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

Science.gov (United States)

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.

Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

Energy Technology Data Exchange (ETDEWEB)

Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko; Zhu, Yanyi; Atadja, Peter W.; Claiborne, Tavina; Grob, Jonathan E.; McRiner, Andrew; Pancost, Margaret R.; Patnaik, Anup; Shao, Wenlin; Shultz, Michael; Tichkule, Ritesh; Tommasi, Ruben A.; Vash, Brian; Wang, Ping; Stams, Travis (Novartis)

2013-11-20

Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

Channel and delay estimation for base-station–based cooperative communications in frequency-selective fading channels

Directory of Open Access Journals (Sweden)

Hongjun Xu

2011-07-01

Full Text Available A channel and delay estimation algorithm for both positive and negative delay, based on the distributed Alamouti scheme, has been recently discussed for base-station–based asynchronous cooperative systems in frequency-flat fading channels. This paper extends the algorithm, the maximum likelihood estimator, to work in frequency-selective fading channels. The minimum mean square error (MMSE performance of channel estimation for both packet schemes and normal schemes is discussed in this paper. The symbol error rate (SER performance of equalisation and detection for both time-reversal space-time block code (STBC and single-carrier STBC is also discussed in this paper. The MMSE simulation results demonstrated the superior performance of the packet scheme over the normal scheme with an improvement in performance of up to 6 dB when feedback was used in the frequency-selective channel at a MSE of 3 x 10^–2. The SER simulation results showed that, although both the normal and packet schemes achieved similar diversity orders, the packet scheme demonstrated a 1 dB coding gain over the normal scheme at a SER of 10^–5. Finally, the SER simulations showed that the frequency-selective fading system outperformed the frequency-flat fading system.

Relay selection in cooperative communication systems over continuous time-varying fading channel

Directory of Open Access Journals (Sweden)

Ke Geng

2017-02-01

Full Text Available In this paper, we study relay selection under outdated channel state information (CSI in a decode-and-forward (DF cooperative system. Unlike previous researches on cooperative communication under outdated CSI, we consider that the channel varies continuously over time, i.e., the channel not only changes between relay selection and data transmission but also changes during data transmission. Thus the level of accuracy of the CSI used in relay selection degrades with data transmission. We first evaluate the packet error rate (PER of the cooperative system under continuous time-varying fading channel, and find that the PER performance deteriorates more seriously under continuous time-varying fading channel than when the channel is assumed to be constant during data transmission. Then, we propose a repeated relay selection (RRS strategy to improve the PER performance, in which the forwarded data is divided into multiple segments and relay is reselected before the transmission of each segment based on the updated CSI. Finally, we propose a combined relay selection (CRS strategy which takes advantage of three different relay selection strategies to further mitigate the impact of outdated CSI.

Multiple flow profiles for two-phase flow in single microfluidic channels through site-selective channel coating.

Science.gov (United States)

Logtenberg, Hella; Lopez-Martinez, Maria J; Feringa, Ben L; Browne, Wesley R; Verpoorte, Elisabeth

2011-06-21

An approach to control two-phase flow systems in a poly(dimethylsiloxane) (PDMS) microfluidic device using spatially selective surface modification is demonstrated. Side-by-side flows of ethanol : water solutions containing different polymers are used to selectively modify both sides of a channel by laminar flow patterning. Introduction of air pockets during modification allows for control over the length of the channel section that is modified. This approach makes it possible to achieve slug flow and side-by-side flow of water : 1-octanol simultaneously within the same PDMS channel, without the need of additional structural elements. A key finding is that conditioning of the PDMS channels with 1-octanol before polymer deposition is crucial to achieving stable side-by-side flows.

Sniffer Channel Selection for Monitoring Wireless LANs

Science.gov (United States)

Song, Yuan; Chen, Xian; Kim, Yoo-Ah; Wang, Bing; Chen, Guanling

Wireless sniffers are often used to monitor APs in wireless LANs (WLANs) for network management, fault detection, traffic characterization, and optimizing deployment. It is cost effective to deploy single-radio sniffers that can monitor multiple nearby APs. However, since nearby APs often operate on orthogonal channels, a sniffer needs to switch among multiple channels to monitor its nearby APs. In this paper, we formulate and solve two optimization problems on sniffer channel selection. Both problems require that each AP be monitored by at least one sniffer. In addition, one optimization problem requires minimizing the maximum number of channels that a sniffer listens to, and the other requires minimizing the total number of channels that the sniffers listen to. We propose a novel LP-relaxation based algorithm, and two simple greedy heuristics for the above two optimization problems. Through simulation, we demonstrate that all the algorithms are effective in achieving their optimization goals, and the LP-based algorithm outperforms the greedy heuristics.

Channel Selection Based on Trust and Multiarmed Bandit in Multiuser, Multichannel Cognitive Radio Networks

Directory of Open Access Journals (Sweden)

Fanzi Zeng

2014-01-01

Full Text Available This paper proposes a channel selection scheme for the multiuser, multichannel cognitive radio networks. This scheme formulates the channel selection as the multiarmed bandit problem, where cognitive radio users are compared to the players and channels to the arms. By simulation negotiation we can achieve the potential reward on each channel after it is selected for transmission; then the channel with the maximum accumulated rewards is formally chosen. To further improve the performance, the trust model is proposed and combined with multi-armed bandit to address the channel selection problem. Simulation results validate the proposed scheme.

Protein structure and ionic selectivity in calcium channels: selectivity filter size, not shape, matters.

Science.gov (United States)

Malasics, Attila; Gillespie, Dirk; Nonner, Wolfgang; Henderson, Douglas; Eisenberg, Bob; Boda, Dezso

2009-12-01

Calcium channels have highly charged selectivity filters (4 COO(-) groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na(+) and Ca(2+)) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca(2+) is more efficient in balancing the charge of the filter because it provides twice the charge as Na(+) while occupying the same space. The CSC mechanism further implies that the main determinant of Ca(2+) versus Na(+) selectivity is the density of charged particles in the selectivity filter, i.e., the volume of the filter (after fixing the number of charged groups in the filter). In this paper we test this hypothesis by changing filter length and/or radius (shape) of the cylindrical selectivity filter of our reduced model. We show that varying volume and shape together has substantially stronger effects than varying shape alone with volume fixed. Our simulations show the importance of depletion zones of ions in determining channel conductance calculated with the integrated Nernst-Planck equation. We show that confining the protein side chains with soft or hard walls does not influence selectivity.

An Improved User Selection Algorithm in Multiuser MIMO Broadcast with Channel Prediction

Science.gov (United States)

Min, Zhi; Ohtsuki, Tomoaki

In multiuser MIMO-BC (Multiple-Input Multiple-Output Broadcasting) systems, user selection is important to achieve multiuser diversity. The optimal user selection algorithm is to try all the combinations of users to find the user group that can achieve the multiuser diversity. Unfortunately, the high calculation cost of the optimal algorithm prevents its implementation. Thus, instead of the optimal algorithm, some suboptimal user selection algorithms were proposed based on semiorthogonality of user channel vectors. The purpose of this paper is to achieve multiuser diversity with a small amount of calculation. For this purpose, we propose a user selection algorithm that can improve the orthogonality of a selected user group. We also apply a channel prediction technique to a MIMO-BC system to get more accurate channel information at the transmitter. Simulation results show that the channel prediction can improve the accuracy of channel information for user selections, and the proposed user selection algorithm achieves higher sum rate capacity than the SUS (Semiorthogonal User Selection) algorithm. Also we discuss the setting of the algorithm threshold. As the result of a discussion on the calculation complexity, which uses the number of complex multiplications as the parameter, the proposed algorithm is shown to have a calculation complexity almost equal to that of the SUS algorithm, and they are much lower than that of the optimal user selection algorithm.

Protein structure and ionic selectivity in calcium channels: Selectivity filter size, not shape, matters

OpenAIRE

Malasics, Attila; Gillespie, Dirk; Nonner, Wolfgang; Henderson, Douglas; Eisenberg, Bob; Boda, Dezső

2009-01-01

Calcium channels have highly charged selectivity filters (4 COO− groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na+ and Ca2+) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca2+ is more efficient in balancing the charge of the filter because it provides twice the charge as Na+ while occupy...

Substrate channel in nitrogenase revealed by a molecular dynamics approach.

Science.gov (United States)

Smith, Dayle; Danyal, Karamatullah; Raugei, Simone; Seefeldt, Lance C

2014-04-15

Mo-dependent nitrogenase catalyzes the biological reduction of N2 to two NH3 molecules at FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized submicrosecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel. The viability of this observed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, resulting in the discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment and that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

Channel selection for simultaneous and proportional myoelectric prosthesis control of multiple degrees-of-freedom

Science.gov (United States)

Hwang, Han-Jeong; Hahne, Janne Mathias; Müller, Klaus-Robert

2014-10-01

Objective. Recent studies have shown the possibility of simultaneous and proportional control of electrically powered upper-limb prostheses, but there has been little investigation on optimal channel selection. The objective of this study is to find a robust channel selection method and the channel subsets most suitable for simultaneous and proportional myoelectric prosthesis control of multiple degrees-of-freedom (DoFs). Approach. Ten able-bodied subjects and one person with congenital upper-limb deficiency took part in this study, and performed wrist movements with various combinations of two DoFs (flexion/extension and radial/ulnar deviation). During the experiment, high density electromyographic (EMG) signals and the actual wrist angles were recorded with an 8 × 24 electrode array and a motion tracking system, respectively. The wrist angles were estimated from EMG features with ridge regression using the subsets of channels chosen by three different channel selection methods: (1) least absolute shrinkage and selection operator (LASSO), (2) sequential feature selection (SFS), and (3) uniform selection (UNI). Main results. SFS generally showed higher estimation accuracy than LASSO and UNI, but LASSO always outperformed SFS in terms of robustness, such as noise addition, channel shift and training data reduction. It was also confirmed that about 95% of the original performance obtained using all channels can be retained with only 12 bipolar channels individually selected by LASSO and SFS. Significance. From the analysis results, it can be concluded that LASSO is a promising channel selection method for accurate simultaneous and proportional prosthesis control. We expect that our results will provide a useful guideline to select optimal channel subsets when developing clinical myoelectric prosthesis control systems based on continuous movements with multiple DoFs.

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

Directory of Open Access Journals (Sweden)

Yang Li

Full Text Available 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.

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

Science.gov (United States)

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.

Secured Communication over Frequency-Selective Fading Channels: A Practical Vandermonde Precoding

Directory of Open Access Journals (Sweden)

Debbah Mérouane

2009-01-01

Full Text Available We study the frequency-selective broadcast channel with confidential messages (BCC where the transmitter sends a confidential message to receiver 1 and a common message to receivers 1 and 2. In the case of a block transmission of symbols followed by a guard interval of symbols, the frequency-selective channel can be modeled as a Toeplitz matrix. For this special type of multiple-input multiple-output channels, we propose a practical Vandermonde precoding that projects the confidential messages in the null space of the channel seen by receiver 2 while superposing the common message. For this scheme, we provide the achievable rate region and characterize the optimal covariance for some special cases of interest. Interestingly, the proposed scheme can be applied to other multiuser scenarios such as the -user frequency-selective BCC with confidential messages and the two-user frequency-selective BCC with two confidential messages. For each scenario, we provide the secrecy degree of freedom (s.d.o.f. region of the corresponding channel and prove the optimality of the Vandermonde precoding. One of the appealing features of the proposed scheme is that it does not require any specific secrecy encoding technique but can be applied on top of any existing powerful encoding schemes.

Single channel speech enhancement in the modulation domain: New insights in the modulation channel selection framework

DEFF Research Database (Denmark)

Boldt, Jesper B.; Bertelsen, Andreas Thelander; Gran, Fredrik

2015-01-01

Recently, the ideal binary mask has been introduced in the modulation domain by extending the ideal channel selection method to modulation channel selection [1]. This new method shows substantial improvement in speech intelligibility but less than its predecessor despite the higher complexity. Here......, we extend the previous finding from [1] and provide a more direct comparison of binary masking in the modulation domain with binary masking in the time-frequency domain. Subjective and objective evaluations are performed and provide additional insight into modulation domain processing....

OPRA capacity bounds for selection diversity over generalized fading channels

KAUST Repository

Hanif, Muhammad Fainan

2014-05-01

Channel side information at the transmitter can increase the average capacity by enabling optimal power and rate adaptation. The resulting optimal power and rate adaptation (OPRA) capacity rarely has a closed-form analytic expression. In this paper, lower and upper bounds on OPRA capacity for selection diversity scheme are presented. These bounds hold for variety of fading channels including log-normal and generalized Gamma distributed models and have very simple analytic expressions for easy evaluation even for kth best path selection. Some selected numerical results show that the newly proposed bounds closely approximate the actual OPRA capacity. © 2014 IEEE.

Distinct interactions of Na+ and Ca2+ ions with the selectivity filter of the bacterial sodium channel NaVAb

International Nuclear Information System (INIS)

Ke, Song; Zangerl, Eva-Maria; Stary-Weinzinger, Anna

2013-01-01

Highlights: ► Ca 2+ translocates slowly in the filter, due to lack of “loose” knock-on mechanism. ► Identification of a high affinity binding site in Na V Ab selectivity filter. ► Changes of EEEE locus triggered by electrostatic interactions with Ca 2+ ions. -- Abstract: Rapid and selective ion transport is essential for the generation and regulation of electrical signaling pathways in living organisms. In this study, we use molecular dynamics simulations and free energy calculations to investigate how the bacterial sodium channel Na V Ab (Arcobacter butzleri) differentiates between Na + and Ca 2+ ions. Multiple nanosecond molecular dynamics simulations revealed distinct binding patterns for these two cations in the selectivity filter and suggested a high affinity calcium binding site formed by backbone atoms of residues Leu-176 and Thr-175 (S CEN ) in the sodium channel selectivity filter

Thermodynamic coupling between activation and inactivation gating in potassium channels revealed by free energy molecular dynamics simulations.

Science.gov (United States)

Pan, Albert C; Cuello, Luis G; Perozo, Eduardo; Roux, Benoît

2011-12-01

The amount of ionic current flowing through K(+) channels is determined by the interplay between two separate time-dependent processes: activation and inactivation gating. Activation is concerned with the stimulus-dependent opening of the main intracellular gate, whereas inactivation is a spontaneous conformational transition of the selectivity filter toward a nonconductive state occurring on a variety of timescales. A recent analysis of multiple x-ray structures of open and partially open KcsA channels revealed the mechanism by which movements of the inner activation gate, formed by the inner helices from the four subunits of the pore domain, bias the conformational changes at the selectivity filter toward a nonconductive inactivated state. This analysis highlighted the important role of Phe103, a residue located along the inner helix, near the hinge position associated with the opening of the intracellular gate. In the present study, we use free energy perturbation molecular dynamics simulations (FEP/MD) to quantitatively elucidate the thermodynamic basis for the coupling between the intracellular gate and the selectivity filter. The results of the FEP/MD calculations are in good agreement with experiments, and further analysis of the repulsive, van der Waals dispersive, and electrostatic free energy contributions reveals that the energetic basis underlying the absence of inactivation in the F103A mutation in KcsA is the absence of the unfavorable steric interaction occurring with the large Ile100 side chain in a neighboring subunit when the intracellular gate is open and the selectivity filter is in a conductive conformation. Macroscopic current analysis shows that the I100A mutant indeed relieves inactivation in KcsA, but to a lesser extent than the F103A mutant.

Secured Communication over Frequency-Selective Fading Channels: A Practical Vandermonde Precoding

Directory of Open Access Journals (Sweden)

Mari Kobayashi

2009-01-01

Full Text Available We study the frequency-selective broadcast channel with confidential messages (BCC where the transmitter sends a confidential message to receiver 1 and a common message to receivers 1 and 2. In the case of a block transmission of N symbols followed by a guard interval of L symbols, the frequency-selective channel can be modeled as a N×(N+L Toeplitz matrix. For this special type of multiple-input multiple-output channels, we propose a practical Vandermonde precoding that projects the confidential messages in the null space of the channel seen by receiver 2 while superposing the common message. For this scheme, we provide the achievable rate region and characterize the optimal covariance for some special cases of interest. Interestingly, the proposed scheme can be applied to other multiuser scenarios such as the K+1-user frequency-selective BCC with K confidential messages and the two-user frequency-selective BCC with two confidential messages. For each scenario, we provide the secrecy degree of freedom (s.d.o.f. region of the corresponding channel and prove the optimality of the Vandermonde precoding. One of the appealing features of the proposed scheme is that it does not require any specific secrecy encoding technique but can be applied on top of any existing powerful encoding schemes.

Electrostatics of aquaporin and aquaglyceroporin channels correlates with their transport selectivity

Science.gov (United States)

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

Program scheme using common source lines in channel stacked NAND flash memory with layer selection by multilevel operation

Science.gov (United States)

Kim, Do-Bin; Kwon, Dae Woong; Kim, Seunghyun; Lee, Sang-Ho; Park, Byung-Gook

2018-02-01

To obtain high channel boosting potential and reduce a program disturbance in channel stacked NAND flash memory with layer selection by multilevel (LSM) operation, a new program scheme using boosted common source line (CSL) is proposed. The proposed scheme can be achieved by applying proper bias to each layer through its own CSL. Technology computer-aided design (TCAD) simulations are performed to verify the validity of the new method in LSM. Through TCAD simulation, it is revealed that the program disturbance characteristics is effectively improved by the proposed scheme.

Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing

International Nuclear Information System (INIS)

Dev, Jyoti; Brüschweiler, Sven; Ouyang, Bo; Chou, James J.

2015-01-01

The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity and that the action of the drug is attenuating this motion. Here, we determined the conformational dynamics and solvent accessibility of the p7 channel. The proton exchange measurements show that the cavity-lining residues are largely water accessible, consistent with the overall funnel shape of the channel. Our relaxation dispersion data show that residues Val7 and Leu8 near the asparagine ring are subject to large chemical exchange, suggesting significant intrinsic channel breathing at the tip of the funnel. Moreover, the hinge regions connecting the narrow and wide regions of the funnel show strong relaxation dispersion and these regions are the binding sites for rimantadine. Presence of rimantadine decreases the conformational dynamics near the asparagine ring and the hinge area. Our data provide direct observation of μs–ms dynamics of the p7 channel and support the molecular wedge mechanism of rimantadine inhibition of the HCV p7 channel

Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing

Energy Technology Data Exchange (ETDEWEB)

Dev, Jyoti; Brüschweiler, Sven [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States); Ouyang, Bo [Chinese Academy of Sciences, State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology (China); Chou, James J., E-mail: james-chou@hms.harvard.edu [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States)

2015-04-15

The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity and that the action of the drug is attenuating this motion. Here, we determined the conformational dynamics and solvent accessibility of the p7 channel. The proton exchange measurements show that the cavity-lining residues are largely water accessible, consistent with the overall funnel shape of the channel. Our relaxation dispersion data show that residues Val7 and Leu8 near the asparagine ring are subject to large chemical exchange, suggesting significant intrinsic channel breathing at the tip of the funnel. Moreover, the hinge regions connecting the narrow and wide regions of the funnel show strong relaxation dispersion and these regions are the binding sites for rimantadine. Presence of rimantadine decreases the conformational dynamics near the asparagine ring and the hinge area. Our data provide direct observation of μs–ms dynamics of the p7 channel and support the molecular wedge mechanism of rimantadine inhibition of the HCV p7 channel.

Use of color-coded sleeve shutters accelerates oscillograph channel selection

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Asymptotic analysis for Nakagami-m fading channels with relay selection

KAUST Repository

Zhong, Caijun; Wong, Kaikit; Jin, Shi; Alouini, Mohamed-Slim; Ratnarajah, Tharm

2011-01-01

In this paper, we analyze the asymptotic outage probability performance of both decode-and-forward (DF) and amplify-and-forward (AF) relaying systems using partial relay selection and the "best" relay selection schemes for Nakagami-m fading channels

Thermal responsive ion selectivity of uranyl peroxide nanocages: an inorganic mimic of K{sup +} ion channels

Energy Technology Data Exchange (ETDEWEB)

Gao, Yunyi; Sun, Xinyu; Liu, Tianbo [Department of Polymer Science, University of Akron, Akron, OH (United States); Szymanowski, Jennifer E.S.; Burns, Peter C. [Department of Civil Engineering and Geological Sciences, University of Notre Dame, Notre Dame, IN (United States)

2016-06-06

An actinyl peroxide cage cluster, Li{sub 48+m}K{sub 12}(OH){sub m}[UO{sub 2}(O{sub 2})(OH)]{sub 60} (H{sub 2}O){sub n} (m∼20 and n∼310; U{sub 60}), discriminates precisely between Na{sup +} and K{sup +} ions when heated to certain temperatures, a most essential feature for K{sup +} selective filters. The U{sub 60} clusters demonstrate several other features in common with K{sup +} ion channels, including passive transport of K{sup +} ions, a high flux rate, and the dehydration of U{sub 60} and K{sup +} ions. These qualities make U{sub 60} (a pure inorganic cluster) a promising ion channel mimic in an aqueous environment. Laser light scattering (LLS) and isothermal titration calorimetry (ITC) studies revealed that the tailorable ion selectivity of U{sub 60} clusters is a result of the thermal responsiveness of the U{sub 60} hydration shells. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Thermal responsive ion selectivity of uranyl peroxide nanocages. An inorganic mimic of K{sup +} ion channels

Energy Technology Data Exchange (ETDEWEB)

Gao, Yunyi; Sun, Xinyu; Liu, Tianbo [Akron Univ., OH (United States). Dept. of Polymer Science; Szymanowski, Jennifer E.S.; Burns, Peter C. [Notre Dame Univ., IN (United States). Dept. of Civil Engineering and Geological Sciences

2016-06-06

An actinyl peroxide cage cluster, Li{sub 48+m}K{sub 12}(OH){sub m}[UO{sub 2}(O{sub 2})(OH)]{sub 60} (H{sub 2}O){sub n} (m∼20 and n∼310; U{sub 60}), discriminates precisely between Na{sup +} and K{sup +} ions when heated to certain temperatures, a most essential feature for K{sup +} selective filters. The U{sub 60} clusters demonstrate several other features in common with K{sup +} ion channels, including passive transport of K{sup +} ions, a high flux rate, and the dehydration of U{sub 60} and K{sup +} ions. These qualities make U{sub 60} (a pure inorganic cluster) a promising ion channel mimic in an aqueous environment. Laser light scattering (LLS) and isothermal titration calorimetry (ITC) studies revealed that the tailorable ion selectivity of U{sub 60} clusters is a result of the thermal responsiveness of the U{sub 60} hydration shells.

A new Infrared Atmospheric Sounding Interferometer channel selection and assessment of its impact on Met Office NWP forecasts

Science.gov (United States)

Noh, Young-Chan; Sohn, Byung-Ju; Kim, Yoonjae; Joo, Sangwon; Bell, William; Saunders, Roger

2017-11-01

A new set of Infrared Atmospheric Sounding Interferometer (IASI) channels was re-selected from 314 EUMETSAT channels. In selecting channels, we calculated the impact of the individually added channel on the improvement in the analysis outputs from a one-dimensional variational analysis (1D-Var) for the Unified Model (UM) data assimilation system at the Met Office, using the channel score index (CSI) as a figure of merit. Then, 200 channels were selected in order by counting each individual channel's CSI contribution. Compared with the operationally used 183 channels for the UM at the Met Office, the new set shares 149 channels, while the other 51 channels are new. Also examined is the selection from the entropy reduction method with the same 1D-Var approach. Results suggest that channel selection can be made in a more objective fashion using the proposed CSI method. This is because the most important channels can be selected across the whole IASI observation spectrum. In the experimental trial runs using the UM global assimilation system, the new channels had an overall neutral impact in terms of improvement in forecasts, as compared with results from the operational channels. However, upper-tropospheric moist biases shown in the control run with operational channels were significantly reduced in the experimental trial with the newly selected channels. The reduction of moist biases was mainly due to the additional water vapor channels, which are sensitive to the upper-tropospheric water vapor.

Theoretical analysis of selectivity mechanisms in molecular transport through channels and nanopores

International Nuclear Information System (INIS)

Agah, Shaghayegh; Pasquali, Matteo; Kolomeisky, Anatoly B.

2015-01-01

Selectivity is one of the most fundamental concepts in natural sciences, and it is also critically important in various technological, industrial, and medical applications. Although there are many experimental methods that allow to separate molecules, frequently they are expensive and not efficient. Recently, a new method of separation of chemical mixtures based on utilization of channels and nanopores has been proposed and successfully tested in several systems. However, mechanisms of selectivity in the molecular transport during the translocation are still not well understood. Here, we develop a simple theoretical approach to explain the origin of selectivity in molecular fluxes through channels. Our method utilizes discrete-state stochastic models that take into account all relevant chemical transitions and can be solved analytically. More specifically, we analyze channels with one and two binding sites employed for separating mixtures of two types of molecules. The effects of the symmetry and the strength of the molecular-pore interactions are examined. It is found that for one-site binding channels, the differences in the strength of interactions for two species drive the separation. At the same time, in more realistic two-site systems, the symmetry of interaction potential becomes also important. The most efficient separation is predicted when the specific binding site is located near the entrance to the nanopore. In addition, the selectivity is higher for large entrance rates into the channel. It is also found that the molecular transport is more selective for repulsive interactions than for attractive interactions. The physical-chemical origin of the observed phenomena is discussed

Optimal Channel Selection Based on Online Decision and Offline Learning in Multichannel Wireless Sensor Networks

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Mu Qiao

2017-01-01

Full Text Available We propose a channel selection strategy with hybrid architecture, which combines the centralized method and the distributed method to alleviate the overhead of access point and at the same time provide more flexibility in network deployment. By this architecture, we make use of game theory and reinforcement learning to fulfill the optimal channel selection under different communication scenarios. Particularly, when the network can satisfy the requirements of energy and computational costs, the online decision algorithm based on noncooperative game can help each individual sensor node immediately select the optimal channel. Alternatively, when the network cannot satisfy the requirements of energy and computational costs, the offline learning algorithm based on reinforcement learning can help each individual sensor node to learn from its experience and iteratively adjust its behavior toward the expected target. Extensive simulation results validate the effectiveness of our proposal and also prove that higher system throughput can be achieved by our channel selection strategy over the conventional off-policy channel selection approaches.

Develop A Framework for Selection of Intermediary in Marketing Channel

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Hamid Reza Irani

2011-03-01

Full Text Available This study seeks to examine how a company can select the best intermediary for itsMarketing channels with minimum of criteria and time. A theoretical framework is proposed basedon the most important tasks of intermediary and the criteria to measure them. There are four basictasks and thirty criteria in three independent levels. Subsequently, an exploratory case study inIranian Food industry is described to illustrate the value of the framework. It is possible to apply thetheoretical framework to select the intermediary for any industry or country. However, there mightbe possible location-specific or industry-specific limitations. Moreover, the framework has provedto be useful in improving the selection of the intermediary in marketing channel. This is a notableand promising side-effect of the exploratory study, at least from a managerial point of view.

Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels.

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Radhakrishnan Gnanasambandam

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

The transport kinetics and selectivity of HpUreI, the urea channel from Helicobacter pylori†

Science.gov (United States)

Gray, Lawrence R; Gu, Sean X; Quick, Matthias; Khademi, Shahram

2017-01-01

Helicobacter pylori’s unique ability to colonize and survive in the acidic environment of the stomach is critically dependent on uptake of urea through the urea channel, HpUreI. Hence, HpUreI may represent a promising target for the development of specific drugs against this human pathogen. To obtain insight into the structure/function relationship of this channel, we have developed conditions for the high-yield expression and purification of stable recombinant HpUreI that allowed its detailed kinetic characterization in solubilized form and reconstituted into liposomes. Detergent-solubilized HpUreI forms homo-trimer, as determined by chemical cross-linking. Urea dissociation kinetics of purified HpUreI were determined by means of the scintillation proximity assay (SPA), whereas urea efflux was measured in HpUreI-containing proteoliposomes using stopped-flow spectrometry to determine the kinetics and selectivity of the urea channel. The kinetic analyses revealed that urea conduction in HpUreI is pH sensitive and saturable with a half-saturation concentration (or K0.5) of ~163 mM. Binding of urea by HpUreI was increased at lower pH; however, the apparent affinity of urea binding (~150 mM) was not significantly pH dependent. The solute selectivity analysis indicated that HpUreI is highly selective for urea and hydroxyurea. Removing either amino group of urea molecules diminishes their permeability through HpUreI. Similar to urea conduction, water diffusion through HpUreI is pH-dependent with low water permeability at neutral pH. PMID:21877689

Overlay Cognitive Radios With Channel-Aware Adaptive Link Selection and Buffer-Aided Relaying

KAUST Repository

Shaqfeh, Mohammad

2015-08-01

The aim of this work is to maximize the long-term average achievable rate region of a primary and a secondary source-destination pairs operating in an overlay setup over block-fading channels. To achieve this objective, we propose an opportunistic strategy to grant channel access to the primary and secondary sources based on the channel conditions in order to exploit the available multiple-link diversity gains in the system. The secondary source has causal knowledge of the primary messages and it acts as a relay of the primary source in return for getting access to the channel. To maximize the gains of relaying, the relay and destination are equipped with buffers to enable the use of channel-aware adaptive link selection. We propose and optimize different link selection policies and characterize their expected achievable rates. Also, we provide several numerical results to demonstrate the evident mutual benefits of buffer-aided cooperation and adaptive link selection to the primary and the secondary source-destination pairs. © 1972-2012 IEEE.

Overlay Cognitive Radios With Channel-Aware Adaptive Link Selection and Buffer-Aided Relaying

KAUST Repository

Shaqfeh, Mohammad; Zafar, Ammar; Alnuweiri, Hussein; Alouini, Mohamed-Slim

2015-01-01

The aim of this work is to maximize the long-term average achievable rate region of a primary and a secondary source-destination pairs operating in an overlay setup over block-fading channels. To achieve this objective, we propose an opportunistic strategy to grant channel access to the primary and secondary sources based on the channel conditions in order to exploit the available multiple-link diversity gains in the system. The secondary source has causal knowledge of the primary messages and it acts as a relay of the primary source in return for getting access to the channel. To maximize the gains of relaying, the relay and destination are equipped with buffers to enable the use of channel-aware adaptive link selection. We propose and optimize different link selection policies and characterize their expected achievable rates. Also, we provide several numerical results to demonstrate the evident mutual benefits of buffer-aided cooperation and adaptive link selection to the primary and the secondary source-destination pairs. © 1972-2012 IEEE.

Bandwidth efficient channel estimation method for airborne hyperspectral data transmission in sparse doubly selective communication channels

Science.gov (United States)

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.

The role of solvation in the binding selectivity of the L-type calcium channel.

Science.gov (United States)

Boda, Dezső; Henderson, Douglas; Gillespie, Dirk

2013-08-07

We present grand canonical Monte Carlo simulation results for a reduced model of the L-type calcium channel. While charged residues of the protein amino acids in the selectivity filter are treated explicitly, most of the degrees of freedom (including the rest of the protein and the solvent) are represented by their dielectric response, i.e., dielectric continua. The new aspect of this paper is that the dielectric coefficient in the channel is different from that in the baths. The ions entering the channel, thus, cross a dielectric boundary at the entrance of the channel. Simulating this case has been made possible by our recent methodological development [D. Boda, D. Henderson, B. Eisenberg, and D. Gillespie, J. Chem. Phys. 135, 064105 (2011)]. Our main focus is on the effect of solvation energy (represented by the Born energy) on monovalent vs. divalent ion selectivity in the channel. We find no significant change in selectivity by changing the dielectric coefficient in the channel because the larger solvation penalty is counterbalanced by the enhanced Coulomb attraction inside the channel as soon as we use the Born radii (fitted to experimental hydration energies) to compute the solvation penalty from the Born equation.

Channel selection in e-commerce age: A strategic analysis of co-op advertising models

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Yongmei Liu

2013-03-01

Full Text Available Purpose: The purpose of this paper is to develop and compare two co-op advertising models: advertising model under traditional channel and co-op advertising model under dual channel, to select optimal channel structure to sell products for manufacturer and to derive optimal co-op advertising strategies for the manufacturer and the retailer.Design/methodology/approach: Stackelberg game theoretical is used to develop two co-op advertising models: co-op advertising model under traditional channel and co-op advertising model under dual channel. Then we compare the two models to select optimal channel structure to sell products for manufacturer and to derive optimal co-op advertising strategies for the manufacturer and the retailer. Furthermore, we analyze the impact of product web-fit on these optimal strategies and illustrate by some numeral examples. Based on our results, we provide some significant theories and managerial insights, and derive some probable paths of future research.Findings: We provide a framework for researching optimal co-op advertising strategies in a two-level supply chain considering different marketing channel structures. First, we discuss the traditional channel co-op adverting model and the dual channel co-op advertising model based on Stackelberg game theoretical, and we derive optimal co-op advertising strategies. Next, comparisons of these two channel structures are discussed and we find that the manufacturer always benefits from dual channel. But the retailer not always benefits from dual channel structure, and dual channel structure is better than retail channel with certain conditions. Also, the optimal co-op advertising strategies for the manufacturer and the retailer are obtained.Research limitations/implications: First, we focus on the aforementioned two channel structures; a further comparison with other channel structures can be investigated. Second, we ignore some factors that influence the demand of product

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

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Leandro Zúñiga

2011-01-01

Full Text Available 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 K(2P) potassium channel by an electrostatic effect of basic sensor residues on the selectivity filter.

Science.gov (United States)

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.

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

Science.gov (United States)

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

Optimized Irregular Low-Density Parity-Check Codes for Multicarrier Modulations over Frequency-Selective Channels

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Valérian Mannoni

2004-09-01

Full Text Available This paper deals with optimized channel coding for OFDM transmissions (COFDM over frequency-selective channels using irregular low-density parity-check (LDPC codes. Firstly, we introduce a new characterization of the LDPC code irregularity called “irregularity profile.” Then, using this parameterization, we derive a new criterion based on the minimization of the transmission bit error probability to design an irregular LDPC code suited to the frequency selectivity of the channel. The optimization of this criterion is done using the Gaussian approximation technique. Simulations illustrate the good performance of our approach for different transmission channels.

Relay Selections for Security and Reliability in Mobile Communication Networks over Nakagami-m Fading Channels

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Hongji Huang

2017-01-01

Full Text Available This paper studies the relay selection schemes in mobile communication system over Nakagami-m channel. To make efficient use of licensed spectrum, both single relay selection (SRS scheme and multirelays selection (MRS scheme over the Nakagami-m channel are proposed. Also, the intercept probability (IP and outage probability (OP of the proposed SRS and MRS for the communication links depending on realistic spectrum sensing are derived. Furthermore, this paper assesses the manifestation of conventional direct transmission scheme to compare with the proposed SRS and MRS ones based on the Nakagami-m channel, and the security-reliability trade-off (SRT performance of the proposed schemes and the conventional schemes is well investigated. Additionally, the SRT of the proposed SRS and MRS schemes is demonstrated better than that of direct transmission scheme over the Nakagami-m channel, which can protect the communication transmissions against eavesdropping attacks. Additionally, simulation results show that our proposed relay selection schemes achieve better SRT performance than that of conventional direct transmission over the Nakagami-m channel.

Partial relay selection based on shadowing side information over generalized composite fading channels

KAUST Repository

Yilmaz, Ferkan

2011-11-01

In this paper, in contrast to the relay selection protocols available in the literature, we propose a partial relay selection protocol utilizing only the shadowing side information of the relays instead of their full channel side information in order to select a relay in a dual-hop relaying system through the available limited feedback channels and power budget. We then presented an exact unified performance expression combining the average bit error probability, ergodic capacity, and moments-generating function of the proposed partial relay selection over generalized fading channels. Referring to the unified performance expression introduced in [1], we explicitly offer a generic unified performance expression that can be easily calculated and that is applicable to a wide variety of fading scenarios. Finally, as an illustration of the mathematical formalism, some numerical and simulation results are generated for an extended generalized-K fading environment, and these numerical and simulation results are shown to be in perfect agreement. © 2011 IEEE.

Channel-Selectable Optical Link Based on a Silicon Microring for on-Chip Interconnection

International Nuclear Information System (INIS)

Qiu Chen; Hu Ting; Wang Wan-Jun; Yu Ping; Jiang Xiao-Qing; Yang Jian-Yi

2012-01-01

A channel-selectable optical link based on a silicon microring resonator is proposed and demonstrated. This optical link consists of the wavelength-tunable microring modulators and the filters, defined on a silicon-on-insulator (SOI) platform. With a p—i—n junction embedded in the microring modulator, light at the resonant wavelength of the ring resonator is modulated. The 2 nd -order microring add-drop filter routes the modulated light. The channel selectivity is demonstrated by heating the microrings. With a thermal tuning efficiency of 5.9 mW/nm, the filter drop port response was successfully tuned with 0.8 nm channel spacing. We also show that modulation can be achieved in these channels. This device aims to offer flexibility and increase the bandwidth usage efficiency in optical interconnection

Simultaneous Channel and Feature Selection of Fused EEG Features Based on Sparse Group Lasso

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Jin-Jia Wang

2015-01-01

Full Text Available Feature extraction and classification of EEG signals are core parts of brain computer interfaces (BCIs. Due to the high dimension of the EEG feature vector, an effective feature selection algorithm has become an integral part of research studies. In this paper, we present a new method based on a wrapped Sparse Group Lasso for channel and feature selection of fused EEG signals. The high-dimensional fused features are firstly obtained, which include the power spectrum, time-domain statistics, AR model, and the wavelet coefficient features extracted from the preprocessed EEG signals. The wrapped channel and feature selection method is then applied, which uses the logistical regression model with Sparse Group Lasso penalized function. The model is fitted on the training data, and parameter estimation is obtained by modified blockwise coordinate descent and coordinate gradient descent method. The best parameters and feature subset are selected by using a 10-fold cross-validation. Finally, the test data is classified using the trained model. Compared with existing channel and feature selection methods, results show that the proposed method is more suitable, more stable, and faster for high-dimensional feature fusion. It can simultaneously achieve channel and feature selection with a lower error rate. The test accuracy on the data used from international BCI Competition IV reached 84.72%.

