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Sample records for channel selectivity revealed

  1. BLIND CHANNEL ESTIMATION IN DELAY DIVERSITY FOR FREQUENCY SELECTIVE CHANNELS

    Institute of Scientific and Technical Information of China (English)

    Zhao Zheng; Jia Ying; Yin Qinye

    2003-01-01

    Delay diversity is an effective transmit diversity technique to combat adverse ef-fects of fading. Thus far, previous work in delay diversity assumed that perfect estimates ofcurrent channel fading conditions are available at the receiver and training symbols are requiredto estimate the channel from the transmitter to the receiver. However, increasing the number ofthe antennas increases the required training interval and reduces the available time within whichdata may be transmitted. Learning the channel coefficients becomes increasingly difficult for thefrequency selective channels. In this paper, with the subspace method and the delay character ofdelay diversity, a channel estimation method is proposed, which does not use training symbols. Itaddresses the transmit diversity for a frequency selective channel from a single carrier perspectivein the form of a simple equivalent fiat fading model. Monte Carlo simulations give the perfor-mance of channel estimation and the performance comparison of our channel-estimation-baseddetector with decision feedback equalization, which uses the perfect channel information.

  2. Channel selection for automatic seizure detection

    DEFF Research Database (Denmark)

    Duun-Henriksen, Jonas; Kjaer, Troels Wesenberg; Madsen, Rasmus Elsborg

    2012-01-01

    of an automatic channel selection method. The characteristics of the seizures are extracted by the use of a wavelet analysis and classified by a support vector machine. The best channel selection method is based upon maximum variance during the seizure. Results: Using only three channels, a seizure detection...

  3. Ion selectivity strategies of sodium channel selectivity filters.

    Science.gov (United States)

    Dudev, Todor; Lim, Carmay

    2014-12-16

    CONSPECTUS: Sodium ion channels selectively transport Na(+) cations across the cell membrane. These integral parts of the cell machinery are implicated in regulating the cardiac, skeletal and smooth muscle contraction, nerve impulses, salt and water homeostasis, as well as pain and taste perception. Their malfunction often results in various channelopathies of the heart, brain, skeletal muscles, and lung; thus, sodium channels are key drug targets for various disorders including cardiac arrhythmias, heart attack, stroke, migraine, epilepsy, pain, cancer, and autoimmune disorders. The ability of sodium channels to discriminate the native Na(+) among other competing ions in the surrounding fluids is crucial for proper cellular functions. The selectivity filter (SF), the narrowest part of the channel's open pore, lined with amino acid residues that specifically interact with the permeating ion, plays a major role in determining Na(+) selectivity. Different sodium channels have different SFs, which vary in the symmetry, number, charge, arrangement, and chemical type of the metal-ligating groups and pore size: epithelial/degenerin/acid-sensing ion channels have generally trimeric SFs lined with three conserved neutral serines and/or backbone carbonyls; eukaryotic sodium channels have EKEE, EEKE, DKEA, and DEKA SFs with an invariant positively charged lysine from the second or third domain; and bacterial voltage-gated sodium (Nav) channels exhibit symmetrical EEEE SFs, reminiscent of eukaryotic voltage-gated calcium channels. How do these different sodium channel SFs achieve high selectivity for Na(+) over its key rivals, K(+) and Ca(2+)? What factors govern the metal competition in these SFs and which of these factors are exploited to achieve Na(+) selectivity in the different sodium channel SFs? The free energies for replacing K(+) or Ca(2+) bound inside different model SFs with Na(+), evaluated by a combination of density functional theory and continuum dielectric

  4. Vector Broadcast Channels: Optimal Threshold Selection Problem

    CERN Document Server

    Samarasinghe, Tharaka; Evans, Jamie

    2011-01-01

    Threshold feedback policies are well known and provably rate-wise optimal selective feedback techniques for communication systems requiring partial channel state information (CSI). However, optimal selection of thresholds at mobile users to maximize information theoretic data rates subject to feedback constraints is an open problem. In this paper, we focus on the optimal threshold selection problem, and provide a solution for this problem for finite feedback systems. Rather surprisingly, we show that using the same threshold values at all mobile users is not always a rate-wise optimal feedback strategy, even for a system with identical users experiencing statistically the same channel conditions. By utilizing the theory of majorization, we identify an underlying Schur-concave structure in the rate function and obtain sufficient conditions for a homogenous threshold feedback policy to be optimal. Our results hold for most fading channel models, and we illustrate an application of our results to familiar Raylei...

  5. The Diversity Potential of Relay Selection with Practical Channel Estimation

    CERN Document Server

    Michalopoulos, Diomidis S; Schober, Robert; Karagiannidis, George K

    2011-01-01

    We investigate the diversity order of decode-and-forward relay selection in Nakagami-m fading, in cases where practical channel estimation techniques are applied. In this respect, we introduce a unified model for the imperfect channel estimates, where the effects of noise, time-varying channels, and feedback delays are jointly considered. Based on this model, the correlation between the actual and the estimated channel values, \\rho, is expressed as a function of the signal-to-noise ratio (SNR), yielding closed-form expressions for the overall outage probability as a function of \\rho. The resulting diversity order and power gain reveal a high dependence of the performance of relay selection on the high SNR behavior of \\rho, thus shedding light onto the effect of channel estimation on the overall performance. It is shown that when the channel estimates are not frequently updated in applications involving time-varying channels, or when the amount of power allocated for channel estimation is not sufficiently high...

  6. Selection of effective EEG channels in brain computer interfaces based on inconsistencies of classifiers.

    Science.gov (United States)

    Yang, Huijuan; Guan, Cuntai; Ang, Kai Keng; Phua, Kok Soon; Wang, Chuanchu

    2014-01-01

    This paper proposed a novel method to select the effective Electroencephalography (EEG) channels for the motor imagery tasks based on the inconsistencies from multiple classifiers. The inconsistency criterion for channel selection was designed based on the fluctuation of the classification accuracies among different classifiers when the noisy channels were included. These noisy channels were then identified and removed till a required number of channels was selected or a predefined classification accuracy with reference to baseline was obtained. Experiments conducted on a data set of 13 healthy subjects performing hand grasping and idle revealed that the EEG channels from the motor area were most frequently selected. Furthermore, the mean increases of 4.07%, 3.10% and 1.77% of the averaged accuracies in comparison with the four existing channel selection methods were achieved for the non-feedback, feedback and calibration sessions, respectively, by selecting as low as seven channels. These results further validated the effectiveness of our proposed method.

  7. Structural dynamics of potassium-channel gating revealed by single-molecule FRET.

    Science.gov (United States)

    Wang, Shizhen; Vafabakhsh, Reza; Borschel, William F; Ha, Taekjip; Nichols, Colin G

    2016-01-01

    Crystallography has provided invaluable insights regarding ion-channel selectivity and gating, but to advance understanding to a new level, dynamic views of channel structures within membranes are essential. We labeled tetrameric KirBac1.1 potassium channels with single donor and acceptor fluorophores at different sites and then examined structural dynamics within lipid membranes by single-molecule fluorescence resonance energy transfer (FRET). We found that the extracellular region is structurally rigid in both closed and open states, whereas the N-terminal slide helix undergoes marked conformational fluctuations. The cytoplasmic C-terminal domain fluctuates between two major structural states, both of which become less dynamic and move away from the pore axis and away from the membrane in closed channels. Our results reveal mobile and rigid conformations of functionally relevant KirBac1.1 channel motifs, implying similar dynamics for similar motifs in eukaryotic Kir channels and in cation channels in general.

  8. Structural dynamics of potassium channel gating revealed by single molecule FRET

    Science.gov (United States)

    Borschel, William F.; Ha, Taekjip; Nichols, Colin G.

    2016-01-01

    Crystallography has provided invaluable insights to ion channel selectivity and gating, but to advance understanding to a new level, dynamic views of channel structures within membranes are essential. We labeled tetrameric KirBac1.1 potassium channels with single donor and acceptor fluorophores at different sites, and examined structural dynamics within lipid membranes by single molecule FRET. We found that the extracellular region is structurally rigid in both closed and open states, whereas the N-terminal slide helix undergoes marked conformational fluctuations. The cytoplasmic C-terminal domain fluctuates between two major structural states both of which become less dynamic and move away from the pore axis and away from the membrane in closed channels. Our results reveal mobile and rigid conformations of functionally relevant KirBac1.1 channel motifs, implying similar dynamics for similar motifs in eukaryotic Kir channels and for cation channels in general. PMID:26641713

  9. NALCN ion channels have alternative selectivity filters resembling calcium channels or sodium channels.

    Directory of Open Access Journals (Sweden)

    Adriano Senatore

    Full Text Available NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single gene compared to the calcium and sodium channels which diversified into twenty genes in humans. The single NALCN gene has alternatively-spliced exons at exons 15 or exon 31 that splices in novel selectivity filter residues that resemble calcium channels (EEEE or sodium channels (EKEE or EEKE. NALCN channels with alternative calcium, (EEEE and sodium, (EKEE or EEKE -selective pores are conserved in simple bilaterally symmetrical animals like flatworms to non-chordate deuterostomes. The single NALCN gene is limited as a sodium channel with a lysine (K-containing pore in vertebrates, but originally NALCN was a calcium-like channel, and evolved to operate as both a calcium channel and sodium channel for different roles in many invertebrates. Expression patterns of NALCN-EKEE in pond snail, Lymnaea stagnalis suggest roles for NALCN in secretion, with an abundant expression in brain, and an up-regulation in secretory organs of sexually-mature adults such as albumen gland and prostate. NALCN-EEEE is equally abundant as NALCN-EKEE in snails, but is greater expressed in heart and other muscle tissue, and 50% less expressed in the brain than NALCN-EKEE. Transfected snail NALCN-EEEE and NALCN-EKEE channel isoforms express in HEK-293T cells. We were not able to distinguish potential NALCN currents from background, non-selective leak conductances in HEK293T cells. Native leak currents without expressing NALCN genes in HEK-293T cells are NMDG(+ impermeant and blockable with 10 µM Gd(3+ ions and are indistinguishable from the hallmark currents ascribed to mammalian NALCN currents expressed in vitro by Lu et al. in Cell. 2007 Apr 20;129(2:371-83.

  10. The structure and regulation of magnesium selective ion channels.

    Science.gov (United States)

    Payandeh, Jian; Pfoh, Roland; Pai, Emil F

    2013-11-01

    The magnesium ion (Mg(2+)) is the most abundant divalent cation within cells. In man, Mg(2+)-deficiency is associated with diseases affecting the heart, muscle, bone, immune, and nervous systems. Despite its impact on human health, little is known about the molecular mechanisms that regulate magnesium transport and storage. Complete structural information on eukaryotic Mg(2+)-transport proteins is currently lacking due to associated technical challenges. The prokaryotic MgtE and CorA magnesium transport systems have recently succumbed to structure determination by X-ray crystallography, providing first views of these ubiquitous and essential Mg(2+)-channels. MgtE and CorA are unique among known membrane protein structures, each revealing a novel protein fold containing distinct arrangements of ten transmembrane-spanning α-helices. Structural and functional analyses have established that Mg(2+)-selectivity in MgtE and CorA occurs through distinct mechanisms. Conserved acidic side-chains appear to form the selectivity filter in MgtE, whereas conserved asparagines coordinate hydrated Mg(2+)-ions within the selectivity filter of CorA. Common structural themes have also emerged whereby MgtE and CorA sense and respond to physiologically relevant, intracellular Mg(2+)-levels through dedicated regulatory domains. Within these domains, multiple primary and secondary Mg(2+)-binding sites serve to staple these ion channels into their respective closed conformations, implying that Mg(2+)-transport is well guarded and very tightly regulated. The MgtE and CorA proteins represent valuable structural templates to better understand the related eukaryotic SLC41 and Mrs2-Alr1 magnesium channels. Herein, we review the structure, function and regulation of MgtE and CorA and consider these unique proteins within the expanding universe of ion channel and transporter structural biology.

  11. A review of channel selection algorithms for EEG signal processing

    Science.gov (United States)

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

    2015-12-01

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

  12. Tuning the ion selectivity of two-pore channels

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jiangtao; Zeng, Weizhong; Jiang, Youxing (UTSMC)

    2017-01-17

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

  13. Quantum Interference and Selectivity through Biological Ion Channels

    Science.gov (United States)

    Salari, Vahid; Naeij, Hamidreza; Shafiee, Afshin

    2017-01-01

    The mechanism of selectivity in ion channels is still an open question in biology for more than half a century. Here, we suggest that quantum interference can be a solution to explain the selectivity mechanism in ion channels since interference happens between similar ions through the same size of ion channels. In this paper, we simulate two neighboring ion channels on a cell membrane with the famous double-slit experiment in physics to investigate whether there is any possibility of matter-wave interference of ions via movement through ion channels. Our obtained decoherence timescales indicate that the quantum states of ions can only survive for short times, i.e. ≈100 picoseconds in each channel and ≈17–53 picoseconds outside the channels, giving the result that the quantum interference of ions seems unlikely due to environmental decoherence. However, we discuss our results and raise few points, which increase the possibility of interference. PMID:28134331

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

    KAUST Repository

    Sungjoon Park,

    2011-11-01

    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 for opportunistic relaying in the channel, and validate the results by comparing it with the exact outage probability. Also, we suggest a new relay selection algorithm that incorporates shadowing. We consider a protocol of broadcasting the channel gain of the previously selected relay. This saves resources in slow fading channel by reducing collisions in relay selection. We further investigate the optimal relay selection period to maximize the throughput while avoiding selection overhead. © 2011 IEEE.

  15. DISTRIBUTION CHANNELS SELECTION USING PCA-DEA APPROACH

    Directory of Open Access Journals (Sweden)

    Milan Andrejić

    2015-03-01

    Full Text Available Strategic decision making is very important in logistics. One of the most important strategic decisions in logistics is the selection of distribution channels. This paper proposes the efficiency of distribution channels as one of the main selection criteria. The efficiency of distribution channels simultaneously affects logistics costs and customer satisfaction. Based on the main characteristics of the distribution channels, such as delivery time, service level, volume of business, the level of errors and the different cost categories in this paper the PCA-DEA approach for measuring the efficiency and selection of certain types of distribution channels is proposed. Model is tested on the numerical example. Results show the great capability of the proposed model.

  16. 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.

  17. Anion conductance selectivity mechanism of the CFTR chloride channel.

    Science.gov (United States)

    Linsdell, Paul

    2016-04-01

    All ion channels are able to discriminate between substrate ions to some extent, a process that involves specific interactions between permeant anions and the so-called selectivity filter within the channel pore. In the cystic fibrosis transmembrane conductance regulator (CFTR) anion-selective channel, both anion relative permeability and anion relative conductance are dependent on anion free energy of hydration--anions that are relatively easily dehydrated tend to show both high permeability and low conductance. In the present work, patch clamp recording was used to investigate the relative conductance of different anions in CFTR, and the effect of mutations within the channel pore. In constitutively-active E1371Q-CFTR channels, the anion conductance sequence was Cl(-) > NO3(-) > Br(-) > formate > SCN(-) > I(-). A mutation that disrupts anion binding in the inner vestibule of the pore (K95Q) disrupted anion conductance selectivity, such that anions with different permeabilities showed almost indistinguishable conductances. Conversely, a mutation at the putative narrowest pore region that is known to disrupt anion permeability selectivity (F337A) had minimal effects on anion relative conductance. Ion competition experiments confirmed that relatively tight binding of permeant anions resulted in relatively low conductance. These results suggest that the relative affinity of ion binding in the inner vestibule of the pore controls the relative conductance of different permeant anions in CFTR, and that the pore has two physically distinct anion selectivity filters that act in series to control anion conductance selectivity and anion permeability selectivity respectively.

  18. A Framework for Selection of Intermediary in Marketing Channel

    Directory of Open Access Journals (Sweden)

    Hamid Reza Irani

    2011-10-01

    Full Text Available Purpose – This study seeks to examine how company can select the best intermediary for its Marketing channels with minimum of criteria and time. Design/methodology/approach – A theoretical framework is proposed based on the most
    importance tasks of intermediary and criteria for measuring them. There are four basic tasks and 30 criteria in three independent levels. Subsequently, an exploratory case study in Iranian Food industry is described that illustrates the value of the framework. Findings – It is possible, for example, to apply the theoretical framework to select the intermediary for any industry or any country. Research limitations/implications – The study has possible location- and industry-specific limitations.
    Originality/value – Moreover, the framework has proven to be useful in improving the selection of the intermediary in marketing channel. This is a notable and promising side-effect of the exploratory study, at least from a managerial point of view.
    Keywords: Marketing channel, Distribution channel, Channel design, Selection criteria, channel members, Intermediary selection

  19. Morphodynamics of submarine channel inception revealed by new experimental approach

    Science.gov (United States)

    de Leeuw, Jan; Eggenhuisen, Joris T.; Cartigny, Matthieu J. B.

    2016-03-01

    Submarine channels are ubiquitous on the seafloor and their inception and evolution is a result of dynamic interaction between turbidity currents and the evolving seafloor. However, the morphodynamic links between channel inception and flow dynamics have not yet been monitored in experiments and only in one instance on the modern seafloor. Previous experimental flows did not show channel inception, because flow conditions were not appropriately scaled to sustain suspended sediment transport. Here we introduce and apply new scaling constraints for similarity between natural and experimental turbidity currents. The scaled currents initiate a leveed channel from an initially featureless slope. Channelization commences with deposition of levees in some slope segments and erosion of a conduit in other segments. Channel relief and flow confinement increase progressively during subsequent flows. This morphodynamic evolution determines the architecture of submarine channel deposits in the stratigraphic record and efficiency of sediment bypass to the basin floor.

  20. Dynamic Channel Selection for Cognitive Femtocells

    DEFF Research Database (Denmark)

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

    2014-01-01

    , 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...... 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...... the traditional planning and optimization techniques. This leads to uncoordinated deployment by the end-user. Second, the high density of femtocells, including vertical reuse, leads to very different inter-cell interference patterns than the ones traditionally considered in cellular networks. And last...

  1. 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.

  2. Selective transmission and channel estimation in massive MIMO systems

    Institute of Scientific and Technical Information of China (English)

    杨睿哲

    2016-01-01

    Massive MIMO systems have got extraordinary spectral efficiency using a large number of base station antennas, but it is in the challenge of pilot contamination using the aligned pilots.To address this issue, a selective transmission is proposed using time-shifted pilots with cell grouping, where the strong interfering users in downlink transmission cells are temporally stopped during the pilots transmission in uplink cells.Based on the spatial characteristics of physical channel models, the strong interfering users are selected to minimize the inter-cell interference and the cell grouping is designed to have less temporally stopped users within a smaller area.Furthermore, a Kalman estima-tor is proposed to reduce the unexpected effect of residual interferences in channel estimation, which exploits both the spatial-time correlation of channels and the share of the interference information. The numerical results show that our scheme significantly improves the channel estimation accuracy and the data rates.

  3. Maximum-Likelihood Semiblind Equalization of Doubly Selective Channels Using the EM Algorithm

    Directory of Open Access Journals (Sweden)

    Gideon Kutz

    2010-01-01

    Full Text Available Maximum-likelihood semi-blind joint channel estimation and equalization for doubly selective channels and single-carrier systems is proposed. We model the doubly selective channel as an FIR filter where each filter tap is modeled as a linear combination of basis functions. This channel description is then integrated in an iterative scheme based on the expectation-maximization (EM principle that converges to the channel description vector estimation. We discuss the selection of the basis functions and compare various functions sets. To alleviate the problem of convergence to a local maximum, we propose an initialization scheme to the EM iterations based on a small number of pilot symbols. We further derive a pilot positioning scheme targeted to reduce the probability of convergence to a local maximum. Our pilot positioning analysis reveals that for high Doppler rates it is better to spread the pilots evenly throughout the data block (and not to group them even for frequency-selective channels. The resulting equalization algorithm is shown to be superior over previously proposed equalization schemes and to perform in many cases close to the maximum-likelihood equalizer with perfect channel knowledge. Our proposed method is also suitable for coded systems and as a building block for Turbo equalization algorithms.

  4. BK channels reveal novel phosphate sensitivity in SNr neurons.

    Directory of Open Access Journals (Sweden)

    Juan Juan Ji

    Full Text Available Whether large conductance Ca(2+-activated potassium (BK channels are present in the substantia nigra pars reticulata (SNr is a matter of debate. Using the patch-clamp technique, we examined the functional expression of BK channels in neurons of the SNr and showed that the channels were activated or inhibited by internal high-energy phosphates (IHEPs at positive and negative membrane potentials, respectively. SNr neurons showed membrane potential hyperpolarization under glucose-deprivation conditions which was attenuated by paxilline, a specific BK channel blocker. In addition, Fluo-3 fluorescence recording detected an increase in the level of internal free calcium ([Ca(2+](i during ischemic hyperpolarization. These results confirm that BK channels are present in SNr neurons and indicate that their unique IHEP sensitivity is requisite in neuronal ischemic responses. Bearing in mind that the K(ATP channel blocker tolbutamide also attenuated the hyperpolarization, we suggest that BK channels may play a protective role in the basal ganglia by modulating the excitability of SNr neurons along with K(ATP channels under ischemic stresses.

  5. Highly Selective Artificial K(+) Channels: An Example of Selectivity-Induced Transmembrane Potential.

    Science.gov (United States)

    Gilles, Arnaud; Barboiu, Mihail

    2016-01-13

    Natural KcsA K(+) channels conduct at high rates with an extraordinary selectivity for K(+) cations, excluding the Na(+) or other cations. Biomimetic artificial channels have been designed in order to mimick the ionic activity of KcSA channels, but simple artificial systems presenting high K(+)/Na(+) selectivity are rare. Here we report an artificial ion channel of H-bonded hexyl-benzoureido-15-crown-5-ether, where K(+) cations are highly preferred to Na(+) cations. The K(+)-channel conductance is interpreted as arising in the formation of oligomeric highly cooperative channels, resulting in the cation-induced membrane polarization and enhanced transport rates without or under pH-active gradient. These channels are selectively responsive to the presence of K(+) cations, even in the presence of a large excess of Na(+). From the conceptual point of view, these channels express a synergistic adaptive behavior: the addition of the K(+) cation drives the selection and the construction of constitutional polarized ion channels toward the selective conduction of the K(+) cation that promotes their generation in the first place.

  6. Statistical Theory of Selectivity and Conductivity in Biological Channels

    CERN Document Server

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

    2016-01-01

    We present an equilibrium statistical-mechanical theory of selectivity in biological ion channels. In doing so, we introduce a grand canonical ensemble for ions in a channel's selectivity filter coupled to internal and external bath solutions for a mixture of ions at arbitrary concentrations, we use linear response theory to find the current through the filter for small gradients of electrochemical potential, and we show that the conductivity of the filter is given by the generalized Einstein relation. We apply the theory to the permeation of ions through the potassium selectivity filter, and are thereby able to resolve the long-standing paradox of why the high selectivity of the filter brings no associated delay in permeation. We show that the Eisenman selectivity relation follows directly from the condition of diffusion-limited conductivity through the filter. We also discuss the effect of wall fluctuations on the filter conductivity.

  7. Adaptive codebook selection schemes for image classification in correlated channels

    Science.gov (United States)

    Hu, Chia Chang; Liu, Xiang Lian; Liu, Kuan-Fu

    2015-09-01

    The multiple-input multiple-output (MIMO) system with the use of transmit and receive antenna arrays achieves diversity and array gains via transmit beamforming. Due to the absence of full channel state information (CSI) at the transmitter, the transmit beamforming vector can be quantized at the receiver and sent back to the transmitter by a low-rate feedback channel, called limited feedback beamforming. One of the key roles of Vector Quantization (VQ) is how to generate a good codebook such that the distortion between the original image and the reconstructed image is the minimized. In this paper, a novel adaptive codebook selection scheme for image classification is proposed with taking both spatial and temporal correlation inherent in the channel into consideration. The new codebook selection algorithm is developed to select two codebooks from the discrete Fourier transform (DFT) codebook, the generalized Lloyd algorithm (GLA) codebook and the Grassmannian codebook to be combined and used as candidates of the original image and the reconstructed image for image transmission. The channel is estimated and divided into four regions based on the spatial and temporal correlation of the channel and an appropriate codebook is assigned to each region. The proposed method can efficiently reduce the required information of feedback under the spatially and temporally correlated channels, where each region is adaptively. Simulation results show that in the case of temporally and spatially correlated channels, the bit-error-rate (BER) performance can be improved substantially by the proposed algorithm compared to the one with only single codebook.

  8. 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.

  9. Distinct regions that control ion selectivity and calcium-dependent activation in the bestrophin ion channel.

    Science.gov (United States)

    Vaisey, George; Miller, Alexandria N; Long, Stephen B

    2016-11-22

    Cytoplasmic calcium (Ca(2+)) activates the bestrophin anion channel, allowing chloride ions to flow down their electrochemical gradient. Mutations in bestrophin 1 (BEST1) cause macular degenerative disorders. Previously, we determined an X-ray structure of chicken BEST1 that revealed the architecture of the channel. Here, we present electrophysiological studies of purified wild-type and mutant BEST1 channels and an X-ray structure of a Ca(2+)-independent mutant. From these experiments, we identify regions of BEST1 responsible for Ca(2+) activation and ion selectivity. A "Ca(2+) clasp" within the channel's intracellular region acts as a sensor of cytoplasmic Ca(2+). Alanine substitutions within a hydrophobic "neck" of the pore, which widen it, cause the channel to be constitutively active, irrespective of Ca(2+). We conclude that the primary function of the neck is as a "gate" that controls chloride permeation in a Ca(2+)-dependent manner. In contrast to what others have proposed, we find that the neck is not a major contributor to the channel's ion selectivity. We find that mutation of a cytosolic "aperture" of the pore does not perturb the Ca(2+) dependence of the channel or its preference for anions over cations, but its mutation dramatically alters relative permeabilities among anions. The data suggest that the aperture functions as a size-selective filter that permits the passage of small entities such as partially dehydrated chloride ions while excluding larger molecules such as amino acids. Thus, unlike ion channels that have a single "selectivity filter," in bestrophin, distinct regions of the pore govern anion-vs.-cation selectivity and the relative permeabilities among anions.

  10. A New Adaptive Channel Estimation for Frequency Selective Time Varying Fading OFDM Channels

    CERN Document Server

    Afifi, Wessam M

    2010-01-01

    In this paper a new algorithm for adaptive dynamic channel estimation for frequency selective time varying fading OFDM channels is proposed. The new algorithm adopts a new strategy that successfully increases OFDM symbol rate. Instead of using a fixed training pilot sequence, the proposed algorithm uses a logic controller to choose among several available training patterns. The controller choice is based on the cross-correlation between pilot symbols over two consecutive time instants (which is considered to be a suitable measure of channel stationarity) as well as the deviation from the desired BER. Simulation results of the system performance confirm the effectiveness of this new channel estimation technique over traditional non-adaptive estimation methods in increasing the data rate of OFDM symbols while maintaining the same probability of error.

  11. Selective activation of mechanosensitive ion channels using magnetic particles.

    Science.gov (United States)

    Hughes, Steven; McBain, Stuart; Dobson, Jon; El Haj, Alicia J

    2008-08-01

    This study reports the preliminary development of a novel magnetic particle-based technique that permits the application of highly localized mechanical forces directly to specific regions of an ion-channel structure. We demonstrate that this approach can be used to directly and selectively activate a mechanosensitive ion channel of interest, namely TREK-1. It is shown that manipulation of particles targeted against the extended extracellular loop region of TREK-1 leads to changes in whole-cell currents consistent with changes in TREK-1 activity. Responses were absent when particles were coated with RGD (Arg-Gly-Asp) peptide or when magnetic fields were applied in the absence of magnetic particles. It is concluded that changes in whole-cell current are the result of direct force application to the extracellular loop region of TREK-1 and thus these results implicate this region of the channel structure in mechano-gating. It is hypothesized that the extended loop region of TREK-1 may act as a tension spring that acts to regulate sensitivity to mechanical forces, in a nature similar to that described for MscL. The development of a technique that permits the direct manipulation of mechanosensitive ion channels in real time without the need for pharmacological drugs has huge potential benefits not only for basic biological research of ion-channel gating mechanisms, but also potentially as a tool for the treatment of human diseases caused by ion-channel dysfunction.

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

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Gnanasambandam

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

  13. Joint Relay Selection and Power Allocation for Cooperative Communication over Frequency Selective Fading Channels

    Directory of Open Access Journals (Sweden)

    Youhua Ma

    2012-08-01

    Full Text Available In this paper, we consider the joint problem of relay selection and optimal power allocation for multi-relay amplify-and-forward (AF cooperative communication system over frequency selective fading channels. An optimization model combined relay selection and power allocation under a total transmission power budget is formulated. Then, this combinatorial problem is solved in a distributed strategy. Relay selection with a new threshold-based multiple-relay selection (MRS scheme is implemented at first, and then power is allocated between source and the selected relays in an optimized way to maximize channel capacity. Simulation result shows that the proposed joint scenario with relay selection and power allocation achieves better throughput performance than that of parallel-relay scenario (means that random relay is selected to forward data and allocated part of total power on average. Furthermore, the performances of the new MRS scheme and other relay selection strategies are also investigated.

  14. Clinical Application of Same-Name Channel Point Selection

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ The namesake channel point selection is a method adopted in acupuncture treatment, in which the points on the six pairs of channels on the upper and lower extremities with same names are selected and needled. Clinically, this method is mainly used for some acute soft tissue injuries, for instance, needling point Yangchi (TE 4) with reducing method for sprain of external malleolus, needling Qiuxu (GB 40) with reducing method for sprain of dorsal carpus, and needling Tiaokou (ST 38) for lateral shoulder pain. The therapeutic effect given by this point selection method is often superior to that given by the conventional needling method. In clinical practice, the author has found some typical cases, which respond well to this method, and reports them below.

  15. Develop A Framework for Selection of Intermediary in Marketing Channel

    Directory of Open Access Journals (Sweden)

    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.

  16. Is ion channel selectivity mediated by confined water?

    CERN Document Server

    Prada-Gracia, Diego

    2012-01-01

    Ion channels form pores across the lipid bilayer, selectively allowing inorganic ions to cross the membrane down their electrochemical gradient. While the study of ion desolvation free-energies have attracted much attention, the role of water inside the pore is less clear. Here, molecular dynamics simulations of a reduced model of the KcsA selectivity filter indicate that the equilibrium position of Na+, but not of K+, is strongly influenced by confined water. The latter forms a stable complex with Na+, moving the equilibrium position of the ion to the plane of the backbone carbonyls. Almost at the centre of the binding site, the water molecule is trapped by favorable electrostatic interactions and backbone hydrogen-bonds. In the absence of confined water the equilibrium position of both Na+ and K+ is identical. Our observations strongly suggest a previously unnoticed active role of confined water in the selectivity mechanism of ion channels.

  17. 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.

  18. Insight toward epithelial Na+ channel mechanism revealed by the acid-sensing ion channel 1 structure.

    Science.gov (United States)

    Stockand, James D; Staruschenko, Alexander; Pochynyuk, Oleh; Booth, Rachell E; Silverthorn, Dee U

    2008-09-01

    The epithelial Na(+) channel/degenerin (ENaC/DEG) protein family includes a diverse group of ion channels, including nonvoltage-gated Na(+) channels of epithelia and neurons, and the acid-sensing ion channel 1 (ASIC1). In mammalian epithelia, ENaC helps regulate Na(+) and associated water transport, making it a critical determinant of systemic blood pressure and pulmonary mucosal fluidity. In the nervous system, ENaC/DEG proteins are related to sensory transduction. While the importance and physiological function of these ion channels are established, less is known about their structure. One hallmark of the ENaC/DEG channel family is that each channel subunit has only two transmembrane domains connected by an exceedingly large extracellular loop. This subunit structure was recently confirmed when Jasti and colleagues determined the crystal structure of chicken ASIC1, a neuronal acid-sensing ENaC/DEG channel. By mapping ENaC to the structural coordinates of cASIC1, as we do here, we hope to provide insight toward ENaC structure. ENaC, like ASIC1, appears to be a trimeric channel containing 1alpha, 1beta, and 1gamma subunit. Heterotrimeric ENaC and monomeric ENaC subunits within the trimer possibly contain many of the major secondary, tertiary, and quaternary features identified in cASIC1 with a few subtle but critical differences. These differences are expected to have profound effects on channel behavior. In particular, they may contribute to ENaC insensitivity to acid and to its constitutive activity in the absence of time- and ligand-dependent inactivation. Experiments resulting from this comparison of cASIC1 and ENaC may help clarify unresolved issues related to ENaC architecture, and may help identify secondary structures and residues critical to ENaC function.

  19. River Channel Expansion Reveals Ice Sheet Runoff Variations

    Science.gov (United States)

    Overeem, I.; Hudson, B. D.; Welty, E.; LeWinter, A.; Mikkelsen, A. B.

    2013-12-01

    The Greenland Ice Sheet has been rapidly melting over the last decades. To quantify its contribution to global sea-level rise, we urgently need to understand flux of meltwater into proglacial rivers. Direct measurements of river runoff at the Greenlandic coast are sparse due to the dynamic braided channels with unstable banks, which makes in-situ discharge monitoring challenging. Here, we explore the use of ';inundation-discharge' relationships through analysis of both time-lapse camera imagery and MODIS remote-sensing reflectance data to provide us with a proxy record of river discharge for proglacial systems. We utilize MODIS band6 (mid IR 1628 - 1652 nm). Light in this band is strongly absorbed by water, and reflectance is not sensitive to sediment suspended in the water, making it an appropriate proxy for river braidplain inundation. Our focus is on two Greenlandic river systems; the Watson River near Kangerlussuaq and the Naujat Kuat River near Nuuk, to track band6 reflectance characteristics over all cloud-free days for the summers of 2000-2012. For validation, a ground-based inundation record is assembled from time-lapse imagery overlooking the Watson River for 2012. Exponential inundation-discharge relationships were established using our in-situ discharge records for the Watson River near Kangerlussuaq (2007-2012, R2=0.55) and the Naujat Kuat River near Nuuk (2011-2012, R2 = 0.42). Using these relationships to predict total annual river discharge proves reasonably accurate for most years of the observational record (varying between 96-86%). Interestingly, the extreme melt year of 2012 was not reliably predicted using the established relationship. We compared these predictions against an inundation record from the in-situ time-lapse camera and found that a ground-based observations track extreme discharge events more reliably (R2 = 0.60). This methodology allows us to extend existing river records back beyond the 5 or 2 years of in-situ observations

  20. Specification for Digital Channel Selection Filters in a Bluetooth Capable HiperLAN/2 Receiver

    NARCIS (Netherlands)

    Hoeksema, Fokke; Schiphorst, Roel; Slump, Kees

    2002-01-01

    In this paper we first briefly describe how the analog part of the channel selection function for a HiperLAN/2 receiver can be used as part of the channel selection function for a Bluetooth receiver. Thereafter we proceed to specify the overall requirements for the Bluetooth channel selection functi

  1. Channel selection based on trust and multiarmed bandit in multiuser, multichannel cognitive radio networks.

    Science.gov (United States)

    Zeng, Fanzi; Shen, Xinwang

    2014-01-01

    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.

  2. 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.

  3. Selective alteration of sodium channel gating by Australian funnel-web spider toxins.

    Science.gov (United States)

    Nicholson, G M; Little, M J; Tyler, M; Narahashi, T

    1996-01-01

    The actions of potent mammalian neurotoxins isolated from the venom of two Australian funnel-web spiders were investigated using both electrophysiological and neurochemical techniques. Whole-cell patch clamp recording of sodium currents in rat dorsal root ganglion neurons revealed that versutoxin (VTX), isolated from the venom of Hadronyche versuta, produced a concentration-dependent slowing or removal of tetrodotoxin-sensitive (TTX-S) sodium current inactivation and a reduction in peak TTX-S sodium current. In contrast, VTX had no effect on tetrodotoxin-resistant (TTX-R) sodium currents or potassium currents. VTX also shifted the voltage dependence of sodium channel activation in the hyperpolarizing direction and increased the rate of recovery from inactivation. Ion flux studies performed in rat brain synaptosomes also revealed that robustoxin (RTX), from the venom of Atrax robustus, and VTX both produced a partial activation of 22Na+ flux and an inhibition of batrachotoxin-activated 22Na+ flux. This inhibition of flux through batrachotoxin-activated channels was not due to an interaction with neurotoxin receptor site 1 since [3H]saxitoxin binding was unaffected. In addition, the partial activation of 22Na+ flux was not enhanced in the presence of alpha-scorpion toxin and further experiments suggest that VTX also enhances [3H]batrachotoxin binding. These selective actions of funnel-web spider toxins on sodium channel function are comparable to those of alpha-scorpion and sea anemone toxins which bind to neurotoxin receptor site 3 on the channel to slow channel inactivation profoundly. Also, these modifications of sodium channel gating and kinetics are consistent with actions of the spider toxins to produce repetitive firing of action potentials.

  4. Design of Nonuniform Filter Bank Transceivers for Frequency Selective Channels

    Science.gov (United States)

    Chiang, Han-Ting; Phoong, See-May; Lin, Yuan-Pei

    2006-12-01

    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.

  5. [Potential-dependent Cation Selective Ion Channels Formed by Peroxiredoxin 6 in the Lipid Bilayer].

    Science.gov (United States)

    Grigoriev, P A; Sharapov, M G; Novoselov, V I

    2015-01-01

    The antioxidant enzyme peroxiredoxin 6 forms cation selective ion cluster-type channels in the lipid bilayer. Channel clustering as oligomeric structure consists of three or more subunits--channels with conductance of about 350 pS in the 200 mM KCl. Mean dwell time of the channel's open states decreases with increasing membrane voltage. A possible molecular mechanism of the observed potential-dependent inactivation of the channel cluster is discussed.

  6. Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

    Energy Technology Data Exchange (ETDEWEB)

    Fritsch, Sebastian M [ORNL; Ivanov, Ivaylo N [ORNL; Wang, Hailong [Mayo Clinic College of Medicine; Cheng, Xiaolin [ORNL

    2011-01-01

    The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor (nAChR) that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential of mean force (PMF) profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel is open for a sodium ion to transport, but presents a ~10 kcal/mol free energy barrier for a chloride ion, which arises primarily from the unfavorable interactions with a ring of negatively charged glutamate residues (E-2 ) at the intracellular end and a ring of hydrophobic residues (I9 ) in the middle of the transmembrane domain. Our collective findings further suggest that the charge selection mechanism can, to a large extent, be attributed to the narrow intracellular end and a ring of glutamate residues in this position their strong negative electrostatics and ability to bind cations. By contrast, E19 at the extracellular entrance only plays a minor role in ion selectivity of GLIC. In addition to electrostatics, both ion hydration and protein dynamics are found to be crucial for ion conduction as well, which explains why a chloride ion experiences a much greater barrier than a sodium ion in the hydrophobic region of the pore.

  7. Quantum Model for the Selectivity Filter in K$^{+}$ Ion Channel

    CERN Document Server

    Cifuentes, A A

    2013-01-01

    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 thorough 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 driving frequencie...

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

    Science.gov (United States)

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

    2016-10-01

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

  9. Structure selection and coordination in dual-channel supply chains

    Directory of Open Access Journals (Sweden)

    Jingjing Cai

    2015-04-01

    Full Text Available Purpose: This paper investigates the influence of channel structures and channel coordination on the supplier, the retailer and the entire supply chain in the context of two different kinds of marketing models: The common retailer and the exclusive shop.Methodology: With suppliers who manufacture the alternative commodities and retailers in the dual-channel supply chains as the object of the research, this paper compares suppliers' profits, consumer utility without coordination and contrasts suppliers' and retailers' profits with coordination to determine the range of the revenue sharing rates and which parameters are related.Findings: The analysis suggests the preference lists of the supplier and the retailer over channel structures with and without coordination are different, and depend on parameters like channel basic demand, channel cost and channel substitutability.Originality/value: In this research, new sales model for two suppliers should choose the same retailer or the exclusive retailers to sell their commodities.

  10. Electrochemical evaluation of chemical selectivity of glutamate receptor ion channel proteins with a multi-channel sensor.

    Science.gov (United States)

    Sugawara, M; Hirano, A; Rehák, M; Nakanishi, J; Kawai, K; Sato, H; Umezawa, Y

    1997-01-01

    A new method for evaluating chemical selectivity of agonists towards receptor ion channel proteins is proposed by using glutamate receptor (GluR) ion channel proteins and their agonists N-methyl-D-aspartic acid (NMDA), L-glutamate, and (2S, 3R, 4S) isomer of 2-(carboxycyclopropyl)glycine (L-CCG-IV). Integrated multi-channel currents, corresponding to the sum of total amount of ions passed through the multiple open channels, were used as a measure of agonists' selectivity to recognize ion channel proteins and induce channel currents. GluRs isolated from rat synaptic plasma membranes were incorporated into planar bilayer lipid membranes (BLMs) formed by the folding method. The empirical factors that affect the selectivity were demonstrated: (i) the number of GluRs incorporated into BLMs varied from one membrane to another; (ii) each BLM contained different subtypes of GluRs (NMDA and/or non-NMDA subtypes); and (iii) the magnitude of multi-channel responses induced by L-glutamate at negative applied potentials was larger than at positive potentials, while those by NMDA and L-CCG-IV were linearly related to applied potentials. The chemical selectivity among NMDA, L-glutamate and L-CCG-IV for NMDA subtype of GluRs was determined with each single BLM in which only NMDA subtype of GluRs was designed to be active by inhibiting the non-NMDA subtypes using a specific antagonist DNQX. The order of selectivity among the relevant agonists for the NMDA receptor subtype was found to be L-CCG-IV > L-glutamate > NMDA, which is consistent with the order of binding affinity of these agonists towards the same NMDA subtypes. The potential use of this approach for evaluating chemical selectivity towards non-NMDA receptor subtypes of GluRs and other receptor ion channel proteins is discussed.

  11. Concatenated hERG1 tetramers reveal stoichiometry of altered channel gating by RPR-260243.

    Science.gov (United States)

    Wu, Wei; Gardner, Alison; Sanguinetti, Michael C

    2015-01-01

    Activation of human ether-a-go-go-related gene 1 (hERG1) K(+) channels mediates repolarization of action potentials in cardiomyocytes. RPR-260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluorophenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid] (RPR) slows deactivation and attenuates inactivation of hERG1 channels. A detailed understanding of the molecular mechanism of hERG1 agonists such as RPR may facilitate the design of more selective and potent compounds for prevention of arrhythmia associated with abnormally prolonged ventricular repolarization. RPR binds to a hydrophobic pocket located between two adjacent hERG1 subunits, and, hence, a homotetrameric channel has four identical RPR binding sites. To investigate the stoichiometry of altered channel gating induced by RPR, we constructed and characterized tetrameric hERG1 concatemers containing a variable number of wild-type subunits and subunits containing a point mutation (L553A) that rendered the channel insensitive to RPR, ostensibly by preventing ligand binding. The slowing of deactivation by RPR was proportional to the number of wild-type subunits incorporated into a concatenated tetrameric channel, and four wild-type subunits were required to achieve maximal slowing of deactivation. In contrast, a single wild-type subunit within a concatenated tetramer was sufficient to achieve half of the maximal RPR-induced shift in the voltage dependence of hERG1 inactivation, and maximal effect was achieved in channels containing three or four wild-type subunits. Together our findings suggest that the allosteric modulation of channel gating involves distinct mechanisms of coupling between drug binding and altered deactivation and inactivation.

  12. 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

    -palmitoyloleylphosphatidylethanolamine membrane was used for the simulations. During the simulations, water molecules pass through the channel in single file. The movement of the single. le water molecules through the channel is concerted, and we show that it can be described by a continuous-time random-walk model. The integrity......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...... of the single file remains intact during the permeation, indicating that a disrupted water chain is unlikely to be the mechanism of proton exclusion in aquaporins. Specific hydrogen bonds between permeating water and protein at the channel center (at two conserved Asp-Pro-Ala "NPA'' motifs), together...

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

    NARCIS (Netherlands)

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

    2011-01-01

    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

  14. Directional postcopulatory sexual selection revealed by artificial insemination.

    Science.gov (United States)

    Evans, Jonathan P; Zane, Lorenzo; Francescato, Samuela; Pilastro, Andrea

    2003-01-23

    Postcopulatory sexual selection comprises both sperm competition, where the sperm from different males compete for fertilization, and cryptic female choice, where females bias sperm use in favour of particular males. Despite intense current interest in both processes as potential agents of directional sexual selection, few studies have attributed the success of attractive males to events that occur exclusively after insemination. This is because the interactions between pre- and post-insemination episodes of sexual selection can be important sources of variation in paternity. The use of artificial insemination overcomes this difficulty because it controls for variation in male fertilization success attributable to the female's perception of male quality, as well as effects due to mating order and the relative contribution of sperm from competing males. Here, we adopt this technique and show that in guppies, when equal numbers of sperm from two males compete for fertilization, relatively colourful individuals achieve greater parentage than their less ornamented counterparts. This finding indicates that precopulatory female mating preferences can be reinforced exclusively through postcopulatory processes occurring at a physiological level. Our analysis also revealed that relatively small individuals were advantaged in sperm competition, suggesting a possible trade-off between sperm competitive ability and body growth.

  15. Non-equilibrium dynamics contribute to ion selectivity in the KcsA channel.

    Directory of Open Access Journals (Sweden)

    Van Ngo

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

  16. Solute restriction reveals an essential role for clag3-associated channels in malaria parasite nutrient acquisition.

    Science.gov (United States)

    Pillai, Ajay D; Nguitragool, Wang; Lyko, Brian; Dolinta, Keithlee; Butler, Michelle M; Nguyen, Son T; Peet, Norton P; Bowlin, Terry L; Desai, Sanjay A

    2012-12-01

    The plasmodial surface anion channel (PSAC) increases erythrocyte permeability to many solutes in malaria but has uncertain physiological significance. We used a PSAC inhibitor with different efficacies against channels from two Plasmodium falciparum parasite lines and found concordant effects on transport and in vitro parasite growth when external nutrient concentrations were reduced. Linkage analysis using this growth inhibition phenotype in the Dd2 × HB3 genetic cross mapped the clag3 genomic locus, consistent with a role for two clag3 genes in PSAC-mediated transport. Altered inhibitor efficacy, achieved through allelic exchange or expression switching between the clag3 genes, indicated that the inhibitor kills parasites through direct action on PSAC. In a parasite unable to undergo expression switching, the inhibitor selected for ectopic homologous recombination between the clag3 genes to increase the diversity of available channel isoforms. Broad-spectrum inhibitors, which presumably interact with conserved sites on the channel, also exhibited improved efficacy with nutrient restriction. These findings indicate that PSAC functions in nutrient acquisition for intracellular parasites. Although key questions regarding the channel and its biological role remain, antimalarial drug development targeting PSAC should be pursued.

  17. Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels.

    Science.gov (United States)

    Fanger, C M; Rauer, H; Neben, A L; Miller, M J; Rauer, H; Wulff, H; Rosa, J C; Ganellin, C R; Chandy, K G; Cahalan, M D

    2001-04-13

    To maintain Ca(2+) entry during T lymphocyte activation, a balancing efflux of cations is necessary. Using three approaches, we demonstrate that this cation efflux is mediated by Ca(2+)-activated K(+) (K(Ca)) channels, hSKCa2 in the human leukemic T cell line Jurkat and hIKCa1 in mitogen-activated human T cells. First, several recently developed, selective and potent pharmacological inhibitors of K(Ca) channels but not K(V) channels reduce Ca(2+) entry in Jurkat and in mitogen-activated human T cells. Second, dominant-negative suppression of the native K(Ca) channel in Jurkat T cells by overexpression of a truncated fragment of the cloned hSKCa2 channel decreases Ca(2+) influx. Finally, introduction of the hIKCa1 channel into Jurkat T cells maintains rapid Ca(2+) entry despite pharmacological inhibition of the native small conductance K(Ca) channel. Thus, K(Ca) channels play a vital role in T cell Ca(2+) signaling.

  18. Activating Mutations of the TRPML1 Channel Revealed by Proline-scanning Mutagenesis*

    OpenAIRE

    2009-01-01

    The mucolipin TRP (TRPML) proteins are a family of endolysosomal cation channels with genetically established importance in humans and rodent. Mutations of human TRPML1 cause type IV mucolipidosis, a devastating pediatric neurodegenerative disease. Our recent electrophysiological studies revealed that, although a TRPML1-mediated current can only be recorded in late endosome and lysosome (LEL) using the lysosome patch clamp technique, a proline substitution in TRPML1 (TRPML1V432P) results in a...

  19. Determination of channel change for selected streams, Maricopa County, Arizona

    Science.gov (United States)

    Capesius, Joseph P.; Lehman, Ted W.

    2002-01-01

    In Maricopa County, Arizona, 10 sites on seven streams were studied to determine the lateral and vertical change of the channel. Channel change was studied over time scales ranging from individual floods to decades using cross-section surveys, discharge measurements, changes in the point of zero flow, and repeat photography. All of the channels showed some change in cross-section area or hydraulic radius over the time scales studied, but the direction and mag-nitude of change varied considerably from one flow, or series of flows, to another. The documentation of cross-section geometry for streams in Maricopa County for long-term monitoring was begun in this study.

