore processors, a 6-core AMD Istanbul and a 4-core Intel Nehalem-EP, for amore » wide range of production applications shows that there is a diminishing return when increasing the number of memory channels per memory controller. In addition, we show that this performance degradation can be efficiently addressed by increasing the ratio of memory controllers to channels while keeping the number of memory channels constant. Significant performance improvements can be achieved in this scheme, up to 28%, in the case of using two memory controllers with each with one channel compared with one controller with two memory channels.« less

A mechatronics platform to study prosthetic hand control using EMG signals.

PubMed

Geethanjali, P

2016-09-01

In this paper, a low-cost mechatronics platform for the design and development of robotic hands as well as a surface electromyogram (EMG) pattern recognition system is proposed. This paper also explores various EMG classification techniques using a low-cost electronics system in prosthetic hand applications. The proposed platform involves the development of a four channel EMG signal acquisition system; pattern recognition of acquired EMG signals; and development of a digital controller for a robotic hand. Four-channel surface EMG signals, acquired from ten healthy subjects for six different movements of the hand, were used to analyse pattern recognition in prosthetic hand control. Various time domain features were extracted and grouped into five ensembles to compare the influence of features in feature-selective classifiers (SLR) with widely considered non-feature-selective classifiers, such as neural networks (NN), linear discriminant analysis (LDA) and support vector machines (SVM) applied with different kernels. The results divulged that the average classification accuracy of the SVM, with a linear kernel function, outperforms other classifiers with feature ensembles, Hudgin's feature set and auto regression (AR) coefficients. However, the slight improvement in classification accuracy of SVM incurs more processing time and memory space in the low-level controller. The Kruskal-Wallis (KW) test also shows that there is no significant difference in the classification performance of SLR with Hudgin's feature set to that of SVM with Hudgin's features along with AR coefficients. In addition, the KW test shows that SLR was found to be better in respect to computation time and memory space, which is vital in a low-level controller. Similar to SVM, with a linear kernel function, other non-feature selective LDA and NN classifiers also show a slight improvement in performance using twice the features but with the drawback of increased memory space requirement and time. This prototype facilitated the study of various issues of pattern recognition and identified an efficient classifier, along with a feature ensemble, in the implementation of EMG controlled prosthetic hands in a laboratory setting at low-cost. This platform may help to motivate and facilitate prosthetic hand research in developing countries.

Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

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

Fritsch, Sebastian; Ivanov, Ivaylo; Wang, Hailong

2010-01-01

The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high-resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential-of-mean-force profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel ismore » open for a sodium ion to transport, but presents a 11 kcal/mol free energy barrier for a chloride ion. Our collective findings identify three distinct contributions to the observed preference for the permeant ions. First, there is a substantial contribution due to a ring of negatively charged glutamate residues (E-2 ) at the narrow intracellular end of the channel. The negative electrostatics of this region and the ability of the glutamate side chains to directly bind cations would strongly favor the passage of sodium ions while hindering translocation of chloride ions. Second, our results imply a significant hydrophobic contribution to selectivity linked to differences in the desolvation penalty for the sodium versus chloride ions in the central hydrophobic region of the pore. This hydrophobic contribution is evidenced by the large free energy barriers experienced by Cl in the middle of the pore for both GLIC and the E-2 A mutant. Finally, there is a distinct contribution arising from the overall negative electrostatics of the channel.« less

Mechanism of resveratrol-induced relaxation of the guinea pig fundus.

PubMed

Tsai, Ching-Chung; Tey, Shu-Leei; Lee, Ming-Che; Liu, Ching-Wen; Su, Yu-Tsun; Huang, Shih-Che

2018-04-01

Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. We studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). The results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. This study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia. Copyright © 2018 Elsevier GmbH. All rights reserved.

Dual control active superconductive devices

DOEpatents

Martens, Jon S.; Beyer, James B.; Nordman, James E.; Hohenwarter, Gert K. G.