MONETARY TRANSMISSION CHANNELS IN FLEXIBLE MONETARY AND EXCHANGE RATE REGIMES: THE CASE OF SELECTED TRANSITION ECONOMIES

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Kosta JOSIFIDIS

2010-01-01

Full Text Available The paper explores selected monetary transmission channels in the case of transition economies. Namely, an exchange rate channel, an interest rate channel, direct and indirect influence to an exchange rate, are focused. Specific (former transition economies are differentiated according the combination of implemented monetary and exchange rate regimes: exchange rate as a nominal anchor and rigid exchange rate regimes, exchange rate as a nominal anchor and intermediate exchange rate regimes, and implicit/explicit inflation targeting monetary regime and floating (managed/free exchange rate regime. The monetary transmission is tracked during different phases in a transition process towards the EU and compared between different nominal anchors and exchange rate regimes. In order to track the influence of a monetary policy instruments (impulses to different goals of a monetary policy (responses during the period from 6-24 months, we use VAR and VEC models. Monthly frequency of following time series are used in the models: nominal exchange rates, consumer price indexes, foreign exchange reserves, and reference interest rates. The aim of the paper is to point to the distinction between de jure and de facto exchange rate regimes, and to the adequacy of used combination of monetary and exchange rate regimes having in mind revealed features of investigated monetary transmission channels.

OPRA capacity bounds for selection diversity over generalized fading channels

KAUST Repository

Hanif, Muhammad Fainan; Yang, Hongchuan; Alouini, Mohamed-Slim

2014-01-01

, lower and upper bounds on OPRA capacity for selection diversity scheme are presented. These bounds hold for variety of fading channels including log-normal and generalized Gamma distributed models and have very simple analytic expressions for easy

A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

Science.gov (United States)

Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.

2015-01-01

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

Optimal Training for Time-Selective Wireless Fading Channels Using Cutoff Rate

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Tong Lang

2006-01-01

Full Text Available We consider the optimal allocation of resources—power and bandwidth—between training and data transmissions for single-user time-selective Rayleigh flat-fading channels under the cutoff rate criterion. The transmitter exploits statistical channel state information (CSI in the form of the channel Doppler spectrum to embed pilot symbols into the transmission stream. At the receiver, instantaneous, though imperfect, CSI is acquired through minimum mean-square estimation of the channel based on some set of pilot observations. We compute the ergodic cutoff rate for this scenario. Assuming estimator-based interleaving and -PSK inputs, we study two special cases in-depth. First, we derive the optimal resource allocation for the Gauss-Markov correlation model. Next, we validate and refine these insights by studying resource allocation for the Jakes model.

Discovery and characterization of a potent and selective inhibitor of Aedes aegypti inward rectifier potassium channels.

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Rene Raphemot

Full Text Available Vector-borne diseases such as dengue fever and malaria, which are transmitted by infected female mosquitoes, affect nearly half of the world's population. The emergence of insecticide-resistant mosquito populations is reducing the effectiveness of conventional insecticides and threatening current vector control strategies, which has created an urgent need to identify new molecular targets against which novel classes of insecticides can be developed. We previously demonstrated that small molecule inhibitors of mammalian Kir channels represent promising chemicals for new mosquitocide development. In this study, high-throughput screening of approximately 30,000 chemically diverse small-molecules was employed to discover potent and selective inhibitors of Aedes aegypti Kir1 (AeKir1 channels heterologously expressed in HEK293 cells. Of 283 confirmed screening 'hits', the small-molecule inhibitor VU625 was selected for lead optimization and in vivo studies based on its potency and selectivity toward AeKir1, and tractability for medicinal chemistry. In patch clamp electrophysiology experiments of HEK293 cells, VU625 inhibits AeKir1 with an IC50 value of 96.8 nM, making VU625 the most potent inhibitor of AeKir1 described to date. Furthermore, electrophysiology experiments in Xenopus oocytes revealed that VU625 is a weak inhibitor of AeKir2B. Surprisingly, injection of VU625 failed to elicit significant effects on mosquito behavior, urine excretion, or survival. However, when co-injected with probenecid, VU625 inhibited the excretory capacity of mosquitoes and was toxic, suggesting that the compound is a substrate of organic anion and/or ATP-binding cassette (ABC transporters. The dose-toxicity relationship of VU625 (when co-injected with probenecid is biphasic, which is consistent with the molecule inhibiting both AeKir1 and AeKir2B with different potencies. This study demonstrates proof-of-concept that potent and highly selective inhibitors of mosquito

Frequency selective tunable spin wave channeling in the magnonic network

Energy Technology Data Exchange (ETDEWEB)

Sadovnikov, A. V., E-mail: sadovnikovav@gmail.com; Nikitov, S. A. [Laboratory “Metamaterials,” Saratov State University, Saratov 410012 (Russian Federation); Kotel' nikov Institute of Radioengineering and Electronics, Russian Academy of Sciences, Moscow 125009 (Russian Federation); Beginin, E. N.; Odincov, S. A.; Sheshukova, S. E.; Sharaevskii, Yu. P. [Laboratory “Metamaterials,” Saratov State University, Saratov 410012 (Russian Federation); Stognij, A. I. [Scientific-Practical Materials Research Center, National Academy of Sciences of Belarus, 220072 Minsk (Belarus)

2016-04-25

Using the space-resolved Brillouin light scattering spectroscopy, we study the frequency and wavenumber selective spin-wave channeling. We demonstrate the frequency selective collimation of spin-wave in an array of magnonic waveguides, formed between the adjacent magnonic crystals on the surface of yttrium iron garnet film. We show the control over spin-wave propagation length by the orientation of an in-plane bias magnetic field. Fabricated array of magnonic crystal can be used as a magnonic platform for multidirectional frequency selective signal processing applications in magnonic networks.

Selective block of KATP channels: why the anti-diabetic sulphonylureas and rosiglitazone have more in common than we thought

Science.gov (United States)

Dart, Caroline

2012-01-01

Rosiglitazone, the thiazolidinedione class anti-diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP-sensitive potassium (KATP) channels. This seems little cause for excitement given that the closure of pancreatic KATP channels is integral to insulin secretion; and sulphonylureas, which inhibit KATP channels, are widely used to treat type II diabetes. However, rosiglitazone, whose primary targets are nuclear transcription factors that regulate genes involved in lipid metabolism, blocks KATP channels by a novel mechanism different to that of the sulphonylureas and has a worrying preference for blood flow–regulating vascular KATP channels. Identification of a new molecule that modulates KATP channel gating will not only tell us more about how these complex metabolic sensors work but also raises questions as to whether rosiglitazone suppresses the cardiovascular system's ability to cope with metabolic stress – a claim that has dogged the sulphonylureas for many years. LINKED ARTICLE This article is a commentary on Yu et al., pp. 26–36 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01934.x PMID:22506686

Evoked potential correlates of selective attention with multi-channel auditory inputs

Science.gov (United States)

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.

Aluminium and hydrogen ions inhibit a mechanosensory calcium-selective cation channel

Science.gov (United States)

Ding, J. P.; Pickard, B. G.

1993-01-01

The tension-dependent activity of mechanosensory calcium-selective cation channels in excised plasmalemmal patches from onion bulb scale epidermis is modulated by pH in the physiologically meaningful range between 4.5 and 7.2. It is rapidly lowered by lowering pH and rapidly raised by raising pH. Channel activity is effectively inhibited by low levels of aluminium ions and activity can be partially restored by washing for a few minutes. We suggest that under normal conditions the sensitivity of the mechanosensory channels to pH of the wall free space plays important roles in regulation of plant activities such as growth. We further suggest that, when levels of acid and aluminium ions in the soil solution are high, they might inhibit similar sensory channels in cells of the root tip, thus contributing critically to the acid soil syndrome.

Game Theoretical Approaches for Transport-Aware Channel Selection in Cognitive Radio Networks

Directory of Open Access Journals (Sweden)

Chen Shih-Ho

2010-01-01

Full Text Available Effectively sharing channels among secondary users (SUs is one of the greatest challenges in cognitive radio network (CRN. In the past, many studies have proposed channel selection schemes at the physical or the MAC layer that allow SUs swiftly respond to the spectrum states. However, they may not lead to enhance performance due to slow response of the transport layer flow control mechanism. This paper presents a cross-layer design framework called Transport Aware Channel Selection (TACS scheme to optimize the transport throughput based on states, such as RTT and congestion window size, of TCP flow control mechanism. We formulate the TACS problem as two different game theoretic approaches: Selfish Spectrum Sharing Game (SSSG and Cooperative Spectrum Sharing Game (CSSG and present novel distributed heuristic algorithms to optimize TCP throughput. Computer simulations show that SSSG and CSSG could double the SUs throughput of current MAC-based scheme when primary users (PUs use their channel infrequently, and with up to 12% to 100% throughput increase when PUs are more active. The simulation results also illustrated that CSSG performs up to 20% better than SSSG in terms of the throughput.

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

Science.gov (United States)

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.

Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

Science.gov (United States)

Ravens, Ursula

2017-11-01

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K + ) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two-pore domain K + (K2P) channels (tandem of P domains, weak inward-rectifying K + channels (TWIK-1), TWIK-related acid-sensitive K + channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

High spin spectroscopy near the N=Z line: Channel selection and excitation energy systematics

Energy Technology Data Exchange (ETDEWEB)

Svensson, C.E.; Cameron, J.A.; Flibotte, S. [McMaster Univ., Ontario (Canada)] [and others

1996-12-31

The total {gamma}-ray and charged-particle energies emitted in fusion-evaporation reactions leading to N=Z compound systems in the A = 50-70 mass region have been measured with the 8{pi} {gamma}-ray spectrometer and the miniball charged-particle detector array. A new method of channel selection has been developed which combines particle identification with these total energy measurements and greatly improves upon the selectivity possible with particle detection alone. In addition, the event by event measurement of total {gamma}-ray energies using the BGO ball of the 8{pi} spectrometer has allowed a determination of excitation energies following particle evaporation for a large number of channels in several different reactions. The new channel selection procedure and excitation energy systematics are illustrated with data from the reaction of {sup 24}Mg on {sup 40}Ca at E{sub lab} = 80MeV.

Selecting participants for listening tests of multi-channel reproduced sound

DEFF Research Database (Denmark)

Wickelmaier, Florian; Choisel, Sylvain

2005-01-01

A selection procedure was devised in order to select listeners for experiments in which their main task will be to judge multi-channel reproduced sound. 91 participants filled in a web-based questionnaire. 78 of them took part in an assessment of their hearing thresholds, their spatial hearing......, and their verbal production abilities. The listeners displayed large individual differences in their performance. 40 subjects were selected based on the test results. The self-assessed listening habits and experience in the web questionnaire could not predict the results of the selection procedure. Further......, the hearing thresholds did not correlate with the spatial-hearing test. This leads to the conclusion that task-specific performance tests might be the preferable means of selecting a listening panel....

Asymptotic analysis for Nakagami-m fading channels with relay selection

KAUST Repository

Zhong, Caijun

2011-06-01

In this paper, we analyze the asymptotic outage probability performance of both decode-and-forward (DF) and amplify-and-forward (AF) relaying systems using partial relay selection and the "best" relay selection schemes for Nakagami-m fading channels. We derive their respective outage probability expressions in the asymptotic high signal-to-noise ratio (SNR) regime, from which the diversity order and coding gain are analyzed. In addition, we investigate the impact of power allocation between the source and relay terminals and derive the diversity-multiplexing tradeoff (DMT) for these relay selection systems. The theoretical findings suggest that partial relay selection can improve the diversity of the system and can achieve the same DMT as the "best" relay selection scheme under certain conditions. © 2011 IEEE.

New selection criteria for channel refueling of a Candu-6 reactor: introduction to floppy rules

International Nuclear Information System (INIS)

Brissette, D.

2001-01-01

A revised set of rules is in use at Gentilly-2 NGS for the selection of channels for refuelling. Traditional hard channel rejection rules (of go/no-go type) have been replaced by a more efficient set of soft evaluation rules based on concepts borrowed to the Fuzzy Logic. New evaluation rules, labelled as 'Floppy Rules', enable to assess and rate the channel suitability for refuelling by using a smooth and natural continuum of values qualifying excellent, good, fair and poor choices. Global channel suitability for refuelling is measured by combining separate ratings obtained from individual evaluation rules. Each evaluation rule is based on a specific control parameter related to local or lumped core properties. Two new software codes (NEWRULES and REFUEL) designed around the concept of Floppy Rules enable to perform a very efficient selection of optimized channel refuelling sequences either in manual and automatic mode. (author)

Transmit selection algorithms for imperfect threshold-based receive MRC in the presence of co-channel interference

KAUST Repository

Radaydeh, Redha Mahmoud Mesleh

2010-01-01

The performance of transmit antenna selection for threshold-based maximal ratio combining (MRC) diversity receivers in the presence of multiple co-channel interfering signals is studied. The impact of imperfect channel estimation of desired user signals is considered, and the effect of phase and time misalignments between desired and undesired signals is incorporated in the analysis. Precise formulation for Nakagami-m faded interfering signals is presented. The analysis is applicable for arbitrary transmit antenna selection, which is based on the receiver combined signal-to-noise ratios (SNRs) or combined signal-to-interference-plus-noise ratios (SINRs) for different transmit channels. New expressions for the distribution of combined SINR and outage probability performance are derived considering SNR-based as well as SINR-based selection algorithms. The results can be used to study the performance of different system architectures under various channel conditions when the implementation complexity is of interest. ©2010 IEEE.

Distributive estimation of frequency selective channels for massive MIMO systems

KAUST Repository

Zaib, Alam

2015-12-28

We consider frequency selective channel estimation in the uplink of massive MIMO-OFDM systems, where our major concern is complexity. A low complexity distributed LMMSE algorithm is proposed that attains near optimal channel impulse response (CIR) estimates from noisy observations at receive antenna array. In proposed method, every antenna estimates the CIRs of its neighborhood followed by recursive sharing of estimates with immediate neighbors. At each step, every antenna calculates the weighted average of shared estimates which converges to near optimal LMMSE solution. The simulation results validate the near optimal performance of proposed algorithm in terms of mean square error (MSE). © 2015 EURASIP.

Pharmacological targeting of native CatSper channels reveals a required role in maintenance of sperm hyperactivation.

Directory of Open Access Journals (Sweden)

Anne E Carlson

2009-08-01

Full Text Available The four sperm-specific CatSper ion channel proteins are required for hyperactivated motility and male fertility, and for Ca(2+ entry evoked by alkaline depolarization. In the absence of external Ca(2+, Na(+ carries current through CatSper channels in voltage-clamped sperm. Here we show that CatSper channel activity can be monitored optically with the [Na(+](i-reporting probe SBFI in populations of intact sperm. Removal of external Ca(2+ increases SBFI signals in wild-type but not CatSper2-null sperm. The rate of the indicated rise of [Na(+](i is greater for sperm alkalinized with NH(4Cl than for sperm acidified with propionic acid, reflecting the alkaline-promoted signature property of CatSper currents. In contrast, the [Na(+](i rise is slowed by candidate CatSper blocker HC-056456 (IC(50 approximately 3 microM. HC-056456 similarly slows the rise of [Ca(2+](i that is evoked by alkaline depolarization and reported by fura-2. HC-056456 also selectively and reversibly decreased CatSper currents recorded from patch-clamped sperm. HC-056456 does not prevent activation of motility by HCO(3 (- but does prevent the development of hyperactivated motility by capacitating incubations, thus producing a phenocopy of the CatSper-null sperm. When applied to hyperactivated sperm, HC-056456 causes a rapid, reversible loss of flagellar waveform asymmetry, similar to the loss that occurs when Ca(2+ entry through the CatSper channel is terminated by removal of external Ca(2+. Thus, open CatSper channels and entry of external Ca(2+ through them sustains hyperactivated motility. These results indicate that pharmacological targeting of the CatSper channel may impose a selective late-stage block to fertility, and that high-throughput screening with an optical reporter of CatSper channel activity may identify additional selective blockers with potential for male-directed contraception.

Joint duplex mode selection, channel allocation, and power control for full-duplex cognitive femtocell networks

Directory of Open Access Journals (Sweden)

Mingjie Feng

2015-02-01

Full Text Available In this paper, we aim to maximize the sum rate of a full-duplex cognitive femtocell network (FDCFN as well as guaranteeing the quality of service (QoS of users in the form of a required signal to interference plus noise ratios (SINR. We first consider the case of a pair of channels, and develop optimum-achieving power control solutions. Then, for the case of multiple channels, we formulate joint duplex model selection, power control, and channel allocation as a mixed integer nonlinear problem (MINLP, and propose an iterative framework to solve it. The proposed iterative framework consists of a duplex mode selection scheme, a near-optimal distributed power control algorithm, and a greedy channel allocation algorithm. We prove the convergence of the proposed iterative framework as well as a lower bound for the greedy channel allocation algorithm. Numerical results show that the proposed schemes effectively improve the sum rate of FDCFNs.

Divalent Metal Ion Transport across Large Biological Ion Channels and Their Effect on Conductance and Selectivity

Directory of Open Access Journals (Sweden)

Elena García-Giménez

2012-01-01

Full Text Available Electrophysiological characterization of large protein channels, usually displaying multi-ionic transport and weak ion selectivity, is commonly performed at physiological conditions (moderate gradients of KCl solutions at decimolar concentrations buffered at neutral pH. We extend here the characterization of the OmpF porin, a wide channel of the outer membrane of E. coli, by studying the effect of salts of divalent cations on the transport properties of the channel. The regulation of divalent cations concentration is essential in cell metabolism and understanding their effects is of key importance, not only in the channels specifically designed to control their passage but also in other multiionic channels. In particular, in porin channels like OmpF, divalent cations modulate the efficiency of molecules having antimicrobial activity. Taking advantage of the fact that the OmpF channel atomic structure has been resolved both in water and in MgCl2 aqueous solutions, we analyze the single channel conductance and the channel selectivity inversion aiming to separate the role of the electrolyte itself, and the counterion accumulation induced by the protein channel charges and other factors (binding, steric effects, etc. that being of minor importance in salts of monovalent cations become crucial in the case of divalent cations.

Use of nonelectrolytes reveals the channel size and oligomeric constitution of the Borrelia burgdorferi P66 porin.

Directory of Open Access Journals (Sweden)

Iván Bárcena-Uribarri

Full Text Available In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than 'normal' Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be ≤1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66-induced membrane conductance could be blocked by 80-90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex.

Optimal complex exponentials BEM and channel estimation in doubly selective channel

International Nuclear Information System (INIS)

Song, Lijun; Lei, Xia; Yu, Feng; Jin, Maozhu

2016-01-01

Over doubly selective channel, the optimal complex exponentials BEM (CE-BEM) is required to characterize the transmission in transform domain in order to reducing the huge number of the estimated parameters during directly estimating the impulse response in time domain. This paper proposed an improved CE-BEM to alleviating the high frequency sampling error caused by conventional CE-BEM. On the one hand, exploiting the improved CE-BEM, we achieve the sampling point is in the Doppler spread spectrum and the maximum sampling frequency is equal to the maximum Doppler shift. On the other hand we optimize the function and dimension of basis in CE-BEM respectively ,and obtain the closed solution of the EM based channel estimation differential operator by exploiting the above optimal BEM. Finally, the numerical results and theoretic analysis show that the dimension of basis is mainly depend on the maximum Doppler shift and signal-to-noise ratio (SNR), and if fixing the number of the pilot symbol, the dimension of basis is higher, the modeling error is smaller, while the accuracy of the parameter estimation is reduced, which implies that we need to achieve a tradeoff between the modeling error and the accuracy of the parameter estimation and the basis function influences the accuracy of describing the Doppler spread spectrum after identifying the dimension of the basis.

Energy and spectral efficiency analysis for selective ARQ multi-channel systems

KAUST Repository

Shafique, Taniya

2017-07-31

In this paper, we develop selective retransmission schemes for multiple-channel systems. The proposed schemes are selective automatic repeat request with fixed bandwidth (SARQ-FB), selective chase combining with fixed bandwidth (SCC-FB) and selective automatic repeat request with variable bandwidth (SARQ-VB). The main objective of the proposed schemes is to use the available power and bandwidth budget effectively along with the selective retransmission to deliver the required data successfully within a limited number of transmissions. To investigate the performance of each scheme, we first analyze the average spectral and energy efficiency and derive closed form expressions for each scheme. Then, we compare the EE and SE of each scheme through numerical results.

On channel selection and shape co-existence

International Nuclear Information System (INIS)

Dracoulis, G.D.

1993-08-01

Ambivalence with respect to a favoured shape is emerging as a ubiquitous phenomenon in nuclei. Multiple minima in the nuclear potential well occur because of the delicate balance in nuclei between the long and short-range properties of the nuclear force and the contribution specific particle orbitals make in forcing the nucleus to a decision. Exploration of the dependence of the resulting shape co-existence on particle number and orbital is a prominent area of research. Experimental aspects of spectroscopy studies using heavy ion fusion, evaporation reactions and channel selection are discussed, with focus on shape co-existence in the light Os-Pt-Hg-Pb region. 42 refs., 8 figs

Selective and lithography-independent fabrication of 20 nm nano-gap electrodes and nano-channels for nanoelectrofluidics applications

International Nuclear Information System (INIS)

Zhang, J Y; Wang, X F; Wang, X D; Fan, Z C; Li, Y; Ji, An; Yang, F H

2010-01-01

A new method has been developed to selectively fabricate nano-gap electrodes and nano-channels by conventional lithography. Based on a sacrificial spacer process, we have successfully obtained sub-100-nm nano-gap electrodes and nano-channels and further reduced the dimensions to 20 nm by shrinking the sacrificial spacer size. Our method shows good selectivity between nano-gap electrodes and nano-channels due to different sacrificial spacer etch conditions. There is no length limit for the nano-gap electrode and the nano-channel. The method reported in this paper also allows for wafer scale fabrication, high throughput, low cost, and good compatibility with modern semiconductor technology.

Objective ARX Model Order Selection for Multi-Channel Human Operator Identification

NARCIS (Netherlands)

Roggenkämper, N; Pool, D.M.; Drop, F.M.; van Paassen, M.M.; Mulder, M.

2016-01-01

In manual control, the human operator primarily responds to visual inputs but may elect to make use of other available feedback paths such as physical motion, adopting a multi-channel control strategy. Hu- man operator identification procedures generally require a priori selection of the model

Performance analysis of selective cooperation with fixed gain relays in Nakagami-m channels

KAUST Repository

Hussain, Syed Imtiaz; Hasna, Mazen Omar; Alouini, Mohamed-Slim

2012-01-01

Selecting the best relay using the maximum signal to noise ratio (SNR) among all the relays ready to cooperate saves system resources and utilizes the available bandwidth more efficiently compared to the regular all-relay cooperation. In this paper, we analyze the performance of the best relay selection scheme with fixed gain relays operating in Nakagami-. m channels. We first derive the probability density function (PDF) of upper bounded end-to-end SNR of the relay link. Using this PDF, we derive some key performance parameters for the system including average bit error probability and average channel capacity. The analytical results are verified through Monte Carlo simulations. © 2012 Elsevier B.V.

Performance analysis of selective cooperation with fixed gain relays in Nakagami-m channels

KAUST Repository

Hussain, Syed Imtiaz

2012-09-01

Selecting the best relay using the maximum signal to noise ratio (SNR) among all the relays ready to cooperate saves system resources and utilizes the available bandwidth more efficiently compared to the regular all-relay cooperation. In this paper, we analyze the performance of the best relay selection scheme with fixed gain relays operating in Nakagami-. m channels. We first derive the probability density function (PDF) of upper bounded end-to-end SNR of the relay link. Using this PDF, we derive some key performance parameters for the system including average bit error probability and average channel capacity. The analytical results are verified through Monte Carlo simulations. © 2012 Elsevier B.V.

Transmit selection algorithms for imperfect threshold-based receive MRC in the presence of co-channel interference

KAUST Repository

Radaydeh, Redha Mahmoud Mesleh; Alouini, Mohamed-Slim

2010-01-01

The performance of transmit antenna selection for threshold-based maximal ratio combining (MRC) diversity receivers in the presence of multiple co-channel interfering signals is studied. The impact of imperfect channel estimation of desired user

Contribution of two-pore K+ channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes.

Science.gov (United States)

Chai, Sam; Wan, Xiaoping; Nassal, Drew M; Liu, Haiyan; Moravec, Christine S; Ramirez-Navarro, Angelina; Deschênes, Isabelle

2017-06-01

Two-pore K + (K 2p ) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K 2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K 2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and ischemic (iHF) and nonischemic heart failure tissues (niHF). We detected 10 K 2p channels in the heart. Comparing quantitative PCR expression of K 2p channels between human heart tissue and iPSC-CMs revealed K 2p 1.1, K 2p 2.1, K 2p 5.1, and K 2p 17.1 to be higher expressed in cHVT, whereas K 2p 3.1 and K 2p 13.1 were higher in iPSC-CMs. Notably, K 2p 17.1 was significantly lower in niHF tissues compared with cHVT. Action potential recordings in iCells after K 2p small interfering RNA knockdown revealed prolongations in action potential depolarization at 90% repolarization for K 2p 2.1, K 2p 3.1, K 2p 6.1, and K 2p 17.1. Here, we report the expression level of 10 human K 2p channels in iPSC-CMs and how they compared with cHVT. Importantly, our functional electrophysiological data in human iPSC-CMs revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K 2p 17.1 as significantly reduced in niHF tissues and K 2p 4.1 as reduced in niHF compared with iHF. Thus, we advance the notion that K 2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias. NEW & NOTEWORTHY Two-pore K + (K 2p ) channels are traditionally regarded as merely background leak channels in myriad

Performance Analysis of Secrecy Outage Probability for AF-Based Partial Relay Selection with Outdated Channel Estimates

Directory of Open Access Journals (Sweden)

Kyu-Sung Hwang

2017-01-01

Full Text Available We study the secrecy outage probability of the amplify-and-forward (AF relaying protocol, which consists of one source, one destination, multiple relays, and multiple eavesdroppers. In this system, the aim is to transmit the confidential messages from a source to a destination via the selected relay in presence of eavesdroppers. Moreover, partial relay selection scheme is utilized for relay selection based on outdated channel state information where only neighboring channel information (source-relays is available and passive eavesdroppers are considered where a transmitter does not have any knowledge of eavesdroppers’ channels. Specifically, we offer the exact secrecy outage probability of the proposed system in a one-integral form as well as providing the asymptotic secrecy outage probability in a closed-form. Numerical examples are given to verify our provided analytical results for different system conditions.

Sub-micron resolution selected area electron channeling patterns.

Science.gov (United States)

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.

Distributed Antenna Channels with Regenerative Relaying: Relay Selection and Asymptotic Capacity

Directory of Open Access Journals (Sweden)

Aitor del Coso

2007-11-01

Full Text Available Multiple-input-multiple-output (MIMO techniques have been widely proposed as a means to improve capacity and reliability of wireless channels, and have become the most promising technology for next generation networks. However, their practical deployment in current wireless devices is severely affected by antenna correlation, which reduces their impact on performance. One approach to solve this limitation is relaying diversity. In relay channels, a set of N wireless nodes aids a source-destination communication by relaying the source data, thus creating a distributed antenna array with uncorrelated path gains. In this paper, we study this multiple relay channel (MRC following a decode-and-forward (D&F strategy (i.e., regenerative forwarding, and derive its achievable rate under AWGN. A half-duplex constraint on relays is assumed, as well as distributed channel knowledge at both transmitter and receiver sides of the communication. For this channel, we obtain the optimum relay selection algorithm and the optimum power allocation within the network so that the transmission rate is maximized. Likewise, we bound the ergodic performance of the achievable rate and derive its asymptotic behavior in the number of relays. Results show that the achievable rate of regenerative MRC grows as the logarithm of the Lambert W function of the total number of relays, that is, 𝒞=log⁡2(W0(N. Therefore, D&F relaying, cannot achieve the capacity of actual MISO channels.

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Science.gov (United States)

Kobayashi, Toru; Washiyama, Kazuo; Ikeda, Kazutaka

2010-01-01

Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attention-deficit/hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified. G-protein-activated inwardly rectifying K+ (GIRK or Kir3) channels have an important function in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to be a potential treatment for several neuropsychiatric disorders and cardiac arrhythmias. In this study, we investigated the effects of atomoxetine and reboxetine on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, extracellular application of atomoxetine or reboxetine reversibly reduced GIRK currents. The inhibitory effects were concentration-dependent, but voltage-independent, and time-independent during each voltage pulse. However, Kir1.1 and Kir2.1 channels were insensitive to atomoxetine and reboxetine. Atomoxetine and reboxetine also inhibited GIRK currents induced by activation of cloned A1 adenosine receptors or by intracellularly applied GTPγS, a nonhydrolyzable GTP analogue. Furthermore, the GIRK currents induced by ethanol were concentration-dependently inhibited by extracellularly applied atomoxetine but not by intracellularly applied atomoxetine. The present results suggest that atomoxetine and reboxetine inhibit brain- and cardiac-type GIRK channels, revealing a novel characteristic of clinically used NRIs. GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function. PMID:20393461

Outage performance of Decode-and-Forward partial selection in Nakagami-m fading channels

KAUST Repository

Benjillali, Mustapha

2010-01-01

In this paper, we investigate the outage performance of Decode-and-Forward with partial selection relaying in dualhop cooperative Nakagami-m fading links. The source, based on the unique knowledge of local first hop channel state information, selects the best relay to increase the chances of successful decoding and hence the possibility of cooperation when the direct link is also available. After deriving the exact distribution of the sum of two gamma variates with the same shape parameter, the outage probability of the system-with and without the direct link-is obtained in closed-form. We also derive the ε-outage capacity in different particular cases, and the obtained results- when the channel model is reduced to a Rayleigh fading-are either new or correspond to those previously obtained in other works. Simulation results confirm the accuracy of our analysis for a large selection of system and fading parameters. © 2009 IEEE.

Transmit selection for imperfect threshold-based receive MRC in Rayleigh fading channels

KAUST Repository

Radaydeh, Redha Mahmoud Mesleh

2010-01-01

The performance of multiple-antenna diversity systems in which the receiver combines signal replicas per thresholdbased maximal ratio combining (MRC) and the transmitter uses only a single antenna according to receive combined signal strength is studied. The impact of imperfect channel estimation is considered when the received signal replicas undergo independent and flat multipath fading. The analysis is applicable for arbitrary transmit antenna selection when the multiple-antenna channels experience identically distributed and non-identically distributed Rayleigh fading conditions. New closed-form expressions for the combined SNR statistics and some performance measures are presented. The system models adopted herein and the presented analytical results can be used to study the performance of different system architectures under various channel conditions when the implementation complexity is of interest. © 2009 IEEE.

Channel Selection Policy in Multi-SU and Multi-PU Cognitive Radio Networks with Energy Harvesting for Internet of Everything

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Feng Hu

2016-01-01

Full Text Available Cognitive radio, which will become a fundamental part of the Internet of Everything (IoE, has been identified as a promising solution for the spectrum scarcity. In a multi-SU and multi-PU cognitive radio network, selecting channels is a fundamental problem due to the channel competition among secondary users (SUs and packet collision between SUs and primary users (PUs. In this paper, we adopt cooperative sensing method to avoid the packet collision between SUs and PUs and focus on how to collect the spectrum sensing data of SUs for cooperative sensing. In order to reduce the channel competition among SUs, we first consider the hybrid transmission model for single SU where a SU can opportunistically access both idle channels operating either the Overlay or the Underlay model and the busy channels by using the energy harvesting technology. Then we propose a competitive set based channel selection policy for multi-SU where all SUs competing for data transmission or energy harvesting in the same channel will form a competitive set. Extensive simulations show that the proposed cooperative sensing method and the channel selection policy outperform previous solutions in terms of false alarm, average throughput, average waiting time, and energy harvesting efficiency of SUs.

User Adapted Motor-Imaginary Brain-Computer Interface by means of EEG Channel Selection Based on Estimation of Distributed Algorithms

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Aitzol Astigarraga

2016-01-01

Full Text Available Brain-Computer Interfaces (BCIs have become a research field with interesting applications, and it can be inferred from published papers that different persons activate different parts of the brain to perform the same action. This paper presents a personalized interface design method, for electroencephalogram- (EEG- based BCIs, based on channel selection. We describe a novel two-step method in which firstly a computationally inexpensive greedy algorithm finds an adequate search range; and, then, an Estimation of Distribution Algorithm (EDA is applied in the reduced range to obtain the optimal channel subset. The use of the EDA allows us to select the most interacting channels subset, removing the irrelevant and noisy ones, thus selecting the most discriminative subset of channels for each user improving accuracy. The method is tested on the IIIa dataset from the BCI competition III. Experimental results show that the resulting channel subset is consistent with motor-imaginary-related neurophysiological principles and, on the other hand, optimizes performance reducing the number of channels.

Mapping of Residues Forming the Voltage Sensor of the Voltage-Dependent Anion-Selective Channel

Science.gov (United States)

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.

Anomalously-dense firn in an ice-shelf channel revealed by wide-angle radar

Science.gov (United States)

Drews, R.; Brown, J.; Matsuoka, K.; Witrant, E.; Philippe, M.; Hubbard, B.; Pattyn, F.

2015-10-01

The thickness of ice shelves, a basic parameter for mass balance estimates, is typically inferred using hydrostatic equilibrium for which knowledge of the depth-averaged density is essential. The densification from snow to ice depends on a number of local factors (e.g. temperature and surface mass balance) causing spatial and temporal variations in density-depth profiles. However, direct measurements of firn density are sparse, requiring substantial logistical effort. Here, we infer density from radio-wave propagation speed using ground-based wide-angle radar datasets (10 MHz) collected at five sites on Roi Baudouin Ice Shelf (RBIS), Dronning Maud Land, Antarctica. Using a novel algorithm including traveltime inversion and raytracing with a prescribed shape of the depth-density relationship, we show that the depth to internal reflectors, the local ice thickness and depth-averaged densities can reliably be reconstructed. For the particular case of an ice-shelf channel, where ice thickness and surface slope change substantially over a few kilometers, the radar data suggests that firn inside the channel is about 5 % denser than outside the channel. Although this density difference is at the detection limit of the radar, it is consistent with a similar density anomaly reconstructed from optical televiewing, which reveals 10 % denser firn inside compared to outside the channel. The denser firn in the ice-shelf channel should be accounted for when using the hydrostatic ice thickness for determining basal melt rates. The radar method presented here is robust and can easily be adapted to different radar frequencies and data-acquisition geometries.

MONETARY TRANSMISSION CHANNELS IN FLEXIBLE MONETARY AND EXCHANGE RATE REGIMES: THE CASE OF SELECTED TRANSITION ECONOMIES

OpenAIRE

JOSIFIDIS, Kosta; PUCAR, Emilija Beker; SUPIĆ, Novica

2010-01-01

The paper explores selected monetary transmission channels in the case of transition economies. Namely, an exchange rate channel, an interest rate channel, direct and indirect influence to an exchange rate, are focused. Specific (former) transition economies are differentiated according the combination of implemented monetary and exchange rate regimes: exchange rate as a nominal anchor and rigid exchange rate regimes, exchange rate as a nominal anchor and intermediate exchange rate regimes, a...

Adaptive Modulation with Best User Selection over Non-Identical Nakagami Fading Channels

KAUST Repository

Rao, Anlei

2012-09-08

In this paper, we analyze the performance of adaptive modulation with single-cell multiuser scheduling over independent but not identical distributed (i.n.i.d.) Nakagami fading channels. Closed-form expressions are derived for the average channel capacity, spectral efficiency, and bit-error-rate (BER) for both constant-power variable-rate and variable-power variable-rate uncoded M-ary quadrature amplitude modulation (M-QAM) schemes. We also study the impact of time delay on the average BER of adaptive M-QAM. Selected numerical results show that the multiuser diversity brings a considerably better performance even over i.n.i.d. fading environments.

A selectivity filter at the intracellular end of the acid-sensing ion channel pore

DEFF Research Database (Denmark)

Lynagh, Timothy; Flood, Emelie; Boiteux, Céline

2017-01-01

Increased extracellular proton concentrations during neurotransmission are converted to excitatory sodium influx by acid-sensing ion channels (ASICs). 10-fold sodium/potassium selectivity in ASICs has long been attributed to a central constriction in the channel pore, but experimental verificatio...... at the "GAS belt" in the central constriction. Instead, we identified a band of glutamate and aspartate side chains at the lower end of the pore that enables preferential sodium conduction....

Adaptive Equalizer Using Selective Partial Update Algorithm and Selective Regressor Affine Projection Algorithm over Shallow Water Acoustic Channels

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Masoumeh Soflaei

2014-01-01

Full Text Available One of the most important problems of reliable communications in shallow water channels is intersymbol interference (ISI which is due to scattering from surface and reflecting from bottom. Using adaptive equalizers in receiver is one of the best suggested ways for overcoming this problem. In this paper, we apply the family of selective regressor affine projection algorithms (SR-APA and the family of selective partial update APA (SPU-APA which have low computational complexity that is one of the important factors that influences adaptive equalizer performance. We apply experimental data from Strait of Hormuz for examining the efficiency of the proposed methods over shallow water channel. We observe that the values of the steady-state mean square error (MSE of SR-APA and SPU-APA decrease by 5.8 (dB and 5.5 (dB, respectively, in comparison with least mean square (LMS algorithm. Also the families of SPU-APA and SR-APA have better convergence speed than LMS type algorithm.

Low-Complexity Iterative Receiver for Space-Time Coded Signals over Frequency Selective Channels

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Mohamed Siala

2002-05-01

Full Text Available We propose a low-complexity turbo-detector scheme for frequency selective multiple-input multiple-output channels. The detection part of the receiver is based on a List-type MAP equalizer which is a state-reduction algorithm of the MAP algorithm using per-survivor technique. This alternative achieves a good tradeoff between performance and complexity provided a small amount of the channel is neglected. In order to induce the good performance of this equalizer, we propose to use a whitened matched filter (WMF which leads to a white-noise “minimum phase” channel model. Simulation results show that the use of the WMF yields significant improvement, particularly over severe channels. Thanks to the iterative turbo processing (detection and decoding are iterated several times, the performance loss due to the use of the suboptimum List-type equalizer is recovered.