  20. Dynamics of the EAG1 K(+) channel selectivity filter assessed by molecular dynamics simulations.

    Science.gov (United States)

    Bernsteiner, Harald; Bründl, Michael; Stary-Weinzinger, Anna

    2017-02-26

    EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4. Further, ions tended to dissociate away from S0 within less than 20 ns, due to increased filter flexibility. This was followed by water influx from the extracellular side, leading to a widening of the filter in this region, and likely non-conductive filter configurations. Simulations with the inactivation-enhancing mutant Y464A or Na(+) ions lead to trapped water molecules behind the SF, suggesting that these simulations captured early conformational changes linked to C-type inactivation.

  1. 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.

  2. Sub-surface channels in sapphire made by ultraviolet picosecond laser irradiation and selective etching.

    Science.gov (United States)

    Moser, Rüdiger; Ojha, Nirdesh; Kunzer, Michael; Schwarz, Ulrich T

    2011-11-21

    We demonstrate the realization of sub-surface channels in sapphire prepared by ultraviolet picosecond laser irradiation and subsequent selective wet etching. By optimizing the pulse energy and the separation between individual laser pulses, an optimization of channel length can be achieved with an aspect ratio as high as 3200. Due to strong variation in channel length, further investigation was done to improve the reproducibility. By multiple irradiations the standard deviation of the channel length could be reduced to 2.2%. The achieved channel length together with the high reproducibility and the use of a commercial picosecond laser system makes the process attractive for industrial application.

  3. How to Achieve the Optimal DMT of Selective Fading MIMO Channels?

    CERN Document Server

    Mroueh, Lina

    2010-01-01

    In this paper, we consider a particular class of selective fading channel corresponding to a channel that is selective either in time or in frequency. For this class of channel, we propose a systematic way to achieve the optimal DMT derived in Coronel and B\\"olcskei, IEEE ISIT, 2007 by extending the non-vanishing determinant (NVD) criterion to the selective channel case. A new code construction based on split NVD parallel codes is then proposed to satisfy the NVD parallel criterion. This result is of significant interest not only in its own right, but also because it settles a long-standing debate in the literature related to the optimal DMT of selective fading channels.

  4. 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.

  5. CYCLOSTATIONARITY-BASED OFDM SIGNAL SENSING OVER DOUBLY-SELECTIVE FADING CHANNELS

    Institute of Scientific and Technical Information of China (English)

    Tian Jinfeng; Jiang Yonglei; Chen Huaxia; Hu Honglin

    2011-01-01

    In this paper,using cyclostationarity-based sensing method to detect the presence of Orthogonal Frequency Division Multiplexing (OFDM) signal over doubly-selective fading channels is studied.By approximating the channel with Basis Expansion Model (BEM),we derive the second-order cyclostationary statistics of the received OFDM signal over doubly-selective fading channels.Theoretical analysis indicates that new cyclostationary signatures produced by Doppler spread and multipath delay can be further exploited in the detecting process.Simulation examples demonstrate that the sensing methods using channel-induced cyclostationary features provide substantial improvements on detection performance.

  6. Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules.

    Science.gov (United States)

    Bevans, C G; Kordel, M; Rhee, S K; Harris, A L

    1998-01-30

    Intercellular connexin channels (gap junction channels) have long been thought to mediate molecular signaling between cells, but the nature of the signaling has been unclear. This study shows that connexin channels from native tissue have selective permeabilities, partially based on pore diameter, that discriminate among cytoplasmic second messenger molecules. Permeability was assessed by measurement of selective loss/retention of tracers from liposomes containing reconstituted connexin channels. The tracers employed were tritiated cyclic nucleotides and a series of oligomaltosaccharides derivatized with a small uncharged fluorescent moiety. The data define different size cut-off limits for permeability through homomeric connexin-32 channels and through heteromeric connexin-32/connexin-26 channels. Connexin-26 contributes to a narrowed pore. Both cAMP and cGMP were permeable through the homomeric connexin-32 channels. cAMP was permeable through only a fraction of the heteromeric channels. Surprisingly, cGMP was permeable through a substantially greater fraction of the heteromeric channels than was cAMP. The data suggest that isoform stoichiometry and/or arrangement within a connexin channel determines whether cyclic nucleotides can permeate, and which ones. This is the first evidence for connexin-specific selectivity among biological signaling molecules.

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

    Directory of Open Access Journals (Sweden)

    R. Drews

    2015-10-01

    Full Text Available 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.

  8. Activating mutations of the TRPML1 channel revealed by proline-scanning mutagenesis.

    Science.gov (United States)

    Dong, Xian-ping; Wang, Xiang; Shen, Dongbiao; Chen, Su; Liu, Meiling; Wang, Yanbin; Mills, Eric; Cheng, Xiping; Delling, Markus; Xu, Haoxing

    2009-11-13

    The mucolipin TRP (TRPML) proteins are a family of endolysosomal cation channels with genetically established importance in humans and rodent. Mutations of human TRPML1 cause type IV mucolipidosis, a devastating pediatric neurodegenerative disease. Our recent electrophysiological studies revealed that, although a TRPML1-mediated current can only be recorded in late endosome and lysosome (LEL) using the lysosome patch clamp technique, a proline substitution in TRPML1 (TRPML1(V432P)) results in a large whole cell current. Thus, it remains unknown whether the large TRPML1(V432P)-mediated current results from an increased surface expression (trafficking), elevated channel activity (gating), or both. Here we performed systemic Pro substitutions in a region previously implicated in the gating of various 6 transmembrane cation channels. We found that several Pro substitutions displayed gain-of-function (GOF) constitutive activities at both the plasma membrane (PM) and endolysosomal membranes. Although wild-type TRPML1 and non-GOF Pro substitutions localized exclusively in LEL and were barely detectable in the PM, the GOF mutations with high constitutive activities were not restricted to LEL compartments, and most significantly, exhibited significant surface expression. Because lysosomal exocytosis is Ca(2+)-dependent, constitutive Ca(2+) permeability due to Pro substitutions may have resulted in stimulus-independent intralysosomal Ca(2+) release, hence the surface expression and whole cell current of TRPML1. Indeed, surface staining of lysosome-associated membrane protein-1 (Lamp-1) was dramatically increased in cells expressing GOF TRPML1 channels. We conclude that TRPML1 is an inwardly rectifying, proton-impermeable, Ca(2+) and Fe(2+)/Mn(2+) dually permeable cation channel that may be gated by unidentified cellular mechanisms through a conformational change in the cytoplasmic face of the transmembrane 5 (TM5). Furthermore, activation of TRPML1 in LEL may lead to the

  9. Single Channel Recordings Reveal Differential β2 Subunit Modulations Between Mammalian and Drosophila BKCa(β2) Channels

    Science.gov (United States)

    Zhong, Ling; Guo, Xiying; Weng, Anxi; Xiao, Feng; Zeng, Wenping; Zhang, Yan; Ding, Jiuping; Hou, Panpan

    2016-01-01

    Large-conductance Ca2+- and voltage-activated potassium (BK) channels are widely expressed in tissues. As a voltage and calcium sensor, BK channels play significant roles in regulating the action potential frequency, neurotransmitter release, and smooth muscle contraction. After associating with the auxiliary β2 subunit, mammalian BK(β2) channels (mouse or human Slo1/β2) exhibit enhanced activation and complete inactivation. However, how the β2 subunit modulates the Drosophila Slo1 channel remains elusive. In this study, by comparing the different functional effects on heterogeneous BK(β2) channel, we found that Drosophila Slo1/β2 channel exhibits “paralyzed”-like and incomplete inactivation as well as slow activation. Further, we determined three different modulations between mammalian and Drosophila BK(β2) channels: 1) dSlo1/β2 doesn’t have complete inactivation. 2) β2(K33,R34,K35) delays the dSlo1/Δ3-β2 channel activation. 3) dSlo1/β2 channel has enhanced pre-inactivation than mSlo1/β2 channel. The results in our study provide insights into the different modulations of β2 subunit between mammalian and Drosophila Slo1/β2 channels and structural basis underlie the activation and pre-inactivation of other BK(β) complexes. PMID:27755549

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Energetics of ion competition in the DEKA selectivity filter of neuronal sodium channels

    Directory of Open Access Journals (Sweden)

    D. Boda

    2015-03-01

    Full Text Available The energetics of ionic selectivity in the neuronal sodium channels is studied. A simple model constructed for the selectivity filter of the channel is used. The selectivity filter of this channel type contains aspartate (D, glutamate (E, lysine (K, and alanine (A residues (the DEKA locus. We use Grand Canonical Monte Carlo simulations to compute equilibrium binding selectivity in the selectivity filter and to obtain various terms of the excess chemical potential from a particle insertion procedure based on Widom's method. We show that K+ ions in competition with Na+ are efficiently excluded from the selectivity filter due to entropic hard sphere exclusion. The dielectric constant of protein has no effect on this selectivity. Ca2+ ions, on the other hand, are excluded from the filter due to a free energetic penalty which is enhanced by the low dielectric constant of protein.

  12. NFkappaB Selectivity of Estrogen Receptor Ligands Revealed By Comparative Crystallographic Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Nettles, K.W.; Bruning, J.B.; Gil, G.; Nowak, J.; Sharma, S.K.; Hahm, J.B.; Kulp, K.; Hochberg, R.B.; Zhou, H.; Katzenellenbogen, J.A.; Katzenllenbogen, B.S.; Kim, Y.; Joachmiak, A.; Greene, G.L.

    2009-05-22

    Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NF{kappa}B-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure.

  13. Signatures of selection in tilapia revealed by whole genome resequencing.

    Science.gov (United States)

    Xia, Jun Hong; Bai, Zhiyi; Meng, Zining; Zhang, Yong; Wang, Le; Liu, Feng; Jing, Wu; Wan, Zi Yi; Li, Jiale; Lin, Haoran; Yue, Gen Hua

    2015-09-16

    Natural selection and selective breeding for genetic improvement have left detectable signatures within the genome of a species. Identification of selection signatures is important in evolutionary biology and for detecting genes that facilitate to accelerate genetic improvement. However, selection signatures, including artificial selection and natural selection, have only been identified at the whole genome level in several genetically improved fish species. Tilapia is one of the most important genetically improved fish species in the world. Using next-generation sequencing, we sequenced the genomes of 47 tilapia individuals. We identified a total of 1.43 million high-quality SNPs and found that the LD block sizes ranged from 10-100 kb in tilapia. We detected over a hundred putative selective sweep regions in each line of tilapia. Most selection signatures were located in non-coding regions of the tilapia genome. The Wnt signaling, gonadotropin-releasing hormone receptor and integrin signaling pathways were under positive selection in all improved tilapia lines. Our study provides a genome-wide map of genetic variation and selection footprints in tilapia, which could be important for genetic studies and accelerating genetic improvement of tilapia.

  14. A Bintree Energy Approach for Colour Image Segmentation Using Adaptive Channel Selection

    Institute of Scientific and Technical Information of China (English)

    TU Sheng-xian; ZHANG Su; CHEN Ya-zhu; XIAO Chang-yan; ZHANG Lei

    2008-01-01

    A new hierarchical approach called bintree energy segmentation was presented for color image seg-mentation. The image features are extracted by adaptive clustering on multi-channel data at each level and used as the criteria to dynamically select the best chromatic channel, where the segmentation is carried out. In this approach, an extended direct energy computation method based on the Chan-Vese model was proposed to segment the selected channel, and the segmentation outputs are then fused with other channels into new images,from which a new channel with better features is selected for the second round segmentation. This procedure is repeated until the preset condition is met. Finally, a binary segmentation tree is formed, in which each leaf represents a class of objects with a distinctive color. To facilitate the data organization, image background is employed in segmentation and channels fusion. The bintree energy segmentation exploits color information involved in all channels data and tries to optimize the global segmentation result by choosing the "best" chan-nel for segmentation at each level. The experiments show that the method is effective in speed, accuracy and flexibility.

  15. 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.

  16. Synthetic Channel-forming Peptides and Ion Selectivity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Introduction Peptides made up of alternating L- and D- amino acids can form β-helices as in gramicidin A or cyclic peptides that aggregate to form tubes[1]. In both cases the structures are hollow with all the side chains projecting outwards. Kennedy et al. [2] postulated that peptides having the (LLLD)n configuration could form helices with every fourth side chain projecting inward.It is a fact that synthetic N-formyl-( LeuSerLeuGly)6-OH, when added to a lipid bilayer, dimerizes, to form ion channels having conductances greater than that of gramicidin.

  17. 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.

  18. On Optimal Input Design and Model Selection for Communication Channels

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan [ORNL; Djouadi, Seddik M [ORNL; Olama, Mohammed M [ORNL

    2013-01-01

    In this paper, the optimal model (structure) selection and input design which minimize the worst case identification error for communication systems are provided. The problem is formulated using metric complexity theory in a Hilbert space setting. It is pointed out that model selection and input design can be handled independently. Kolmogorov n-width is used to characterize the representation error introduced by model selection, while Gel fand and Time n-widths are used to represent the inherent error introduced by input design. After the model is selected, an optimal input which minimizes the worst case identification error is shown to exist. In particular, it is proven that the optimal model for reducing the representation error is a Finite Impulse Response (FIR) model, and the optimal input is an impulse at the start of the observation interval. FIR models are widely popular in communication systems, such as, in Orthogonal Frequency Division Multiplexing (OFDM) systems.

  19. Classic selective sweeps revealed by massive sequencing in cattle.

    Directory of Open Access Journals (Sweden)

    Saber Qanbari

    2014-02-01

    Full Text Available Human driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern cattle. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying domestication-related genes that ultimately may help to further genetically improve this economically important animal. To this end, we employed a panel of more than 15 million autosomal SNPs identified from re-sequencing of 43 Fleckvieh animals. We mainly applied two somewhat complementary statistics, the integrated Haplotype Homozygosity Score (iHS reflecting primarily ongoing selection, and the Composite of Likelihood Ratio (CLR having the most power to detect completed selection after fixation of the advantageous allele. We find 106 candidate selection regions, many of which are harboring genes related to phenotypes relevant in domestication, such as coat coloring pattern, neurobehavioral functioning and sensory perception including KIT, MITF, MC1R, NRG4, Erbb4, TMEM132D and TAS2R16, among others. To further investigate the relationship between genes with signatures of selection and genes identified in QTL mapping studies, we use a sample of 3062 animals to perform four genome-wide association analyses using appearance traits, body size and somatic cell count. We show that regions associated with coat coloring significantly (P<0.0001 overlap with the candidate selection regions, suggesting that the selection signals we identify are associated with traits known to be affected by selection during domestication. Results also provide further evidence regarding the complexity of the genetics underlying coat coloring in cattle. This study illustrates the potential of population genetic approaches for identifying genomic regions affecting domestication-related phenotypes and further helps to identify specific regions targeted by selection during speciation, domestication and

  20. Direct selection on genetic robustness revealed in the yeast transcriptome.

    Directory of Open Access Journals (Sweden)

    Stephen R Proulx

    Full Text Available BACKGROUND: Evolutionary theory predicts that organisms should evolve the ability to produce high fitness phenotypes in the face of environmental disturbances (environmental robustness or genetic mutations (genetic robustness. While several studies have uncovered mechanisms that lead to both environmental and genetic robustness, we have yet to understand why some components of the genome are more robust than others. According to evolutionary theory, environmental and genetic robustness will have different responses to selective forces. Selection on environmental robustness for a trait is expected to be strong and related to the fitness costs of altering that trait. In contrast to environmental robustness, selection on genetic robustness for a trait is expected to be largely independent of the fitness cost of altering the trait and instead should correlate with the standing genetic variation for the trait that can potentially be buffered. Several mechanisms that provide both environmental and genetic robustness have been described, and this correlation could be explained by direct selection on both forms of robustness (direct selection hypothesis, or through selection on environmental robustness and a correlated response in genetic robustness (congruence hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Using both published and novel data on gene expression in the yeast Saccharomyces cerevisiae, we find that genetic robustness is correlated with environmental robustness across the yeast genome as predicted by the congruence hypothesis. However, we also show that environmental robustness, but not genetic robustness, is related to per-gene fitness effects. In contrast, genetic robustness is significantly correlated with network position, suggesting that genetic robustness has been under direct selection. CONCLUSIONS/SIGNIFICANCE: We observed a significant correlation between our measures of genetic and environmental robustness, in agreement with the

  1. 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.

  2. Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes.

    Science.gov (United States)

    Furukawa, T; Yamakawa, T; Midera, T; Sagawa, T; Mori, Y; Nukada, T

    1999-11-01

    Some dihydropyridines (DHPs), such as amlodipine and cilnidipine, have been shown to block not only L-type but also N-type Ca(2+) channels; therefore, DHPs are no longer considered as L-type-specific Ca(2+) channel blockers. However, selectivity of DHPs for Ca(2+) channel subtypes including N-, P/Q-, and R-types are poorly understood. To address this issue at the molecular level, blocking effects of 10 DHPs (nifedipine, nilvadipine, barnidipine, nimodipine, nitrendipine, amlodipine, nicardipine, benidipine, felodipine, and cilnidipine) on four subtypes of Ca(2+) channels (L-, N-, P/Q-, and R-types) were investigated in the Xenopus oocyte expression system with the use of the two-microelectrode voltage-clamp technique. L-type Ca(2+) channels expressed as alpha(1C)alpha(2)beta(1a) combination were profoundly blocked by all DHPs examined, whereas blocking actions of these DHPs on R-type (alpha(1E)alpha(2)beta(1a)) channels were equally weak. In contrast, 5 of the 10 DHPs (amlodipine, benidipine, cilnidipine, nicardipine, and barnidipine) significantly blocked N-type (alpha(1B)alpha(2)beta(1a)) and P/Q-type (alpha(1A)alpha(2)beta(1a)) Ca(2+) channels. These selectivities of DHPs in blocking Ca(2+) channel subtypes would provide useful pharmacological and clinical information on the mode of action of the drugs including side effects and adverse effects.

  3. Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter.

    Science.gov (United States)

    Tilegenova, Cholpon; Cortes, D Marien; Cuello, Luis G

    2017-03-21

    Mode-shift or hysteresis has been reported in ion channels. Voltage-shift for gating currents is well documented for voltage-gated cation channels (VGCC), and it is considered a voltage-sensing domain's (VSD) intrinsic property. However, uncoupling the Shaker K(+) channel's pore domain (PD) from the VSD prevented the mode-shift of the gating currents. Consequently, it was proposed that an open-state stabilization of the PD imposes a mechanical load on the VSD, which causes its mode-shift. Furthermore, the mode-shift displayed by hyperpolarization-gated cation channels is likely caused by structural changes at the channel's PD similar to those underlying C-type inactivation. To demonstrate that the PD of VGCC undergoes hysteresis, it is imperative to study its gating process in the absence of the VSD. A back-door strategy is to use KcsA (a K(+) channel from the bacteria Streptomyces lividans) as a surrogate because it lacks a VSD and exhibits an activation coupled to C-type inactivation. By directly measuring KcsA's activation gate opening and closing in conditions that promote or halt C-type inactivation, we have found (i) that KcsA undergoes mode-shift of gating when having K(+) as the permeant ion; (ii) that Cs(+) or Rb(+), known to halt C-inactivation, prevented mode-shift of gating; and (iii) that, in the total absence of C-type inactivation, KcsA's mode-shift was prevented. Finally, our results demonstrate that an allosteric communication causes KcsA's activation gate to "remember" the conformation of the selectivity filter, and hence KcsA requires a different amount of energy for opening than for closing.

  4. The S4-S5 loop contributes to the ion-selective pore of potassium channels.

    Science.gov (United States)

    Slesinger, P A; Jan, Y N; Jan, L Y

    1993-10-01

    Mutagenesis experiments on voltage-gated K+ channels have suggested that the ion-selective pore is comprised mostly of H5 segments. To see whether regions outside of the H5 segment might also contribute to the pore structure, we have studied the effect of single amino acid substitutions in the segment that connects the S4 and S5 putative transmembrane segments (S4-S5 loop) on various permeation properties of Shaker K+ channels. Mutations in the S4-S5 loop alter the Rb+ selectivity, the single-channel K+ and Rb+ conductances, and the sensitivity to open channel block produced by intracellular tetraethylammonium ion, Ba2+, and Mg2+. The block of Shaker K+ channels by intracellular Mg2+ is surprising, but is reminiscent of the internal Mg2+ blockade of inward rectifier K+ channels. The results suggest that the S4-S5 loop constitutes part of the ion-selective pore. Thus, the S4-S5 loop and the H5 segment are likely to contribute to the long pore characteristic of voltage-gated K+ channels.

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

    Directory of Open Access Journals (Sweden)

    Chi-Chun Lo

    2016-02-01

    Full Text Available 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  8. The relationship between mean channel selection and the calculated coefficient of variation.

    Science.gov (United States)

    Schuette, W H; Carducci, E; Marti, G E; Shackney, S E; Eden, M

    1985-09-01

    Calculated coefficients of variation (CV) taken from the quotient of the standard deviation (S.D.) and the mean value of measured distributions are often used as an indicator of system performance in linear flow cytometry (FCM). The ability of the calculated CV to estimate the true CV of the underlying experiment before grouping (channelization) is dependent on the relationship between the width of the data channels and the magnitude of the S.D. of the measured distribution. When the channel width is equal to the S.D. of a distribution, the calculated CV is approximately 20% larger than the true CV of an experiment. By the time the S.D. is only one-half of a channel width, the calculated CV is unreliable. When the distribution S.D. is narrower than a channel's width, small changes in the distribution mean value will cause large variations in the calculated CV. As the true CV decreases, the calculation must be made with higher mean channel values. This dependence of calculated CV accuracy upon the relationship between S.D. and channel width places limitations upon mean channel selection that must be considered when using CV calculations for evaluating system performance, especially when looking for small improvements during optical alignment procedures. When an instrument is assumed to have a constant CV and the data are collected linearly, it is possible to improve the CV estimation accuracy by placing distributions in higher-numbered channels.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. 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.

  10. Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.

    Science.gov (United States)

    Xin, D; Wang, H; Yang, J; Su, Y-F; Fan, G-W; Wang, Y-F; Zhu, Y; Gao, X-M

    2010-02-01

    The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.

  11. Hydrodynamic filtration in microfluidic channels as size-selection process for giant unilamellar vesicles.

    Science.gov (United States)

    Woo, Youngjun; Heo, Youhee; Shin, Kwanwoo; Yi, Gi-Ra

    2013-04-01

    We have developed hydrodynamic filtration method in microfluidic device for the efficient size-selection of polydisperse lipid vesicles for giant unilamellar vesicles (GUVs), in which vesicles were formed by electroformation method. Combining pinched flow channel design before hydrodynamic filtration, GUVs were flowed and guided to filtration channels, in which small lipid vesicles were further filtered and GUV were remained in main flow channels. For increasing the selectivity of GUV in outlets, length of slit section, or relative flow rate were controlled and drain channels were introduced for avoiding back flow. At higher flow rate in a pinched flow, the fraction of recovered GUVs (>10 microm) were increased, in which most of small vesicles were filtered.

  12. Wavelength-selective fluorescence in ion channels formed by gramicidin A in membranes

    Indian Academy of Sciences (India)

    Amitabha Chattopadhyay; Satinder S Rawat

    2007-03-01

    Gramicidins are linear peptides that form ion channels that are specific for monovalent cations in membranes. The tryptophan residues in the gramicidin channel play a crucial role in the organization and function of the channel. The natural mixture of gramicidins, denoted as gramicidin A', consists of mostly gramicidin A, but also contains gramicidins B, C and D as minor components. We have previously shown that the tryptophan residues in ion channels formed by the naturally occurring peptide, gramicidin A', display wavelength-dependent fluorescence characteristics due to the motionally restricted environment in which they are localized. In order to check the influence of ground-state heterogeneity in the observed wavelength-selective fluorescence of gramicidin A' in membranes, we performed similar experiments with pure gramicidin A in model membranes. Our results show that the observed wavelength-selective fluorescence characteristics of naturally occurring gramicidin A' are not due to groundstate heterogeneity.

  13. 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.

  14. Performance Evaluation of DWT based Multicarrier Systems over Frequency Selective Channels

    OpenAIRE

    Suganya.M; Ramanathan R

    2015-01-01

    In this work, the performance of DWT based OFDM is studied and compared it with conventional FFT based OFDM over frequency selective channels in different test environments. The Bit Error Rate (BER) estimation is done to evaluate the performance of both the systems. In DWT based OFDM, different wavelet families such as haar, daubechies, coiflet and biorthogonal were used with different levels of decomposition. The simulation results show that in all channels, DWT based OFDM requires less SNR ...

  15. Optimal Relay Selection with Channel Probing in Wireless Sensor Networks

    CERN Document Server

    Naveen, K P

    2011-01-01

    Motivated by the problem of distributed geographical packet forwarding in a wireless sensor network with sleep-wake cycling nodes, we propose a local forwarding model comprising a node that wishes to forward a packet towards a destination, and a set of next-hop relay nodes, each of which is associated with a reward that summarises the cost/benefit of forwarding the packet through that relay. The relays wake up at random times, at which instants they reveal only the probability distributions of their rewards (e.g., by revealing their locations). To determine a relay's exact reward, the forwarding node has to further probe the relay, incurring a probing cost. Thus, at each relay wake-up instant, the source, given a set of relay reward distributions, has to decide whether to stop (and forward the packet to an already probed relay), continue waiting for further relays to wake-up, or probe an unprobed relay. We formulate the problem as a Markov decision process, with the objective being to minimize the packet forw...

  16. Robust EEG Channel Selection across Subjects for Brain-Computer Interfaces

    Directory of Open Access Journals (Sweden)

    Lal Thomas Navin

    2005-01-01

    Full Text Available Most EEG-based brain-computer interface (BCI paradigms come along with specific electrode positions, for example, for a visual-based BCI, electrode positions close to the primary visual cortex are used. For new BCI paradigms it is usually not known where task relevant activity can be measured from the scalp. For individual subjects, Lal et al. in 2004 showed that recording positions can be found without the use of prior knowledge about the paradigm used. However it remains unclear to what extent their method of recursive channel elimination (RCE can be generalized across subjects. In this paper we transfer channel rankings from a group of subjects to a new subject. For motor imagery tasks the results are promising, although cross-subject channel selection does not quite achieve the performance of channel selection on data of single subjects. Although the RCE method was not provided with prior knowledge about the mental task, channels that are well known to be important (from a physiological point of view were consistently selected whereas task-irrelevant channels were reliably disregarded.

  17. PERFORMANCE OF LDPC CODED FMT SYSTEMS OVER FREQUENCY SELECTIVE FADING CHANNEL

    Institute of Scientific and Technical Information of China (English)

    Li Qiang; Bi Guangguo; Du Peng

    2005-01-01

    This paper proposes the Low Density Parity Check (LDPC) coded Filtered MultiTone (FMT) systems with high-order modulation for the high data rate reliable transmission over frequency selective fading channel. For the purpose of accomplishing soft input soft output iterative decoding of LDPC codes, a new soft decision metric generation method is proposed,which obviates the need of the noise variance estimation, for M-PSK/M-QAM-type high-order modulation over frequency selective fading channel. Computer simulation indicates that, there is no performance loss with our new metric, but the complexity of implementation is reduced, and that the LDPC codes are effective to improve the Bit Error Rate (BER) of FMT in frequency selective fading channel.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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%.

  20. Simultaneous channel and feature selection of fused EEG features based on Sparse Group Lasso.

    Science.gov (United States)

    Wang, Jin-Jia; Xue, Fang; Li, Hui

    2015-01-01

    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%.

  1. 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.

  2. 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.

  3. Clustering and Functional Coupling of Diverse Ion Channels and Signaling Proteins Revealed by Super-resolution STORM Microscopy in Neurons.

    Science.gov (United States)

    Zhang, Jie; Carver, Chase M; Choveau, Frank S; Shapiro, Mark S

    2016-10-19

    The fidelity of neuronal signaling requires organization of signaling molecules into macromolecular complexes, whose components are in intimate proximity. The intrinsic diffraction limit of light makes visualization of individual signaling complexes using visible light extremely difficult. However, using super-resolution stochastic optical reconstruction microscopy (STORM), we observed intimate association of individual molecules within signaling complexes containing ion channels (M-type K(+), L-type Ca(2+), or TRPV1 channels) and G protein-coupled receptors coupled by the scaffolding protein A-kinase-anchoring protein (AKAP)79/150. Some channels assembled as multi-channel supercomplexes. Surprisingly, we identified novel layers of interplay within macromolecular complexes containing diverse channel types at the single-complex level in sensory neurons, dependent on AKAP79/150. Electrophysiological studies revealed that such ion channels are functionally coupled as well. Our findings illustrate the novel role of AKAP79/150 as a molecular coupler of different channels that conveys crosstalk between channel activities within single microdomains in tuning the physiological response of neurons.

  4. Comparison of the single channel and multichannel (multivariate) concepts of selectivity in analytical chemistry.

    Science.gov (United States)

    Dorkó, Zsanett; Verbić, Tatjana; Horvai, George

    2015-07-01

    Different measures of selectivity are in use for single channel and multichannel linear analytical measurements, respectively. It is important to understand that these two measures express related but still distinctly different features of the respective measurements. These relationships are clarified by introducing new arguments. The most widely used selectivity measure of multichannel linear methods (which is based on the net analyte signal, NAS, concept) expresses the sensitivity to random errors of a determination where all bias from interferents is computationally eliminated using pure component spectra. The conventional selectivity measure of single channel linear measurements, on the other hand, helps to estimate the bias caused by an interferent in a biased measurement. In single channel methods expert knowledge about the samples is used to limit the possible range of interferent concentrations. The same kind of expert knowledge allows improved (lower mean squared error, MSE) analyte determinations also in "classical" multichannel measurements if those are intractable due to perfect collinearity or to high noise inflation. To achieve this goal bias variance tradeoff is employed, hence there remains some bias in the results and therefore the concept of single channel selectivity can be extended in a natural way to multichannel measurements. This extended definition and the resulting selectivity measure can also be applied to the so-called inverse multivariate methods like partial least squares regression (PLSR), principal component regression (PCR) and ridge regression (RR).

  5. Conserved BK channel-protein interactions reveal signals relevant to cell death and survival.

    Directory of Open Access Journals (Sweden)

    Bernd Sokolowski

    Full Text Available The large-conductance Ca(2+-activated K(+ (BK channel and its β-subunit underlie tuning in non-mammalian sensory or hair cells, whereas in mammals its function is less clear. To gain insights into species differences and to reveal putative BK functions, we undertook a systems analysis of BK and BK-Associated Proteins (BKAPS in the chicken cochlea and compared these results to other species. We identified 110 putative partners from cytoplasmic and membrane/cytoskeletal fractions, using a combination of coimmunoprecipitation, 2-D gel, and LC-MS/MS. Partners included 14-3-3γ, valosin-containing protein (VCP, stathmin (STMN, cortactin (CTTN, and prohibitin (PHB, of which 16 partners were verified by reciprocal coimmunoprecipitation. Bioinformatics revealed binary partners, the resultant interactome, subcellular localization, and cellular processes. The interactome contained 193 proteins involved in 190 binary interactions in subcellular compartments such as the ER, mitochondria, and nucleus. Comparisons with mice showed shared hub proteins that included N-methyl-D-aspartate receptor (NMDAR and ATP-synthase. Ortholog analyses across six species revealed conserved interactions involving apoptosis, Ca(2+ binding, and trafficking, in chicks, mice, and humans. Functional studies using recombinant BK and RNAi in a heterologous expression system revealed that proteins important to cell death/survival, such as annexinA5, γ-actin, lamin, superoxide dismutase, and VCP, caused a decrease in BK expression. This revelation led to an examination of specific kinases and their effectors relevant to cell viability. Sequence analyses of the BK C-terminus across 10 species showed putative binding sites for 14-3-3, RAC-α serine/threonine-protein kinase 1 (Akt, glycogen synthase kinase-3β (GSK3β and phosphoinositide-dependent kinase-1 (PDK1. Knockdown of 14-3-3 and Akt caused an increase in BK expression, whereas silencing of GSK3β and PDK1 had the opposite

  6. An ion selectivity filter in the extracellular domain of Cys-loop receptors reveals determinants for ion conductance.

    Science.gov (United States)

    Hansen, Scott B; Wang, Hai-Long; Taylor, Palmer; Sine, Steven M

    2008-12-26

    Neurotransmitter binding to Cys-loop receptors promotes a prodigious transmembrane flux of several million ions/s, but to date, structural determinants of ion flux have been identified flanking the membrane-spanning region. Using x-ray crystallography, sequence analysis, and single-channel recording, we identified a novel determinant of ion conductance near the point of entry of permeant ions. Co-crystallization of acetylcholine-binding protein with sulfate anions revealed coordination of SO4(2-) with a ring of lysines at a position equivalent to 24 A above the lipid membrane in homologous Cys-loop receptors. Analysis of multiple sequence alignments revealed that residues equivalent to the ring of lysines are negatively charged in cation-selective receptors but are positively charged in anion-selective receptors. Charge reversal of side chains at homologous positions in the nicotinic receptor from the motor end plate decreases unitary conductance up to 80%. Selectivity filters stemming from transmembrane alpha-helices have similar pore diameters and compositions of amino acids. These findings establish that when the channel opens under a physiological electrochemical gradient, permeant ions are initially stabilized within the extracellular vestibule of Cys-loop receptors, and this stabilization is a major determinant of ion conductance.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a

    Science.gov (United States)

    Bende, Niraj S.; Dziemborowicz, Sławomir; Mobli, Mehdi; Herzig, Volker; Gilchrist, John; Wagner, Jordan; Nicholson, Graham M.; King, Glenn F.; Bosmans, Frank

    2014-07-01

    β-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1-S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.

  13. Coulomb blockade model of permeation and selectivity in biological ion channels

    Science.gov (United States)

    Kaufman, I. Kh; McClintock, P. V. E.; Eisenberg, R. S.

    2015-08-01

    Biological ion channels are protein nanotubes embedded in, and passing through, the bilipid membranes of cells. Physiologically, they are of crucial importance in that they allow ions to pass into and out of cells, fast and efficiently, though in a highly selective way. Here we show that the conduction and selectivity of calcium/sodium ion channels can be described in terms of ionic Coulomb blockade in a simplified electrostatic and Brownian dynamics model of the channel. The Coulomb blockade phenomenon arises from the discreteness of electrical charge, the strong electrostatic interaction, and an electrostatic exclusion principle. The model predicts a periodic pattern of Ca2+ conduction versus the fixed charge Qf at the selectivity filter (conduction bands) with a period equal to the ionic charge. It thus provides provisional explanations of some observed and modelled conduction and valence selectivity phenomena, including the anomalous mole fraction effect and the calcium conduction bands. Ionic Coulomb blockade and resonant conduction are similar to electronic Coulomb blockade and resonant tunnelling in quantum dots. The same considerations may also be applicable to other kinds of channel, as well as to charged artificial nanopores.

  14. Towards low power N-Path filters for flexible RF-Channel selection

    NARCIS (Netherlands)

    Klumperink, Eric A.M.; Soer, Michiel C.M.; Struiksma, Remko E.; Vliet, van Frank E.; Nauta, Bram

    2015-01-01

    N-path filters can offer high-linearity high-Q channel selection filtering at a flexibly programmable RF center frequency, which is highly wanted for Software Defined Radio. Relying on capacitors and MOSFET switches, driven by digital non-overlapping clocks, N-path filters fit well to CMOS and benef

  15. Quantised transistor response to ion channels revealed by nonstationary noise analysis

    Science.gov (United States)

    Becker-Freyseng, C.; Fromherz, P.

    2011-11-01

    We report on the quantised response of a field-effect transistor to molecular ion channels in a biomembrane. HEK293-type cells overexpressing the Shaker B potassium channel were cultured on a silicon chip. An enhanced noise of the transistor is observed when the ion channels are activated. The analysis of the fluctuations in terms of binomial statistics identifies voltage quanta of about 1 μV on the gate. They are attributed to the channel currents that affect the gate voltage according to the Green's function of the cell-chip junction.

  16. 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.

  17. 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.

  18. Vestibular role of KCNQ4 and KCNQ5 K+ channels revealed by mouse models

    NARCIS (Netherlands)

    G. Spitzmaul (Guillermo); L. Tolosa (Leonardo); B.H.J. Winkelman (Beerend); M. Heidenreich (Matthias); M.A. Frens (Maarten); C. Chabbert (Christian); C.I. de Zeeuw (Chris); T.J. Jentsch (Thomas)

    2013-01-01

    textabstractThe function of sensory hair cells of the cochlea and vestibular organs depends on an influx of K+ through apical mechanosensitive ion channels and its subsequent removal over their basolateral membrane. The KCNQ4 (Kv7.4) K+ channel, which is mutated in DFNA2 human hearing loss, is expre

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    del Coso Aitor

    2007-01-01

    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 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, . Therefore, D&F relaying, cannot achieve the capacity of actual MISO channels.

  1. The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels.

    Science.gov (United States)

    Chong, Youmie; Hayes, Jessica L; Sollod, Brianna; Wen, Suping; Wilson, David T; Hains, Peter G; Hodgson, Wayne C; Broady, Kevin W; King, Glenn F; Nicholson, Graham M

    2007-08-15

    The omega-atracotoxins (omega-ACTX) are a family of arthropod-selective peptide neurotoxins from Australian funnel-web spider venoms (Hexathelidae: Atracinae) that are candidates for development as biopesticides. We isolated a 37-residue insect-selective neurotoxin, omega-ACTX-Ar1a, from the venom of the Sydney funnel-web spider Atrax robustus, with high homology to several previously characterized members of the omega-ACTX-1 family. The peptide induced potent excitatory symptoms, followed by flaccid paralysis leading to death, in acute toxicity tests in house crickets. Using isolated smooth and skeletal nerve-muscle preparations, the toxin was shown to lack overt vertebrate toxicity at concentrations up to 1 microM. To further characterize the target of the omega-ACTXs, voltage-clamp analysis using the whole-cell patch-clamp technique was undertaken using cockroach dorsal unpaired median neurons. It is shown here for the first time that omega-ACTX-Ar1a, and its homolog omega-ACTX-Hv1a from Hadronyche versuta, reversibly block both mid-low- (M-LVA) and high-voltage-activated (HVA) insect calcium channel (Ca(v)) currents. This block occurred in the absence of alterations in the voltage-dependence of Ca(v) channel activation, and was voltage-independent, suggesting that omega-ACTX-1 family toxins are pore blockers rather than gating modifiers. At a concentration of 1 microM omega-ACTX-Ar1a failed to significantly affect global K(v) channel currents. However, 1 microM omega-ACTX-Ar1a caused a modest 18% block of insect Na(v) channel currents, similar to the minor block of Na(v) channels reported for other insect Ca(v) channel blockers such as omega-agatoxin IVA. These findings validate both M-LVA and HVA Ca(v) channels as potential targets for insecticides.

  2. Selectivity Mechanism of the Voltage-gated Proton Channel, HV1

    Science.gov (United States)

    Dudev, Todor; Musset, Boris; Morgan, Deri; Cherny, Vladimir V.; Smith, Susan M. E.; Mazmanian, Karine; Decoursey, Thomas E.; Lim, Carmay

    2015-05-01

    Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp-Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O+ protonated the SF, breaking the Asp-Arg linkage and opening the conduction pathway, whereas Na+ or Cl- was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp-Lys SF behaved like the Asp-Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH0-H2O0-Arg+ interactions with hydronium but unfavorable Asp--X-/X+-Arg+ interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis, and signaling.

  3. Poorly selective cation channels in the apical membrane of A6 cells.

    Science.gov (United States)

    Van Driessche, W; De Smet, P; de Smedt, H

    1994-03-01

    This paper describes a Ca(2+)-blockable, poorly selective cation pathway in the apical membrane of A6 epithelia. This pathway has properties that resemble the cation-selective channels in the toad urinary bladder and frog skin. Transepithelial short circuit currents (Isc) and power density spectra (PDS) of the fluctuations in current were recorded. The basolateral surface of the tissues was exposed to Cl- or SO4(2-) solutions with Na+ as the major cation. Ca(2+)-blockable inward oriented currents and Lorentzian noise were recorded with isotonic (215 mosmol/kg) mucosal Cl- and hypotonic (144 mos-mol/kg serosal SO4(2-) solution with Na+, K+, Rb+ or Cs+ as the major mucosal cation. Experiments with mucosal K+ demonstrated that the cation-selective channel was markedly activated by serosal hypotonicity. Effects of an increased electrical driving force were excluded on the basis of the results obtained with microelectrode experiments and transepithelial voltage clamping. Cell volume expansion induced by isotonic replacements of serosal sucrose by glycerol or urea also activated the cation-selective pathway. Furthermore, the presence of Cl- in the mucosal solution was a prerequisite for a sustained response to hypotonicity or replacements of the organic compounds. Moreover, we found that the cation-selective channels are mainly expressed in the cells during the early period of epithelial growth.

  4. 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.

  5. Analysis of the selectivity filter of the voltage-gated sodium channel NavRh

    Institute of Scientific and Technical Information of China (English)

    Xu Zhang; Mengdie Xia; Yang Li; Huihui Liu; Xin Jiang; Wenlin Ren; Jianping Wu

    2013-01-01

    NaChBac is a bacterial voltage-gated sodium (Nav) channel that shows sequence similarity to voltage-gated calcium channels.To understand the ion-permeation mechanism of Nav channels,we combined molecular dynamics simulation,structural biology and electrophysiological approaches to investigate the recently determined structure of NavRh,a marine bacterial NaChBac ortholog.Two Na+ binding sites are identified in the selectivity filter (SF) in our simulations:The extracellular Na+ ion first approaches site 1 constituted by the side groups of Ser181 and Glu183,and then spontaneously arrives at the energetically more favorable site 2 formed by the carbonyi oxygens of Leu179 and Thr178.In contrast,Ca2+ ions are prone to being trapped by Glu183 at site 1,which then blocks the entrance of both Na+ and Ca2+ to the vestibule of the SF.In addition,Na+ permeates through the selective filter in an asymmetrical manner,a feature that resembles that of the mammalian Nav orthologs.The study reported here provides insights into the mechanism of ion selectivity on Na+ over Ca2+ in mammalian Nav channels.

  6. A Greedy Algorithm of Data-Dependent User Selection for Fast Fading Gaussian Vector Broadcast Channels

    CERN Document Server

    Takeuchi, Keigo

    2012-01-01

    User selection (US) with Zero-forcing beamforming (ZF-BF) is considered in fast fading Gaussian vector broadcast channels (VBCs) with perfect channel state information (CSI) at the transmitter. A novel criterion for US is proposed, which depends on both CSI and the data symbols, while the conventional criteria only depend on CSI. Since the optimization of US based on the proposed criterion is infeasible, a greedy algorithm of data-dependent US is proposed to perform the optimization approximately. An overhead issue arises in fast fading channels: On every update of US, the transmitter may inform each user whether he/she has been selected, using a certain fraction of resources. This overhead results in a significant rate loss for fast fading channels. In order to circumvent this overhead issue, iterative detection and decoding schemes are derived on the basis of belief propagation (BP). The proposed iterative schemes require no information about whether each user has been selected. The proposed US scheme is co...

  7. Identification of selective sweeps reveals divergent selection between Chinese Holstein and Simmental cattle populations

    DEFF Research Database (Denmark)

    Chen, Minhui; Pan, Dunfei; Ren, Hongyan;

    2016-01-01

    , including LRH, XP-EHH and FST, based on the Illumina 770K high-density single nucleotide polymorphism (SNP) array, to enable more comprehensive detection. RESULTS: We successfully constructed profiles of selective signals in both cattle populations. To further annotate these regions, we identified a set......-minor allele frequency bin, we found a higher proportion of low-FST SNPs in the exons of the bovine genome, which indicates strong purifying selection of the exons. CONCLUSIONS: The selection signatures identified in these two populations demonstrated positive selection pressure on a set of important genes...... with potential functions that are involved in many biological processes. We also demonstrated that in the bovine genome, exons were under strong purifying selection. Our findings provide insight into the mechanisms of artificial selection and will facilitate follow-up functional studies of potential candidate...

  8. Proline Scan of the hERG Channel S6 Helix Reveals the Location of the Intracellular Pore Gate

    Science.gov (United States)

    Thouta, Samrat; Sokolov, Stanislav; Abe, Yuki; Clark, Sheldon J.; Cheng, Yen M.; Claydon, Tom W.

    2014-01-01

    In Shaker-like channels, the activation gate is formed at the bundle crossing by the convergence of the inner S6 helices near a conserved proline-valine-proline motif, which introduces a kink that allows for electromechanical coupling with voltage sensor motions via the S4-S5 linker. Human ether-a-go-go-related gene (hERG) channels lack the proline-valine-proline motif and the location of the intracellular pore gate and how it is coupled to S4 movement is less clear. Here, we show that proline substitutions within the S6 of hERG perturbed pore gate closure, trapping channels in the open state. Performing a proline scan of the inner S6 helix, from Ile655 to Tyr667 revealed that gate perturbation occurred with proximal (I655P-Q664P), but not distal (R665P-Y667P) substitutions, suggesting that Gln664 marks the position of the intracellular gate in hERG channels. Using voltage-clamp fluorimetry and gating current analysis, we demonstrate that proline substitutions trap the activation gate open by disrupting the coupling between the voltage-sensing unit and the pore of the channel. We characterize voltage sensor movement in one such trapped-open mutant channel and demonstrate the kinetics of what we interpret to be intrinsic hERG voltage sensor movement. PMID:24606930

  9. EMG feature assessment for myoelectric pattern recognition and channel selection: a study with incomplete spinal cord injury.

    Science.gov (United States)

    Liu, Jie; Li, Xiaoyan; Li, Guanglin; Zhou, Ping

    2014-07-01

    Myoelectric pattern recognition with a large number of electromyogram (EMG) channels provides an approach to assessing motor control information available from the recorded muscles. In order to develop a practical myoelectric control system, a feature dependent channel reduction method was developed in this study to determine a small number of EMG channels for myoelectric pattern recognition analysis. The method selects appropriate raw EMG features for classification of different movements, using the minimum Redundancy Maximum Relevance (mRMR) and the Markov random field (MRF) methods to rank a large number of EMG features, respectively. A k-nearest neighbor (KNN) classifier was used to evaluate the performance of the selected features in terms of classification accuracy. The method was tested using 57 channels' surface EMG signals recorded from forearm and hand muscles of individuals with incomplete spinal cord injury (SCI). Our results demonstrate that appropriate selection of a small number of raw EMG features from different recording channels resulted in similar high classification accuracies as achieved by using all the EMG channels or features. Compared with the conventional sequential forward selection (SFS) method, the feature dependent method does not require repeated classifier implementation. It can effectively reduce redundant information not only cross different channels, but also cross different features in the same channel. Such hybrid feature-channel selection from a large number of EMG recording channels can reduce computational cost for implementation of a myoelectric pattern recognition based control system.

  10. Relay selection based on MAP estimation for cooperative communication with outdated channel state information

    Institute of Scientific and Technical Information of China (English)

    Ding Wenrui; Fei Li; Gao Qiang; Liu Shuo

    2013-01-01

    In this paper,we consider an amplify-and-forward (AF) cooperative communication system when the channel state information (CSI) used in relay selection differs from that during data transmission,i.e.,the CSI used in relay selection is outdated.The selected relay may not be actually the best for data transmission and the outage performance of the cooperative system will deteriorate.To improve its performance,we propose a relay selection strategy based on maximum a posteriori (MAP) estimation,where relay is selected based on predicted signal-to-noise ratio (SNR).To reduce the computation complexity,we approximate the a posteriori probability density of SNR and obtain a closed-form predicted SNR,and a relay selection strategy based on the approximate MAP estimation (RS-AMAP) is proposed.The simulation results show that this approximation leads to trivial performance loss from the perspective of outage probability.Compared with relay selection strategies given in the literature,the outage probability is reduced largely through RS-AMAP for medium-to-large transmitting powers and medium-to-high channel correlation coefficients.

  11. Selective modulation of cellular voltage dependent calcium channels by hyperbaric pressure - a suggested HPNS partial mechanism

    Directory of Open Access Journals (Sweden)

    Ben eAviner

    2014-05-01

    Full Text Available Professional deep sea divers experience motor and cognitive impairment, known as High Pressure Neurological Syndrome (HPNS, when exposed to pressures of 100 msw (1.1MPa and above, considered to be the result of synaptic transmission alteration. Previous studies have indicated modulation of presynaptic Ca2+ currents at high pressure. We directly measured for the first time pressure effects on the currents of voltage dependent Ca2+ channels (VDCCs expressed in Xenopus oocytes. Pressure selectivity augmented the current in CaV1.2 and depressed it in CaV3.2 channels. Pressure application also affected the channels' kinetics, such as ƮRise, ƮDecay. Pressure modulation of VDCCs seems to play an important role in generation of HPNS signs and symptoms.