1993-07-20

A superconducting active device has dual control inputs and is constructed such that the output of the device is effectively a linear mix of the two input signals. The device is formed of a film of superconducting material on a substrate and has two main conduction channels, each of which includes a weak link region. A first control line extends adjacent to the weak link region in the first channel and a second control line extends adjacent to the weak link region in the second channel. The current flowing from the first channel flows through an internal control line which is also adjacent to the weak link region of the second channel. The weak link regions comprise small links of superconductor, separated by voids, through which the current flows in each channel. Current passed through the control lines causes magnetic flux vortices which propagate across the weak link regions and control the resistance of these regions. The output of the device taken across the input to the main channels and the output of the second main channel and the internal control line will constitute essentially a linear mix of the two input signals imposed on the two control lines. The device is especially suited to microwave applications since it has very low input capacitance, and is well suited to being formed of high temperature superconducting materials since all of the structures may be formed coplanar with one another on a substrate.

An ion channel library for drug discovery and safety screening on automated platforms.

PubMed

Wible, Barbara A; Kuryshev, Yuri A; Smith, Stephen S; Liu, Zhiqi; Brown, Arthur M

2008-12-01

Ion channels represent the third largest class of targets in drug discovery after G-protein coupled receptors and kinases. In spite of this ranking, ion channels continue to be under exploited as drug targets compared with the other two groups for several reasons. First, with 400 ion channel genes and an even greater number of functional channels due to mixing and matching of individual subunits, a systematic collection of ion channel-expressing cell lines for drug discovery and safety screening has not been available. Second, the lack of high-throughput functional assays for ion channels has limited their use as drug targets. Now that automated electrophysiology has come of age and provided the technology to assay ion channels at medium to high throughput, we have addressed the need for a library of ion channel cell lines by constructing the Ion Channel Panel (ChanTest Corp., Cleveland, OH). From 400 ion channel genes, a collection of 82 of the most relevant human ion channels for drug discovery, safety, and human disease has been assembled.Each channel has been stably overexpressed in human embryonic kidney 293 or Chinese hamster ovary cells. Cell lines have been selected and validated on automated electrophysiology systems to facilitate cost-effective screening for safe and selective compounds at earlier stages in the drug development process. The screening and validation processes as well as the relative advantages of different screening platforms are discussed.

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 nanotubular assembly, rather than the individual molecules of 3, is required to partition into the lipid bilayer in order for these macrocycles to act as channels. Further structural modification has led to fourth-generation macrocycles 4 having readily-tunable cavities (Chapter 4). Macrocycles 4 , with a hybrid backbone composed half of the oligoamide and half of the phenylene ethynylene moieties, exhibits similar self-assembling behavior by forming nanotubular stacks. The results of a preliminary study based on LUVs-assays and BLM single channel recording experiments are summarized and clearly indicate that ion channels formed by this fourth-generation exhibit high stability and differing ion selectivity largely consistent with the corresponding structural modification of the interior cavity. Especially, the increased anion conductance observed for 4d indicates that our strategy of tuning supramolecular function based on synthetic modification of the backbone and pore is effective. In Chapter 5, our four-residue tetraurea macrocycles 5 have shown significant potency to selectively interact with the G-quadruplex, leading to a strong stabilization effect for G-quadruplex without binding to duplex DNA as observed by UV-melt assays. The ready synthetic availability of these macrocycles makes them amenable to future chemical modification, which allows systematic improvement of binding affinity and specificity. Moreover, it has been discovered that these macrocycles can partition into lipid bilayers and form very stable transmembrane ion channels with a pore size of ˜5 A. Preliminary data shows that this smaller ion channel may lead to exceptional ion conducting selectivity, which is rarely seen in the field of synthetic ion pores. These molecules may serve as a unique platform for the rational development of potent and versatile therapeutic agents. The exceptional ion conducting properties of these channels place aromatic oligoamide macrocycles 3 and 4 at a unique position with both high conductance and long channel-opening duration. These results demonstrate that oligoamide macrocycles provide us a reliable platform based on which further development of highly conducting and selective synthetic mass-transporting channels, with functions that are comparable to or even rival those of natural channels and pores, may be developed. Further improvement of these synthetic channels could lead to numerous applications, such as those for complementing ion channel deficiency in clinical medicine, designing biosensors, and the development of new materials, as well as their use in separation and purifications.