Joint beam design and user selection over non-binary coded MIMO interference channel

Science.gov (United States)

Li, Haitao; Yuan, Haiying

2013-03-01

In this paper, we discuss the problem of sum rate improvement for coded MIMO interference system, and propose joint beam design and user selection over interference channel. Firstly, we have formulated non-binary LDPC coded MIMO interference networks model. Then, the least square beam design for MIMO interference system is derived, and the low complexity user selection is presented. Simulation results confirm that the sum rate can be improved by the joint user selection and beam design comparing with single interference aligning beamformer.

Performance analysis of best relay selection scheme for amplify-and-forward cooperative networks in identical Nakagami-m channels

KAUST Repository

Hussain, Syed Imtiaz

2010-06-01

In cooperative communication networks, the use of multiple relays between the source and the destination was proposed to increase the diversity gain. Since the source and all the relays must transmit on orthogonal channels, multiple relay cooperation is considered inefficient in terms of channel resources and bandwidth utilization. To overcome this problem, the concept of best relay selection was recently proposed. In this paper, we analyze the performance of the best relay selection scheme for a cooperative network with multiple relays operating in amplify-and-forward (AF) mode over identical Nakagami-m channels using exact source-relay-destination signal to noise ratio (SNR) expression. We derive accurate closed form expressions for various system parameters including probability density function (pdf) of end-to-end SNR, average output SNR, average probability of bit error and average channel capacity. T he analytical results are verified through extensive simulations. It is shown that the best relay selection scheme performs better than the regular all relay cooperation.

Crystal structure of the epithelial calcium channel TRPV6.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

Science.gov (United States)

Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

2015-09-15

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

Evaluation and selection of hot channel (peaking) factors for research reactor applications

International Nuclear Information System (INIS)

Woodruff, W.L.

1987-01-01

A proposed method for selecting and applying hot channel factors is presented along with some justification for these selections. The method is illustrated by example, and the sensitivity to some of the choices is examined. The uncertainty in the heat transfer coefficient is a major contributor to the reduction in thermal-hydraulic safety margins. The uncertainty introduced by the heterogeneity in the fuel is another important contributor and an area where more information may be useful in reducing this uncertainty. (Author)

Outage Performance Analysis of Relay Selection Schemes in Wireless Energy Harvesting Cooperative Networks over Non-Identical Rayleigh Fading Channels.

Science.gov (United States)

Do, Nhu Tri; Bao, Vo Nguyen Quoc; An, Beongku

2016-02-26

In this paper, we study relay selection in decode-and-forward wireless energy harvesting cooperative networks. In contrast to conventional cooperative networks, the relays harvest energy from the source's radio-frequency radiation and then use that energy to forward the source information. Considering power splitting receiver architecture used at relays to harvest energy, we are concerned with the performance of two popular relay selection schemes, namely, partial relay selection (PRS) scheme and optimal relay selection (ORS) scheme. In particular, we analyze the system performance in terms of outage probability (OP) over independent and non-identical (i.n.i.d.) Rayleigh fading channels. We derive the closed-form approximations for the system outage probabilities of both schemes and validate the analysis by the Monte-Carlo simulation. The numerical results provide comprehensive performance comparison between the PRS and ORS schemes and reveal the effect of wireless energy harvesting on the outage performances of both schemes. Additionally, we also show the advantages and drawbacks of the wireless energy harvesting cooperative networks and compare to the conventional cooperative networks.

Performance of Antenna Selection in MIMO System Using Channel Reciprocity with Measured Data

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Peerapong Uthansakul

2011-01-01

Full Text Available The channel capacity of MIMO system increases as a function of antenna pairs between transmitter and receiver but it suffers from multiple expensive RF chains. To reduce cost of RF chains, antenna selection (AS method can offer a good tradeoff between expense and performance. For a transmitting AS system, channel state information (CSI feedback is required to choose the best subset of available antennas. However, the delay and error in feedback channel are the most dominant factors to degrade performances. In this paper, the concept of AS method using reciprocal CSI instead of feedback channel is proposed. The capacity performance of proposed system is investigated by own developing Testbed. The obtained results indicate that the reciprocity technique offers a capacity close to a system with perfect CSI and gains a higher capacity than a system without AS method. This benefit is from 0.9 to 2.2 bps/Hz at SNR 10 dB.

Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia

DEFF Research Database (Denmark)

Zakrzewska, Joanna M; Palmer, Joanne; Morisset, Valerie

2017-01-01

BACKGROUND: Current standard of care for trigeminal neuralgia is treatment with the sodium channel blockers carbamazepine and oxcarbazepine, which although effective are associated with poor tolerability and the need for titration. BIIB074, a Nav1.7-selective, state-dependent sodium-channel blocker...

Equivalence of Linear MMSE Detection in DS-CDMA and MC-CDMA Systems over Time and Frequency Selective Channels

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Tamer A. Kadous

2003-01-01

Full Text Available The goal of this paper is to compare the performance of the linear minimum mean square error (MMSE detector for a class of code division multiple access (CDMA systems in time and frequency selective channels. Specifically, we consider direct sequence (DS-CDMA, multicarrier (MC-CDMA, and the MC-DS-CDMA systems. Two key tools are used in our development. First, a general time-frequency framework that includes the different CDMA systems as special cases. Second, the duality between time and frequency domains that is used to derive equivalences between the different CDMA systems operating over purely frequency selective and purely time selective channels. We then combine the insights obtained from these special cases to assess the performance of CDMA systems over time and frequency selective channels. We provide sufficient conditions for the codes employed by the CDMA systems for the equivalences to hold. Numerical results are presented to illustrate the results.

TWIK-1 two-pore domain potassium channels change ion selectivity and conduct inward leak sodium currents in hypokalemia.

Science.gov (United States)

Ma, Liqun; Zhang, Xuexin; Chen, Haijun

2011-06-07

Background potassium (K+) channels, which are normally selectively permeable to K+, maintain the cardiac resting membrane potential at around -80 mV. In subphysiological extracellular K+ concentrations ([K+]o), which occur in pathological hypokalemia, the resting membrane potential of human cardiomyocytes can depolarize to around -50 mV, whereas rat and mouse cardiomyocytes become hyperpolarized, consistent with the Nernst equation for K+. This paradoxical depolarization of cardiomyocytes in subphysiological [K+]o, which may contribute to cardiac arrhythmias, is thought to involve an inward leak sodium (Na+) current. Here, we show that human cardiac TWIK-1 (also known as K2P1) two-pore domain K+ channels change ion selectivity, becoming permeable to external Na+, and conduct inward leak Na+ currents in subphysiological [K+]o. A specific threonine residue (Thr118) within the pore selectivity sequence TxGYG was required for this altered ion selectivity. Mouse cardiomyocyte-derived HL-1 cells exhibited paradoxical depolarization with ectopic expression of TWIK-1 channels, whereas TWIK-1 knockdown in human spherical primary cardiac myocytes eliminated paradoxical depolarization. These findings indicate that ion selectivity of TWIK-1 K+ channels changes during pathological hypokalemia, elucidate a molecular basis for inward leak Na+ currents that could trigger or contribute to cardiac paradoxical depolarization in lowered [K+]o, and identify a mechanism for regulating cardiac excitability.

The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

Science.gov (United States)

Pickard, B. G.; Ding, J. P.

1993-01-01

Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

Bit Error Rate Performance Analysis of a Threshold-Based Generalized Selection Combining Scheme in Nakagami Fading Channels

Directory of Open Access Journals (Sweden)

Kousa Maan

2005-01-01

Full Text Available The severity of fading on mobile communication channels calls for the combining of multiple diversity sources to achieve acceptable error rate performance. Traditional approaches perform the combining of the different diversity sources using either the conventional selective diversity combining (CSC, equal-gain combining (EGC, or maximal-ratio combining (MRC schemes. CSC and MRC are the two extremes of compromise between performance quality and complexity. Some researches have proposed a generalized selection combining scheme (GSC that combines the best branches out of the available diversity resources ( . In this paper, we analyze a generalized selection combining scheme based on a threshold criterion rather than a fixed-size subset of the best channels. In this scheme, only those diversity branches whose energy levels are above a specified threshold are combined. Closed-form analytical solutions for the BER performances of this scheme over Nakagami fading channels are derived. We also discuss the merits of this scheme over GSC.

Channel selective tunnelling through a nanographene assembly

International Nuclear Information System (INIS)

Wong, H S; Durkan, C; Feng, X; Müllen, K; Chandrasekhar, N

2012-01-01

We report selective tunnelling through a nanographene intermolecular tunnel junction achieved via scanning tunnelling microscope tip functionalization with hexa-peri-hexabenzocoronene (HBC) molecules. This leads to an offset in the alignment between the energy levels of the tip and the molecular assembly, resulting in the imaging of a variety of distinct charge density patterns in the HBC assembly, not attainable using a bare metallic tip. Different tunnelling channels can be selected by the application of an electric field in the tunnelling junction, which changes the condition of the HBC on the tip. Density functional theory-based calculations relate the imaged HBC patterns to the calculated molecular orbitals at certain energy levels. These patterns bear a close resemblance to the π-orbital states of the HBC molecule calculated at the relevant energy levels, mainly below the Fermi energy of HBC. This correlation demonstrates the ability of an HBC functionalized tip as regards accessing an energy range that is restricted to the usual operating bias range around the Fermi energy with a normal metallic tip at room temperature. Apart from relating to molecular orbitals, some patterns could also be described in association with the Clar aromatic sextet formula. Our observations may help pave the way towards the possibility of controlling charge transport between organic interfaces. (paper)

Chloride channels as tools for developing selective insecticides.

Science.gov (United States)

Bloomquist, Jeffrey R

2003-12-01

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

Outage Performance Analysis of Relay Selection Schemes in Wireless Energy Harvesting Cooperative Networks over Non-Identical Rayleigh Fading Channels †

Science.gov (United States)

Do, Nhu Tri; Bao, Vo Nguyen Quoc; An, Beongku

2016-01-01

In this paper, we study relay selection in decode-and-forward wireless energy harvesting cooperative networks. In contrast to conventional cooperative networks, the relays harvest energy from the source’s radio-frequency radiation and then use that energy to forward the source information. Considering power splitting receiver architecture used at relays to harvest energy, we are concerned with the performance of two popular relay selection schemes, namely, partial relay selection (PRS) scheme and optimal relay selection (ORS) scheme. In particular, we analyze the system performance in terms of outage probability (OP) over independent and non-identical (i.n.i.d.) Rayleigh fading channels. We derive the closed-form approximations for the system outage probabilities of both schemes and validate the analysis by the Monte-Carlo simulation. The numerical results provide comprehensive performance comparison between the PRS and ORS schemes and reveal the effect of wireless energy harvesting on the outage performances of both schemes. Additionally, we also show the advantages and drawbacks of the wireless energy harvesting cooperative networks and compare to the conventional cooperative networks. PMID:26927119

Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity.

Science.gov (United States)

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)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.

Novel asymptotic results on the high-order statistics of the channel capacity over generalized fading channels

KAUST Repository

Yilmaz, Ferkan

2012-06-01

The exact analysis of the higher-order statistics of the channel capacity (i.e., higher-order ergodic capacity) often leads to complicated expressions involving advanced special functions. In this paper, we provide a generic framework for the computation of the higher-order statistics of the channel capacity over generalized fading channels. As such, this novel framework for the higher-order statistics results in simple, closed-form expressions which are shown to be asymptotically tight bounds in the high signal-to-noise ratio (SNR) regime of a variety of fading environment. In addition, it reveals the existence of differences (i.e., constant capacity gaps in log-domain) among different fading environments. By asymptotically tight bound we mean that the high SNR limit of the difference between the actual higher-order statistics of the channel capacity and its asymptotic bound (i.e., lower bound) tends to zero. The mathematical formalism is illustrated with some selected numerical examples that validate the correctness of our newly derived results. © 2012 IEEE.

Harnessing mode-selective nonlinear optics for on-chip multi-channel all-optical signal processing

Directory of Open Access Journals (Sweden)

Ming Ma

2016-11-01

Full Text Available All-optical signal processing based on nonlinear optical effects allows for the realization of important functions in telecommunications including wavelength conversion, optical multiplexing/demultiplexing, Fourier transformation, and regeneration, amongst others, on ultrafast time scales to support high data rate transmission. In integrated photonic subsystems, the majority of all-optical signal processing systems demonstrated to date typically process only a single channel at a time or perform a single processing function, which imposes a serious limitation on the functionality of integrated solutions. Here, we demonstrate how nonlinear optical effects can be harnessed in a mode-selective manner to perform simultaneous multi-channel (two and multi-functional optical signal processing (i.e., regenerative wavelength conversion in an integrated silicon photonic device. This approach, which can be scaled to a higher number of channels, opens up a new degree of freedom for performing a broad range of multi-channel nonlinear optical signal processing functions using a single integrated photonic device.

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

Science.gov (United States)

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.

Study of Internal Channel Surface Roughnesses Manufactured by Selective Laser Melting in Aluminum and Titanium Alloys

Science.gov (United States)

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.

ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters.

Science.gov (United States)

Hanukoglu, Israel

2017-02-01

The acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) are members of a superfamily of channels that play critical roles in mechanosensation, chemosensation, nociception, and regulation of blood volume and pressure. These channels look and function like a tripartite funnel that directs the flow of Na + ions into the cytoplasm via the channel pore in the membrane. The subunits that form these channels share a common structure with two transmembrane segments (TM1 and TM2) and a large extracellular part. In most vertebrates, there are five paralogous genes that code for ASICs (ASIC1-ASIC5), and four for ENaC subunits alpha, beta, gamma, and delta (α, β, γ, and δ). While ASICs can form functional channels as a homo- or heterotrimer, ENaC functions as an obligate heterotrimer composed of α-β-γ or β-γ-δ subunits. The structure of ASIC has been determined in several conformations, including desensitized and open states. This review presents a comparison of the structures of these states using easy-to-understand molecular models of the full complex, the central tunnel that includes an outer vestibule, the channel pore, and ion selectivity filter. The differences in the secondary, tertiary, and quaternary structures of the states are summarized to pinpoint the conformational changes responsible for channel opening. Results of site-directed mutagenesis studies of ENaC subunits are examined in light of ASIC1 models. Based on these comparisons, a molecular model for the selectivity filter of ENaC is built by in silico mutagenesis of an ASIC1 structure. These models suggest that Na + ions pass through the filter in a hydrated state. © 2016 Federation of European Biochemical Societies.

A novel potassium channel in photosynthetic cyanobacteria.

Directory of Open Access Journals (Sweden)

Manuela Zanetti

Full Text Available Elucidation of the structure-function relationship of a small number of prokaryotic ion channels characterized so far greatly contributed to our knowledge on basic mechanisms of ion conduction. We identified a new potassium channel (SynK in the genome of the cyanobacterium Synechocystis sp. PCC6803, a photosynthetic model organism. SynK, when expressed in a K(+-uptake-system deficient E. coli strain, was able to recover growth of these organisms. The protein functions as a potassium selective ion channel when expressed in Chinese hamster ovary cells. The location of SynK in cyanobacteria in both thylakoid and plasmamembranes was revealed by immunogold electron microscopy and Western blotting of isolated membrane fractions. SynK seems to be conserved during evolution, giving rise to a TPK (two-pore K(+ channel family member which is shown here to be located in the thylakoid membrane of Arabidopsis. Our work characterizes a novel cyanobacterial potassium channel and indicates the molecular nature of the first higher plant thylakoid cation channel, opening the way to functional studies.

Channel-morphology data for the Tongue River and selected tributaries, southeastern Montana, 2001-02

Science.gov (United States)

Chase, Katherine J.

2004-01-01

Coal-bed methane exploration and production have begun within the Tongue River watershed in southeastern Montana. The development of coal-bed methane requires production of large volumes of ground water, some of which may be discharged to streams, potentially increasing stream discharge and sediment load. Changes in stream discharge or sediment load may result in changes to channel morphology through changes in erosion and vegetation. These changes might be subtle and difficult to detect without baseline data that indicate stream-channel conditions before extensive coal-bed methane development began. In order to provide this baseline channel-morphology data, the U.S. Geological Survey, in cooperation with the Bureau of Land Management, collected channel-morphology data in 2001-02 to document baseline conditions for several reaches along the Tongue River and selected tributaries. This report presents channel-morphology data for five sites on the mainstem Tongue River and four sites on its tributaries. Bankfull, water-surface, and thalweg elevations, channel sections, and streambed-particle sizes were measured along reaches near streamflow-gaging stations. At each site, the channel was classified using methods described by Rosgen. For six sites, bankfull discharge was determined from the stage- discharge relation at the gage for the stage corresponding to the bankfull elevation. For three sites, the step-backwater computer model HEC-RAS was used to estimate bankfull discharge. Recurrence intervals for the bankfull discharge also were estimated for eight of the nine sites. Channel-morphology data for each site are presented in maps, tables, graphs, and photographs.

λ-Selection Strategy in C+L Band 1-Pbit/s (448 WDM/19-Core/128 Gbit/s/channel) Flex-Grid Space Division Multiplexed Transmission

DEFF Research Database (Denmark)

Asif, Rameez; Ye, Feihong; Morioka, Toshio

2015-01-01

In this paper, an inter-core crosstalk based wavelength selection scheme has been proposed for flex-grid superchannels in space division multiplexed transmission. The two λ-selection strategies are categorized as: (a) aligned wavelength super-channels (Aλ-SCs), where all super-channels are placed...... at same λ in all the cores and (b) interleaved wavelength super-channels (Iλ-SCs), where all super-channels are placed at different λ in all the neighboring cores. It is depicted that system performance is improved for DP-16QAM channels in 1-Pbit/s (448 WDM/19 Core/128 Gbit/s/channel) 60 km fiber link...

Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.

Science.gov (United States)

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.

Multi-Channel Electroencephalogram (EEG) Signal Acquisition and its Effective Channel selection with De-noising Using AWICA for Biometric System

OpenAIRE

B.Sabarigiri; D.Suganyadevi

2014-01-01

the embedding of low cost electroencephalogram (EEG) sensors in wireless headsets gives improved authentication based on their brain wave signals has become a practical opportunity. In this paper signal acquisition along with effective multi-channel selection from a specific area of the brain and denoising using AWICA methods are proposed for EEG based personal identification. At this point, to develop identification system the steps are as follows. (i) the high-quality device with the least ...

Drainage basins, channels, and flow characteristics of selected streams in central Pennsylvania

Science.gov (United States)

Brush, Lucien M.

1961-01-01

The hydraulic, basin, and geologic characteristics of 16 selected streams in central Pennsylvania were measured for the purpose of studying the relations among these general characteristics and their process of development. The basic parameters which were measured include bankfull width and depth, channel slope, bed material size and shape, length of stream from drainage divide, and size of drainage area. The kinds of bedrock over which the streams flow were noted. In these streams the bankfull channel is filled by flows approximating the 2.3-year flood. By measuring the breadth and mean depth of the channel, it was possible to compute the bankfull mean velocity for each of the 119 sampling stations. These data were then used to compute the downstream changes in hydraulic geometry of the streams studied. This method has been called an indirect computation of the hydraulic geometry. The results obtained by the indirect method are similar to those of the direct method of other workers. The basins were studied by examining the relations of drainage area, discharge, and length of stream from drainage divide. For the streams investigated, excellent correlations were found to exist between drainage area and the 2.3-year flood, as well as between length of stream from the basin divide and drainage area. From these correlations it is possible to predict the discharge for the 2.3-year flood at any arbitrary point along the length of the stream. The long, intermediate, and short axes of pebbles sampled from the bed of the stream were recorded to study both size and sphericity changes along individual streams and among the streams studied. No systematic downstream changes in sphericity were found. Particle size changes are erratic and show no consistent relation to channel slope. Particle size decreases downstream in many streams but remains constant or increases in others. Addition of material by tributaries is one factor affecting particle size and another is the parent

Exponential decay and exponential recovery of modal gains in high count rate channel electron multipliers

International Nuclear Information System (INIS)

Hahn, S.F.; Burch, J.L.

1980-01-01

A series of data on high count rate channel electron multipliers revealed an initial drop and subsequent recovery of gains in exponential fashion. The FWHM of the pulse height distribution at the initial stage of testing can be used as a good criterion for the selection of operating bias voltage of the channel electron multiplier

A simple and highly selective 2,2-diferrocenylpropane-based multi-channel ion pair receptor for Pb(2+) and HSO4(-).

Science.gov (United States)

Wan, Qian; Zhuo, Ji-Bin; Wang, Xiao-Xue; Lin, Cai-Xia; Yuan, Yao-Feng

2015-03-28

A structurally simple, 2,2-diferrocenylpropane-based ion pair receptor 1 was synthesized and characterized by (1)H NMR, (13)C NMR, HRMS, elemental analyses, and single-crystal X-ray diffraction. The ion pair receptor 1 showed excellent selectivity and sensitivity towards Pb(2+) with multi-channel responses: a fluorescence enhancement (more than 42-fold), a notable color change from yellow to red, redox anodic shift (ΔE1/2 = 151 mV), while HSO4(-) promoted fluorescence enhancement when Pb(2+) or Zn(2+) was bonded to the cation binding-site. (1)H NMR titration and density functional theory were performed to reveal the sensing mechanism based on photo-induced electron transfer (PET).

AFM imaging reveals the tetrameric structure of the TRPC1 channel

International Nuclear Information System (INIS)

Barrera, Nelson P.; Shaifta, Yasin; McFadzean, Ian; Ward, Jeremy P.T.; Henderson, Robert M.; Edwardson, J. Michael

2007-01-01

We have determined the subunit stoichiometry of the transient receptor potential C1 (TRPC1) channel by imaging isolated channels using atomic force microscopy (AFM). A frequency distribution of the molecular volumes of individual channel particles had two peaks, at 170 and 720 nm 3 , corresponding with the expected sizes of TRPC1 monomers and tetramers, respectively. Complexes were formed between TRPC1 channels and antibodies against a V5 epitope tag present on each subunit. The frequency distribution of angles between pairs of bound antibodies had two peaks, at 88 o and 178 o . This result again indicates that the channel assembles as a tetramer

EEG Channel Selection Using Particle Swarm Optimization for the Classification of Auditory Event-Related Potentials

Directory of Open Access Journals (Sweden)

Alejandro Gonzalez

2014-01-01

Full Text Available Brain-machine interfaces (BMI rely on the accurate classification of event-related potentials (ERPs and their performance greatly depends on the appropriate selection of classifier parameters and features from dense-array electroencephalography (EEG signals. Moreover, in order to achieve a portable and more compact BMI for practical applications, it is also desirable to use a system capable of accurate classification using information from as few EEG channels as possible. In the present work, we propose a method for classifying P300 ERPs using a combination of Fisher Discriminant Analysis (FDA and a multiobjective hybrid real-binary Particle Swarm Optimization (MHPSO algorithm. Specifically, the algorithm searches for the set of EEG channels and classifier parameters that simultaneously maximize the classification accuracy and minimize the number of used channels. The performance of the method is assessed through offline analyses on datasets of auditory ERPs from sound discrimination experiments. The proposed method achieved a higher classification accuracy than that achieved by traditional methods while also using fewer channels. It was also found that the number of channels used for classification can be significantly reduced without greatly compromising the classification accuracy.

A proton wire and water channel revealed in the crystal structure of isatin hydrolase

DEFF Research Database (Denmark)

Bjerregaard-Andersen, Kaare; Sommer, Theis; Jensen, Jan Kristian

2014-01-01

to a novel family of metalloenzymes that include the bacterial kynurenine formamidase. The product state, mimicked by bound thioisatinate, reveals a water molecule that bridges the thioisatinate to a proton wire in an adjacent water channel and thus allows the proton released by the reaction to escape only...... when the product is formed. The functional proton wire present in IH-b represents a unique catalytic feature common to all hydrolases is here trapped and visualized for the first time. The local molecular environment required to coordinate thioisatinate allows stronger and more confident identification...

Optimized Energy Harvesting, Cluster-Head Selection and Channel Allocation for IoTs in Smart Cities

Science.gov (United States)

Aslam, Saleem; Hasan, Najam Ul; Jang, Ju Wook; Lee, Kyung-Geun

2016-01-01

This paper highlights three critical aspects of the internet of things (IoTs), namely (1) energy efficiency, (2) energy balancing and (3) quality of service (QoS) and presents three novel schemes for addressing these aspects. For energy efficiency, a novel radio frequency (RF) energy-harvesting scheme is presented in which each IoT device is associated with the best possible RF source in order to maximize the overall energy that the IoT devices harvest. For energy balancing, the IoT devices in close proximity are clustered together and then an IoT device with the highest residual energy is selected as a cluster head (CH) on a rotational basis. Once the CH is selected, it assigns channels to the IoT devices to report their data using a novel integer linear program (ILP)-based channel allocation scheme by satisfying their desired QoS. To evaluate the presented schemes, exhaustive simulations are carried out by varying different parameters, including the number of IoT devices, the number of harvesting sources, the distance between RF sources and IoT devices and the primary user (PU) activity of different channels. The simulation results demonstrate that our proposed schemes perform better than the existing ones. PMID:27918424

Optimized Energy Harvesting, Cluster-Head Selection and Channel Allocation for IoTs in Smart Cities.

Science.gov (United States)

Aslam, Saleem; Hasan, Najam Ul; Jang, Ju Wook; Lee, Kyung-Geun

2016-12-02

This paper highlights three critical aspects of the internet of things (IoTs), namely (1) energy efficiency, (2) energy balancing and (3) quality of service (QoS) and presents three novel schemes for addressing these aspects. For energy efficiency, a novel radio frequency (RF) energy-harvesting scheme is presented in which each IoT device is associated with the best possible RF source in order to maximize the overall energy that the IoT devices harvest. For energy balancing, the IoT devices in close proximity are clustered together and then an IoT device with the highest residual energy is selected as a cluster head (CH) on a rotational basis. Once the CH is selected, it assigns channels to the IoT devices to report their data using a novel integer linear program (ILP)-based channel allocation scheme by satisfying their desired QoS. To evaluate the presented schemes, exhaustive simulations are carried out by varying different parameters, including the number of IoT devices, the number of harvesting sources, the distance between RF sources and IoT devices and the primary user (PU) activity of different channels. The simulation results demonstrate that our proposed schemes perform better than the existing ones.

Optimized Energy Harvesting, Cluster-Head Selection and Channel Allocation for IoTs in Smart Cities

Directory of Open Access Journals (Sweden)

Saleem Aslam

2016-12-01

Full Text Available This paper highlights three critical aspects of the internet of things (IoTs, namely (1 energy efficiency, (2 energy balancing and (3 quality of service (QoS and presents three novel schemes for addressing these aspects. For energy efficiency, a novel radio frequency (RF energy-harvesting scheme is presented in which each IoT device is associated with the best possible RF source in order to maximize the overall energy that the IoT devices harvest. For energy balancing, the IoT devices in close proximity are clustered together and then an IoT device with the highest residual energy is selected as a cluster head (CH on a rotational basis. Once the CH is selected, it assigns channels to the IoT devices to report their data using a novel integer linear program (ILP-based channel allocation scheme by satisfying their desired QoS. To evaluate the presented schemes, exhaustive simulations are carried out by varying different parameters, including the number of IoT devices, the number of harvesting sources, the distance between RF sources and IoT devices and the primary user (PU activity of different channels. The simulation results demonstrate that our proposed schemes perform better than the existing ones.

Inversion of membrane surface charge by trivalent cations probed with a cation-selective channel.

Science.gov (United States)

Gurnev, Philip A; Bezrukov, Sergey M

2012-11-13

We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying the multivalent ion accumulation at the surfaces of charged lipid membranes and the "charge inversion" phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the channel exhibits current rectification, which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed 50 mV. Analysis of the changes in the voltage-dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations, which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine.

Asymptotic Performance Analysis of the k-th Best Link Selection over Wireless Fading Channels: An Extreme Value Theory Approach

KAUST Repository

Al-Badarneh, Yazan Hussein

2018-01-25

We consider a general selection-diversity (SD) scheme in which the k-th best link is selected from a number of links. We use extreme value theory (EVT) to derive simple closed-form asymptotic expressions for the average throughput, effective throughput and average bit error probability (BEP) for the k-th best link over various channel models that are widely used to characterize fading in wireless communication systems. As an application example, we consider the Weibull fading channel model and verify the accuracy of the derived asymptotic expressions through Monte Carlo simulations.

Asymptotic Performance Analysis of the k-th Best Link Selection over Wireless Fading Channels: An Extreme Value Theory Approach

KAUST Repository

Al-Badarneh, Yazan Hussein; Georghiades, Costas; Alouini, Mohamed-Slim

2018-01-01

We consider a general selection-diversity (SD) scheme in which the k-th best link is selected from a number of links. We use extreme value theory (EVT) to derive simple closed-form asymptotic expressions for the average throughput, effective throughput and average bit error probability (BEP) for the k-th best link over various channel models that are widely used to characterize fading in wireless communication systems. As an application example, we consider the Weibull fading channel model and verify the accuracy of the derived asymptotic expressions through Monte Carlo simulations.

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

Directory of Open Access Journals (Sweden)

Darryl W Hondorp

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

The molecular mechanism of multi-ion conduction in K{sup +} channels

Energy Technology Data Exchange (ETDEWEB)

Gwan, J.F.

2007-01-19

Steered molecular dynamics (SMD) simulation method is applied to a fully solvated membrane-channel model for studying the ion permeation process in potassium channels. The channel model is based on the crystallographic structure of a prokaryotic K{sup +} channel- the KcsA channel, which is a representative of most known eukaryotic K{sup +} channels. It has long been proposed that the ion transportation in a conventional K{sup +}-channel follows a multi-ion fashion: permeating ions line in a queue in the channel pore and move in a single file through the channel. The conventional view of multi-ion transportation is that the electrostatic repulsion between ions helps to overcome the attraction between ions and the channel pore. In this study, we proposed two SMD simulation schemes, referred to 'the single-ion SMD' simulations and 'the multi-ion SMD' simulations. Concerted movements of a K-W-K sequence in the selectivity filter were observed in the single-ion SMD simulations. The analysis of the concerted movement reveals the molecular mechanism of the multi-ion transportation. It shows that, rather than the long range electrostatic interaction, the short range polar interaction is a more dominant factor in the multi-ion transportation. The polar groups which play a role in the concerted transportation are the water molecules and the backbone carbonyl groups of the selectivity filter. The polar interaction is sensitive to the relative orientation of the polar groups. By changing the orientation of a polar group, the interaction may switch from attractive to repulsive or vice versa. By this means, the energy barrier between binding sites in the selectivity filter can be switched on and off, and therefore the K{sup +} may be able to move to the neighboring binding site without an external driving force. The concerted transportation in the selectivity filter requires a delicate cooperation between K{sup +}, waters, and the backbone carbonyl groups. To

Landuse Types within Channel Corridor and River Channel Morphology of River Ona, Ibadan, Nigeria

Directory of Open Access Journals (Sweden)

Olutoyin Fashae

2017-12-01

Full Text Available The importance of river a corridor warrants a well thought out and balanced management approach because it helps in improving or maintaining water quality, protecting wetlands, etc. Hence, this study seeks to identify major landuse types within the River Ona Corridor; examine the impact of these landuse types within the River Ona corridor on its channel morphology and understand the risk being posed by these landuse types. The study is designed by selecting two reaches of six times the average width from each of the four major landuse types that exist along the river corridor. This study revealed that along the downstream section of Eleyele Dam of River Ona, natural forest stabilizes river channel banks, thereby presenting a narrow and shallow width and depth respectively but the widest of all is found at the agricultural zones.

Cooperative Orthogonal Space-Time-Frequency Block Codes over a MIMO-OFDM Frequency Selective Channel

Directory of Open Access Journals (Sweden)

M. Rezaei

2016-03-01

Full Text Available In this paper, a cooperative algorithm to improve the orthogonal space-timefrequency block codes (OSTFBC in frequency selective channels for 2*1, 2*2, 4*1, 4*2 MIMO-OFDM systems, is presented. The algorithm of three node, a source node, a relay node and a destination node is formed, and is implemented in two stages. During the first stage, the destination and the relay antennas receive the symbols sent by the source antennas. The destination node and the relay node obtain the decision variables employing time-space-frequency decoding process by the received signals. During the second stage, the relay node transmits decision variables to the destination node. Due to the increasing diversity in the proposed algorithm, decision variables in the destination node are increased to improve system performance. The bit error rate of the proposed algorithm at high SNR is estimated by considering the BPSK modulation. The simulation results show that cooperative orthogonal space-time-frequency block coding, improves system performance and reduces the BER in a frequency selective channel.

Diversity Techniques for Single-Carrier Packet Retransmissions over Frequency-Selective Channels

Directory of Open Access Journals (Sweden)

Assimi Abdel-Nasser

2009-01-01

Full Text Available In data packet communication systems over multipath frequency-selective channels, hybrid automatic repeat request (HARQ protocols are usually used in order to ensure data reliability. For single-carrier packet transmission in slow fading environment, an identical retransmission of the same packet, due to a decoding failure, does not fully exploit the available time diversity in retransmission-based HARQ protocols. In this paper, we compare two transmit diversity techniques, namely, cyclic frequency-shift diversity and bit-interleaving diversity. Both techniques can be integrated in the HARQ scheme in order to improve the performance of the joint detector. Their performance in terms of pairwise error probability is investigated using maximum likelihood detection and decoding. The impact of the channel memory and the modulation order on the performance gain is emphasized. In practice, we use low complexity linear filter-based equalization which can be efficiently implemented in the frequency domain. The use of iterative equalization and decoding is also considered. The performance gain in terms of frame error rate and data throughput is evaluated by numerical simulations.

Performance analysis of selective cooperation in amplify-and-forward relay networks over identical Nakagami-m channels

KAUST Repository

Hussain, Syed Imtiaz; Alouini, Mohamed-Slim; Hasna, Mazen Omar

2011-01-01

In cooperative communications, multiple relays between a source and a destination can increase the diversity gain. Because all the nodes must use orthogonal channels, multiple-relay cooperation becomes spectrally inefficient. Therefore, a bestrelay selection scheme was recently proposed. In this paper, we analyzed the performance of this scheme for a system with the relays operating in amplify-and-forward mode over identical Nakagami-m channels using an exact source-relay-destination signal-to-noise ratio (SNR).We derived accurate closed-form expressions for various system parameters including the probability density function of end-to-end SNR, the average output SNR, the bit error probability, and the channel capacity. The analytical results were verified through Monte Carlo simulations. Copyright © 2011 John Wiley & Sons, Ltd.

Performance analysis of selective cooperation in amplify-and-forward relay networks over identical Nakagami-m channels

KAUST Repository

Hussain, Syed Imtiaz

2011-05-02

In cooperative communications, multiple relays between a source and a destination can increase the diversity gain. Because all the nodes must use orthogonal channels, multiple-relay cooperation becomes spectrally inefficient. Therefore, a bestrelay selection scheme was recently proposed. In this paper, we analyzed the performance of this scheme for a system with the relays operating in amplify-and-forward mode over identical Nakagami-m channels using an exact source-relay-destination signal-to-noise ratio (SNR).We derived accurate closed-form expressions for various system parameters including the probability density function of end-to-end SNR, the average output SNR, the bit error probability, and the channel capacity. The analytical results were verified through Monte Carlo simulations. Copyright © 2011 John Wiley & Sons, Ltd.

Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3.

Science.gov (United States)

Wright, Paul D; Veale, Emma L; McCoull, David; Tickle, David C; Large, Jonathan M; Ococks, Emma; Gothard, Gemma; Kettleborough, Catherine; Mathie, Alistair; Jerman, Jeffrey

2017-11-04

Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K + channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators. After screening a library of 1000 compounds, including drug-like and FDA approved molecules, we identified Terbinafine as an activator of TASK3. In a thallium flux assay a pEC50 of 6.2 ( ±0.12) was observed. When Terbinafine was screened against TASK2, TREK2, THIK1, TWIK1 and TRESK no activation was observed in thallium flux assays. Several analogues of Terbinafine were also purchased and structure activity relationships examined. To confirm Terbinafine's activation of TASK3 whole cell patch clamp electrophysiology was carried out and clear potentiation observed in both the wild type channel and the pathophysiological, Birk-Barel syndrome associated, G236R TASK3 mutant. No activity at TASK1 was observed in electrophysiology studies. In conclusion, we have identified the first selective activator of the two-pore domain potassium channel TASK3. Copyright © 2017 Elsevier Inc. All rights reserved.

Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

Science.gov (United States)

Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

2017-09-01

The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

Blind CP-OFDM and ZP-OFDM Parameter Estimation in Frequency Selective Channels

Directory of Open Access Journals (Sweden)

Vincent Le Nir

2009-01-01

Full Text Available A cognitive radio system needs accurate knowledge of the radio spectrum it operates in. Blind modulation recognition techniques have been proposed to discriminate between single-carrier and multicarrier modulations and to estimate their parameters. Some powerful techniques use autocorrelation- and cyclic autocorrelation-based features of the transmitted signal applying to OFDM signals using a Cyclic Prefix time guard interval (CP-OFDM. In this paper, we propose a blind parameter estimation technique based on a power autocorrelation feature applying to OFDM signals using a Zero Padding time guard interval (ZP-OFDM which in particular excludes the use of the autocorrelation- and cyclic autocorrelation-based techniques. The proposed technique leads to an efficient estimation of the symbol duration and zero padding duration in frequency selective channels, and is insensitive to receiver phase and frequency offsets. Simulation results are given for WiMAX and WiMedia signals using realistic Stanford University Interim (SUI and Ultra-Wideband (UWB IEEE 802.15.4a channel models, respectively.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Receptor model for the molecular basis of tissue selectivity of 1,4-dihydropyridine calcium channel drugs

Science.gov (United States)

Langs, David A.; Strong, Phyllis D.; Triggle, David J.