  12. Ultra-Wideband Channel Sounder – Design, Construction and Selected Applications

    Directory of Open Access Journals (Sweden)

    R. Zetik

    2013-06-01

    Full Text Available The paper describes construction, design, and application of a real-time ultra-wideband channel sounder. Its specific architecture allows measurements of time-variant radio propagation channels in different frequency bands. The sounder’s stimulation signal is the maximum length binary sequence. Synchronous multi-channel operation is supported by its excellent timing stability and by its low power consumption of miniature sized low temperature co-fired ceramics modules that comprise custom integrated SiGe circuits. This is a prerequisite to build a multiple-input-multiple-output sounder which is suitable for sounding even in distributed scenarios such as sensor networks. Selected application examples demonstrated the performance and possibilities of the sounder.

  13. Complexity-reduced ICI cancellation for OFDM system over doubly-selective channels

    Institute of Scientific and Technical Information of China (English)

    Xi Xiaoping; Zhang Can

    2009-01-01

    In doubly-selective fading wireless channel, the conventional orthogonal frequency division multiplexing (OFDM) receivers for inter-carrier interference (ICI) compensation require extensive computations. To obtain an effective balance between performance and complexity, the whole channel response matrix was decomposed into a sequence of submatrix, and then a novel equalizer based on minimum mean square error (MMSE) criterion was presented to combat the ICI. Furthermore, a simple ordering-based decision-feedback equalizer (DFE) was derived to exploit the temperal diversity gain offered by mobile channels. Numerical studies illustrate that although the MMSE equalizer still suffers from error floor, whereas the DFE equalizer exhibits significant performance improvement. The advantage of the proposed scheme indicates its potential applications in the future broadband wireless systems.

  14. Key Generation in Wireless Sensor Networks Based on Frequency-selective Channels - Design, Implementation, and Analysis

    CERN Document Server

    Wilhelm, Matthias; Schmitt, Jens B

    2010-01-01

    Key management in wireless sensor networks faces several new challenges. The scale, resource limitations, and new threats such as node capture necessitate the use of an on-line key generation by the nodes themselves. However, the cost of such schemes is high since their secrecy is based on computational complexity. Recently, several research contributions justified that the wireless channel itself can be used to generate information-theoretic secure keys. By exchanging sampling messages during movement, a bit string can be derived that is only known to the involved entities. Yet, movement is not the only possibility to generate randomness. The channel response is also strongly dependent on the frequency of the transmitted signal. In our work, we introduce a protocol for key generation based on the frequency-selectivity of channel fading. The practical advantage of this approach is that we do not require node movement. Thus, the frequent case of a sensor network with static motes is supported. Furthermore, the...

  15. 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.

  16. Krebs cycle metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry.

    Science.gov (United States)

    Wu, Fei; Minteer, Shelley

    2015-02-02

    It has been hypothesized that the high metabolic flux in the mitochondria is due to the self-assembly of enzyme supercomplexes (called metabolons) that channel substrates from one enzyme to another, but there has been no experimental confirmation of this structure or the channeling. A structural investigation of enzyme organization within the Krebs cycle metabolon was accomplished by in vivo cross-linking and mass spectrometry. Eight Krebs cycle enzyme components were isolated upon chemical fixation, and interfacial residues between mitochondrial malate dehydrogenase, citrate synthase, and aconitase were identified. Using constraint protein docking, a low-resolution structure for the three-enzyme complex was achieved, as well as the two-fold symmetric octamer. Surface analysis showed formation of electrostatic channeling upon protein-protein association, which is the first structural evidence of substrate channeling in the Krebs cycle metabolon.

  17. 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.

  18. Promoter Methylation Analysis Reveals that KCNA5 Ion Channel Silencing Supports Ewing Sarcoma Cell Proliferation

    Science.gov (United States)

    Ryland, Katherine E; Hawkins, Allegra G.; Weisenberger, Daniel J.; Punj, Vasu; Borinstein, Scott C.; Laird, Peter W.; Martens, Jeffrey R.; Lawlor, Elizabeth R.

    2015-01-01

    Polycomb proteins are essential regulators of gene expression in stem cells and development. They function to reversibly repress gene transcription via post-translational modification of histones and chromatin compaction. In many human cancers, genes that are repressed by polycomb in stem cells are subject to more stable silencing via DNA methylation of promoter CpG islands. Ewing sarcoma is an aggressive bone and soft tissue tumor that is characterized by over-expression of polycomb proteins. This study investigates the DNA methylation status of polycomb target gene promoters in Ewing sarcoma tumors and cell lines and observes that the promoters of differentiation genes are frequent targets of CpG-island DNA methylation. In addition, the promoters of ion channel genes are highly differentially methylated in Ewing sarcoma compared to non-malignant adult tissues. Ion channels regulate a variety of biological processes, including proliferation, and dysfunction of these channels contributes to tumor pathogenesis. In particular, reduced expression of the voltage-gated Kv1.5 channel has been implicated in tumor progression. These data show that DNA methylation of the KCNA5 promoter contributes to stable epigenetic silencing of Kv1.5 channel. This epigenetic repression is reversed by exposure to the DNA methylation inhibitor decitabine, which inhibits Ewing sarcoma cell proliferation through mechanisms that include restoration of Kv1.5 channel function. Implications This study demonstrates that promoters of ion channels are aberrantly methylated in Ewing sarcoma and that epigenetic silencing of KCNA5 contributes to tumor cell proliferation, thus providing further evidence of the importance of ion channel dyregulation to tumorigenesis. PMID:26573141

  19. Functional mutagenesis screens reveal the 'cap structure' formation in disulfide-bridge free TASK channels.

    Science.gov (United States)

    Goldstein, Matthias; Rinné, Susanne; Kiper, Aytug K; Ramírez, David; Netter, Michael F; Bustos, Daniel; Ortiz-Bonnin, Beatriz; González, Wendy; Decher, Niels

    2016-01-22

    Two-pore-domain potassium (K2P) channels have a large extracellular cap structure formed by two M1-P1 linkers, containing a cysteine for dimerization. However, this cysteine is not present in the TASK-1/3/5 subfamily. The functional role of the cap is poorly understood and it remained unclear whether K2P channels assemble in the domain-swapped orientation or not. Functional alanine-mutagenesis screens of TASK-1 and TRAAK were used to build an in silico model of the TASK-1 cap. According to our data the cap structure of disulfide-bridge free TASK channels is similar to that of other K2P channels and is most likely assembled in the domain-swapped orientation. As the conserved cysteine is not essential for functional expression of all K2P channels tested, we propose that hydrophobic residues at the inner leaflets of the cap domains can interact with each other and that this way of stabilizing the cap is most likely conserved among K2P channels.

  20. 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.

  1. Selecting participants for listening tests of multi-channel reproduced sound

    DEFF Research Database (Denmark)

    Wickelmaier, Florian; Choisel, Sylvain

    2005-01-01

    , 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......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......, 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....

  2. Possible roles of exceptionally conserved residues around the selectivity filters of sodium and calcium channels.

    Science.gov (United States)

    Tikhonov, Denis B; Zhorov, Boris S

    2011-01-28

    In the absence of x-ray structures of sodium and calcium channels their homology models are used to rationalize experimental data and design new experiments. A challenge is to model the outer-pore region that folds differently from potassium channels. Here we report a new model of the outer-pore region of the NaV1.4 channel, which suggests roles of highly conserved residues around the selectivity filter. The model takes from our previous study (Tikhonov, D. B., and Zhorov, B. S. (2005) Biophys. J. 88, 184-197) the general disposition of the P-helices, selectivity filter residues, and the outer carboxylates, but proposes new intra- and inter-domain contacts that support structural stability of the outer pore. Glycine residues downstream from the selectivity filter are proposed to participate in knob-into-hole contacts with the P-helices and S6s. These contacts explain the adapted tetrodotoxin resistance of snakes that feed on toxic prey through valine substitution of isoleucine in the P-helix of repeat IV. Polar residues five positions upstream from the selectivity filter residues form H-bonds with the ascending-limb backbones. Exceptionally conserved tryptophans are engaged in inter-repeat H-bonds to form a ring whose π-electrons would facilitate passage of ions from the outer carboxylates to the selectivity filter. The outer-pore model of CaV1.2 derived from the NaV1.4 model is also stabilized by the ring of exceptionally conservative tryptophans and H-bonds between the P-helices and ascending limbs. In this model, the exceptionally conserved aspartate downstream from the selectivity-filter glutamate in repeat II facilitates passage of calcium ions to the selectivity-filter ring through the tryptophan ring. Available experimental data are discussed in view of the models.

  3. Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle.

    Directory of Open Access Journals (Sweden)

    Ting Zhang

    Full Text Available Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs. In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs precontracted with acetylcholine (ACH. In the presence of nifedipine (10 µM, ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs, and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs were blocked by chloroquine. Pyrazole 3 (Pyr3, an inhibitor of transient receptor potential C3 (TRPC3 channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.

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

    CERN Document Server

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

    2013-01-01

    We use Brownian dynamics simulations to study the permeation properties of a generic electrostatic model of a biological ion channel as a function of the fixed charge Q_f at its selectivity filter. We reconcile the recently-discovered discrete calcium conduction bands M0 (Q_f=1e), M1 (3e), M2 (5e) with the set of sodium conduction bands L0 (0.5-0.7e), L1 (1.5-2e) thereby obtaining a completed pattern of conduction and selectivity bands v Q_f for the sodium-calcium channels family. An increase of Q_f leads to an increase of calcium selectivity: L0 (sodium selective, non-blocking channel) -> M0 (non-selective channel) -> L1 (sodium selective channel with divalent block) -> M1 (calcium selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L1 band is identified with the eukaryotic (DEKA) sodium channel, and L0 (speculatively) with the bacterial NaChBac channel. The scheme created is able to account for the experimentally observed mutation-induced ...

  5. Secured Communication over Frequency-Selective Fading Channels: a practical Vandermonde precoding

    CERN Document Server

    Kobayashi, Mari; Shamai, Shlomo

    2009-01-01

    In this paper, we study the frequency-selective broadcast channel with confidential messages (BCC) in which 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 (MIMO) channels, we propose a practical Vandermonde precoding that consists of projecting 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, i.e. the rate-tuple of the common and confidential messages, and characterize the optimal covariance inputs for some special cases of interest. It is proved that the proposed scheme achieves the optimal degree of freedom (d.o.f) region. More specifically, it enables to send l <= L confidential messages and N-l common mes...

  6. 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.

  7. Precoded OFDM System for ICI Mitigation over Time-Frequency Selective Fading Channels

    Institute of Scientific and Technical Information of China (English)

    LONG Yi; KUANG Linling; LU Jianhua

    2009-01-01

    In orthogonal frequency-division multiplexing (OFDM) systems, the capability to support high mo-bility is greatly limited by the intercarrier interference (ICI) caused by time-frequency selective fading chan-nels. This paper presents a precoded OFDM system for ICI mitigation. A precoder is introduced to relieve the ICI by transmitting N-point composite information symbols at twice the subcarrier interval. A Ha-damard-matrix-like pilot pattern is used to recover the composite information symbols in a postprocessor at the receiver. Simulations show that, compared to the conventional self-cancellation scheme, this scheme gives much better signal-to-interference-noise ratio performance with much less overhead. Furthermore, the scheme can support twice the vehicle speed in time-frequency selective fading channels than the standard OFDM systems without ICI mitigation.

  8. 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.

  9. Applying Theoretical Approach for Predicting the Selective Calcium Channel Blockers Pharmacological Parameter by Biopartitioning Micellar Chromatography

    Institute of Scientific and Technical Information of China (English)

    WANG Su-Min; YANG Geng-Liang; LI Zhi-Wei; LIU Hai-Yan; GUO Hui-Juan

    2006-01-01

    The usefulness of biopartitioning micellar chromatography (BMC) for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model (an LD50 model) and the second order polynomial models (apparent bioavailability model) have been obtained using the retention data of the selective calcium channel blockers to predict pharmacological properties of compounds. The use of BMC is simple, reproducible and can provide key information about the acute toxicity and transport properties of new compounds during the drug discovery process.

  10. Distributed Channel Selection in CRAHNs with Heterogeneous Spectrum Opportunities: A Local Congestion Game Approach

    Science.gov (United States)

    Xu, Yuhua; Wu, Qihui; Wang, Jinlong; Min, Neng; Anpalagan, Alagan

    This letter investigates the problem of distributed channel selection in cognitive radio ad hoc networks (CRAHNs) with heterogeneous spectrum opportunities. Firstly, we formulate this problem as a local congestion game, which is proved to be an exact potential game. Then, we propose a spatial best response dynamic (SBRD) to rapidly achieve Nash equilibrium via local information exchange. Moreover, the potential function of the game reflects the network collision level and can be used to achieve higher throughput.

  11. Properties of Hydrated Alkali Metals Aimed at the Ion Channel Selectivity

    Institute of Scientific and Technical Information of China (English)

    AN Hai-Long; LIU Yu-Zhi; ZHANG Su-Hua; ZHAN Yong; ZHANG Hai-Lin

    2008-01-01

    The hydration structure properties of different alkali metal ions with eight water molecules and potassium ions with different numbers of water molecules are studied using the mixed density functional theory, B3LYP, with 6-311G basis set. The hydration structures are obtained from structure optimization and the optimum numbers of water molecules in the innermost hydration shell for the alkali metal ions are found. Some useful information about the ion channel selectivity is presented.

  12. Spreading Code Assignment Strategies for MIMO-CDMA Systems Operating in Frequency-Selective Channels

    Directory of Open Access Journals (Sweden)

    Dahmane AdelOmar

    2009-01-01

    Full Text Available Abstract Code Division Multiple Access (CDMA and multiple input multiple output- (MIMO- CDMA systems suffer from multiple access interference (MAI which limits the spectral efficiency of these systems. By making these systems more power efficient, we can increase the overall spectral efficiency. This can be achieved through the use of improved modulation and coding techniques. Conventional MIMO-CDMA systems use fixed spreading code assignments. By strategically selecting the spreading codes as a function of the data to be transmitted, we can achieve coding gain and introduce additional degrees of freedom in the decision variables at the output of the matched filters. In this paper, we examine the bit error rate performance of parity bit-selected spreading and permutation spreading under different wireless channel conditions. A suboptimal detection technique based on maximum likelihood detection is proposed for these systems operating in frequency selective channels. Simulation results demonstrate that these code assignment techniques provide an improvement in performance in terms of bit error rate (BER while providing increased spectral efficiency compared to the conventional system. Moreover, the proposed strategies are more robust to channel estimation errors as well as spatial correlation.

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

    Directory of Open Access Journals (Sweden)

    Gelle Guillaume

    2004-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Recent (circa 1998 to 2011) channel-migration rates of selected streams in Indiana

    Science.gov (United States)

    Robinson, Bret A.

    2013-01-01

    An investigation was completed to document recent (circa 1998 to 2011) channel-migration rates at 970 meander bends along 38 of the largest streams in Indiana. Data collection was completed by using the Google Earth™ platform and, for each selected site, identifying two images with capture dates separated by multiple years. Within each image, the position of the meander-bend cutbank was measured relative to a fixed local landscape feature visible in both images, and an average channel-migration rate was calculated at the point of maximum cutbank displacement. From these data it was determined that 65 percent of the measured sites have recently been migrating at a rate less than 1 ft/yr, 75 percent of the sites have been migrating at a rate less than 10 ft/yr, and while some sites are migrating in excess of 20 ft/yr, these occurrences are rare. In addition, it is shown that recent channel-migration activity is not evenly distributed across Indiana. For the stream reaches studied, far northern and much of far southern Indiana are drained by streams that recently have been relatively stationary. At the same time, this study shows that most of the largest streams in west-central Indiana and many of the largest streams in east-central Indiana have shown significant channel-migration activity during the recent past. It is anticipated that these results will support several fluvial-erosion-hazard mitigation activities currently being undertaken in Indiana.

  16. Evidence for a common pharmacological interaction site on K(Ca)2 channels providing both selective activation and selective inhibition of the human K(Ca)2.1 subtype

    DEFF Research Database (Denmark)

    Hougaard, Charlotte; Hammami, Sofia; Eriksen, Birgitte L;

    2012-01-01

    ]pyrimidines, act either as activators or as inhibitors of the human K(Ca)2.1 channel. Whereas (-)-CM-TPMF activates K(Ca)2.1 with an EC(50) value of 24 nM, (-)-B-TPMF inhibits the channel with an IC(50) value of 31 nM. In contrast, their (+)-enantiomers are 40 to 100 times less active. Both (-)-CM-TPMF and (-)-B......-TPMF are subtype-selective, with 10- to 20-fold discrimination toward other K(Ca)2 channels and the K(Ca)3 channel. Coapplication experiments reveal competitive-like functional interactions between the effects of (-)-CM-TPMF and (-)-B-TPMF. Despite belonging to a different chemical class than GW542573X, the K(Ca)2......-TPMF is 10 times more potent on K(Ca)2.1 than NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime), an unselective but hitherto the most potent K(Ca)3/K(Ca)2 channel activator. (-)-B-TPMF is the first small-molecule inhibitor with significant selectivity among the K(Ca)2 channel subtypes. In contrast to peptide...

  17. Ryanodine Receptors Selectively Interact with L Type Calcium Channels in Mouse Taste Cells.

    Directory of Open Access Journals (Sweden)

    Michelle R Rebello

    Full Text Available WE REPORTED THAT RYANODINE RECEPTORS ARE EXPRESSED IN TWO DIFFERENT TYPES OF MAMMALIAN PERIPHERAL TASTE RECEPTOR CELLS: Type II and Type III cells. Type II cells lack voltage-gated calcium channels (VGCCs and chemical synapses. In these cells, ryanodine receptors contribute to the taste-evoked calcium signals that are initiated by opening inositol trisphosphate receptors located on internal calcium stores. In Type III cells that do have VGCCs and chemical synapses, ryanodine receptors contribute to the depolarization-dependent calcium influx.The goal of this study was to establish if there was selectivity in the type of VGCC that is associated with the ryanodine receptor in the Type III taste cells or if the ryanodine receptor opens irrespective of the calcium channels involved. We also wished to determine if the ryanodine receptors and VGCCs require a physical linkage to interact or are simply functionally associated with each other. Using calcium imaging and pharmacological inhibitors, we found that ryanodine receptors are selectively associated with L type VGCCs but likely not through a physical linkage.Taste cells are able to undergo calcium induced calcium release through ryanodine receptors to increase the initial calcium influx signal and provide a larger calcium response than would otherwise occur when L type channels are activated in Type III taste cells.

  18. Eigen-Based Transceivers for the MIMO Broadcast Channel With Semi-Orthogonal User Selection

    Science.gov (United States)

    Sun, Liang; McKay, Matthew R.

    2010-10-01

    This paper studies the sum rate performance of two low complexity eigenmode-based transmission techniques for the MIMO broadcast channel, employing greedy semi-orthogonal user selection (SUS). The first approach, termed ZFDPC-SUS, is based on zero-forcing dirty paper coding; the second approach, termed ZFBF-SUS, is based on zero-forcing beamforming. We first employ new analytical methods to prove that as the number of users K grows large, the ZFDPC-SUS approach can achieve the optimal sum rate scaling of the MIMO broadcast channel. We also prove that the average sum rates of both techniques converge to the average sum capacity of the MIMO broadcast channel for large K. In addition to the asymptotic analysis, we investigate the sum rates achieved by ZFDPC-SUS and ZFBF-SUS for finite K, and show that ZFDPC-SUS has significant performance advantages. Our results also provide key insights into the benefit of multiple receive antennas, and the effect of the SUS algorithm. In particular, we show that whilst multiple receive antennas only improves the asymptotic sum rate scaling via the second-order behavior of the multi-user diversity gain; for finite K, the benefit can be very significant. We also show the interesting result that the semi-orthogonality constraint imposed by SUS, whilst facilitating a very low complexity user selection procedure, asymptotically does not reduce the multi-user diversity gain in either first (log K) or second-order (loglog K) terms.

  19. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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.

  2. A Concatenated ML Decoder for ST/SFBC-OFDM Systems in Double Selective Fading Channels

    Institute of Scientific and Technical Information of China (English)

    李明齐; 张文军

    2004-01-01

    This paper presented a concatenated maximum-likelihood (ML) decoder for space-time/space-frequency block coded orthogonal frequency diversion multiplexing (ST/SFBC-OFDM) systems in double selective fading channels. The proposed decoder first detects space-time or space-frequency codeword elements separately. Then, according to the coarsely estimated codeword elements, the ML decoding is performed in a smaller constellation element set to searching final codeword. It is proved that the proposed decoder has optimal performances if and only if subchannels are constant during a codeword interval. The simulation results show that the performances of proposed decoder is close to that of the optimal ML decoder in severe Doppler and delay spread channels. However, the complexity of proposed decoder is much lower than that of the optimal ML decoder.

  3. Putative resolution of the EEEE selectivity paradox in L-type Ca2+ and bacterial Na+ biological ion channels

    Science.gov (United States)

    Kaufman, I. Kh; Luchinsky, D. G.; Gibby, W. A. T.; McClintock, P. V. E.; Eisenberg, R. S.

    2016-05-01

    The highly selective permeation of ions through biological ion channels can be described and explained in terms of fluctuational dynamics under the influence of powerful electrostatic forces. Hence valence selectivity, e.g. between Ca2+ and Na+ in calcium and sodium channels, can be described in terms of ionic Coulomb blockade, which gives rise to distinct conduction bands and stop-bands as the fixed negative charge Q f at the selectivity filter of the channel is varied. This picture accounts successfully for a wide range of conduction phenomena in a diversity of ion channels. A disturbing anomaly, however, is that what appears to be the same electrostatic charge and structure (the so-called EEEE motif) seems to select Na+ conduction in bacterial channels but Ca2+ conduction in mammalian channels. As a possible resolution of this paradox it is hypothesised that an additional charged protein residue on the permeation path of the mammalian channel increases |{{Q}f}| by e, thereby altering the selectivity from Na+ to Ca2+. Experiments are proposed that will enable the hypothesis to be tested.

  4. Fractionation of a herbal antidiarrheal medicine reveals eugenol as an inhibitor of Ca2+-Activated Cl- channel TMEM16A.

    Directory of Open Access Journals (Sweden)

    Zhen Yao

    Full Text Available The Ca(2+-activated Cl(- channel TMEM16A is involved in epithelial fluid secretion, smooth muscle contraction and neurosensory signaling. We identified a Thai herbal antidiarrheal formulation that inhibited TMEM16A Cl(- conductance. C18-reversed-phase HPLC fractionation of the herbal formulation revealed >98% of TMEM16A inhibition activity in one out of approximately 20 distinct peaks. The purified, active compound was identified as eugenol (4-allyl-2-methoxyphenol, the major component of clove oil. Eugenol fully inhibited TMEM16A Cl(- conductance with single-site IC(50~150 µM. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl(- channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities.

  5. Effect of La3+ on myocardiac potassium channels revealed by patch-clamp technique

    Institute of Scientific and Technical Information of China (English)

    XUE Shaowu; YANG Pin

    2005-01-01

    The effect of La3+ on potassium channels in rat ventricular myocytes was investigated using the whole-cell patch-clamp recording mode. The Ca2+-independent voltage- activated outward K+ current was activated by the depolarizing pulse in enzymatically isolated rat ventricular myocytes. After addition of different concentrations La3+ to the bath solution, the outward K+ current was depressed gradually. The inhibition effect was in a concentration-dependent manner. The phenomena of the outward K+ current, being the main repolarizing current suppressed by La3+, suggest that the effect of lanthanides on myocardial function should be exploited further.

  6. A Non-orthogonal STFC-OFDM on Frequency-Selective Fading Channels

    Institute of Scientific and Technical Information of China (English)

    XUE Yi; JIANG Ling-ge; HE Chen

    2005-01-01

    A new non-orthogonal space-time-frequency code (STFC) was proposed. In conjunction with orthogonal frequency-division multiplexing (OFDM), it is appropriate for the application on frequency-selective fading channels. On the basis of the existing non-orthogonal STC, frequency diversity is studied and a new non-orthogonal STFC is further designed. Monte-Carlo simulations show that the non-orthogonal STFC-OFDM has the advantage of large diversity order, high bandwidth efficiency and better BER performance when compared with the orthogonal STC/STFC OFDM and non-orthogonal STC-OFDM systems.

  7. Complexity Iterative Receiver for Turbo-BLAST over Frequency Selective Fading Channels

    Institute of Scientific and Technical Information of China (English)

    DU Na; XU Da-zhuan

    2008-01-01

    The computationally efficient iterative receiver is investigated for Turbo-BLAST ( Bell Labs layered space time) system over frequency selective fading channels. Compared with the conventional receiver based on soft interference cancellation ( SIC), an iterative detection scheme based on bit-level cancellation is presented to reduce the complexity of the receiver by decomposing of an M-QAM constellation into a linear combination of binary constellations. Simulation results demonstrate that compared with the conventional SIC scheme, the proposed scheme based on bit-level cancellation performs almost as well as the SIC scheme after several iterations while proving a lot of saving in computational complexity.

  8. Eigen-Based Transceivers for the MIMO Broadcast Channel with Semi-Orthogonal User Selection

    CERN Document Server

    Sun, Liang

    2010-01-01

    This paper studies the sum rate performance of two low complexity eigenmode-based transmission techniques for the MIMO broadcast channel, employing greedy semi-orthogonal user selection (SUS). The first approach, termed ZFDPC-SUS, is based on zero-forcing dirty paper coding; the second approach, termed ZFBF-SUS, is based on zero-forcing beamforming. We first employ new analytical methods to prove that as the number of users K grows large, the ZFDPC-SUS approach can achieve the optimal sum rate scaling of the MIMO broadcast channel. We also prove that the average sum rates of both techniques converge to the average sum capacity of the MIMO broadcast channel for large K. In addition to the asymptotic analysis, we investigate the sum rates achieved by ZFDPC-SUS and ZFBF-SUS for finite K, and show that ZFDPC-SUS has significant performance advantages. Our results also provide key insights into the benefit of multiple receive antennas, and the effect of the SUS algorithm. In particular, we show that whilst multipl...

  9. Wavenumber selection for small-wavelength Goertler vortices in curved channel flows

    Science.gov (United States)

    Dando, Andrew; Hall, Philip

    1995-04-01

    The problem of wavenumber selection for fully nonlinear, small-wavelength Goertler vortices in a curved channel flow is considered. These types of Goertler vortices were first considered by Hall & Lakin (1988) for an external boundary layer flow. They proved particularly amenable to asymptotic description, it was possible to consider vortices large enough so that the mean flow correction driven by them is as large as the basic state, and this prompted the authors to consider them in a curved channel flow as an initial application of the phase-equation approach to Goertler vortices. This involves the assumption that the phase variable of these Goertler vortices varies on slow spanwise and time scales, then an analysis of both inside and outside the core region, to which vortex activity is restricted, leads to a system of partial differential equations which can be solved numerically for the wavenumber. The authors consider in particular the effect on the wavenumber of the outer channel wall varying on the same slow spanwise scale as the phase variable.

  10. Recombinant Expression and Functional Characterization of Martentoxin: A Selective Inhibitor for BK Channel (α + β4

    Directory of Open Access Journals (Sweden)

    Jie Tao

    2014-04-01

    Full Text Available Martentoxin (MarTX, a 37-residue peptide purified from the venom of East-Asian scorpion (Buthus martensi Karsch, was capable of blocking large-conductance Ca2+-activated K+ (BK channels. Here, we report an effective expression and purification approach for this toxin. The cDNA encoding martentoxin was expressed by the prokaryotic expression system pGEX-4T-3 which was added an enterokinase cleavage site by PCR. The fusion protein (GST-rMarTX was digested by enterokinase to release hetero-expressed toxin and further purified via reverse-phase HPLC. The molecular weight of the hetero-expressed rMarTX was 4059.06 Da, which is identical to that of the natural peptide isolated from scorpion venom. Functional characterization through whole-cell patch clamp showed that rMarTX selectively and potently inhibited the currents of neuronal BK channels (α + β4 (IC50 = 186 nM, partly inhibited mKv1.3, but hardly having any significant effect on hKv4.2 and hKv3.1a even at 10 μM. Successful expression of martentoxin lays basis for further studies of structure-function relationship underlying martentoxin or other potassium-channel specific blockers.

  11. Differences between main-channel and off-channel food webs in the upper Mississippi River revealed by fatty acid profiles of consumers

    Science.gov (United States)

    Larson, James H.; Bartsch, Michelle; Gutreuter, Steve; Knights, Brent C.; Bartsch, Lynn; Richardson, William B.; Vallazza, Jonathan M.; Arts, Michael T.

    2015-01-01

    Large river systems are often thought to contain a mosaic of patches with different habitat characteristics driven by differences in flow and mixing environments. Off-channel habitats (e.g., backwater areas, secondary channels) can become semi-isolated from main-channel water inputs, leading to the development of distinct biogeochemical environments. Observations of adult bluegill (Lepomis macrochirus) in the main channel of the Mississippi River led to speculation that the main channel offered superior food resources relative to off-channel areas. One important aspect of food quality is the quantity and composition of polyunsaturated fatty acids (PUFA). We sampled consumers from main-channel and backwater habitats to determine whether they differed in PUFA content. Main-channel individuals for relatively immobile species (young-of-year bluegill, zebra mussels [Dreissena polymorpha], and plain pocketbook mussels [Lampsilis cardium]) had significantly greater PUFA content than off-channel individuals. No difference in PUFA was observed for the more mobile gizzard shad (Dorsoma cepedianum), which may move between main-channel and off-channel habitats even at early life-history stages. As off-channel habitats become isolated from main-channel waters, flow and water column nitrogen decrease, potentially improving conditions for nitrogen-fixing cyanobacteria and vascular plants that, in turn, have low PUFA content. We conclude that main-channel food webs of the upper Mississippi River provide higher quality food resources for some riverine consumers as compared to food webs in off-channel habitats.

  12. COMPUTER AIDED DESIGN OF SELECTIVE CALCIUM CHANNEL BLOCKERS: USING PHARMACOPHORE - BASED AND DOCKING SIMULATIONS

    Directory of Open Access Journals (Sweden)

    Reetu

    2012-03-01

    Full Text Available In the present study, 3-D QSAR analysis was performed on the previously synthesized and evaluated derivatives of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers. Calcium Channel blockers is the molecular target responsible for the treatment of neuropathic and inflammatory pain. The 3D-QSAR study based on the principle of the alignment of pharmacophoric features by PHASE module of Schrodinger suite has been carried out on the same set of calcium channel blockers. Statistically significant 3-D QSAR model (R2=0.9288 were generated using 21 molecules in the training set. The predictive ability of model was determined using a randomly chosen test set of 6 molecules which gave predictive correlation coefficients (R2pred of 0.946 for 3-D models, indicating good predictive power. PHASE pharmacophore hypothesis AAHR.13 may correspond very closely to the interactions recorded in the active site of the ligand bound complex. These studies produced models with high correlation coefficient and good predictive abilities. Docking studies were also carried out wherein these analogues were docked into the active sites of COX-2 to analyze the receptor-ligand interactions that confer selectivity for COX-2. Compound 2 have the highest dock score (-7.28. In the active site, there are some strong hydrogen-bonding interactions observed between residues GLU67, ALA103, ASP96, SER184 and ASP22. Additionally a correlation of the quantitative structure –activity relationship data and the docking results is found to validate each other and suggest the importance of the binding step in overall drug action.

  13. Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity

    Directory of Open Access Journals (Sweden)

    Piotr Bregestovski

    2009-12-01

    Full Text Available This review briefly discusses the main approaches for monitoring chloride (Cl−, the most abundant physiological anion. Noninvasive monitoring of intracellular Cl− ([Cl−]i is a challenging task owing to two main difficulties: (i the low transmembrane ratio for Cl−, approximately 10:1; and (ii the small driving force for Cl−, as the Cl− reversal potential (ECl is usually close to the resting potential of the cells. Thus, for reliable monitoring of intracellular Cl−, one has to use highly sensitive probes. From several methods for intracellular Cl− analysis, genetically encoded chloride indicators represent the most promising tools. Recent achievements in the development of genetically encoded chloride probes are based on the fact that yellow fluorescent protein (YFP exhibits Cl−-sensitivity. YFP-based probes have been successfully used for quantitative analysis of Cl− transport in different cells and for high-throughput screening of modulators of Cl−-selective channels. Development of a ratiometric genetically encoded probe, Clomeleon, has provided a tool for noninvasive estimation of intracellular Cl− concentrations. While the sensitivity of this protein to Cl− is low (EC50 about 160 mM, it has been successfully used for monitoring intracellular Cl− in different cell types. Recently a CFP–YFP-based probe with a relatively high sensitivity to Cl− (EC50 about 30 mM has been developed. This construct, termed Cl-Sensor, allows ratiometric monitoring using the fluorescence excitation ratio. Of particular interest are genetically encoded probes for monitoring of ion channel distribution and activity. A new molecular probe has been constructed by introducing into the cytoplasmic domain of the Cl−-selective glycine receptor (GlyR channel the CFP–YFP-based Cl-Sensor. This construct, termed BioSensor-GlyR, has been successfully expressed in cell lines. The new genetically encoded chloride probes offer means of screening

  14. Frequency-Shift Zero-Forcing Time-Varying Equalization for Doubly Selective SIMO Channels

    Directory of Open Access Journals (Sweden)

    Verde Francesco

    2006-01-01

    Full Text Available This paper deals with the problem of designing linear time-varying (LTV finite-impulse response zero-forcing (ZF equalizers for time- and frequency-selective (so-called doubly selective single-input multiple-output (SIMO channels. Specifically, relying on a basis expansion model (BEM of the rapidly time-varying channel impulse response, we derive the canonical frequency-domain representation of the minimal norm LTV-ZF equalizer, which allows one to implement it as a parallel bank of linear time-invariant filters having, as input signals, different frequency-shift (FRESH versions of the received data. Moreover, on the basis of this FRESH representation, we propose a simple and effective low-complexity version of the minimal norm LTV-ZF equalizer and we discuss the relationships between the devised FRESH equalizers and a LTV-ZF equalizer recently proposed in the literature. The performance analysis, carried out by means of computer simulations, shows that the proposed FRESH-LTV-ZF equalizers significantly outperform their competitive alternative.

  15. Crystal structure of Caulobacter crescentus polynucleotide phosphorylase reveals a mechanism of RNA substrate channelling and RNA degradosome assembly.

    Science.gov (United States)

    Hardwick, Steven W; Gubbey, Tobias; Hug, Isabelle; Jenal, Urs; Luisi, Ben F

    2012-04-01

    Polynucleotide phosphorylase (PNPase) is an exoribonuclease that cleaves single-stranded RNA substrates with 3'-5' directionality and processive behaviour. Its ring-like, trimeric architecture creates a central channel where phosphorolytic active sites reside. One face of the ring is decorated with RNA-binding K-homology (KH) and S1 domains, but exactly how these domains help to direct the 3' end of single-stranded RNA substrates towards the active sites is an unsolved puzzle. Insight into this process is provided by our crystal structures of RNA-bound and apo Caulobacter crescentus PNPase. In the RNA-free form, the S1 domains adopt a 'splayed' conformation that may facilitate capture of RNA substrates. In the RNA-bound structure, the three KH domains collectively close upon the RNA and direct the 3' end towards a constricted aperture at the entrance of the central channel. The KH domains make non-equivalent interactions with the RNA, and there is a marked asymmetry within the catalytic core of the enzyme. On the basis of these data, we propose that structural non-equivalence, induced upon RNA binding, helps to channel substrate to the active sites through mechanical ratcheting. Structural and biochemical analyses also reveal the basis for PNPase association with RNase E in the multi-enzyme RNA degradosome assembly of the α-proteobacteria.

  16. 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.

  17. A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue.

    Science.gov (United States)

    Li, Wei; Feng, Zhaoyang; Sternberg, Paul W; Xu, X Z Shawn

    2006-03-30

    The nematode Caenorhabditis elegans is commonly used as a genetic model organism for dissecting integration of the sensory and motor systems. Despite extensive genetic and behavioural analyses that have led to the identification of many genes and neural circuits involved in regulating C. elegans locomotion behaviour, it remains unclear whether and how somatosensory feedback modulates motor output during locomotion. In particular, no stretch receptors have been identified in C. elegans, raising the issue of whether stretch-receptor-mediated proprioception is used by C. elegans to regulate its locomotion behaviour. Here we have characterized TRP-4, the C. elegans homologue of the mechanosensitive TRPN channel. We show that trp-4 mutant worms bend their body abnormally, exhibiting a body posture distinct from that of wild-type worms during locomotion, suggesting that TRP-4 is involved in stretch-receptor-mediated proprioception. We show that TRP-4 acts in a single neuron, DVA, to mediate its function in proprioception, and that the activity of DVA can be stimulated by body stretch. DVA both positively and negatively modulates locomotion, providing a unique mechanism whereby a single neuron can fine-tune motor activity. Thus, DVA represents a stretch receptor neuron that regulates sensory-motor integration during C. elegans locomotion.

  18. Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain

    Directory of Open Access Journals (Sweden)

    Shifeng Wang

    2016-08-01

    Full Text Available The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1, a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC50 of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity.

  19. Multi-Input Multi-Output Fading Channel Equalization with Constellation Selection and Space-Time Precoders

    Directory of Open Access Journals (Sweden)

    Ankita Shukla

    2011-09-01

    Full Text Available We consider multiplexing systems in correlated multiple-input multiple-output (MIMO fading channels with equal power allocated to each transmit antenna. Under several constraints, the number and subset of transmit antennas together with the transmit symbol constellations are determined assuming knowledge of the channel correlation matrices. The maximum outage data rate of the SCR receiver is seen to be close to the outage channel capacity. Identification of the channel matrix is of main concern in wireless multiple input multiple output (MIMO systems. To maximize the SNR, the best way to utilize a MIMO system is to communicate on the top singular vectors of the channel matrix. In this paper we addresses t several issues and the problem of channel tracking and equalization for multi-input multi-output (MIMO time-varying frequency-selective channels. These channels model the effects of inter-symbol interference (ISI, co-channel interference (CCI, and noise. Via singular value decomposition (SVD analysis, the precoder is used to be shown to outperform the orthogonal frequency division multiplexing (OFDM precoder in bit-error-rate (BER, transmission rate, and receiver implementation.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Selective recognition and discrimination of water-soluble azo dyes by a seven-channel molecularly imprinted polymer sensor array.

    Science.gov (United States)

    Long, Zerong; Lu, Yi; Zhang, Mingliang; Qiu, Hongdeng

    2014-10-01

    A seven-channel molecularly imprinted polymer sensor array was prepared and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, UV-Vis spectroscopy, and nitrogen physisorption studies. The results revealed that the imprinted polymers have distinct-binding affinities from those of structurally similar azo dyes. Analysis of the UV-Vis spectral response patterns of the seven dye analytes against the imprinted polymer array suggested that the different selectivity patterns of the array were closely connected to the imprinting process. To evaluate the effectiveness of the array format, the binding of a series of analytes was individually measured for each of the seven polymers, made with different templates (including one control polymer synthesized without the use of a template). The response patterns of the array to the selected azo dyes were processed by canonical discriminant analysis. The results showed that the molecularly imprinted array was able to discriminate each analyte with 100% accuracy. Moreover, the azo dyes in two real samples, spiked chrysoidin in smoked bean curd extract and Fanta lime soda (containing tartrazine), were successfully classified by the array.

  2. Inhibition of T cell proliferation by selective block of Ca(2+)-activated K(+) channels

    DEFF Research Database (Denmark)

    Jensen, B S; Odum, Niels; Jorgensen, N K;

    1999-01-01

    T lymphocytes express a plethora of distinct ion channels that participate in the control of calcium homeostasis and signal transduction. Potassium channels play a critical role in the modulation of T cell calcium signaling, and the significance of the voltage-dependent K channel, Kv1.3, is well...... established. The recent cloning of the Ca(2+)-activated, intermediate-conductance K(+) channel (IK channel) has enabled a detailed investigation of the role of this highly Ca(2+)-sensitive K(+) channel in the calcium signaling and subsequent regulation of T cell proliferation. The role IK channels play in T...

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

    Directory of Open Access Journals (Sweden)

    Inbar Fijalkow

    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.

  4. Performance of a Cognitive Relay Network under AF Relay Selection Scheme with Imperfect Channel Estimation

    Directory of Open Access Journals (Sweden)

    B. Prasad

    2016-06-01

    Full Text Available In this paper outage performance of a secondary user (SU is evaluated under amplify and forward (AF relay selection scheme with an imperfect channel state information (CSIwhile sharing spectrum in an underlay cognitive radio network (CRN. In underlay, the SU coexists with primary user (PU in the same band provided the interference produced by SU at the PU receiver is below the interference threshold of PU which limits the transmission power of SU and coverage area. Relays help to improve the performance of SU in underlay. However relays are also constrained in transmit power due to interference constraint imposed by PU. Closed form expression of the outage probability of SU with maximum transmit power constraint of relay under imperfect CSI is derived. A scaling factor based power control is used for the SU transmitter and the relay in order to maintain the interference constraint at PU receiver due to imperfect CSI. The impact of different parameters viz. correlation coefficient, channel estimation error, tolerable interference threshold, number of relays and the maximum transmit power constraint of relay on SU performance is investigated. A MATLAB based test bed has also been developed to carry out simulation in order to validate the theoretical result.

  5. Osteoinduction of porous Ti implants with a channel structure fabricated by selective laser melting.

    Science.gov (United States)

    Fukuda, A; Takemoto, M; Saito, T; Fujibayashi, S; Neo, M; Pattanayak, Deepak K; Matsushita, T; Sasaki, K; Nishida, N; Kokubo, T; Nakamura, T

    2011-05-01

    Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 μm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5mm from the end of the implants. A distance of 5mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes.

  6. 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.

  7. Single-Tap Precoders and Decoders for Multiuser MIMO FBMC-OQAM Under Strong Channel Frequency Selectivity

    Science.gov (United States)

    Rottenberg, Francois; Mestre, Xavier; Horlin, Francois; Louveaux, Jerome

    2017-02-01

    The design of linear precoders or decoders for multiuser (MU) multiple-input multiple-output (MIMO) filterbank multicarrier (FBMC) modulations in the case of strong channel frequency selectivity is presented. The users and the base station (BS) communicate using space division multiple access (SDMA). The low complexity proposed solution is based on a single tap per-subcarrier precoding/decoding matrix at the base station (BS) in the downlink/uplink. As opposed to classical approaches that assume flat channel frequency selectivity at the subcarrier level, the BS does not make this assumption and takes into account the distortion caused by channel frequency selectivity. The expression of the FBMC asymptotic mean squared error (MSE) in the case of strong channel selectivity derived in earlier works is developed and extended. The linear precoders and decoders are found by optimizing the MSE formula under two design criteria, namely zero forcing (ZF) or minimum mean squared error (MMSE). Finally, simulation results demonstrate the performance of the optimized design. As long as the number of BS antennas is larger than the number of users, it is shown that those extra degrees of freedom can be used to compensate for the channel frequency selectivity.

  8. Contribution of a lysine residue in the first transmembrane segment to the selectivity filter region in the CFTR chloride channel.

    Science.gov (United States)

    Negoda, Alexander; El Hiani, Yassine; Cowley, Elizabeth A; Linsdell, Paul

    2017-02-21

    The anion selectivity and conductance of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel are determined predominantly by interactions between permeant anions and the narrow region of the channel pore. This narrow region has therefore been described as functioning as the "selectivity filter" of the channel. Multiple pore-lining transmembrane segments (TMs) have previously been shown to contribute to the selectivity filter region. However, little is known about the three-dimensional organization of this region, or how multiple TMs combine to determine its functional properties. In the present study we have used patch clamp recording to identify changes in channel function associated with the formation of disulfide cross-links between cysteine residues introduced into different TMs within the selectivity filter. Cysteine introduced at position L102 in TM1 was able to form disulfide bonds with F337C and T338C in TM6, two positions that are known to play key roles in determining anion permeation properties. Consistent with this proximal arrangement of L102, F337 and T338, different mutations at L102 altered anion selectivity and conductance properties in a way that suggests that this residue plays an important role in determining selectivity filter function, albeit a much lesser role than that of F337. These results suggest an asymmetric three-dimensional arrangement of the key selectivity filter region of the pore, as well as having important implications regarding the molecular mechanism of anion permeation.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. THE THEORETICAL BER PERFORMANCE ANALYSIS OF A COOPERATIVE DIVERSITY SCHEME IN FREQUENCY SELECTIVE FADING CHANNEL

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A novel cooperative diversity scheme based on Distributed Space-Time Block Coding and Multi-Carrier Code Division Multiple Access (DSTBC-MC-CDMA) is proposed which works well in frequency selective fading channels with multiple single-antenna users. And an analytical error model is established to describe the symbol decoding errors between interusers, based on which a close form expression for theoretical Bit Error Rate (BER) performance of the scheme is derived to analyze the influence of the interuser decoding errors on the BER performance of the scheme. Then simulation is complimented to verify the analytic result above, which also shows that the BER performance of DSTBC-MC-CDMA outgoes that of non-cooperative MC-CDMA with considerable gains. Furthermore, the simulations coincide with the theoretical results well.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel.

    Science.gov (United States)

    Amodeo, Giuseppe Federico; Scorciapino, Mariano Andrea; Messina, Angela; De Pinto, Vito; Ceccarelli, Matteo

    2014-01-01

    Voltage Dependent Anion-selective Channels (VDACs) are pore-forming proteins located in the outer mitochondrial membrane. They are responsible for the access of ions and energetic metabolites into the inner membrane transport systems. Three VDAC isoforms exist in mammalian, but their specific role is unknown. In this work we have performed extensive (overall ∼5 µs) Molecular Dynamics (MD) simulations of the human VDAC isoforms to detect structural and conformational variations among them, possibly related to specific functional roles of these proteins. Secondary structure analysis of the N-terminal domain shows a high similarity among the three human isoforms of VDAC but with a different plasticity. In particular, the N-terminal domain of the hVDAC1 is characterized by a higher plasticity, with a ∼20% occurrence for the 'unstructured' conformation throughout the folded segment, while hVDAC2, containing a peculiar extension of 11 amino acids at the N-terminal end, presents an additional 310-helical folded portion comprising residues 10' to 3, adhering to the barrel wall. The N-terminal sequences of hVDAC isoforms are predicted to have a low flexibility, with possible consequences in the dynamics of the human VDACs. Clear differences were found between hVDAC1 and hVDAC3 against hVDAC2: a significantly modified dynamics with possible important consequence on the voltage-gating mechanism. Charge distribution inside and at the mouth of the pore is responsible for a different preferential localization of ions with opposite charge and provide a valuable rationale for hVDAC1 and hVDAC3 having a Cl-/K+ selectivity ratio of 1.8, whereas hVDAC2 of 1.4. Our conclusion is that hVDAC isoforms, despite sharing a similar scaffold, have modified working features and a biological work is now requested to give evidence to the described dissimilarities.

  14. 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.

  15. Structure of the SthK carboxy-terminal region reveals a gating mechanism for cyclic nucleotide-modulated ion channels.

    Directory of Open Access Journals (Sweden)

    Divya Kesters

    Full Text Available Cyclic nucleotide-sensitive ion channels are molecular pores that open in response to cAMP or cGMP, which are universal second messengers. Binding of a cyclic nucleotide to the carboxyterminal cyclic nucleotide binding domain (CNBD of these channels is thought to cause a conformational change that promotes channel opening. The C-linker domain, which connects the channel pore to this CNBD, plays an important role in coupling ligand binding to channel opening. Current structural insight into this mechanism mainly derives from X-ray crystal structures of the C-linker/CNBD from hyperpolarization-activated cyclic nucleotide-modulated (HCN channels. However, these structures reveal little to no conformational changes upon comparison of the ligand-bound and unbound form. In this study, we take advantage of a recently identified prokaryote ion channel, SthK, which has functional properties that strongly resemble cyclic nucleotide-gated (CNG channels and is activated by cAMP, but not by cGMP. We determined X-ray crystal structures of the C-linker/CNBD of SthK in the presence of cAMP or cGMP. We observe that the structure in complex with cGMP, which is an antagonist, is similar to previously determined HCN channel structures. In contrast, the structure in complex with cAMP, which is an agonist, is in a more open conformation. We observe that the CNBD makes an outward swinging movement, which is accompanied by an opening of the C-linker. This conformation mirrors the open gate structures of the Kv1.2 channel or MthK channel, which suggests that the cAMP-bound C-linker/CNBD from SthK represents an activated conformation. These results provide a structural framework for better understanding cyclic nucleotide modulation of ion channels, including HCN and CNG channels.

  16. Rock infromation of the moon revealed by multi-channel microwave radiometer data

    Science.gov (United States)

    Hu, Guo-Ping; Zheng, Yong-Chun; Chan, Kwing Lam; Xu, Ao-Ao; This work is supported by Science and Technology Development Fund in Macao SAR 048/2012/A2 and 039/2013/A2, and the NSFC program (41490633). The CE data was supported by the Key Laboratory of Lunar and Deep Space Exploration (2013DP173157), National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012, China.