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.

Apparatus and method for routing a transmission line through a downhole tool

DOEpatents

Hall, David R.; Hall, Jr., H. Tracy; Pixton, David S.; Briscoe, Michael; Reynolds, Jay

2006-07-04

A method for routing a transmission line through a tool joint having a primary and secondary shoulder, a central bore, and a longitudinal axis, includes drilling a straight channel, at a positive, nominal angle with respect to the longitudinal axis, through the tool joint from the secondary shoulder to a point proximate the inside wall of the centtral bore. The method further includes milling back, from within the central bore, a second channel to merge with the straight channel, thereby forming a continuous channel from the secondary shoulder to the central bore. In selected embodiments, drilling is accomplished by gun-drilling the straight channel. In other embodiments, the method includes tilting the tool joint before drilling to produce the positive, nominal angle. In selected embodiments, the positive, nominal angle is less than or equal to 15 degrees.

Modulation of mechanosensitive calcium-selective cation channels by temperature

NASA Technical Reports Server (NTRS)

Ding, J. P.; Pickard, B. G.

1993-01-01

Gating of associations of mechanosensitive Ca(2+)-selective cation co-channels in the plasmalemma of onion epidermis has a strong and unusual temperature dependence. Tension-dependent activity rises steeply as temperature is lowered from 25 degrees C to about 6 degrees C, but drops to a low level at about 5 degrees C. Under the conditions tested (with Mg2+ and K+ at the cytosolic face of outside-out membrane patches), promotion results both from more bursting at all observed linkage levels and from longer duration of bursts of co-channels linked as quadruplets and quintuplets. Co-channel conductance decreases linearly, but only modestly, with declining temperature. It is proposed that these and related mechanosensitive channels may participate in a variety of responses to temperature, including thermonasty, thermotropism, hydrotropism, and both cold damage and cold acclimation.

Measurement of multipath delay profile in land mobile satellite channels

NASA Technical Reports Server (NTRS)

Ikegami, Tetsushi; Arakaki, Yoshiya; Wakana, Hiromitsu; Suzuki, Ryutaro

1993-01-01

Mobile satellite communication channel has been evaluated mainly with fading statistics of signal. When bandwidth of transmitting signal becomes wider, frequency selectivity of fading becomes a significant factor of the channel. Channel characteristics, not only signal variation but multipath delay spread should be evaluated. A multipath measurement system is proposed and developed for mobile satellite applications. With this system and ETS-V satellite, multipath delay profiles are measured in various environments including Tokyo metropolis and Sapporo city at 1.5 GHz. Results show that the maximum excess delay is within 1 microsec and the maximum delay spread is 0.2 microsecs at elevation angles of 40 to 47 degrees. In wideband signal transmission of about 1 MHz and more, designers should consider the effect of selective fading due to the multipath of land mobile satellite channel.

Integration of multi-interface conversion channel using FPGA for modular photonic network

NASA Astrophysics Data System (ADS)

Janicki, Tomasz; Pozniak, Krzysztof T.; Romaniuk, Ryszard S.

2010-09-01

The article discusses the integration of different types of interfaces with FPGA circuits using a reconfigurable communication platform. The solution has been implemented in practice in a single node of a distributed measurement system. Construction of communication platform has been presented with its selected hardware modules, described in VHDL and implemented in FPGA circuits. The graphical user interface (GUI) has been described that allows a user to control the operation of the system. In the final part of the article selected practical solutions have been introduced. The whole measurement system resides on multi-gigabit optical network. The optical network construction is highly modular, reconfigurable and scalable.

Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function.