1990-09-01

Our analysis of the solid state conformations of nifedipine [dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate] and its 1,4-dihydropyridine (1,4-DHP) analogues produced a cartoon description of the important interactions between these drugs and their voltage-dependent calcium channel receptor. In the present study a molecular-level detailed model of the 1,4-DHP receptor binding site has been built from the published amino acid sequence of the 215-1 subunit of the voltage-dependent calcium channel isolated from rabbit skeletal muscle transverse tubule membranes. The voltage-sensing component of the channel described in this work differs from others reported for the homologous sodium channel in that it incorporates a water structure and a staggered, rather than eclipsed, hydrogen bonded S4 helix conformation. The major recognition surfaces of the receptor lie in helical grooves on the S4 or voltagesensing α-helix that is positioned in the center of the bundle of transmembrane helices that define each of the four calcium channel domains. Multiple binding clefts defined by Arg-X-X-Arg-P-X-X-S `reading frames' exist on the S4 strand. The tissue selectivity of nifedipine and its analogues may arise, in part, from conservative changes in the amino acid residues at the P and S positions of the reading frame that define the ester-binding regions of receptors from different tissues. The crystal structures of two tissue-selective nifedipine analogues, nimodipine [isopropyl (2-methoxyethyl) 1,4-dihydro-2,6- dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] and nitrendipine [ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] are reported. Nimodipine was observed to have an unusual ester side chain conformation that enhances the fit to the proposed ester-sensing region of the receptor.

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

Science.gov (United States)

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.

Optogenetic analysis of a nociceptor neuron and network reveals ion channels acting downstream of primary sensors

Science.gov (United States)

Husson, Steven J.; Costa, Wagner Steuer; Wabnig, Sebastian; Stirman, Jeffrey N.; Watson, Joseph D.; Spencer, W. Clay; Akerboom, Jasper; Looger, Loren L.; Treinin, Millet; Miller, David M.; Lu, Hang; Gottschalk, Alexander

2012-01-01

Summary Background Nociception generally evokes rapid withdrawal behavior in order to protect the tissue from harmful insults. Most nociceptive neurons responding to mechanical insults display highly branched dendrites, an anatomy shared by Caenorhabditis elegans FLP and PVD neurons, which mediate harsh touch responses. Although several primary molecular nociceptive sensors have been characterized, less is known about modulation and amplification of noxious signals within nociceptor neurons. First, we analyzed the FLP/PVD network by optogenetics and studied integration of signals from these cells in downstream interneurons. Second, we investigated which genes modulate PVD function, based on prior single neuron mRNA profiling of PVD. Results Selectively photoactivating PVD, FLP and downstream interneurons using Channelrhodopsin-2 (ChR2) enabled functionally dissecting this nociceptive network, without interfering signals by other mechanoreceptors. Forward or reverse escape behaviors were determined by PVD and FLP, via integration by command interneurons. To identify mediators of PVD function, acting downstream of primary nocisensor molecules, we knocked down PVD-specific transcripts by RNAi and quantified light-evoked PVD-dependent behavior. Cell-specific disruption of synaptobrevin or voltage-gated Ca2+-channels (VGCCs) showed that PVD signals chemically to command interneurons. Knocking down the DEG/ENaC channel ASIC-1 and the TRPM channel GTL-1 indicated that ASIC-1 may extend PVD’s dynamic range and that GTL-1 may amplify its signals. These channels act cell-autonomously in PVD, downstream of primary mechanosensory molecules. Conclusions Our work implicates TRPM channels in modifying excitability of, and DEG/ENaCs in potentiating signal output from a mechano-nociceptor neuron. ASIC-1 and GTL-1 homologues, if functionally conserved, may denote valid targets for novel analgesics. PMID:22483941

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

Science.gov (United States)

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

Point mutations in the transmembrane region of the clic1 ion channel selectively modify its biophysical properties.

Directory of Open Access Journals (Sweden)

Stefania Averaimo

Full Text Available Chloride intracellular Channel 1 (CLIC1 is a metamorphic protein that changes from a soluble cytoplasmic protein into a transmembrane protein. Once inserted into membranes, CLIC1 multimerises and is able to form chloride selective ion channels. Whilst CLIC1 behaves as an ion channel both in cells and in artificial lipid bilayers, its structure in the soluble form has led to some uncertainty as to whether it really is an ion channel protein. CLIC1 has a single putative transmembrane region that contains only two charged residues: arginine 29 (Arg29 and lysine 37 (Lys37. As charged residues are likely to have a key role in ion channel function, we hypothesized that mutating them to neutral alanine to generate K37A and R29A CLIC1 would alter the electrophysiological characteristics of CLIC1. By using three different electrophysiological approaches: i single channel Tip-Dip in artificial bilayers using soluble recombinant CLIC1, ii cell-attached and iii whole-cell patch clamp recordings in transiently transfected HEK cells, we determined that the K37A mutation altered the single-channel conductance while the R29A mutation affected the single-channel open probability in response to variation in membrane potential. Our results show that mutation of the two charged amino acids (K37 and R29 in the putative transmembrane region of CLIC1 alters the biophysical properties of the ion channel in both artificial bilayers and cells. Hence these charged residues are directly involved in regulating its ion channel activity. This strongly suggests that, despite its unusual structure, CLIC1 itself is able to form a chloride ion channel.

Channel properties of Nax expressed in neurons.

Directory of Open Access Journals (Sweden)

Masahito Matsumoto

Full Text Available Nax is a sodium-concentration ([Na+]-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons. We herein verified that Nax was expressed in neurons in the lateral amygdala of mice using an antibody that was newly generated against mouse Nax. To investigate the channel properties of Nax expressed in neurons, we established an inducible cell line of Nax using the mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the expression of Nax. Functional analyses of this cell line revealed that the [Na+]-sensitivity of Nax in neuronal cells was similar to that expressed in glial cells. The cation selectivity sequence of the Nax channel in cations was revealed to be Na+ ≈ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that Nax bound to postsynaptic density protein 95 (PSD95 through its PSD95/Disc-large/ZO-1 (PDZ-binding motif at the C-terminus in neurons. The interaction between Nax and PSD95 may be involved in promoting the surface expression of Nax channels because the depletion of endogenous PSD95 resulted in a decrease in Nax at the plasma membrane. These results indicated, for the first time, that Nax functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells.

Decisions about design and selection of marketing channels

OpenAIRE

Marjanova Jovanov, Tamara; Temjanovski, Riste

2016-01-01

The significance of the distribution strategy stems from its participation in the costs included in the price, the conditioning of the information in the promotional message, the connection with the desired market position of the product. The distribution includes management of all functions (physical flow, promotion, ordering and payment information, negotiation, risk taking) involved in the channel. Distribution channel...

On Secrecy Outage of Relay Selection in Underlay Cognitive Radio Networks over Nakagami-m Fading Channels

KAUST Repository

Lei, Hongjiang; Zhang, Huan; Ansari, Imran Shafique; Ren, Zhi; Pan, Gaofeng; Qaraqe, Khalid A.; Alouini, Mohamed-Slim

2017-01-01

In this paper, the secrecy outage performance of an underlay cognitive decode-and-forward relay network over independent but not necessarily identical distributed (i.n.i.d) Nakagami-m fading channels is investigated, in which the secondary user transmitter communicates with the secondary destination via relays, and an eavesdropper attempts to overhear the information. Based on whether the channel state information (CSI) of the wiretap links is available or not, we analyze the secrecy outage performance with optimal relay selection (ORS) and suboptimal relay selection (SRS) schemes, and multiple relays combining scheme (MRC) scheme is considered for comparison purpose. The exact and asymptotic closed-form expressions for the secrecy outage probability with three different relay selection schemes are derived and verified by Monte-Carlo simulations. The numerical results illustrate that ORS scheme always outperforms SRS and MRC schemes, and SRS scheme is better than MRC scheme in the lower fading parameters scenario. Furthermore, through asymptotic analysis, we find that these three different schemes achieve the same secrecy diversity order, which is determined by the number of the relays, and the fading parameters of the links among the relays and the destination.

On Secrecy Outage of Relay Selection in Underlay Cognitive Radio Networks over Nakagami-m Fading Channels

KAUST Repository

Lei, Hongjiang

2017-10-02

In this paper, the secrecy outage performance of an underlay cognitive decode-and-forward relay network over independent but not necessarily identical distributed (i.n.i.d) Nakagami-m fading channels is investigated, in which the secondary user transmitter communicates with the secondary destination via relays, and an eavesdropper attempts to overhear the information. Based on whether the channel state information (CSI) of the wiretap links is available or not, we analyze the secrecy outage performance with optimal relay selection (ORS) and suboptimal relay selection (SRS) schemes, and multiple relays combining scheme (MRC) scheme is considered for comparison purpose. The exact and asymptotic closed-form expressions for the secrecy outage probability with three different relay selection schemes are derived and verified by Monte-Carlo simulations. The numerical results illustrate that ORS scheme always outperforms SRS and MRC schemes, and SRS scheme is better than MRC scheme in the lower fading parameters scenario. Furthermore, through asymptotic analysis, we find that these three different schemes achieve the same secrecy diversity order, which is determined by the number of the relays, and the fading parameters of the links among the relays and the destination.

Baseline Channel Geometry and Aquatic Habitat Data for Selected Streams in the Matanuska-Susitna Valley, Alaska

Science.gov (United States)

Curran, Janet H.; Rice, William J.

2009-01-01

Small streams in the rapidly developing Matanuska-Susitna Valley in south-central Alaska are known to support anadromous and resident fish but little is known about their hydrologic and riparian conditions, or their sensitivity to the rapid development of the area or climate variability. To help address this need, channel geometry and aquatic habitat data were collected in 2005 as a baseline of stream conditions for selected streams. Three streams were selected as representative of various stream types, and one drainage network, the Big Lake drainage basin, was selected for a systematic assessment. Streams in the Big Lake basin were drawn in a Geographic Information System (GIS), and 55 reaches along 16 miles of Meadow Creek and its primary tributary Little Meadow Creek were identified from orthoimagery and field observations on the basis of distinctive physical and habitat parameters, most commonly gradient, substrate, and vegetation. Data-collection methods for sites at the three representative reaches and the 55 systematically studied reaches consisted of a field survey of channel and flood-plain geometry and collection of 14 habitat attributes using published protocols or slight modifications. Width/depth and entrenchment ratios along the Meadow-Little Meadow Creek corridor were large and highly variable upstream of Parks Highway and lower and more consistent downstream of Parks Highway. Channel width was strongly correlated with distance, increasing downstream in a log-linear relation. Runs formed the most common habitat type, and instream vegetation dominated the habitat cover types, which collectively covered 53 percent of the channel. Gravel suitable for spawning covered isolated areas along Meadow Creek and about 29 percent of Little Meadow Creek. Broad wetlands were common along both streams. For a comprehensive assessment of small streams in the Mat-Su Valley, critical additional data needs include hydrologic, geologic and geomorphic, and biologic data

Achieving high permeability and enhanced selectivity for Angstrom-scale separations using artificial water channel membranes.

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Shen, Yue-Xiao; Song, Woochul C; Barden, D Ryan; Ren, Tingwei; Lang, Chao; Feroz, Hasin; Henderson, Codey B; Saboe, Patrick O; Tsai, Daniel; Yan, Hengjing; Butler, Peter J; Bazan, Guillermo C; Phillip, William A; Hickey, Robert J; Cremer, Paul S; Vashisth, Harish; Kumar, Manish

2018-06-12

Synthetic polymer membranes, critical to diverse energy-efficient separations, are subject to permeability-selectivity trade-offs that decrease their overall efficacy. These trade-offs are due to structural variations (e.g., broad pore size distributions) in both nonporous membranes used for Angstrom-scale separations and porous membranes used for nano to micron-scale separations. Biological membranes utilize well-defined Angstrom-scale pores to provide exceptional transport properties and can be used as inspiration to overcome this trade-off. Here, we present a comprehensive demonstration of such a bioinspired approach based on pillar[5]arene artificial water channels, resulting in artificial water channel-based block copolymer membranes. These membranes have a sharp selectivity profile with a molecular weight cutoff of ~ 500 Da, a size range challenging to achieve with current membranes, while achieving a large improvement in permeability (~65 L m -2  h -1  bar -1  compared with 4-7 L m -2  h -1  bar -1 ) over similarly rated commercial membranes.

Electrostatic tuning of permeation and selectivity in aquaporin water channels

DEFF Research Database (Denmark)

Jensen, Mogens O Stibius; Tajkhorshid, E.; Schulten, K.

2003-01-01

Water permeation and electrostatic interactions between water and channel are investigated in the Escherichia coli glycerol uptake facilitator GlpF, a member of the aquaporin water channel family, by molecular dynamics simulations. A tetrameric model of the channel embedded in a 16:0/ 18:1c9...... with the protein electrostatic fields enforce a bipolar water configuration inside the channel with dipole inversion at the NPA motifs. At the NPA motifs water-protein electrostatic interactions facilitate this inversion. Furthermore, water-water electrostatic interactions are in all regions inside the channel...... stronger than water-protein interactions, except near a conserved, positively charged Arg residue. We find that variations of the protein electrostatic field through the channel, owing to preserved structural features, completely explain the bipolar orientation of water. This orientation persists despite...

Whether and How to Select Inertia and Acceleration of Discrete Particle Swarm Optimization Algorithm: A Study on Channel Assignment

Directory of Open Access Journals (Sweden)

Min Jin

2014-01-01

Full Text Available There is recently a great deal of interest and excitement in understanding the role of inertia and acceleration in the motion equation of discrete particle swarm optimization (DPSO algorithms. It still remains unknown whether the inertia section should be abandoned and how to select the appropriate acceleration in order for DPSO to show the best convergence performance. Adopting channel assignment as a case study, this paper systematically conducts experimental filtering research on this issue. Compared with other channel assignment schemes, the proposed scheme and the selection of inertia and acceleration are verified to have the advantage to channel assignment in three respects of convergence rate, convergence speed, and the independency of the quality of initial solution. Furthermore, the experimental result implies that DSPO might have the best convergence performance when its motion equation includes an inertia section in a less medium weight, a bigger acceleration coefficient for global-search optimum, and a smaller acceleration coefficient for individual-search optimum.

Ultrastructural observations reveal the presence of channels between cork cells.

Science.gov (United States)

Teixeira, Rita Teresa; Pereira, Helena

2009-12-01

The ultrastructure of phellem cells of Quercus suber L. (cork oak) and Calotropis procera (Ait) R. Br. were analyzed using electron transmission microscopy to determine the presence or absence of plasmodesmata (PD). Different types of Q. suber cork samples were studied: one year shoots; virgin cork (first periderm), reproduction cork (traumatic periderm), and wet cork. The channel structures of PD were found in all the samples crossing adjacent cell walls through the suberin layer of the secondary wall. Calotropis phellem also showed PD crossing the cell walls of adjacent cells but in fewer numbers compared to Q. suber. In one year stems of cork oak, it was possible to follow the physiologically active PD with ribosomic accumulation next to the aperture of the channel seen in the phellogen cells to the completely obstructed channels in the dead cells that characterize the phellem tissue.

Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes

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Pedro L. Flores

2017-06-01

Full Text Available 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.

A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels

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Cerrone Cabanos

2017-08-01

Full Text Available Lipid regulation of ion channels by low-abundance signaling lipids phosphatidylinositol 4,5-bisphosphate (PIP2 and phosphatidic acid (PA has emerged as a central cellular mechanism for controlling ion channels and the excitability of nerves. A lack of robust assays suitable for facile detection of a lipid bound to a channel has hampered the probing of the lipid binding sites and measuring the pharmacology of putative lipid agonists for ion channels. Here, we show a fluorescent PIP2 competition assay for detergent-purified potassium channels, including TWIK-1-related K+-channel (TREK-1. Anionic lipids PA and phosphatidylglycerol (PG bind dose dependently (9.1 and 96 μM, respectively and agonize the channel. Our assay shows PIP2 binds with high affinity (0.87 μM but surprisingly can directly antagonize TREK-1 in liposomes. We propose a model for TREK-1 lipid regulation where PIP2 can compete with PA and PG agonism based on the affinity of the lipid for a site within the channel.

Strategies for sustainable channel relations in mobile telecom sector

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Githa Heggde

2011-01-01

Full Text Available The telecom sector in India largely comprises of wireless connections for phones. As of today, there are approximately 21 network providers in the country with about 7 per each circle, each offering competitive pricing to the consumers. The main objective of the study is to provide an accurate role for the company executive in developing channel relations. Further to this, the study explores the strategies which can sustain a good working relationship between the company and its channel members in the mobile telecom sector. The constructs identified for developing sustainable relationships were Setting distribution objectives, Channel design, Logistics, Image Building, Inventory management, Channel management, Payment & credit, Promotional assistance, Setting targets, Coverage frequency , Motivating channel members to perform. The sample selected contained distributors from the Mobile telecom sector and company executives/channel managers of leading telecom companies. Factor analysis and Friedman’s test was applied. The findings revealed a correlation in attitude between distributors and the executives. Motivating distributors was rated as the most important strategy by the company. The distributors felt that all channel partners needed to have positive attitude towards the channel while company executives felt that aggression made channel members perform effectively. Such findings will be of use to mobile telecom companies who are new entrants to the Indian market and to existing companies who plan to expand their coverage.

Gabapentin Modulates HCN4 Channel Voltage-Dependence

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Han-Shen Tae

2017-08-01

Full Text Available Gabapentin (GBP is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on hyperpolarization-activated cation (HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2, and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+ or calretinin positive (CR+ inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100 μM caused a hyperpolarizing shift in the voltage of half activation (V1/2 thereby reducing the currents. Gabapentin had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1 channels. Gabapentin also caused a hyperpolarizing shift in the V1/2 of Ih measured from HCN4-expressing PV+ inhibitory neurons in the spinal dorsal horn. Gabapentin had minimal effect on Ih recorded from CR+ neurons. Consistent with this, immunohistochemical analysis revealed that the majority of CR+ inhibitory neurons do not express somatic HCN4 channels. In conclusion, GBP reduces HCN4 channel-mediated currents through a hyperpolarized shift in the V1/2. The HCN channel subtype selectivity of GBP provides a unique tool for investigating HCN4 channel function in the central nervous system. The HCN4 channel is a candidate molecular target for the acute analgesic and anticonvulsant actions of GBP.

Ion channel profile of TRPM8 cold receptors reveals a novel role of TASK-3 potassium channels in thermosensation

Science.gov (United States)

Morenilla-Palao, Cruz; Luis, Enoch; Fernández-Peña, Carlos; Quintero, Eva; Weaver, Janelle L.; Bayliss, Douglas A.; Viana, Félix

2017-01-01

Summary Animals sense cold ambient temperatures through the activation of peripheral thermoreceptors that express TRPM8, a cold- and menthol-activated ion channel. These receptors can discriminate a very wide range of temperatures from innocuous to noxious. The molecular mechanism responsible for the variable sensitivity of individual cold receptors to temperature is unclear. To address this question, we performed a detailed ion channel expression analysis of cold sensitive neurons, combining BAC transgenesis with a molecular profiling approach in FACS purified TRPM8 neurons. We found that TASK-3 leak potassium channels are highly enriched in a subpopulation of these sensory neurons. The thermal threshold of TRPM8 cold neurons is decreased during TASK-3 blockade and in mice lacking TASK-3 and, most importantly, these mice display hypersensitivity to cold. Our results demonstrate a novel role of TASK-3 channels in thermosensation, showing that a channel-based combinatorial strategy in TRPM8 cold thermoreceptors leads to molecular specialization and functional diversity. PMID:25199828

TRESK potassium channel in human T lymphoblasts

International Nuclear Information System (INIS)

Sánchez-Miguel, Dénison Selene; García-Dolores, Fernando; Rosa Flores-Márquez, María; Delgado-Enciso, Iván; Pottosin, Igor; Dobrovinskaya, Oxana

2013-01-01

Highlights: • TRESK (KCNK18) mRNA is present in different T lymphoblastic cell lines. • KCNK18 mRNA was not found in resting peripheral blood lymphocytes. • Clinical samples of T lymphoblastic leukemias and lymphomas were positive for TRESK. • TRESK in T lymphoblasts has dual localization, in plasma membrane and intracellular. -- Abstract: TRESK (TWIK-related spinal cord K + ) channel, encoded by KCNK18 gene, belongs to the double-pore domain K + channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K + channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed

TRESK potassium channel in human T lymphoblasts

Energy Technology Data Exchange (ETDEWEB)

Sánchez-Miguel, Dénison Selene, E-mail: amurusk@hotmail.com [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); García-Dolores, Fernando, E-mail: garciaddf@yahoo.com [Department of Pathology, Institute of Forensic Sciences, Av. Niños Héroes 130, Col. Doctores, C.P. 06720 Mexico, DF (Mexico); Rosa Flores-Márquez, María, E-mail: mariafo31@yahoo.com.mx [National Medical Center of Occident (CMNO) IMSS, Belisario Dominguez 735, Col. Independencia Oriente, C.P. 44340 Guadalajara, Jalisco (Mexico); Delgado-Enciso, Iván [University of Colima, School of Medicine, Av. Universidad 333, Col. Las Viboras, C.P. 28040 Colima (Mexico); Pottosin, Igor, E-mail: pottosin@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); Dobrovinskaya, Oxana, E-mail: oxana@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico)

2013-05-03

Highlights: • TRESK (KCNK18) mRNA is present in different T lymphoblastic cell lines. • KCNK18 mRNA was not found in resting peripheral blood lymphocytes. • Clinical samples of T lymphoblastic leukemias and lymphomas were positive for TRESK. • TRESK in T lymphoblasts has dual localization, in plasma membrane and intracellular. -- Abstract: TRESK (TWIK-related spinal cord K{sup +}) channel, encoded by KCNK18 gene, belongs to the double-pore domain K{sup +} channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K{sup +} channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed.

Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27

Science.gov (United States)

Balana, Bartosz; Maslennikov, Innokentiy; Kwiatkowski, Witek; Stern, Kalyn M.; Bahima, Laia; Choe, Senyon; Slesinger, Paul A.

2011-01-01

G protein-gated inwardly rectifying potassium (GIRK) channels are important gatekeepers of neuronal excitability. The surface expression of neuronal GIRK channels is regulated by the psychostimulant-sensitive sorting nexin 27 (SNX27) protein through a class I (-X-Ser/Thr-X-Φ, where X is any residue and Φ is a hydrophobic amino acid) PDZ-binding interaction. The G protein-insensitive inward rectifier channel (IRK1) contains the same class I PDZ-binding motif but associates with a different synaptic PDZ protein, postsynaptic density protein 95 (PSD95). The mechanism by which SNX27 and PSD95 discriminate these channels was previously unclear. Using high-resolution structures coupled with biochemical and functional analyses, we identified key amino acids upstream of the channel's canonical PDZ-binding motif that associate electrostatically with a unique structural pocket in the SNX27-PDZ domain. Changing specific charged residues in the channel's carboxyl terminus or in the PDZ domain converts the selective association and functional regulation by SNX27. Elucidation of this unique interaction site between ion channels and PDZ-containing proteins could provide a therapeutic target for treating brain diseases. PMID:21422294

Seismarmara experiment: results from reprocessing of selected multi-channel seismic reflection profiles

Science.gov (United States)

Cetin, S.; Voogd, B.; Carton, H.; Laigle, M.; Becel, A.; Saatcilar, R.; Singh, S.; Hirn, A.

2003-04-01

The North Anatolian Fault (NAF) has been responsible for the earthquakes of Izmit and Duzce in 1999. The occurrence of these earthquakes has drawn scientific attention into the Sea of Marmara since the NAF enters into the Sea of Marmara where the latest Izmit earthquake rupture stopped. The SEISMARMARA-2001 survey is a combined seismic reflection, refraction and earthquake experiment carried out in 2001 in the Marmara Region in Turkey by French-Turkish scientific cooperation. The objectives of this survey were to image the various branches of the NAF and related other fault systems. R/V Le Nadir was equipped with a 4.5 km long streamer with 360 channels and a large airgun source. During Leg 1, a grid of large regional lines encompassing the whole Marmara trough was shot. For part of them a strong 8100 cu.in. source for deepest penetration was used, with a 150 m shot interval giving a 15-fold coverage. Another part was shot for a higher resolution with a 2900 cu. in. array at a 50m or 38 m interval to give a 45 or 60-fold coverage. The latter acquisition parameters were used for Leg 2 that was devoted to a very dense grid of lines in the Cinarcik Basin Reprocessing of the multi-channel seismic data is currently being undertaken in several Institutions using different seismic processing softwares (GeoVecteur, ProMAX, Focus), to take advantage of the diverse acquisitions and cope with their limitations, for instance high fold-order for Leg 2 and strength of signal but loose spatial sampling for the bigger source. The main objectives of the reprocessing of the selected profiles are to do a detailed velocity analysis and stacking after deconvolution, filtering to remove or suppress deep sea bottom multiples and out of plane reflections, and time-migration and depth conversion and thus reveal both the shallow and deeper reflection image of the crust in the Sea of Marmara. We show that choosing an appropriate processing sequence for different sources and acquisition

Joint source/channel coding of scalable video over noisy channels

Energy Technology Data Exchange (ETDEWEB)

Cheung, G.; Zakhor, A. [Department of Electrical Engineering and Computer Sciences University of California Berkeley, California94720 (United States)

1997-01-01

We propose an optimal bit allocation strategy for a joint source/channel video codec over noisy channel when the channel state is assumed to be known. Our approach is to partition source and channel coding bits in such a way that the expected distortion is minimized. The particular source coding algorithm we use is rate scalable and is based on 3D subband coding with multi-rate quantization. We show that using this strategy, transmission of video over very noisy channels still renders acceptable visual quality, and outperforms schemes that use equal error protection only. The flexibility of the algorithm also permits the bit allocation to be selected optimally when the channel state is in the form of a probability distribution instead of a deterministic state. {copyright} {ital 1997 American Institute of Physics.}

Atomic force microscopy imaging reveals the formation of ASIC/ENaC cross-clade ion channels

International Nuclear Information System (INIS)

Jeggle, Pia; Smith, Ewan St. J.; Stewart, Andrew P.; Haerteis, Silke; Korbmacher, Christoph; Edwardson, J. Michael

2015-01-01

ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a. AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. - Highlights: • There is evidence for a close association between ASIC and ENaC. • We used AFM to test whether ASIC1a and ENaC subunits form cross-clade ion channels. • Isolated proteins were incubated with subunit-specific antibodies and Fab fragments. • Some proteins were doubly decorated at ∼120° by an antibody and a Fab fragment. • Our results indicate the formation of ASIC1a/ENaC heterotrimers

Atomic force microscopy imaging reveals the formation of ASIC/ENaC cross-clade ion channels

Energy Technology Data Exchange (ETDEWEB)

Jeggle, Pia; Smith, Ewan St. J.; Stewart, Andrew P. [Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD (United Kingdom); Haerteis, Silke; Korbmacher, Christoph [Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstrasse 6, 91054 Erlangen (Germany); Edwardson, J. Michael, E-mail: jme1000@cam.ac.uk [Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD (United Kingdom)

2015-08-14

ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a. AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. - Highlights: • There is evidence for a close association between ASIC and ENaC. • We used AFM to test whether ASIC1a and ENaC subunits form cross-clade ion channels. • Isolated proteins were incubated with subunit-specific antibodies and Fab fragments. • Some proteins were doubly decorated at ∼120° by an antibody and a Fab fragment. • Our results indicate the formation of ASIC1a/ENaC heterotrimers.

Bathymetric survey of the Cayuga Inlet flood-control channel and selected tributaries in Ithaca, New York, 2016

Science.gov (United States)

Wernly, John F.; Nystrom, Elizabeth A.; Coon, William F.

2017-09-08

From July 14 to July 20, 2016, the U.S. Geological Survey, in cooperation with the City of Ithaca, New York, and the New York State Department of State, surveyed the bathymetry of the Cayuga Inlet flood-control channel and the mouths of selected tributaries to Cayuga Inlet and Cayuga Lake in Ithaca, N.Y. The flood-control channel, built by the U.S. Army Corps of Engineers between 1965 and 1970, was designed to convey flood flows from the Cayuga Inlet watershed through the City of Ithaca and minimize possible flood damages. Since that time, the channel has infrequently been maintained by dredging, and sediment accumulation and resultant shoaling have greatly decreased the conveyance of the channel and its navigational capability.U.S. Geological Survey personnel collected bathymetric data by using an acoustic Doppler current profiler. The survey produced a dense dataset of water depths that were converted to bottom elevations. These elevations were then used to generate a geographic information system bathymetric surface. The bathymetric data and resultant bathymetric surface show the current condition of the channel and provide the information that governmental agencies charged with maintaining the Cayuga Inlet for flood-control and navigational purposes need to make informed decisions regarding future maintenance measures.

Sculpting ion channel functional expression with engineered ubiquitin ligases

Science.gov (United States)

Kanner, Scott A; Morgenstern, Travis

2017-01-01

The functional repertoire of surface ion channels is sustained by dynamic processes of trafficking, sorting, and degradation. Dysregulation of these processes underlies diverse ion channelopathies including cardiac arrhythmias and cystic fibrosis. Ubiquitination powerfully regulates multiple steps in the channel lifecycle, yet basic mechanistic understanding is confounded by promiscuity among E3 ligase/substrate interactions and ubiquitin code complexity. Here we targeted the catalytic domain of E3 ligase, CHIP, to YFP-tagged KCNQ1 ± KCNE1 subunits with a GFP-nanobody to selectively manipulate this channel complex in heterologous cells and adult rat cardiomyocytes. Engineered CHIP enhanced KCNQ1 ubiquitination, eliminated KCNQ1 surface-density, and abolished reconstituted K+ currents without affecting protein expression. A chemo-genetic variation enabling chemical control of ubiquitination revealed KCNQ1 surface-density declined with a ~ 3.5 hr t1/2 by impaired forward trafficking. The results illustrate utility of engineered E3 ligases to elucidate mechanisms underlying ubiquitin regulation of membrane proteins, and to achieve effective post-translational functional knockdown of ion channels. PMID:29256394

Incorporating Born solvation energy into the three-dimensional Poisson-Nernst-Planck model to study ion selectivity in KcsA K+ channels

Science.gov (United States)

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 ) .

An iterative detection method of MIMO over spatial correlated frequency selective channel: using list sphere decoding for simplification

Science.gov (United States)

Shi, Zhiping; Yan, Bing

2010-08-01

In multiple-input multiple-output(MIMO) wireless systems, combining good channel codes(e.g., Non-binary Repeat Accumulate codes) with adaptive turbo equalization is a good option to get better performance and lower complexity under Spatial Correlated Frequency Selective(SCFS) Channel. The key of this method is after joint antennas MMSE detection (JAD/MMSE) based on interruption cancelling using soft information, considering the detection result as an output of a Gaussian equivalent flat fading channel, and performing maximum likelihood detection(ML) to get more correct estimated result. But the using of ML brings great complexity increase, which is not allowed. In this paper, a low complexity method called list sphere decoding is introduced and applied to replace the ML in order to simplify the adaptive iterative turbo equalization system.

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

Directory of Open Access Journals (Sweden)

Chiao-Ling Lo

2016-08-01

Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

Science.gov (United States)

Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

2016-08-01

Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

On the performance of arbitrary transmit selection for threshold-based receive MRC with and without co-channel interference

KAUST Repository

Radaydeh, Redha Mahmoud Mesleh

2011-11-01

The performance of multiple-antenna diversity systems in which the receiver combines signal replicas per threshold-based maximal ratio combining (MRC) and transmitter uses only a single antenna according to receive combined signal strength is studied. The impact of imperfect channel estimation and the effect of phase and time misalignments between desired and undesired signals are implicitly investigated. It is assumed that the desired signal replicas and interfering signals undergo statistically independent flat Rayleigh fading. The analysis is applicable for arbitrary transmit antenna selection, based either on receive combined signal-to-noise ratio (SNR) or receive combined signal-to-interference-plus-noise ratio (SINR). For the scenario of identical multiple-antenna channels, closed-form analytical results for the combined SNR statistics and some performance measures are first presented. The SNR-based and SINR-based selection algorithms are then employed to obtain expressions for the distribution of combined SINR and outage probability performance, which are applicable for different statistical models of interfering signals. The adopted system models herein as well as the analytical development add enhancements on many existing results, and can be used to study the performance of different architectures under various channel conditions when the implementation complexity is of interest. © 2011 IEEE.

On the performance of arbitrary transmit selection for threshold-based receive MRC with and without co-channel interference

KAUST Repository

Radaydeh, Redha Mahmoud Mesleh; Alouini, Mohamed-Slim

2011-01-01

The performance of multiple-antenna diversity systems in which the receiver combines signal replicas per threshold-based maximal ratio combining (MRC) and transmitter uses only a single antenna according to receive combined signal strength is studied. The impact of imperfect channel estimation and the effect of phase and time misalignments between desired and undesired signals are implicitly investigated. It is assumed that the desired signal replicas and interfering signals undergo statistically independent flat Rayleigh fading. The analysis is applicable for arbitrary transmit antenna selection, based either on receive combined signal-to-noise ratio (SNR) or receive combined signal-to-interference-plus-noise ratio (SINR). For the scenario of identical multiple-antenna channels, closed-form analytical results for the combined SNR statistics and some performance measures are first presented. The SNR-based and SINR-based selection algorithms are then employed to obtain expressions for the distribution of combined SINR and outage probability performance, which are applicable for different statistical models of interfering signals. The adopted system models herein as well as the analytical development add enhancements on many existing results, and can be used to study the performance of different architectures under various channel conditions when the implementation complexity is of interest. © 2011 IEEE.

Mechanisms of molecular transport through the urea channel of Helicobacter pylori

Science.gov (United States)

McNulty, Reginald; Ulmschneider, Jakob P.; Luecke, Hartmut; Ulmschneider, Martin B.

2013-12-01

Helicobacter pylori survival in acidic environments relies on cytoplasmic hydrolysis of gastric urea into ammonia and carbon dioxide, which buffer the pathogen’s periplasm. Urea uptake is greatly enhanced and regulated by HpUreI, a proton-gated inner membrane channel protein essential for gastric survival of H. pylori. The crystal structure of HpUreI describes a static snapshot of the channel with two constriction sites near the center of the bilayer that are too narrow to allow passage of urea or even water. Here we describe the urea transport mechanism at atomic resolution, revealed by unrestrained microsecond equilibrium molecular dynamics simulations of the hexameric channel assembly. Two consecutive constrictions open to allow conduction of urea, which is guided through the channel by interplay between conserved residues that determine proton rejection and solute selectivity. Remarkably, HpUreI conducts water at rates equivalent to aquaporins, which might be essential for efficient transport of urea at small concentration gradients.

Broadband Mm-Wave OFDM Communications in Doubly Selective Channel: Performance Evaluation Using Measured Mm-Wave Channel

DEFF Research Database (Denmark)

Chen, Xiaoming; Fan, Wei; Pedersen, Gert F.

2018-01-01

In this work, we evaluate the performance of the broadband millimeter-wave (mm-wave) OFDM system in the presence of phase noise (PN) of phase-locked loop based oscillator and delay spread of measured mm-wave channel. It is shown, using Akaike's information criterion, that the channel tap...... coefficients of the broadband mm-wave channel do not follow Gaussian distribution due to the broad bandwidth. It is also shown that, given a cyclic prefix (CP) length for a certain delay spread, an effective PN mitigation scheme enables a PN corrupted OFDM system to function with small subcarrier spacing and...

Design of Nonuniform Filter Bank Transceivers for Frequency Selective Channels

Directory of Open Access Journals (Sweden)

Yuan-Pei Lin

2007-01-01

Full Text Available In recent years, there has been considerable interest in the theory and design of filter bank transceivers due to their superior frequency response. In many applications, it is desired to have transceivers that can support multiple services with different incoming data rates and different quality-of-service requirements. To meet these requirements, we can either do resource allocation or design transceivers with a nonuniform bandwidth partition. In this paper, we propose a method for the design of nonuniform filter bank transceivers for frequency selective channels. Both frequency response and signal-to-interference ratio (SIR can be incorporated in the transceiver design. Moreover, the technique can be extended to the case of nonuniform filter bank transceivers with rational sampling factors. Simulation results show that nonuniform filter bank transceivers with good filter responses as well as high SIR can be obtained by the proposed design method.

Can combining web and mobile communication channels reveal concealed customer value?

OpenAIRE

Bothorel, Grégoire; Vanheems, Régine; Guérin, Anne

2015-01-01

International audience; Many firms have implemented a customer-value based segmentation to improve the efficiency of MARCOM campaigns as part of their long term customer relationship strategies (Kumar 2010, Thomas et al. 2005).If distribution channel addition may increase the intrinsic customer value (Kumar 2005, Rangaswamy 2005) in a US context as well as in a French context (Vanheems 2009), few studies have been conducted about the impact of adding a new communication channel during the sam...

Synthesis, structural characterization and selectively catalytic properties of metal-organic frameworks with nano-sized channels: A modular design strategy

International Nuclear Information System (INIS)

Qiu Lingguang; Gu Lina; Hu Gang; Zhang Lide

2009-01-01

Modular design method for designing and synthesizing microporous metal-organic frameworks (MOFs) with selective catalytical activity was described. MOFs with both nano-sized channels and potential catalytic activities could be obtained through self-assembly of a framework unit and a catalyst unit. By selecting hexaaquo metal complexes and the ligand BTC (BTC=1,3,5-benzenetricarboxylate) as framework-building blocks and using the metal complex [M(phen) 2 (H 2 O) 2 ] 2+ (phen=1,10-phenanthroline) as a catalyst unit, a series of supramolecular MOFs 1-7 with three-dimensional nano-sized channels, i.e. [M 1 (H 2 O) 6 ].[M 2 (phen) 2 (H 2 O) 2 ] 2 .2(BTC).xH 2 O (M 1 , M 2 =Co(II), Ni(II), Cu(II), Zn(II), or Mn(II), phen=1,10-phenanthroline, BTC=1,3,5-benzenetricarboxylate, x=22-24), were synthesized through self-assembly, and their structures were characterized by IR, elemental analysis, and single-crystal X-ray diffraction. These supramolecular microporous MOFs showed significant size and shape selectivity in the catalyzed oxidation of phenols, which is due to catalytic reactions taking place in the channels of the framework. Design strategy, synthesis, and self-assembly mechanism for the construction of these porous MOFs were discussed. - Grapical abstract: A modular design strategy has been developed to synthesize microporous metal-organic frameworks with potential catalytic activity by self-assembly of the framework-building blocks and the catalyst unit

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.