    2016-10-01

    Rock abundance on lunar surface is an important consideration for understanding the physical properties of the Moon. With the deeper penetration power of the microwave, data from Chang'E (CE) multichannel (3.0-, 7.8-, 19.35-, and 37-GHz) microwave radiometer (MRM) are used to constrain the rock distribution on the Moon. The contrasting thermo-physical properties between rocks and regolith fines cause multiple brightness temperature (TB) to be present within the field of view of CE microwave data. But these variations could be easily masked by the more significant effect of ilmenite on TB, especially in the mare regions which are rich in ilmenite.To highlight the rock effect in TB, the diurnal TB difference, which has the effect of enlarging the TB difference caused by the rock abundance and reducing the absolute error of the CE microwave data, is considered here. The rock information in TB data is distinguished from the ilmenite effect by comparing the diurnal TB difference with a statistical TB model of the mare regions which are relatively low in rock abundance. The employed statistical TB model is a polynomial fitting formula between the selected CE TB data from mare regions and the corresponding TiO2 content data from Clementine UVVIS data. The correlation coefficients of the polynomial fit between TB and TiO2 content are 0.94 at lunar daytime and 0.84 at lunar nighttime, respectively. This polynomial fit forms an approximated relationship between the TiO2 content and TB when rock abundance is zero, with a standard error determined from the regression procedure.Based on the TiO2 map retrieved from Clementine UVVIS data, the TB map that is deflated to a lower TiO2 content shows a distribution trend similar to the rock abundance map retrieved by LRO data, except for the mare regions at the nearside of the Moon. The bigger diurnal TB difference in the mare regions could be either caused by the rich ilmenite rocks or the smaller rocks which cannot be recognized by

  17. Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion alpha-toxins on sodium channels.

    Science.gov (United States)

    Gur, Maya; Kahn, Roy; Karbat, Izhar; Regev, Noa; Wang, Jinti; Catterall, William A; Gordon, Dalia; Gurevitz, Michael

    2011-10-07

    Neurotoxin receptor site-3 at voltage-gated Na(+) channels is recognized by various peptide toxin inhibitors of channel inactivation. Despite extensive studies of the effects of these toxins, their mode of interaction with the channel remained to be described at the molecular level. To identify channel constituents that interact with the toxins, we exploited the opposing preferences of LqhαIT and Lqh2 scorpion α-toxins for insect and mammalian brain Na(+) channels. Construction of the DIV/S1-S2, DIV/S3-S4, DI/S5-SS1, and DI/SS2-S6 external loops of the rat brain rNa(v)1.2a channel (highly sensitive to Lqh2) in the background of the Drosophila DmNa(v)1 channel (highly sensitive to LqhαIT), and examination of toxin activity on the channel chimera expressed in Xenopus oocytes revealed a substantial decrease in LqhαIT effect, whereas Lqh2 was as effective as at rNa(v)1.2a. Further substitutions of individual loops and specific residues followed by examination of gain or loss in Lqh2 and LqhαIT activities highlighted the importance of DI/S5-S6 (pore module) and the C-terminal region of DIV/S3 (gating module) of rNa(v)1.2a for Lqh2 action and selectivity. In contrast, a single substitution of Glu-1613 to Asp at DIV/S3-S4 converted rNa(v)1.2a to high sensitivity toward LqhαIT. Comparison of depolarization-driven dissociation of Lqh2 and mutant derivatives off their binding site at rNa(v)1.2a mutant channels has suggested that the toxin core domain interacts with the gating module of DIV. These results constitute the first step in better understanding of the way scorpion α-toxins interact with voltage-gated Na(+)-channels at the molecular level.

  18. Performance analysis of MC-2D-CDMA with orthogonal restore combination(ORC) over frequency selective channel

    Institute of Scientific and Technical Information of China (English)

    强蔚; 张中兆; 沙学军

    2002-01-01

    a method is proposed to improve the performance of MC-2D-CDMA in frequency selective fading channel. Each chip of spreading spectrum sequence is contained in two sub-carriers, so when fading is deep in one sub-carrier, the other will compensate and the performance of this model is improved in frequency selective channel. Orthogonal restore combination (ORC) is used to explain the method. Computer simulation is used to exam the relation of signal noise ratio (SNR) and probability of bit error (BER), and the number of subscribers and BER. Then performance is compared among MC-2D-CDMA, MC-DS-CDMA and MC-CDMA.

  19. Identification and characterization of a selective allosteric antagonist of human P2X4 receptor channels.

    Science.gov (United States)

    Ase, Ariel R; Honson, Nicolette S; Zaghdane, Helmi; Pfeifer, Tom A; Séguéla, Philippe

    2015-04-01

    P2X4 is an ATP-gated nonselective cation channel highly permeable to calcium. There is increasing evidence that this homomeric purinoceptor, which is expressed in several neuronal and immune cell types, is involved in chronic pain and inflammation. The current paucity of unambiguous pharmacological tools available to interrogate or modulate P2X4 function led us to pursue the search for selective antagonists. In the high-throughput screen of a compound library, we identified the phenylurea BX430 (1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea, molecular weight = 413), with antagonist properties on human P2X4-mediated calcium uptake. Patch-clamp electrophysiology confirmed direct inhibition of P2X4 currents by extracellular BX430, with submicromolar potency (IC50 = 0.54 µM). BX430 is highly selective, having virtually no functional impact on all other P2X subtypes, namely, P2X1-P2X3, P2X5, and P2X7, at 10-100 times its IC50. Unexpected species differences were noticed, as BX430 is a potent antagonist of zebrafish P2X4 but has no effect on rat and mouse P2X4 orthologs. The concentration-response curve for ATP on human P2X4 in the presence of BX430 shows an insurmountable blockade, indicating a noncompetitive allosteric mechanism of action. Using a fluorescent dye uptake assay, we observed that BX430 also effectively suppresses ATP-evoked and ivermectin-potentiated membrane permeabilization induced by P2X4 pore dilation. Finally, in single-cell calcium imaging, we validated its selective inhibitory effects on native P2X4 channels at the surface of human THP-1 cells that were differentiated into macrophages. In summary, this ligand provides a novel molecular probe to assess the specific role of P2X4 in inflammatory and neuropathic conditions, where ATP signaling has been shown to be dysfunctional.

  20. Transcriptome analysis reveals positive selection on the divergent between topmouth culter and zebrafish.

    Science.gov (United States)

    Ren, Li; Tan, Xing-Jun; Xiong, Ya-Feng; Xu, Kang; Zhou, Yi; Zhong, Huan; Liu, Yun; Hong, Yun-Han; Liu, Shao-Jun

    2014-12-01

    The topmouth culter (Erythroculter ilishaeformis) is a predatory cyprinid fish that distributes widely in the East Asia. Here we report the liver transcriptome in this organism as a model of predatory fish. Sequencing of 5 Gb raw reads led to 27,741 unigenes and produced 11,131 annotatable genes. A total of 7093 (63.7%) genes were found to have putative functions by gene ontology analysis. Importantly, a blast search revealed 4033 culter genes that were orthologous to the zebrafish. Extracted from 38 candidate positive selection genes, 4 genes exhibit strong positive selection based on the ratio of nonsynonymous (Ka) to synonymous substitutions (Ks). In addition, the four genes also indicated the strong positive selection by comparing them between blunt snout bream (Megalobrama amblycephala) and zebrafish. These genes were involved in activator of gene expression, metabolic processes and development. The transcriptome variation may be reflective of natural selection in the early life history of Cyprinidae. Based on Ks ratios, date of the separation between topmouth culter and zebrafish is approximately 64 million years ago. We conclude that natural selection acts in diversifying the genomes between topmouth culter and zebrafish.

  1. The selectivity of different external binding sites for quaternary ammonium ions in cloned potassium channels.

    Science.gov (United States)

    Jarolimek, W; Soman, K V; Brown, A M; Alam, M

    1995-09-01

    Tetraethylammonium (TEA) is thought to be the most effective quaternary ammonium (QA) ion blocker at the external site of K+ channels, and small changes to the TEA ion reduce its potency. To examine the properties of the external QA receptor, we applied a variety of QA ions to excised patches from human embryonic kidney cells or Xenopus oocytes transfected with the delayed rectifying K+ channels Kv 2.1 and Kv 3.1. In outside-out patches of Kv 3.1, the relative potencies were TEA > tetrapropylammonium (TPA) > tetrabutylammonium (TBA). In contrast to Kv 3.1, the relative potencies in Kv 2.1 were TBA > TEA > TPA. In Kv 3.1 and Kv 2.1, external tetrapentylammonium (TPeA) blocked K+ currents in a fast, reversible and, in contrast to TEA, time-dependent manner. The external binding of TPeA appeared to be voltage independent, unlike the effects of TPeA applied to inside-out patches. External n-alkyl-triethylammonium compounds (C8, C10 chain length) had a lower affinity than TEA in Kv 3.1, but a higher affinity than TEA in Kv 2.1. In Kv 3.1, the decrease in QA affinity was large when one or two methyl groups were substituted for ethyl groups in TEA, but minor when propyl groups replaced ethyl groups. Changes in the free energy of binding could be correlated to changes in the free energy of hydration of TEA derivatives calculated by continuum methodology. These results reveal a substantial hydrophobic component of external QA ion binding to Kv 2.1, and to a lesser degree to Kv 3.1, in addition to the generally accepted electrostatic interactions. The chain length of hydrophobic TEA derivatives affects the affinity for the hydrophobic binding site, whereas the hydropathy of QA ions determines the electrostatic interaction energy.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Xu, Yan; Furutani, Shogo; Ihara, Makoto; Ling, Yun; Yang, Xinling; Kai, Kenji; Hayashi, Hideo; Matsuda, Kazuhiko

    2015-01-01

    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.

  4. Double Space Time Transmit Diversity OFDM System with Antenna Shuffling in Spatial Correlated Frequency Selective MIMO Channels

    Science.gov (United States)

    Zhou, Liang; Shimizu, Masahiko

    In this paper, we study low complexity transceiver for double space time transmit diversity (DSTTD) and orthogonal frequency division multiplexing (OFDM) system with antenna shuffling. Firstly, we propose a novel antenna shuffling method based on the criterion of minimizing the condition number of channel correlation matrix. The condition number is an indicator about the quality of the channel. By selecting the minimum of condition number which has better channel quality, consequently, a linear detector with respect to this new channel may achieve better performance results. A low complexity variant of the condition number calculation is also proposed, and it is shown that this criterion can be reduced to the minimum mean square error (MMSE) based criterion. Furthermore, the weighted soft decision Viterbi decoding is applied to mitigate noise enhancement inherent to zero forcing (ZF) and MMSE linear receivers and improve error rate performance. Next, we propose an algorithm to reduce the amount of feedback by exploiting the fact that the channel frequency responses across OFDM subcarriers are correlated. In the proposed algorithm, subcarriers are clustered in blocks, which are allocated the same shuffling pattern with the largest number of the shuffling patterns in the cluster. This way, the signaling overhead can be reduced in comparison with each subcarrier based feedback. Extensive simulations show that the proposed techniques for DSTTD-OFDM system outperform other existing techniques under both uncorrelated and highly spatial correlated frequency selective MIMO fading channels.

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

    Directory of Open Access Journals (Sweden)

    Jennifer K Pirri

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

  6. SNC-80-induced preconditioning: selective activation of the mitochondrial adenosine triphosphate-gated potassium channel.

    Science.gov (United States)

    Fischbach, Peter S; Barrett, Terrance D; Reed, Nathan J; Lucchesi, Benedict R

    2003-05-01

    Pharmacologic preconditioning by delta-opioid agonists occurs via activation of an adenosine triphosphate (ATP)-gated potassium channel (I(KATP)). Opening of mitochondrial I(KATP) confers pharmacologic preconditioning whereas opening the sarcolemmal I(KATP) shortens action potential duration and is proarrhythmic. This study investigated whether SNC-80, a selective delta-opioid agonist, is associated with development of ventricular arrhythmia due to activation of I(KATP). Rabbit isolated hearts were subjected to 12 min of hypoxia and 40 min of reoxygenation after pretreatment with SNC-80 (1 microM, n = 6), pinacidil (1.25 microM, n = 12), or BMS-191095 (6.0 microM, n = 4). Nine additional hearts served as controls. The cytoprotective effects of SNC-80 at a concentration of 1 microM were confirmed using 30 min of regional ischemia followed by 120 min of reperfusion. Ventricular fibrillation (VF) developed in 11 of 12 pinacidil-treated hearts whereas none of the SNC-80-treated (zero of six) hearts developed VF (P SNC-80 reduced infarct size expressed as a percentage of the area at risk from 33 +/- 4% to 14 +/- 3% (P = 0.004) compared with control. SNC-80, which selectively activates the delta-opioid receptor, provided cytoprotection but did not induce VF after hypoxia reoxygenation. The results indicate that pinacidil-induced nonselective activation of I(KATP) results in proarrhythmia that is dependent on activation of the sarcolemmal I(KATP). Selectivity for the mitochondrial I(KATP) is necessary to prevent induction of a proarrhythmic state.

  7. Evaluation of agonist selectivity for the NMDA receptor ion channel in bilayer lipid membranes based on integrated single-channel currents.

    Science.gov (United States)

    Hirano, A; Sugawara, M; Umezawa, Y; Uchino, S; Nakajima-Iijima, S

    2000-06-01

    A new method for evaluating chemical selectivity of agonists to activate the N-methyl-D-aspartate (NMDA) receptor was presented by using typical agonists NMDA, L-glutamate and (2S, 3R, 4S)-2-(carboxycyclopropyl)glycine (L-CCG-IV) and the mouse epsilon1/zeta1 NMDA receptor incorporated in bilayer lipid membranes (BLMs) as an illustrative example. The method was based on the magnitude of an agonist-induced integrated single-channel current corresponding to the number of total ions passed through the open channel. The very magnitudes of the integrated single-channel currents were compared with the different BLMs as a new measure of agonist selectivity. The epsilon1/zeta1 NMDA receptor was partially purified from Chinese hamster ovary (CHO) cells expressing the epsilon1/zeta1 NMDA receptor and incorporated in BLMs formed by the tip-dip method. The agonist-induced integrated single-channel currents were obtained at 50 microM agonist concentration, where the integrated current for NMDA was shown to reach its saturated value. The obtained integrated currents were found to be (4.5 +/- 0.55) x 10(-13) C/s for NMDA, (5.8 +/- 0.72) x 10(-13) C/s for L-glutamate and (6.6 +/- 0.61) x 10(-13) C/s for L-CCG-IV, respectively. These results suggest that the agonist selectivity in terms of the total ion flux through the single epsilon1/zeta1 NMDA receptor is in the order of L-CCG-IV approximately = L-glutamate > NMDA.

  8. 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.

  9. Mouse sperm patch-clamp recordings reveal single Cl- channels sensitive to niflumic acid, a blocker of the sperm acrosome reaction.

    Science.gov (United States)

    Espinosa, F; de la Vega-Beltrán, J L; López-González, I; Delgado, R; Labarca, P; Darszon, A

    1998-04-10

    Ion channels lie at the heart of gamete signaling. Understanding their regulation will improve our knowledge of sperm physiology, and may lead to novel contraceptive strategies. Sperm are tiny (approximately 3 microm diameter) and, until now, direct evidence of ion channel activity in these cells was lacking. Using patch-clamp recording we document here, for the first time, the presence of cationic and anionic channels in mouse sperm. Anion selective channels were blocked by niflumic acid (NA) (IC50 = 11 microM). The blocker was effective also in inhibiting the acrosome reaction induced by the zona pellucida, GABA or progesterone. These observations suggest that Cl- channels participate in the sperm acrosome reaction in mammals.

  10. 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.

  11. 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.

  12. Exact Performance Analysis of Partial Relay Selection Based on Shadowing Side Information over Generalized Composite Fading Channels

    CERN Document Server

    Yilmaz, Ferkan

    2011-01-01

    Relay technology has recently gained great interest in millimeter wave (60 GHz or above) radio frequencies as a promising transmission technique improving the quality of service, providing high data rate, and extending the coverage area without additional transmit power in deeply shadowed wireless environments. The performance of relay-based systems depends considerably on which relay selection protocols are used. These protocols are typically using the channel side information (CSI). Specifically, the relay terminal (RT) is chosen among all available RTs by a centralized entity (CE) which receives all RTs' CSI via feedback channels. However, in the millimeter wave radio frequencies, the rate of the variation of the CSI is much higher than that of a classical system operating in 6 GHz frequencies under the same mobility conditions, which evidently results in a serious problem causing outdated (inaccurate) CSI for the relay selection protocol at the CE since the feedback channels have a backhaul / transmission...

  13. Distinct interactions of Na{sup +} and Ca{sup 2+} ions with the selectivity filter of the bacterial sodium channel Na{sub V}Ab

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Song, E-mail: song.ke@univie.ac.at [Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, UZA 2, A-1090 Vienna (Austria); Zangerl, Eva-Maria, E-mail: a0509032@unet.univie.ac.at [Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, UZA 2, A-1090 Vienna (Austria); Stary-Weinzinger, Anna, E-mail: anna.stary@univie.ac.at [Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, UZA 2, A-1090 Vienna (Austria)

    2013-01-25

    Highlights: ► Ca{sup 2+} translocates slowly in the filter, due to lack of “loose” knock-on mechanism. ► Identification of a high affinity binding site in Na{sub V}Ab selectivity filter. ► Changes of EEEE locus triggered by electrostatic interactions with Ca{sup 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{sub V}Ab (Arcobacter butzleri) differentiates between Na{sup +} and Ca{sup 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{sub CEN}) in the sodium channel selectivity filter.

  14. Wavelet Packet Feature Assessment for High-density Myoelectric Pattern Recognition and Channel Selection toward Stroke Rehabilitation

    Directory of Open Access Journals (Sweden)

    Dongqing Wang

    2016-11-01

    Full Text Available This study presented wavelet packet feature assessment of neural control information in paretic upper-limb muscles of stroke survivors for myoelectric pattern recognition, taking advantage of high-resolution time-frequency representations of surface electromyographic (EMG signals. On this basis, a novel channel selection method was developed by combining the Fisher's class separability index (FCSI and the sequential feedforward selection (SFS analyses, in order to determine a small number of appropriate EMG channels from original high-density EMG electrode array. The advantages of the wavelet packet features and the channel selection analyses were further illustrated by comparing with previous conventional approaches, in terms of classification performance when identifying 20 functional arm/hand movements implemented by 12 stroke survivors. This study offers a practical approach including paretic EMG feature extraction and channel selection that enables active myoelectric control of multiple degrees of freedom with paretic muscles. All these efforts will facilitate upper-limb dexterity restoration and improved stroke rehabilitation.

  15. Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations.

    Science.gov (United States)

    Cui, Yuanyuan; Yang, Fan; Cao, Xu; Yarov-Yarovoy, Vladimir; Wang, KeWei; Zheng, Jie

    2012-04-01

    The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-08-19

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

  17. Outage Performance of Cooperative Relay Selection with Multiple Source and Destination Antennas over Dissimilar Nakagami-m Fading Channels

    Science.gov (United States)

    Lee, Wooju; Yoon, Dongweon

    Cooperative relay selection, in which one of multiple relays is selected to retransmit the source signal to the destination, has received considerable attention in recent years, because it is a simple way to obtain cooperative diversity in wireless networks. The exact expression of outage probability for a decode-and-forward cooperative relay selection with multiple source and destination antennas over Rayleigh fading channels was recently derived in [9]. In this letter, we derive the exact expressions of outage probability and diversity-multiplexing tradeoff over independent and non-identically distributed Nakagami-m fading channels as an extension of [9]. We then analyze the effects of various parameters such as fading conditions, number of relays, and number of source and destination antennas on the outage probability.

  18. 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.

  19. 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.

  20. The effect of external divalent cations on spontaneous non-selective cation channel currents in rabbit portal vein myocytes.

    Science.gov (United States)

    Albert, A P; Large, W A

    2001-10-15

    1. The effects of external divalent cations on spontaneous single non-selective cation channel currents were studied in outside-out patches from rabbit portal vein smooth muscle cells in K+-free conditions. 2. In an external medium containing 1.5 mM Ca2+ (Ca2+o) the majority of spontaneous channel currents had a unitary conductance of 23 pS, reversal potential (Vr) of +10 mV and a low open probability (Po) at negative patch potentials. Some channels opened to a lower conductance state of about 13 pS suggesting that the cation channels have two conductance states. Open time and burst duration distributions could both be described by two exponentials with time constants of about of 1 ms and 7 ms for open times and 3 ms and 16 ms for burst durations. 3. In 0 Ca2+o the majority of spontaneous cation channels had a unitary conductance of 13 pS and Vr was shifted to +4 mV. Moreover the longer open time and longer burst duration time constants were both reduced to approximately half the values in 1.5 mM Ca2+o. 4. Compared to 0 Ca2+o the single channel currents in 3 microM and 100 microM Ca2+o had a 5- to 6-fold increase in Po which was accompanied by increases in both open times and burst durations. In 3 microM and 100 microM Ca2+o the unitary conductance of the single channel currents was between 22 and 26 pS. 5. At positive membrane potentials the single channel currents had an increased Po compared to negative potentials which was associated with increased open times and burst durations but these values were similar in 3 microM, 100 microM and 1.5 mM Ca2+o. 6. In 1.5 mM Sr2+o and 1.5 mM Ba2+o channels opened to the higher conductance state of about 22-25 pS and had a 3- to 7-fold greater Po than in 0 Ca2+o. 7. In conclusion, external divalent cations have marked effects on the unitary conductance and kinetic behaviour of non-selective cation channels in rabbit portal vein smooth muscle cells.

  1. Wavelet Packet Function Based RAKE/Adaptive Multichannel DFE for a WPMA System over Frequency Selective Rayleigh Fading Channels

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiaodong; BI Guangguo

    2001-01-01

    A wavelet packet function based multiple access (WPMA) system is developed in this paper to maximize capacity and improve receiver performance over frequency selective multipath fading channels. To design an efficient receiver that mitigates residual multiple access interference (MAI) and intersymbol interference, while improving received signal-to-interference and noise ratio (SINR) simultaneously on the uplink, a multichannel decision feedback equalizer (DFE) following a wavelet packet function based RAKE receiver is proposed. Simulation results show that, over GSM TU channels the developed receiver performs quite well if the power of each user is perfectly controlled or the space diversity combining (SDC) technique is applied.

  2. Tackling the Combined Effects of Reverberation and Masking Noise Using Ideal Channel Selection

    Science.gov (United States)

    Hazrati, Oldooz; Loizou, Philipos C.

    2012-01-01

    Purpose: In this article, a new signal-processing algorithm is proposed and evaluated for the suppression of the combined effects of reverberation and noise. Method: The proposed algorithm decomposes, on a short-term basis (every 20 ms), the reverberant stimuli into a number of channels and retains only a subset of the channels satisfying a…

  3. Heat transfer in plate heat exchanger channels: Experimental validation of selected correlation equations

    Directory of Open Access Journals (Sweden)

    Cieśliński Janusz T.

    2016-09-01

    Full Text Available This study is focused on experimental investigation of selected type of brazed plate heat exchanger (PHEx. The Wilson plot approach was applied in order to estimate heat transfer coefficients for the PHEx passages. The main aim of the paper was to experimentally check ability of several correlations published in the literature to predict heat transfer coefficients by comparison experimentally obtained data with appropriate predictions. The results obtained revealed that Hausen and Dittus-Boelter correlations underestimated heat transfer coefficient for the tested PHEx by an order of magnitude. The Aspen Plate code overestimated heat transfer coefficient by about 50%, while Muley-Manglik correlation overestimated it from 1% to 25%, dependent on the value of Reynolds number and hot or cold liquid side.

  4. T-type channels become highly permeable to sodium ions using an alternative extracellular turret region (S5-P) outside the selectivity filter.

    Science.gov (United States)

    Senatore, Adriano; Guan, Wendy; Boone, Adrienne N; Spafford, J David

    2014-04-25

    T-type (Cav3) channels are categorized as calcium channels, but invertebrate ones can be highly sodium-selective channels. We illustrate that the snail LCav3 T-type channel becomes highly sodium-permeable through exon splicing of an extracellular turret and descending helix in domain II of the four-domain Cav3 channel. Highly sodium-permeable T-type channels are generated without altering the invariant ring of charged residues in the selectivity filter that governs calcium selectivity in calcium channels. The highly sodium-permeant T-type channel expresses in the brain and is the only splice isoform expressed in the snail heart. This unique splicing of turret residues offers T-type channels a capacity to serve as a pacemaking sodium current in the primitive heart and brain in lieu of Nav1-type sodium channels and to substitute for voltage-gated sodium channels lacking in many invertebrates. T-type channels would also contribute substantially to sodium leak conductances at rest in invertebrates because of their large window currents.

  5. Data Refinement and Channel Selection for a Portable E-Nose System by the Use of Feature Feedback

    Directory of Open Access Journals (Sweden)

    Yoonseok Yang

    2010-11-01

    Full Text Available We propose a data refinement and channel selection method for vapor classification in a portable e-nose system. For the robust e-nose system in a real environment, we propose to reduce the noise in the data measured by sensor arrays and distinguish the important part in the data by the use of feature feedback. Experimental results on different volatile organic compounds data show that the proposed data refinement method gives good clustering for different classes and improves the classification performance. Also, we design a new sensor array that consists only of the useful channels. For this purpose, each channel is evaluated by measuring its discriminative power based on the feature mask used in the data refinement. Through the experimental results, we show that the new sensor array improves both the classification rates and the efficiency in computation and data storage.

  6. 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.

  7. Whole genome resequencing of the human parasite Schistosoma mansoni reveals population history and effects of selection

    Science.gov (United States)

    Crellen, Thomas; Allan, Fiona; David, Sophia; Durrant, Caroline; Huckvale, Thomas; Holroyd, Nancy; Emery, Aidan M.; Rollinson, David; Aanensen, David M.; Berriman, Matthew; Webster, Joanne P.; Cotton, James A.

    2016-01-01

    Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5–147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20–90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16–19th Century Atlantic Slave Trade. PMID:26879532

  8. Examining the Relationship Between Flexible Resources and Health Information Channel Selection.

    Science.gov (United States)

    Manierre, Matthew

    2016-01-01

    This study examines how variations in flexible resources influence where individuals begin their search for health information. Access to flexible resources such as money, power, and knowledge can alter the accessibility of channels for health information, such as doctors, the Internet, and print media. Using the HINTS 3 sample, whether information channel utilization is predicted by the same factors in two groups with distinct levels of access to flexible resources, as approximated by high and low levels of education, is investigated. Differences in access to flexible resources are hypothesized to produce variations in channel utilization in bivariate analyses, as well as changes in coefficient strength and statistical significance in multivariate models. Multinomial logit models were used to assess how a number of variables influence the probability of using a specific information channel first in either flexible resource group. Results suggest that individuals with higher levels of education, a proxy for flexible resources, are more likely to report seeking information from the Internet first, which is consistent with research on the digital divide. It appears that diminished access to flexible resources is also associated with heightened utilization of offline channels, including doctors. A handful of differences in predictors were found between the low and high flexible resource groups when multivariate models were compared. Future research should take into account the distinctions between different offline channels while also seeking to further understand how social inequality relates to the utilization of different channels and corresponding health outcomes.

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

    Directory of Open Access Journals (Sweden)

    B.Sabarigiri

    2014-05-01

    Full Text Available 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 numbers of channels are essential for the EEG signal acquisition and Selecting the equipment and verdict the best portions on the scalp is the primary step. (ii Scrutiny of the acquired EEG signals and de-noising from EMG, ECG, EOG Signals and power line artifacts using AWICA (iii Obtain the features from the Enhanced EEG signals by Wavelet Transform (WT and LS-SVM Classification in the MATLAB Environment. Based on the outcome, there is possibility for implementation of an EEG based Practical biometric system.

  10. Voltage-sensing phosphatase reveals temporal regulation of TRPC3/C6/C7 channels by membrane phosphoinositides.

    Science.gov (United States)

    Itsuki, Kyohei; Imai, Yuko; Okamura, Yasushi; Abe, Kihachiro; Inoue, Ryuji; Mori, Masayuki X

    2012-01-01

    TRPC3/C6/C7 channels, a subgroup of classical/canonical TRP channels, are activated by diacylglycerol produced via activation of phospholipase C (PLC)-coupled receptors. Recognition of the physiological importance of these channels has been steadily growing, but the mechanism by which they are regulated remains largely unknown. We recently used a membrane-resident danio rerio voltage-sensing phosphatase (DrVSP) to study TRPC3/C6/C7 regulation and found that the channel activity was controlled by PtdIns(4,5)P(2)-DAG signaling in a self-limiting manner (Imai Y et al., the Journal of Physiology, 2012). In this addendum, we present the advantages of using DrVSP as a molecular tool to study PtdIns(4,5)P(2) regulation. DrVSP should be readily applicable for studying phosphoinositide metabolism-linked channel regulation as well as lipid dynamics. Furthermore, in comparison to other modes of self-limiting ion channel regulation, the regulation of TRPC3/C6/C7 channels seems highly susceptible to activation signal strength, which could potentially affect both open duration and the time to peak activation and inactivation. Dysfunction of such self-limiting regulation may contribute to the pathology of the cardiovascular system, gastrointestinal tract and brain, as these channels are broadly distributed and affected by numerous neurohormonal agonists.

  11. Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Anna Koczula

    2017-02-01

    Full Text Available Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq. In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism. In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.

  12. Genome-wide Selective Sweeps in Natural Bacterial Populations Revealed by Time-series Metagenomics

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Leong-Keat; Bendall, Matthew L.; Malfatti, Stephanie; Schwientek, Patrick; Tremblay, Julien; Schackwitz, Wendy; Martin, Joel; Pati, Amrita; Bushnell, Brian; Foster, Brian; Kang, Dongwan; Tringe, Susannah G.; Bertilsson, Stefan; Moran, Mary Ann; Shade, Ashley; Newton, Ryan J.; Stevens, Sarah; McMahon, Katherine D.; Malmstrom, Rex R.

    2014-06-18

    Multiple evolutionary models have been proposed to explain the formation of genetically and ecologically distinct bacterial groups. Time-series metagenomics enables direct observation of evolutionary processes in natural populations, and if applied over a sufficiently long time frame, this approach could capture events such as gene-specific or genome-wide selective sweeps. Direct observations of either process could help resolve how distinct groups form in natural microbial assemblages. Here, from a three-year metagenomic study of a freshwater lake, we explore changes in single nucleotide polymorphism (SNP) frequencies and patterns of gene gain and loss in populations of Chlorobiaceae and Methylophilaceae. SNP analyses revealed substantial genetic heterogeneity within these populations, although the degree of heterogeneity varied considerably among closely related, co-occurring Methylophilaceae populations. SNP allele frequencies, as well as the relative abundance of certain genes, changed dramatically over time in each population. Interestingly, SNP diversity was purged at nearly every genome position in one of the Chlorobiaceae populations over the course of three years, while at the same time multiple genes either swept through or were swept from this population. These patterns were consistent with a genome-wide selective sweep, a process predicted by the ‘ecotype model’ of diversification, but not previously observed in natural populations.

  13. Genome-wide Selective Sweeps in Natural Bacterial Populations Revealed by Time-series Metagenomics

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Leong-Keat; Bendall, Matthew L.; Malfatti, Stephanie; Schwientek, Patrick; Tremblay, Julien; Schackwitz, Wendy; Martin, Joel; Pati, Amrita; Bushnell, Brian; Foster, Brian; Kang, Dongwan; Tringe, Susannah G.; Bertilsson, Stefan; Moran, Mary Ann; Shade, Ashley; Newton, Ryan J.; Stevens, Sarah; McMcahon, Katherine D.; Mamlstrom, Rex R.

    2014-05-12

    Multiple evolutionary models have been proposed to explain the formation of genetically and ecologically distinct bacterial groups. Time-series metagenomics enables direct observation of evolutionary processes in natural populations, and if applied over a sufficiently long time frame, this approach could capture events such as gene-specific or genome-wide selective sweeps. Direct observations of either process could help resolve how distinct groups form in natural microbial assemblages. Here, from a three-year metagenomic study of a freshwater lake, we explore changes in single nucleotide polymorphism (SNP) frequencies and patterns of gene gain and loss in populations of Chlorobiaceae and Methylophilaceae. SNP analyses revealed substantial genetic heterogeneity within these populations, although the degree of heterogeneity varied considerably among closely related, co-occurring Methylophilaceae populations. SNP allele frequencies, as well as the relative abundance of certain genes, changed dramatically over time in each population. Interestingly, SNP diversity was purged at nearly every genome position in one of the Chlorobiaceae populations over the course of three years, while at the same time multiple genes either swept through or were swept from this population. These patterns were consistent with a genome-wide selective sweep, a process predicted by the ecotype model? of diversification, but not previously observed in natural populations.

  14. The Pathogenic A116V Mutation Enhances Ion-Selective Channel Formation by Prion Protein in Membranes.

    Science.gov (United States)

    Sabareesan, Ambadi Thody; Singh, Jogender; Roy, Samrat; Udgaonkar, Jayant B; Mathew, M K

    2016-04-26

    Prion diseases are a group of fatal neurodegenerative disorders that afflict mammals. Misfolded and aggregated forms of the prion protein (PrP(Sc)) have been associated with many prion diseases. A transmembrane form of PrP favored by the pathogenic mutation A116V is associated with Gerstmann-Sträussler-Scheinker syndrome, but no accumulation of PrP(Sc) is detected. However, the role of the transmembrane form of PrP in pathological processes leading to neuronal death remains unclear. This study reports that the full-length mouse PrP (moPrP) significantly increases the permeability of living cells to K(+), and forms K(+)- and Ca(2+)-selective channels in lipid membranes. Importantly, the pathogenic mutation A116V greatly increases the channel-forming capability of moPrP. The channels thus formed are impermeable to sodium and chloride ions, and are blocked by blockers of voltage-gated ion channels. Hydrogen-deuterium exchange studies coupled with mass spectrometry (HDX-MS) show that upon interaction with lipid, the central hydrophobic region (109-132) of the protein is protected against exchange, making it a good candidate for inserting into the membrane and lining the channel. HDX-MS also shows a dramatic increase in the protein-lipid stoichiometry for A116V moPrP, providing a rationale for its increased channel-forming capability. The results suggest that ion channel formation may be a possible mechanism of PrP-mediated neurodegeneration by the transmembrane forms of PrP.

  15. How Much Feedback Is Required for TDD Multi-Antenna Broadcast Channels with User Selection?

    Directory of Open Access Journals (Sweden)

    Salim Umer

    2010-01-01

    Full Text Available The enormous gains in a multi-antenna transmitter broadcast channel require the Channel State Information at the Transmitter (CSIT. Although the fundamental question "How much feedback is required for a broadcast channel?" has been treated in the literature to some extent, a more comprehensive treatment is certainly desirable. We study the time-division duplex broadcast channel with initial assumption of channel state information (CSI neither at the base station (BS nor at the users' side. We provide two transmission strategies through which the BS and the users get necessary CSI. We derive novel lower and upper bounds for the sum rate reflecting the rate loss compared to a perfect CSIT system. Corresponding approximate sum rate expressions are also developed for both schemes. These expressions fully capture the benefits of the CSIT feedback, allowing multi-user diversity gain and better inter-user interference cancellation, and the cost of exchange of information required. These expressions can be optimized for any set of system parameters to unveil the trade-off between the cost and the gains associated to feedback. Thus they allow to characterize the optimal amount of feedback which maximizes the sum rate of the broadcast channel, a well-accepted metric of system performance at the physical layer.

  16. Characterization of Kbot21 Reveals Novel Side Chain Interactions of Scorpion Toxins Inhibiting Voltage-Gated Potassium Channels.

    Directory of Open Access Journals (Sweden)

    Rym ElFessi-Magouri

    Full Text Available Scorpion toxins are important pharmacological tools for probing the physiological roles of ion channels which are involved in many physiological processes and as such have significant therapeutic potential. The discovery of new scorpion toxins with different specificities and affinities is needed to further characterize the physiology of ion channels. In this regard, a new short polypeptide called Kbot21 has been purified to homogeneity from the venom of Buthus occitanus tunetanus scorpion. Kbot21 is structurally related to BmBKTx1 from the venom of the Asian scorpion Buthus martensii Karsch. These two toxins differ by only two residues at position 13 (R /V and 24 (D/N.Despite their very similar sequences, Kbot21 and BmBKTx1 differ in their electrophysiological activities. Kbot21 targets KV channel subtypes whereas BmBKTx1 is active on both big conductance (BK and small conductance (SK Ca2+-activated K+ channel subtypes, but has no effects on Kv channel subtypes. The docking model of Kbot21 with the Kv1.2 channel shows that the D24 and R13 side-chain of Kbot21 are critical for its interaction with KV channels.

  17. Characterization of Kbot21 Reveals Novel Side Chain Interactions of Scorpion Toxins Inhibiting Voltage-Gated Potassium Channels.

    Science.gov (United States)

    ElFessi-Magouri, Rym; Peigneur, Steve; Othman, Houcemeddine; Srairi-Abid, Najet; ElAyeb, Mohamed; Tytgat, Jan; Kharrat, Riadh

    2015-01-01

    Scorpion toxins are important pharmacological tools for probing the physiological roles of ion channels which are involved in many physiological processes and as such have significant therapeutic potential. The discovery of new scorpion toxins with different specificities and affinities is needed to further characterize the physiology of ion channels. In this regard, a new short polypeptide called Kbot21 has been purified to homogeneity from the venom of Buthus occitanus tunetanus scorpion. Kbot21 is structurally related to BmBKTx1 from the venom of the Asian scorpion Buthus martensii Karsch. These two toxins differ by only two residues at position 13 (R /V) and 24 (D/N).Despite their very similar sequences, Kbot21 and BmBKTx1 differ in their electrophysiological activities. Kbot21 targets KV channel subtypes whereas BmBKTx1 is active on both big conductance (BK) and small conductance (SK) Ca2+-activated K+ channel subtypes, but has no effects on Kv channel subtypes. The docking model of Kbot21 with the Kv1.2 channel shows that the D24 and R13 side-chain of Kbot21 are critical for its interaction with KV channels.

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

    Directory of Open Access Journals (Sweden)

    Sulyman Ahmed Iyanda

    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 M branches out of the L available diversity resources (M ≤ L . 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.

  19. Functional mutagenesis screens reveal the ‘cap structure’ formation in disulfide-bridge free TASK channels

    Science.gov (United States)

    Goldstein, Matthias; Rinné, Susanne; Kiper, Aytug K.; Ramírez, David; Netter, Michael F.; Bustos, Daniel; Ortiz-Bonnin, Beatriz; González, Wendy; Decher, Niels

    2016-01-01

    Two-pore-domain potassium (K2P) channels have a large extracellular cap structure formed by two M1-P1 linkers, containing a cysteine for dimerization. However, this cysteine is not present in the TASK-1/3/5 subfamily. The functional role of the cap is poorly understood and it remained unclear whether K2P channels assemble in the domain-swapped orientation or not. Functional alanine-mutagenesis screens of TASK-1 and TRAAK were used to build an in silico model of the TASK-1 cap. According to our data the cap structure of disulfide-bridge free TASK channels is similar to that of other K2P channels and is most likely assembled in the domain-swapped orientation. As the conserved cysteine is not essential for functional expression of all K2P channels tested, we propose that hydrophobic residues at the inner leaflets of the cap domains can interact with each other and that this way of stabilizing the cap is most likely conserved among K2P channels. PMID:26794006

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

    Directory of Open Access Journals (Sweden)

    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.

  1. A 66 MHz, 32-channel analog memory circuit with data selection for fast silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Munday, D.; Parker, A. (Cavendish Lab., Univ. Cambridge (United Kingdom)); Anghinolfi, F.; Aspell, P.; Campbell, M.; Jarron, P.; Heijne, E.H.M.; Meddeler, G.; Santiard, J.C.; Verweij, H. (CERN, Geneva (Switzerland)); Goessling, C. (Inst. fuer Physik, Univ. Dortmund (Germany)); Bonino, R.; Clark, A.G.; Couyoumtzelis, C.; La Marra, D.; Wu, X. (DPNC, Geneva Univ. (Switzerland)); Moorhead, G. (School of Physics, Univ. Melbourne, Parkville (Ausralia)); Weidberg, A. (Dept. of Nuclear Physics, Oxford Univ. (United Kingdom)); Campbell, D.; Murray, P.; Seller, P.; Stevens, R. (Rutherford Appleton Lab., Chilton (United Kingdom)); Beuville, E.; Rouger, M.; Teiger, J. (Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France)); RD2 Collaboration

    1993-03-01

    An analog memory array with 64 memory cells for each channel has been designed and manufactured in CMOS. A new skip logic controller allows to write at 66 MHz without dead time and to read out at a lower frequency simultaneously. The input circuit is charge-sensitive and integrates continuously. Pedestal nonuniformity is 1.4 mV rms from cell-to-cell and 3.5 mV rms between channels. The linearity range is -2.5 to +1.5 V, which corresponds to 11 bits. The chip has been used in a particle detection test. (orig.).

  2. Unexpected substrate specificity of T4 DNA ligase revealed by in vitro selection

    Science.gov (United States)

    Harada, Kazuo; Orgel, Leslie E.

    1993-01-01

    We have used in vitro selection techniques to characterize DNA sequences that are ligated efficiently by T4 DNA ligase. We find that the ensemble of selected sequences ligates about 50 times as efficiently as the random mixture of sequences used as the input for selection. Surprisingly many of the selected sequences failed to produce a match at or close to the ligation junction. None of the 20 selected oligomers that we sequenced produced a match two bases upstream from the ligation junction.

  3. 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.

  4. 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.

  5. 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.

  6. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    Science.gov (United States)

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  7. 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

    caused by one such mutation in Kir6.2, E282K. The study led to the discovery that Kir6.2 contains a di-acidic ER exit signal, (280)DLE(282), which promotes concentration of the channel into COPII-enriched ER exit sites prior to ER export via a process that requires Sar1-GTPase. The E282K mutation...... together, we conclude that surface expression of K(ATP) channels is critically dependent on the Sar1-GTPase-dependent ER exit mechanism and abrogation of the di-acidic ER exit signal leads to CHI....

  8. Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption

    DEFF Research Database (Denmark)

    Ellekvist, Peter; Maciel, Jorge; Mlambo, Godfree;

    2008-01-01

    through the mosquito vector remains unknown. We hypothesize that these two K(+) channels mediate the transport of K(+) in the parasites, and thus are important for parasite survival. To test this hypothesis, we identified the orthologue of one of the P. falciparum K(+) channels, PfKch1, in the rodent...... inhibition of the development of PbKch1-null parasites in Anopheles stephensi mosquitoes. In conclusion, these studies demonstrate that PbKch1 contributes to the transport of K(+) in P. berghei parasites and supports the growth of the parasites, in particular the development of oocysts in the mosquito midgut...

  9. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

    Science.gov (United States)

    Kim, Han Sol; Li, Hongliang; Kim, Hye Won; Shin, Sung Eun; Choi, Il-Whan; Firth, Amy L; Bang, Hyoweon; Bae, Young Min; Park, Won Sun

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertraline decreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 mu M and a slope value (Hill coefficient) of 0.61. Although the application of 1 mu M sertraline did not affect the steady-state activation curves, sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine, had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From these results, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptake inhibition by shifting inactivation curves to a more negative potential.

  10. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

    Indian Academy of Sciences (India)

    HAN SOL KIM; HONGLIANG LI; HYE WON KIM; SUNG EUN SHIN; IL-WHAN CHOI; AMY L FIRTH; HYOWEON BANG; YOUNG MIN BAE; WON SUN PARK

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv)channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertralinedecreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 μM and a slope value (Hillcoefficient) of 0.61. Although the application of 1 μM sertraline did not affect the steady-state activation curves,sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine,had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From theseresults, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptakeinhibition by shifting inactivation curves to a more negative potential.

  11. 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.

  12. Vibrational excitons in ionophores: Experimental probes for quantum coherence-assisted ion transport and selectivity in ion channels

    CERN Document Server

    Ganim, Ziad; Vaziri, Alipasha

    2011-01-01

    Despite a large body of work, the exact molecular details underlying ion-selectivity and transport in the potassium channel have not been fully laid to rest. One major reason has been the lack of experimental methods that can probe these mechanisms dynamically on their biologically relevant time scales. Recently it was suggested that quantum coherence and its interplay with thermal vibration might be involved in mediating ion-selectivity and transport. In this work we present an experimental strategy for using time resolved infrared spectroscopy to investigate these effects. We show the feasibility by demonstrating the IR absorption and Raman spectroscopic signatures of potassium binding model molecules that mimic the transient interactions of potassium with binding sites of the selectivity filter during ion conduction. In addition to guide our experiments on the real system we have performed molecular dynamic-based simulations of the FTIR and 2DIR spectra of the entire KcsA complex, which is the largest comp...

  13. Walker mutations reveal loose relationship between catalytic and channel-gating activities of purified CFTR (cystic fibrosis transmembrane conductance regulator).

    Science.gov (United States)

    Ramjeesingh, M; Li, C; Garami, E; Huan, L J; Galley, K; Wang, Y; Bear, C E

    1999-02-02

    The cystic fibrosis transmembrane conductance regulator (CFTR) functions as an ATPase and as a chloride channel. It has been hypothesized, on the basis of electrophysiological findings, that the catalytic activity of CFTR is tightly coupled to the opening and closing of the channel gate. In the present study, to determine the structural basis for the ATPase activity of CFTR, we assessed the effect of mutations within the "Walker A" consensus motifs on ATP hydrolysis by the purified, intact protein. Mutation of the lysine residue in the "Walker A" motif of either the first nucleotide binding fold (CFTRK464A) or the second nucleotide binding fold (CFTRK1250A) inhibited the ATPase activity of the purified intact CFTR protein significantly, by greater than 50%. This finding suggests that the two nucleotide binding folds of CFTR are functioning cooperatively in catalysis. However, the rate of channel gating was only significantly inhibited in one of these purified mutants, CFTRK1250A, suggesting that ATPase activity may not be tightly coupled to channel gating as previously hypothesized.

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

    Directory of Open Access Journals (Sweden)

    Zeineb Es-Salah-Lamoureux

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

  15. On Frequency Offset Estimation Using the iNET Preamble in Frequency Selective Fading Channels

    Science.gov (United States)

    2014-03-01

    ASM fields; (bottom) the relationship between the indexes of the received samples r(n), the signal samples s(n), the preamble samples p (n) and the short...frequency offset estimators for SOQPSK-TG equipped with the iNET preamble and operating in ISI channels. Four of the five estimators exam - ined here are...sync marker ( ASM ), and data bits (an LDPC codeword). The availability of a preamble introduces the possibility of data-aided synchro- nization in

  16. Selected topics from single top t-channel (XS and other properties)

    CERN Document Server

    Maier, Benedikt

    2015-01-01

    Measurements of the cross section and of the interactions happening at the tWb vertext are performed in the single top $t$-channel at center-of-mass energies of $\\sqrt{s}=7$ and $8$\\,TeV. Results of both ATLAS and CMS collaborations are presented. No indications for new physics and no deviations from the Standard Model predictions within the experimental and theoretical uncertainties are found.

  17. Capacity bounds for kth best path selection over generalized fading channels

    KAUST Repository

    Hanif, Muhammad Fainan

    2014-02-01

    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 have simple analytic expressions which allow their fast evaluation. Numerical results show that the newly proposed bounds closely approximate the exact ergodic capacity for a large variety of system configurations. © 1997-2012 IEEE.

  18. Developing a Comparative Docking Protocol for the Prediction of Peptide Selectivity Profiles: Investigation of Potassium Channel Toxins

    Directory of Open Access Journals (Sweden)

    Serdar Kuyucak

    2012-02-01

    Full Text Available During the development of selective peptides against highly homologous targets, a reliable tool is sought that can predict information on both mechanisms of binding and relative affinities. These tools must first be tested on known profiles before application on novel therapeutic candidates. We therefore present a comparative docking protocol in HADDOCK using critical motifs, and use it to “predict” the various selectivity profiles of several major αKTX scorpion toxin families versus Kv1.1, Kv1.2 and Kv1.3. By correlating results across toxins of similar profiles, a comprehensive set of functional residues can be identified. Reasonable models of channel-toxin interactions can be then drawn that are consistent with known affinity and mutagenesis. Without biological information on the interaction, HADDOCK reproduces mechanisms underlying the universal binding of αKTX-2 toxins, and Kv1.3 selectivity of αKTX-3 toxins. The addition of constraints encouraging the critical lysine insertion confirms these findings, and gives analogous explanations for other families, including models of partial pore-block in αKTX-6. While qualitatively informative, the HADDOCK scoring function is not yet sufficient for accurate affinity-ranking. False minima in low-affinity complexes often resemble true binding in high-affinity complexes, despite steric/conformational penalties apparent from visual inspection. This contamination significantly complicates energetic analysis, although it is usually possible to obtain correct ranking via careful interpretation of binding-well characteristics and elimination of false positives. Aside from adaptations to the broader potassium channel family, we suggest that this strategy of comparative docking can be extended to other channels of interest with known structure, especially in cases where a critical motif exists to improve docking effectiveness.

  19. SIGNAL CONSTELLATIONS DESIGN FOR DIFFERENTIAL UNITARY SPACE-TIME IN MIMO-OFDM SYSTEM OVER FREQUENCY-SELECTIVE FADING CHANNELS

    Institute of Scientific and Technical Information of China (English)

    Chen Jing; Zhu Qi

    2008-01-01

    In this paper, the design of signal constellations parameters is studied for Differential Unitary Space-Time Modulation (DUSTM) based on the design criterion of maximizing the diversity product. Farther, noninteger searching method for the signal constellation parameters design is proposed in order to get better codes. Experimental results show that under the different Doppler spread and data transmission rate, the proposed design performs better than the previous design using integer parameters in Multiple Input Multiple Output Orthogonal Frequency Division Multiplexing(MIMO-OFDM) system over frequency-selective fading channels.