PubMed

Wang, Xinrui; Fitts, Robert H

2017-08-01

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the β-adrenergic receptor agonist dose-response curve rightward compared with controls by reducing β 1 -adrenergic receptor responsiveness and that, at the high activation rate, myocytes from trained animals showed higher K ATP channel function. Copyright © 2017 the American Physiological Society.

Innovative polymer nanocomposite electrolytes: nanoscale manipulation of ion channels by functionalized graphenes.

PubMed

Choi, Bong Gill; Hong, Jinkee; Park, Young Chul; Jung, Doo Hwan; Hong, Won Hi; Hammond, Paula T; Park, Hoseok

2011-06-28

The chemistry and structure of ion channels within the polymer electrolytes are of prime importance for studying the transport properties of electrolytes as well as for developing high-performance electrochemical devices. Despite intensive efforts on the synthesis of polymer electrolytes, few studies have demonstrated enhanced target ion conduction while suppressing unfavorable ion or mass transport because the undesirable transport occurs through an identical pathway. Herein, we report an innovative, chemical strategy for the synthesis of polymer electrolytes whose ion-conducting channels are physically and chemically modulated by the ionic (not electronic) conductive, functionalized graphenes and for a fundamental understanding of ion and mass transport occurring in nanoscale ionic clusters. The functionalized graphenes controlled the state of water by means of nanoscale manipulation of the physical geometry and chemical functionality of ionic channels. Furthermore, the confinement of bound water within the reorganized nanochannels of composite membranes was confirmed by the enhanced proton conductivity at high temperature and the low activation energy for ionic conduction through a Grotthus-type mechanism. The selectively facilitated transport behavior of composite membranes such as high proton conductivity and low methanol crossover was attributed to the confined bound water, resulting in high-performance fuel cells.

Incorporating Born solvation energy into the three-dimensional Poisson-Nernst-Planck model to study ion selectivity in KcsA K+ channels

NASA Astrophysics Data System (ADS)

Liu, Xuejiao; Lu, Benzhuo

2017-12-01

Potassium channels are much more permeable to potassium than sodium ions, although potassium ions are larger and both carry the same positive charge. This puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP) theory of electrodiffusion because the PNP model treats all ions as point charges, does not incorporate ion size information, and therefore cannot discriminate potassium from sodium ions. The PNP model can qualitatively capture some macroscopic properties of certain channel systems such as current-voltage characteristics, conductance rectification, and inverse membrane potential. However, the traditional PNP model is a continuum mean-field model and has no or underestimates the discrete ion effects, in particular the ion solvation or self-energy (which can be described by Born model). It is known that the dehydration effect (closely related to ion size) is crucial to selective permeation in potassium channels. Therefore, we incorporated Born solvation energy into the PNP model to account for ion hydration and dehydration effects when passing through inhomogeneous dielectric channel environments. A variational approach was adopted to derive a Born-energy-modified PNP (BPNP) model. The model was applied to study a cylindrical nanopore and a realistic KcsA channel, and three-dimensional finite element simulations were performed. The BPNP model can distinguish different ion species by ion radius and predict selectivity for K+ over Na+ in KcsA channels. Furthermore, ion current rectification in the KcsA channel was observed by both the PNP and BPNP models. The I -V curve of the BPNP model for the KcsA channel indicated an inward rectifier effect for K+ (rectification ratio of ˜3 /2 ) but indicated an outward rectifier effect for Na+ (rectification ratio of ˜1 /6 ) .

Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy.

PubMed

Priganc, Mariana; Zigová, Michaela; Boroňová, Iveta; Bernasovská, Jarmila; Dojčáková, Dana; Szabadosová, Viktória; Mydlárová Blaščáková, Marta; Tóthová, Iveta; Kmec, Ján; Bernasovský, Ivan