Science.gov (United States)

Tikhonov, Denis B; Zhorov, Boris S

2017-04-03

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. © 2017 Tikhonov and Zhorov.

Broadband Mm-Wave OFDM Communications in Doubly Selective Channel: Performance Evaluation Using Measured Mm-Wave Channel

DEFF Research Database (Denmark)

Chen, Xiaoming; Fan, Wei; Pedersen, Gert F.

2018-01-01

coefficients of the broadband mm-wave channel do not follow Gaussian distribution due to the broad bandwidth. It is also shown that, given a cyclic prefix (CP) length for a certain delay spread, an effective PN mitigation scheme enables a PN corrupted OFDM system to function with small subcarrier spacing and......In this work, we evaluate the performance of the broadband millimeter-wave (mm-wave) OFDM system in the presence of phase noise (PN) of phase-locked loop based oscillator and delay spread of measured mm-wave channel. It is shown, using Akaike's information criterion, that the channel tap......, therefore, small CP overhead, with only slight degradation of the error rate performance....

Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

Directory of Open Access Journals (Sweden)

Yue Huang

Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

An information-guided channel-hopping scheme for block-fading channels with estimation errors

KAUST Repository

Yang, Yuli

2010-12-01

Information-guided channel-hopping technique employing multiple transmit antennas was previously proposed for supporting high data rate transmission over fading channels. This scheme achieves higher data rates than some mature schemes, such as the well-known cyclic transmit antenna selection and space-time block coding, by exploiting the independence character of multiple channels, which effectively results in having an additional information transmitting channel. Moreover, maximum likelihood decoding may be performed by simply decoupling the signals conveyed by the different mapping methods. In this paper, we investigate the achievable spectral efficiency of this scheme in the case of having channel estimation errors, with optimum pilot overhead for minimum meansquare error channel estimation, when transmitting over blockfading channels. Our numerical results further substantiate the robustness of the presented scheme, even with imperfect channel state information. ©2010 IEEE.

Development of in-situ laser cutting technique for removal of single selected coolant channel from pressurized heavy water reactor

International Nuclear Information System (INIS)

Vishwakarma, S.C.; Upadhyaya, B.N.

2016-01-01

We report on the development of a pulsed Nd:YAG laser based cutting technique for removal of single coolant channel from pressurized heavy water reactor (PHWR). It includes development of special tools/manipulators and optimization of laser cutting process parameters for cutting of liner tube, end fitting, bellow lip weld joint, and pressure tube stubs. For each cutting operation, a special tool with precision motion control is utilized. These manipulators/tools hold and move the laser cutting nozzle in the required manner and are fixed on the same coolant channel, which has to be removed. This laser cutting technique has been successfully deployed for removal of selected coolant channels Q-16, Q-15 and N-6 of KAPS-2 reactor with minimum radiation dose consumption and in short time. (author)

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

Science.gov (United States)

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

Calcium channels in the brain as targets for the calcium-channel modulators used in the treatment of neurological disorders

NARCIS (Netherlands)

Peters, Thies; WILFFERT, B; VANHOUTTE, PM; VANZWIETEN, PA

1991-01-01

Recent investigations of calcium channels in brain cells by voltage-clamp techniques have revealed that, in spite of electrophysiological similarities, the pharmacological properties of these channels differ considerably from channels in peripheral tissues, e.g., heart and smooth muscle. Therefore,

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

Directory of Open Access Journals (Sweden)

Sigrid Marie Blom

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Ayanjeet, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Gai, Feng, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Hochstrasser, Robin M. [Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Wang, Jun; DeGrado, William F. [Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94143 (United States); Moroz, Yurii S.; Korendovych, Ivan V. [Department of Chemistry, Syracuse University, Syracuse, New York 13244 (United States); Zanni, Martin [Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706 (United States)

2014-06-21

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

Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels.

Science.gov (United States)

Moran, Yehu; Kahn, Roy; Cohen, Lior; Gur, Maya; Karbat, Izhar; Gordon, Dalia; Gurevitz, Michael

2007-08-15

Av3 is a short peptide toxin from the sea anemone Anemonia viridis shown to be active on crustaceans and inactive on mammals. It inhibits inactivation of Na(v)s (voltage-gated Na+ channels) like the structurally dissimilar scorpion alpha-toxins and type I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Na(v)s, we established a system for its expression, mutagenized it throughout, and analysed it in toxicity, binding and electrophysiological assays. The recombinant Av3 was found to be highly toxic to blowfly larvae (ED50=2.65+/-0.46 pmol/100 mg), to compete well with the site-3 toxin LqhalphaIT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (K(i)=21.4+/-7.1 nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNa(v)1, but not that of mammalian Na(v)s expressed in Xenopus oocytes. Moreover, like other site-3 toxins, the activity of Av3 was synergically enhanced by ligands of receptor site-4 (e.g. scorpion beta-toxins). The bioactive surface of Av3 was found to consist mainly of aromatic residues and did not resemble any of the bioactive surfaces of other site-3 toxins. These analyses have portrayed a toxin that might interact with receptor site-3 in a different fashion compared with other ligands of this site. This assumption was corroborated by a D1701R mutation in DmNa(v)1, which has been shown to abolish the activity of all other site-3 ligands, except Av3. All in all, the present study provides further evidence for the heterogeneity of receptor site-3, and raises Av3 as a unique model for design of selective anti-insect compounds.

On conduction in a bacterial sodium channel.

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Simone Furini

Full Text Available Voltage-gated Na⁺-channels are transmembrane proteins that are responsible for the fast depolarizing phase of the action potential in nerve and muscular cells. Selective permeability of Na⁺ over Ca²⁺ or K⁺ ions is essential for the biological function of Na⁺-channels. After the emergence of the first high-resolution structure of a Na⁺-channel, an anionic coordination site was proposed to confer Na⁺ selectivity through partial dehydration of Na⁺ via its direct interaction with conserved glutamate side chains. By combining molecular dynamics simulations and free-energy calculations, a low-energy permeation pathway for Na⁺ ion translocation through the selectivity filter of the recently determined crystal structure of a prokaryotic sodium channel from Arcobacter butzleri is characterised. The picture that emerges is that of a pore preferentially occupied by two ions, which can switch between different configurations by crossing low free-energy barriers. In contrast to K⁺-channels, the movements of the ions appear to be weakly coupled in Na⁺-channels. When the free-energy maps for Na⁺ and K⁺ ions are compared, a selective site is characterised in the narrowest region of the filter, where a hydrated Na⁺ ion, and not a hydrated K⁺ ion, is energetically stable.

Pore size matters for potassium channel conductance

Science.gov (United States)

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

The Extended-Window Channel Estimator for Iterative Channel-and-Symbol Estimation

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Barry John R

2005-01-01

Full Text Available The application of the expectation-maximization (EM algorithm to channel estimation results in a well-known iterative channel-and-symbol estimator (ICSE. The EM-ICSE iterates between a symbol estimator based on the forward-backward recursion (BCJR equalizer and a channel estimator, and may provide approximate maximum-likelihood blind or semiblind channel estimates. Nevertheless, the EM-ICSE has high complexity, and it is prone to misconvergence. In this paper, we propose the extended-window (EW estimator, a novel channel estimator for ICSE that can be used with any soft-output symbol estimator. Therefore, the symbol estimator may be chosen according to performance or complexity specifications. We show that the EW-ICSE, an ICSE that uses the EW estimator and the BCJR equalizer, is less complex and less susceptible to misconvergence than the EM-ICSE. Simulation results reveal that the EW-ICSE may converge faster than the EM-ICSE.

Dynamic Channel Selection for Cognitive Femtocells

DEFF Research Database (Denmark)

Da Costa, Gustavo Wagner Oliveira; Cattoni, Andrea Fabio; Mogensen, Preben

2014-01-01

on state-of-art techniques to manage the radio resources in order to cope with inter-cell interference in cognitive femtocells. Different techniques are presented as examples of gradually increasing sophistication of the cognitive femtocells, allowing for dynamic channel allocation, dynamic reuse......, but not least, the possibility of having closed-subscriber-groups aggravates the inter-cell interference problems. In order to tackle these issues we consider the implementation of some aspects of cognitive radio technology into femtocells, leading to the concept of cognitive femtocells. This chapter focuses...

Cation gating and selectivity in a purified, reconstituted, voltage-dependent sodium channel

International Nuclear Information System (INIS)

Barchi, R.L.; Tanaka, J.C.

1984-01-01

In excitable membranes, the voltage-dependent sodium channel controls the primary membrane conductance change necessary for the generation of an action potential. Over the past four decades, the time- and voltage-dependent sodium currents gated by this channel have been thoroughly documented with increasingly sophisticated voltage-clamp techniques. Recent advances in the biochemistry of membrane proteins have led to the solubilization and purification of this channel protein from nerve (6) and from muscle (4) or muscle-derived (1) membranes, and have provided an approach to the correlation of the channel's molecular structure with its functional properties. Each of these sodium channel preparations appears to contain a large glycoprotein either as its sole component (2) or in association with several small subunits (6, 3). Evidence that these purified proteins represent the excitable membrane sodium channel is presented. 8 refs., 1 fig., 1 tab

Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.

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Marcoline, Frank V; Bethel, Neville; Guerriero, Christopher J; Brodsky, Jeffrey L; Grabe, Michael

2015-08-04

The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diphtheria toxin-induced channels in Vero cells selective for monovalent cations

International Nuclear Information System (INIS)

Sandvig, K.; Olsnes, S.

1988-01-01

Ion fluxes associated with translocation of diphtheria toxin across the surface membrane of Vero cells were studied. When cells with surface-bound toxin were exposed to low pH to induce toxin entry, the cells became permeable to Na+, K+, H+, choline+, and glucosamine+. There was no increased permeability to Cl-, SO4(-2), glucose, or sucrose, whereas the uptake of 45 Ca2+ was slightly increased. The influx of Ca2+, which appears to be different from that of monovalent cations, was reduced by several inhibitors of anion transport and by verapamil, Mn2+, Co2+, and Ca2+, but not by Mg2+. The toxin-induced fluxes of N+, K+, and protons were inhibited by Cd2+. Cd2+ also protected the cells against intoxication by diphtheria toxin, suggesting that the open cation-selective channel is required for toxin translocation. The involvement of the toxin receptor is discussed

Single-channel kinetics of BK (Slo1 channels

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Yanyan eGeng

2015-01-01

Full Text Available Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1 channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD attached to four surrounding transmembrane voltage sensing domains (VSD and a large intracellular cytosolic domain (CTD, also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.

Atomic force microscopy imaging reveals the formation of ASIC/ENaC cross-clade ion channels.

Science.gov (United States)

Jeggle, Pia; Smith, Ewan St J; Stewart, Andrew P; Haerteis, Silke; Korbmacher, Christoph; Edwardson, J Michael

2015-08-14

ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a. AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. Copyright © 2015 Elsevier Inc. All rights reserved.

Channel Estimation in DCT-Based OFDM

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Wang, Yulin; Zhang, Gengxin; Xie, Zhidong; Hu, Jing

2014-01-01

This paper derives the channel estimation of a discrete cosine transform- (DCT-) based orthogonal frequency-division multiplexing (OFDM) system over a frequency-selective multipath fading channel. Channel estimation has been proved to improve system throughput and performance by allowing for coherent demodulation. Pilot-aided methods are traditionally used to learn the channel response. Least square (LS) and mean square error estimators (MMSE) are investigated. We also study a compressed sensing (CS) based channel estimation, which takes the sparse property of wireless channel into account. Simulation results have shown that the CS based channel estimation is expected to have better performance than LS. However MMSE can achieve optimal performance because of prior knowledge of the channel statistic. PMID:24757439

The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations.

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Lorant Janosi

Full Text Available Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins. The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5 shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value.

Antenna Selection for Full-Duplex MIMO Two-Way Communication Systems

KAUST Repository

Wilson-Nunn, Daniel; Chaaban, Anas; Sezgin, Aydin; Alouini, Mohamed-Slim

2017-01-01

Antenna selection for full-duplex communication between two nodes, each equipped with a predefined number of antennae and transmit/receive chains, is studied. Selection algorithms are proposed based on magnitude, orthogonality, and determinant criteria. The algorithms are compared to optimal selection obtained by exhaustive search as well as random selection, and are shown to yield performance fairly close to optimal at a much lower complexity. Performance comparison for a Rayleigh fading symmetric channel reveals that selecting a single transmit antenna is best at low signal-to-noise ratio (SNR), while selecting an equal number of transmit and receive antennae is best at high SNR.

Antenna Selection for Full-Duplex MIMO Two-Way Communication Systems

KAUST Repository

Wilson-Nunn, Daniel

2017-03-11

Antenna selection for full-duplex communication between two nodes, each equipped with a predefined number of antennae and transmit/receive chains, is studied. Selection algorithms are proposed based on magnitude, orthogonality, and determinant criteria. The algorithms are compared to optimal selection obtained by exhaustive search as well as random selection, and are shown to yield performance fairly close to optimal at a much lower complexity. Performance comparison for a Rayleigh fading symmetric channel reveals that selecting a single transmit antenna is best at low signal-to-noise ratio (SNR), while selecting an equal number of transmit and receive antennae is best at high SNR.

Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies.

Science.gov (United States)

Bezençon, Olivier; Heidmann, Bibia; Siegrist, Romain; Stamm, Simon; Richard, Sylvia; Pozzi, Davide; Corminboeuf, Olivier; Roch, Catherine; Kessler, Melanie; Ertel, Eric A; Reymond, Isabelle; Pfeifer, Thomas; de Kanter, Ruben; Toeroek-Schafroth, Michael; Moccia, Luca G; Mawet, Jacques; Moon, Richard; Rey, Markus; Capeleto, Bruno; Fournier, Elvire

2017-12-14

We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.

Language Planning, Channel Management, and ESP.

Science.gov (United States)

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…

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

Science.gov (United States)

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

Compressive Sensing Based Bayesian Sparse Channel Estimation for OFDM Communication Systems: High Performance and Low Complexity

Science.gov (United States)

Xu, Li; Shan, Lin; Adachi, Fumiyuki

2014-01-01

In orthogonal frequency division modulation (OFDM) communication systems, channel state information (CSI) is required at receiver due to the fact that frequency-selective fading channel leads to disgusting intersymbol interference (ISI) over data transmission. Broadband channel model is often described by very few dominant channel taps and they can be probed by compressive sensing based sparse channel estimation (SCE) methods, for example, orthogonal matching pursuit algorithm, which can take the advantage of sparse structure effectively in the channel as for prior information. However, these developed methods are vulnerable to both noise interference and column coherence of training signal matrix. In other words, the primary objective of these conventional methods is to catch the dominant channel taps without a report of posterior channel uncertainty. To improve the estimation performance, we proposed a compressive sensing based Bayesian sparse channel estimation (BSCE) method which cannot only exploit the channel sparsity but also mitigate the unexpected channel uncertainty without scarifying any computational complexity. The proposed method can reveal potential ambiguity among multiple channel estimators that are ambiguous due to observation noise or correlation interference among columns in the training matrix. Computer simulations show that proposed method can improve the estimation performance when comparing with conventional SCE methods. PMID:24983012

Thermodynamics of competitive molecular channel transport: application to artificial nuclear pores.

Science.gov (United States)

Bauer, Wolfgang R; Nadler, Walter

2010-12-13

In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species' translocation probability when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules.

A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

Science.gov (United States)

Kajma, Anna; Szewczyk, Adam

2012-10-01

Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells.

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Erin K Purcell

Full Text Available The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitability are unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type potassium current by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (~30%, ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection.

Science.gov (United States)

Wang, Yong; Wu, Qiao-Feng; Chen, Chen; Wu, Ling-Yun; Yan, Xian-Zhong; Yu, Shu-Guang; Zhang, Xiang-Sun; Liang, Fan-Rong

2012-01-01

Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use. In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment. Specifically, we generate and investigate the high-throughput metabolic profiles of acupuncture treatment at several acupoints in human. To select the subsets of metabolites that best characterize the acupuncture effect for each meridian point, an optimization model is proposed to identify biomarkers from high-dimensional metabolic data from case and control samples. Importantly, we use nearest centroid as the prototype to simultaneously minimize the number of selected features and the leave-one-out cross validation error of classifier. We compared the performance of LPFS to several state-of-the-art methods, such as SVM recursive feature elimination (SVM-RFE) and sparse multinomial logistic regression approach (SMLR). We find that our LPFS method tends to reveal a small set of metabolites with small standard deviation and large shifts, which exactly serves our requirement for good biomarker. Biologically, several metabolite biomarkers for acupuncture treatment are revealed and serve as the candidates for further mechanism investigation. Also biomakers derived from five meridian points, Zusanli (ST36), Liangmen (ST21), Juliao (ST3), Yanglingquan (GB34), and Weizhong (BL40), are compared for their similarity and difference, which provide evidence for the specificity of acupoints. Our result demonstrates that metabolic profiling might be a promising method to

Optimal channel choice for collaborative ad-hoc dissemination

DEFF Research Database (Denmark)

Hu, Liang; Boudec, J-Y. L.; Vojnovic, M.

2010-01-01

Collaborative ad-hoc dissemination of information has been proposed as an efficient means to disseminate information among devices in a wireless ad-hoc network. Devices help in forwarding the information channels to the entire network, by disseminating the channels they subscribe to, plus others...... by a Metropolis-Hastings sampling algorithm. We also give a variant that accounts for battery level. This leads to a practical channel selection and re-selection algorithm that can be implemented without any central control....

Identification and analysis of genome-wide SNPs provide insight into signatures of selection and domestication in channel catfish (Ictalurus punctatus.

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Luyang Sun

Full Text Available Domestication and selection for important performance traits can impact the genome, which is most often reflected by reduced heterozygosity in and surrounding genes related to traits affected by selection. In this study, analysis of the genomic impact caused by domestication and artificial selection was conducted by investigating the signatures of selection using single nucleotide polymorphisms (SNPs in channel catfish (Ictalurus punctatus. A total of 8.4 million candidate SNPs were identified by using next generation sequencing. On average, the channel catfish genome harbors one SNP per 116 bp. Approximately 6.6 million, 5.3 million, 4.9 million, 7.1 million and 6.7 million SNPs were detected in the Marion, Thompson, USDA103, Hatchery strain, and wild population, respectively. The allele frequencies of 407,861 SNPs differed significantly between the domestic and wild populations. With these SNPs, 23 genomic regions with putative selective sweeps were identified that included 11 genes. Although the function for the majority of the genes remain unknown in catfish, several genes with known function related to aquaculture performance traits were included in the regions with selective sweeps. These included hypoxia-inducible factor 1β. HIFιβ.. and the transporter gene ATP-binding cassette sub-family B member 5 (ABCB5. HIF1β. is important for response to hypoxia and tolerance to low oxygen levels is a critical aquaculture trait. The large numbers of SNPs identified from this study are valuable for the development of high-density SNP arrays for genetic and genomic studies of performance traits in catfish.

Private selective sweeps identified from next-generation pool-sequencing reveal convergent pathways under selection in two inbred Schistosoma mansoni strains.

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Julie A J Clément

Full Text Available BACKGROUND: The trematode flatworms of the genus Schistosoma, the causative agents of schistosomiasis, are among the most prevalent parasites in humans, affecting more than 200 million people worldwide. In this study, we focused on two well-characterized strains of S. mansoni, to explore signatures of selection. Both strains are highly inbred and exhibit differences in life history traits, in particular in their compatibility with the intermediate host Biomphalaria glabrata. METHODOLOGY/PRINCIPAL FINDINGS: We performed high throughput sequencing of DNA from pools of individuals of each strain using Illumina technology and identified single nucleotide polymorphisms (SNP and copy number variations (CNV. In total, 708,898 SNPs were identified and roughly 2,000 CNVs. The SNPs revealed low nucleotide diversity (π = 2 × 10(-4 within each strain and a high differentiation level (Fst = 0.73 between them. Based on a recently developed in-silico approach, we further detected 12 and 19 private (i.e. specific non-overlapping selective sweeps among the 121 and 151 sweeps found in total for each strain. CONCLUSIONS/SIGNIFICANCE: Functional annotation of transcripts lying in the private selective sweeps revealed specific selection for functions related to parasitic interaction (e.g. cell-cell adhesion or redox reactions. Despite high differentiation between strains, we identified evolutionary convergence of genes related to proteolysis, known as a key virulence factor and a potential target of drug and vaccine development. Our data show that pool-sequencing can be used for the detection of selective sweeps in parasite populations and enables one to identify biological functions under selection.

Coassembly of big conductance Ca2+-activated K+ channels and L-type voltage-gated Ca2+ channels in rat brain

DEFF Research Database (Denmark)

Grunnet, Morten; Kaufmann, Walter A

2004-01-01

Based on electrophysiological studies, Ca(2+)-activated K(+) channels and voltage-gated Ca(2+) channels appear to be located in close proximity in neurons. Such colocalization would ensure selective and rapid activation of K(+) channels by local increases in the cytosolic calcium concentration...

Molecular type channeling of relativistic electrons in crystals

International Nuclear Information System (INIS)

Vyatkin, E.G.; Filimonov, Yu.M.; Taratin, A.M.; Vorobiev, S.A.

1983-01-01

Channeling of relativistic electrons in direction in a diamond crystal and the channeling radiation spectra are investigated using computer simulation by the binary collision model and using the model of a continuum potential of the atomic rows. In a computer experiment the atomic- and molecular-type states of channeled elcetrons are revealed, and the orientational dependence of the electron trapping probability in these states is obtained. The peculiarities revealed of the angular distributions and radiation spectra of electrons in the molecular-type states allow to discover these states in the experiment. (author)

Thermodynamics of competitive molecular channel transport: application to artificial nuclear pores.

Directory of Open Access Journals (Sweden)

Wolfgang R Bauer

Full Text Available In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species' translocation probability when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules.

Channel Selection and Feature Projection for Cognitive Load Estimation Using Ambulatory EEG

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Tian Lan

2007-01-01

Full Text Available We present an ambulatory cognitive state classification system to assess the subject's mental load based on EEG measurements. The ambulatory cognitive state estimator is utilized in the context of a real-time augmented cognition (AugCog system that aims to enhance the cognitive performance of a human user through computer-mediated assistance based on assessments of cognitive states using physiological signals including, but not limited to, EEG. This paper focuses particularly on the offline channel selection and feature projection phases of the design and aims to present mutual-information-based techniques that use a simple sample estimator for this quantity. Analyses conducted on data collected from 3 subjects performing 2 tasks (n-back/Larson at 2 difficulty levels (low/high demonstrate that the proposed mutual-information-based dimensionality reduction scheme can achieve up to 94% cognitive load estimation accuracy.

Symbol Error Probability of DF Relay Selection over Arbitrary Nakagami-m Fading Channels

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George C. Alexandropoulos

2013-01-01

Full Text Available We present a new analytical expression for the moment generating function (MGF of the end-to-end signal-to-noise ratio of dual-hop decode-and-forward (DF relaying systems with relay selection when operating over Nakagami-m fading channels. The derived MGF expression, which is valid for arbitrary values of the fading parameters of both hops, is subsequently utilized to evaluate the average symbol error probability (ASEP of M-ary phase shift keying modulation for the considered DF relaying scheme under various asymmetric fading conditions. It is shown that the MGF-based ASEP performance evaluation results are in excellent agreement with equivalent ones obtained by means of computer simulations, thus validating the correctness of the presented MGF expression.

A Robust Threshold for Iterative Channel Estimation in OFDM Systems

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A. Kalaycioglu

2010-04-01

Full Text Available A novel threshold computation method for pilot symbol assisted iterative channel estimation in OFDM systems is considered. As the bits are transmitted in packets, the proposed technique is based on calculating a particular threshold for each data packet in order to select the reliable decoder output symbols to improve the channel estimation performance. Iteratively, additional pilot symbols are established according to the threshold and the channel is re-estimated with the new pilots inserted to the known channel estimation pilot set. The proposed threshold calculation method for selecting additional pilots performs better than non-iterative channel estimation, no threshold and fixed threshold techniques in poor HF channel simulations.

TRPV3, a thermosensitive channel is expressed in mouse distal colon epithelium

International Nuclear Information System (INIS)

Ueda, Takashi; Yamada, Takahiro; Ugawa, Shinya; Ishida, Yusuke; Shimada, Shoichi

2009-01-01

The thermo-transient receptor potential (thermoTRP) subfamily is composed of channels that are important in nociception and thermo-sensing. Here, we show a selective expression of TRPV3 channel in the distal colon throughout the gastrointestinal tract. Expression analyses clearly revealed that TRPV3 mRNA and proteins were expressed in the superficial epithelial cells of the distal colon, but not in those of the stomach, duodenum or proximal colon. In a subset of primary epithelial cells cultured from the distal colon, carvacrol, an agonist for TRPV3, elevated cytosolic Ca 2+ concentration in a concentration-dependent manner. This response was inhibited by ruthenium red, a TRPV channel antagonist. Organotypic culture supported that the carvacrol-responsive cells were present in superficial epithelial cells. Moreover, application of carvacrol evoked ATP release in primary colonic epithelial cells. We conclude that TRPV3 is present in absorptive cells in the distal colon and may be involved in a variety of cellular functions.

Performance Analysis of Amplify-and-Forward Two-Way Relaying with Co-Channel Interference and Channel Estimation Error

KAUST Repository

Liang Yang,

2013-06-01

In this paper, we consider the performance of a two-way amplify-and-forward relaying network (AF TWRN) in the presence of unequal power co-channel interferers (CCI). Specifically, we first consider AF TWRN with an interference-limited relay and two noisy-nodes with channel estimation errors and CCI. We derive the approximate signal-to-interference plus noise ratio expressions and then use them to evaluate the outage probability, error probability, and achievable rate. Subsequently, to investigate the joint effects of the channel estimation error and CCI on the system performance, we extend our analysis to a multiple-relay network and derive several asymptotic performance expressions. For comparison purposes, we also provide the analysis for the relay selection scheme under the total power constraint at the relays. For AF TWRN with channel estimation error and CCI, numerical results show that the performance of the relay selection scheme is not always better than that of the all-relay participating case. In particular, the relay selection scheme can improve the system performance in the case of high power levels at the sources and small powers at the relays.

BK channel modulators: a comprehensive overview

DEFF Research Database (Denmark)

Nardi, Antonio; Olesen, Søren-Peter

2008-01-01

channels as a potentially attractive target, the design and synthesis of potent and selective BK modulators continue based on novel chemical ideas. A comprehensive overview of BK channel modulators is therefore timely and important to the current medicinal chemist for review, summary, and classification...

Nanobody mediated crystallization of an archeal mechanosensitive channel.

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Christian Löw

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

Multiplicative properties of quantum channels

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Rahaman, Mizanur

2017-08-01

In this paper, we study the multiplicative behaviour of quantum channels, mathematically described by trace preserving, completely positive maps on matrix algebras. It turns out that the multiplicative domain of a unital quantum channel has a close connection to its spectral properties. A structure theorem (theorem 2.5), which reveals the automorphic property of an arbitrary unital quantum channel on a subalgebra, is presented. Various classes of quantum channels (irreducible, primitive, etc) are then analysed in terms of this stabilising subalgebra. The notion of the multiplicative index of a unital quantum channel is introduced, which measures the number of times a unital channel needs to be composed with itself for the multiplicative algebra to stabilise. We show that the maps that have trivial multiplicative domains are dense in completely bounded norm topology in the set of all unital completely positive maps. Some applications in quantum information theory are discussed.

Highly selective water channel activity measured by voltage clamp: analysis of planar lipid bilayers reconstituted with purified AqpZ.

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Pohl, P; Saparov, S M; Borgnia, M J; Agre, P

2001-08-14

Aquaporins are membrane channels selectively permeated by water or water plus glycerol. Conflicting reports have described ion conductance associated with some water channels, raising the question of whether ion conductance is a general property of the aquaporin family. To clarify this question, a defined system was developed to simultaneously measure water permeability and ion conductance. The Escherichia coli water channel aquaporin-Z (AqpZ) was studied, because it is a highly stable tetramer. Planar lipid bilayers were formed from unilamellar vesicles containing purified AqpZ. The hydraulic conductivity of bilayers made from the total extract of E. coli lipids increased 3-fold if reconstituted with AqpZ, but electric conductance was unchanged. No channel activity was detected under voltage-clamp conditions, indicating that less than one in 10(9) transport events is electrogenic. Microelectrode measurements were simultaneously undertaken adjacent to the membrane. Changes in sodium concentration profiles accompanying transmembrane water flow permitted calculation of the activation energies: 14 kcal/mol for protein-free lipid bilayers and 4 kcal/mol for lipid bilayers containing AqpZ. Neither the water permeability nor the electric conductivity exhibited voltage dependence. This sensitive system demonstrated that AqpZ is permeated by water but not charged ions and should permit direct analyses of putative electrogenic properties of other aquaporins.

Quantum model for a periodically driven selectivity filter in a K+ ion channel

International Nuclear Information System (INIS)

Cifuentes, A A; Semião, F L

2014-01-01

In this work, we present a quantum transport model for the selectivity filter in the KcsA potassium ion channel. This model is fully consistent with the fact that two conduction pathways are involved in the translocation of ions through the filter, and we show that the presence of a second path may actually bring advantages for the filter as a result of quantum interference. To highlight interferences and resonances in the model, we consider the selectivity filter to be driven by a controlled time-dependent external field, which changes the free-energy scenario and consequently the conduction of the ions. In particular, we demonstrate that the two-pathway conduction mechanism is more advantageous for the filter when dephasing in the transient configurations is lower than in the main configurations. As a matter of fact, K + ions in the main configurations are highly coordinated by oxygen atoms of the filter backbone, and this increases noise. Moreover, we also show that for a wide range of dephasing rates and driving frequencies, the two-pathway conduction used by the filter leads to higher ionic currents than the single–path model. (paper)

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

Science.gov (United States)

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

Impedance spectroscopy of micro-Droplets reveals activation of Bacterial Mechanosensitive Channels in Hypotonic Solutions

Science.gov (United States)

Ebrahimi, Aida; Alam, Muhammad A.

Rapid detection of bacterial pathogens is of great importance in healthcare, food safety, environmental monitoring, and homeland security. Most bacterial detection platforms rely on binary fission (i.e. cell growth) to reach a threshold cell population that can be resolved by the sensing method. Since cell division depends on the bacteria type, the detection time of such methods can vary from hours to days. In contrast, in this work, we show that bacteria cells can be detected within minutes by relying on activation of specific protein channels, i.e. mechanosensitive channels (MS channels). When cells are exposed to hypotonic solutions, MS channels allow efflux of solutes to the external solution which leads to release the excessive membrane tension. Release of the cytoplasmic solutes, in turn, results in increase of the electrical conductance measured by droplet-based impedance sensing. The approach can be an effective technique for fast, pre-screening of bacterial contamination at ultra-low concentration.

The structure of a conserved Piezo channel domain reveals a novel beta sandwich fold

Science.gov (United States)

Kamajaya, Aron; Kaiser, Jens; Lee, Jonas; Reid, Michelle; Rees, Douglas C.

2014-01-01

Summary Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a novel beta sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in Dehydrated Hereditary Stomatocytosis (DHS) patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. PMID:25242456

Structure of the Cyanuric Acid Hydrolase TrzD Reveals Product Exit Channel.

Science.gov (United States)

Bera, Asim K; Aukema, Kelly G; Elias, Mikael; Wackett, Lawrence P

2017-03-27

Cyanuric acid hydrolases are of industrial importance because of their use in aquatic recreational facilities to remove cyanuric acid, a stabilizer for the chlorine. Degradation of excess cyanuric acid is necessary to maintain chlorine disinfection in the waters. Cyanuric acid hydrolase opens the cyanuric acid ring hydrolytically and subsequent decarboxylation produces carbon dioxide and biuret. In the present study, we report the X-ray structure of TrzD, a cyanuric acid hydrolase from Acidovorax citrulli. The crystal structure at 2.19 Å resolution shows a large displacement of the catalytic lysine (Lys163) in domain 2 away from the active site core, whereas the two other active site lysines from the two other domains are not able to move. The lysine displacement is proposed here to open up a channel for product release. Consistent with that, the structure also showed two molecules of the co-product, carbon dioxide, one in the active site and another trapped in the proposed exit channel. Previous data indicated that the domain 2 lysine residue plays a role in activating an adjacent serine residue carrying out nucleophilic attack, opening the cyanuric acid ring, and the mobile lysine guides products through the exit channel.

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

Energy Technology Data Exchange (ETDEWEB)

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong; Kim, Sunghoon; She, Ji; Cang, Chunlei; Ren, Dejian; Jiang , Youxing (UPENN); (UTSMC); (HHMI)

2017-07-19

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 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.

Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women.

Science.gov (United States)

Reinl, Erin L; Cabeza, Rafael; Gregory, Ismail A; Cahill, Alison G; England, Sarah K

2015-10-01

Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+)-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cooperative AF Relaying in Spectrum-Sharing Systems: Outage Probability Analysis under Co-Channel Interferences and Relay Selection

KAUST Repository

Xia, Minghua

2012-11-01

For cooperative amplify-and-forward (AF) relaying in spectrum-sharing wireless systems, secondary users share spectrum resources originally licensed to primary users to communicate with each other and, thus, the transmit power of secondary transmitters is strictly limited by the tolerable interference powers at primary receivers. Furthermore, the received signals at a relay and at a secondary receiver are inevitably interfered by the signals from primary transmitters. These co-channel interferences (CCIs) from concurrent primary transmission can significantly degrade the performance of secondary transmission. This paper studies the effect of CCIs on outage probability of the secondary link in a spectrum-sharing environment. In particular, in order to compensate the performance loss due to CCIs, the transmit powers of a secondary transmitter and its relaying node are respectively optimized with respect to both the tolerable interference powers at the primary receivers and the CCIs from the primary transmitters. Moreover, when multiple relays are available, the technique of opportunistic relay selection is exploited to further improve system performance with low implementation complexity. By analyzing lower and upper bounds on the outage probability of the secondary system, this study reveals that it is the tolerable interference powers at primary receivers that dominate the system performance, rather than the CCIs from primary transmitters. System designers will benefit from this result in planning and designing next-generation broadband spectrum-sharing systems.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Affinity purification of the voltage-sensitive sodium channel from electroplax with resins selective for sialic acid

Energy Technology Data Exchange (ETDEWEB)

James, W.M.; Emerick, M.C.; Agnew, W.S. (Yale Univ. School of medicine, New Haven, CT (USA))

1989-07-11

The voltage-sensitive sodium channel present in the eel (Electrophorus electricus) has an unusually high content of sialic acid, including {alpha}-(2{yields}8)-linked polysialic acid, not found in other electroplax membrane glycopeptides. Lectins from Limax flavus (LFA) and wheat germ (WGA) proved the most effective of 11 lectin resins tried. The most selective resin was prepared from IgM antibodies against Neisseria meningitidis {alpha}-(2{yields}8)-polysialic acid which were affinity purified and coupled to Sepharose 4B. The sodium channel was found to bind to WGA, LFA, and IgM resins and was readily eluted with the appropriate soluble carbohydrates. Experiments with LFA and IgM resins demonstrated binding and unbinding rates and displacement kinetics, which suggest highly specific binding at multiple sites on the sodium channel protein. In preparative-scale purification of protein previously fractionated by anion-exchange chromatography, without stabilizing TTX, high yields were reproducibly obtained. Further, when detergent extracts were prepared from electroplax membranes fractionated by low-speed sedimentation, a single step over the IgM resin provided a 70-fold purification, yielding specific activities of 3,200 pmol of ({sup 3}H)TTX-binding sites/mg of protein and a single polypeptide of {approximately}285,000 Da on SDS-acrylamide gels. No small peptides were observed after this 5-h isolation. The authors describe a cation-dependent stabilization with millimolar levels of monovalent and micromolar levels of divalent species.

Regional two-dimensional magnetotelluric profile in West Bohemia/Vogtland reveals deep conductive channel into the earthquake swarm region

Science.gov (United States)

Muñoz, Gerard; Weckmann, Ute; Pek, Josef; Kováčiková, Světlana; Klanica, Radek

2018-03-01

The West Bohemia/Vogtland region, characterized by the intersection of the Eger (Ohře) Rift and the Mariánské Lázně fault, is a geodynamically active area exhibiting repeated occurrence of earthquake swarms, massive CO2 emanations and mid Pleistocene volcanism. The Eger Rift is the only known intra-continental region in Europe where such deep seated, active lithospheric processes currently take place. We present an image of electrical resistivity obtained from two-dimensional inversion of magnetotelluric (MT) data acquired along a regional profile crossing the Eger Rift. At the near surface, the Cheb basin and the aquifer feeding the mofette fields of Bublák and Hartoušov have been imaged as part of a region of very low resistivity. The most striking resistivity feature, however, is a deep reaching conductive channel which extends from the surface into the lower crust spatially correlated with the hypocentres of the seismic events of the Nový Kostel Focal Zone. This channel has been interpreted as imaging a pathway from a possible mid-crustal fluid reservoir to the surface. The resistivity model reinforces the relation between the fluid circulation along deep-reaching faults and the generation of the earthquakes. Additionally, a further conductive channel has been revealed to the south of the profile. This other feature could be associated to fossil hydrothermal alteration related to Mýtina and/or Neualbenreuth Maar structures or alternatively could be the signature of a structure associated to the suture between the Saxo-Thuringian and Teplá-Barrandian zones, whose surface expression is located only a few kilometres away.

Adaptive evolution of the vertebrate skeletal muscle sodium channel

Directory of Open Access Journals (Sweden)

Jian Lu

2011-01-01

Full Text Available Tetrodotoxin (TTX is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Na v. The skeletal muscle Na v (Na v1.4 channels in most pufferfish species and certain North American garter snakes are resistant to TTX, whereas in most mammals they are TTX-sensitive. It still remains unclear as to whether the difference in this sensitivity among the various vertebrate species can be associated with adaptive evolution. In this study, we investigated the adaptive evolution of the vertebrate Na v1.4 channels. By means of the CODEML program of the PAML 4.3 package, the lineages of both garter snakes and pufferfishes were denoted to be under positive selection. The positively selected sites identified in the p-loop regions indicated their involvement in Na v1.4 channel sensitivity to TTX. Most of these sites were located in the intracellular regions of the Na v1.4 channel, thereby implying the possible association of these regions with the regulation of voltage-sensor movement.

Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+-induced hERG endocytic degradation.

Science.gov (United States)

Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D; Fisher, John T; Zhang, Shetuan

2011-10-07

Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks). Decreases in I(Kr) or I(Ks) cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K(+) concentration ([K(+)](o)) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether I(Ks) compensates for the reduced I(Kr) under low K(+) conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mM K(+) for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mM K(+)-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mM K(+) conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS.

Relativistic laser channeling in plasmas for fast ignition

Science.gov (United States)

Lei, A. L.; Pukhov, A.; Kodama, R.; Yabuuchi, T.; Adumi, K.; Endo, K.; Freeman, R. R.; Habara, H.; Kitagawa, Y.; Kondo, K.; Kumar, G. R.; Matsuoka, T.; Mima, K.; Nagatomo, H.; Norimatsu, T.; Shorokhov, O.; Snavely, R.; Yang, X. Q.; Zheng, J.; Tanaka, K. A.

2007-12-01

We report an experimental observation suggesting plasma channel formation by focusing a relativistic laser pulse into a long-scale-length preformed plasma. The channel direction coincides with the laser axis. Laser light transmittance measurement indicates laser channeling into the high-density plasma with relativistic self-focusing. A three-dimensional particle-in-cell simulation reproduces the plasma channel and reveals that the collimated hot-electron beam is generated along the laser axis in the laser channeling. These findings hold the promising possibility of fast heating a dense fuel plasma with a relativistic laser pulse.

Ion channels in plants.

Science.gov (United States)

Hedrich, Rainer

2012-10-01

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K(+)-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K(+) channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

Computational Fluid Dynamics Study of Channel Geometric Effect for Fischer-Tropsch Microchannel Reactor

International Nuclear Information System (INIS)

Na, Jonggeol; Jung, Ikhwan; Kshetrimayum, Krishnadash S.; Park, Seongho; Park, Chansaem; Han, Chonghun

2014-01-01

Driven by both environmental and economic reasons, the development of small to medium scale GTL(gas-to-liquid) process for offshore applications and for utilizing other stranded or associated gas has recently been studied increasingly. Microchannel GTL reactors have been preferred over the conventional GTL reactors for such applications, due to its compactness, and additional advantages of small heat and mass transfer distance desired for high heat transfer performance and reactor conversion. In this work, multi-microchannel reactor was simulated by using commercial CFD code, ANSYS FLUENT, to study the geometric effect of the microchannels on the heat transfer phenomena. A heat generation curve was first calculated by modeling a Fischer-Tropsch reaction in a single-microchannel reactor model using Matlab-ASPEN integration platform. The calculated heat generation curve was implemented to the CFD model. Four design variables based on the microchannel geometry namely coolant channel width, coolant channel height, coolant channel to process channel distance, and coolant channel to coolant channel distance, were selected for calculating three dependent variables namely, heat flux, maximum temperature of coolant channel, and maximum temperature of process channel. The simulation results were visualized to understand the effects of the design variables on the dependent variables. Heat flux and maximum temperature of cooling channel and process channel were found to be increasing when coolant channel width and height were decreased. Coolant channel to process channel distance was found to have no effect on the heat transfer phenomena. Finally, total heat flux was found to be increasing and maximum coolant channel temperature to be decreasing when coolant channel to coolant channel distance was decreased. Using the qualitative trend revealed from the present study, an appropriate process channel and coolant channel geometry along with the distance between the adjacent

A novel reduced-complexity group detection structure in MIMO frequency selective fading channels

KAUST Repository

Qaraqe, Khalid A.; Ahimian, Nariman R.; Alouini, Mohamed-Slim

2010-01-01

In this paper a novel reduced complexity detection method named modified symbol flipping method is introduced and its advantages on reducing the burden of the calculations at the receiver compared to the optimum maximum likelihood detection method on multiple input- multiple output frequency selective fading channels are explained. The initial concept of the symbol flipping method is derived from a preliminary detection scheme named bit flipping which was introduced in [1]. The detection structure employed in this paper is ing, detection, and cancellation. On the detection stage, the proposed method is employed and the results are compared to the group maximum likelihood detection scheme proposed in [2]. Simulation results show that a 6 dB performance gain can be achieved at the expense of a slight increase in complexity in comparison with the conventional symbol flipping scheme. © 2010 Crown.

A novel reduced-complexity group detection structure in MIMO frequency selective fading channels

KAUST Repository

Qaraqe, Khalid A.

2010-09-01

In this paper a novel reduced complexity detection method named modified symbol flipping method is introduced and its advantages on reducing the burden of the calculations at the receiver compared to the optimum maximum likelihood detection method on multiple input- multiple output frequency selective fading channels are explained. The initial concept of the symbol flipping method is derived from a preliminary detection scheme named bit flipping which was introduced in [1]. The detection structure employed in this paper is ing, detection, and cancellation. On the detection stage, the proposed method is employed and the results are compared to the group maximum likelihood detection scheme proposed in [2]. Simulation results show that a 6 dB performance gain can be achieved at the expense of a slight increase in complexity in comparison with the conventional symbol flipping scheme. © 2010 Crown.

TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons.

Science.gov (United States)

Memon, Tosifa; Chase, Kevin; Leavitt, Lee S; Olivera, Baldomero M; Teichert, Russell W

2017-06-14

The molecular sensor of innocuous (painless) cold sensation is well-established to be transient receptor potential cation channel, subfamily M, member 8 (TRPM8). However, the role of transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in noxious (painful) cold sensation has been controversial. We find that TRPA1 channels contribute to the noxious cold sensitivity of mouse somatosensory neurons, independent of TRPM8 channels, and that TRPA1-expressing neurons are largely non-overlapping with TRPM8-expressing neurons in mouse dorsal-root ganglia (DRG). However, relatively few TRPA1-expressing neurons (e.g., responsive to allyl isothiocyanate or AITC, a selective TRPA1 agonist) respond overtly to cold temperature in vitro, unlike TRPM8-expressing neurons, which almost all respond to cold. Using somatosensory neurons from TRPM8-/- mice and subtype-selective blockers of TRPM8 and TRPA1 channels, we demonstrate that responses to cold temperatures from TRPA1-expressing neurons are mediated by TRPA1 channels. We also identify two factors that affect the cold-sensitivity of TRPA1-expressing neurons: (1) cold-sensitive AITC-sensitive neurons express relatively more TRPA1 transcripts than cold-insensitive AITC-sensitive neurons and (2) voltage-gated potassium (K V ) channels attenuate the cold-sensitivity of some TRPA1-expressing neurons. The combination of these two factors, combined with the relatively weak agonist-like activity of cold temperature on TRPA1 channels, partially explains why few TRPA1-expressing neurons respond to cold. Blocking K V channels also reveals another subclass of noxious cold-sensitive DRG neurons that do not express TRPM8 or TRPA1 channels. Altogether, the results of this study provide novel insights into the cold-sensitivity of different subclasses of somatosensory neurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes.

Science.gov (United States)

Zhang, Xiao-Dong; Coulibaly, Zana A; Chen, Wei Chun; Ledford, Hannah A; Lee, Jeong Han; Sirish, Padmini; Dai, Gu; Jian, Zhong; Chuang, Frank; Brust-Mascher, Ingrid; Yamoah, Ebenezer N; Chen-Izu, Ye; Izu, Leighton T; Chiamvimonvat, Nipavan

2018-03-16

Small-conductance Ca 2+ -activated K + (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca 2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca 2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca 2+ microdomains necessary for SK channel activation. SK currents coupled with Ca 2+ influx via L-type Ca 2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca 2+ store, suggesting that LTCCs provide the immediate Ca 2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Ca v 1.2 Ca 2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Ca v 1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca 2+ signaling.

Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides

Science.gov (United States)

Borbiro, Istvan; Badheka, Doreen; Rohacs, Tibor

2015-01-01

Capsaicin is an activator of the heat-sensitive TRPV1 (transient receptor potential vanilloid 1) ion channels and has been used as a local analgesic. We found that activation of TRPV1 channels with capsaicin either in dorsal root ganglion neurons or in a heterologous expression system inhibited the mechanosensitive Piezo1 and Piezo2 channels by depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and its precursor PI(4)P from the plasma membrane through Ca2+-induced phospholipase Cδ (PLCδ) activation. Experiments with chemically inducible phosphoinositide phosphatases and receptor-induced activation of PLCβ indicated that inhibition of Piezo channels required depletion of both PI(4)P and PI(4,5)P2. The mechanically activated current amplitudes decreased substantially in the excised inside-out configuration, where the membrane patch containing Piezo1 channels is removed from the cell. PI(4,5)P2 and PI(4)P applied to these excised patches inhibited this decrease. Thus, we concluded that Piezo channel activity requires the presence of phosphoinositides, and the combined depletion of PI(4,5)P2 or PI(4)P reduces channel activity. In addition to revealing a role for distinct membrane lipids in mechanosensitive ion channel regulation, these data suggest that inhibition of Piezo2 channels may contribute to the analgesic effect of capsaicin. PMID:25670203

The elusive character of discontinuous deep-water channels: New insights from Lucia Chica channel system, offshore California

Science.gov (United States)

Maier, K.L.; Fildani, A.; Paull, C.K.; Graham, S.A.; McHargue, T.R.; Caress, D.W.; McGann, M.

2011-01-01

New high-resolution autonomous underwater vehicle (AUV) seafloor images, with 1 m lateral resolution and 0.3 m vertical resolution, reveal unexpected seafloor rugosity and low-relief (thalwegs were interpreted originally from lower-resolution images, but newly acquired AUV data indicate that a single sinuous channel fed a series of discontinuous lower-relief channels. These discontinuous channels were created by at least four avulsion events. Channel relief, defined as the height from the thalweg to the levee crest, controls avulsions and overall stratigraphic architecture of the depositional area. Flowstripped turbidity currents separated into and reactivated multiple channels to create a distributary pattern and developed discontinuous trains of cyclic scours and megaflutes, which may be erosional precursors to continuous channels. The diverse features now imaged in the Lucia Chica channel system (offshore California) are likely common in modern and ancient systems with similar overall morphologies, but have not been previously mapped with lower-resolution detection methods in any of these systems. ?? 2011 Geological Society of America.

New Conotoxin SO-3 Targeting N-type Voltage-Sensitive Calcium Channels

Directory of Open Access Journals (Sweden)

Lei Wen

2006-04-01

Full Text Available Selective blockers of the N-type voltage-sensitive calcium (CaV channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type CaV channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-loop, 6-cysteine framework (C-C-CC-C-C as O-superfamily conotoxins. The synthetic SO-3 has high analgesic activity similar to ω-conotoxin MVIIA (MVIIA, a selective N-type CaV channel blocker approved in the USA and Europe for the alleviation of persistent pain states. In electrophysiological studies, SO-3 shows more selectivity towards the N-type CaV channels than MVIIA. The dissimilarity between SO-3 and MVIIA in the primary and tertiary structures is further discussed in an attempt to illustrate the difference in selectivity of SO-3 and MVIIA towards N-type CaV channels.

Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart.

Science.gov (United States)

Herrmann, Stefan; Layh, Beate; Ludwig, Andreas

2011-12-01

HCN pacemaker channels (I(f) channels) are believed to contribute to important functions in the heart; thus these channels became an attractive target for generating transgenic mouse mutants to elucidate their role in physiological and pathophysiological cardiac conditions. A full understanding of cardiac I(f) and the interpretation of studies using HCN mouse mutants require detailed information about the expression profile of the individual HCN subunits. Here we investigate the cardiac expression pattern of the HCN isoforms at the mRNA as well as at the protein level. The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals. We find a low, but highly differential HCN expression profile outside the cardiac conduction pathway including left and right atria and ventricles. Additionally HCN distribution was investigated in tissue slices of the sinoatrial node, the atrioventricular node, the bundle of His and the bundle branches. The conduction system was marked by acetylcholine esterase staining. HCN4 was confirmed as the predominant isoform of the primary pacemaker followed by a distinct expression of HCN1. In contrast HCN2 shows only a confined expression to individual pacemaker cells. Immunolabeling of the AV-node reveals also a pronounced specificity for HCN1 and HCN4. Compared to the SN and AVN we found a low but selective expression of HCN4 as the only isoform in the atrioventricular bundle. However in the bundle branches HCN1, HCN4 and also HCN2 show a prominent and selective expression pattern. Our results display a characteristic distribution of individual HCN isoforms in several cardiac compartments and reveal that beside HCN4, HCN1 represents the isoform which is selectively expressed in most parts of the conduction system suggesting a substantial contribution of HCN1 to pacemaking. 2011 Elsevier Ltd. All rights reserved.

Clofilium inhibits Slick and Slack potassium channels.

Science.gov (United States)

de Los Angeles Tejada, Maria; Stolpe, Kathleen; Meinild, Anne-Kristine; Klaerke, Dan A

2012-01-01

Slick and Slack high-conductance potassium channels have been recently discovered, and are found in the central nervous system and in the heart. Both channels are activated by Na(+) and Cl(-), and Slick channels are also inhibited by adenosine triphospate (ATP). An important role of setting the resting membrane potential and controlling the basal excitability of neurons has been suggested for these channels. In addition, no specific blockers for these channels are known up to the present. With the purpose of studying the pharmacological characteristics of Slick and Slack channels, the effects of exposure to the antiarrhythmic compound clofilium were evaluated. Clofilium was able to modulate the activity of Slick and Slack channels effectively, with a stronger effect on Slack than Slick channels. In order to evaluate the pharmacological behavior of Slick and Slack channels further, 38 commonly used potassium channel blockers were tested. Screening of these compounds did not reveal any modulators of Slick and Slack channels, except for clofilium. The present study provides a first approach towards elucidating the pharmacological characteristics of Slick and Slack channels and could be the basis for future studies aimed at developing potent and specific blockers and activators for these channels.

A model for the distribution channels planning process

NARCIS (Netherlands)

Neves, M.F.; Zuurbier, P.; Campomar, M.C.

2001-01-01

Research of existing literature reveals some models (sequence of steps) for companies that want to plan distribution channels. None of these models uses strong contributions from transaction cost economics, bringing a possibility to elaborate on a "distribution channels planning model", with these

Variable Bandwidth Analog Channel Filters for Software Defined Radio

NARCIS (Netherlands)

Arkesteijn, V.J.; Klumperink, Eric A.M.; Nauta, Bram

2001-01-01

An important aspect of Software Defined Radio is the ability to define the bandwidth of the filter that selects the desired channel. This paper first explains the importance of channel filtering. Then the advantage of analog channel filtering with a variable bandwidth in a Software Defined Radio is

Temporary Nerve Block at Selected Digits Revealed Hand Motor Deficits in Grasping Tasks

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Aude Carteron

2016-11-01

Full Text Available Peripheral sensory feedback plays a crucial role in ensuring correct motor execution throughout hand grasp control. Previous studies utilized local anesthesia to deprive somatosensory feedback in the digits or hand, observations included sensorimotor deficits at both corticospinal and peripheral levels. However, the questions of how the disturbed and intact sensory input integrate and interact with each other to assist the motor program execution, and whether the motor coordination based on motor output variability between affected and non-affected elements (e.g., digits becomes interfered by the local sensory deficiency, have not been answered. The current study aims to investigate the effect of peripheral deafferentation through digital nerve blocks at selective digits on motor performance and motor coordination in grasp control. Our results suggested that the absence of somatosensory information induced motor deficits in hand grasp control, as evidenced by reduced maximal force production ability in both local and non-local digits, impairment of force and moment control during object lift and hold, and attenuated motor synergies in stabilizing task performance variables, namely the tangential force and moment of force. These findings implied that individual sensory input is shared across all the digits and the disturbed signal from local sensory channel(s has a more comprehensive impact on the process of the motor output execution in the sensorimotor integration process. Additionally, a feedback control mechanism with a sensation-based component resides in the formation process for the motor covariation structure.

Evaluation of habitat quality for selected wildlife species associated with back channels.

Science.gov (United States)

Anderson, James T.; Zadnik, Andrew K.; Wood, Petra Bohall; Bledsoe, Kerry

2013-01-01

The islands and associated back channels on the Ohio River, USA, are believed to provide critical habitat features for several wildlife species. However, few studies have quantitatively evaluated habitat quality in these areas. Our main objective was to evaluate the habitat quality of back and main channel areas for several species using habitat suitability index (HSI) models. To test the effectiveness of these models, we attempted to relate HSI scores and the variables measured for each model with measures of relative abundance for the model species. The mean belted kingfisher (Ceryle alcyon) HSI was greater on the main than back channel. However, the model failed to predict kingfisher abundance. The mean reproduction component of the great blue heron (Ardea herodias) HSI, total common muskrat (Ondatra zibethicus) HSI, winter cover component of the snapping turtle (Chelydra serpentina) HSI, and brood-rearing component of the wood duck (Aix sponsa) HSI were all greater on the back than main channel, and were positively related with the relative abundance of each species. We found that island back channels provide characteristics not found elsewhere on the Ohio River and warrant conservation as important riparian wildlife habitat. The effectiveness of using HSI models to predict species abundance on the river was mixed. Modifications to several of the models are needed to improve their use on the Ohio River and, likely, other large rivers.

Marketing channels and competitive advantage

Directory of Open Access Journals (Sweden)

Jovičić Dragoljub

2005-01-01

Full Text Available Issue that can already be seen and will be very clear in the future is that the central problem in the market of tube caps will not be the product or the price or promotion, but marketing channels. Therefore, the competitive advantage will most probably be built on marketing channels and not the production - as it has been so far, so, the questions of choice functioning and modification of marketing channels, as well as selection of the most appropriate members of channels will become more and more important. Accordingly, it may freely be said that the choice, i.e. the movement of marketing channels represents one of the strategic decisions which has to be made by a company management and which will subsequently very significantly influence the functioning and efficacy of not only the system of distribution, but also the entire business transactions.

Corynebacterium jeikeium jk0268 constitutes for the 40 amino acid long PorACj, which forms a homooligomeric and anion-selective cell wall channel.

Directory of Open Access Journals (Sweden)

Narges Abdali

Full Text Available Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.

A Statistical Thermodynamic Model for Ligands Interacting With Ion Channels: Theoretical Model and Experimental Validation of the KCNQ2 Channel

Directory of Open Access Journals (Sweden)

Fang Bai

2018-03-01

Full Text Available Ion channels are important therapeutic targets, and their pharmacology is becoming increasingly important. However, knowledge of the mechanism of interaction of the activators and ion channels is still limited due to the complexity of the mechanisms. A statistical thermodynamic model has been developed in this study to characterize the cooperative binding of activators to ion channels. By fitting experimental concentration-response data, the model gives eight parameters for revealing the mechanism of an activator potentiating an ion channel, i.e., the binding affinity (KA, the binding cooperative coefficients for two to four activator molecules interacting with one channel (γ, μ, and ν, and the channel conductance coefficients for four activator binding configurations of the channel (a, b, c, and d. Values for the model parameters and the mechanism underlying the interaction of ztz240, a proven KCNQ2 activator, with the wild-type channel have been obtained and revealed by fitting the concentration-response data of this activator potentiating the outward current amplitudes of KCNQ2. With these parameters, our model predicted an unexpected bi-sigmoid concentration-response curve of ztz240 activation of the WT-F137A mutant heteromeric channel that was in good agreement with the experimental data determined in parallel in this study, lending credence to the assumptions on which the model is based and to the model itself. Our model can provide a better fit to the measured data than the Hill equation and estimates the binding affinity, as well as the cooperative coefficients for the binding of activators and conductance coefficients for binding states, which validates its use in studying ligand-channel interaction mechanisms.

Chemical Selectivity and Sensitivity of a 16-Channel Electronic Nose for Trace Vapour Detection

Directory of Open Access Journals (Sweden)

Drago Strle

2017-12-01

Full Text Available Good chemical selectivity of sensors for detecting vapour traces of targeted molecules is vital to reliable detection systems for explosives and other harmful materials. We present the design, construction and measurements of the electronic response of a 16 channel electronic nose based on 16 differential microcapacitors, which were surface-functionalized by different silanes. The e-nose detects less than 1 molecule of TNT out of 10+12 N2 molecules in a carrier gas in 1 s. Differently silanized sensors give different responses to different molecules. Electronic responses are presented for TNT, RDX, DNT, H2S, HCN, FeS, NH3, propane, methanol, acetone, ethanol, methane, toluene and water. We consider the number density of these molecules and find that silane surfaces show extreme affinity for attracting molecules of TNT, DNT and RDX. The probability to bind these molecules and form a surface-adsorbate is typically 10+7 times larger than the probability to bind water molecules, for example. We present a matrix of responses of differently functionalized microcapacitors and we propose that chemical selectivity of multichannel e-nose could be enhanced by using artificial intelligence deep learning methods.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

Science.gov (United States)

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.

Science.gov (United States)

Kamajaya, Aron; Kaiser, Jens T; Lee, Jonas; Reid, Michelle; Rees, Douglas C

2014-10-07

Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. Copyright © 2014 Elsevier Ltd. All rights reserved.

A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain.

Science.gov (United States)

Bohlen, Christopher J; Chesler, Alexander T; Sharif-Naeini, Reza; Medzihradszky, Katalin F; Zhou, Sharleen; King, David; Sánchez, Elda E; Burlingame, Alma L; Basbaum, Allan I; Julius, David

2011-11-16

Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation. Plant-derived irritants have predominated in this regard, but animal venoms have also evolved to avert predators by targeting neurons and receptors whose activation produces noxious sensations. As such, venoms provide a rich and varied source of small molecule and protein pharmacophores that can be exploited to characterize and manipulate key components of the pain-signalling pathway. With this in mind, here we perform an unbiased in vitro screen to identify snake venoms capable of activating somatosensory neurons. Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain, excites a large cohort of sensory neurons. The purified active species (MitTx) consists of a heteromeric complex between Kunitz- and phospholipase-A2-like proteins that together function as a potent, persistent and selective agonist for acid-sensing ion channels (ASICs), showing equal or greater efficacy compared with acidic pH. MitTx is highly selective for the ASIC1 subtype at neutral pH; under more acidic conditions (pH 100-fold) proton-evoked activation of ASIC2a channels. These observations raise the possibility that ASIC channels function as coincidence detectors for extracellular protons and other, as yet unidentified, endogenous factors. Purified MitTx elicits robust pain-related behaviour in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibres. These findings reveal a mechanism whereby snake venoms produce pain, and highlight an unexpected contribution of ASIC1 channels to nociception. © 2011 Macmillan Publishers Limited. All rights reserved

Voltage-gated sodium channels as targets for pyrethroid insecticides.

Science.gov (United States)

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.

Chimeras Reveal a Single Lipid-Interface Residue that Controls MscL Channel Kinetics as well as Mechanosensitivity

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Li-Min Yang

2013-02-01

Full Text Available MscL, the highly conserved bacterial mechanosensitive channel of large conductance, serves as an osmotic “emergency release valve,” is among the best-studied mechanosensors, and is a paradigm of how a channel senses and responds to membrane tension. Although all homologs tested thus far encode channel activity, many show functional differences. We tested Escherichia coli and Staphylococcus aureus chimeras and found that the periplasmic region of the protein, particularly E. coli I49 and the equivalent S. aureus F47 at the periplasmic lipid-aqueous interface of the first transmembrane domain, drastically influences both the open dwell time and the threshold of channel opening. One mutant shows a severe hysteresis, confirming the importance of this residue in determining the energy barriers for channel gating. We propose that this site acts similarly to a spring for a clasp knife, adjusting the resistance for obtaining and stabilizing an open or closed channel structure.

Opportunistic relaying in multipath and slow fading channel: Relay selection and optimal relay selection period

KAUST Repository

Sungjoon Park,; Stark, Wayne E.

2011-01-01

In this paper we present opportunistic relay communication strategies of decode and forward relaying. The channel that we are considering includes pathloss, shadowing, and fast fading effects. We find a simple outage probability formula

Ripple Design of LT Codes for BIAWGN Channels

DEFF Research Database (Denmark)

Sørensen, Jesper Hemming; Koike-Akino, Toshiaki; Orlik, Philip

2014-01-01

This paper presents a novel framework, which enables a design of rateless codes for binary input additive white Gaussian noise (BIAWGN) channels, using the ripple-based approach known from the works for the binary erasure channel (BEC). We reveal that several aspects of the analytical results from...

Ergodic Capacity for the SIMO Nakagami- Channel

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Vagenas EfstathiosD

2009-01-01

Full Text Available This paper presents closed-form expressions for the ergodic channel capacity of SIMO (single-input and multiple output wireless systems operating in a Nakagami- fading channel. As the performance of SIMO channel is closely related to the diversity combining techniques, we present closed-form expressions for the capacity of maximal ratio combining (MRC, equal gain combining (EGC, selection combining (SC, and switch and stay (SSC diversity systems operating in Nakagami- fading channels. Also, the ergodic capacity of a SIMO system in a Nakagami- fading channel without any diversity technique is derived. The latter scenario is further investigated for a large amount of receive antennas. Finally, numerical results are presented for illustration.

Fuel channel refilling

International Nuclear Information System (INIS)

Shoukri, M.; Abdul-Razzak, A.

1992-11-01

This report extends the work reported in document INFO-0370 on fuel channel refilling by providing analysis of the refilling tests conducted using the RD-14 and RD-14M test facilities. The analysis focuses on the general thermal-hydraulic characteristics of the facilities following various small and large inlet and outlet header breaks with emergency coolant injection. The two-fluid model thermal-hydraulic computer code CATHENA was tested against results obtained from selected experiments carried out in the two facilities. Conclusions related to the effect of break size, mode of emergency core injection, primary pump operation and parallel channels are presented. (Author) (116 figs., 17 tabs., 53 refs.)

Battle of the Retail Channels: How Product Selection and Geography Drive Cross-Channel Competition

OpenAIRE

Erik Brynjolfsson; Yu (Jeffrey) Hu; Mohammad S. Rahman

2009-01-01

A key question for Internet commerce is the nature of competition with traditional brick-and-mortar retailers. Although traditional retailers vastly outsell Internet retailers in most product categories, research on Internet retailing has largely neglected this fundamental dimension of competition. Is cross-channel competition significant, and if so, how and where can Internet retailers win this battle? This paper attempts to answer these questions using a unique combination of data sets. We ...

Improved Sparse Channel Estimation for Cooperative Communication Systems

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Guan Gui

2012-01-01

Full Text Available Accurate channel state information (CSI is necessary at receiver for coherent detection in amplify-and-forward (AF cooperative communication systems. To estimate the channel, traditional methods, that is, least squares (LS and least absolute shrinkage and selection operator (LASSO, are based on assumptions of either dense channel or global sparse channel. However, LS-based linear method neglects the inherent sparse structure information while LASSO-based sparse channel method cannot take full advantage of the prior information. Based on the partial sparse assumption of the cooperative channel model, we propose an improved channel estimation method with partial sparse constraint. At first, by using sparse decomposition theory, channel estimation is formulated as a compressive sensing problem. Secondly, the cooperative channel is reconstructed by LASSO with partial sparse constraint. Finally, numerical simulations are carried out to confirm the superiority of proposed methods over global sparse channel estimation methods.

Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves.

Science.gov (United States)

Bierer, Julie Arenberg; Faulkner, Kathleen F

2010-04-01

The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, and tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve (PTC) measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar (pTP) electrode configuration are predictive of wide or tip-shifted PTCs. Data were collected from five cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp., Sylmar, CA). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the pTP configuration for which a fraction of current (sigma) from a center-active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked PTCs were obtained for channels with the highest, lowest, and median tripolar (sigma = 1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (sigma = 0) or a more focused pTP (sigma > or = 0.55) configuration. The masker channel and level were varied, whereas the configuration was fixed to sigma = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, sigma, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel thresholds, when measured with a

Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers.

Science.gov (United States)

Ravens, Ursula; Odening, Katja E

2017-08-01

Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K + ) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two pore domain K + (K2P) channels TWIK-1, TASK-1 and TASK-3 that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Here, we briefly review the characteristics of these K + channels and their roles in atrial fibrillation. The antiarrhythmic potential of drugs targeting the described channels is discussed as well as their putative value in treatment of atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

Dynamics of ions in the selectivity filter of the KcsA channel: Towards a coupled Brownian particle description

OpenAIRE

Cosseddu, Salvatore M.; Khovanov, Igor A.; Allen, Michael P.; Rodger, P. M.; Luchinsky, Dmitry G.; McClintock, Peter V. E.

2013-01-01

The statistical and dynamical properties of ions in the selectivity filter of the KcsA ion channel are considered on the basis of molecular dynamics (MD) simulations of the KcsA protein embedded in a lipid membrane surrounded by an ionic solution. A new approach to the derivation of a Brownian dynamics (BD) model of ion permeation through the filter is discussed, based on unbiased MD simulations. It is shown that depending on additional assumptions, ion’s dynamics can be described either by u...

Grafting voltage and pharmacological sensitivity in potassium channels.

Science.gov (United States)

Lan, Xi; Fan, Chunyan; Ji, Wei; Tian, Fuyun; Xu, Tao; Gao, Zhaobing

2016-08-01

A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.

Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release

Science.gov (United States)

Estacion, Mark; Turner, Jamie; Mis, Malgorzata A.; Wilbrey, Anna; Payne, Elizabeth C.; Gutteridge, Alex; Cox, Peter J.; Doyle, Rachel; Printzenhoff, David; Lin, Zhixin; Marron, Brian E.; West, Christopher; Swain, Nigel A.; Storer, R. Ian; Stupple, Paul A.; Castle, Neil A.; Hounshell, James A.; Rivara, Mirko; Randall, Andrew; Dib-Hajj, Sulayman D.; Krafte, Douglas; Waxman, Stephen G.; Patel, Manoj K.; Butt, Richard P.; Stevens, Edward B.

2016-01-01

Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7) is a key molecular determinant of pain sensation. However, defining the Nav1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Nav1.7’s role in nociceptor physiology. We report that Nav1.7 is the predominant functional TTX-sensitive Nav in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Nav1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission. PMID:27050761

Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release.

Directory of Open Access Journals (Sweden)

Aristos J Alexandrou

Full Text Available Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7 is a key molecular determinant of pain sensation. However, defining the Nav1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Nav1.7's role in nociceptor physiology. We report that Nav1.7 is the predominant functional TTX-sensitive Nav in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Nav1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission.

Relay Selection with Limited and Noisy Feedback

KAUST Repository

Eltayeb, Mohammed E.

2016-01-28

Relay selection is a simple technique that achieves spatial diversity in cooperative relay networks. Nonetheless, relay selection algorithms generally require error-free channel state information (CSI) from all cooperating relays. Practically, CSI acquisition generates a great deal of feedback overhead that could result in significant transmission delays. In addition to this, the fed back channel information is usually corrupted by additive noise. This could lead to transmission outages if the central node selects the set of cooperating relays based on inaccurate feedback information. In this paper, we propose a relay selection algorithm that tackles the above challenges. Instead of allocating each relay a dedicated channel for feedback, all relays share a pool of feedback channels. Following that, each relay feeds back its identity only if its effective channel (source-relay-destination) exceeds a threshold. After deriving closed-form expressions for the feedback load and the achievable rate, we show that the proposed algorithm drastically reduces the feedback overhead and achieves a rate close to that obtained by selection algorithms with dedicated error-free feedback from all relays. © 2015 IEEE.

Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

Science.gov (United States)

Naranjo, David; Wen, Hua; Brehm, Paul

2015-01-01

The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

Decoding LDPC Convolutional Codes on Markov Channels

Directory of Open Access Journals (Sweden)

Kashyap Manohar

2008-01-01

Full Text Available Abstract This paper describes a pipelined iterative technique for joint decoding and channel state estimation of LDPC convolutional codes over Markov channels. Example designs are presented for the Gilbert-Elliott discrete channel model. We also compare the performance and complexity of our algorithm against joint decoding and state estimation of conventional LDPC block codes. Complexity analysis reveals that our pipelined algorithm reduces the number of operations per time step compared to LDPC block codes, at the expense of increased memory and latency. This tradeoff is favorable for low-power applications.

Decoding LDPC Convolutional Codes on Markov Channels

Directory of Open Access Journals (Sweden)

Chris Winstead

2008-04-01

Full Text Available This paper describes a pipelined iterative technique for joint decoding and channel state estimation of LDPC convolutional codes over Markov channels. Example designs are presented for the Gilbert-Elliott discrete channel model. We also compare the performance and complexity of our algorithm against joint decoding and state estimation of conventional LDPC block codes. Complexity analysis reveals that our pipelined algorithm reduces the number of operations per time step compared to LDPC block codes, at the expense of increased memory and latency. This tradeoff is favorable for low-power applications.

Channel stability of Turkey Creek, Nebraska

Science.gov (United States)

Rus, David L.; Soenksen, Philip J.

1998-01-01

Channelization on Turkey Creek and its receiving stream, the South Fork Big Nemaha River, has disturbed the equilibrium of Turkey Creek and has led to channel-stability problems, such as degradation and channel widening, which pose a threat to bridges and land adjacent to the stream. As part of a multiagency study, the U.S. Geological Survey assessed channel stability at two bridge sites on upper and middle portions of Turkey Creek by analyzing streambed-elevation data for gradation changes, comparing recent cross-section surveys and historic accounts, identifying bank-failure blocks, and analyzing tree-ring samples. These results were compared to gradation data and trend results for a U.S. Geological Survey streamflow-gaging station near the mouth of Turkey Creek from a previous study. Examination of data on streambed elevations reveals that degradation has occurred. The streambed elevation declined 0.5 m at the upper site from 1967-97. The streambed elevation declined by 3.2 m at the middle site from 1948-97 and exposed 2 m of the pilings of the Nebraska Highway 8 bridge. Channel widening could not be verified at the two sites from 1967-97, but a historic account indicates widening at the middle site to be two to three times that of the 1949 channel width. Small bank failures were evident at the upper site and a 4-m-wide bank failure occurred at the middle site in 1987 according to tree ring analyses. Examination of streambed-elevation data from a previous study at the lower site reveals a statistically significant aggrading trend from 1958-93. Further examination of these data suggests minor degradation occurred until 1975, followed by aggradation.

Sedimentary processes of the lower Monterey Fan channel and channel-mouth lobe

Science.gov (United States)

Klaucke, I.; Masson, D.G.; Kenyon, Neil H.; Gardner, J.V.

2004-01-01

The distribution of deposits, sediment transport pathways and processes on the lower Monterey Fan channel and channel-mouth lobe (CML) are studied through the integration of GLORIA and TOBI sidescan sonar data with 7-kHz subbottom profiler records and sediment cores for ground-truthing. The lower Monterey channel is characterised by an up to 30-m-deep channel with poorly developed levees and alternating muddy and silty muddy overbank deposits. The channel is discontinuous, disappearing where gradients are less than about 1:350. Ground-truthing of the large CML shows that the entire CML is characterised by widespread deposits of generally fine sand, with coarser sand at the base of turbidites. Sand is particularly concentrated in finger-like areas of low-backscatter intensity and is interpreted as the result of non-turbulent sediment-gravity flows depositing metres thick massive, fine sand. TOBI sidescan sonar data reveal recent erosional features in the form of scours, secondary channels, large flow slides, and trains of blocks at the distal end of the CML. Erosion is probably related to increasing gradient as the CML approaches Murray Fracture zone and to differential loading of sandy submarine fan deposits onto pelagic clays. Reworking of older flow slides by sediment transport processes on the lobe produces trains of blocks that are several metres in diameter and aligned parallel to the flow direction. ?? 2004 Elsevier B.V. All rights reserved.

Skyrmion-based multi-channel racetrack

Science.gov (United States)

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.

Geographical gradients in selection can reveal genetic constraints for evolutionary responses to ocean acidification.

Science.gov (United States)

Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D; Bodrossy, Levente; Hobday, Alistair J

2017-02-01

Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO 2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA. © 2017 The Author(s).

Channel estimation for physical layer network coding systems

CERN Document Server

Gao, Feifei; Wang, Gongpu

2014-01-01

This SpringerBrief presents channel estimation strategies for the physical later network coding (PLNC) systems. Along with a review of PLNC architectures, this brief examines new challenges brought by the special structure of bi-directional two-hop transmissions that are different from the traditional point-to-point systems and unidirectional relay systems. The authors discuss the channel estimation strategies over typical fading scenarios, including frequency flat fading, frequency selective fading and time selective fading, as well as future research directions. Chapters explore the performa

End-to-End Joint Antenna Selection Strategy and Distributed Compress and Forward Strategy for Relay Channels

Directory of Open Access Journals (Sweden)

Rahul Vaze

2009-01-01

Full Text Available Multihop relay channels use multiple relay stages, each with multiple relay nodes, to facilitate communication between a source and destination. Previously, distributed space-time codes were proposed to maximize the achievable diversity-multiplexing tradeoff; however, they fail to achieve all the points of the optimal diversity-multiplexing tradeoff. In the presence of a low-rate feedback link from the destination to each relay stage and the source, this paper proposes an end-to-end antenna selection (EEAS strategy as an alternative to distributed space-time codes. The EEAS strategy uses a subset of antennas of each relay stage for transmission of the source signal to the destination with amplifying and forwarding at each relay stage. The subsets are chosen such that they maximize the end-to-end mutual information at the destination. The EEAS strategy achieves the corner points of the optimal diversity-multiplexing tradeoff (corresponding to maximum diversity gain and maximum multiplexing gain and achieves better diversity gain at intermediate values of multiplexing gain, versus the best-known distributed space-time coding strategies. A distributed compress and forward (CF strategy is also proposed to achieve all points of the optimal diversity-multiplexing tradeoff for a two-hop relay channel with multiple relay nodes.

Ice Penetrating Radar Reveals Spatially Variable Features in Basal Channel under the Nansen Ice Shelf, Terra Nova Bay, Antarctica

Science.gov (United States)

Wray, P. L.; Dow, C. F.; Mueller, D.; Lee, W. S.; Lindzey, L.; Greenbaum, J. S.; Blankenship, D. D.