  20. Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami

    Science.gov (United States)

    Herzig, Volker; Ikonomopoulou, Maria; Smith, Jennifer J.; Dziemborowicz, Sławomir; Gilchrist, John; Kuhn-Nentwig, Lucia; Rezende, Fernanda Oliveira; Moreira, Luciano Andrade; Nicholson, Graham M.; Bosmans, Frank; King, Glenn F.

    2016-07-01

    The inexorable decline in the armament of registered chemical insecticides has stimulated research into environmentally-friendly alternatives. Insecticidal spider-venom peptides are promising candidates for bioinsecticide development but it is challenging to find peptides that are specific for targeted pests. In the present study, we isolated an insecticidal peptide (Ae1a) from venom of the African spider Augacephalus ezendami (family Theraphosidae). Injection of Ae1a into sheep blowflies (Lucilia cuprina) induced rapid but reversible paralysis. In striking contrast, Ae1a was lethal to closely related fruit flies (Drosophila melanogaster) but induced no adverse effects in the recalcitrant lepidopteran pest Helicoverpa armigera. Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. We show that Ae1a interacts with the domain II voltage sensor and that sensitivity to the toxin is conferred by natural sequence variations in the S1–S2 loop of domain II. The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species.

  1. Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami

    Science.gov (United States)

    Herzig, Volker; Ikonomopoulou, Maria; Smith, Jennifer J.; Dziemborowicz, Sławomir; Gilchrist, John; Kuhn-Nentwig, Lucia; Rezende, Fernanda Oliveira; Moreira, Luciano Andrade; Nicholson, Graham M.; Bosmans, Frank; King, Glenn F.

    2016-01-01

    The inexorable decline in the armament of registered chemical insecticides has stimulated research into environmentally-friendly alternatives. Insecticidal spider-venom peptides are promising candidates for bioinsecticide development but it is challenging to find peptides that are specific for targeted pests. In the present study, we isolated an insecticidal peptide (Ae1a) from venom of the African spider Augacephalus ezendami (family Theraphosidae). Injection of Ae1a into sheep blowflies (Lucilia cuprina) induced rapid but reversible paralysis. In striking contrast, Ae1a was lethal to closely related fruit flies (Drosophila melanogaster) but induced no adverse effects in the recalcitrant lepidopteran pest Helicoverpa armigera. Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. We show that Ae1a interacts with the domain II voltage sensor and that sensitivity to the toxin is conferred by natural sequence variations in the S1–S2 loop of domain II. The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species. PMID:27383378

  2. Selecting participants for listening tests of multi-channel reproduced sound

    DEFF Research Database (Denmark)

    Wickelmaier, Florian Maria; Choisel, Sylvain

    2005-01-01

    , their spatial hearing, and their verbal production abilities. The listeners displayed large individual differences in their performance. Forty subjects were selected based on the test results. The self-assessed listening habits and experience in the web-questionnaire could not predict the results......A selection procedure was devised in order to select listeners for experiments in which their main task will be to judge multichannel reproduced sound. Ninety-one participants filled in a web-based questionnaire. Seventy-eight of them took part in an assessment of their hearing thresholds...... 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  4. MDIMP, a novel cardiac Ca(2+) channel blocker with atrial selectivity.

    Science.gov (United States)

    Santamaria-Herrera, Mireille Aline; Ríos-Pérez, Erick Benjamín; de la Rosa, Juan Antonio Manuel; García-Castañeda, Maricela; Osornio-Garduño, Diana Stephanie; Ramos-Mondragón, Roberto; Mancilla-Percino, Teresa; Avila, Guillermo

    2016-06-15

    In cardiac muscle cells both T-and L-type Ca(2+) channels (TTCCs and LTCCs, respectively) are expressed, and the latter are relevant to a process known as excitation-contraction coupling (ECC). Evidence obtained from docking studies suggests that isoindolines derived from α-amino acids bind to the LTCC CaV1.2. In the present study, we investigated whether methyl (S)-2-(1,3-dihydroisoindol-2-yl)-4-methylpentanoate (MDIMP), which is derived from L-leucine, modulates both Ca(2+) channels and ECC. To this end, mechanical properties, as well as Ca(2+) transients and currents, were all investigated in isolated cardiac myocytes. The effects of MDIMP on CaV1.2 (transiently expressed in 293T/17 cells) were also studied. In this system, evidence was found for an inhibitory action that develops and recovers in min, with an IC50 of 450µM. With respect to myocytes: atrial-TTCCs, atrial-LTCCs, and ventricular-LTCCs were also inhibited, in that order of potency. Accordingly, Ca(2+) transients, contractions, and window currents of LTCCs were all reduced more strongly in atrial cells. Interestingly, while the modulation of LTCCs was state-independent in these cells, it was state-dependent, and dual, on the ventricular ones. Furthermore, practically all of the ventricular LTCCs were closed at resting membrane potentials. This could explain their resistance to MDIMP, as they were affected in only open or inactivated states. All these features in turn explain the preferential down-regulation of the atrial ECC. Thus, our results support the view that isoindolines bind to Ca(2+) channels, improve our knowledge of the corresponding structure-function relationship, and may be relevant for conditions where decreased atrial activity is desired.

  5. Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

    Science.gov (United States)

    Oliver, A. E.; Deamer, D. W.

    1994-01-01

    Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two

  6. Fish habitat selection in a large hydropeaking river: Strong individual and temporal variations revealed by telemetry.

    Science.gov (United States)

    Capra, Hervé; Plichard, Laura; Bergé, Julien; Pella, Hervé; Ovidio, Michaël; McNeil, Eric; Lamouroux, Nicolas

    2017-02-01

    Modeling individual fish habitat selection in highly variable environments such as hydropeaking rivers is required for guiding efficient management decisions. We analyzed fish microhabitat selection in the heterogeneous hydraulic and thermal conditions (modeled in two-dimensions) of a reach of the large hydropeaking Rhône River locally warmed by the cooling system of a nuclear power plant. We used modern fixed acoustic telemetry techniques to survey 18 fish individuals (five barbels, six catfishes, seven chubs) signaling their position every 3s over a three-month period. Fish habitat selection depended on combinations of current microhabitat hydraulics (e.g. velocity, depth), past microhabitat hydraulics (e.g. dewatering risk or maximum velocities during the past 15days) and to a lesser extent substrate and temperature. Mixed-effects habitat selection models indicated that individual effects were often stronger than specific effects. In the Rhône, fish individuals appear to memorize spatial and temporal environmental changes and to adopt a "least constraining" habitat selection. Avoiding fast-flowing midstream habitats, fish generally live along the banks in areas where the dewatering risk is high. When discharge decreases, however, they select higher velocities but avoid both dewatering areas and very fast-flowing midstream habitats. Although consistent with the available knowledge on static fish habitat selection, our quantitative results demonstrate temporal variations in habitat selection, depending on individual behavior and environmental history. Their generality could be further tested using comparative experiments in different environmental configurations.

  7. Neural evidence reveals the rapid effects of reward history on selective attention.

    Science.gov (United States)

    MacLean, Mary H; Giesbrecht, Barry

    2015-05-05

    Selective attention is often framed as being primarily driven by two factors: task-relevance and physical salience. However, factors like selection and reward history, which are neither currently task-relevant nor physically salient, can reliably and persistently influence visual selective attention. The current study investigated the nature of the persistent effects of irrelevant, physically non-salient, reward-associated features. These features affected one of the earliest reliable neural indicators of visual selective attention in humans, the P1 event-related potential, measured one week after the reward associations were learned. However, the effects of reward history were moderated by current task demands. The modulation of visually evoked activity supports the hypothesis that reward history influences the innate salience of reward associated features, such that even when no longer relevant, nor physically salient, these features have a rapid, persistent, and robust effect on early visual selective attention.

  8. Post-selection technique for quantum channels with applications to quantum cryptography

    Energy Technology Data Exchange (ETDEWEB)

    Christandl, Matthias [University of Munich (Germany); Koenig, Robert [California Institute of Technology, Pasadena, CA (United States); Renner, Renato [ETH Zurich (Switzerland)

    2009-07-01

    We propose a general method for studying properties of quantum channels acting on an n-partite system, whose action is invariant under permutations of the subsystems. Our main result is that, in order to prove that a certain property holds for any arbitrary input, it is sufficient to consider the special case where the input is a particular de Finetti-type state, i.e., a state which consists of n identical and independent copies of an (unknown) state on a single subsystem. A similar statement holds for more general channels which are covariant with respect to the action of an arbitrary finite or locally compact group. Our technique can be applied to the analysis of information-theoretic problems. For example, in quantum cryptography, we get a simple proof for the fact that security of a discrete-variable quantum key distribution protocol against collective attacks implies security of the protocol against the most general attacks. The resulting security bounds are tighter than previously known bounds obtained by proofs relying on the exponential de Finetti theorem.

  9. A plasma membrane-targeted cytosolic domain of STIM1 selectively activates ARC channels, an arachidonate-regulated store-independent Orai channel.

    Science.gov (United States)

    Thompson, Jill L; Shuttleworth, Trevor J

    2012-01-01

    The Orai family of calcium channels includes the store-operated CRAC channels and store-independent, arachidonic acid (AA)-regulated ARC channels. Both depend on STIM1 for their activation but, whereas CRAC channel activation involves sensing the depletion of intracellular calcium stores via a luminal N terminal EF-hand of STIM1 in the endoplasmic reticulum (ER) membrane, ARC channels are exclusively activated by the pool of STIM1 that constitutively resides in the plasma membrane (PM). Here, the EF-hand is extracellular and unlikely to ever lose its bound calcium, suggesting that STIM1-dependent activation of ARC channels is very different from that of CRAC channels. We now show that attachment of the cytosolic portion of STIM1 to the inner face of the PM via an N terminal Lck-domain sequence is sufficient to enable normal AA-dependent activation of ARC channels, while failing to allow activation of store-operated CRAC channels. Introduction of a point mutation within the Lck-domain resulted in the loss of both PM localization and ARC channel activation. Reversing the orientation of the PM-anchored STIM1 C terminus via a C-terminal CAAX-box fails to support either CRAC or ARC channel activation. Finally, the Lck-anchored STIM1 C-terminal domain also enabled the exclusive activation of the ARC channels following physiological agonist addition. These data demonstrate that simple tethering of the cytosolic C-terminal domain of STIM1 to the inner face of the PM is sufficient to allow the full, normal and exclusive activation of ARC channels, and that the N-terminal regions of STIM1 (including the EF-hand domain) play no significant role in this activation.

  10. Improving Performance of Wi-Fi by Compact MIMO Systems by using Gama Frequency-Selective Fading Channels

    Directory of Open Access Journals (Sweden)

    Sudesh Gupta

    2011-12-01

    Full Text Available In this paper we propose a compact MIMO system in frequency-selective fading channels which improves the performance of Wireless Media. A MIMO beam forming system model with mutual coupling and matching network is proposed to cope with frequency-selective fading channels. The overall system proposed transfer matrix is derived using Z-parameter method. The system using the transform matrix which accepts the relay and the delay matrix for the computation. Then apply the diversity criteria by which we can make the code output pair which is distinct. So we can obtain two different pairs one is shows the below value in the MIMO System one is the Higher value. It is the only way to achieve orthogonally. One particular problem with this is that it has uneven power among the symbols it transmits. This means that the signal does not have a constant envelope and that the power each antenna must transmit has to vary, both of which are undesirable. We can take the middle value which overcomes this problem.

  11. Improving Performance of Wi-Fi by Compact MIMO Systems by using Gama Frequency-Selective Fading Channels

    Directory of Open Access Journals (Sweden)

    Mr. Sudesh Gupta

    2011-09-01

    Full Text Available In this paper we propose a compact MIMO system in frequency-selective fading channels which improves the performance of Wireless Media. A MIMO beam forming system model with mutual coupling and matching network is proposed to cope with frequency-selective fading channels. The overall system proposed transfer matrix is derived using Z-parameter method. The system using the transform matrix which accepts the relay and the delay matrix for the computation. Then apply the diversity criteria by which we can make the code output pair which is distinct. So we can obtain two different pairs one is shows the below value in the MIMO System one is the Higher value. It is the only way to achieve orthogonally. One particular problem with this is that it has uneven power among the symbols it transmits. This means that the signal does not have a constant envelope and that the power each antenna must transmit has to vary, both of which are undesirable. We can take the middle value which overcomes this problem.

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

    Science.gov (United States)

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

    2006-05-01

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

  13. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles.

    Science.gov (United States)

    Orozco-terWengel, Pablo; Kapun, Martin; Nolte, Viola; Kofler, Robert; Flatt, Thomas; Schlötterer, Christian

    2012-10-01

    The genomic basis of adaptation to novel environments is a fundamental problem in evolutionary biology that has gained additional importance in the light of the recent global change discussion. Here, we combined laboratory natural selection (experimental evolution) in Drosophila melanogaster with genome-wide next generation sequencing of DNA pools (Pool-Seq) to identify alleles that are favourable in a novel laboratory environment and traced their trajectories during the adaptive process. Already after 15 generations, we identified a pronounced genomic response to selection, with almost 5000 single nucleotide polymorphisms (SNP; genome-wide false discovery rates heterogeneous, with the alleles falling into two distinct classes: (i) alleles that continuously rise in frequency; and (ii) alleles that at first increase rapidly but whose frequencies then reach a plateau. Our data thus suggest that the genomic response to selection can involve a large number of selected SNPs that show unexpectedly complex evolutionary trajectories, possibly due to nonadditive effects.

  14. Sperm Proteomics Reveals Intensified Selection on Mouse Sperm Membrane and Acrosome Genes

    OpenAIRE

    Dorus, Steve; Wasbrough, Elizabeth R.; Busby, Jennifer; Wilkin, Elaine C.; Karr, Timothy L.

    2010-01-01

    Spermatozoa are a focal point for the impact of sexual selection due to sperm competition and sperm–female interactions in a wide range of sexually reproducing organisms. In-depth molecular investigation of the ramifications of these selective regimes has been limited due to a lack of information concerning the molecular composition of sperm. In this study, we utilize three previously published proteomic data sets in conjunction with our whole mouse sperm proteomic analysis to delineate cellu...

  15. Genome-wide analysis reveals selection for important traits in domestic horse breeds.

    Directory of Open Access Journals (Sweden)

    Jessica L Petersen

    Full Text Available Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3. The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

  16. A sodium channel mutation identified in Aedes aegypti selectively reduces cockroach sodium channel sensitivity to type I, but not type II pyrethroids.

    Science.gov (United States)

    Hu, Zhaonong; Du, Yuzhe; Nomura, Yoshiko; Dong, Ke

    2011-01-01

    Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Numerous point mutations in sodium channel genes have been identified in pyrethroid-resistant insect species, and many have been confirmed to reduce or abolish sensitivity of channels expressed in Xenopus oocytes to pyrethroids. Recently, several novel mutations were reported in sodium channel genes of pyrethroid-resistant Aedes mosquito populations. One of the mutations is a phenylalanine (F) to cysteine (C) change in segment 6 of domain III (IIIS6) of the Aedes mosquito sodium channel. Curiously, a previous study showed that alanine substitution of this F did not alter the action of deltamethrin, a type II pyrethroid, on a cockroach sodium channel. In this study, we changed this F to C in a pyrethroid-sensitive cockroach sodium channel and examined mutant channel sensitivity to permethrin as well as five other type I or type II pyrethroids in Xenopus oocytes. Interestingly, the F to C mutation drastically reduced channel sensitivity to three type I pyrethroids, permethrin, NRDC 157 (a deltamethrin analogue lacking the α-cyano group) and bioresemthrin, but not to three type II pyrethroids, cypermethrin, deltamethrin and cyhalothrin. These results confirm the involvement of the F to C mutation in permethrin resistance, and raise the possibility that rotation of type I and type II pyrethroids might be considered in the control of insect pest populations where this particular mutation is present.

  17. Performance analysis of selective cooperation in underlay cognitive networks over Rayleigh channels

    KAUST Repository

    Hussain, Syed Imtiaz

    2011-06-01

    Underlay cognitive networks should follow strict interference thresholds to operate in parallel with primary networks. This constraint limits their transmission power and eventually the area of coverage. Therefore, it is very likely that the underlay networks will make use of relays to transmit signals to the distant secondary users. In this paper, we propose a secondary relay selection scheme which maximizes the end-to-end signal to noise ratio (SNR) for the secondary link while keeping the interference levels to the primary network below a certain threshold. We derive closed form expressions for the probability density function (PDF) of the SNR at the secondary destination, average bit error probability and outage probability. Analytical results are verified through simulations which also give insight about the benefits and tradeoffs of the selective cooperation in underlay cognitive networks. It is shown that, in contrast to non-cognitive selective cooperation, this scheme performs better in low SNR region for cognitive networks. © 2011 IEEE.

  18. Multiplex multivariate recurrence network from multi-channel signals for revealing oil-water spatial flow behavior

    Science.gov (United States)

    Gao, Zhong-Ke; Dang, Wei-Dong; Yang, Yu-Xuan; Cai, Qing

    2017-03-01

    The exploration of the spatial dynamical flow behaviors of oil-water flows has attracted increasing interests on account of its challenging complexity and great significance. We first technically design a double-layer distributed-sector conductance sensor and systematically carry out oil-water flow experiments to capture the spatial flow information. Based on the well-established recurrence network theory, we develop a novel multiplex multivariate recurrence network (MMRN) to fully and comprehensively fuse our double-layer multi-channel signals. Then we derive the projection networks from the inferred MMRNs and exploit the average clustering coefficient and the spectral radius to quantitatively characterize the nonlinear recurrent behaviors related to the distinct flow patterns. We find that these two network measures are very sensitive to the change of flow states and the distributions of network measures enable to uncover the spatial dynamical flow behaviors underlying different oil-water flow patterns. Our method paves the way for efficiently analyzing multi-channel signals from multi-layer sensor measurement system.

  19. Functional interaction between S1 and S4 segments in voltage-gated sodium channels revealed by human channelopathies.

    Science.gov (United States)

    Amarouch, Mohamed-Yassine; Kasimova, Marina A; Tarek, Mounir; Abriel, Hugues

    2014-01-01

    The p.I141V mutation of the voltage-gated sodium channel is associated with several clinical hyper-excitability phenotypes. To understand the structural bases of the p.I141V biophysical alterations, molecular dynamics simulations were performed. These simulations predicted that the p.I141V substitution induces the formation of a hydrogen bond between the Y168 residue of the S2 segment and the R225 residue of the S4 segment. We generated a p.I141V-Y168F double mutant for both the Nav1.4 and Nav1.5 channels. The double mutants demonstrated the abolition of the functional effects of the p.I141V mutation, consistent with the formation of a specific interaction between Y168-S2 and R225-S4. The single p.Y168F mutation, however, positively shifted the activation curve, suggesting a compensatory role of these residues on the stability of the voltage-sensing domain.

  20. Subcellular localization of the K+ channel subunit Kv3.1b in selected rat CNS neurons.

    Science.gov (United States)

    Sekirnjak, C; Martone, M E; Weiser, M; Deerinck, T; Bueno, E; Rudy, B; Ellisman, M

    1997-08-22

    Voltage-gated potassium channels constitute the largest group of heteromeric ion channels discovered to date. Over 20 genes have been isolated, encoding different channel subunit proteins which form functional tetrameric K+ channels. We have analyzed the subcellular localization of subunit Kv3.1b, a member of the Kv3 (Shaw-like) subfamily, in rat brain at the light and electron microscopic level, using immunocytochemical detection. Detailed localization was carried out in specific neurons of the neocortex, hippocampus and cerebellum. The identity of Kv3.1b-positive neurons was established using double labeling with markers for specific neuronal populations. In the neocortex, the Kv3.1b subunit was expressed in most parvalbumin-containing bipolar, basket or chandelier cells, and in some bipolar or double bouquet neurons containing calbindin. In the hippocampus, Kv3.1b was expressed in many parvalbumin-containing basket cells, as well as in calbindin-positive neurons in the stratum oriens, and in a small number of interneurons that did not stain for either parvalbumin or calbindin. Kv3.1b protein was not present in pyramidal cells in the neocortex and the hippocampus, but these cells were outlined by labeled presynaptic terminals from interneuron axons that surround the postsynaptic cell. In the cerebellar cortex, granule cells were the only population expressing the channel protein. Careful examination of individual granule cells revealed a non-uniform distribution of Kv3.1 staining on the somata: circular bands of labeling were present in the vicinity of the axon hillock. In cortical and hippocampal interneurons, as well as in cerebellar granule cells, the Kv3.1b subunit was present in somatic and unmyelinated axonal membranes and adjacent cytoplasm, as well as in the most proximal portion of dendritic processes, but not throughout most of the dendrite. Labeling was also seen in the terminals of labeled axons, but not at a higher concentration than in other parts

  1. Gain of Imaging Fidelity by Employing a Higher Number of Independent Transmit Channels Together with Slice-Selective Radio-Frequency (RF Shimming at 7T

    Directory of Open Access Journals (Sweden)

    Niravkumar Darji

    2013-12-01

    Full Text Available Dielectric resonance effects and radio-frequency (RF power deposition have become challenging issues for magnetic resonance imaging at ultrahigh-field (UHF strengths. The use of transmit (Tx coil arrays with independently-driven RF sources using a parallel transmission system is a promising method for alleviating the resulting RF inhomogeneities. In this study, the effect on homogeneity and RF-power when employing a higher number of transmit channels with multi-slice acquisition in vivo at high field strength (7T is scrutinized. An 8-channel head coil array was driven to emulate circular polarized (CP and 2-, 4-, and 8-channel independent transmit configurations at 7T. Static RF shimming was employed on human subjects in order to homogenize the B1+ field in the excited volume. Slice-selective and global RF shimming methods were applied with CP and 2-, 4-, and 8-channel transmit channel configurations. RF shimming was performed from CP to 2-, 4-, and 8-channel Tx configurations globally and slice-selectively. Systematic improvement in B1+ homogeneity and/or reduction in RF-power were observed. RF shimming in the human brain with 8-channel transmit and slice-selective shimming yields an increase in B1+ homogeneity of 43% and/or reduces RF-power by 68% when compared with CP global RF shimming at 7T.

  2. The Scorpion Toxin Analogue BmKTX-D33H as a Potential Kv1.3 Channel-Selective Immunomodulator for Autoimmune Diseases.

    Science.gov (United States)

    Ye, Fang; Hu, Youtian; Yu, Weiwei; Xie, Zili; Hu, Jun; Cao, Zhijian; Li, Wenxin; Wu, Yingliang

    2016-04-19

    The Kv1.3 channel-acting scorpion toxins usually adopt the conserved anti-parallel β-sheet domain as the binding interface, but it remains challenging to discover some highly selective Kv1.3 channel-acting toxins. In this work, we investigated the pharmacological profile of the Kv1.3 channel-acting BmKTX-D33H, a structural analogue of the BmKTX scorpion toxin. Interestingly, BmKTX-D33H, with its conserved anti-parallel β-sheet domain as a Kv1.3 channel-interacting interface, exhibited more than 1000-fold selectivity towards the Kv1.3 channel as compared to other K⁺ channels (including Kv1.1, Kv1.2, Kv1.7, Kv11.1, KCa2.2, KCa2.3, and KCa3.1). As expected, BmKTX-D33H was found to inhibit the cytokine production and proliferation of both Jurkat cells and human T cells in vitro. It also significantly improved the delayed-type hypersensitivity (DTH) responses, an autoreactive T cell-mediated inflammation in rats. Amino acid sequence alignment and structural analysis strongly suggest that the "evolutionary" Gly11 residue of BmKTX-D33H interacts with the turret domain of Kv1 channels; it appears to be a pivotal amino acid residue with regard to the selectivity of BmKTX-D33H towards the Kv1.3 channel (in comparison with the highly homologous scorpion toxins). Together, our data indicate that BmKTX-D33H is a Kv1.3 channel-specific blocker. Finally, the remarkable selectivity of BmKTX-D33H highlights the great potential of evolutionary-guided peptide drug design in future studies.

  3. An Improved Endmember Selection Method Based on Vector Length for MODIS Reflectance Channels

    Directory of Open Access Journals (Sweden)

    Yuanliu Xu

    2015-05-01

    Full Text Available Endmember selection is the basis for sub-pixel land cover classifications using multiple endmember spectral mixture analysis (MESMA that adopts variant endmember matrices for each pixel to mitigate errors caused by endmember variability in SMA. A spectral library covering a large number of endmembers can account for endmember variability, but it also lowers the computational efficiency. Therefore, an efficient endmember selection scheme to optimize the library is crucial to implement MESMA. In this study, we present an endmember selection method based on vector length. The spectra of a land cover class were divided into subsets using vector length intervals of the spectra, and the representative endmembers were derived from these subsets. Compared with the available endmember average RMSE (EAR method, our approach improved the computational efficiency in endmember selection. The method accuracy was further evaluated using spectral libraries derived from the ground reference polygon and Moderate Resolution Imaging Spectroradiometer (MODIS imagery respectively. Results using the different spectral libraries indicated that MESMA combined with the new approach performed slightly better than EAR method, with Kappa coefficient improved from 0.75 to 0.78. A MODIS image was used to test the mapping fraction, and the representative spectra based on vector length successfully modeled more than 90% spectra of the MODIS pixels by 2-endmember models.

  4. Artificial Selection Reveals High Genetic Variation in Phenology at the Trailing Edge of a Species Range.

    Science.gov (United States)

    Sheth, Seema Nayan; Angert, Amy Lauren

    2016-02-01

    Species responses to climate change depend on the interplay of migration and adaptation, yet we know relatively little about the potential for adaptation. Genetic adaptations to climate change often involve shifts in the timing of phenological events, such as flowering. If populations at the edge of a species range have lower genetic variation in phenological traits than central populations, then their persistence under climate change could be threatened. To test this hypothesis, we performed artificial selection experiments using the scarlet monkeyflower (Mimulus cardinalis) and compared genetic variation in flowering time among populations at the latitudinal center, northern edge, and southern edge of the species range. We also assessed whether selection on flowering time yielded correlated responses in functional traits, potentially representing a cost associated with early or late flowering. Contrary to prediction, southern populations exhibited greater responses to selection on flowering time than central or northern populations. Further, selection for early flowering resulted in correlated increases in specific leaf area and leaf nitrogen, whereas selection for late flowering led to decreases in these traits. These results provide critical insights about how spatial variation in the potential for adaptation may affect population persistence under changing climates.

  5. Analysis of Adaptive Evolution in Lyssavirus Genomes Reveals Pervasive Diversifying Selection during Species Diversification

    Directory of Open Access Journals (Sweden)

    Carolina M. Voloch

    2014-11-01

    Full Text Available Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. Although numerous studies have examined pattern-related questions concerning Lyssavirus evolution, analyses of the evolutionary processes acting on Lyssavirus diversification are scarce. To clarify the relevance of positive natural selection in Lyssavirus diversification, we conducted a comprehensive scan for episodic diversifying selection across all lineages and codon sites of the five coding regions in lyssavirus genomes. Although the genomes of these viruses are generally conserved, the glycoprotein (G, RNA-dependent RNA polymerase (L and polymerase (P genes were frequently targets of adaptive evolution during the diversification of the genus. Adaptive evolution is particularly manifest in the glycoprotein gene, which was inferred to have experienced the highest density of positively selected codon sites along branches. Substitutions in the L gene were found to be associated with the early diversification of phylogroups. A comparison between the number of positively selected sites inferred along the branches of RABV population branches and Lyssavirus intespecies branches suggested that the occurrence of positive selection was similar on the five coding regions of the genome in both groups.

  6. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles

    Science.gov (United States)

    Orozco-terWengel, Pablo; Kapun, Martin; Nolte, Viola; Kofler, Robert; Flatt, Thomas; Schlötterer, Christian

    2012-01-01

    The genomic basis of adaptation to novel environments is a fundamental problem in evolutionary biology that has gained additional importance in the light of the recent global change discussion. Here, we combined laboratory natural selection (experimental evolution) in Drosophila melanogaster with genome-wide next generation sequencing of DNA pools (Pool-Seq) to identify alleles that are favourable in a novel laboratory environment and traced their trajectories during the adaptive process. Already after 15 generations, we identified a pronounced genomic response to selection, with almost 5000 single nucleotide polymorphisms (SNP; genome-wide false discovery rates < 0.005%) deviating from neutral expectation. Importantly, the evolutionary trajectories of the selected alleles were heterogeneous, with the alleles falling into two distinct classes: (i) alleles that continuously rise in frequency; and (ii) alleles that at first increase rapidly but whose frequencies then reach a plateau. Our data thus suggest that the genomic response to selection can involve a large number of selected SNPs that show unexpectedly complex evolutionary trajectories, possibly due to nonadditive effects. PMID:22726122

  7. Transcriptome sequencing of Eucalyptus camaldulensis seedlings subjected to water stress reveals functional single nucleotide polymorphisms and genes under selection

    Directory of Open Access Journals (Sweden)

    Thumma Bala R

    2012-08-01

    Full Text Available Abstract Background Water stress limits plant survival and production in many parts of the world. Identification of genes and alleles responding to water stress conditions is important in breeding plants better adapted to drought. Currently there are no studies examining the transcriptome wide gene and allelic expression patterns under water stress conditions. We used RNA sequencing (RNA-seq to identify the candidate genes and alleles and to explore the evolutionary signatures of selection. Results We studied the effect of water stress on gene expression in Eucalyptus camaldulensis seedlings derived from three natural populations. We used reference-guided transcriptome mapping to study gene expression. Several genes showed differential expression between control and stress conditions. Gene ontology (GO enrichment tests revealed up-regulation of 140 stress-related gene categories and down-regulation of 35 metabolic and cell wall organisation gene categories. More than 190,000 single nucleotide polymorphisms (SNPs were detected and 2737 of these showed differential allelic expression. Allelic expression of 52% of these variants was correlated with differential gene expression. Signatures of selection patterns were studied by estimating the proportion of nonsynonymous to synonymous substitution rates (Ka/Ks. The average Ka/Ks ratio among the 13,719 genes was 0.39 indicating that most of the genes are under purifying selection. Among the positively selected genes (Ka/Ks > 1.5 apoptosis and cell death categories were enriched. Of the 287 positively selected genes, ninety genes showed differential expression and 27 SNPs from 17 positively selected genes showed differential allelic expression between treatments. Conclusions Correlation of allelic expression of several SNPs with total gene expression indicates that these variants may be the cis-acting variants or in linkage disequilibrium with such variants. Enrichment of apoptosis and cell death gene

  8. State-to-state mode selectivity in the HD + OH reaction: Perspectives from two product channels

    Science.gov (United States)

    Zhao, Bin; Sun, Zhigang; Guo, Hua

    2016-06-01

    The state-to-state quantum dynamics (Jtot = 0) of the HD + OH(υ2 = 0, 1) reaction is studied using a reactant coordinate based method, which allows the analysis of both the H + DOH and D + HOH channels with a single propagation. The stretching vibration of the newly formed bond, namely, the OD bond in DOH and one OH bond in HOH, is excited, thanks to its strong coupling with the reaction coordinate at the transition state. On the other hand, the vibrational energy deposited into the OH reactant (υ2 = 1) is sequestered during the reaction in the spectator OH mode. The combined effect leads to the excitation of both the OD and OH stretching modes in the DOH product, and the dominance of the (002) normal-mode state population in the HOH product, which in the local-mode picture corresponds to the excitation of both OH bonds with one quantum each. The energy flow in this prototypical tetratomic reaction can be understood in terms of the sudden vector projection model.

  9. Genome Sequencing Reveals Loci under Artificial Selection that Underlie Disease Phenotypes in the Laboratory Rat

    NARCIS (Netherlands)

    Atanur, Santosh S.; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R.; Kaisaki, Pamela J.; Otto, Georg W.; Ma, Man Chun John; Keane, Thomas M.; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R.; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J.; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J.

    2013-01-01

    Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and ins

  10. Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat

    NARCIS (Netherlands)

    Atanur, S.S.; Diaz, A.G.; Maratou, K.; Sarkis, A.; Rotival, M.; Game, L.; Tschannen, M.R.; Kaisaki, P.J.; Otto, G.W.; Ma, M.C.; Keane, T.M.; Hummel, O.; Saar, K.; Chen, W.; Guryev, V.; Gopalakrishnan, K.; Garrett, M.R.; Joe, B.; Citterio, L.; Bianchi, G.; McBride, M.; Dominiczak, A.; Adams, D.J.; Serikawa, T.; Flicek, P.; Cuppen, E.; Hubner, N.; Petretto, E.; Gauguier, D.; Kwitek, A.; Jacob, H.; Aitman, T.J.

    2013-01-01

    Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and ins

  11. DNA indels in coding regions reveal selective constraints on protein evolution in the human lineage

    Directory of Open Access Journals (Sweden)

    Messer Philipp W

    2007-10-01

    Full Text Available Abstract Background Insertions and deletions of DNA segments (indels are together with substitutions the major mutational processes that generate genetic variation. Here we focus on recent DNA insertions and deletions in protein coding regions of the human genome to investigate selective constraints on indels in protein evolution. Results Frequencies of inserted and deleted amino acids differ from background amino acid frequencies in the human proteome. Small amino acids are overrepresented, while hydrophobic, aliphatic and aromatic amino acids are strongly suppressed. Indels are found to be preferentially located in protein regions that do not form important structural domains. Amino acid insertion and deletion rates in genes associated with elementary biochemical reactions (e. g. catalytic activity, ligase activity, electron transport, or catabolic process are lower compared to those in other genes and are therefore subject to stronger purifying selection. Conclusion Our analysis indicates that indels in human protein coding regions are subject to distinct levels of selective pressure with regard to their structural impact on the amino acid sequence, as well as to general properties of the genes they are located in. These findings confirm that many commonly accepted characteristics of selective constraints for substitutions are also valid for amino acid insertions and deletions.

  12. Adaptation to real motion reveals direction-selective interactions between real and implied motion processing

    NARCIS (Netherlands)

    Lorteije, J.A.M.; Kenemans, J.L.; Jellema, T.; Lubbe, R.H.J. van der; Lommers, M.W.; Wezel, R.J.A. van

    2007-01-01

    Viewing static pictures of running humans evokes neural activity in the dorsal motion-sensitive cortex. To establish whether this response arises from direction-selective neurons that are also involved in real motion processing, we measured the visually evoked potential to implied motion following a

  13. Adaptation to Real Motion Reveals Direction-selective Interactions between Real and Implied Motion Processing

    NARCIS (Netherlands)

    Lorteije, Jeannette A.M.; Kenemans, Leon; Jellema, Tjeerd; Lubbe, van der Rob H.J.; Lommers, Marjolein W.; Wezel, van Richard J.A.

    2007-01-01

    Viewing static pictures of running humans evokes neural activity in the dorsal motion-sensitive cortex. To establish whether this response arises from direction-selective neurons that are also involved in real motion processing, we measured the visually evoked potential to implied motion following a

  14. Movement reveals scale dependence in habitat selection of a large ungulate.

    Science.gov (United States)

    Northrup, Joseph M; Anderson, Charles R; Hooten, Mevin B; Wittemyer, George

    2016-12-01

    Ecological processes operate across temporal and spatial scales. Anthropogenic disturbances impact these processes, but examinations of scale dependence in impacts are infrequent. Such examinations can provide important insight to wildlife-human interactions and guide management efforts to reduce impacts. We assessed spatiotemporal scale dependence in habitat selection of mule deer (Odocoileus hemionus) in the Piceance Basin of Colorado, USA, an area of ongoing natural gas development. We employed a newly developed animal movement method to assess habitat selection across scales defined using animal-centric spatiotemporal definitions ranging from the local (defined from five hour movements) to the broad (defined from weekly movements). We extended our analysis to examine variation in scale dependence between night and day and assess functional responses in habitat selection patterns relative to the density of anthropogenic features. Mule deer displayed scale invariance in the direction of their response to energy development features, avoiding well pads and the areas closest to roads at all scales, though with increasing strength of avoidance at coarser scales. Deer displayed scale-dependent responses to most other habitat features, including land cover type and habitat edges. Selection differed between night and day at the finest scales, but homogenized as scale increased. Deer displayed functional responses to development, with deer inhabiting the least developed ranges more strongly avoiding development relative to those with more development in their ranges. Energy development was a primary driver of habitat selection patterns in mule deer, structuring their behaviors across all scales examined. Stronger avoidance at coarser scales suggests that deer behaviorally mediated their interaction with development, but only to a degree. At higher development densities than seen in this area, such mediation may not be possible and thus maintenance of sufficient habitat

  15. Photonic Crystal Fiber-Based Surface Plasmon Resonance Sensor with Selective Analyte Channels and Graphene-Silver Deposited Core

    Directory of Open Access Journals (Sweden)

    Ahmmed A. Rifat

    2015-05-01

    Full Text Available We propose a surface plasmon resonance (SPR sensor based on photonic crystal fiber (PCF with selectively filled analyte channels. Silver is used as the plasmonic material to accurately detect the analytes and is coated with a thin graphene layer to prevent oxidation. The liquid-filled cores are placed near to the metallic channel for easy excitation of free electrons to produce surface plasmon waves (SPWs. Surface plasmons along the metal surface are excited with a leaky Gaussian-like core guided mode. Numerical investigations of the fiber’s properties and sensing performance are performed using the finite element method (FEM. The proposed sensor shows maximum amplitude sensitivity of 418 Refractive Index Units (RIU−1 with resolution as high as 2.4 × 10−5 RIU. Using the wavelength interrogation method, a maximum refractive index (RI sensitivity of 3000 nm/RIU in the sensing range of 1.46–1.49 is achieved. The proposed sensor is suitable for detecting various high RI chemicals, biochemical and organic chemical analytes. Additionally, the effects of fiber structural parameters on the properties of plasmonic excitation are investigated and optimized for sensing performance as well as reducing the sensor’s footprint.

  16. ZD7288, a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity

    Institute of Scientific and Technical Information of China (English)

    Xiao-xue Zhang; Xiao-chun Min; Xu-lin Xu; Min Zheng; Lian-jun Guo

    2016-01-01

    The selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimeth-yl-6-(methylamino) pyrimidinium chloride (ZD7288) blocks the induction of long-term potentiation in the perforant path–CA3 region in rat hippocampusin vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path–CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hip-pocampal neurons using high performance liquid chromatography, and determined intracellular Ca2+ concentration ([Ca2+]i) using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspeciifc HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Further-more, ZD7288 attenuated glutamate-induced rises in [Ca2+]i in a concentration-dependent manner and reversed 8-Br-cAMP-mediated facilitation of these glutamate-induced [Ca2+]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both gluta-mate release and resultant [Ca2+]i increases in rat hippocampal neurons.

  17. Photonic crystal fiber-based surface plasmon resonance sensor with selective analyte channels and graphene-silver deposited core.

    Science.gov (United States)

    Rifat, Ahmmed A; Mahdiraji, G Amouzad; Chow, Desmond M; Shee, Yu Gang; Ahmed, Rajib; Adikan, Faisal Rafiq Mahamd

    2015-05-19

    We propose a surface plasmon resonance (SPR) sensor based on photonic crystal fiber (PCF) with selectively filled analyte channels. Silver is used as the plasmonic material to accurately detect the analytes and is coated with a thin graphene layer to prevent oxidation. The liquid-filled cores are placed near to the metallic channel for easy excitation of free electrons to produce surface plasmon waves (SPWs). Surface plasmons along the metal surface are excited with a leaky Gaussian-like core guided mode. Numerical investigations of the fiber's properties and sensing performance are performed using the finite element method (FEM). The proposed sensor shows maximum amplitude sensitivity of 418 Refractive Index Units (RIU-1) with resolution as high as 2.4 × 10(-5) RIU. Using the wavelength interrogation method, a maximum refractive index (RI) sensitivity of 3000 nm/RIU in the sensing range of 1.46-1.49 is achieved. The proposed sensor is suitable for detecting various high RI chemicals, biochemical and organic chemical analytes. Additionally, the effects of fiber structural parameters on the properties of plasmonic excitation are investigated and optimized for sensing performance as well as reducing the sensor's footprint.

  18. Photonic Crystal Fiber-Based Surface Plasmon Resonance Sensor with Selective Analyte Channels and Graphene-Silver Deposited Core

    Science.gov (United States)

    Rifat, Ahmmed A.; Mahdiraji, G. Amouzad; Chow, Desmond M.; Shee, Yu Gang; Ahmed, Rajib; Adikan, Faisal Rafiq Mahamd

    2015-01-01

    We propose a surface plasmon resonance (SPR) sensor based on photonic crystal fiber (PCF) with selectively filled analyte channels. Silver is used as the plasmonic material to accurately detect the analytes and is coated with a thin graphene layer to prevent oxidation. The liquid-filled cores are placed near to the metallic channel for easy excitation of free electrons to produce surface plasmon waves (SPWs). Surface plasmons along the metal surface are excited with a leaky Gaussian-like core guided mode. Numerical investigations of the fiber’s properties and sensing performance are performed using the finite element method (FEM). The proposed sensor shows maximum amplitude sensitivity of 418 Refractive Index Units (RIU−1) with resolution as high as 2.4 × 10−5 RIU. Using the wavelength interrogation method, a maximum refractive index (RI) sensitivity of 3000 nm/RIU in the sensing range of 1.46–1.49 is achieved. The proposed sensor is suitable for detecting various high RI chemicals, biochemical and organic chemical analytes. Additionally, the effects of fiber structural parameters on the properties of plasmonic excitation are investigated and optimized for sensing performance as well as reducing the sensor’s footprint. PMID:25996510

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Genetic Diversity of Selected Mangifera Species Revealed by Inter Simple Sequence Repeats Markers

    OpenAIRE

    2015-01-01

    ISSR markers were employed to reveal genetic diversity and genetic relatedness among 28 Mangifera accessions collected from Yan (Kedah), Bukit Gantang (Perak), Sibuti (Sarawak), and Papar (Sabah). A total of 198 markers were generated using nine anchored primers and one nonanchored primer. Genetic variation among the 28 accessions of Mangifera species including wild relatives, landraces, and clonal varieties is high, with an average degree of polymorphism of 98% and mean Shannon index, H0=7.5...

  2. An easy prepared dual-channel chemosensor for selective and instant detection of fluoride based on double Schiff-base

    Science.gov (United States)

    Leng, Yan-Li; Zhang, Jian-Hui; Li, Qiao; Zhang, You-Ming; Lin, Qi; Yao, Hong; Wei, Tai-Bao

    2016-10-01

    A colorimetric and fluorescent dual-channel fluoride chemosensor N,N‧-bis (4-diethylaminosalicylidene) hydrazine (sensor S) bearing two imine groups has been designed and synthesized. This structurally simple probe displays rapid response and high selectivity for fluoride over other common anions (Cl-, Br-, I-, AcO-, H2PO4-, HSO4-, ClO4-, CN- and SCN-) in a highly polar aqueous DMSO solution. Mechanism studies suggested that the sensor firstly combined with F- through hydrogen bonds and then experienced the deprotonation process at higher concentrations of F- anion to the two Ar-OH groups. The detection limit was 5.78 × 10- 7 M of F-, which points to the high detection sensitivity. Test strips based on sensor S were fabricated, which could act as a convenient and efficient F- test kit to detect F- for "in-the-field" measurement.

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

    CERN Document Server

    Cosseddu, Salvatore M; 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 under-damped Langevin equation with constant damping and white noise or by Langevin equation with a fractional memory kernel. A comparison of the potential of the mean force derived from unbiased MD simulations with the potential produced by the umbrella sampling method demonstrates significant differences in these potentials. The origin of these differences is an open question that requires further clarifications.

  4. Adaptation of ASTC in a Correlated Rayleigh Frequency-Selective Fading Channels in OFDM systems with PAPR Reduction

    Directory of Open Access Journals (Sweden)

    Ahmed BANNOUR

    2010-05-01

    Full Text Available In this paper we suggest to use the ASTC (Algebraic Space Time Codes as powerful coding technique for IEEE802.11x OFDM standard combined with PAPR reduction scheme. ASTC with their very Algebraic- constructionbased on Quaternionic algebra, have a full rate, full diversity, non-vanishing constant minimum determinant forincreasing spectral efficiency, uniform average transmitted energy per antenna and good shaping, readily lendthemselves to high data rate situations. However, by their construction they require a nonselective flat fadingchannels belonging to narrow-band systems. In fact, such systems are not readily found in airs interfaces. Inopen air we have what are commonly called frequency-selective fading channels. As a matter of fact, it becomesextremely necessary to harness their power for wide-band systems.

  5. Whole-Genome Analysis Revealed the Positively Selected Genes during the Differentiation of indica and Temperate japonica Rice

    Science.gov (United States)

    Sun, Xinli; Jia, Qi; Guo, Yuchun; Zheng, Xiujuan; Liang, Kangjing

    2015-01-01

    To investigate the selective pressures acting on the protein-coding genes during the differentiation of indica and japonica, all of the possible orthologous genes between the Nipponbare and 93–11 genomes were identified and compared with each other. Among these genes, 8,530 pairs had identical sequences, and 27,384 pairs shared more than 90% sequence identity. Only 2,678 pairs of genes displaying a Ka/Ks ratio significantly greater than one were revealed, and most of these genes contained only nonsynonymous sites. The genes without synonymous site were further analyzed with the SNP data of 1529 O. sativa and O. rufipogon accessions, and 1068 genes were identified to be under positive selection during the differentiation of indica and temperate japonica. The positively selected genes (PSGs) are unevenly distributed on 12 chromosomes, and the proteins encoded by the PSGs are dominant with binding, transferase and hydrolase activities, and especially enriched in the plant responses to stimuli, biological regulations, and transport processes. Meanwhile, the most PSGs of the known function and/or expression were involved in the regulation of biotic/abiotic stresses. The evidence of pervasive positive selection suggested that many factors drove the differentiation of indica and japonica, which has already started in wild rice but is much lower than in cultivated rice. Lower differentiation and less PSGs revealed between the Or-It and Or-IIIt wild rice groups implied that artificial selection provides greater contribution on the differentiation than natural selection. In addition, the phylogenetic tree constructed with positively selected sites showed that the japonica varieties exhibited more diversity than indica on differentiation, and Or-III of O. rufipogon exhibited more than Or-I. PMID:25774680

  6. Joint random beam and spectrum selection for spectrum sharing systems with partial channel state information

    KAUST Repository

    Abdallah, Mohamed M.

    2013-11-01

    In this work, we develop joint interference-aware random beam and spectrum selection scheme that provide enhanced performance for the secondary network under the condition that the interference observed at the primary receiver is below a predetermined acceptable value. We consider a secondary link composed of a transmitter equipped with multiple antennas and a single-antenna receiver sharing the same spectrum with a set of primary links composed of a single-antenna transmitter and a single-antenna receiver. The proposed schemes jointly select a beam, among a set of power-optimized random beams, as well as the primary spectrum that maximizes the signal-to-interference-plus-noise ratio (SINR) of the secondary link while satisfying the primary interference constraint. In particular, we consider the case where the interference level is described by a q-bit description of its magnitude, whereby we propose a technique to find the optimal quantizer thresholds in a mean square error (MSE) sense. © 2013 IEEE.

  7. 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

    2012-02-01

    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.

  8. 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.

  9. Characterization of edible film fabricated with channel catfish (Ictalurus punctatus) gelatin extract using selected pretreatment methods.

    Science.gov (United States)

    Zhang, S; Wang, Y; Herring, J L; Oh, J-H

    2007-11-01

    Farm-raised catfish are important to the economy of the southeastern states in the United States, and catfish processing produces about 55% of by-products for inexpensive sale. Therefore, the utilization of catfish by-products is of great interest to the catfish industry. The objectives of this research were to determine the optimum pretreatment method to extract catfish gelatin for edible film application, and to characterize physical, mechanical, and barrier properties of edible films fabricated with catfish skin gelatin. Catfish skins obtained from a local plant were treated with 6 selected pretreatment methods. The main extraction was performed with deionized water at 50 degrees C after pretreatment. The gelatin yield was calculated and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to characterize molecular weight (MW) profile. Color, tensile strength (TS), elongation, and water barrier property were determined to characterize the fabricated catfish gelatin films. From the results of gelatin yield, color, SDS-PAGE, as well as mechanical and barrier properties of the film, the pretreatment method with 0.25 M NaOH and 0.09 M acetic acid, followed by extraction at 50 degrees C for 3 h, was determined as the optimum extraction method. The catfish gelatin exhibited higher MW fractions than commercial mammalian gelatin. The catfish gelatin extracts possessed film-forming properties determined by TS, elongation, and water vapor permeability (WVP) comparable to those of commercial mammalian gelatin. The selected formula for catfish gelatin film was determined as 1% gelatin and 20% glycerol, resulting in greatest TS and lowest WVP.

  10. Tityus gamma toxin, a high affinity effector of the Na+ channel in muscle, with a selectivity for channels in the surface membrane.