2017-03-01

Mutations in ion channels genes are potential cause of cardiomyopathy. The SCN5A gene (sodium channel, voltage gated, type V alpha subunit gene; 3p21) belongs to the family of cardiac sodium channel genes. Mutations in SCN5A gene lead to decreased Na+ current and ion unbalance. The SCN5A gene mutations are found in approximately 2% of patients with dilated cardiomyopathy (DCM), and they may be potential phenotype modifiers in hypertrophic cardiomyopathy (HCM). The role of SCN5A gene mutations in cardiomyopathy is not fully elucidated. Three selected exons (12, 20, and 21) of the SCN5A gene in the cohort of 58 East Slovak patients with dilated and HCM were analyzed by the Sanger sequencing method in order to detect etiopathogenic mutations associated with dilated and HCM. The mutation screening of three selected exons of SCN5A gene in the cohort of 27 DCM, 12 HCM patients, and 16 controls identified 10 missense genetic variants. Three of them (T1247I, A1260D, and G1262S), all in exon 21 of the SCN5A gene, were potentially damaging and disease-causing variants. Data from this study demonstrate that SCN5A gene variants have important role in the etiopathogenesis of dilated and HCM. © 2016 Wiley Periodicals, Inc.

Morphine- and CaMKII dependent enhancement of GIRK channel signaling in hippocampal neurons

PubMed Central

Nassirpour, Rounak; Bahima, Laia; Lalive, Arnaud L.; Lüscher, Christian; Luján, Rafael; Slesinger, Paul A.

2010-01-01

G protein-gated inwardly rectifying potassium (GIRK) channels, which help control neuronal excitability, are important for the response to drugs of abuse. Here, we describe a novel pathway for morphine-dependent enhancement of GIRK channel signaling in hippocampal neurons. Morphine treatment for ~20 h increased the colocalization of GIRK2 with PSD95, a dendritic spine marker. Western blot analysis and quantitative immuno-electron microscopy revealed an increase in GIRK2 protein and targeting to dendritic spines. In vivo administration of morphine also produced an upregulation of GIRK2 protein in the hippocampus. The mechanism engaged by morphine required elevated intracellular Ca2+ and was insensitive to pertussis toxin, implicating opioid receptors that may couple to Gq G proteins. met-enkephalin, but not the μ-selective (DAMGO) and δ-selective (DPDPE) opioid receptor agonists, mimicked the effect of morphine suggesting involvement of a heterodimeric opioid receptor complex. Peptide (KN-93) inhibition of CaMKII prevented the morphine-dependent change in GIRK localization while expression of a constitutively activated form of CaMKII mimicked the effects of morphine. Coincident with an increase in GIRK2 surface expression, functional analyses revealed that morphine-treatment increased the size of serotonin-activated GIRK currents and Ba2+-sensitive basal K+ currents in neurons. These results demonstrate plasticity in neuronal GIRK signaling that may contribute to the abusive effects of morphine. PMID:20926668

Music-induced positive mood broadens the scope of auditory attention.

PubMed

Putkinen, Vesa; Makkonen, Tommi; Eerola, Tuomas

2017-07-01

Previous studies indicate that positive mood broadens the scope of visual attention, which can manifest as heightened distractibility. We used event-related potentials (ERP) to investigate whether music-induced positive mood has comparable effects on selective attention in the auditory domain. Subjects listened to experimenter-selected happy, neutral or sad instrumental music and afterwards participated in a dichotic listening task. Distractor sounds in the unattended channel elicited responses related to early sound encoding (N1/MMN) and bottom-up attention capture (P3a) while target sounds in the attended channel elicited a response related to top-down-controlled processing of task-relevant stimuli (P3b). For the subjects in a happy mood, the N1/MMN responses to the distractor sounds were enlarged while the P3b elicited by the target sounds was diminished. Behaviorally, these subjects tended to show heightened error rates on target trials following the distractor sounds. Thus, the ERP and behavioral results indicate that the subjects in a happy mood allocated their attentional resources more diffusely across the attended and the to-be-ignored channels. Therefore, the current study extends previous research on the effects of mood on visual attention and indicates that even unfamiliar instrumental music can broaden the scope of auditory attention via its effects on mood. © The Author (2017). Published by Oxford University Press.