2017-12-01

The stability of Antarctic ice shelves is of great concern as their current thinning and future collapse will contribute to sea-level rise via the acceleration of grounded tributary glaciers into the ocean. The study of the sub-ice-shelf environment is essential for understanding ice-ocean interaction, where warming ocean temperatures have already begun to threaten the long-term viability of Antarctic ice shelves. Obtaining direct measurements of the sub-ice-shelf cavity remains challenging. Here, we demonstrate that ground-based geophysical methods can deliver high resolution monitoring and mapping of the spatial and temporal changes in features, melt rates, and ice mass transport of this environment. In November 2016, 84 km of ground-based, low frequency, Ice Penetrating Radar (IPR) surveys were completed on three sites over the Nansen Ice Shelf in Terra Nova Bay, Antarctica. The surveys examined an ocean-sourced basal channel incised into the bottom of the shelf, originally detected from a large surface depression. Results reveal high resolution features of a several kilometre-wide, 100 m high channel, with 40 m high sub-channels, zones of significant marine ice accumulation, and basal crevasses penetrating large fractions of the ice shelf thickness. Data from multiple airborne geophysical surveys were compared to the November 2016 IPR data to calculate mass change both spatially and temporally. Many of the smaller scale features we detected are not represented through hydrostatic equilibrium as calculated from ice thicknesses, due to bridging stresses, and as such can not be detected with satellite based remote sensing methods. Our in-field geophysical methods produced high-resolution information of these features, which underscores the need for similar surveys over vulnerable ice shelves to better understand ice-ocean processes.

A dye laser with a partial-selective resonator

Energy Technology Data Exchange (ETDEWEB)

Makogon, M M; Sukhanov, V B

1977-04-01

The possibility of controlling the width and spectral position of the generation line of an organic dye laser (Rhodamine 6Zh) whose resonator represents a combination of selective and non-selective channels is demonstrated. The selective channel entails an unsymmetrically mounted prism with whose angular displacement the spectral width can be changed within broad ranges; the non-selective channel maintains the resonator's quality at a sufficiently high level. An expression is given which makes it possible to determine the generation's spectral width when fixing the prism's angular position. The change in the rearrangement band was studied in relation to the qualities of the selective and non-selective channels as determined by the form of the active medium's amplification contour (a narrowing of the spectrum from 0.15 to 0.0019 nm led to a reduction of the rearrangement area from 38.4 to 28.3 nm).

Efficient collaborative sparse channel estimation in massive MIMO

KAUST Repository

Masood, Mudassir

2015-08-12

We propose a method for estimation of sparse frequency selective channels within MIMO-OFDM systems. These channels are independently sparse and share a common support. The method estimates the impulse response for each channel observed by the antennas at the receiver. Estimation is performed in a coordinated manner by sharing minimal information among neighboring antennas to achieve results better than many contemporary methods. Simulations demonstrate the superior performance of the proposed method.

Efficient collaborative sparse channel estimation in massive MIMO

KAUST Repository

Masood, Mudassir; Afify, Laila H.; Al-Naffouri, Tareq Y.

2015-01-01

We propose a method for estimation of sparse frequency selective channels within MIMO-OFDM systems. These channels are independently sparse and share a common support. The method estimates the impulse response for each channel observed by the antennas at the receiver. Estimation is performed in a coordinated manner by sharing minimal information among neighboring antennas to achieve results better than many contemporary methods. Simulations demonstrate the superior performance of the proposed method.

Shaker-related voltage-gated K+ channel expression and vasomotor function in human coronary resistance arteries.

Science.gov (United States)

Nishijima, Yoshinori; Korishettar, Ankush; Chabowski, Dawid S; Cao, Sheng; Zheng, Xiaodong; Gutterman, David D; Zhang, David X

2018-01-01

K V channels are important regulators of vascular tone, but the identity of specific K V channels involved and their regulation in disease remain less well understood. We determined the expression of K V 1 channel subunits and their role in cAMP-mediated dilation in coronary resistance arteries from subjects with and without CAD. HCAs from patients with and without CAD were assessed for mRNA and protein expression of K V 1 channel subunits with molecular techniques and for vasodilator response with isolated arterial myography. Assays of mRNA transcripts, membrane protein expression, and vascular cell-specific localization revealed abundant expression of K V 1.5 in vascular smooth muscle cells of non-CAD HCAs. Isoproterenol and forskolin, two distinct cAMP-mediated vasodilators, induced potent dilation of non-CAD arterioles, which was inhibited by both the general K V blocker 4-AP and the selective K V 1.5 blocker DPO-1. The cAMP-mediated dilation was reduced in CAD and was accompanied by a loss of or reduced contribution of 4-AP-sensitive K V channels. K V 1.5, as a major 4-AP-sensitive K V 1 channel expressed in coronary VSMCs, mediates cAMP-mediated dilation in non-CAD arterioles. The cAMP-mediated dilation is reduced in CAD coronary arterioles, which is associated with impaired 4-AP-sensitive K V channel function. © 2017 John Wiley & Sons Ltd.

Channeling effect for low energy ion implantation in Si

International Nuclear Information System (INIS)

Cho, K.; Allen, W.R.; Finstad, T.G.; Chu, W.K.; Liu, J.; Wortman, J.J.

1985-01-01

Ion implantation is one of the most important processes in semiconductor device fabrication. Due to the crystalline nature of Si, channeling of implanted ions occurs during this process. Modern devices become smaller and shallower and therefore require ion implantation at lower energies. The effect of channeling on ion implantation becomes a significant problem for low energy ion implantation. The critical angle for axial and planar channeling increases with decreasing energy. This corresponds to an increased probability for channeling with lowering of ion energy. The industry approach to avoid the channeling problem is to employ a tilt angle of 7 0 between the ion implantation direction and the surface normal. We approach the problem by mapping major crystalline axes and planes near the [100] surface normal. Our analysis indicates that a 7 0 tilt is not an optimum selection in channeling reduction. Tilt angles in the range 5 0 to 6 0 combined with 7 0 +- 0.5 0 rotation from the (100) plane are better selections for the reduction of the channeling effect. The range of suitable angles is a function of the implantation energy. Implantations of boron along well specified crystallographic directions have been carried out by careful alignment and the resulting boron profiles measured by SIMS. (orig.)

Opportunistic Relay Selection With Limited Feedback

KAUST Repository

Eltayeb, Mohammed E.

2015-08-01

Relay selection is a simple technique that achieves spatial diversity in cooperative relay networks. Generally, relay selection algorithms require channel state information (CSI) feedback from all cooperating relays to make a selection decision. This requirement poses two important challenges, which are often neglected in the literature. Firstly, the fed back channel information is usually corrupted by additive noise. Secondly, CSI feedback generates a great deal of feedback overhead (air-time) that could result in significant performance hits. In this paper, we propose a compressive sensing (CS) based relay selection algorithm that reduces the feedback overhead of relay networks under the assumption of noisy feedback channels. The proposed algorithm exploits CS to first obtain the identity of a set of relays with favorable channel conditions. Following that, the CSI of the identified relays is estimated using least squares estimation without any additional feedback. Both single and multiple relay selection cases are considered. After deriving closed-form expressions for the asymptotic end-to-end SNR at the destination and the feedback load for different relaying protocols, we show that CS-based selection drastically reduces the feedback load and achieves a rate close to that obtained by selection algorithms with dedicated error-free feedback. © 1972-2012 IEEE.

VKCDB: Voltage-gated potassium channel database

Directory of Open Access Journals (Sweden)

Gallin Warren J

2004-01-01

Full Text Available Abstract Background The family of voltage-gated potassium channels comprises a functionally diverse group of membrane proteins. They help maintain and regulate the potassium ion-based component of the membrane potential and are thus central to many critical physiological processes. VKCDB (Voltage-gated potassium [K] Channel DataBase is a database of structural and functional data on these channels. It is designed as a resource for research on the molecular basis of voltage-gated potassium channel function. Description Voltage-gated potassium channel sequences were identified by using BLASTP to search GENBANK and SWISSPROT. Annotations for all voltage-gated potassium channels were selectively parsed and integrated into VKCDB. Electrophysiological and pharmacological data for the channels were collected from published journal articles. Transmembrane domain predictions by TMHMM and PHD are included for each VKCDB entry. Multiple sequence alignments of conserved domains of channels of the four Kv families and the KCNQ family are also included. Currently VKCDB contains 346 channel entries. It can be browsed and searched using a set of functionally relevant categories. Protein sequences can also be searched using a local BLAST engine. Conclusions VKCDB is a resource for comparative studies of voltage-gated potassium channels. The methods used to construct VKCDB are general; they can be used to create specialized databases for other protein families. VKCDB is accessible at http://vkcdb.biology.ualberta.ca.

Biomarker selection for determining bone biocompatibility of pure magnesium processed by equal channel angular pressing (ECAP) using immunohistochemistry

Science.gov (United States)

Handayani, Lisa; Sulistyani, Lilies Dwi; Supriadi, Sugeng; Priosoeryanto, Bambang Pontjo; Latief, Benny Syariefsyah

2018-02-01

Since grain refinement is proved to be favorable to improve mechanical properties and corrosion resistance, a new conceptual metal forming process, equal channel angular pressing (ECAP), has been carried out on magnesium, a very promising biodegradable material in the field of oral and maxillofacial surgery. The popularity of immunohisto-chemistry (IHC) has been rising following the discovery of biomarker. In the meantime, more antibodies being produced for research have been continuously rising and becoming more varied. This review provides a conceptual framework to understand the roles of IHC on determination of bone biocompatibility to ECAP magnesium by selecting biomarker and point needed to either select or make an antibody to the target. From the review, it has been concluded that the most suitable biomarkers for biocompatibility test of bone implanted with ECAP magnesium are collagen-1, osteocalcin, smooth muscle actin, and CD68.

Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection

Science.gov (United States)

Kijas, James W.; Lenstra, Johannes A.; Hayes, Ben; Boitard, Simon; Porto Neto, Laercio R.; San Cristobal, Magali; Servin, Bertrand; McCulloch, Russell; Whan, Vicki; Gietzen, Kimberly; Paiva, Samuel; Barendse, William; Ciani, Elena; Raadsma, Herman; McEwan, John; Dalrymple, Brian

2012-01-01

Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species. PMID:22346734

Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection.

Directory of Open Access Journals (Sweden)

James W Kijas

2012-02-01

Full Text Available Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species.

Identification of an HV 1 voltage-gated proton channel in insects.

Science.gov (United States)

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.

Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism

DEFF Research Database (Denmark)

Taneja, Tarvinder K; Mankouri, Jamel; Karnik, Rucha

2009-01-01

The ATP-sensitive potassium (K(ATP)) channel controls insulin secretion by coupling glucose metabolism to excitability of the pancreatic beta-cell membrane. The channel comprises four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by KCNJ11 and ABCC8, respectively. Mutatio...

Atomic basis for therapeutic activation of neuronal potassium channels

DEFF Research Database (Denmark)

Kim, Robin Y; Yau, Michael C; Galpin, Jason D

2015-01-01

Retigabine is a recently approved anticonvulsant that acts by potentiating neuronal M-current generated by KCNQ2-5 channels, interacting with a conserved Trp residue in the channel pore domain. Using unnatural amino-acid mutagenesis, we subtly altered the properties of this Trp to reveal specific...

Differential subcellular distribution of ion channels and the diversity of neuronal function.

Science.gov (United States)

Nusser, Zoltan

2012-06-01

Following the astonishing molecular diversity of voltage-gated ion channels that was revealed in the past few decades, the ion channel repertoire expressed by neurons has been implicated as the major factor governing their functional heterogeneity. Although the molecular structure of ion channels is a key determinant of their biophysical properties, their subcellular distribution and densities on the surface of nerve cells are just as important for fulfilling functional requirements. Recent results obtained with high resolution quantitative localization techniques revealed complex, subcellular compartment-specific distribution patterns of distinct ion channels. Here I suggest that within a given neuron type every ion channel has a unique cell surface distribution pattern, with the functional consequence that this dramatically increases the computational power of nerve cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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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

Cooperative Spectrum Sensing over Non-Identical Nakagami Fading Channels

KAUST Repository

Rao, Anlei

2012-09-08

Previous works in cooperative spectrum sensing assumed that the channels for sensing and reporting are independent identical distributed (i.i.d). A more practical and appropriate assumption, however, should be that the sensing channels and reporting channels are independent but not necessarily identically distributed (i.n.i.d). In this paper, we derive the false-alarm probability and the detection probability of cooperative spectrum sensing with energy fusion over i.n.i.d Nakagami fading channels. Selected numerical results show that cooperative spectrum sensing still gives considerably better performance results even over i.n.i.d fading channels.

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

Science.gov (United States)

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

2016-04-01

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

The Kinetics and the Permeation Properties of Piezo Channels.

Science.gov (United States)

Gnanasambandam, R; Gottlieb, P A; Sachs, F

2017-01-01

Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300kD monomer has an N-terminal propeller blade-like mechanosensing module, which can confer mechanosensing capabilities on ASIC-1 (the trimeric non-MSC, acid-sensing ion channel-1) and a C-terminal pore module, which influences conductance, selectivity, and channel inactivation. Repeated stimulation can cause domain fracture and diffusion of these channels leading to synchronous loss of inactivation. The reconstituted channels spontaneously open only in asymmetric bilayers but lack inactivation. Mutations that cause hereditary xerocytosis alter PIEZO1 kinetics. The kinetics of the wild-type PIEZO1 and alterations thereof in mutants (M2225R, R2456K, and DhPIEZO1) are summarized in the form of a quantitative model and hosted online. The pore is permeable to alkali ions although Li + permeates poorly. Divalent cations, notably Ca 2+ , traverse the channel and inhibit the flux of monovalents. The large monovalent organic cations such as tetramethyl ammonium and tetraethyl ammonium can traverse the channel, but slowly, suggesting a pore diameter of ∼8Å, and the estimated in-plane area change upon opening is around 6-20nm 2 . Ruthenium red can enter the channel only from the extracellular side and seems to bind in a pocket close to residue 2496. Copyright © 2017 Elsevier Inc. All rights reserved.

Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect GABA-Gated Chloride Channels.

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Yan Xu

Full Text Available Meroterpenoid chrodrimanins, produced from Talaromyces sp. YO-2, are known to paralyze silkworm (Bombyx mori larvae, but their target is unknown. We have investigated the actions of chrodrimanin B on ligand-gated ion channels of silkworm larval neurons using patch-clamp electrophysiology. Chrodrimanin B had no effect on membrane currents when tested alone at 1 μM. However, it completely blocked the γ-aminobutyric acid (GABA-induced current and showed less pronounced actions on acetylcholine- and L-glutamate-induced currents, when delivered at 1 μM for 1 min prior to co-application with transmitter GABA. Thus, chrodrimanins were also tested on a wild-type isoform of the B. mori GABA receptor (GABAR RDL using two-electrode voltage-clamp electrophysiology. Chrodrimanin B attenuated the peak current amplitude of the GABA response of RDL with an IC50 of 1.66 nM. The order of the GABAR-blocking potency of chrodrimanins B > D > A was in accordance with their reported insecticidal potency. Chrodrimanin B had no open channel blocking action when tested at 3 nM on the GABA response of RDL. Co-application with 3 nM chrodrimanin B shifted the GABA concentration response curve to a higher concentration and further increase of chrodrimanin B concentration to 10 nM; it reduced maximum current amplitude of the GABA response, pointing to a high-affinity competitive action and a lower affinity non-competitive action. The A282S;T286V double mutation of RDL, which impairs the actions of fipronil, hardly affected the blocking action of chrodrimanin B, indicating a binding site of chrodrimanin B distinct from that of fipronil. Chrodrimanin B showed approximately 1,000-fold lower blocking action on human α1β2γ2 GABAR compared to RDL and thus is a selective blocker of insect GABARs.

Comparison of different turbulence models in open channels with smooth-rough bedforms

International Nuclear Information System (INIS)

Ghani, U.

2013-01-01

The turbulence models play an important role in all types of computational fluid dynamics based numerical modelling. There is no universal turbulence model which can be applied in all the scenarios. Therefore, if a suitable closure model is used in a simulation work, only then the successful numerical modelling will be achieved. This paper presents the evaluation of three turbulence models in numerical modelling of open channel flows having beds comprising of two parallel strips, one being smooth and the other one being rough. The roughness on the rough side of the channel was created with the help of gravels. The turbulence models tested for their suitability in this case were Reynolds stress model, k-model and RNG based k-model. A structured mesh was used in this simulation work. Grid independence test was also conducted in the simulation. The evaluation of the turbulence models was made through the primary velocity contours and secondary velocity vectors over the cross section of the channel. It was revealed that Reynolds stress model simulated the flow behaviour successfully and results obtained through this model matched very closely to that of the experimental data whereas k-model and RNG based k-model failed to reproduce the flow field successfully. These results will be helpful for CFD (Computational Fluid Dynamics) modellers in correct selection of the turbulence model in these types of channels. (author)

Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex.

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Danko Georgiev

Full Text Available The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV or somatostatin (SST. Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K(+ channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K(+ channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with (35S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.

In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.

Science.gov (United States)

Singh, Prabhat; Sharma, Bhupesh; Gupta, Surbhi; Sharma, B M

2015-01-01

Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Present study has been structured to investigate the role of insulin and pharmacological modulator of KATP channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro. In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2)) were assessed. Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Insulin and gliclazide (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.

Reduction of channel zapping delay in IPTV services

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F. Moumtadi

2008-07-01

Full Text Available This paper analyses the existing delay within an IPTV system when a user selects an other channel, and a new algorithm is used to reduce it. Based on the adjacent groups method, which reduces the time acquisition of a new channel placing the order not only for that channel but also for the adjacent channels. There are two principles under coonsideration, one that there exists a sufficient bandwidht, and the other, a multicast transmission (Chunglae, 2004. At the end of the paper, the obtained results are compared against the present ones and the possibilities of the algorithm are determined.

Evolutionary origins of mechanosensitive ion channels.

Science.gov (United States)

Martinac, Boris; Kloda, Anna

2003-01-01

According to the recent revision, the universal phylogenetic tree is composed of three domains: Eukarya (eukaryotes), Bacteria (eubacteria) and Archaea (archaebacteria). Mechanosensitive (MS) ion channels have been documented in cells belonging to all three domains suggesting their very early appearance during evolution of life on Earth. The channels show great diversity in conductance, selectivity and voltage dependence, while sharing the property of being gated by mechanical stimuli exerted on cell membranes. In prokaryotes, MS channels were first documented in Bacteria followed by their discovery in Archaea. The finding of MS channels in archaeal cells helped to recognize and establish the evolutionary relationship between bacterial and archaeal MS channels and to show that this relationship extends to eukaryotic Fungi (Schizosaccharomyces pombe) and Plants (Arabidopsis thaliana). Similar to their bacterial and archaeal homologues, MS channels in eukaryotic cell-walled Fungi and Plants may serve in protecting the cellular plasma membrane from excessive dilation and rupture that may occur during osmotic stress. This review summarizes briefly some of the recent developments in the MS channel research field that may ultimately lead to elucidation of the biophysical and evolutionary principles underlying the mechanosensory transduction in living cells.

Chip-Level Channel Equalization in WCDMA Downlink

Directory of Open Access Journals (Sweden)

Kari Hooli

2002-08-01

Full Text Available The most important third generation (3G cellular communications standard is based on wideband CDMA (WCDMA. Receivers based on TDMA style channel equalization at the chip level have been proposed for a WCDMA downlink employing long spreading sequences to ensure adequate performance even with a high number of active users. These receivers equalize the channel prior to despreading, thus restoring the orthogonality of users and resulting in multiple-access interference (MAI suppression. In this paper, an overview of chip-level channel equalizers is delivered with special attention to adaptation methods suitable for the WCDMA downlink. Numerical examples on the equalizers′ performance are given in Rayleigh fading frequency-selective channels.

A Mathematical Model of Membrane Gas Separation with Energy Transfer by Molecules of Gas Flowing in a Channel to Molecules Penetrating this Channel from the Adjacent Channel

Directory of Open Access Journals (Sweden)

Szwast Maciej

2015-06-01

Full Text Available The paper presents the mathematical modelling of selected isothermal separation processes of gaseous mixtures, taking place in plants using membranes, in particular nonporous polymer membranes. The modelling concerns membrane modules consisting of two channels - the feeding and the permeate channels. Different shapes of the channels cross-section were taken into account. Consideration was given to co-current and counter-current flows, for feeding and permeate streams, respectively, flowing together with the inert gas receiving permeate. In the proposed mathematical model it was considered that pressure of gas changes along the length of flow channels was the result of both - the drop of pressure connected with flow resistance, and energy transfer by molecules of gas flowing in a given channel to molecules which penetrate this channel from the adjacent channel. The literature on membrane technology takes into account only the drop of pressure connected with flow resistance. Consideration given to energy transfer by molecules of gas flowing in a given channel to molecules which penetrate this channel from the adjacent channel constitute the essential novelty in the current study. The paper also presents results of calculations obtained by means of a computer program which used equations of the derived model. Physicochemical data concerning separation of the CO2/CH4 mixture with He as the sweep gas and data concerning properties of the membrane made of PDMS were assumed for calculations.

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

Science.gov (United States)

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.

Scheduling for Multiuser MIMO Downlink Channels with Ranking-Based Feedback

Science.gov (United States)

Kountouris, Marios; Sälzer, Thomas; Gesbert, David

2008-12-01

We consider a multi-antenna broadcast channel with more single-antenna receivers than transmit antennas and partial channel state information at the transmitter (CSIT). We propose a novel type of CSIT representation for the purpose of user selection, coined as ranking-based feedback. Each user calculates and feeds back the rank, an integer between 1 and W + 1, of its instantaneous channel quality information (CQI) among a set of W past CQI measurements. Apart from reducing significantly the required feedback load, ranking-based feedback enables the transmitter to select users that are on the highest peak (quantile) with respect to their own channel distribution, independently of the distribution of other users. It can also be shown that this feedback metric can restore temporal fairness in heterogeneous networks, in which users' channels are not identically distributed and mobile terminals experience different average signal-to-noise ratio (SNR). The performance of a system that performs user selection using ranking-based CSIT in the context of random opportunistic beamforming is analyzed, and we provide design guidelines on the number of required past CSIT samples and the impact of finite W on average throughput. Simulation results show that feedback reduction of order of 40-50% can be achieved with negligible decrease in system throughput.

TRIC-B channels display labile gating: evidence from the TRIC-A knockout mouse model.

Science.gov (United States)

Venturi, Elisa; Matyjaszkiewicz, Antoni; Pitt, Samantha J; Tsaneva-Atanasova, Krasimira; Nishi, Miyuki; Yamazaki, Daiju; Takeshima, Hiroshi; Sitsapesan, Rebecca

2013-08-01

Sarcoplasmic/endoplasmic reticulum (SR) and nuclear membranes contain two related cation channels named TRIC-A and TRIC-B. In many tissues, both subtypes are co-expressed, making it impossible to distinguish the distinct single-channel properties of each subtype. We therefore incorporated skeletal muscle SR vesicles derived from Tric-a-knockout mice into bilayers in order to characterise the biophysical properties of native TRIC-B without possible misclassification of the channels as TRIC-A, and without potential distortion of functional properties by detergent purification protocols. The native TRIC-B channels were ideally selective for cations. In symmetrical 210 mM K(+), the maximum (full) open channel level (199 pS) was equivalent to that observed when wild-type SR vesicles were incorporated into bilayers. Analysis of TRIC-B gating revealed complex and variable behaviour. Four main sub-conductance levels were observed at approximately 80 % (161 pS), 60 % (123 pS), 46 % (93 pS), and 30 % (60 pS) of the full open state. Seventy-five percent of the channels were voltage sensitive with Po being markedly reduced at negative holding potentials. The frequent, rapid transitions between TRIC-B sub-conductance states prevented development of reliable gating models using conventional single-channel analysis. Instead, we used mean-variance plots to highlight key features of TRIC-B gating in a more accurate and visually useful manner. Our study provides the first biophysical characterisation of native TRIC-B channels and indicates that this channel would be suited to provide counter current in response to Ca(2+) release from the SR. Further experiments are required to distinguish the distinct functional properties of TRIC-A and TRIC-B and understand their individual but complementary physiological roles.

Charge-Transfer-Induced p-Type Channel in MoS2 Flake Field Effect Transistors.

Science.gov (United States)

Min, Sung-Wook; Yoon, Minho; Yang, Sung Jin; Ko, Kyeong Rok; Im, Seongil

2018-01-31

The two-dimensional transition-metal dichalcogenide semiconductor MoS 2 has received extensive attention for decades because of its outstanding electrical and mechanical properties for next-generation devices. One weakness of MoS 2 , however, is that it shows only n-type conduction, revealing its limitations for homogeneous PN diodes and complementary inverters. Here, we introduce a charge-transfer method to modify the conduction property of MoS 2 from n- to p-type. We initially deposited an n-type InGaZnO (IGZO) film on top of the MoS 2 flake so that electron charges might be transferred from MoS 2 to IGZO during air ambient annealing. As a result, electron charges were depleted in MoS 2 . Such charge depletion lowered the MoS 2 Fermi level, which makes hole conduction favorable in MoS 2 when optimum source/drain electrodes with a high work function are selected. Our IGZO-supported MoS 2 flake field effect transistors (FETs) clearly display channel-type conversion from n- to p-channel in this way. Under short- and long-annealing conditions, n- and p-channel MoS 2 FETs are achieved, respectively, and a low-voltage complementary inverter is demonstrated using both channels in a single MoS 2 flake.

Reducing Channel Interaction Through Cochlear Implant Programming May Improve Speech Perception

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Julie A. Bierer

2016-06-01

Full Text Available Speech perception among cochlear implant (CI listeners is highly variable. High degrees of channel interaction are associated with poorer speech understanding. Two methods for reducing channel interaction, focusing electrical fields, and deactivating subsets of channels were assessed by the change in vowel and consonant identification scores with different program settings. The main hypotheses were that (a focused stimulation will improve phoneme recognition and (b speech perception will improve when channels with high thresholds are deactivated. To select high-threshold channels for deactivation, subjects’ threshold profiles were processed to enhance the peaks and troughs, and then an exclusion or inclusion criterion based on the mean and standard deviation was used. Low-threshold channels were selected manually and matched in number and apex-to-base distribution. Nine ears in eight adult CI listeners with Advanced Bionics HiRes90k devices were tested with six experimental programs. Two, all-channel programs, (a 14-channel partial tripolar (pTP and (b 14-channel monopolar (MP, and four variable-channel programs, derived from these two base programs, (c pTP with high- and (d low-threshold channels deactivated, and (e MP with high- and (f low-threshold channels deactivated, were created. Across subjects, performance was similar with pTP and MP programs. However, poorer performing subjects (scoring  2. These same subjects showed slightly more benefit with the reduced channel MP programs (5 and 6. Subjective ratings were consistent with performance. These finding suggest that reducing channel interaction may benefit poorer performing CI listeners.

The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures.

Science.gov (United States)

Mayer, Mark L

2017-11-21

Ion channels activated by glutamate mediate excitatory synaptic transmission in the central nervous system. Similar to other ligand-gated ion channels, their gating cycle begins with transitions from a ligand-free closed state to glutamate-bound active and desensitized states. In an attempt to reveal the molecular mechanisms underlying gating, numerous structures for glutamate receptors have been solved in complexes with agonists, antagonists, allosteric modulators, and auxiliary proteins. The embarrassingly rich library of structures emerging from this work reveals very dynamic molecules with a more complex conformational spectrum than anticipated from functional studies. Unanticipated conformations solved for complexes with competitive antagonists and a lack of understanding of the structural basis for ion channel subconductance states further highlight challenges that have yet to be addressed. Published by Elsevier Inc.

Identification of mud crab reovirus VP12 and its interaction with the voltage-dependent anion-selective channel protein of mud crab Scylla paramamosain.

Science.gov (United States)

Xu, Hai-Dong; Su, Hong-Jun; Zou, Wei-Bin; Liu, Shan-Shan; Yan, Wen-Rui; Wang, Qian-Qian; Yuan, Li-Li; Chan, Siuming Francis; Yu, Xiao-Qiang; He, Jian-Guo; Weng, Shao-Ping

2015-05-01

Mud crab reovirus (MCRV) is the causative agent of a severe disease in cultured mud crab (Scylla paramamosain), which has caused huge economic losses in China. MCRV is a double-stranded RNA virus with 12 genomic segments. In this paper, SDS-PAGE, mass spectrometry and Western blot analyses revealed that the VP12 protein encoded by S12 gene is a structural protein of MCRV. Immune electron microscopy assay indicated that MCRV VP12 is a component of MCRV outer shell capsid. Yeast two hybrid cDNA library of mud crab was constructed and mud crab voltage-dependent anion-selective channel (mcVDAC) was obtained by MCRV VP12 screening. The full length of mcVDAC was 1180 bp with an open reading frame (ORF) of 849 bp encoding a 282 amino acid protein. The mcVDAC had a constitutive expression pattern in different tissues of mud crab. The interaction between MCRV VP12 and mcVDAC was determined by co-immunoprecipitation assay. The results of this study have provided an insight on the mechanisms of MCRV infection and the interactions between the virus and mud crab. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures.

Directory of Open Access Journals (Sweden)

Moon Young Lee

Full Text Available Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC, which serve as slow-wave electrical pacemakers for gastrointestinal (GI smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

[Channels: a new way to revisit pathology].

Science.gov (United States)

Fournier, Emmanuel

2014-02-01

Many "essential" diseases that manifest themselves in the form of crises or fits (epilepsies, episodic ataxia, periodic paralyses, myotonia, heart rhythm disorders, etc.) are due to ionic channel dysfunction and are thus referred to as "channelopathies". Some of these disorders are congenital, due to mutations of genes encoding channel subunits, while others result from toxic, immune or hormonal disturbances affecting channelfunction. Channelopathies take on a wide variety of clinical forms, depending on the type of channel (sodium, potassium, calcium, chloride...) and the type of dysfunction (loss or gain of function). Some apparently unrelated diseases affecting distinct organs are due to a similar dysfunction of the same channel, revealing unsuspected relationships between organs and between medical specialties. In addition, a given syndrome can be caused by distinct channel dysfunctions. This provides new opportunities for diferential diagnosis and specific correction of the causal defects, although some treatments find applications across multiple medical specialties.

Adaptive transmit selection with interference suppression

KAUST Repository

Radaydeh, Redha Mahmoud Mesleh

2010-01-01

This paper studies the performance of adaptive transmit channel selection in multipath fading channels. The adaptive selection algorithms are configured for single-antenna bandwidth-efficient or power-efficient transmission with as low transmit channel estimations as possible. Due to the fact that the number of active co-channel interfering signals and their corresponding powers experience random behavior, the adaptation to channels conditions, assuming uniform buffer and traffic loading, is proposed to be jointly based on the transmit channels instantaneous signal-to-noise ratios (SNRs) and signal-to- interference-plus- noise ratios (SINRs). Two interference cancelation algorithms, which are the dominant cancelation and the less complex arbitrary cancelation, are considered, for which the receive antenna array is assumed to have small angular spread. Analytical formulation for some performance measures in addition to several processing complexity and numerical comparisons between various adaptation schemes are presented. ©2010 IEEE.

Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms.

Science.gov (United States)

Cristofori-Armstrong, Ben; Rash, Lachlan D

2017-12-01

Acid-sensing ion channels (ASICs) are proton-activated cation channels that are expressed in a variety of neuronal and non-neuronal tissues. As proton-gated channels, they have been implicated in many pathophysiological conditions where pH is perturbed. Venom derived compounds represent the most potent and selective modulators of ASICs described to date, and thus have been invaluable as pharmacological tools to study ASIC structure, function, and biological roles. There are now ten ASIC modulators described from animal venoms, with those from snakes and spiders favouring ASIC1, while the sea anemones preferentially target ASIC3. Some modulators, such as the prototypical ASIC1 modulator PcTx1 have been studied in great detail, while some of the newer members of the club remain largely unstudied. Here we review the current state of knowledge on venom derived ASIC modulators, with a particular focus on their molecular interaction with ASICs, what they have taught us about channel structure, and what they might still reveal about ASIC function and pathophysiological roles. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Site-specific distribution of claudin-based paracellular channels with roles in biological fluid flow and metabolism.

Science.gov (United States)

Tanaka, Hiroo; Tamura, Atsushi; Suzuki, Koya; Tsukita, Sachiko

2017-10-01

The claudins are a family of membrane proteins with at least 27 members in humans and mice. The extracellular regions of claudin proteins play essential roles in cell-cell adhesion and the paracellular barrier functions of tight junctions (TJs) in epithelial cell sheets. Furthermore, the extracellular regions of some claudins function as paracellular channels in the paracellular barrier that allow the selective passage of water, ions, and/or small organic solutes across the TJ in the extracellular space. Structural analyses have revealed a common framework of transmembrane, cytoplasmic, and extracellular regions among the claudin-based paracellular barriers and paracellular channels; however, differences in the claudins' extracellular regions, such as their charges and conformations, determine their properties. Among the biological systems that involve fluid flow and metabolism, it is noted that hepatic bile flow, renal Na + reabsorption, and intestinal nutrient absorption are dynamically regulated via site-specific distributions of paracellular channel-forming claudins in tissue. Here, we focus on how site-specific distributions of claudin-2- and claudin-15-based paracellular channels drive their organ-specific functions in the liver, kidney, and intestine. © 2017 New York Academy of Sciences.

Venom-derived peptides inhibiting Kir channels: Past, present, and future.

Science.gov (United States)

Doupnik, Craig A

2017-12-01

Inwardly rectifying K + (Kir) channels play a significant role in vertebrate and invertebrate biology by regulating the movement of K + ions involved in membrane transport and excitability. Yet unlike other ion channels including their ancestral K + -selective homologs, there are very few venom toxins known to target and inhibit Kir channels with the potency and selectivity found for the Ca 2+ -activated and voltage-gated K + channel families. It is unclear whether this is simply due to a lack of discovery, or instead a consequence of the evolutionary processes that drive the development of venom components towards their targets based on a collective efficacy to 1) elicit pain for defensive purposes, 2) promote paralysis for prey capture, or 3) facilitate delivery of venom components into the circulation. The past two decades of venom screening has yielded three venom peptides with inhibitory activity towards mammalian Kir channels, including the discovery of tertiapin, a high-affinity pore blocker from the venom of the European honey bee Apis mellifera. Venomics and structure-based computational approaches represent exciting new frontiers for venom peptide development, where re-engineering peptide 'scaffolds' such as tertiapin may aid in the quest to expand the palette of potent and selective Kir channel blockers for future research and potentially new therapeutics. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Kv7 channels can function without constitutive calmodulin tethering.

Directory of Open Access Journals (Sweden)

Juan Camilo Gómez-Posada

Full Text Available M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC, a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.

Performance Analysis of the IEEE 802.11A WLAN Standard Optimum and Sub-Optimum Receiver in Frequency-Selective, Slowly Fading Nakagami Channels with AWGN and Pulsed Noise Jamming

National Research Council Canada - National Science Library

Kalogrias, Christos

2004-01-01

... 802.11a wireless local area network (WLAN) standard receiver when the signal is transmitted over a frequency selective, slow fading Nakagami channel in a worst case, pulse-noise jamming environment...

Mode Switching for the Multi-Antenna Broadcast Channel Based on Delay and Channel Quantization

Directory of Open Access Journals (Sweden)

Jun Zhang

2009-01-01

Full Text Available Imperfect channel state information degrades the performance of multiple-input multiple-output (MIMO communications; its effects on single-user (SU and multiuser (MU MIMO transmissions are quite different. In particular, MU-MIMO suffers from residual interuser interference due to imperfect channel state information while SU-MIMO only suffers from a power loss. This paper compares the throughput loss of both SU and MU-MIMO in the broadcast channel due to delay and channel quantization. Accurate closed-form approximations are derived for achievable rates for both SU and MU-MIMO. It is shown that SU-MIMO is relatively robust to delayed and quantized channel information, while MU-MIMO with zero-forcing precoding loses its spatial multiplexing gain with a fixed delay or fixed codebook size. Based on derived achievable rates, a mode switching algorithm is proposed, which switches between SU and MU-MIMO modes to improve the spectral efficiency based on average signal-to-noise ratio (SNR, normalized Doppler frequency, and the channel quantization codebook size. The operating regions for SU and MU modes with different delays and codebook sizes are determined, and they can be used to select the preferred mode. It is shown that the MU mode is active only when the normalized Doppler frequency is very small, and the codebook size is large.

Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+-activated K(+ channels.

Directory of Open Access Journals (Sweden)

Kiril L Hristov

Full Text Available Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO, which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM large conductance Ca(2+-activated K(+ (BK channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR, perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

The selective flow of volatile organic compounds in conductive polymer-coated microchannels

Science.gov (United States)

Hossein-Babaei, Faramarz; Hooshyar Zare, Ali

2017-02-01

Many gaseous markers of critical biological, physicochemical, or industrial occurrences are masked by the cross-sensitivity of the sensors to the other active components present at higher concentrations. Here, we report the strongly selective diffusion and drift of contaminant molecules in air-filled conductive polymer-coated microfluidic channels for the first time. Monitoring the passage of different target molecules through microchannels coated with Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) revealed that contaminants such as hexane, benzene, and CO pass through the channel unaffected by the coating while methanol, ethanol, and partly acetone are blocked. The observations are explained with reference to the selective interactions between the conductive polymer surface and target gas molecules amplified by the large wall/volume ratio in microchannels. The accumulated quantitative data point at the hydrogen bonding as the mechanism of wall adsorption; dipole-dipole interactions are relatively insignificant. The presented model facilitates a better understanding of how the conductive polymer-based chemical sensors operate.

Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

Science.gov (United States)

Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

2012-06-01

The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

Mechanosensitive channels: feeling tension in a world under pressure

Directory of Open Access Journals (Sweden)

Peyronnet eRemi

2014-10-01

Full Text Available Plants, like other organisms, are facing multiple mechanical constraints generated both in their tissues and by the surrounding environment. They need to sense and adapt to these forces throughout their lifetime. To do so, different mechanisms devoted to force transduction have emerged. Here we focus on fascinating proteins: the mechanosenstive (MS channels. Mechanosensing in plants has been described for centuries but the molecular identification of MS channels occurred only recently. This review is aimed at plant biologists and plant biomechanists who want to be introduced to MS channel identity, how do they work and what they might do in planta? In this review, electrophysiological properties, regulations and functions of well characterized MS channels belonging to bacteria and animals are compared with those of plant . Common and specific properties are discussed. We deduce which tools and concepts from animal and bacterial fields could be helpful for improving our understanding of plant mechanotransduction. MS channel embedded in its plasma membrane is sandwiched between the cell wall and the cytoskeleton. The consequences of this peculiar situation are analyzed and discussed. We also stress how important it is to probe mechanical forces at cellular and subcellular levels in planta in order to reveal the intimate relationship linking the membrane with MS channel activity. Finally we will propose new tracks to help to reveal their physiological functions at tissue and plant levels.

DFT-based channel estimation and noise variance estimation techniques for single-carrier FDMA

OpenAIRE

Huang, G; Nix, AR; Armour, SMD

2010-01-01

Practical frequency domain equalization (FDE) systems generally require knowledge of the channel and the noise variance to equalize the received signal in a frequency-selective fading channel. Accurate channel estimate and noise variance estimate are thus desirable to improve receiver performance. In this paper we investigate the performance of the denoise channel estimator and the approximate linear minimum mean square error (A-LMMSE) channel estimator with channel power delay profile (PDP) ...

Metaflumizone is a novel sodium channel blocker insecticide.

Science.gov (United States)

Salgado, V L; Hayashi, J H

2007-12-15

Metaflumizone is a novel semicarbazone insecticide, derived chemically from the pyrazoline sodium channel blocker insecticides (SCBIs) discovered at Philips-Duphar in the early 1970s, but with greatly improved mammalian safety. This paper describes studies confirming that the insecticidal action of metaflumizone is due to the state-dependent blockage of sodium channels. Larvae of the moth Spodoptera eridania injected with metaflumizone became paralyzed, concomitant with blockage of all nerve activity. Furthermore, tonic firing of abdominal stretch receptor organs from Spodoptera frugiperda was blocked by metaflumizone applied in the bath, consistent with the block of voltage-dependent sodium channels. Studies on native sodium channels, in primary-cultured neurons isolated from the CNS of the larvae of the moth Manduca sexta and on Para/TipE sodium channels heterologously expressed in Xenopus (African clawed frog) oocytes, confirmed that metaflumizone blocks sodium channels by binding selectively to the slow-inactivated state, which is characteristic of the SCBIs. The results confirm that metaflumizone is a novel sodium channel blocker insecticide.

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

Science.gov (United States)

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 m

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels.

Science.gov (United States)

Cooper, Jacob C; Phadnis, Nitin

2017-07-01

Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Performance of adaptive MS-GSC with co-channel interference

KAUST Repository

Daghfous, Mohamed A.

2011-06-01

Minimum selection generalized selection combining(MS-GSC) scheme has been proposed as a generalized power-saving variant of the conventional generalized selection combining(GSC) scheme. Previous analysis of the performance of MS-GSC has focused on interference-free environments. This paper aims to investigate the performance of adaptive signal-to-noise ratio (SNR)-based MS-GSC in the presence of co-channel interference over multipath fading channels. The adaptation thresholds are selected to enhance either the spectral efficiency or power efficiency of discrete-time rectangular signaling system. New closed-form expressions for the statistics of combined signal-to-interference-plus-noise ratio (SINR) are presented, which are then used to obtain analytical formulations for various performance measures. Numerical and simulation comparisons for the performance of the adaptation scheme are provided. © 2011 IEEE.

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

Directory of Open Access Journals (Sweden)

Jiuqi Han

2018-04-01

Full Text Available 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.

A Micromechanical RF Channelizer

Science.gov (United States)

Akgul, Mehmet

The power consumption of a radio generally goes as the number and strength of the RF signals it must process. In particular, a radio receiver would consume much less power if the signal presented to its electronics contained only the desired signal in a tiny percent bandwidth frequency channel, rather than the typical mix of signals containing unwanted energy outside the desired channel. Unfortunately, a lack of filters capable of selecting single channel bandwidths at RF forces the front-ends of contemporary receivers to accept unwanted signals, and thus, to operate with sub-optimal efficiency. This dissertation focuses on the degree to which capacitive-gap transduced micromechanical resonators can achieve the aforementioned RF channel-selecting filters. It aims to first show theoretically that with appropriate scaling capacitive-gap transducers are strong enough to meet the needed coupling requirements; and second, to fully detail an architecture and design procedure needed to realize said filters. Finally, this dissertation provides an actual experimentally demonstrated RF channel-select filter designed using the developed procedures and confirming theoretical predictions. Specifically, this dissertation introduces four methods that make possible the design and fabrication of RF channel-select filters. The first of these introduces a small-signal equivalent circuit for parallel-plate capacitive-gap transduced micromechanical resonators that employs negative capacitance to model the dependence of resonance frequency on electrical stiffness in a way that facilitates the analysis of micromechanical circuits loaded with arbitrary electrical impedances. The new circuit model not only correctly predicts the dependence of electrical stiffness on the impedances loading the input and output electrodes of parallel-plate capacitive-gap transduced micromechanical device, but does so in a visually intuitive way that identifies current drive as most appropriate for

Topology of transmembrane channel-like gene 1 protein.

Science.gov (United States)

Labay, Valentina; Weichert, Rachel M; Makishima, Tomoko; Griffith, Andrew J

2010-10-05

Mutations of transmembrane channel-like gene 1 (TMC1) cause hearing loss in humans and mice. TMC1 is the founding member of a family of genes encoding proteins of unknown function that are predicted to contain multiple transmembrane domains. The goal of our study was to define the topology of mouse TMC1 expressed heterologously in tissue culture cells. TMC1 was retained in the endoplasmic reticulum (ER) membrane of five tissue culture cell lines that we tested. We used anti-TMC1 and anti-HA antibodies to probe the topologic orientation of three native epitopes and seven HA epitope tags along full-length TMC1 after selective or complete permeabilization of transfected cells with digitonin or Triton X-100, respectively. TMC1 was present within the ER as an integral membrane protein containing six transmembrane domains and cytosolic N- and C-termini. There is a large cytoplasmic loop, between the fourth and fifth transmembrane domains, with two highly conserved hydrophobic regions that might associate with or penetrate, but do not span, the plasma membrane. Our study is the first to demonstrate that TMC1 is a transmembrane protein. The topologic organization revealed by this study shares some features with that of the shaker-TRP superfamily of ion channels.

KCa2 and KCa3 channels in learning and memory processes, and neurodegeneration

Directory of Open Access Journals (Sweden)

Els F. E. Kuiper

2012-06-01

Full Text Available Calcium-activated potassium (KCa channels are present throughout the central nervous system as well as many peripheral tissues. Activation of KCa channels is essential for maintenance of the neuronal membrane potential and was shown to underlie the afterhyperpolarization (AHP that regulates action potential firing and limits the firing frequency of repetitive action potentials. Different subtypes of KCa channels were anticipated on the basis of their physiological and pharmacological profiles, and cloning revealed two well defined but phylogenetic distantly related groups of channels. The group subject of this review includes both the small-conductance KCa2 channels (KCa2.1, KCa2.2, and KCa2.3 and the intermediate-conductance (KCa3.1 channel. These channels are activated by submicromolar intracellular Ca2+ concentrations and are voltage independent. Of all KCa channels only the KCa2 channels can be potently but differentially blocked by the bee-venom apamin. In the past few years modulation of KCa channel activation revealed new roles for KCa2 channels in controlling dendritic excitability, synaptic functioning and synaptic plasticity. Furthermore, KCa2 channels appeared to be involved in neurodegeneration, and learning and memory processes. In this review, we focus on the role of KCa2 and KCa3 channels in these latter mechanisms with emphasis on learning and memory, Alzheimer’s disease and on the interplay between neuroinflammation and different neurotransmitters/neuromodulators, their signalling components and KCa channel activation.

Channel Power in Multi-Channel Environments

NARCIS (Netherlands)

M.G. Dekimpe (Marnik); B. Skiera (Bernd)

2004-01-01

textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

New Role of P/Q-type Voltage-gated Calcium Channels

DEFF Research Database (Denmark)

Hansen, Pernille B L

2015-01-01

Voltage-gated calcium channels are important for the depolarization-evoked contraction of vascular smooth muscle cells (SMCs), with L-type channels being the classical channel involved in this mechanism. However, it has been demonstrated that the CaV2.1 subunit, which encodes a neuronal isoform...... of the voltage-gated calcium channels (P/Q-type), is also expressed and contributes functionally to contraction of renal blood vessels in both mice and humans. Furthermore, preglomerular vascular SMCs and aortic SMCs coexpress L-, P-, and Q-type calcium channels within the same cell. Calcium channel blockers...... are widely used as pharmacological treatments. However, calcium channel antagonists vary in their selectivity for the various calcium channel subtypes, and the functional contribution from P/Q-type channels as compared with L-type should be considered. Confirming the presence of P/Q-type voltage...

Anomalous passage of ultrarelativistic electrons in thick single crystals in axial channeling

Energy Technology Data Exchange (ETDEWEB)

Khokonov, M.K. (Moskovskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Yadernoj Fiziki); Telegin, V.I. (Gosudarstvennyj Komitet po Ispol' zovaniyu Atomnoj Ehnergii SSSR, Moscow. Inst. Atomnoj Ehnergii)

1983-07-01

The dynamics of ultrarelativistic axially channeled electrons in thick crystals is studied. It is revealed that a certain fraction of initial electrons have anomalously large dechanneling depths. It is shown also that the dechanneling depth in heavy and light crystals are comparable. In some cases, the number of channeled electrons can strongly increase at the expense of quasi-channeled electrons. The problem of quasi-channeling is also considered.

Cell swelling activates K⁺ and Cl^- channels as well as nonselective, stretch-activated cation channels in ehrlich ascites tumor cells

DEFF Research Database (Denmark)

Christensen, Ove; Hoffmann, Else Kay

1992-01-01

Cell-attached patch-clamp recordings from Ehrlich ascites tumor cells reveal nonselective cation channels which are activated by mechanical deformation of the membrane. These channels are seen when suction is applied to the patch pipette or after osmotic cell swelling. The channel activation does...... system. In isolated insideout patches a Ca2+-dependent, inwardly rectifying K+ channel is demonstrated. The single-channel conductance recorded with symmetrical 150 mm K+ solutions is for inward current estimated at 40 pS and for outward current at 15 pS. Activation of the K+ channel takes place after...... by membrane stretch (suction). The time-averaged number of open K+ channels during regulatory volume decrease (RVD) can be estimated at 40 per cell. The number of open K+ channels following addition of Ca2+ plus ionophore A23187 was estimated at 250 per cell. Concurrent activation in cell-attached patches...

Fluid escape structures in the Graham Bank region (Sicily Channel, Central Mediterranean) revealing volcanic and neotectonic activity.

Science.gov (United States)

Spatola, Daniele; Pennino, Valentina; Basilone, Luca; Interbartolo, Francesco; Micallef, Aaron; Sulli, Attilio; Basilone, Walter

2016-04-01

morphometric analysis of these volcanoes has been conducted: they are up to about 115-160 m high and 500-1500 m wide. Most of them show very strongly inclined flanks with 30° of average slope. The SCV2 and SCV3 form the Graham Bank, 3.5X2.8 km wide, elongated in the NW-SE direction. At the top of SCV2 focused seepage plumes were observed in the entire water column, through the CHIRP data, where we calculated that they release, a volume of about 10950 m3 and 43960 m3of gases, respectively. In this work, we present the first results of a data collection that have got as main result the identification and mapping of the fluid escape structures revealing the relationship between the active tectonic with migration of fluids, to be used to assess the Submarine Geo-Hazard in the Sicily Channel. We identified two fluid escape fields whose genesis and evolution appear linked to the neotectonic and volcanic activities respectively, that represent the main controlling factors for the migration of fluid; considering the good correlation between pockmarks and the main identified fault systems. In conclusion, our results suggest that the degassing of fluids in this region is rooted at depth, and is mainly aligned with the NW-SE dip/strike slip fault systems, repeatedly reactivated, and linked to the volcanic activity.

Selective carbon dioxide sorption by a new breathing three-dimensional Zn-MOF with Lewis basic nitrogen-rich channels.

Science.gov (United States)

Kim, Hyun-Chul; Huh, Seong; Lee, Do Nam; Kim, Youngmee

2018-04-03

Lewis basic heteroatoms orderly located inside the well-defined channels of metal-organic frameworks (MOFs) are potentially ideal active sites for selective gas sorption and catalysis. To develop functional MOFs with Lewis basic sites inside channels, a new C2h-symmetric dicarboxylate-based bridging ligand, 3,3'-(pyrazine-2,5-diyl)dibenzoic acid (3,3'-PDBA), was prepared by a Suzuki coupling reaction. Subsequently, two new Zn-MOFs containing the C2h-symmetric 3,3'-PDBA bridging ligand and two different bis(pyridyl)-based pillars, 1,2-bis(4-pyridyl)ethane (bpa) or 1,2-bis(4-pyridyl)ethylene (bpe), were prepared through a thermal reaction in N,N-dimethylformamide (DMF). The resulting two Zn-MOFs of the general formula of three-dimensional (3D) [Zn2(μ4-3,3'-PDBA)2(μ2-bpa)]3·(DMF)5(H2O)13 (1) or 3D-like 2D [Zn2(μ4-3,3'-PDBA)2(μ2-bpe)]·(H2O) (2) displayed primitive cubic pcu net and 2D sql net, respectively. Both Zn-MOFs 1 and 2 contain uncoordinated Lewis basic pyrazinyl nitrogen atoms in the frameworks. The solvent-free 1 with flexible bpa linkers only showed a potential porosity of 15.9% by PLATON analysis. Zn-MOF 1 with openly accessible Lewis basic sites exhibited selective sorption of CO2 over N2, H2, and CH4 at low temperature. The adsorption and desorption isotherms for CO2 sorption at 196 K showed phenomenal hysteretic behaviour indicative of a breathing process through an adsorbate-discriminatory gate-opening process toward CO2 at a low gas pressure.

Unsupervised Idealization of Ion Channel Recordings by Minimum Description Length

DEFF Research Database (Denmark)

Gnanasambandam, Radhakrishnan; Nielsen, Morten S; Nicolai, Christopher

2017-01-01

and characterize an idealization algorithm based on Rissanen's Minimum Description Length (MDL) Principle. This method uses minimal assumptions and idealizes ion channel recordings without requiring a detailed user input or a priori assumptions about channel conductance and kinetics. Furthermore, we demonstrate...... that correlation analysis of conductance steps can resolve properties of single ion channels in recordings contaminated by signals from multiple channels. We first validated our methods on simulated data defined with a range of different signal-to-noise levels, and then showed that our algorithm can recover...... channel currents and their substates from recordings with multiple channels, even under conditions of high noise. We then tested the MDL algorithm on real experimental data from human PIEZO1 channels and found that our method revealed the presence of substates with alternate conductances....

Capacity bounds for kth best path selection over generalized fading channels

KAUST Repository

Hanif, Muhammad Fainan; Yang, Hongchuan; Alouini, Mohamed-Slim

2014-01-01

Exact ergodic capacity calculation for fading wireless channels typically involves time-consuming numerical evaluation of infinite integrals. In this paper, lower and upper bounds on ergodic capacity for kth best path are presented. These bounds

Plant ion channels: gene families, physiology, and functional genomics analyses.

Science.gov (United States)

Ward, John M; Mäser, Pascal; Schroeder, Julian I

2009-01-01

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

Bifurcation Mode of Relativistic and Charge-Displacement Self-Channeling

International Nuclear Information System (INIS)

BORISOV, A.B.; CAMERON, STEWART M.; LUK, TING S.; NELSON, THOMAS R.; VAN TASSLE, A.J.; SANTORO, J.; SCHROEDER, W.A.; DAI, Y.; LONGWORTH, J.W.; BOYER, K.; RHODES, C.K.

2000-01-01

Stable self-channeling of ultra-powerful (P 0 - 1 TW -1 PW) laser pulses in dense plasmas is a key process for many applications requiring the controlled compression of power at high levels. Theoretical computations predict that the transition zone between the stable and highly unstable regimes of relativistic/charge-displacement self-channeling is well characterized by a form of weakly unstable behavior that involves bifurcation of the propagating energy into two powerful channels. Recent observations of channel instability with femtosecond 248 nm pulses reveal a mode of bifurcation that corresponds well to these theoretical predictions. It is further experimentally shown that the use of a suitable longitudinal gradient in the plasma density can eliminate this unstable behavior and restore the efficient formation of stable channels

Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei.

Directory of Open Access Journals (Sweden)

Melisa Gualdron-López

Full Text Available BACKGROUND: Glycosomes are a specialized form of peroxisomes (microbodies present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear. METHODS/PRINCIPAL FINDINGS: We hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T. brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70-80 pA, 20-25 pA, and 8-11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte. All channels were in fully open state in a range of voltages ±150 mV and showed no sub-conductance transitions. The channel with current amplitude 20-25 pA is anion-selective (P(K+/P(Cl-∼0.31, while the other two types of channels are slightly selective for cations (P(K+/P(Cl- ratios ∼1.15 and ∼1.27 for the high- and low-conductance channels, respectively. The anion-selective channel showed an intrinsic current rectification that may suggest a functional asymmetry of the channel's pore. CONCLUSIONS/SIGNIFICANCE: These results indicate that the membrane of glycosomes

K+ Block Is the Mechanism of Functional Asymmetry in Bacterial Na(v Channels.

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Van Ngo

2016-01-01

Full Text Available 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 in bacterial Na(v 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 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 Na(v 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

Performance analysis of OFDM modulation on indoor broadband PLC channels

Science.gov (United States)

Antonio Cortés, José; Díez, Luis; Cañete, Francisco Javier; Sánchez-Martínez, Juan José; Entrambasaguas, José Tomás

2011-12-01

Indoor broadband power-line communications is a suitable technology for home networking applications. In this context, orthogonal frequency-division multiplexing (OFDM) is the most widespread modulation technique. It has recently been adopted by the ITU-T Recommendation G.9960 and is also used by most of the commercial systems, whose number of carriers has gone from about 100 to a few thousands in less than a decade. However, indoor power-line channels are frequency-selective and exhibit periodic time variations. Hence, increasing the number of carriers does not always improves the performance, since it reduces the distortion because of the frequency selectivity, but increases the one caused by the channel time variation. In addition, the long impulse response of power-line channels obliges to use an insufficient cyclic prefix. Increasing its value reduces the distortion, but also the symbol rate. Therefore, there are optimum values for both modulation parameters. This article evaluates the performance of an OFDM system as a function of the number of carriers and the cyclic prefix length, determining their most appropriate values for the indoor power-line scenario. This task must be accomplished by means of time-consuming simulations employing a linear time-varying filtering, since no consensus on a tractable statistical channel model has been reached yet. However, this study presents a simpler procedure in which the distortion because of the frequency selectivity is computed using a time-invariant channel response, and an analytical expression is derived for the one caused by the channel time variation.

Low-Complexity Bayesian Estimation of Cluster-Sparse Channels

KAUST Repository

Ballal, Tarig

2015-09-18

This paper addresses the problem of channel impulse response estimation for cluster-sparse channels under the Bayesian estimation framework. We develop a novel low-complexity minimum mean squared error (MMSE) estimator by exploiting the sparsity of the received signal profile and the structure of the measurement matrix. It is shown that due to the banded Toeplitz/circulant structure of the measurement matrix, a channel impulse response, such as underwater acoustic channel impulse responses, can be partitioned into a number of orthogonal or approximately orthogonal clusters. The orthogonal clusters, the sparsity of the channel impulse response and the structure of the measurement matrix, all combined, result in a computationally superior realization of the MMSE channel estimator. The MMSE estimator calculations boil down to simpler in-cluster calculations that can be reused in different clusters. The reduction in computational complexity allows for a more accurate implementation of the MMSE estimator. The proposed approach is tested using synthetic Gaussian channels, as well as simulated underwater acoustic channels. Symbol-error-rate performance and computation time confirm the superiority of the proposed method compared to selected benchmark methods in systems with preamble-based training signals transmitted over clustersparse channels.

Low-Complexity Bayesian Estimation of Cluster-Sparse Channels

KAUST Repository

Ballal, Tarig; Al-Naffouri, Tareq Y.; Ahmed, Syed

2015-01-01

This paper addresses the problem of channel impulse response estimation for cluster-sparse channels under the Bayesian estimation framework. We develop a novel low-complexity minimum mean squared error (MMSE) estimator by exploiting the sparsity of the received signal profile and the structure of the measurement matrix. It is shown that due to the banded Toeplitz/circulant structure of the measurement matrix, a channel impulse response, such as underwater acoustic channel impulse responses, can be partitioned into a number of orthogonal or approximately orthogonal clusters. The orthogonal clusters, the sparsity of the channel impulse response and the structure of the measurement matrix, all combined, result in a computationally superior realization of the MMSE channel estimator. The MMSE estimator calculations boil down to simpler in-cluster calculations that can be reused in different clusters. The reduction in computational complexity allows for a more accurate implementation of the MMSE estimator. The proposed approach is tested using synthetic Gaussian channels, as well as simulated underwater acoustic channels. Symbol-error-rate performance and computation time confirm the superiority of the proposed method compared to selected benchmark methods in systems with preamble-based training signals transmitted over clustersparse channels.

Drugability of extracellular targets: discovery of small molecule drugs targeting allosteric, functional, and subunit-selective sites on GPCRs and ion channels.

Science.gov (United States)

Grigoriadis, Dimitri E; Hoare, Samuel R J; Lechner, Sandra M; Slee, Deborah H; Williams, John A

2009-01-01

Beginning with the discovery of the structure of deoxyribose nucleic acid in 1953, by James Watson and Francis Crick, the sequencing of the entire human genome some 50 years later, has begun to quantify the classes and types of proteins that may have relevance to human disease with the promise of rapidly identifying compounds that can modulate these proteins so as to have a beneficial and therapeutic outcome. This so called 'drugable space' involves a variety of membrane-bound proteins including the superfamily of G-protein-coupled receptors (GPCRs), ion channels, and transporters among others. The recent number of novel therapeutics targeting membrane-bound extracellular proteins that have reached the market in the past 20 years however pales in magnitude when compared, during the same timeframe, to the advancements made in the technologies available to aid in the discovery of these novel therapeutics. This review will consider select examples of extracellular drugable targets and focus on the GPCRs and ion channels highlighting the corticotropin releasing factor (CRF) type 1 and gamma-aminobutyric acid receptors, and the Ca(V)2.2 voltage-gated ion channel. These examples will elaborate current technological advancements in drug discovery and provide a prospective framework for future drug development.

Regional Relations in Bankfull Channel Characteristics determined from flow measurements at selected stream-gaging stations in West Virginia, 1911-2002

Science.gov (United States)

Messinger, Terence; Wiley, Jeffrey B.

2004-01-01

Three bankfull channel characteristics?cross-sectional area, width, and depth?were significantly correlated with drainage area in regression equations developed for two regions in West Virginia. Channel characteristics were determined from analysis of flow measurements made at 74 U.S. Geological Survey stream-gaging stations at flows between 0.5 and 5.0 times bankfull flow between 1911 and 2002. Graphical and regression analysis were used to delineate an 'Eastern Region' and a 'Western Region,' which were separated by the boundary between the Appalachian Plateaus and Valley and Ridge Physiographic Provinces. Streams that drained parts of both provinces had channel characteristics typical of the Eastern Region, and were grouped with it. Standard error for the six regression equations, three for each region, ranged between 8.7 and 16 percent. Cross-sectional area and depth were greater relative to drainage area for the Western Region than they were for the Eastern Region. Regression equations were defined for streams draining between 46.5 and 1,619 square miles for the Eastern Region, and between 2.78 and 1,354 square miles for the Western Region. Stream-gaging stations with two or more cross sections where flow had been measured at flows between 0.5 and 5.0 times the 1.5-year flow showed poor replication of channel characteristics compared to the 95-percent confidence intervals of the regression, suggesting that within-reach variability for the stream-gaging stations may be substantial. A disproportionate number of the selected stream-gaging stations were on large (drainage area greater than 100 square miles) streams in the central highlands of West Virginia, and only one stream-gaging station that met data-quality criteria was available to represent the region within about 50 miles of the Ohio River north of Parkersburg, West Virginia. Many of the cross sections were at bridges, which can change channel shape. Although the data discussed in this report may not be

Green Lightning Channels From the Chaiten Volcano in Chile Photographed By Carlos Gutierrez May 2-3, 2008

Science.gov (United States)

Few, A. A.

2013-12-01

The two photographs containing the green lightning channels appeared on the Boston.com web site (The Big Picture, June 4, 2008). These web photographs were of limited resolution (176 Kb) making the interpretation of the green channels difficult. The agent for Gutierrez, Landov LLC, made available the two photographs as high resolution digital photographs (1.4 Mb and 1.5 Mb) that appear on the poster. Upon close examination of the green channels it is possible to exclude negative discharges or their remnants as being the source of the green channels; negative discharges require white-hot ionization processes at the leading tip of the channel. There are several examples of the white negative channels on the photographs. The green channels might be positive streamers. In thunderstorms positive streamers propagate within the negative charged region of the cloud collecting electrons, which are supplied to the connected negative discharge channel, hence they are not observed in thunderstorms. They can be detected and mapped inside the thunderstorm from observations of their electromagnetic radiations. Positive streamers are cooler than negative discharges because electrons are convergent on the leading tip of the positive streamer maintaining its conductivity. For the negative leading tips the electrons are divergent and new electrons must be generated by hot ionization processes. A close examination reveals that the green channels track the edge of the ash cloud, which if a positive streamer would indicate a negative surface charge on the cloud. Most likely the green color results from excited oxygen atoms returning to the ground state and emitting a green photon. This is the process that produces the green aurora, and if this produces green lightning, it places several constraints on the conditions of the channel. The two photographs below are selected clips from the much larger photographs; these show the green lightning channels.

ReliefF-Based EEG Sensor Selection Methods for Emotion Recognition.

Science.gov (United States)

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

The functions of store-operated calcium channels.

Science.gov (United States)

Putney, James W; Steinckwich-Besançon, Natacha; Numaga-Tomita, Takuro; Davis, Felicity M; Desai, Pooja N; D'Agostin, Diane M; Wu, Shilan; Bird, Gary S

2017-06-01

Store-operated calcium channels provide calcium signals to the cytoplasm of a wide variety of cell types. The basic components of this signaling mechanism include a mechanism for discharging Ca 2+ stores (commonly but not exclusively phospholipase C and inositol 1,4,5-trisphosphate), a sensor in the endoplasmic reticulum that also serves as an activator of the plasma membrane channel (STIM1 and STIM2), and the store-operated channel (Orai1, 2 or 3). The advent of mice genetically altered to reduce store-operated calcium entry globally or in specific cell types has provided important tools to understand the functions of these widely encountered channels in specific and clinically important physiological systems. This review briefly discusses the history and cellular properties of store-operated calcium channels, and summarizes selected studies of their physiological functions in specific physiological or pathological contexts. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Published by Elsevier B.V.

Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing.

Science.gov (United States)

Numata, Tomohiro; Tsumoto, Kunichika; Yamada, Kazunori; Kurokawa, Tatsuki; Hirose, Shinichi; Nomura, Hideki; Kawano, Mitsuhiro; Kurachi, Yoshihisa; Inoue, Ryuji; Mori, Yasuo

2017-08-29

Numerical model-based simulations provide important insights into ion channel gating when experimental limitations exist. Here, a novel strategy combining numerical simulations with patch clamp experiments was used to investigate the net positive charges in the putative transmembrane segment 4 (S4) of the atypical, positively-shifted voltage-dependence of polycystic kidney disease 2-like 1 (PKD2L1) channel. Charge-neutralising mutations (K452Q, K455Q and K461Q) in S4 reduced gating charges, positively shifted the Boltzmann-type activation curve [i.e., open probability (P open )-V curve] and altered the time-courses of activation/deactivation of PKD2L1, indicating that this region constitutes part of a voltage sensor. Numerical reconstruction of wild-type (WT) and mutant PKD2L1-mediated currents necessitated, besides their voltage-dependent gating parameters, a scaling factor that describes the voltage-dependence of maximal conductance, G max . Subsequent single-channel conductance (γ) measurements revealed that voltage-dependence of G max in WT can be explained by the inward-rectifying property of γ, which is greatly changed in PKD2L1 mutants. Homology modelling based on PKD2 and Na V Ab structures suggest that such voltage dependence of P open and γ in PKD2L1 could both reflect the charged state of the S4 domain. The present conjunctive experimental and theoretical approaches provide a framework to explore the undetermined mechanism(s) regulating TRP channels that possess non-classical voltage-dependent properties.

From in silico to in vitro: a trip to reveal flavonoid binding on the Rattus norvegicus Kir6.1 ATP-sensitive inward rectifier potassium channel.

Science.gov (United States)

Trezza, Alfonso; Cicaloni, Vittoria; Porciatti, Piera; Langella, Andrea; Fusi, Fabio; Saponara, Simona; Spiga, Ottavia

2018-01-01

ATP-sensitive inward rectifier potassium channels (Kir), are a potassium channel family involved in many physiological processes. K ATP dysfunctions are observed in several diseases such as hypoglycaemia, hyperinsulinemia, Prinzmetal angina-like symptoms, cardiovascular diseases. A broader view of the K ATP mechanism is needed in order to operate on their regulation, and in this work we clarify the structure of the Rattus norvegicus ATP-sensitive inward rectifier potassium channel 8 (Kir6.1), which has been obtained through a homology modelling procedure. Due to the medical use of flavonoids, a considerable increase in studies on their influence on human health has recently been observed, therefore our aim is to study, through computational methods, the three-dimensional (3D) conformation together with mechanism of action of Kir6.1 with three flavonoids. Computational analysis by performing molecular dynamics (MD) and docking simulation on rat 3D modelled structure have been completed, in its closed and open conformation state and in complex with Quercetin, 5-Hydroxyflavone and Rutin flavonoids. Our study showed that only Quercetin and 5-Hydroxyflavone were responsible for a significant down-regulation of the Kir6.1 activity, stabilising it in a closed conformation. This hypothesis was supported by in vitro experiments demonstrating that Quercetin and 5-Hydroxyflavone were capable to inhibit K ATP currents of rat tail main artery myocytes recorded by the patch-clamp technique. Combined methodological approaches, such as molecular modelling, docking and MD simulations of Kir6.1 channel, used to elucidate flavonoids intrinsic mechanism of action, are introduced, revealing a new potential druggable protein site.

Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.

Science.gov (United States)

Wu, Wei; Sanguinetti, Michael C

2016-06-01

Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

Voltage-Gated Sodium Channels: Evolutionary History and Distinctive Sequence Features.

Science.gov (United States)

Kasimova, M A; Granata, D; Carnevale, V

2016-01-01

Voltage-gated sodium channels (Nav) are responsible for the rising phase of the action potential. Their role in electrical signal transmission is so relevant that their emergence is believed to be one of the crucial factors enabling development of nervous system. The presence of voltage-gated sodium-selective channels in bacteria (BacNav) has raised questions concerning the evolutionary history of the ones in animals. Here we review some of the milestones in the field of Nav phylogenetic analysis and discuss some of the most important sequence features that distinguish these channels from voltage-gated potassium channels and transient receptor potential channels. Copyright © 2016 Elsevier Inc. All rights reserved.

Regret of Multi-Channel Bandit Game in Cognitive Radio Networks

Directory of Open Access Journals (Sweden)

Ma Jun

2016-01-01

Full Text Available The problem of how to evaluate the rate of convergence to Nash equilibrium solutions in the process of channel selection under incomplete information is studied. In this paper, the definition of regret is used to reflect the convergence rates of online algorithms. The process of selecting an idle channel for each secondary user is modeled as a multi-channel bandit game. The definition of the maximal averaged regret is given. Two existing online learning algorithms are used to obtain the Nash equilibrium for each SU. The maximal averaged regrets are used to evaluate the performances of online algorithms. When there is a pure strategy Nash equilibrium in the multi-channel bandit game, the maximal averaged regrets are finite. A cooperation mechanism is also needed in the process of calculating the maximal averaged regrets. Simulation results show the maximal averaged regrets are finite and the online algorithm with greater convergence rate has less maximal averaged regrets.

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

Directory of Open Access Journals (Sweden)

Zeineb Es-Salah-Lamoureux

2010-05-01

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

Distributary channel meandering and bifurcation patterns on the Amazon deep-sea fan as revealed by long-range side-scan sonar (GLORIA)

Science.gov (United States)

Damuth, John E.; Kolla, Venkatarathnam; Flood, Roger D.; Kowsmann, Renato O.; Monteiro, Marcelo C.; Gorini, Marcus A.; Palma, Jorge J. C.; Belderson, Robert H.

1983-02-01

We mapped the distributary channel system of the Amazon deep-sea fan using the GLORIA long-range side-scan sonar. Individual channels were continuously traced for distances of up to 150 km. Channel bifurcation, although observed in only a few places, results in many cases from breaching of channel levees on the outsides of meander loops. Whether both channels remain active after branching or the original channel is abandoned by avulsion generally cannot be determined. The most striking channel characteristic is high sinuosity that results in extensive, intricate, often recurving meanders. Cutoffs and abandoned meander loops (oxbows) are observed in a few places. These meandering channels are comparable in size and appearance to those of mature fluvial systems on land, such as on the lower Mississippi River. The formation, maintenance, and modification of such extensive, well-developed meander systems would seem to require large volumes of continuous turbidity flow through the channels for relatively long time periods. This may challenge the traditional concept that channel formation and modification are accomplished by intermittent or sporadic turbidity-current events. *Present address: Superior Oil Company, 12401 Westheimer, Houston, Texas 77077

ASIC3 channels in multimodal sensory perception.

Science.gov (United States)

Li, Wei-Guang; Xu, Tian-Le

2011-01-19

Acid-sensing ion channels (ASICs), which are members of the sodium-selective cation channels belonging to the epithelial sodium channel/degenerin (ENaC/DEG) family, act as membrane-bound receptors for extracellular protons as well as nonproton ligands. At least five ASIC subunits have been identified in mammalian neurons, which form both homotrimeric and heterotrimeric channels. The highly proton sensitive ASIC3 channels are predominantly distributed in peripheral sensory neurons, correlating with their roles in multimodal sensory perception, including nociception, mechanosensation, and chemosensation. Different from other ASIC subunit composing ion channels, ASIC3 channels can mediate a sustained window current in response to mild extracellular acidosis (pH 7.3-6.7), which often occurs accompanied by many sensory stimuli. Furthermore, recent evidence indicates that the sustained component of ASIC3 currents can be enhanced by nonproton ligands including the endogenous metabolite agmatine. In this review, we first summarize the growing body of evidence for the involvement of ASIC3 channels in multimodal sensory perception and then discuss the potential mechanisms underlying ASIC3 activation and mediation of sensory perception, with a special emphasis on its role in nociception. We conclude that ASIC3 activation and modulation by diverse sensory stimuli represent a new avenue for understanding the role of ASIC3 channels in sensory perception. Furthermore, the emerging implications of ASIC3 channels in multiple sensory dysfunctions including nociception allow the development of new pharmacotherapy.

Sandhill crane roost selection, human disturbance, and forage resources

Science.gov (United States)

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 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.

Sandhill crane roost selection, human disturbance, and forage resources

Science.gov (United States)

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

Ion channel regulation by phosphoinositides analyzed with VSPs – PI(4,5P2 affinity, phosphoinositide selectivity, and PI(4,5P2 pool accessibility

Directory of Open Access Journals (Sweden)

Alexandra eRjasanow

2015-06-01

Full Text Available The activity of many proteins depends on the phosphoinositide (PI content of the membrane. E.g., dynamic changes of the concentration of PI(4,5P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids.Voltage-sensitive phosphatases (VSPs turn over PI(4,5P2 to PI(4P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5P2. Because cellular PI(4,5P2 is resynthesized rapidly, steady state PI(4,5P2 changes with the degree of VSP activation and thus depends on membrane potential.Here we show that titration of endogenous PI(4,5P2 with Ci-VSP allows for the quantification of relative PI(4,5P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5P2 and PI(4P was insensitive to VSP.Surprisingly, despite comparable PI(4,5P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5P2 that differ in their accessibility to PLC and VSPs.

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

Science.gov (United States)

Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Quantum Channeling Effects for 1 MeV Positrons

International Nuclear Information System (INIS)

Haakenaasen, R.; Vestergaard Hau, L.; Golovchenko, J.A.; Palathingal, J.C.; Peng, J.P.; Asoka-Kumar, P.; Lynn, K.G.

1995-01-01

A high resolution angular study of positrons transmitted through a thin single crystal of Si clearly reveals a detailed fine structure due to strong quantum channeling effects. The beam transmitted in the forward direction displays many features associated with dynamical diffraction effects and long coherence lengths. Calculations are presented showing that in flight annihilation of channeled positrons can serve as a solid state probe of electron and spin densities in thin crystals

GWA Mapping of Anthocyanin Accumulation Reveals Balancing Selection of MYB90 in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Johanna A Bac-Molenaar

Full Text Available Induction of anthocyanin accumulation by osmotic stress was assessed in 360 accessions of Arabidopsis thaliana. A wide range of natural variation, with phenotypes ranging from green to completely red/purple rosettes, was observed. A genome wide association (GWA mapping approach revealed that sequence diversity in a small 15 kb region on chromosome 1 explained 40% of the variation observed. Sequence and expression analyses of alleles of the candidate gene MYB90 identified a causal polymorphism at amino acid (AA position 210 of this transcription factor of the anthocyanin biosynthesis pathway. This amino acid discriminates the two most frequent alleles of MYB90. Both alleles are present in a substantial part of the population, suggesting balancing selection between these two alleles. Analysis of the geographical origin of the studied accessions suggests that the macro climate is not the driving force behind positive or negative selection for anthocyanin accumulation. An important role for local climatic conditions is, therefore, suggested. This study emphasizes that GWA mapping is a powerful approach to identify alleles that are under balancing selection pressure in nature.