    Science.gov (United States)

    Barhanin, J; Ildefonse, M; Rougier, O; Sampaio, S V; Giglio, J R; Lazdunski, M

    1984-01-01

    Toxin gamma from the venom of Tityus serrulatus scorpion produces a partial block of the surface Na+ channel in frog muscle. This block occurs with no change in the voltage-dependence or in the kinetics of the remaining surface Na+ current. The partial blockade of Na+ channel activity occurs with no change in tubular Na+ currents nor in twitch tension. The maximum effect of the toxin is attained at concentrations as low as 3 X 10(-10) M. Hyperpolarization to potentials more negative than the resting potential (E = -90 mV) reduces or abolishes the effect of the toxin. Radioiodinated toxin gamma binds to frog muscle membranes with a very high affinity corresponding to a dissociation constant of about 1 X 10(-11) M. Data obtained with both rabbit and frog muscle indicate that toxin gamma is specific for Na+ channels in surface membranes. Toxin gamma does not seem to bind to Na+ channels in T-tubule membranes. The biochemical data are in good agreement with electrophysiological studies and data on contraction. There is one Tityus gamma toxin binding site per tetrodotoxin binding site in surface membranes. Competition experiments have confirmed that Tityus gamma toxin binds to a new toxin receptor site on the Na+ channel structure. This site is the same that the toxin II from Centruroides suffusus binding site, but this toxin has 100 times less affinity for the Na+ channel than Tityus gamma toxin.

  11. [Salmonella typhi vaccination response study reveals defective antibody production selective IgA deficiency patient].

    Science.gov (United States)

    Pleguezuelo, Daniel E; Gianelli, Carla

    2015-01-01

    Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre-vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production.

  12. Aiptasia sp. larvae as a model to reveal mechanisms of symbiont selection in cnidarians

    KAUST Repository

    Wolfowicz, Iliona

    2016-09-01

    Symbiosis, defined as the persistent association between two distinct species, is an evolutionary and ecologically critical phenomenon facilitating survival of both partners in diverse habitats. The biodiversity of coral reef ecosystems depends on a functional symbiosis with photosynthetic dinoflagellates of the highly diverse genus Symbiodinium, which reside in coral host cells and continuously support their nutrition. The mechanisms underlying symbiont selection to establish a stable endosymbiosis in non-symbiotic juvenile corals are unclear. Here we show for the first time that symbiont selection patterns for larvae of two Acropora coral species and the model anemone Aiptasia are similar under controlled conditions. We find that Aiptasia larvae distinguish between compatible and incompatible symbionts during uptake into the gastric cavity and phagocytosis. Using RNA-Seq, we identify a set of candidate genes potentially involved in symbiosis establishment. Together, our data complement existing molecular resources to mechanistically dissect symbiont phagocytosis in cnidarians under controlled conditions, thereby strengthening the role of Aiptasia larvae as a powerful model for cnidarian endosymbiosis establishment.

  13. Adaptation to real motion reveals direction-selective interactions between real and implied motion processing.

    Science.gov (United States)

    Lorteije, Jeannette A M; Kenemans, J Leon; Jellema, Tjeerd; van der Lubbe, Rob H J; Lommers, Marjolein W; van Wezel, Richard J A

    2007-08-01

    Viewing static pictures of running humans evokes neural activity in the dorsal motion-sensitive cortex. To establish whether this response arises from direction-selective neurons that are also involved in real motion processing, we measured the visually evoked potential to implied motion following adaptation to static or moving random dot patterns. The implied motion response was defined as the difference between evoked potentials to pictures with and without implied motion. Interaction between real and implied motion was found as a modulation of this difference response by the preceding motion adaptation. The amplitude of the implied motion response was significantly reduced after adaptation to motion in the same direction as the implied motion, compared to motion in the opposite direction. At 280 msec after stimulus onset, the average difference in amplitude reduction between opposite and same adapted direction was 0.5 muV on an average implied motion amplitude of 2.0 muV. These results indicate that the response to implied motion arises from direction-selective motion-sensitive neurons. This is consistent with interactions between real and implied motion processing at a neuronal level.

  14. Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes.

    Science.gov (United States)

    Van Le, Quan; Isbell, Lynne A; Matsumoto, Jumpei; Nguyen, Minh; Hori, Etsuro; Maior, Rafael S; Tomaz, Carlos; Tran, Anh Hai; Ono, Taketoshi; Nishijo, Hisao

    2013-11-19

    Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates' heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage.

  15. SEXUAL SELECTION. Irrationality in mate choice revealed by túngara frogs.

    Science.gov (United States)

    Lea, Amanda M; Ryan, Michael J

    2015-08-28

    Mate choice models derive from traditional microeconomic decision theory and assume that individuals maximize their Darwinian fitness by making economically rational decisions. Rational choices exhibit regularity, whereby the relative strength of preferences between options remains stable when additional options are presented. We tested female frogs with three simulated males who differed in relative call attractiveness and call rate. In binary choice tests, females' preferences favored stimulus caller B over caller A; however, with the addition of an inferior "decoy" C, females reversed their preferences and chose A over B. These results show that the relative valuation of mates is not independent of inferior alternatives in the choice set and therefore cannot be explained with the rational choice models currently used in sexual selection theory.

  16. Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes

    Science.gov (United States)

    Van Le, Quan; Isbell, Lynne A.; Matsumoto, Jumpei; Nguyen, Minh; Hori, Etsuro; Maior, Rafael S.; Tomaz, Carlos; Tran, Anh Hai; Ono, Taketoshi; Nishijo, Hisao

    2013-01-01

    Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates’ heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage. PMID:24167268

  17. Chemical proteomics with sulfonyl fluoride probes reveals selective labeling of functional tyrosines in glutathione transferases.

    Science.gov (United States)

    Gu, Christian; Shannon, D Alexander; Colby, Tom; Wang, Zheming; Shabab, Mohammed; Kumari, Selva; Villamor, Joji Grace; McLaughlin, Christopher J; Weerapana, Eranthie; Kaiser, Markus; Cravatt, Benjamin F; van der Hoorn, Renier A L

    2013-04-18

    Chemical probes have great potential for identifying functional residues in proteins in crude proteomes. Here we studied labeling sites of chemical probes based on sulfonyl fluorides (SFs) on plant and animal proteomes. Besides serine proteases and many other proteins, SF-based probes label Tyr residues in glutathione transferases (GSTs). The labeled GSTs represent four different GST classes that share less than 30% sequence identity. The targeted Tyr residues are located at similar positions in the promiscuous substrate binding site and are essential for GST function. The high selectivity of SF-based probes for functional Tyr residues in GSTs illustrates how these probes can be used for functional studies of GSTs and other proteins in crude proteomes.

  18. Ultrafast nuclear dynamics in halomethanes studied with time-resolved Coulomb explosion imaging and channel-selective Fourier spectroscopy

    Science.gov (United States)

    Malakar, Y.; Kaderiya, B.; Pearson, W. L.; Ziaee, F.; Kanaka Raju, P.; Zohrabi, M.; Jensen, K.; Rajput, J.; Ben-Itzhak, I.; Rolles, D.; Rudenko, A.

    2016-05-01

    Halomethanes have recently attracted considerable attention since they often serve as prototype systems for laser-controlled chemistry (e.g., selective bond breaking or concerted elimination reactions), and are important molecules in atmospheric chemistry. Here we combine a femtosecond laser pump-probe setup with coincident 3D ion momentum imaging apparatus to study strong-field induced nuclear dynamics in methane and several of its halogenated derivatives (CH3 I, CH2 I2, CH2 ICl). We apply a time-resolved Coulomb explosion imaging technique to map the nuclear motion on both, bound and continuum potential surfaces, disentangle different fragmentation pathways and, for halogenated molecules, observe clear signatures of vibrational wave packets in neutral or ionized states. Channel-selective and kinetic-energy resolved Fourier analysis of these data allows for unique identification of different electronic states and vibrational modes responsible for a particular structure. Supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. DOE. K. R. P. and W. L. P. supported by NSF Award No. IIA-143049. K.J. supported by the NSF-REU Grant No. PHYS-1461251.

  19. Metagenome sequence analysis of filamentous microbial communities obtained from geochemically distinct geothermal channels reveals specialization of three aquificales lineages

    DEFF Research Database (Denmark)

    Takacs-Vesbach, Cristina; Inskeep, William P; Jay, Zackary J;

    2013-01-01

    containing 16S rRNA genes as well as conserved protein-encoding genes revealed that the composition and function of these communities varied across geochemical conditions. Each Aquificales lineage contained genes for CO2 fixation by the reverse-TCA cycle, but only the Sulfurihydrogenibium populations perform......The Aquificales are thermophilic microorganisms that inhabit hydrothermal systems worldwide and are considered one of the earliest lineages of the domain Bacteria. We analyzed metagenome sequence obtained from six thermal "filamentous streamer" communities (∼40 Mbp per site), which targeted three...... types of heme Cu oxidases (subunit I) involved in oxygen reduction. The distribution of Aquificales populations and differences among functional genes involved in energy generation and electron transport is consistent with the hypothesis that geochemical parameters (e.g., pH, sulfide, H2, O2) have...

  20. Metagenome Sequence Analysis of Filamentous Microbial Communities Obtained from Geochemically Distinct Geothermal Channels Reveals Specialization of Three Aquificales Lineages

    Directory of Open Access Journals (Sweden)

    Cristina eTakacs-vesbach

    2013-05-01

    Full Text Available The Aquificales are thermophilic microorganisms that inhabit hydrothermal systems worldwide and are considered one of the earliest lineages of the domain Bacteria. We analyzed metagenome sequence obtained from six thermal ‘filamentous streamer’ communities (~40 Mbp per site, which targeted three different groups of Aquificales found in Yellowstone National Park (YNP. Unassembled metagenome sequence and PCR-amplified 16S rRNA gene libraries revealed that acidic, sulfidic sites were dominated by Hydrogenobaculum (Aquificaceae populations, whereas the circumneutral pH (6.5 - 7.8 sites containing dissolved sulfide were dominated by Sulfurihydrogenibium spp. (Hydrogenothermaceae. Thermocrinis (Aquificaceae populations were found primarily in the circumneutral sites with undetectable sulfide, and to a lesser extent in one sulfidic system at pH 8. Phylogenetic analysis of assembled sequence containing 16S rRNA genes as well as conserved protein-encoding genes revealed that the composition and function of these communities varied across geochemical conditions. Each Aquificales lineage contained genes for CO2 fixation by the reverse TCA cycle, but only the Sulfurihydrogenibium populations perform citrate cleavage using ATP citrate lyase (Acl. The Aquificaceae populations use an alternative pathway catalyzed by two separate enzymes, citryl CoA synthetase (Ccs and citryl CoA lyase (Ccl. All three Aquificales lineages contained evidence of aerobic respiration, albeit due to completely different types of heme Cu oxidases (subunit I involved in oxygen reduction. The distribution of Aquificales populations and differences among functional genes involved in energy generation and electron transport is consistent with the hypothesis that geochemical parameters (e.g., pH, sulfide, H2, O2 have resulted in niche specialization among members of the Aquificales.

  1. 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.

  2. Genetic Diversity of Selected Mangifera Species Revealed by Inter Simple Sequence Repeats Markers

    Directory of Open Access Journals (Sweden)

    Zulhairil Ariffin

    2015-01-01

    Full Text Available ISSR markers were employed to reveal genetic diversity and genetic relatedness among 28 Mangifera accessions collected from Yan (Kedah, Bukit Gantang (Perak, Sibuti (Sarawak, and Papar (Sabah. A total of 198 markers were generated using nine anchored primers and one nonanchored primer. Genetic variation among the 28 accessions of Mangifera species including wild relatives, landraces, and clonal varieties is high, with an average degree of polymorphism of 98% and mean Shannon index, H0=7.50. Analysis on 18 Mangifera indica accessions also showed high degree of polymorphism of 99% and mean Shannon index, H0=5.74. Dice index of genetic similarity ranged from 0.0938 to 0.8046 among the Mangifera species. The dendrogram showed that the Mangifera species were grouped into three main divergent clusters. Cluster 1 comprised 14 accessions from Kedah and Perak. Cluster II and cluster III comprised 14 accessions from Sarawak and Sabah. Meanwhile, the Dice index of genetic similarity for 18 accessions of Mangifera indica ranged from 0.2588 to 0.7742. The dendrogram also showed the 18 accessions of Mangifera indica were grouped into three main clusters. Cluster I comprised 10 landraces of Mangifera indica from Kedah. Cluster II comprised 7 landraces of Mangifera indica followed by Chokanan to form Cluster III.

  3. Selection for Oil Content During Soybean Domestication Revealed by X-Ray Tomography of Ancient Beans

    Science.gov (United States)

    Zong, Yunbing; Yao, Shengkun; Crawford, Gary W.; Fang, Hui; Lang, Jianfeng; Fan, Jiadong; Sun, Zhibin; Liu, Yang; Zhang, Jianhua; Duan, Xiulan; Zhou, Guangzhao; Xiao, Tiqiao; Luan, Fengshi; Wang, Qing; Chen, Xuexiang; Jiang, Huaidong

    2017-01-01

    When and under what circumstances domestication related traits evolved in soybean (Glycine max) is not well understood. Seed size has been a focus of archaeological attention because increased soybean seed weight/size is a trait that distinguishes most modern soybeans from their ancestors; however, archaeological seed size analysis has had limited success. Modern domesticated soybean has a significantly higher oil content than its wild counterpart so oil content is potentially a source of new insight into soybean domestication. We investigated soybean oil content using X-ray computed tomography (CT; specifically, synchrotron radiation X-ray CT or SRX-CT) of charred, archaeological soybean seeds. CT identified holes in the specimens that are associated with oil content. A high oil content facilitates the development of small holes, whereas a high protein content results in larger holes. The volume of small holes increased slowly from 7,500 to 4,000 cal B.P. We infer that human selection for higher oil content began as early as 7,500 cal B.P. and that high oil content cultivars were well established by 4,000 cal B.P. PMID:28240321

  4. Selection for Oil Content During Soybean Domestication Revealed by X-Ray Tomography of Ancient Beans

    Science.gov (United States)

    Zong, Yunbing; Yao, Shengkun; Crawford, Gary W.; Fang, Hui; Lang, Jianfeng; Fan, Jiadong; Sun, Zhibin; Liu, Yang; Zhang, Jianhua; Duan, Xiulan; Zhou, Guangzhao; Xiao, Tiqiao; Luan, Fengshi; Wang, Qing; Chen, Xuexiang; Jiang, Huaidong

    2017-02-01

    When and under what circumstances domestication related traits evolved in soybean (Glycine max) is not well understood. Seed size has been a focus of archaeological attention because increased soybean seed weight/size is a trait that distinguishes most modern soybeans from their ancestors; however, archaeological seed size analysis has had limited success. Modern domesticated soybean has a significantly higher oil content than its wild counterpart so oil content is potentially a source of new insight into soybean domestication. We investigated soybean oil content using X-ray computed tomography (CT; specifically, synchrotron radiation X-ray CT or SRX-CT) of charred, archaeological soybean seeds. CT identified holes in the specimens that are associated with oil content. A high oil content facilitates the development of small holes, whereas a high protein content results in larger holes. The volume of small holes increased slowly from 7,500 to 4,000 cal B.P. We infer that human selection for higher oil content began as early as 7,500 cal B.P. and that high oil content cultivars were well established by 4,000 cal B.P.

  5. Natural selection and the genetic basis of osmoregulation in heteromyid rodents as revealed by RNA-seq.

    Science.gov (United States)

    Marra, Nicholas J; Romero, Andrea; DeWoody, J Andrew

    2014-06-01

    One adaptation of ecological and evolutionary interest is the extraordinary ability of desert rodents to retain water during waste production. Much is known regarding the unique kidney physiology of kangaroo rats (Dipodomys spp.) and their ability to retain water during waste production, yet the genetic basis of these physiological adaptations is relatively unknown. Herein, we utilized RNA-seq data to conduct a comparative study to identify osmoregulatory genes expressed in heteromyid rodents. We sequenced kidney tissue from two temperate desert species (Dipodomys spectabilis and Chaetodipus baileyi) from two separate subfamilies of the Heteromyidae and compared these transcriptomes to a tropical mesic species (Heteromys desmarestianus) from a third subfamily. The evolutionary history of these subfamilies provided a robust phylogenetic control that allowed us to separate shared evolutionary history from convergence. Using two methods to detect differential expression (DE), we identified 1890 genes that showed consistent patterns of DE between the arid and mesic species. A three-species reciprocal BLAST analysis revealed 3511 sets of putative orthologues that, upon comparison to known Mus musculus sequences, revealed 323 annotated and full-length genic regions. Selection tests displayed evidence of positive selection (dn/ds > 1) on six genes in the two desert species and remained significant for one of these genes after correction for multiple testing. Thus, our data suggest that both the coding sequence and expression of genes have been shaped by natural selection to provide the genetic architecture for efficient osmoregulation in desert-adapted heteromyid rodents.

  6. Oligotyping reveals community level habitat selection within the genus Vibrio

    Directory of Open Access Journals (Sweden)

    Victor Thomas Schmidt

    2014-11-01

    Full Text Available The genus Vibrio is a metabolically and genetically diverse group of facultative anaerobic Bacteria, common in aquatic environments and marine hosts. The genus contains several species of importance to human health and aquaculture, including the causative agents of human cholera and fish vibriosis. Vibrios display a wide variety of known life histories, from opportunistic pathogens to long-standing symbioses with individual host species. Studying Vibrio ecology has been challenging as individual species often display a wide range of habitat preferences, and groups of vibrios can act as socially cohesive groups. Although strong associations with salinity, temperature and other environmental variables have been established, the degree of habitat or host specificity at both the individual and community levels is unknown. Here we use oligotyping analyses in combination with a large collection of existing Vibrio 16S ribosomal RNA (rRNA gene sequence data to reveal patterns of Vibrio ecology across a wide range of environmental, host, and abiotic substrate associated habitats. Our data show that individual taxa often display a wide range of habitat preferences yet tend to be highly abundant in either substrate-associated or free-living environments. Our analyses show that Vibrio communities share considerable overlap between two distinct hosts (i.e., sponge and fish yet are distinct from the abiotic plastic substrates. Lastly, evidence for habitat specificity at the community level exists in some habitats, despite considerable stochasticity in others. In addition to providing insights into Vibrio ecology across a broad range of habitats, our study shows the utility of oligotyping as a facile, high-throughput and unbiased method for large scale analyses of publicly available sequence data repositories and suggests its wide application could greatly extend the range of possibilities to explore microbial ecology.

  7. Linear and nonlinear analyses of multi-channel mechanomyographic recordings reveal heterogeneous activation of wrist extensors in presence of delayed onset muscle soreness.

    Science.gov (United States)

    Madeleine, Pascal; Hansen, Ernst A; Samani, Afshin

    2014-12-01

    In this study, we applied multi-channel mechanomyographic (MMG) recordings in combination with linear and nonlinear analyses to investigate muscular and musculotendinous effects of high intensity eccentric exercise. Twelve accelerometers arranged in a 3 × 4 matrix over the dominant elbow muscles were used to detect MMG activity in 12 healthy participants. Delayed onset muscle soreness was induced by repetitive high intensity eccentric contractions of the wrist extensor muscles. Average rectified values (ARV) as well as percentage of recurrence (%REC) and percentage of determinism (%DET) extracted from recurrence quantification analysis were computed from data obtained during static-dynamic contractions performed before exercise, immediately after exercise, and in presence of muscle soreness. A linear mixed model was used for the statistical analysis. The ARV, %REC, and %DET maps revealed heterogeneous MMG activity over the wrist extensor muscles before, immediately after, and in presence of muscle soreness (P<0.01). The ARVs were higher while the %REC and %DET were lower in presence of muscle soreness compared with before exercise (P<0.05). The study provides new key information on linear and nonlinear analyses of multi-channel MMG recordings of the wrist extensor muscles following eccentric exercise that results in muscle soreness. Recurrence quantification analysis can be suggested as a tool for detection of MMG changes in presence of muscle soreness.

  8. Performance Analysis of Selection Combining Over Correlated Nakagami-m Fading Channels with Constant Correlation Model for Desired Signal and Cochannel Interference

    Directory of Open Access Journals (Sweden)

    C. Stefanovic

    2013-12-01

    Full Text Available A very efficient technique that reduces fading and channel interference influence is selection diversity based on the signal to interference ratio (SIR. In this pa¬per, system performances of selection combiner (SC over correlated Nakagami-m channels with constant correlation model are analyzed. Closed-form expressions are obtained for the output SIR probability density function (PDF and cumulative distribution function (CDF which is main contribution of this paper. Outage probability and the average error probability for coherent, noncoherent modulation are derived. Numerical results presented in this paper point out the effects of fading severity and cor¬relation on the system performances. The main contribu¬tion of this analysis for multibranch signal combiner is that it has been done for general case of correlated co-channel interference (CCI.

  9. ANALYSIS OF A CUMULANT-BASED 2D-RAKE RECEIVER FOR CDMA SYSTEM OVER FREQUENCY-SELECTIVE FADING CHANNELS

    Institute of Scientific and Technical Information of China (English)

    杨维; 程时昕

    2003-01-01

    The conventional 2D-Rake receivers for code-division multiple access (CDMA) system over frequency-selective fading channels are generally based on the second-order statistics while assuming perfect array conditions. However, the sensor response, location uncertainty, and the use of sample statistics can severely degrade the performance of second-order statistics processing. And in practical application, it is impossible to calibrate the array frequently. In this paper a cumulant-based 2D-Rake receiver for synchronous CDMA system with decorrelator is presented. Decorrelating is a multi-user detection approach that not only provides a fundamental solution to the mutual interference problem in CDMA communications but also makes it convenient for the decoupled signal to be processed spatially and temporally. High-order signal processing has some inherent advantages over that of second-order. Employing second-order statistics it is impossible to estimate source steering vector blindly, while employing higher than second-order cumulants, this purpose can be achieved. The performance analysis shows that employing cumulant-based signal processing technique the proposed 2D-Rake receiver is blind and demonstrates excellent performance.

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

    Directory of Open Access Journals (Sweden)

    Chen Yu-Fan

    2006-01-01

    Full Text Available An adaptive minimum mean-square error (MMSE array receiver based on the fuzzy-logic recursive least-squares (RLS algorithm is developed for asynchronous DS-CDMA interference suppression in the presence of frequency-selective multipath fading. This receiver employs a fuzzy-logic control mechanism to perform the nonlinear mapping of the squared error and squared error variation, denoted by ( , , into a forgetting factor . For the real-time applicability, a computationally efficient version of the proposed receiver is derived based on the least-mean-square (LMS algorithm using the fuzzy-inference-controlled step-size . This receiver is capable of providing both fast convergence/tracking capability as well as small steady-state misadjustment as compared with conventional LMS- and RLS-based MMSE DS-CDMA receivers. Simulations show that the fuzzy-logic LMS and RLS algorithms outperform, respectively, other variable step-size LMS (VSS-LMS and variable forgetting factor RLS (VFF-RLS algorithms at least 3 dB and 1.5 dB in bit-error-rate (BER for multipath fading channels.

  11. Selective inhibition of caspases in skeletal muscle reverses the apoptotic synaptic degeneration in slow-channel myasthenic syndrome.

    Science.gov (United States)

    Zhu, Haipeng; Pytel, Peter; Gomez, Christopher M

    2014-01-01

    Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca(2+) overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgenic mouse models for SCS (mSCS), the endplate regions are shrunken, and there is evidence of DNA damage in the subsynaptic region. Activated caspase-9, -3 and -7 are intensely co-localized at the NMJ, and the Ca(2+)-activated protease, calpain, and the atypical cyclin-dependent kinase (Cdk5) are overactivated in mSCS. Thus, the true mediator(s) of the disease process is not clear. Here, we demonstrate that selective inhibition of effector caspases, caspase-3 and -7, or initiator caspase, caspase-9, in limb muscle in vivo by localized expression of recombinant inhibitor proteins dramatically decreases subsynaptic DNA damage, increases endplate area and improves ultrastructural abnormalities in SCS transgenic mice. Calpain and Cdk5 are not affected by this treatment. On the other hand, inhibition of Cdk5 by expression of a dominant-negative form of Cdk5 has no effect on the degeneration. Together with previous studies, these results indicate that focal activation of caspase activity at the NMJ is the principal pathological process responsible for the synaptic apoptosis in SCS. Thus, treatments that reduce muscle caspase activity are likely to be of benefit for SCS patients.

  12. Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

    Science.gov (United States)

    Wu, Daichao; Guo, Ming; Philips, Michael A; Qu, Lingzhi; Jiang, Longying; Li, Jun; Chen, Xiaojuan; Chen, Zhuchu; Chen, Lin; Chen, Yongheng

    2016-01-01

    Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly.

  13. High-resolution imaging of expertise reveals reliable object selectivity in the fusiform face area related to perceptual performance.

    Science.gov (United States)

    McGugin, Rankin Williams; Gatenby, J Christopher; Gore, John C; Gauthier, Isabel

    2012-10-16

    The fusiform face area (FFA) is a region of human cortex that responds selectively to faces, but whether it supports a more general function relevant for perceptual expertise is debated. Although both faces and objects of expertise engage many brain areas, the FFA remains the focus of the strongest modular claims and the clearest predictions about expertise. Functional MRI studies at standard-resolution (SR-fMRI) have found responses in the FFA for nonface objects of expertise, but high-resolution fMRI (HR-fMRI) in the FFA [Grill-Spector K, et al. (2006) Nat Neurosci 9:1177-1185] and neurophysiology in face patches in the monkey brain [Tsao DY, et al. (2006) Science 311:670-674] reveal no reliable selectivity for objects. It is thus possible that FFA responses to objects with SR-fMRI are a result of spatial blurring of responses from nonface-selective areas, potentially driven by attention to objects of expertise. Using HR-fMRI in two experiments, we provide evidence of reliable responses to cars in the FFA that correlate with behavioral car expertise. Effects of expertise in the FFA for nonface objects cannot be attributed to spatial blurring beyond the scale at which modular claims have been made, and within the lateral fusiform gyrus, they are restricted to a small area (200 mm(2) on the right and 50 mm(2) on the left) centered on the peak of face selectivity. Experience with a category may be sufficient to explain the spatially clustered face selectivity observed in this region.

  14. Direct current stimulation (tDCS) reveals parietal asymmetry in local/global and salience-based selection.

    Science.gov (United States)

    Bardi, Lara; Kanai, Ryota; Mapelli, Daniela; Walsh, Vincent

    2013-03-01

    Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in processing object's global form versus local parts. However the attentional mechanisms subtending visual selection of different levels of information are poorly understood. The classical left hemisphere/local-right hemisphere/global dichotomy has been recently challenged by studies linking the asymmetry of activation in the posterior parietal cortex (PPC) with the relative salience of the stimulus rather than with the local/global level. The present study aimed to assess hemispheric asymmetry in local-global and salience-based selection in hierarchical stimuli by using transcranial direct current stimulation (tDCS). To this end, tDCS has been applied to the PPC of both the hemispheres. Our data revealed that tDCS did affect the selection of the target on the basis of its relative salience in a manner that depended on the tDCS polarity applied to the two hemispheres. This result is in line with previous findings that the left PPC is critically involved in attention for low-salience stimuli in the presence of high-salience distractor information, while right PPC is involved in attending to more salient stimuli. Hemispheric asymmetries were also found in local/global selection. Overall the results suggest that neural activation in the PPC is related to both the salience and the level of stimulus representations mediating responses to hierarchical stimuli. The comparison of the results from Experiments 1 and 2 in local/global-based selection suggests that the effect of stimulation could be completely opposite depending on subtle differences in demands of attentional control (sustained attention vs task switching).

  15. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

    OpenAIRE

    Ivanov, Vadim; Ivanova, Svetlana; KALINOVSKY, TATIANA; NIEDZWIECKI, ALEKSANDRA; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition...

  16. Dissociative Ionization Mechanism and Appearance Energies in Adipic Acid Revealed by Imaging Photoelectron Photoion Coincidence, Selective Deuteration, and Calculations.

    Science.gov (United States)

    Heringa, Maarten F; Slowik, Jay G; Prévôt, André S H; Baltensperger, Urs; Hemberger, Patrick; Bodi, Andras

    2016-05-26

    Adipic acid, a model compound for oxygenated organic aerosol, has been studied at the VUV beamline of the Swiss Light Source. Internal energy selected cations were prepared by threshold photoionization using vacuum ultraviolet synchrotron radiation and imaging photoelectron photoion coincidence spectroscopy (iPEPICO). The threshold photoelectron spectrum yields a vertical ionization energy (IE) of 10.5 eV, significantly above the calculated adiabatic IE of 8.6 eV. The cationic minimum is accessible after vertical ionization by H-transfer from one of the γ-carbons to a carbonyl oxygen and is sufficiently energetic to decay by water loss at the ionization onset. The slope of the breakdown curves, quantum chemical calculations, and selective deuteration of the carboxylic hydrogens establish the dissociative photoionization mechanism. After ionization, one γ-methylene hydrogen and the two carboxylic hydrogens are randomized prior to H2O loss. On the basis of the deuteration degree in the H2O + CO-loss product at higher energies, a direct water-loss channel without complete randomization also exists. The breakdown diagram and center of gravity of the H2O + CO-loss peak were modeled to obtain 0 K appearance energies of 10.77, 10.32, and 11.53 eV for H2O + CO loss, CH2COOH loss, and H2O + CH2COOH loss from adipic acid. These agree well with the CBS-QB3 calculated values of 10.68, 10.45, and 11.57 eV, respectively, which shows that threshold photoionization can yield energetics data as long as the dissociation is statistical, even when the parent ion cannot be observed. The results can be used as a starting point for a deeper understanding of the ionization and low-energy fragmentation of organic aerosol components.

  17. Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?

    Directory of Open Access Journals (Sweden)

    Oscar Sacchi

    Full Text Available The permeability of the nicotinic channel (nAChR at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylcholine (ACh, were thus analyzed in an intact environment as natively expressed by the mature sympathetic neuron. Postsynaptic neuron hyperpolarization (from -40 to -90 mV resulted in a change of the synaptic potassium/sodium permeability ratio (P(K/P(Na from 1.40 to 0.92, corresponding to a reversible shift of the apparent acetylcholine equilibrium potential, E(ACh, by about +10 mV. The effect was accompanied by a decrease of the peak synaptic conductance (g(syn and of the EPSC decay time constant. Reduction of [Cl(-](o to 18 mM resulted in a change of P(K/P(Na from 1.57 (control to 2.26, associated with a reversible shift of E(ACh by about -10 mV. Application of 200 nM αBgTx evoked P(K/P(Na and g(syn modifications similar to those observed in reduced [Cl(-](o. The two treatments were overlapping and complementary, as if the same site/mechanism were involved. The difference current before and after chloride reduction or toxin application exhibited a strongly positive equilibrium potential, which could not be explained by the block of a calcium component of the EPSC. Observations under current-clamp conditions suggest that the driving force modification of the EPSC due to P(K/P(Na changes represent an additional powerful integrative mechanism of neuron behavior. A possible role for chloride ions is suggested: the nAChR selectivity was actually reduced by increased chloride gradient (membrane hyperpolarization, while it was increased, moving towards a channel preferentially permeable for potassium, when the chloride gradient was reduced.

  18. Bioenergetic modeling reveals that Chinese green tree vipers select postprandial temperatures in laboratory thermal gradients that maximize net energy intake.

    Science.gov (United States)

    Tsai, Tein-Shun; Lee, How-Jing; Tu, Ming-Chung

    2009-11-01

    With bioenergetic modeling, we tested the hypothesis that reptiles maximize net energy gain by postprandial thermal selection. Previous studies have shown that Chinese green tree vipers (Trimeresurus s. stejnegeri) have postprandial thermophily (mean preferred temperature T(p) for males =27.8 degrees C) in a linear thigmothermal gradient when seclusion sites and water existed. With some published empirical models of digestion associated factors for this snake, we calculated the average rate (E(net)) and efficiency (K(net)) of net energy gain from possible combinations of meal size, activity level, and feeding frequency at each temperature. The simulations consistently revealed that E(net) maximizes at the T(p) of these snakes. Although the K(net) peaks at a lower temperature than E(net), the value of K(net) remains high (>=0.85 in ratio to maximum) at the peak temperature of E(net). This suggested that the demands of both E(net) and K(net) can be attained by postprandial thermal selection in this snake. In conclusion, the data support our prediction that postprandial thermal selection may maximize net energy gain.

  19. Herschel -ATLAS: revealing dust build-up and decline across gas, dust and stellar mass selected samples - I. Scaling relations

    Science.gov (United States)

    De Vis, P.; Dunne, L.; Maddox, S.; Gomez, H. L.; Clark, C. J. R.; Bauer, A. E.; Viaene, S.; Schofield, S. P.; Baes, M.; Baker, A. J.; Bourne, N.; Driver, S. P.; Dye, S.; Eales, S. A.; Furlanetto, C.; Ivison, R. J.; Robotham, A. S. G.; Rowlands, K.; Smith, D. J. B.; Smith, M. W. L.; Valiante, E.; Wright, A. H.

    2017-02-01

    We present a study of the dust, stars and atomic gas (H I) in an H I-selected sample of local galaxies (z sample reveals a population of very high gas fraction (>80 per cent), low stellar mass sources that appear to be in the earliest stages of their evolution. We compare this sample with dust- and stellar-mass-selected samples to study the dust and gas scaling relations over a wide range of gas fractions (proxy for evolutionary state of a galaxy). The most robust scaling relations for gas and dust are those linked to near-ultraviolet - r (specific star formation rate) and gas fraction; these do not depend on sample selection or environment. At the highest gas fractions, our additional sample shows that the dust content is well below expectations from extrapolating scaling relations for more evolved sources, and dust is not a good tracer of the gas content. The specific dust mass for local galaxies peaks at a gas fraction of ˜75 per cent. The atomic gas depletion time is also longer for high gas fraction galaxies, opposite to the trend found for molecular gas depletion time-scale. We link this trend to the changing efficiency of conversion of H I to H2 as galaxies increase in stellar mass surface density during their evolution. Finally, we show that galaxies start out barely obscured and increase in obscuration as they evolve, yet there is no clear and simple link between obscuration and global galaxy properties.

  20. Fragment library screening reveals remarkable similarities between the G protein-coupled receptor histamine H₄ and the ion channel serotonin 5-HT₃A.

    Science.gov (United States)

    Verheij, Mark H P; de Graaf, Chris; de Kloe, Gerdien E; Nijmeijer, Saskia; Vischer, Henry F; Smits, Rogier A; Zuiderveld, Obbe P; Hulscher, Saskia; Silvestri, Linda; Thompson, Andrew J; van Muijlwijk-Koezen, Jacqueline E; Lummis, Sarah C R; Leurs, Rob; de Esch, Iwan J P

    2011-09-15

    A fragment library was screened against the G protein-coupled histamine H(4) receptor (H(4)R) and the ligand-gated ion channel serotonin 5-HT(3A) (5-HT(3A)R). Interestingly, significant overlap was found between H(4)R and 5-HT(3A)R hit sets. The data indicates that dual active H(4)R and 5 HT(3A)R fragments have a higher complexity than the selective compounds which has important implications for chemical genomics approaches. The results of our fragment-based library screening study illustrate similarities in ligand recognition between H(4)R and 5-HT(3A)R and have important consequences for selectivity profiling in ongoing drug discovery efforts on H(4)R and 5-HT(3A)R. The affinity profiles of our fragment screening studies furthermore match the chemical properties of the H(4)R and 5-HT(3A)R binding sites and can be used to define molecular interaction fingerprints to guide the in silico prediction of protein-ligand interactions and structure.

  1. A new layered space-time detection algorithm for frequency selective fading multiple-input multiple-output channels based on particle filter

    Institute of Scientific and Technical Information of China (English)

    Du Zheng-Cong; Tang Bin; Liu Li-Xin

    2006-01-01

    In this paper, a new observation equation of non-Gaussian frequency selective fading Bell Labs layered space time (BLAST) architecture system is proposed, which is used for frequency selective fading channels and non-Gaussian noise in an application environment of BLAST system. With othogonal matrix triangularization (QR decomposition) of the channel matrix, the static observation equation of frequency selective fading BLAST system is transformed into a dynamic state space model, and then the particle filter is used for space-time layered detection. Making the full use of the finite alphabet of the digital modulation communication signal, the optimal proposal distribution can be chosen to produce particle and update the weight. Incorporated with current method of reducing error propagation, a new space-time layered detection algorithm is proposed. Simulation result shows the validity of the proposed algorithm.

  2. Performance of MMSE Receiver based Multi Input Multi Output-Interleave Division Multiple-Access System with Multi-user Detection over Frequency Selective Wireless Communication Channel

    Directory of Open Access Journals (Sweden)

    Kuttathatti S. Vishvaksenan

    2011-01-01

    Full Text Available Problem statement: This study presents the performance analysis of turbo assisted Interleave Division Multiple-Access (IDMA system with Multi Input Multi Output (MIMO support for multi user scenario over correlated frequency selective and uncorrelated frequency selective channel. Approach: The key principle of IDMA is that interleaver unique which distinguishes the users in contrast to spreading sequence in Code Division Multiple Access System (CDMA. Results: In this work, we assume that Interleavers are generated independently and randomly. At the receiver, we employed Ordered SIC (OSIC technique using ZF and MMSE criterion to combat Inter Antenna Interference (IAI and Multi User Interference (MUI problem along with iterative decoding to improve the performance in terms of BER. The performance of system has been discussed for different channel conditions with realistic channel model using extensive simulation runs based on Monte Carlo simulation trials. We have exhibited the flexibility and robustness provided by MIMO-IDMA. Conclusion/Recommendations: It has been proved from the results that IDMA principle can be applied to realize many potential performance gains highlighted by information theory, including coding gain multiplexing gain and multiuser gain. Simulation results presented to demonstrate the benefits of IDMA with MUD and iterative decoding. It is discerned that IDMA performs better than CDMA in frequency selective channel for high load conditions which is assessed through computer simulation results.

  3. 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

  4. Spectrally Efficient Communication over Time-Varying Frequency-Selective Mobile Channels: Variable-Size Burst Construction and Adaptive Modulation

    Directory of Open Access Journals (Sweden)

    Bui Francis Minhthang

    2006-01-01

    Full Text Available Methods for providing good spectral efficiency, without disadvantaging the delivered quality of service (QoS, in time-varying fading channels are presented. The key idea is to allocate system resources according to the encountered channel. Two approaches are examined: variable-size burst construction, and adaptive modulation. The first approach adapts the burst size according to the channel rate of change. In doing so, the available training symbols are efficiently utilized. The second adaptation approach tracks the operating channel quality, so that the most efficient modulation mode can be invoked while guaranteeing a target QoS. It is shown that these two methods can be effectively combined in a common framework for improving system efficiency, while guaranteeing good QoS. The proposed framework is especially applicable to multistate channels, in which at least one state can be considered sufficiently slowly varying. For such environments, the obtained simulation results demonstrate improved system performance and spectral efficiency.

  5. 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...

  6. A measurement of the top pair production cross-section in the dilepton channel using lepton plus track selection

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Corrinne Elaine [Univ. of California, Santa Barbara, CA (United States)

    2007-06-01

    Using 1.1 fb-1 of data collected by the Collider Detector at Fermilab (CDF) from Run II of the Fermilab Tevatron, they measure the t$\\bar{t}$ production cross section in events with two leptons, significant missing transverse energy, and ≥ 2 jets. As the Run II dataset grows, more stringent tests of Standard Model predictions for the top quark sector are becoming possible. The dilepton channel, where both top quarks decay t → Wb → ℓvb, is of particular interest due to its high purity even in the absence of a b jet 'tagging' requirement. Use of an isolated track as the second lepton significant increases the dilepton acceptance, at the price of some increase in background, particular from W + jets events where one of the jets is identified as a lepton. With the amount of data available, it has been possible to improve the estimate of the contribution from that background, reflected in a reduced systematic uncertainty. Assuming a branching ratio of BR(W → ℓv) = 10.8% and a top mass of mt = 175 GeV/c2, the measured cross-section is σ(p$\\bar{p}$ → t$\\bar{t}$) = 8.3 ± 1.3(stat.) ± 0.7(syst.) ± 0.5(lumi.) pb. The result is consistent with the Standard Model prediction of 6.7$+0.7\\atop{-0.9}$ pb and represents a significant improvement in precision over previous results using this selection.

  7. "Contrasting patterns of selection at Pinus pinaster Ait. Drought stress candidate genes as revealed by genetic differentiation analyses".

    Science.gov (United States)

    Eveno, Emmanuelle; Collada, Carmen; Guevara, M Angeles; Léger, Valérie; Soto, Alvaro; Díaz, Luis; Léger, Patrick; González-Martínez, Santiago C; Cervera, M Teresa; Plomion, Christophe; Garnier-Géré, Pauline H

    2008-02-01

    The importance of natural selection for shaping adaptive trait differentiation among natural populations of allogamous tree species has long been recognized. Determining the molecular basis of local adaptation remains largely unresolved, and the respective roles of selection and demography in shaping population structure are actively debated. Using a multilocus scan that aims to detect outliers from simulated neutral expectations, we analyzed patterns of nucleotide diversity and genetic differentiation at 11 polymorphic candidate genes for drought stress tolerance in phenotypically contrasted Pinus pinaster Ait. populations across its geographical range. We compared 3 coalescent-based methods: 2 frequentist-like, including 1 approach specifically developed for biallelic single nucleotide polymorphisms (SNPs) here and 1 Bayesian. Five genes showed outlier patterns that were robust across methods at the haplotype level for 2 of them. Two genes presented higher F(ST) values than expected (PR-AGP4 and erd3), suggesting that they could have been affected by the action of diversifying selection among populations. In contrast, 3 genes presented lower F(ST) values than expected (dhn-1, dhn2, and lp3-1), which could represent signatures of homogenizing selection among populations. A smaller proportion of outliers were detected at the SNP level suggesting the potential functional significance of particular combinations of sites in drought-response candidate genes. The Bayesian method appeared robust to low sample sizes, flexible to assumptions regarding migration rates, and powerful for detecting selection at the haplotype level, but the frequentist-like method adapted to SNPs was more efficient for the identification of outlier SNPs showing low differentiation. Population-specific effects estimated in the Bayesian method also revealed populations with lower immigration rates, which could have led to favorable situations for local adaptation. Outlier patterns are discussed

  8. The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

    Directory of Open Access Journals (Sweden)

    Matthias Stein

    Full Text Available BACKGROUND: Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics. CONCLUSIONS/SIGNIFICANCE: We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

  9. Structure of a TCR with High Affinity for Self-antigen Reveals Basis for Escape from Negative Selection

    Energy Technology Data Exchange (ETDEWEB)

    Y Yin; Y Li; M Kerzic; R Martin; R Mariuzza

    2011-12-31

    The failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3 conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity.

  10. Genomic sequencing reveals historical, demographic and selective factors associated with the diversification of the fire-associated fungus Neurospora discreta.

    Science.gov (United States)

    Gladieux, Pierre; Wilson, Benjamin A; Perraudeau, Fanny; Montoya, Liliam A; Kowbel, David; Hann-Soden, Christopher; Fischer, Monika; Sylvain, Iman; Jacobson, David J; Taylor, John W

    2015-11-01

    Delineating microbial populations, discovering ecologically relevant phenotypes and identifying migrants, hybrids or admixed individuals have long proved notoriously difficult, thereby limiting our understanding of the evolutionary forces at play during the diversification of microbial species. However, recent advances in sequencing and computational methods have enabled an unbiased approach whereby incipient species and the genetic correlates of speciation can be identified by examining patterns of genomic variation within and between lineages. We present here a population genomic study of a phylogenetic species in the Neurospora discreta species complex, based on the resequencing of full genomes (~37 Mb) for 52 fungal isolates from nine sites in three continents. Population structure analyses revealed two distinct lineages in South-East Asia, and three lineages in North America/Europe with a broad longitudinal and latitudinal range and limited admixture between lineages. Genome scans for selective sweeps and comparisons of the genomic landscapes of diversity and recombination provided no support for a role of selection at linked sites on genomic heterogeneity in levels of divergence between lineages. However, demographic inference indicated that the observed genomic heterogeneity in divergence was generated by varying rates of gene flow between lineages following a period of isolation. Many putative cases of exchange of genetic material between phylogenetically divergent fungal lineages have been discovered, and our work highlights the quantitative importance of genetic exchanges between more closely related taxa to the evolution of fungal genomes. Our study also supports the role of allopatric isolation as a driver of diversification in saprobic microbes.

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

    Science.gov (United States)

    Rjasanow, Alexandra; Leitner, Michael G; Thallmair, Veronika; Halaszovich, Christian R; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. 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(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K(+) channels to Ci-VSP allowed for comparison of PI(4,5)P2 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(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs.

  12. 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.

  13. Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Zhi-ying LIN; Li-min CHEN; Jing ZHANG; Xiao-dong PAN; Yuan-gui ZHU; Qin-yong YE; Hua-pin HUANG; Xiao-chun CHEN

    2012-01-01

    Aim:To investigate the effect of ginsenoside Rb1 on voltage-gated calcium currents in cultured rat hippocampal neurons and the modulatory mechanism.Methods:Cultured hippocampal neurons were prepared from Sprague Dawley rat embryos.Whole-cell configuration of the patchclamp technique was used to record the voltage-gated calcium currents (VGCCs)from the hippocampal neurons,and the effect of Rb1 was examined.Results:Rb1 (2-100 μmol/L)inhibited VGCCs in a concentration-dependent manner,and the current was mostly recovered upon wash-out.The specific L-type Ca2+ channel inhibitor nifedipine (10 μmol/L)occluded Rb1-induced inhibition on VGCCs.Neither the selective N-type Ca2+ channel blocker ω-conotoxin-GVlA (1 μmoVL),nor the selective P/Q-type Ca2+ channel blocker ωo-agatoxin IVA (30 nmol/L)diminished Rb1-sensitive VGCCs.Rb1 induced a leftward shift of the steady-state inactivation curve of Ica to a negative potential without affecting its activation kinetics or reversal potential in the I-V curve.The inhibitory effect of Rb1 was neither abolished by the adenylyl cyclase activator forskolin (10 μmol/L),nor by the PKA inhibitor H-89 (10 μmol/L).Conclusion:Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels,without affecting the N-type or P/Q-type Ca2+ channels in hippocampal neurons,cAMP-PKA signaling pathway is not involved in this effect.

  14. The Slow:Fast substitution ratio reveals changing patterns of natural selection in gamma-proteobacterial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Alm, Eric; Shapiro, B. Jesse

    2009-04-15

    Different microbial species are thought to occupy distinct ecological niches, subjecting each species to unique selective constraints, which may leave a recognizable signal in their genomes. Thus, it may be possible to extract insight into the genetic basis of ecological differences among lineages by identifying unusual patterns of substitutions in orthologous gene or protein sequences. We use the ratio of substitutions in slow versus fast-evolving sites (nucleotides in DNA, or amino acids in protein sequence) to quantify deviations from the typical pattern of selective constraint observed across bacterial lineages. We propose that elevated S:F in one branch (an excess of slow-site substitutions) can indicate a functionally-relevant change, due to either positive selection or relaxed evolutionary constraint. In a genome-wide comparative study of gamma-proteobacterial proteins, we find that cell-surface proteins involved with motility and secretion functions often have high S:F ratios, while information-processing genes do not. Change in evolutionary constraints in some species is evidenced by increased S:F ratios within functionally-related sets of genes (e.g., energy production in Pseudomonas fluorescens), while other species apparently evolve mostly by drift (e.g., uniformly elevated S:F across most genes in Buchnera spp.). Overall, S:F reveals several species-specific, protein-level changes with potential functional/ecological importance. As microbial genome projects yield more species-rich gene-trees, the S:F ratio will become an increasingly powerful tool for uncovering functional genetic differences among species.

  15. Mapping of long-range INS promoter interactions reveals a role for calcium-activated chloride channel ANO1 in insulin secretion.

    Science.gov (United States)

    Xu, Zhixiong; Lefevre, Gaelle M; Gavrilova, Oksana; Foster St Claire, Mark B; Riddick, Gregory; Felsenfeld, Gary

    2014-11-25

    We used circular chromatin conformation capture (4C) to identify a physical contact in human pancreatic islets between the region near the insulin (INS) promoter and the ANO1 gene, lying 68 Mb away on human chromosome 11, which encodes a Ca(2+)-dependent chloride ion channel. In response to glucose, this contact was strengthened and ANO1 expression increased, whereas inhibition of INS gene transcription by INS promoter targeting siRNA decreased ANO1 expression, revealing a regulatory effect of INS promoter on ANO1 expression. Knockdown of ANO1 expression caused decreased insulin secretion in human islets, establishing a physical proximity-dependent feedback loop involving INS transcription, ANO1 expression, and insulin secretion. To explore a possible role of ANO1 in insulin metabolism, we carried out experiments in Ano1(+/-) mice. We observed reduced serum insulin levels and insulin-to-glucose ratios in high-fat diet-fed Ano1(+/-) mice relative to Ano1(+/+) mice fed the same diet. Our results show that determination of long-range contacts within the nucleus can be used to detect novel and physiologically relevant mechanisms. They also show that networks of long-range physical contacts are important to the regulation of insulin metabolism.