Influence of the Selectivity Filter Properties on Proton Selectivity in the Influenza A M2 Channel.

PubMed

Dudev, Todor; Grauffel, Cédric; Lim, Carmay

2016-10-05

The homotetrameric M2 proton channel of influenza A plays a crucial role in the viral life cycle and is thus an important therapeutic target. It selectively conducts protons against a background of other competing cations whose concentrations are up to a million times greater than the proton concentration. Its selectivity is largely determined by a constricted region of its open pore known as the selectivity filter, which is lined by four absolutely conserved histidines. While the mechanism of proton transport through the channel has been studied, the physical principles underlying the selectivity for protons over other cations in the channel's His 4 selectivity filter remain elusive. Furthermore, it is not known if proton selectivity absolutely requires all four histidines with two of the four histidines protonated and if other titratable amino acid residues in lieu of the histidines could bind protons and how they affect proton selectivity. Here, we elucidate how the competition between protons and rival cations such as Na + depends on the selectivity filter's (1) histidine protonation state, (2) solvent exposure, (3) oligomeric state (the number of protein chains and thus the number of His ligands), and (4) ligand composition by evaluating the free energies for replacing monovalent Na + with H 3 O + in various model selectivity filters. We show that tetrameric His 4 filters are more proton-selective than their trimeric His 3 counterparts, and a dicationic His 4 filter where two of the four histidines are protonated is more proton-selective than tetrameric filters with other charge states/composition (different combinations of His protonation states or different metal-ligating ligands). The [His 4 ] 2+ filter achieves proton selectivity by providing suboptimal binding conditions for rival cations such as Na + , which prefers a neutral or negatively charged filter instead of a dicationic one, and three rather than four ligands with oxygen-ligating atoms.

The Drosophila TRPA1 Channel and Neuronal Circuits Controlling Rhythmic Behaviours and Sleep in Response to Environmental Temperature.

PubMed

Roessingh, Sanne; Stanewsky, Ralf

2017-10-03

trpA1 encodes a thermosensitive transient receptor potential channel (TRP channel) that functions in selection of preferred temperatures and noxious heat avoidance. In this review, we discuss the evidence for a role of TRPA1 in the control of rhythmic behaviours in Drosophila melanogaster . Activity levels during the afternoon and rhythmic temperature preference are both regulated by TRPA1. In contrast, TRPA1 is dispensable for temperature synchronisation of circadian clocks. We discuss the neuronal basis of TRPA1-mediated temperature effects on rhythmic behaviours, and conclude that they are mediated by partly overlapping but distinct neuronal circuits. We have previously shown that TRPA1 is required to maintain siesta sleep under warm temperature cycles. Here, we present new data investigating the neuronal circuit responsible for this regulation. First, we discuss the difficulties that remain in identifying the responsible neurons. Second, we discuss the role of clock neurons (s-LNv/DN1 network) in temperature-driven regulation of siesta sleep, and highlight the role of TRPA1 therein. Finally, we discuss the sexual dimorphic nature of siesta sleep and propose that the s-LNv/DN1 clock network could play a role in the integration of environmental information, mating status and other internal drives, to appropriately drive adaptive sleep/wake behaviour.

Microfluidic control of droplet formation from stable emulsions formed by aqueous two-phase systems

NASA Astrophysics Data System (ADS)

Teixeira, Alyne G.; Tsai, Meng-Chiao; Frampton, John P.

2018-02-01

Aqueous two-phase systems (ATPSs) form from the thermodynamic separation of two dissolved incompatible solutes, such as two polymers, a polymer and a salt, and a polymer and a surfactant. At most supercritical concentrations, ATPS emulsions can be formed by vigorous mixing. These emulsions typically settle into distinct layers in minutes to hours. However, it is also possible to choose ATPS compositions with extremely long settling times that resemble stable emulsions. Here, we generated stable emulsions from a polyethylene glycol (PEG)-dextran ATPS by selecting ATPS compositions at the extreme ends of the tie lines connecting the binodal curve delineating phase-separating compositions. Droplets of PEG in a continuous dextran phase did not coalesce appreciably over the course of several days when stored in a conical tube or syringe. However, upon exposure to laminar flow conditions in a microfluidic channel, droplets were observed to coalesce. Through microscopic characterization of droplet volume, an increase in droplet size and decrease in overall droplet number was observed as a function of channel distance, suggesting a progressive droplet merging phenomenon. This novel approach to control droplet size by encouraging coalescence of stable emulsions under laminar flow in a microfluidic channel enables the production of droplets ranging from fL to several pL, which may enable various future biotechnology applications.

Active parallel redundancy for electronic integrator-type control circuits

NASA Technical Reports Server (NTRS)

Peterson, R. A.

1971-01-01

Circuit extends concept of redundant feedback control from type-0 to type-1 control systems. Inactive channels are slaves to the active channel, if latter fails, it is rejected and slave channel is activated. High reliability and elimination of single-component catastrophic failure are important in closed-loop control systems.

Selective-area growth and controlled substrate coupling of transition metal dichalcogenides

NASA Astrophysics Data System (ADS)

Bersch, Brian M.; Eichfeld, Sarah M.; Lin, Yu-Chuan; Zhang, Kehao; Bhimanapati, Ganesh R.; Piasecki, Aleksander F.; Labella, Michael, III; Robinson, Joshua A.

2017-06-01

Developing a means for true bottom-up, selective-area growth of two-dimensional (2D) materials on device-ready substrates will enable synthesis in regions only where they are needed. Here, we demonstrate seed-free, site-specific nucleation of transition metal dichalcogenides (TMDs) with precise control over lateral growth by utilizing an ultra-thin polymeric surface functionalization capable of precluding nucleation and growth. This polymer functional layer (PFL) is derived from conventional photoresists and lithographic processing, and is compatible with multiple growth techniques, precursors (metal organics, solid-source) and TMDs. Additionally, we demonstrate that the substrate can play a major role in TMD transport properties. With proper TMD/substrate decoupling, top-gated field-effect transistors (FETs) fabricated with selectively-grown monolayer MoS2 channels are competitive with current reported MoS2 FETs. The work presented here demonstrates that substrate surface engineering is key to realizing precisely located and geometrically-defined 2D layers via unseeded chemical vapor deposition techniques.

Efficient multichannel acoustic echo cancellation using constrained tap selection schemes in the subband domain

NASA Astrophysics Data System (ADS)

Desiraju, Naveen Kumar; Doclo, Simon; Wolff, Tobias

2017-12-01

Acoustic echo cancellation (AEC) is a key speech enhancement technology in speech communication and voice-enabled devices. AEC systems employ adaptive filters to estimate the acoustic echo paths between the loudspeakers and the microphone(s). In applications involving surround sound, the computational complexity of an AEC system may become demanding due to the multiple loudspeaker channels and the necessity of using long filters in reverberant environments. In order to reduce the computational complexity, the approach of partially updating the AEC filters is considered in this paper. In particular, we investigate tap selection schemes which exploit the sparsity present in the loudspeaker channels for partially updating subband AEC filters. The potential for exploiting signal sparsity across three dimensions, namely time, frequency, and channels, is analyzed. A thorough analysis of different state-of-the-art tap selection schemes is performed and insights about their limitations are gained. A novel tap selection scheme is proposed which overcomes these limitations by exploiting signal sparsity while not ignoring any filters for update in the different subbands and channels. Extensive simulation results using both artificial as well as real-world multichannel signals show that the proposed tap selection scheme outperforms state-of-the-art tap selection schemes in terms of echo cancellation performance. In addition, it yields almost identical echo cancellation performance as compared to updating all filter taps at a significantly reduced computational cost.

Selective stimulation of facial muscles with a penetrating electrode array in the feline model

PubMed Central

Sahyouni, Ronald; Bhatt, Jay; Djalilian, Hamid R.; Tang, William C.; Middlebrooks, John C.; Lin, Harrison W.