  16. Selective inhibition of the Kir2 family of inward rectifier potassium channels by a small molecule probe: the discovery, SAR and pharmacological characterization of ML133

    Science.gov (United States)

    Wang, Hao-Ran; Wu, Meng; Yu, Haibo; Long, Shunyou; Stevens, Amy; Engers, Darren W.; Sackin, Henry; Daniels, J. Scott; Dawson, Eric S.; Hopkins, Corey R.; Lindsley, Craig W.; Li, Min; McManus, Owen B

    2011-01-01

    The Kir inward rectifying potassium channels have a broad tissue distribution and are implicated in a variety of functional roles. At least seven classes (Kir1 – Kir7) of structurally related inward rectifier potassium channels are known, and there are no selective small molecule tools to study their function. In an effort to develop selective Kir2.1 inhibitors, we performed a high-throughput screen (HTS) of more than 300,000 small molecules within the MLPCN for modulators of Kir2.1 function. Here we report one potent Kir2.1 inhibitor, ML133, which inhibits Kir2.1 with IC50 of 1.8 μM at pH 7.4 and 290 nM at pH 8.5, but exhibits little selectivity against other members of Kir2.x family channels. However, ML133 has no effect on Kir1.1 (IC50 > 300 μM), and displays weak activity for Kir4.1 (76 μM) and Kir7.1 (33 μM), making ML133 the most selective small molecule inhibitor of the Kir family reported to date. Due to the high homology within the Kir family, the channels share a common design of a pore region flanked by two transmembrane domains, identification of site(s) critical for isoform specificity would be an important basis for future development of more specific and potent Kir inhibitors. Using chimeric channels between Kir2.1 and Kir1.1 and site-directed mutagenesis, we have identified D172 and I176 within M2 segment of Kir2.1 as molecular determinants critical for the potency of ML133 mediated inhibition. Double mutation of the corresponding residues of Kir1.1 to those of Kir2.1 (N171D and C175I) transplants ML133 inhibition to Kir1.1. Together, the combination of a potent, Kir2 family selective inhibitor and identification of molecular determinants for the specificity provides both a tool and a model system to enable further mechanistic studies of modulation of Kir2 inward rectifier potassium channels. PMID:21615117

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  18. Technical report: Metal concentrations in sediments, and selected biota from mine tailings in Gastineau Channel, Juneau, Alaska [Draft

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Hardrock gold mining occurred in Juneau from 1880 to 1944. Tailings and waste rock from the mines were deposited into Gastineau Channel and formed beaches along...

  19. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    Science.gov (United States)

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia.

  20. Arene guest selectivity and pore flexibility in a metal-organic framework with semi-fluorinated channel walls

    Science.gov (United States)

    Smith, Rebecca; Vitórica-Yrezábal, Iñigo J.; Hill, Adrian; Brammer, Lee

    2017-01-01

    A metal-organic framework (MOF) with one-dimensional channels of approximately hexagonal cross-section [Ag2(O2CCF2CF2CO2)(TMP)] 1 (TMP =2,3,5,6-tetramethylpyrazine) has been synthesized with MeOH filling the channels in its as-synthesized form as [Ag2(O2CCF2CF2CO2)(TMP)]·n(MeOH) 1-MeOH (n = 1.625 by X-ray crystallography). The two types of ligand connect columns of Ag(I) centres in an alternating manner, both around the channels and along their length, leading to an alternating arrangement of hydrocarbon (C-H) and fluorocarbon (C-F) groups lining the channel walls, with the former groups projecting further into the channel than the latter. MeOH solvent in the channels can be exchanged for a variety of arene guests, ranging from xylenes to tetrafluorobenzene, as confirmed by gas chromatography, 1H nuclear magnetic resonance (NMR) spectroscopy, thermogravimetric analysis and 13C cross-polarization magic angle spinning NMR spectroscopy. Alkane and perfluoroalkane guests, however, do not enter the channels. Although exhibiting some stability under a nitrogen atmosphere, sufficient to enable crystal structure determination, the evacuated MOF 1 is unstable for periods of more than minutes under ambient conditions or upon heating, whereupon it undergoes an irreversible solid-state transformation to a non-porous polymorph 2, which comprises Ag2(O2CCF2CF2CO2) coordination layers that are pillared by TMP ligands. This transformation has been followed in situ by powder X-ray diffraction and shown to proceed via a crystalline intermediate. This article is part of the themed issue 'Coordination polymers and metal-organic frameworks: materials by design'.

  1. Arene guest selectivity and pore flexibility in a metal–organic framework with semi-fluorinated channel walls

    Science.gov (United States)

    Smith, Rebecca; Vitórica-Yrezábal, Iñigo J.; Hill, Adrian

    2017-01-01

    A metal–organic framework (MOF) with one-dimensional channels of approximately hexagonal cross-section [Ag2(O2CCF2CF2CO2)(TMP)] 1 (TMP =2,3,5,6-tetramethylpyrazine) has been synthesized with MeOH filling the channels in its as-synthesized form as [Ag2(O2CCF2CF2CO2)(TMP)]·n(MeOH) 1-MeOH (n = 1.625 by X-ray crystallography). The two types of ligand connect columns of Ag(I) centres in an alternating manner, both around the channels and along their length, leading to an alternating arrangement of hydrocarbon (C–H) and fluorocarbon (C–F) groups lining the channel walls, with the former groups projecting further into the channel than the latter. MeOH solvent in the channels can be exchanged for a variety of arene guests, ranging from xylenes to tetrafluorobenzene, as confirmed by gas chromatography, 1H nuclear magnetic resonance (NMR) spectroscopy, thermogravimetric analysis and 13C cross-polarization magic angle spinning NMR spectroscopy. Alkane and perfluoroalkane guests, however, do not enter the channels. Although exhibiting some stability under a nitrogen atmosphere, sufficient to enable crystal structure determination, the evacuated MOF 1 is unstable for periods of more than minutes under ambient conditions or upon heating, whereupon it undergoes an irreversible solid-state transformation to a non-porous polymorph 2, which comprises Ag2(O2CCF2CF2CO2) coordination layers that are pillared by TMP ligands. This transformation has been followed in situ by powder X-ray diffraction and shown to proceed via a crystalline intermediate. This article is part of the themed issue ‘Coordination polymers and metal–organic frameworks: materials by design’. PMID:27895259

  2. Cd(2+) sensitivity and permeability of a low voltage-activated Ca(2+) channel with CatSper-like selectivity filter.

    Science.gov (United States)

    Garza-López, Edgar; Chávez, Julio César; Santana-Calvo, Carmen; López-González, Ignacio; Nishigaki, Takuya

    2016-07-01

    CatSper is a sperm-specific Ca(2+) channel that plays an essential role in the male fertility. However, its biophysical properties have been poorly characterized mainly due to its deficient heterologous expression. As other voltage-gated Ca(2+) channels (CaVs), CatSper possesses a conserved Ca(2+)-selective filter motif ([T/S]x[D/E]xW) in the pore region. Interestingly, CatSper conserves four aspartic acids (DDDD) as the negatively charged residues in this motif while high voltage-activated CaVs have four glutamic acids (EEEE) and low voltage-activated CaVs possess two glutamic acids and two aspartic acids (EEDD). Previous studies based on site-directed mutagenesis of L- and T-type channels showed that the number of D seems to have a negative correlation with their cadmium (Cd(2+)) sensitivity. These results suggest that CatSper (DDDD) would have low sensitivity to Cd(2+). To explore Cd(2+)-sensitivity and -permeability of CatSper, we performed two types of experiments: 1) Electrophysiological analysis of heterologously expressed human CaV3.1 channel and three pore mutants (DEDD, EDDD and DDDD), 2) Cd(2+) imaging of human spermatozoa with FluoZin-1. Electrophysiological studies showed a significant increase in Cd(2+) and manganese (Mn(2+)) currents through the CaV3.1 mutants as well as a reduction in the inhibitory effect of Cd(2+) on the Ca(2+) current. In fluorescence imaging with human sperm, we observed an increase in Cd(2+) influx potentiated by progesterone, a potent activator of CatSper. These results support our hypothesis, namely that Cd(2+)-sensitivity and -permeability are related to the absolute number of D in the Ca(2+)-selective filter independently to the type of the Cav channels.

  3. Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses

    DEFF Research Database (Denmark)

    Haugaard, Maria Mathilde; Hesselkilde, Eva Zander; Pehrson, Steen Michael

    2015-01-01

    BACKGROUND: Small-conductance calcium-activated potassium (SK) channels have been found to play an important role in atrial repolarization and atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to investigate the existence and functional role of SK channels in the equine heart...

  4. MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain.

    Science.gov (United States)

    Singh, H; Li, M; Hall, L; Chen, S; Sukur, S; Lu, R; Caputo, A; Meredith, A L; Stefani, E; Toro, L

    2016-03-11

    Large conductance voltage and calcium-activated potassium (MaxiK) channels are activated by membrane depolarization and elevated cytosolic Ca(2+). In the brain, they localize to neurons and astrocytes, where they play roles such as resetting the membrane potential during an action potential, neurotransmitter release, and neurovascular coupling. MaxiK channels are known to associate with several modulatory proteins and accessory subunits, and each of these interactions can have distinct physiological consequences. To uncover new players in MaxiK channel brain physiology, we applied a directed proteomic approach and obtained MaxiK channel pore-forming α subunit brain interactome using specific antibodies. Controls included immunoprecipitations with rabbit immunoglobulin G (IgG) and with anti-MaxiK antibodies in wild type and MaxiK channel knockout mice (Kcnma1(-/-)), respectively. We have found known and unreported interactive partners that localize to the plasma membrane, extracellular space, cytosol and intracellular organelles including mitochondria, nucleus, endoplasmic reticulum and Golgi apparatus. Localization of MaxiK channel to mitochondria was further confirmed using purified brain mitochondria colabeled with MitoTracker. Independent proof of MaxiK channel interaction with previously unidentified partners is given for GABA transporter 3 (GAT3) and heat shock protein 60 (HSP60). In human embryonic kidney 293 cells containing SV40 T-antigen (HEK293T) cells, both GAT3 and HSP60 coimmunoprecipitated and colocalized with MaxiK channel; colabeling was observed mainly at the cell periphery with GAT3 and intracellularly with HSP60 with protein proximity indices of ∼ 0.6 and ∼ 0.4, respectively. In rat primary hippocampal neurons, colocalization index was identical for GAT3 (∼ 0.6) and slightly higher for HSP60 (∼ 0.5) association with MaxiK channel. The results of this study provide a complete interactome of MaxiK channel the mouse brain, further establish

  5. cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.

    Directory of Open Access Journals (Sweden)

    Alex K Lyashchenko

    Full Text Available Hyperpolarization-activated cyclic nucleotide-regulated HCN channels underlie the Na+-K+ permeable IH pacemaker current. As with other voltage-gated members of the 6-transmembrane KV channel superfamily, opening of HCN channels involves dilation of a helical bundle formed by the intracellular ends of S6 albeit this is promoted by inward, not outward, displacement of S4. Direct agonist binding to a ring of cyclic nucleotide-binding sites, one of which lies immediately distal to each S6 helix, imparts cAMP sensitivity to HCN channel opening. At depolarized potentials, HCN channels are further modulated by intracellular Mg2+ which blocks the open channel pore and blunts the inhibitory effect of outward K+ flux. Here, we show that cAMP binding to the gating ring enhances not only channel opening but also the kinetics of Mg2+ block. A combination of experimental and simulation studies demonstrates that agonist acceleration of block is mediated via acceleration of the blocking reaction itself rather than as a secondary consequence of the cAMP enhancement of channel opening. These results suggest that the activation status of the gating ring and the open state of the pore are not coupled in an obligate manner (as required by the often invoked Monod-Wyman-Changeux allosteric model but couple more loosely (as envisioned in a modular model of protein activation. Importantly, the emergence of second messenger sensitivity of open channel rectification suggests that loose coupling may have an unexpected consequence: it may endow these erstwhile "slow" channels with an ability to exert voltage and ligand-modulated control over cellular excitability on the fastest of physiologically relevant time scales.

  6. 商业银行客户渠道选择偏好研究%Commercial Banks Customers' Preference for Channel Selection

    Institute of Scientific and Technical Information of China (English)

    张群; 董仲慧; 朱治安

    2012-01-01

    为了研究商业银行客户渠道选择偏好的影响因素,通过文献回顾,探讨了影响银行客户渠道选择偏好的易用性、便利性、风险性等关键因素,建立银行客户渠道选择偏好概念模型,通过调查数据运用lisrel8.7软件进行了实证分析,在此基础上,针对不同银行服务渠道(主要是柜台、ATM和网上银行),分析了这些影响因素是如何影响各个渠道的,并给出了相应的研究结论.%In order to study the factors influencing commercial banks customer' preference for channel selection,through literature review, this paper discusses Usability, Convenience, Risk, which are the key factors influencing customers' preference. Then the model of customers' channel selection preference was built. The model was demonstrated by using lisre 18. 7. Software and the data obtained in a survey. Based on the empirical analysis of the model, the paper examines how those factors influence each of bank service channels (mainly Branches, ATM and online Bank) ,with some conclusions reached.

  7. Combining cluster analysis, feature selection and multiple support vector machine models for the identification of human ether-a-go-go related gene channel blocking compounds.

    Science.gov (United States)

    Nisius, Britta; Göller, Andreas H; Bajorath, Jürgen

    2009-01-01

    Blockade of the human ether-a-go-go related gene potassium channel is regarded as a major cause of drug toxicity and associated with severe cardiac side-effects. A variety of in silico models have been reported to aid in the identification of compounds blocking the human ether-a-go-go related gene channel. Herein, we present a classification approach for the detection of diverse human ether-a-go-go related gene blockers that combines cluster analysis of training data, feature selection and support vector machine learning. Compound learning sets are first divided into clusters of similar molecules. For each cluster, independent support vector machine models are generated utilizing preselected MACCS structural keys as descriptors. These models are combined to predict human ether-a-go-go related gene inhibition of our large compound data set with consistent experimental measurements (i.e. only patch clamp measurements on mammalian cell lines). Our combined support vector machine model achieves a prediction accuracy of 85% on this data set and performs better than alternative methods used for comparison. We also find that structural keys selected on the basis of statistical criteria are associated with molecular substructures implicated in human ether-a-go-go related gene channel binding.

  8. Achievable DoF and Its User Scaling Law for Opportunistic User Selection in a $K$-transmitter SIMO Interference Channel

    CERN Document Server

    Lee, Jung Hoon; Love, David J

    2011-01-01

    In this paper, we consider a $K$-transmitter single-input multiple-output (SIMO) interference channel (IC) where each transmitter has its own user group and serves one of the users in its group. When the number of receive antennas at each user is less than $K$ (i.e., $N_Rselection when the number of users per transmitter, $N$, goes to infinity. Using a geometric interpretation of the interfering channels, we propose opportunistic interference alignment (OIA) as a practical implementation of interference alignment. We find that a DoF of one per transmitter is achieved using the OIA scheme when the number of users is scaled as $N\\propto P^{\\alpha (K-N_R)}$ where $P$ is transmit power and $\\alpha$ is the relative path loss of the interfering channel in decibels. This result on the scaling law is extended and shown to be still valid for other user selection schemes such as the minimum interf...

  9. A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction.

    Science.gov (United States)

    Al-Sabi, Ahmed; Daly, Declan; Hoefer, Patrick; Kinsella, Gemma K; Metais, Charles; Pickering, Mark; Herron, Caroline; Kaza, Seshu Kumar; Nolan, Kieran; Dolly, J Oliver

    2017-03-23

    K(+) channels containing Kv1.1 α subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K(+) currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyl)methane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2'-((5,5'(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2'carbonyl)bis(azanediyl)) diethaneamine·2HCl] (8) selectively blocked Kv1.1 channels (IC50 ≈ 15 μM) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K(+) current activation, and slowed its kinetics. It preferentially inhibited channels containing two or more Kv1.1 subunits regardless of their positioning in concatenated tetramers. In slices of corpus callosum from mice subjected to a demyelination protocol, this novel inhibitor improved neuronal conduction, highlighting its potential for alleviating symptoms in multiple sclerosis.

  10. Impact of online channel use on customer revenues and costs to serve : Considering product portfolios and self-selection

    NARCIS (Netherlands)

    Gensler, S.; Leeflang, P.S.H.; Skiera, B.

    2012-01-01

    Developing a strategy for online channels requires knowledge of the effects of customers' online use on their revenue and cost to serve, which ultimately influence customer profitability. The authors theoretically discuss and empirically examine these effects. An empirical study of retail banking cu

  11. 产品交互反馈与知觉通道选择%Product Interactive Feedback and Sensory Channels Selection

    Institute of Scientific and Technical Information of China (English)

    周小舟

    2012-01-01

    产品通过对使用者知觉通道的刺激来达到反馈信息的目的。本文通过对使用者和产品之间信息交流模式的分析,阐述了环境模型下多知觉通道的选择对于交互反馈效果的影响。%The products realize feedback function based on stimulation of user perceived channels.The issue elaborated the influence of multiple sensory channels selection for interactive feedback effect in environmental model through the analysis of exchange information mode between users and products.

  12. A genetic screen for dihydropyridine (DHP-resistant worms reveals new residues required for DHP-blockage of mammalian calcium channels.

    Directory of Open Access Journals (Sweden)

    Trevor C Y Kwok

    2008-05-01

    Full Text Available Dihydropyridines (DHPs are L-type calcium channel (Ca(v1 blockers prescribed to treat several diseases including hypertension. Ca(v1 channels normally exist in three states: a resting closed state, an open state that is triggered by membrane depolarization, followed by a non-conducting inactivated state that is triggered by the influx of calcium ions, and a rapid change in voltage. DHP binding is thought to alter the conformation of the channel, possibly by engaging a mechanism similar to voltage dependent inactivation, and locking a calcium ion in the pore, thereby blocking channel conductance. As a Ca(v1 channel crystal structure is lacking, the current model of DHP action has largely been achieved by investigating the role of candidate Ca(v1 residues in mediating DHP-sensitivity. To better understand DHP-block and identify additional Ca(v1 residues important for DHP-sensitivity, we screened 440,000 randomly mutated Caenorhabditis elegans genomes for worms resistant to DHP-induced growth defects. We identified 30 missense mutations in the worm Ca(v1 pore-forming (alpha(1 subunit, including eleven in conserved residues known to be necessary for DHP-binding. The remaining polymorphisms are in eight conserved residues not previously associated with DHP-sensitivity. Intriguingly, all of the worm mutants that we analyzed phenotypically exhibited increased channel activity. We also created orthologous mutations in the rat alpha(1C subunit and examined the DHP-block of current through the mutant channels in culture. Six of the seven mutant channels examined either decreased the DHP-sensitivity of the channel and/or exhibited significant residual current at DHP concentrations sufficient to block wild-type channels. Our results further support the idea that DHP-block is intimately associated with voltage dependent inactivation and underscores the utility of C. elegans as a screening tool to identify residues important for DHP interaction with mammalian

  13. Hydroxyproline-induced Helical Disruption in Conantokin Rl-B Affects Subunit-selective Antagonistic Activities toward Ion Channels of N-Methyl-d-aspartate Receptors.

    Science.gov (United States)

    Kunda, Shailaja; Yuan, Yue; Balsara, Rashna D; Zajicek, Jaroslav; Castellino, Francis J

    2015-07-17

    Conantokins are ~20-amino acid peptides present in predatory marine snail venoms that function as allosteric antagonists of ion channels of the N-methyl-d-aspartate receptor (NMDAR). These peptides possess a high percentage of post-/co-translationally modified amino acids, particularly γ-carboxyglutamate (Gla). Appropriately spaced Gla residues allow binding of functional divalent cations, which induces end-to-end α-helices in many conantokins. A smaller number of these peptides additionally contain 4-hydroxyproline (Hyp). Hyp should prevent adoption of the metal ion-induced full α-helix, with unknown functional consequences. To address this disparity, as well as the role of Hyp in conantokins, we have solved the high resolution three-dimensional solution structure of a Gla/Hyp-containing 18-residue conantokin, conRl-B, by high field NMR spectroscopy. We show that Hyp(10) disrupts only a small region of the α-helix of the Mn(2+)·peptide complex, which displays cation-induced α-helices on each terminus of the peptide. The function of conRl-B was examined by measuring its inhibition of NMDA/Gly-mediated current through NMDAR ion channels in mouse cortical neurons. The conRl-B displays high inhibitory selectivity for subclasses of NMDARs that contain the functionally important GluN2B subunit. Replacement of Hyp(10) with N(8)Q results in a Mg(2+)-complexed end-to-end α-helix, accompanied by attenuation of NMDAR inhibitory activity. However, replacement of Hyp(10) with Pro(10) allowed the resulting peptide to retain its inhibitory property but diminished its GluN2B specificity. Thus, these modified amino acids, in specific peptide backbones, play critical roles in their subunit-selective inhibition of NMDAR ion channels, a finding that can be employed to design NMDAR antagonists that function at ion channels of distinct NMDAR subclasses.

  14. Identification and Analysis of Genome-Wide SNPs Provide Insight into Signatures of Selection and Domestication in Channel Catfish (Ictalurus punctatus)

    Science.gov (United States)

    Sun, Luyang; Liu, Shikai; Wang, Ruijia; Jiang, Yanliang; Zhang, Yu; Zhang, Jiaren; Bao, Lisui; Kaltenboeck, Ludmilla; Dunham, Rex; Waldbieser, Geoff; Liu, Zhanjiang

    2014-01-01

    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. PMID:25313648

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 基于多臂赌博机模型的信道选择%Channel Selection Based on Multi-armed Bandit

    Institute of Scientific and Technical Information of China (English)

    朱江; 陈红翠; 熊加毫

    2015-01-01

    In the opportunistic spectrum access( OSA) system,in order to solve the problem of channel se-lection without the priori channel statistic information,a novel channel selection strategy is proposed which applies improved upper confidence bound(UCB) based on multi-armed bandit(MAB). Through adding the revenue variance into the confidence factor of UCB index,the proposed strategy can effectively adjust the exploration process of unknown channel environment and reduce the cost of exploration. It is theoreti-cally proved that the proposed strategy has a faster convergent speed and its learning regret curve with time slot is approximately logarithmic and can bring a slower growing rate. The simulation results show that, compared with UCB index algorithm and greedy algorithm,the proposed strategy can adaptively select the channel with better availability,effectively reduce the learning regret and accelerate the convergent speed, thus improving the system throughput.%在择机频谱接入系统中,为解决未知信道环境先验知识下的信道选择问题,提出了一种基于多臂赌博机( MAB )模型的改进 UCB ( Upper Confidence Bound ) 索引选择策略. 该策略是通过在UCB索引的置信因子中引入收益方差值来调整对未知信道环境的探索过程,以降低探索成本. 结合理论证明了本策略有较快的收敛速度,还证明了本策略下的学习后悔值曲线与时隙呈近似对数关系而较缓慢增长. 仿真结果表明,与原UCB策略以及贪心算法相比,所提策略更能自适应地选择可用性较好的信道,有效降低学习后悔值并加快其收敛速度,从而提高了系统吞吐量.

  17. A potent and selective peptide blocker of the Kv1.3 channel: prediction from free-energy simulations and experimental confirmation.

    Directory of Open Access Journals (Sweden)

    M Harunur Rashid

    Full Text Available The voltage-gated potassium channel Kv1.3 is a well-established target for treatment of autoimmune diseases. ShK peptide from a sea anemone is one of the most potent blockers of Kv1.3 but its application as a therapeutic agent for autoimmune diseases is limited by its lack of selectivity against other Kv channels, in particular Kv1.1. Accurate models of Kv1.x-ShK complexes suggest that specific charge mutations on ShK could considerably enhance its specificity for Kv1.3. Here we evaluate the K18A mutation on ShK, and calculate the change in binding free energy associated with this mutation using the path-independent free energy perturbation and thermodynamic integration methods, with a novel implementation that avoids convergence problems. To check the accuracy of the results, the binding free energy differences were also determined from path-dependent potential of mean force calculations. The two methods yield consistent results for the K18A mutation in ShK and predict a 2 kcal/mol gain in Kv1.3/Kv1.1 selectivity free energy relative to wild-type peptide. Functional assays confirm the predicted selectivity gain for ShK[K18A] and suggest that it will be a valuable lead in the development of therapeutics for autoimmune diseases.

  18. Genome-wide association analysis of bacterial cold water disease resistance in rainbow trout reveals the potential of a hybrid approach between genomic selection and marker assisted selection

    Science.gov (United States)

    Genomic selection (GS) simultaneously incorporates dense SNP marker genotypes with phenotypic data from related animals to predict animal-specific genomic breeding value (GEBV), which circumvents the need to measure the disease phenotype in potential breeders. Marker assisted selection (MAS) involv...

  19. The cytochrome P450 genes of channel catfish: their involvement in disease defense responses as revealed by meta-analysis of RNA-Seq datasets

    Science.gov (United States)

    Zhang, Jiaren; Yao, Jun; Wang, Ruijia; Zhang, Yu; Liu, Shikai; Sun, Luyang; Jiang, Yanliang; Feng, Jianbin; Liu, Nannan; Nelson, David; Waldbieser, Geoff; Liu, Zhanjiang

    2015-01-01

    Background Cytochrome P450s (CYPs) encode one of the most diverse enzyme superfamily in nature. They catalyze oxidative reactions of endogenous molecules and exogenous chemicals. Methods We identified CYPs genes through in silico analysis using EST, RNA-Seq and genome databases of channel catfish. Phylogenetic analyses and conserved syntenic analyses were conducted to determine their identities and orthologies. Meta-analysis of RNA-Seq databases was conducted to analyze expression profile of CYP genes following bacterial infection. Results A full set of 61 CYP genes were identified and characterized in channel catfish. Phylogenetic tree and conserved synteny provided strong evidence of their identities and orthorlogy. Lineage-specific gene duplication was evident in a number of clans in channel catfish. CYP46A1 is missing in the catfish genome as observed with syntenic analysis and RT-PCR analysis. Thirty CYPs were found up- or down-regulated in liver, while seven and eight CYPs were observed regulated in intestine and gill following bacterial infection. Conclusion We systematically identified and characterized a full set of 61 CYP genes in channel catfish and studied their expression profiles after bacterial infection. Strikingly large numbers of CYP genes appear to be involved in the bacterial defense processes. General significance This work provides an example to systematically study CYP genes in non-model species. Moreover, it provides a basis for further toxicological and physiological studies in channel catfish. PMID:24780645

  20. Channel-lining residues of the AMPA receptor M2 segment: structural environment of the Q/R site and identification of the selectivity filter.

    Science.gov (United States)

    Kuner, T; Beck, C; Sakmann, B; Seeburg, P H

    2001-06-15

    In AMPA receptor channels, a single amino acid residue (Q/R site) of the M2 segment controls permeation of calcium ions, single-channel conductance, blockade by intracellular polyamines, and permeation of anions. The structural environment of the Q/R site and its positioning with regard to a narrow constriction were probed with the accessibility of substituted cysteines to positively and negatively charged methanethiosulfonate reagents, applied from the extracellular and cytoplasmic sides of the channel. The accessibility patterns confirm that the M2 segment forms a pore loop with the Q/R site positioned at the tip of the loop (position 0) facing the extracellular vestibule. Cytoplasmically accessible residues on the N- and C-terminal sides of position 0 form the ascending alpha-helical (-8 to -1) and descending random coil (+1 to +6) components of the loop, respectively. Substitution of a glycine residue at position +2 with alanine strongly decreased the permeability of organic cations, indicating that position +2 contributes to the narrow constriction. The anionic 2-sulfonatoethyl-methanethiosufonate reacted with a cysteine at position 0 only from the external side and with cysteines at positions +1 to +4 only from the cytoplasmic side. These results suggest that charge selectivity occurs external to the constriction (+2) and possibly involves interactions of ions with the negative electrostatic potential created by the dipole of the alpha-helix formed by the ascending limb of the loop.

  1. Sea Anemone Toxins Affecting Potassium Channels

    Science.gov (United States)

    Diochot, Sylvie; Lazdunski, Michel

    The great diversity of K+ channels and their wide distribution in many tissues are associated with important functions in cardiac and neuronal excitability that are now better understood thanks to the discovery of animal toxins. During the past few decades, sea anemones have provided a variety of toxins acting on voltage-sensitive sodium and, more recently, potassium channels. Currently there are three major structural groups of sea anemone K+ channel (SAK) toxins that have been characterized. Radioligand binding and electrophysiological experiments revealed that each group contains peptides displaying selective activities for different subfamilies of K+ channels. Short (35-37 amino acids) peptides in the group I display pore blocking effects on Kv1 channels. Molecular interactions of SAK-I toxins, important for activity and binding on Kv1 channels, implicate a spot of three conserved amino acid residues (Ser, Lys, Tyr) surrounded by other less conserved residues. Long (58-59 amino acids) SAK-II peptides display both enzymatic and K+ channel inhibitory activities. Medium size (42-43 amino acid) SAK-III peptides are gating modifiers which interact either with cardiac HERG or Kv3 channels by altering their voltage-dependent properties. SAK-III toxins bind to the S3C region in the outer vestibule of Kv channels. Sea anemones have proven to be a rich source of pharmacological tools, and some of the SAK toxins are now useful drugs for the diagnosis and treatment of autoimmune diseases.

  2. Space-time coded eigenbeamforming for downlink frequency-selective correlated fading channels%下行频率选择性相关衰落信道下的空时特征波束编码

    Institute of Scientific and Technical Information of China (English)

    李勇朝; 廖桂生; 仝文宁

    2006-01-01

    To improve the performance of space-time coding over downlink frequency-selective correlated fading channels, a novel transmission scheme combining eigenbeamforming and OFDM is proposed. Provided that the channel correlated statistics are available at the transmitter, the wideband correlated fading channels can be converted into an independent FIR channel with 2 transmitting antennas and N receiving antennas by eigenbeamforming and dimension reduction. OFDM is utilized to convert the FIR channel into a group of independent parallel subchannels to carry space-time codes. With the new structure, the performance of space-time coding over downlink wideband correlated fading channels is greatly improved and the system complexity is reduced. Validity of the proposed system is verified by simulations under different conditions. Comparison between the new structure and an available structure is made both theoretically and computationally.

  3. Selective cognitive deficits and reduced hippocampal brain-derived neurotrophic factor mRNA expression in small-conductance calcium-activated K+ channel deficient mice

    DEFF Research Database (Denmark)

    Jacobsen, J P R; Redrobe, J P; Hansen, H H;

    2009-01-01

    and the question is difficult to address pharmacologically due to the lack of subtype-selective SK-channel modulators. In this study, we used doxycycline-induced conditional SK3-deficient (T/T) mice to address the cognitive consequences of selective SK3 deficiency. In T/T mice SK3 protein is near-eliminated from...... the brain following doxycycline treatment. We tested T/T and wild type (WT) littermate mice in five distinct learning and memory paradigms. In Y-maze spontaneous alternations and five-trial inhibitory avoidance the performance of T/T mice was markedly inferior to WT mice. In contrast, T/T and WT mice...

  4. Genome-wide footprints of pig domestication and selection revealed through massive parallel sequencing of pooled DNA.

    Directory of Open Access Journals (Sweden)

    Andreia J Amaral

    Full Text Available BACKGROUND: Artificial selection has caused rapid evolution in domesticated species. The identification of selection footprints across domesticated genomes can contribute to uncover the genetic basis of phenotypic diversity. METHODOLOGY/MAIN FINDINGS: Genome wide footprints of pig domestication and selection were identified using massive parallel sequencing of pooled reduced representation libraries (RRL representing ∼2% of the genome from wild boar and four domestic pig breeds (Large White, Landrace, Duroc and Pietrain which have been under strong selection for muscle development, growth, behavior and coat color. Using specifically developed statistical methods that account for DNA pooling, low mean sequencing depth, and sequencing errors, we provide genome-wide estimates of nucleotide diversity and genetic differentiation in pig. Widespread signals suggestive of positive and balancing selection were found and the strongest signals were observed in Pietrain, one of the breeds most intensively selected for muscle development. Most signals were population-specific but affected genomic regions which harbored genes for common biological categories including coat color, brain development, muscle development, growth, metabolism, olfaction and immunity. Genetic differentiation in regions harboring genes related to muscle development and growth was higher between breeds than between a given breed and the wild boar. CONCLUSIONS/SIGNIFICANCE: These results, suggest that although domesticated breeds have experienced similar selective pressures, selection has acted upon different genes. This might reflect the multiple domestication events of European breeds or could be the result of subsequent introgression of Asian alleles. Overall, it was estimated that approximately 7% of the porcine genome has been affected by selection events. This study illustrates that the massive parallel sequencing of genomic pools is a cost-effective approach to identify

  5. How to Select the Type of Cable Channel%如何选择电缆沟的类型

    Institute of Scientific and Technical Information of China (English)

    张巧

    2014-01-01

    输变电工程电缆沟道形式多种,选择适合具体工程的电缆沟非常重要。因工程启用后电缆沟道内将布满各种电缆,如果在生产运行中沟道出现问题,几乎无法彻底修复,只能局部维持性的修理,为生产运行留下长期隐患。%There are a variety cable channel forms of power transmission and transformation project, choosing suitable cab-le trench for concrete engineering is very important. Because project enabled with al kinds of cable trench, if there are ch-annel problems in the production operation, almost can not be completely repaired, only can get local maintenance repair, le-aving long-term problems for production and operation.

  6. Relationship between expression of muscle-specific uncoupling protein 2 messenger RNA and genetic selection toward growth in channel catfish.

    Science.gov (United States)

    Kobayashi, Y; Peterson, B C; Waldbieser, G C

    2015-04-01

    This study tested the hypothesis that increased growth in channel catfish is associated with expression of the genes that code for uncoupling proteins (UCP) 2 and 3, members of the mitochondrial channel proteins involved in nutrient sensing and metabolism. The specific objective was to contrast the levels of UCP2 messenger RNA (mRNA) in fast vs slow growing catfish as well as in fed vs fasted catfish. Two distinct UCP2 transcripts were identified and named UCP2a and UCP2b, respectively. Nucleotide and amino acid sequence of catfish UCP2s were highly similar to UCP2 and other UCPs from other fish and mammals (>75%). Expression of UCP2a mRNA was detectable at very low levels in various metabolically active tissues, whereas the expression of UCP2b mRNA was readily detectable in the muscle and heart. In a 21-wk feeding study, fish that grew faster had a greater percent body fat at the end of the study (P muscle was increased (P growth and associated fat accumulation appears to be independent of muscle UCP2b mRNA expression and UCP2b-mediated mechanisms.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Georgiev, Danko; González-Burgos, Guillermo; Kikuchi, Mitsuru; Minabe, Yoshio; Lewis, David A; Hashimoto, Takanori

    2012-01-01

    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 (35)S- 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.

  9. Comparative transcriptional analysis reveals distinct expression patterns of channel catfish genes after the first infection and re-infection with Aeromonas hydrophila

    Science.gov (United States)

    To determine whether transcriptional levels of channel catfish (Ictalurus punctatus) genes are differentially regulated between a first infection with Aeromonas hydrophila and a re-infection, suppression subtractive hybridization (SSH) was performed in this study using anterior kidney cDNA after the...

  10. Large-System Analysis of Joint User Selection and Vector Precoding with Zero-Forcing Transmit Beamforming for MIMO Broadcast Channels

    CERN Document Server

    Takeuchi, Keigo; Kawabata, Tsutomu

    2012-01-01

    Multiple-input multiple-output (MIMO) broadcast channels (BCs) (MIMO-BCs) with perfect channel state information (CSI) at the transmitter are considered. As joint user selection (US) and vector precoding (VP) (US-VP) with zero-forcing transmit beamforming (ZF-BF), US and continuous VP (CVP) (US-CVP) and data-dependent US (DD-US) are investigated. The replica method, developed in statistical physics, is used to analyze the energy penalties for the two US-VP schemes in the large-system limit, where the number of users, the number of selected users, and the number of transmit antennas tend to infinity with their ratios kept constant. Four observations are obtained in the large-system limit: First, the assumptions of replica symmetry (RS) and 1-step replica symmetry breaking (1RSB) for DD-US can provide acceptable approximations for low and moderate system loads, respectively. Secondly, DD-US outperforms CVP with random US in terms of the energy penalty for low-to-moderate system loads. Thirdly, the asymptotic en...

  11. The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility.

    Science.gov (United States)

    Provence, Aaron; Malysz, John; Petkov, Georgi V

    2015-09-01

    The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1-KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca(2+) imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K(+) (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca(2+) concentration in DSM cells, an effect blocked by the L-type Ca(2+) channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels.

  12. Dislocation substructure of mantle-derived olivine as revealed by selective chemical etching and transmission electron microscopy

    Science.gov (United States)

    Kirby, S.H.; Wegner, M.W.

    1978-01-01

    Cleaved and mechanically polished surfaces of olivine from peridotite xenoliths from San Carlos, Arizona, were chemically etched using the techniques of Wegner and Christie (1974). Dislocation etch pits are produced on all surface orientations and they tend to be preferentially aligned along the traces of subgrain boundaries, which are approximately parallel to (100), (010), and (001). Shallow channels were also produced on (010) surfaces and represent dislocations near the surface that are etched out along their lengths. The dislocation etch channel loops are often concentric, and emanate from (100) subgrain boundaries, which suggests that dislocation sources are in the boundaries. Data on subgrain misorientation and dislocation line orientation and arguments based on subgrain boundary energy minimization are used to characterize the dislocation structures of the subgrain boundaries. (010) subgrain boundaries are of the twist type, composed of networks of [100] and [001] screw dislocations. Both (100) and (001) subgrain boundaries are tilt walls composed of arrays of edge dislocation with Burgers vectors b=[100] and [001], respectively. The inferred slip systems are {001} ???100???, {100} ???001???, and {010} ???100??? in order of diminishing importance. Exploratory transmission electron microscopy is in accord with these identifications. The flow stresses associated with the development of the subgrain structure are estimated from the densities of free dislocations and from the subgrain dimensions. Inferred stresses range from 35 to 75 bars using the free dislocation densities and 20 to 100 bars using the subgrain sizes. ?? 1978 Springer-Verlag.

  13. 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.

  14. The non-selective voltage-activated cation channel in the human red blood cell membrane: reconciliation between two conflicting reports and further characterisation

    DEFF Research Database (Denmark)

    Kaestner, Lars; Christophersen, Palle; Bernhardt, Ingolf;

    2000-01-01

    Erythrocyte; Patch-clamp; Non-specific; cation channel; Voltage dependence; Acetylcholin receptor......Erythrocyte; Patch-clamp; Non-specific; cation channel; Voltage dependence; Acetylcholin receptor...

  15. Conformational state of the MscS mechanosensitive channel in solution revealed by pulsed electron-electron double resonance (PELDOR) spectroscopy.

    Science.gov (United States)

    Pliotas, Christos; Ward, Richard; Branigan, Emma; Rasmussen, Akiko; Hagelueken, Gregor; Huang, Hexian; Black, Susan S; Booth, Ian R; Schiemann, Olav; Naismith, James H

    2012-10-02

    The heptameric mechanosensitive channel of small conductance (MscS) provides a critical function in Escherichia coli where it opens in response to increased bilayer tension. Three approaches have defined different closed and open structures of the channel, resulting in mutually incompatible models of gating. We have attached spin labels to cysteine mutants on key secondary structural elements specifically chosen to discriminate between the competing models. The resulting pulsed electron-electron double resonance (PELDOR) spectra matched predicted distance distributions for the open crystal structure of MscS. The fit for the predictions by structural models of MscS derived by other techniques was not convincing. The assignment of MscS as open in detergent by PELDOR was unexpected but is supported by two crystal structures of spin-labeled MscS. PELDOR is therefore shown to be a powerful experimental tool to interrogate the conformation of transmembrane regions of integral membrane proteins.

  16. Selective cognitive deficits and reduced hippocampal brain-derived neurotrophic factor mRNA expression in small-conductance calcium-activated K+ channel deficient mice.

    Science.gov (United States)

    Jacobsen, J P R; Redrobe, J P; Hansen, H H; Petersen, S; Bond, C T; Adelman, J P; Mikkelsen, J D; Mirza, N R

    2009-09-29

    Small-conductance calcium-activated K(+) channels 1-3 (SK1-3) are important for neuronal firing regulation and are considered putative CNS drug targets. For instance non-selective SK blockers improve performance in animal models of cognition. The SK subtype(s) involved herein awaits identification and the question is difficult to address pharmacologically due to the lack of subtype-selective SK-channel modulators. In this study, we used doxycycline-induced conditional SK3-deficient (T/T) mice to address the cognitive consequences of selective SK3 deficiency. In T/T mice SK3 protein is near-eliminated from the brain following doxycycline treatment. We tested T/T and wild type (WT) littermate mice in five distinct learning and memory paradigms. In Y-maze spontaneous alternations and five-trial inhibitory avoidance the performance of T/T mice was markedly inferior to WT mice. In contrast, T/T and WT mice performed equally well in passive avoidance, object recognition and the Morris water maze. Thus, some aspects of working/short-term memory are disrupted in T/T mice. Using in situ hybridization, we further found the cognitive deficits in T/T mice to be paralleled by reduced brain-derived neurotrophic factor (BDNF) mRNA expression in the dentate gyrus and CA3 of the hippocampus. BDNF mRNA levels in the frontal cortex were not affected. BDNF has been crucially implicated in many cognitive processes. Hence, the biological substrate for the cognitive impairments in T/T mice could conceivably entail reduced trophic support of the hippocampus.

  17. How do 2D fingerprints detect structurally diverse active compounds? Revealing compound subset-specific fingerprint features through systematic selection.

    Science.gov (United States)

    Heikamp, Kathrin; Bajorath, Jürgen

    2011-09-26

    In independent studies it has previously been demonstrated that two-dimensional (2D) fingerprints have scaffold hopping ability in virtual screening, although these descriptors primarily emphasize structural and/or topological resemblance of reference and database compounds. However, the mechanism by which such fingerprints enrich structurally diverse molecules in database selection sets is currently little understood. In order to address this question, similarity search calculations on 120 compound activity classes of varying structural diversity were carried out using atom environment fingerprints. Two feature selection methods, Kullback-Leibler divergence and gain ratio analysis, were applied to systematically reduce these fingerprints and generate alternative versions for searching. Gain ratio is a feature selection method from information theory that has thus far not been considered in fingerprint analysis. However, it is shown here to be an effective fingerprint feature selection approach. Following comparative feature selection and similarity searching, the compound recall characteristics of original and reduced fingerprint versions were analyzed in detail. Small sets of fingerprint features were found to distinguish subsets of active compounds from other database molecules. The compound recall of fingerprint similarity searching often resulted from a cumulative detection of distinct compound subsets by different fingerprint features, which provided a rationale for the scaffold hopping potential of these 2D fingerprints.

  18. Long-term fluid expulsion revealed by carbonate crusts and pockmarks connected to subsurface gas anomalies and palaeo-channels in the central North Sea

    Science.gov (United States)

    Chand, Shyam; Crémière, Antoine; Lepland, Aivo; Thorsnes, Terje; Brunstad, Harald; Stoddart, Daniel

    2016-11-01

    Gas seepage through the seafloor into the water column is inferred based on acoustic mapping, video observations and geochemical analyses at multiple locations in the Viking Graben and Utsira High areas of the central North Sea. Flares in the Viking Graben occur both inside and along the periphery of a submarine melt water channel where pockmarks (up to 500 m in diameter) and methane-derived carbonate crusts are found on the seafloor, indicating focussing of fluid flow in the vicinity of the channel. The flares can be related to gas accumulations close to the seafloor as well as in Quaternary and deeper strata, observed as high-amplitude reflections on seismic data. Many palaeo-channels, which act as accumulation zones, are observed in the subsurface of both the Viking Graben and Utsira High areas. The deeper origin of gas is partially supported by results of isotope analyses of headspace gas collected from sediment samples of the Viking Graben, which show a mixed microbial/thermogenic origin whereas isotope data on free seeping gas in the Viking Graben indicate a predominantly microbial origin. Based on these lines of evidence, a structure-controlled fluid flow model is proposed whereby hydrocarbons migrate in limited amount from deep thermogenic reservoirs along faults, and these deep fluids are strongly diluted by microbial methane. Moreover, the existence of subsurface pockmarks at several stratigraphic levels indicates long-term fluid flow, interpreted to be caused by gas hydrate destabilisation and stress-related high overpressures.

  19. Species-scanning mutagenesis of the serotonin transporter reveals residues essential in selective, high-affinity recognition of antidepressants

    DEFF Research Database (Denmark)

    Mortensen, O V; Kristensen, A S; Wiborg, O

    2001-01-01

    of the antidepressants citalopram, fluoxetine, paroxetine and imipramine were several-fold higher at hSERT compared with bSERT. No species selectivity was observed for the antidepressants fluvoxamine, and sertraline or for the psychostimulants cocaine, the cocaine analogue beta-carbomethoxy-3beta-(4-iodophenyl......-180 and phenylalanine-513 to confer species selectivity at hSERT for fluoxetine and imipramine. Results were obtained by doing the forward, bovine to human, mutations and confirmed by doing the reverse mutations. Citalopram analogues were used to define the roles of methionine-180, tyrosine-495...

  20. Temporally isolated lineages of Pink salmon reveal unique signatures of selection on distinct pools of standing genetic variation

    DEFF Research Database (Denmark)

    Limborg, Morten; Waples, R.K.; Seeb, J.E.

    2014-01-01

    A species’ genetic diversity bears the marks of evolutionary processes that have occurred throughout its history. However, robust detection of selection in wild populations is difficult and often impeded by lack of replicate tests. Here, we investigate selection in pink salmon (Oncorhynchus...... gorbuscha) using genome scans coupled with inference from a haploid-assisted linkage map. Pink salmon have a strict 2-year semelparous life history which has resulted in temporally isolated (allochronic) lineages that remain sympatric through sharing of spawning habitats in alternate years. The lineages...

  1. Multi-channel selection algorithm in wireless monitoring networks%无线监测网络中多信道优化选择算法

    Institute of Scientific and Technical Information of China (English)

    丁胜; 蒋建国; 夏娜; 王佩佩

    2016-01-01

    无线监测网络中多电台监测节点通过捕捉和分析无线用户的通信数据 ,可以达到监测网络行为、诊断网络故障和管理网络资源的目的 ,而为多电台监测节点优化选择工作信道、最大化捕获数据量、获得最佳网络监测质量(quality of monitoring ,QoM )是一个关键问题.文章研究了一种基于同步微扰随机近似(SPSA )的信道选择算法.该算法在迭代过程中以随机扰动策略得到目标函数的近似梯度 ,引导搜索过程逐步逼近最优解 ;适合于复杂的多维优化问题求解 ,收敛速度快、复杂度低.实验结果表明 ,该算法可以实现无线监测网络中多电台监测节点的信道优化选择 ,并且性能优良.%In wireless monitoring networks ,multi-radio wireless sniffers are distributed for capturing and analyzing user activities in order to realize network monitoring ,fault diagnosis ,resource manage-ment and so on .Therefore ,it is a key topic to optimize the channel selection for sniffers to maximize the information collected ,so as to maximize the quality of monitoring(QoM ) .In this paper ,a simul-taneous perturbation stochastic approximation (SPSA )-based solution is proposed in order to realize optimal channel selection .During iteration process ,the random perturbation strategy is used to com-pute the approximate gradient of the objective function ,which can lead the searching to the optimal solution .The algorithm is fast in convergence and low in complexity .The results of comparison ex-periments demonstrate that the proposed algorithm can realize the multi-channel selection in wireless monitoring networks with high QoM .

  2. Genome-wide candidate regions for selective sweeps revealed through massive parallel sequencing of DNA across ten turkey populations

    NARCIS (Netherlands)

    Aslam, M.L.; Bastiaansen, J.W.M.; Megens, H.J.W.C.; Crooijmans, R.P.M.A.; Blomberg, L.; Groenen, M.

    2014-01-01

    Background The domestic turkey (Meleagris gallopavo) is an important agricultural species that is largely used as a meat-type bird. Characterizing genetic variation in populations of domesticated species and associating these variation patterns with the evolution, domestication, and selective breedi

  3. Microevolution in time and space: SNP analysis of historical DNA reveals dynamic signatures of selection in Atlantic cod

    DEFF Research Database (Denmark)

    Therkildsen, Nina Overgaard; Hansen, Jakob Hemmer; Als, Thomas Damm

    2013-01-01

    Little is known about how quickly natural populations adapt to changes in their environment and how temporal and spatial variation in selection pressures interact to shape patterns of genetic diversity. We here address these issues with a series of genome scans in four overfished populations...

  4. LIGHT MODULATION: Quasi-collinear tunable acousto-optic paratellurite crystal filters for wavelength division multiplexing and optical channel selection

    Science.gov (United States)

    Molchanov, V. Ya; Voloshinov, V. B.; Makarov, O. Yu

    2009-04-01

    Quasi-collinear acousto-optic interaction is studied in acoustically and optically anisotropic paratellurite crystals. The possible applications of this interaction in acousto-optic tunable filters with a high spectral resolution are discussed. Different modifications of devices are compared and variants of devices intended for processing light beams and selection of light signals in fibreoptic communication systems with wavelength division multiplexing (WDM) at λ simeq 1550 nm are considered.