2017-01-01

Objective Permanent facial nerve injury is a difficult challenge for both patients and physicians given its potential for debilitating functional, cosmetic, and psychological sequelae. Although current surgical interventions have provided considerable advancements in facial nerve rehabilitation, they often fail to fully address all impairments. We aim to introduce an alternative approach to facial nerve rehabilitation. Study design Acute experiments in animals with normal facial function. Methods The study included three anesthetized cats. Four facial muscles (levator auris longus, orbicularis oculi, nasalis, and orbicularis oris) were monitored with a standard electromyographic (EMG) facial nerve monitoring system with needle electrodes. The main trunk of the facial nerve was exposed and a 16-channel penetrating electrode array was placed into the nerve. Electrical current pulses were delivered to each stimulating electrode individually. Elicited EMG voltage outputs were recorded for each muscle. Results Stimulation through individual channels selectively activated restricted nerve populations, resulting in selective contraction of individual muscles. Increasing stimulation current levels resulted in increasing EMG voltage responses. Typically, selective activation of two or more distinct muscles was successfully achieved via a single placement of the multi-channel electrode array by selection of appropriate stimulation channels. Conclusion We have established in the animal model the ability of a penetrating electrode array to selectively stimulate restricted fiber populations within the facial nerve and to selectively elicit contractions in specific muscles and regions of the face. These results show promise for the development of a facial nerve implant system. PMID:27312936

Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors

PubMed Central

Xu, Xiaojun; Sepich, Caraline; Lukas, Ronald J; Zhu, Guonian; Chang, Yongchang

2016-01-01

Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate α7 nAChR, α4β2 nAChR, α1β2γ2 GABAA receptor and ρ1 GABAC receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the α1β2γ2 GABAA receptor. PMID:27049309

Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors.

PubMed

Xu, Xiaojun; Sepich, Caraline; Lukas, Ronald J; Zhu, Guonian; Chang, Yongchang

2016-05-13

Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate α7 nAChR, α4β2 nAChR, α1β2γ2 GABAA receptor and ρ1 GABAC receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the α1β2γ2 GABAA receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes

PubMed Central

Flores, Pedro L.; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

2017-01-01

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels. PMID:28672825

Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes.

PubMed

Flores, Pedro L; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

2017-06-25

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

Pharmacovigilance database search discloses ClC-K channels as a novel target of the AT1 receptor blockers valsartan and olmesartan.

PubMed

Imbrici, Paola; Tricarico, Domenico; Mangiatordi, Giuseppe Felice; Nicolotti, Orazio; Lograno, Marcello Diego; Conte, Diana; Liantonio, Antonella

2017-07-01

Human ClC-K chloride channels are highly attractive targets for drug discovery as they have a variety of important physiological functions and are associated with genetic disorders. These channels are crucial in the kidney as they control chloride reabsorption and water diuresis. In addition, loss-of-function mutations of CLCNKB and BSND genes cause Bartter's syndrome (BS), whereas CLCNKA and CLCNKB gain-of-function polymorphisms predispose to a rare form of salt sensitive hypertension. Both disorders lack a personalized therapy that is in most cases only symptomatic. The aim of this study was to identify novel ClC-K ligands from drugs already on the market, by exploiting the pharmacological side activity of drug molecules available from the FDA Adverse Effects Reporting System database. We searched for drugs having a Bartter-like syndrome as a reported side effect, with the assumption that BS could be causatively related to the block of ClC-K channels. The ability of the selected BS-causing drugs to bind and block ClC-K channels was then validated through an integrated experimental and computational approach based on patch clamp electrophysiology in HEK293 cells and molecular docking simulations. Valsartan and olmesartan were able to block ClC-Ka channels and the molecular requirements for effective inhibition of these channels have been identified. These results suggest additional mechanisms of action for these sartans further to their primary AT 1 receptor antagonism and propose these compounds as leads for designing new potent ClC-K ligands. © 2017 The British Pharmacological Society.