  5. Optimal frequency selection of multi-channel O2-band different absorption barometric radar for air pressure measurements

    Science.gov (United States)

    Lin, Bing; Min, Qilong

    2017-02-01

    Through theoretical analysis, optimal selection of frequencies for O2 differential absorption radar systems on air pressure field measurements is achieved. The required differential absorption optical depth between a radar frequency pair is 0.5. With this required value and other considerations on water vapor absorption and the contamination of radio wave transmission, frequency pairs of present considered radar system are obtained. Significant impacts on general design of differential absorption remote sensing systems are expected from current results.

  6. Selection of Mother Wavelet Functions for Multi-Channel EEG Signal Analysis during a Working Memory Task

    Directory of Open Access Journals (Sweden)

    Noor Kamal Al-Qazzaz

    2015-11-01

    Full Text Available We performed a comparative study to select the efficient mother wavelet (MWT basis functions that optimally represent the signal characteristics of the electrical activity of the human brain during a working memory (WM task recorded through electro-encephalography (EEG. Nineteen EEG electrodes were placed on the scalp following the 10–20 system. These electrodes were then grouped into five recording regions corresponding to the scalp area of the cerebral cortex. Sixty-second WM task data were recorded from ten control subjects. Forty-five MWT basis functions from orthogonal families were investigated. These functions included Daubechies (db1–db20, Symlets (sym1–sym20, and Coiflets (coif1–coif5. Using ANOVA, we determined the MWT basis functions with the most significant differences in the ability of the five scalp regions to maximize their cross-correlation with the EEG signals. The best results were obtained using “sym9” across the five scalp regions. Therefore, the most compatible MWT with the EEG signals should be selected to achieve wavelet denoising, decomposition, reconstruction, and sub-band feature extraction. This study provides a reference of the selection of efficient MWT basis functions.

  7. Selective underexpression of Kv3.2 and Kv3.4 channels in the cortex of rats exposed to ethanol during early postnatal life.

    Science.gov (United States)

    Tavian, Daniela; De Giorgio, Andrea; Granato, Alberto

    2011-08-01

    The expression of voltage-gated potassium channels belonging to the Kv3 family has been studied in the sensori-motor cortex of rats exposed to alcohol inhalation during the first postnatal week (P2-P6). The study was carried out using comparative RT-PCR. At P9, a significant reduction of the expression of Kv3.2 and Kv3.4 subunits occurred in alcohol-treated animals, as compared with controls. The expression of the Kv3.4a splicing variant, which is thought to be critically involved in the high-frequency firing of some cortical interneurons, was also correspondingly reduced. The downregulation of Kv3.2 and Kv3.4a subunits represented a long-lasting effect of alcohol exposure, since it was also observed in P24 animals. The expression of both Kv3.1 and Kv3.3 channels appeared to be not significantly affected by alcohol exposure. An increased susceptibility to apoptotic neuronal death after early postnatal exposure to ethanol was confirmed by the lower bcl-2/bax ratio observed in alcohol-treated animals. Although Kv3.4 subunits are thought to trigger apoptosis, the lack of upregulation in our model argues against their involvement in the mechanism leading to alcohol-induced apoptosis. The possible consequences of the selective downregulation of Kv3 subunits on the cortical function, as well as their relevance for the genesis of fetal alcohol effects, are discussed.

  8. Cell-attached single-channel recordings in intact prefrontal cortex pyramidal neurons reveal compartmentalized D1/D5 receptor modulation of the persistent sodium current.

    Directory of Open Access Journals (Sweden)

    Natalia eGorelova

    2015-02-01

    Full Text Available The persistent Na current (INap is believed to be an important target of dopamine modulation in prefrontal cortex (PFC neurons. While past studies have tested the effects of dopamine on INap, the results have been contradictory largely because of difficulties in measuring INap using somatic whole-cell recordings. To circumvent these confounds we used the cell-attached patch-clamp technique to record single Na channels from the soma, proximal dendrite or proximal axon of intact prefrontal layer V pyramidal neurons. Under baseline conditions, numerous well resolved Na channel openings were recorded that exhibited an extrapolated reversal potential of 73 mV, a slope conductance of 14-19pS and were blocked by TTX. While similar in most respects, the propensity to exhibit prolonged bursts lasting >40ms was many fold greater in the axon than the soma or dendrite. Bath application of the D1 agonist SKF81297 shifted the ensemble current activation curve leftward and increased the number of late events recorded from the proximal dendrite but not the soma or axon. However, the greatest effect was on prolonged bursting where the D1 agonist increased their occurrence 3 fold in the proximal dendrite and nearly 7 fold in the soma, but not at all in the axon. As a result, D1 activation equalized the probability of prolonged burst occurrence across the proximal axosomatodendritic region. Therefore, D1 modulation appears to be targeted mainly to Na channels in the proximal dendrite/soma and not the proximal axon. By circumventing the pitfalls of previous attempts to study the D1R modulation of INap, we demonstrate conclusively that D1R can increase the INap generated proximally, however questions still remain as to how D1R modulates Na currents in the more distal initial segment where most of the INap is normally generated.

  9. The Outcome of Selenium and Vitamin E Cancer Prevention Trial (SELECT) reveals the need for better understanding of selenium biology.

    Science.gov (United States)

    Hatfield, Dolph L; Gladyshev, Vadim N

    2009-02-01

    The recently completed Selenium and Vitamin E Cancer Prevention Trial (SELECT) was one of the largest human cancer prevention trials ever undertaken. Its purpose was to assess the role of selenium and vitamin E in prostate cancer prevention, but SELECT found no decline in prostate cancer. Comparison of this study to other clinical trials involving selenium and to the results of animal studies suggests that the source of the selenium supplement, L-selenomethionine, and the relatively high initial levels of selenium in the enrolled men may have contributed to this outcome. Further analysis of the clinical and animal data highlights the need for mechanistic studies to better understand selenium biology in order to target dietary selenium to appropriate subsets of the human population: those individuals most likely to benefit from this micronutrient.

  10. Phylodynamics of H1N1/2009 influenza reveals the transition from host adaptation to immune-driven selection.

    Science.gov (United States)

    Su, Yvonne C F; Bahl, Justin; Joseph, Udayan; Butt, Ka Man; Peck, Heidi A; Koay, Evelyn S C; Oon, Lynette L E; Barr, Ian G; Vijaykrishna, Dhanasekaran; Smith, Gavin J D

    2015-08-06

    Influenza A H1N1/2009 virus that emerged from swine rapidly replaced the previous seasonal H1N1 virus. Although the early emergence and diversification of H1N1/2009 is well characterized, the ongoing evolutionary and global transmission dynamics of the virus remain poorly investigated. To address this we analyse >3,000 H1N1/2009 genomes, including 214 full genomes generated from our surveillance in Singapore, in conjunction with antigenic data. Here we show that natural selection acting on H1N1/2009 directly after introduction into humans was driven by adaptation to the new host. Since then, selection has been driven by immunological escape, with these changes corresponding to restricted antigenic diversity in the virus population. We also show that H1N1/2009 viruses have been subject to regular seasonal bottlenecks and a global reduction in antigenic and genetic diversity in 2014.

  11. Enhanced bias stability of solution-processed zinc-tin-oxide thin film transistors using self-assembled monolayer as a selective channel passivation.

    Science.gov (United States)

    Heo, Jae-Sang; Park, Sung-Kyu

    2013-10-01

    The enhanced positive bias stability of amorphous zinc-tin-oxide thin-film transistors (a-ZTO TFTs) were obtained by applying self-assembled monolayer (SAM) as a selective passivation layer on the metal-oxide back channel area. The a-ZTO TFTs with passivation layers such as poly(methyl methacylate) (PMMA), SAM, and SAM/PMMA were fabricated by simple solution methods. After deposition of the passivation layers, the electrical characteristics of a-ZTO TFTs have not been changed and the threshold voltage shift (deltaV(th)) under gate-bias stress for around 10(4) seconds was improved. The deltaV(th) of the devices with PMMA, SAM, and SAM/PMMA dual layer were 3.79 V, 3.2 V, and 2.17 V, respectively.

  12. The impact of selection on population genetic structure in the clam Meretrix petechialis revealed by microsatellite markers.

    Science.gov (United States)

    Lu, Xia; Wang, Hongxia; Li, Yan; Liu, Baozhong

    2016-02-01

    The aim of our work is to evaluate the impact of mass selection on genetic structure in artificially closed populations of the clam Meretrix petechialis. In the present study, we performed mass selection over four generations (from 2004 to 2010) on two clam populations [shell features of purple lines (SP) and black dots (SB)] and analyzed their temporal genetic variation and structure using microsatellite makers. The two closed populations originated from the natural Shandong population (SD); thus, a natural SD population (10SD) was used to detect the current genetic structure after 6 years of natural selection. The results showed that the genetic diversity of the four generations of SB and SP was gradually reduced but remained at relatively high levels (SB, A = 18.9.4-16.8, Ho = 0.7389-0.6971, and He = 0.8897-0.8591; SP, A = 20.0-17.8, Ho = 0.7512-0.7043, and He = 0.8938-0.8625), which has not been reduced compared with that of the 10SD population (A = 17.8, Ho = 0.6803, and He = 0.8302). The Ne estimates for the two populations were almost at the same levels as the actual numbers of parental individuals. In addition, a low inbreeding coefficient was detected in the two populations (SB, 0.00201-0.00639; SP, 0.00176-0.00541). Based on the results, the present mass selection has not made a large impact on the population genetic structure of the closed populations. The present investigation provides important information for the development of management strategies for genetic breeding of the clam.

  13. Artificial selection on relative brain size in the guppy reveals costs and benefits of evolving a larger brain.

    Science.gov (United States)

    Kotrschal, Alexander; Rogell, Björn; Bundsen, Andreas; Svensson, Beatrice; Zajitschek, Susanne; Brännström, Ioana; Immler, Simone; Maklakov, Alexei A; Kolm, Niclas

    2013-01-21

    The large variation in brain size that exists in the animal kingdom has been suggested to have evolved through the balance between selective advantages of greater cognitive ability and the prohibitively high energy demands of a larger brain (the "expensive-tissue hypothesis"). Despite over a century of research on the evolution of brain size, empirical support for the trade-off between cognitive ability and energetic costs is based exclusively on correlative evidence, and the theory remains controversial. Here we provide experimental evidence for costs and benefits of increased brain size. We used artificial selection for large and small brain size relative to body size in a live-bearing fish, the guppy (Poecilia reticulata), and found that relative brain size evolved rapidly in response to divergent selection in both sexes. Large-brained females outperformed small-brained females in a numerical learning assay designed to test cognitive ability. Moreover, large-brained lines, especially males, developed smaller guts, as predicted by the expensive-tissue hypothesis, and produced fewer offspring. We propose that the evolution of brain size is mediated by a functional trade-off between increased cognitive ability and reproductive performance and discuss the implications of these findings for vertebrate brain evolution.

  14. Ligand-directed functional selectivity at the mu opioid receptor revealed by label-free integrative pharmacology on-target.

    Directory of Open Access Journals (Sweden)

    Megan Morse

    Full Text Available Development of new opioid drugs that provide analgesia without producing dependence is important for pain treatment. Opioid agonist drugs exert their analgesia effects primarily by acting at the mu opioid receptor (MOR sites. High-resolution differentiation of opioid ligands is crucial for the development of new lead drug candidates with better tolerance profiles. Here, we use a label-free integrative pharmacology on-target (iPOT approach to characterize the functional selectivity of a library of known opioid ligands for the MOR. This approach is based on the ability to detect dynamic mass redistribution (DMR arising from the activation of the MOR in living cells. DMR assays were performed in HEK-MOR cells with and without preconditioning with probe molecules using label-free resonant waveguide grating biosensors, wherein the probe molecules were used to modify the activity of specific signaling proteins downstream the MOR. DMR signals obtained were then translated into high resolution heat maps using similarity analysis based on a numerical matrix of DMR parameters. Our data indicate that the iPOT approach clearly differentiates functional selectivity for distinct MOR signaling pathways among different opioid ligands, thus opening new avenues to discover and quantify the functional selectivity of currently used and novel opioid receptor drugs.

  15. Electrokinetic inversion of ion screening charges in nano-channels

    CERN Document Server

    Zhu, Xin; Ni, Sheng; Zhang, Xingye; Liu, Yang

    2016-01-01

    This work studies a counter-intuitive but basic process of ionic screening in nano-fluidic channels. Numerical simulations and perturbation analysis reveal that, under significant electrokinetic transport, the ion screening charges can be locally inverted in the channels: their charge sign becomes the same as that of the channel surface charges. The process is identified to originate from the coupling of longitudinal transport and junction electrostatics. This finding may revise the common understanding of ionic screening in nano-channels and indicates that their ion selectivity can be locally changed by transport. Furthermore, the charge inversion process results in a body force torque on channel fluids, which is a possible mechanism for vortex generation in the channels.

  16. Distinct abscisic acid signaling pathways for modulation of guard cell versus mesophyll cell potassium channels revealed by expression studies in Xenopus laevis oocytes

    Science.gov (United States)

    Sutton, F.; Paul, S. S.; Wang, X. Q.; Assmann, S. M.; Evans, M. L. (Principal Investigator)

    2000-01-01

    Regulation of guard cell ion transport by abscisic acid (ABA) and in particular ABA inhibition of a guard cell inward K(+) current (I(Kin)) is well documented. However, little is known concerning ABA effects on ion transport in other plant cell types. Here we applied patch clamp techniques to mesophyll cell protoplasts of fava bean (Vicia faba cv Long Pod) plants and demonstrated ABA inhibition of an outward K(+) current (I(Kout)). When mesophyll cell protoplast mRNA (mesophyll mRNA) was expressed in Xenopus laevis oocytes, I(Kout) was generated that displayed similar properties to I(Kout) observed from direct analysis of mesophyll cell protoplasts. I(Kout) expressed by mesophyll mRNA-injected oocytes was inhibited by ABA, indicating that the ABA signal transduction pathway observed in mesophyll cells was preserved in the frog oocytes. Co-injection of oocytes with guard cell protoplast mRNA and cRNA for KAT1, an inward K(+) channel expressed in guard cells, resulted in I(Kin) that was similarly inhibited by ABA. However, oocytes co-injected with mesophyll mRNA and KAT1 cRNA produced I(Kin) that was not inhibited by ABA. These results demonstrate that the mesophyll-encoded signaling mechanism could not substitute for the guard cell pathway. These findings indicate that mesophyll cells and guard cells use distinct and different receptor types and/or signal transduction pathways in ABA regulation of K(+) channels.

  17. Measurement of the top quark pair production cross section in the dilepton channel using lepton+track selection

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Robert Emil [Princeton Univ., NJ (United States)

    2008-11-01

    The production cross section for t$\\bar{t}$ pairs decaying into two lepton final states was measured using data from the D0 detector at Fermilab. The measurement was made using a lepton+track selection, where one lepton is fully identified and the second lepton is observed as an isolated track. This analysis is designed to complement similar studies using two fully identified leptons [1]. The cross section for the lepton+track selection was found to be σ = 5.2-1.4+1.6(stat)-0.8+0.9(syst) ± 0.3(lumi) pb. The combined cross section using both the lepton+track data and the data from the electron+electron, electron+muon, and muon+muon samples is: σ = 6.4-0.9+0.9(stat)-0.7+0.8(syst) ± 0.4(lumi) pb.

  18. Identification and molecular characterization of three new K+-channel specific toxins from the Chinese scorpion Mesobuthus martensii Karsch revealing intronic number polymorphism and alternative splicing in duplicated genes.

    Science.gov (United States)

    Zeng, Xian-Chun; Zhang, Lei; Nie, Yao; Luo, Xuesong

    2012-04-01

    K(+)-channel specific toxins from scorpions are powerful probes used in the structural and functional characterization of different subfamilies of K(+)-channels which are thought to be the most diverse ion channels. However, only a limited number of K(+)-channel toxins have been identified from scorpions so far; moreover, little is known about the mechanisms for the generation of a combinatorial peptide library in a venom gland of a scorpion. Here, we identified and characterized three new K(+)-channel toxin-like peptides from the scorpion Mesobuthus martensii Karsch, which were referred to as BmKcug1, BmKcug2 and BmKcugx, respectively. BmKcug1 and BmKcug2 are two new members of α-KTx1 subfamily, and have been classified as α-KTx1.14 and α-KTx1.15, respectively. BmKcugx represents a new subfamily of K(+)-channel specific toxins which was classified into α-KTx22. BmKcugx was thus classified as α-KTx22.1. Genomic analysis demonstrated that BmKcugx gene has two exons interrupted by an intron inserted in the signal peptide encoding region, whereas BmKcug1a (a close homologue of BmKcug1)/BmKcug2 gene was interrupted by two introns, located within the 5'UTR of the gene and in the signal peptide encoding region, respectively. Transcriptomic analysis for the venom glands of M. martensii Karsch indicated that the abundances of the transcripts of BmKcug1a and BmKcug2 are much higher than that of BmKcugx; it suggests that the intron in 5'UTR could markedly increase the expression level of the K(+)-channel toxins. Alignment of the genomic sequences of BmKcug1a and BmKcug2 revealed that an alternative splicing event occurred at the intron 1-exon 2 junction in the 5'UTR of BmKcug2 transcript.

  19. Selective MS screening reveals a sex pheromone in Caenorhabditis briggsae and species-specificity in indole ascaroside signalling.

    Science.gov (United States)

    Dong, Chuanfu; Dolke, Franziska; von Reuss, Stephan H

    2016-08-14

    The indole ascarosides (icas) represent a highly potent class of nematode-derived modular signalling components that integrate structural inputs from amino acid, carbohydrate, and fatty acid metabolism. Comparative analysis of the crude exo-metabolome of hermaphroditic Caenorhabditis briggsae using a highly sensitive mass spectrometric screen reveals an indole ascaroside blend dominated by two new components. The structures of isolated icas#2 and icas#6.2 were determined by NMR spectroscopy and confirmed by total synthesis and chemical correlation. Low atto- to femtomolar amounts of icas#2 and icas#6.2 act in synergism to attract males indicating a function as sex pheromone. Comparative analysis of 14 Caenorhabditis species further demonstrates that species-specific indole ascaroside biosynthesis is highly conserved in the Elegans group. Functional characterization of the dominating indole ascarosides icas#2, icas#3, and icas#9 reveals a high degree of species-specificity and considerable variability with respect to gender-specificity, thus, confirming that indole ascarosides modulate different biological functions within the Elegans group. Although the nematode response was usually most pronounced towards conspecific signals, Caenorhabditis brenneri, the only species of the Elegans group that does not produce any indole ascarosides, exhibits a robust response to icas#2 suggesting the potential for interspecies interactions.

  20. Multi-country Survey Revealed Prevalent and Novel F1534S Mutation in Voltage-Gated Sodium Channel (VGSC Gene in Aedes albopictus.

    Directory of Open Access Journals (Sweden)

    Jiabao Xu

    2016-05-01

    Full Text Available Aedes albopictus is an important dengue vector because of its aggressive biting behavior and rapid spread out of its native home range in Southeast Asia. Pyrethroids are widely used for adult mosquito control, and resistance to pyrethroids should be carefully monitored because vector control is the only effective method currently available to prevent dengue transmission. The voltage-gated sodium channel gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr. Previous studies reported various mutations in the voltage-gated sodium channel (VGSC gene, but the spatial distribution of kdr mutations in Ae. albopictus has not been systematically examined, and the association between kdr mutation and phenotypic resistance has not been established.A total of 597 Ae. albopictus individuals from 12 populations across Asia, Africa, America and Europe were examined for mutations in the voltage-gated sodium channel gene. Three domains for a total of 1,107 bp were sequenced for every individual. Two populations from southern China were examined for pyrethroid resistance using the World Health Organization standard tube bioassay, and the association between kdr mutations and phenotypic resistance was tested.A total of 29 synonymous mutations were found across domain II, III and IV of the VGSC gene. Non-synonymous mutations in two codons of the VGSC gene were detected in 5 populations from 4 countries. A novel mutation at 1532 codon (I1532T was found in Rome, Italy with a frequency of 19.7%. The second novel mutation at codon 1534 (F1534S was detected in southern China and Florida, USA with a frequency ranging from 9.5-22.6%. The WHO insecticide susceptibility bioassay found 90.1% and 96.1% mortality in the two populations from southern China, suggesting resistance and probable resistance. Positive association between kdr mutations with deltamethrin resistance was established in these two populations.Two novel kdr

  1. Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.

    Directory of Open Access Journals (Sweden)

    Matthew W Parker

    Full Text Available Neuropilin (Nrp receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF family of proangiogenic cytokines and the semaphorin 3 (Sema3 family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.

  2. Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations

    Directory of Open Access Journals (Sweden)

    Accili Eric A

    2008-06-01

    Full Text Available Abstract Background Mutations in HERG and KCNQ1 potassium channels have been associated with Long QT syndrome and atrial fibrillation, and more recently with sudden infant death syndrome and sudden unexplained death. In other proteins, disease-associated amino acid mutations have been analyzed according to the chemical severity of the changes and the locations of the altered amino acids according to their conservation over metazoan evolution. Here, we present the first such analysis of arrhythmia-associated mutations (AAMs in the HERG and KCNQ1 potassium channels. Results Using evolutionary analyses, AAMs in HERG and KCNQ1 were preferentially found at evolutionarily conserved sites and unevenly distributed among functionally conserved domains. Non-synonymous single nucleotide polymorphisms (nsSNPs are under-represented at evolutionarily conserved sites in HERG, but distribute randomly in KCNQ1. AAMs are chemically more severe, according to Grantham's Scale, than changes observed in evolution and their severity correlates with the expected chemical severity of the involved codon. Expected chemical severity of a given amino acid also correlates with its relative contribution to arrhythmias. At evolutionarily variable sites, the chemical severity of the changes is also correlated with the expected chemical severity of the involved codon. Conclusion Unlike nsSNPs, AAMs preferentially locate to evolutionarily conserved, and functionally important, sites and regions within HERG and KCNQ1, and are chemically more severe than changes which occur in evolution. Expected chemical severity may contribute to the overrepresentation of certain residues in AAMs, as well as to evolutionary change.

  3. Two crustal flowing channels and volcanic magma migration underneath the SE margin of the Tibetan Plateau as revealed by surface wave tomography

    Science.gov (United States)

    Wu, Tengfei; Zhang, Shuangxi; Li, Mengkui; Qin, Weibing; Zhang, Chaoyu

    2016-12-01

    The SE margin of the Tibetan Plateau is an important area to develop a better understanding of the plateau uplift and the Indian-Eurasian continental collision dynamics. Previous studies have reported widespread low-velocity anomalies beneath this region, particularly in the Tengchong volcanic field (TCVF). However, the spatial distribution and dynamic processes of these low-velocity anomalies are not well constrained. In this study, a 3-D S-wave velocity structure model of the crust and upper mantle (10-120 km) in the region is constructed by the inversion of surface wave dispersion data. A two-step inversion procedure is adopted to generate the S-wave velocity structure images. The measured phase velocities and inverted S-wave velocities jointly show a large-scale low-velocity anomaly distributed in the crust, consistent with the view that the region is the passageway of the eastward migration of Tibetan Plateau material. Two crustal flowing channels are clearly observed at depths of ∼20 km and ∼30 km, which connect and rotate clockwise around the Eastern Himalaya Syntaxis. Beneath the TCVF, there are two prominent low-velocity anomaly zones at depths of ∼15-25 km and ∼50-80 km, which indicate the existence of magma chambers. One of the crustal flowing channels is connected with the magma chamber of the TCVF, and the other has a short branch north of Kunming toward the Mile-Shizong fault at a depth of 20 km. Based on the distribution of the S-wave velocities under the TCVF, a dynamic model of the Tengchong volcano magma system is proposed to explain the migration patterns of the volcanic material.

  4. Structural and biochemical studies of a fluoroacetyl-CoA-specific thioesterase reveal a molecular basis for fluorine selectivity.

    Science.gov (United States)

    Weeks, Amy M; Coyle, Scott M; Jinek, Martin; Doudna, Jennifer A; Chang, Michelle C Y

    2010-11-02

    We have initiated a broad-based program aimed at understanding the molecular basis of fluorine specificity in enzymatic systems, and in this context, we report crystallographic and biochemical studies on a fluoroacetyl-coenzyme A (CoA) specific thioesterase (FlK) from Streptomyces cattleya. Our data establish that FlK is competent to protect its host from fluoroacetate toxicity in vivo and demonstrate a 10(6)-fold discrimination between fluoroacetyl-CoA (k(cat)/K(M) = 5 × 10⁷ M⁻¹ s⁻¹) and acetyl-CoA (k(cat)/K(M) = 30 M⁻¹ s⁻¹) based on a single fluorine substitution that originates from differences in both substrate reactivity and binding. We show that Thr 42, Glu 50, and His 76 are key catalytic residues and identify several factors that influence substrate selectivity. We propose that FlK minimizes interaction with the thioester carbonyl, leading to selection against acetyl-CoA binding that can be recovered in part by new C═O interactions in the T42S and T42C mutants. We hypothesize that the loss of these interactions is compensated by the entropic driving force for fluorinated substrate binding in a hydrophobic binding pocket created by a lid structure, containing Val 23, Leu 26, Phe 33, and Phe 36, that is not found in other structurally characterized members of this superfamily. We further suggest that water plays a critical role in fluorine specificity based on biochemical and structural studies focused on the unique Phe 36 "gate" residue, which functions to exclude water from the active site. Taken together, the findings from these studies offer molecular insights into organofluorine recognition and design of fluorine-specific enzymes.

  5. Low-dose combination of Rho kinase and L-type Ca(2+) channel antagonists for selective inhibition of depolarization-induced sustained arterial contraction.

    Science.gov (United States)

    Porras-González, Cristina; González-Rodríguez, Patricia; Calderón-Sánchez, Eva; López-Barneo, José; Ureña, Juan

    2014-06-05

    L-type Ca(2+) channels (LTCCs) are involved in the maintenance of tonic arterial contractions and regulate the RhoA/Rho-associated kinase (ROCK) sensitization cascade. We have tested effects of individual and combined low concentrations of LTCCs and ROCK inhibitors to produce arterial relaxation without the adverse side effects of LTCCs antagonists. We have also studied whether this pharmacological strategy alters Ca(2+)-dependent electrical properties of isolated arterial and cardiac myocytes as well as cardiac contractility. Rat basilar, human carotid and coronary arterial rings were mounted on a small-vessel myograph to measure isometric tension and cardiac contractility was measured in Langendorff-perfused rat heart. Simultaneous cytosolic Ca(2+) concentration and arterial diameter were measured in intact pressurized arteries loaded with Fura-2. Patch-clamp techniques were used to measure electrical properties in isolated cardiac and arterial myocytes. Low concentrations of LTCCs and ROCK inhibitors reduced the tonic component of moderate depolarization-evoked contraction, leaving the phasic component practically unaltered. This selective vasorelaxant effect was more marked when the LTCCs and ROCK inhibitors were applied together. In the concentration range used (nM), Ca(2+) currents in arterial myocytes, cardiac action potentials and heart contractility were unaffected by this pharmacological approach. In conclusion, low doses of LTCCs and ROCK inhibitors could be used to selectively relax precontracted arteries in pathologic conditions such as hypertension, and cerebral or coronary spasms with minor side effects on physiological contractile properties of vascular and cardiac myocytes.

  6. Dimensional accuracy of internal cooling channel made by selective laser melting (SLM And direct metal laser sintering (DMLS processes in fabrication of internally cooled cutting tools

    Directory of Open Access Journals (Sweden)

    Ghani S. A. C.

    2017-01-01

    Full Text Available Selective laser melting(SLM and direct metal laser sintering(DMLS are preferred additive manufacturing processes in producing complex physical products directly from CAD computer data, nowadays. The advancement of additive manufacturing promotes the design of internally cooled cutting tool for effectively used in removing generated heat in metal machining. Despite the utilisation of SLM and DMLS in a fabrication of internally cooled cutting tool, the level of accuracy of the parts produced remains uncertain. This paper aims at comparing the dimensional accuracy of SLM and DMLS in machining internally cooled cutting tool with a special focus on geometrical dimensions such as hole diameter. The surface roughness produced by the two processes are measured with contact perthometer. To achieve the objectives, geometrical dimensions of identical tool holders for internally cooled cutting tools fabricated by SLM and DMLS have been determined by using digital vernier calliper and various magnification of a portable microscope. In the current study, comparing internally cooled cutting tools made of SLM and DMLS showed that generally the higher degree of accuracy could be obtained with DMLS process. However, the observed differences in surface roughness between SLM and DMLS in this study were not significant. The most obvious finding to emerge from this study is that the additive manufacturing processes selected for fabricating the tool holders for internally cooled cutting tool in this research are capable of producing the desired internal channel shape of internally cooled cutting tool.

  7. Comparative analysis of a large panel of non-starch polysaccharides reveals structures with selective regulatory properties in dendritic cells

    DEFF Research Database (Denmark)

    Wismar, René; Pedersen, Susanne Brix; Lærke, Helle Nygaard

    2011-01-01

    Scope: Structural-based recognition of foreign molecules is essential for activation of dendritic cells (DCs) that play a key role in regulation of gut mucosal immunity. Orally ingested non-starch polysaccharides (NSP) are ascribed many health-promoting properties, but currently we lack insight i.......Conclusions: Collectively, this comparative study revealed that some plant-derived NSP besides those of microbial origin exert modulation of the DC phenotype, with the exact structure being important for the activity.......Scope: Structural-based recognition of foreign molecules is essential for activation of dendritic cells (DCs) that play a key role in regulation of gut mucosal immunity. Orally ingested non-starch polysaccharides (NSP) are ascribed many health-promoting properties, but currently we lack insight...... into the impact of structure and size for their capacity to affect immune responses.Methods and results: This study addresses the importance of chemical structure, size, origin and presence of contaminants for the capacity of both dietary and non-food NSP to modulate DC. Of 28 NSP products, β-glucans of microbial...

  8. Local Environment and Interactions of Liquid and Solid Interfaces Revealed by Spectral Line Shape of Surface Selective Nonlinear Vibrational Probe

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shun-Li; Fu, Li; Chase, Zizwe A.; Gan, Wei; Wang, Hong-Fei

    2016-11-10

    Vibrational spectral lineshape contains important detailed information of molecular vibration and reports its specific interactions and couplings to its local environment. In this work, recently developed sub-1 cm-1 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) was used to measure the -C≡N stretch vibration in the 4-n-octyl-4’-cyanobiphenyl (8CB) Langmuir or Langmuir-Blodgett (LB) monolayer as a unique vibrational probe, and the spectral lineshape analysis revealed the local environment and interactions at the air/water, air/glass, air/calcium fluoride and air/-quartz interfaces for the first time. The 8CB Langmuir or LB film is uniform and the vibrational spectral lineshape of its -C≡N group has been well characterized, making it a good choice as the surface vibrational probe. Lineshape analysis of the 8CB -C≡N stretch SFG vibrational spectra suggests the coherent vibrational dynamics and the structural and dynamic inhomogeneity of the -C≡N group at each interface are uniquely different. In addition, it is also found that there are significantly different roles for water molecules in the LB films on different substrate surfaces. These results demonstrated the novel capabilities of the surface nonlinear spectroscopy in characterization and in understanding the specific structures and chemical interactions at the liquid and solid interfaces in general.

  9. A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes

    Science.gov (United States)

    Lu, Xiaolong; Malley, Konstantin R.; Brenner, Caitlin C.; Koroleva, Olga; Korolev, Sergey; Downes, Brian P.

    2016-08-01

    Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2~Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s.

  10. Artificial selection on relative brain size reveals a positive genetic correlation between brain size and proactive personality in the guppy.

    Science.gov (United States)

    Kotrschal, Alexander; Lievens, Eva J P; Dahlbom, Josefin; Bundsen, Andreas; Semenova, Svetlana; Sundvik, Maria; Maklakov, Alexei A; Winberg, Svante; Panula, Pertti; Kolm, Niclas

    2014-04-01

    Animal personalities range from individuals that are shy, cautious, and easily stressed (a "reactive" personality type) to individuals that are bold, innovative, and quick to learn novel tasks, but also prone to routine formation (a "proactive" personality type). Although personality differences should have important consequences for fitness, their underlying mechanisms remain poorly understood. Here, we investigated how genetic variation in brain size affects personality. We put selection lines of large- and small-brained guppies (Poecilia reticulata), with known differences in cognitive ability, through three standard personality assays. First, we found that large-brained animals were faster to habituate to, and more exploratory in, open field tests. Large-brained females were also bolder. Second, large-brained animals excreted less cortisol in a stressful situation (confinement). Third, large-brained animals were slower to feed from a novel food source, which we interpret as being caused by reduced behavioral flexibility rather than lack of innovation in the large-brained lines. Overall, the results point toward a more proactive personality type in large-brained animals. Thus, this study provides the first experimental evidence linking brain size and personality, an interaction that may affect important fitness-related aspects of ecology such as dispersal and niche exploration.

  11. Selective induction and subcellular distribution of ACONITASE 3 reveal the importance of cytosolic citrate metabolism during lipid mobilization in Arabidopsis.

    Science.gov (United States)

    Hooks, Mark A; Allwood, J William; Harrison, Joanna K D; Kopka, Joachim; Erban, Alexander; Goodacre, Royston; Balk, Janneke

    2014-10-15

    Arabidopsis thaliana has three genes that encode distinct aconitases (ACO), but little is known about the function of each isoenzyme during plant development. In newly emerged seedlings of Arabidopsis, transcript and protein levels for ACO3 were selectively induced to yield more than 80% of total aconitase activity. Characterization of knockout mutants for each of the three ACOs suggests a major role for only ACO3 in citrate metabolism. The aco3 mutant showed delayed early seedling growth, altered assimilation of [14C]acetate feeding and elevated citrate levels, which were nearly 4-fold greater than in wild-type, aco1 or aco2. However, both ACO1 and ACO2 are active in seedlings as shown by inhibition of aco3 growth by the toxin monofluoroacetate, and altered [14C]acetate assimilation and metabolite levels in aco1 and aco2. Relative levels of fumarate and malate differed between aco2 and aco3, indicating metabolically isolated pools of these metabolites in seedlings. Our inability to enrich ACO protein through mitochondria isolation, and the reduced cytosolic ACO activity of the iron-sulfur centre assembly mutant atm3-1, indicated a cytosolic localization of ACO3 in 3-day-old seedlings. Subsequently, we determined that more than 90% of ACO3 was cytosolic. We conclude that ACO3 is cytosolic in young seedlings and functions in citrate catabolism consistent with the operation of the classic glyoxylate and not direct catabolism of citrate within mitochondria.

  12. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model.

    Directory of Open Access Journals (Sweden)

    Pablo Miguel Casillas-Espinosa

    Full Text Available Temporal lobe epilepsy (TLE is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg was assessed in fully kindled rats (5 class V seizures as compared to vehicle, ethosuximide (ETX, 100mg/kg and carbamazepine (30mg/kg. Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg, ETX (100mg/kg or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (p<0.05, IV (p<0.01 or V (p<0.0001 seizure, and to reach a fully kindled state (p<0.01, than animals receiving vehicle. There was no significant difference in the mRNA expression of the T-type Ca2+ channels in the hippocampus or amygdala. Our results show that selectively targeting T-type Ca2+ channels with Z944 inhibits the progression of amygdala kindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy.

  13. Structural determinants of species-selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies.

    Science.gov (United States)

    Kaufmann, Kristian W; Dawson, Eric S; Henry, L Keith; Field, Julie R; Blakely, Randy D; Meiler, Jens

    2009-02-15

    To identify potential determinants of substrate selectivity in serotonin (5-HT) transporters (SERT), models of human and Drosophila serotonin transporters (hSERT, dSERT) were built based on the leucine transporter (LeuT(Aa)) structure reported by Yamashita et al. (Nature 2005;437:215-223), PBDID 2A65. Although the overall amino acid identity between SERTs and the LeuT(Aa) is only 17%, it increases to above 50% in the first shell of the putative 5-HT binding site, allowing de novo computational docking of tryptamine derivatives in atomic detail. Comparison of hSERT and dSERT complexed with substrates pinpoints likely structural determinants for substrate binding. Forgoing the use of experimental transport and binding data of tryptamine derivatives for construction of these models enables us to critically assess and validate their predictive power: A single 5-HT binding mode was identified that retains the amine placement observed in the LeuT(Aa) structure, matches site-directed mutagenesis and substituted cysteine accessibility method (SCAM) data, complies with support vector machine derived relations activity relations, and predicts computational binding energies for 5-HT analogs with a significant correlation coefficient (R = 0.72). This binding mode places 5-HT deep in the binding pocket of the SERT with the 5-position near residue hSERT A169/dSERT D164 in transmembrane helix 3, the indole nitrogen next to residue Y176/Y171, and the ethylamine tail under residues F335/F327 and S336/S328 within 4 A of residue D98. Our studies identify a number of potential contacts whose contribution to substrate binding and transport was previously unsuspected.

  14. Chromosomal copy number variation, selection and uneven rates of recombination reveal cryptic genome diversity linked to pathogenicity.

    Directory of Open Access Journals (Sweden)

    Rhys A Farrer

    Full Text Available Pathogenic fungi constitute a growing threat to both plant and animal species on a global scale. Despite a clonal mode of reproduction dominating the population genetic structure of many fungi, putatively asexual species are known to adapt rapidly when confronted by efforts to control their growth and transmission. However, the mechanisms by which adaptive diversity is generated across a clonal background are often poorly understood. We sequenced a global panel of the emergent amphibian pathogen, Batrachochytrium dendrobatidis (Bd, to high depth and characterized rapidly changing features of its genome that we believe hold the key to the worldwide success of this organism. Our analyses show three processes that contribute to the generation of de novo diversity. Firstly, we show that the majority of wild isolates manifest chromosomal copy number variation that changes over short timescales. Secondly, we show that cryptic recombination occurs within all lineages of Bd, leading to large regions of the genome being in linkage equilibrium, and is preferentially associated with classes of genes of known importance for virulence in other pathosystems. Finally, we show that these classes of genes are under directional selection, and that this has predominantly targeted the Global Panzootic Lineage (BdGPL. Our analyses show that Bd manifests an unusually dynamic genome that may have been shaped by its association with the amphibian host. The rates of variation that we document likely explain the high levels of phenotypic variability that have been reported for Bd, and suggests that the dynamic genome of this pathogen has contributed to its success across multiple biomes and host-species.

  15. Genetic diversity analysis reveals that geographical environment plays a more important role than rice cultivar in Villosiclava virens population selection.

    Science.gov (United States)

    Wang, Fei; Zhang, Shu; Liu, Mei-Gang; Lin, Xian-Song; Liu, Hui-Jiang; Peng, You-Liang; Lin, Yang; Huang, Jun-Bin; Luo, Chao-Xi

    2014-05-01

    Rice false smut caused by Villosiclava virens is an economically important disease of grains worldwide. The genetic diversity of 153 isolates from six fields located in Wuhan (WH), Yichang Wangjia (YCW), Yichang Yaohe (YCY), Huanggang (HG), Yangxin (YX), and Jingzhou (JZ) in Hubei province of China were phylogenetically analyzed to evaluate the influence of environments and rice cultivars on the V. virens populations. Isolates (43) from Wuhan were from two rice cultivars, Wanxian 98 and Huajing 952, while most of the other isolates from fields YCW, YCY, HG, YX, and JZ originated from different rice cultivars with different genetic backgrounds. Genetic diversity of isolates was analyzed using random amplified polymorphic DNA (RAPD) and single-nucleotide polymorphisms (SNP). The isolates from the same cultivars in Wuhan tended to group together, indicating that the cultivars had an important impact on the fungal population. The 110 isolates from individual fields tended to cluster according to geographical origin. The values of Nei's gene diversity (H) and Shannon's information index (I) showed that the genetic diversity among isolates was higher between than within geographical populations. Furthermore, mean genetic distance between groups (0.006) was higher than mean genetic distance within groups (0.0048) according to MEGA 5.2. The pairwise population fixation index (FST) values also showed significant genetic differentiation between most populations. Higher genetic similarity of isolates from individual fields but different rice cultivars suggested that the geographical factor played a more important role in the selection of V. virens isolates than rice cultivars. This information could be used to improve the management strategy for rice false smut by adjusting the cultivation measures, such as controlling fertilizer, water, and planting density, in the rice field to change the microenvironment.

  16. Genetic differentiation revealed by selective loci of drought-responding EST-SSRs between upland and lowland rice in China.

    Directory of Open Access Journals (Sweden)

    Hui Xia

    Full Text Available Upland and lowland rice (Oryza sativa L. represent two of the most important rice ecotypes adapted to ago-ecosystems with contrasting soil-water conditions. Upland rice, domesticated in the water-limited environment, contains valuable drought-resistant characters that can be used in water-saving breeding. Knowledge about the divergence between upland and lowland rice will provide valuable cues for the evolution of drought-resistance in rice. Genetic differentiation between upland and lowland rice was explored by 47 Simple Sequence Repeats (SSRs located in drought responding expressed sequence tags (ESTs among 377 rice landraces. The morphological traits of drought-resistance were evaluated in the field experiments. Different outlier loci were detected in the japonica and indica subspecies, respectively. Considerable genetic differentiation between upland and lowland rice on these outlier loci was estimated in japonica (Fst = 0.258 and indica (Fst = 0.127. Furthermore, populations of the upland and lowland ecotypes were clustered separately on these outlier loci. A significant correlation between genetic distance matrices and the dissimilarity matrices of drought-resistant traits was determined, indicating a certain relationship between the upland-lowland rice differentiation and the drought-resistance. Divergent selections occur between upland and lowland rice on the drought-resistance as the Qsts of some drought-resistant traits are significantly higher than the neutral Fst. In addition, the upland- and lowland-preferable alleles responded differently among ecotypes or allelic types under osmotic stress. This shows the evolutionary signature of drought resistance at the gene expression level. The findings of this study can strengthen our understanding of the evolution of drought-resistance in rice with significant implications in the improvement of rice drought-resistance.

  17. Gated Channels and Selectivity Tuning of CO2 over N2 Sorption by Post-Synthetic Modification of a UiO-66-Type Metal-Organic Framework.

    Science.gov (United States)

    Kronast, Alexander; Eckstein, Sebastian; Altenbuchner, Peter T; Hindelang, Konrad; Vagin, Sergei I; Rieger, Bernhard

    2016-08-26

    The highly porous and stable metal-organic framework (MOF) UiO-66 was altered using post-synthetic modifications (PSMs). Prefunctionalization allowed the introduction of carbon double bonds into the framework through a four-step synthesis from 2-bromo-1,4-benzenedicarboxylic acid; the organic linker 2-allyl-1,4-benzenedicarboxylic acid was obtained. The corresponding functionalized MOF (UiO-66-allyl) served as a platform for further PSMs. From UiO-66-allyl, epoxy, dibromide, thioether, diamine, and amino alcohol functionalities were synthesized. The abilities of these compounds to adsorb CO2 and N2 were compared, which revealed the structure-selectivity correlations. All synthesized MOFs showed profound thermal stability together with an increased ability for selective CO2 uptake and molecular gate functionalities at low temperatures.

  18. Mass spectrometric proteomics reveals that nuclear protein positive cofactor PC4 selectively binds to cross-linked DNA by a trans-platinum anticancer complex.

    Science.gov (United States)

    Du, Zhifeng; Luo, Qun; Yang, Liping; Bing, Tao; Li, Xianchan; Guo, Wei; Wu, Kui; Zhao, Yao; Xiong, Shaoxiang; Shangguan, Dihua; Wang, Fuyi

    2014-02-26

    An MS-based proteomic strategy combined with chemically functionalized gold nanoparticles as affinity probes was developed and validated by successful identification and quantification of HMGB1, which is well characterized to interact selectively with 1,2-cross-linked DNA by cisplatin, from whole cell lysates. The subsequent application of this method to identify proteins responding to 1,3-cross-linked DNA by a trans-platinum anticancer complex, trans-PtTz (Tz = thiazole), revealed that the human nuclear protein positive cofactor PC4 selectively binds to the damaged DNA, implying that PC4 may play a role in cellular response to DNA damage by trans-PtTz.

  19. On influencing factors of channel selection behavior of consumer based on matching theory%基于匹配理论的消费者渠道选择行为影响因素

    Institute of Scientific and Technical Information of China (English)

    高洋; 王琳雅

    2016-01-01

    With the rapid development of economy and the maturation of e-commerce in China, the advantages of multi-channel marketing in the market have become more and more accepted by companies, the channels selection of consumer has become the focus of companies. From the perspective of matching, the channel selection behavior of consumer is studied; the task-technology fit model is implemented in the multi-channel environment. The influencing factors of channel selection behavior of consumer are analyzed from three aspects of channel characteristics, product characteristics, and consumer characteristics. The matching problem among the factors is studied, in order to provide theoretical basis for the rational and effective multi-channel marketing strategy for companies.%随着我国经济的快速发展以及电子商务的日渐成熟,多渠道在市场营销中的优越性越来越被企业所肯定,消费者的渠道选择成为企业关注的重点. 从匹配视角出发研究消费者渠道选择行为,将任务技术匹配模型落实到多渠道具体环境中,从渠道特性、产品特性、消费者特性三方面对消费者渠道选择的影响因素进行分析,并对因素间的匹配问题进行研究,旨在为企业采用合理有效的多渠道营销战略提供理论基础.

  20. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik;

    2010-01-01

    the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies...

  1. The crystal structure of ferritin from Chlorobium tepidum reveals a new conformation of the 4-fold channel for this protein family.

    Science.gov (United States)

    Arenas-Salinas, Mauricio; Townsend, Philip D; Brito, Christian; Marquez, Valeria; Marabolli, Vanessa; Gonzalez-Nilo, Fernando; Matias, Cata; Watt, Richard K; López-Castro, Juan D; Domínguez-Vera, José; Pohl, Ehmke; Yévenes, Alejandro

    2014-11-01

    Ferritins are ubiquitous iron-storage proteins found in all kingdoms of life. They share a common architecture made of 24 subunits of five α-helices. The recombinant Chlorobium tepidum ferritin (rCtFtn) is a structurally interesting protein since sequence alignments with other ferritins show that this protein has a significantly extended C-terminus, which possesses 12 histidine residues as well as several aspartate and glutamic acid residues that are potential metal ion binding residues. We show that the macromolecular assembly of rCtFtn exhibits a cage-like hollow shell consisting of 24 monomers that are related by 4-3-2 symmetry; similar to the assembly of other ferritins. In all ferritins of known structure the short fifth α-helix adopts an acute angle with respect to the four-helix bundle. However, the crystal structure of the rCtFtn presented here shows that this helix adopts a new conformation defining a new assembly of the 4-fold channel of rCtFtn. This conformation allows the arrangement of the C-terminal region into the inner cavity of the protein shell. Furthermore, two Fe(III) ions were found in each ferroxidase center of rCtFtn, with an average FeA-FeB distance of 3 Å; corresponding to a diferric μ-oxo/hydroxo species. This is the first ferritin crystal structure with an isolated di-iron center in an iron-storage ferritin. The crystal structure of rCtFtn and the biochemical results presented here, suggests that rCtFtn presents similar biochemical properties reported for other members of this protein family albeit with distinct structural plasticity.

  2. Empirical study on selection motivation model of luxury purchasing channel%奢侈品购买渠道选择动因模型的实证研究

    Institute of Scientific and Technical Information of China (English)

    李艺; 王力立

    2015-01-01

    在多种商品不断涌入网络销售的今天,作为高端市场代表的奢侈品也试图借助网络渠道进行销售,然而销售情况不甚理想,是独有的高品质特征还是消费者心理因素造成了这种结果有待探究. 着重分析奢侈品购买渠道选择的动机和影响因素,构建奢侈品购买渠道选择动因模型,通过调研得到结论:求廉动机和渠道可靠性动机是消费者选择奢侈品购买渠道的主要考虑;消费者的个性特征影响其奢侈品购买渠道的选择. 企业和顾客刺激不仅影响消费者奢侈品购买渠道的选择,而且对个性特征和奢侈品购买渠道选择动机的关系具有调节作用. 本研究对经营奢侈品的企业开展电子商务活动,建设奢侈品网络销售渠道具有重要指导意义.%As many goods are pouring into the network marketing, luxury goods as the representative of high-end market are also being tried to sell on the network channel but the sales results are not ideal. It needs to be researched whether due to the unique high quality characteristics or due to the psychological factors of consumer. Starting from analysis on the motivation and influencing factors of channel selection of luxury purchasing, a motivation model is established for channel selection of luxury purchasing. Through the research of buyers, the conclusions are as follows. The motivations of seeking lower prices and higher reliability are the major considerations of channel selection of luxury purchasing. Personal characteristics have significant influence on channel selection of luxury purchasing. Stimuli from enterprises and other customers not only affect the channel selection of luxury purchasing of consumers, but also have a regulatory effect on the relationship between personal characteristics and channel selection. This research has guiding significance for luxury companies to carry out e-commerce activities and to build internet marketing channel of luxury

  3. Inhibition of cell proliferation by a selective inhibitor of the Ca{sup 2+}-activated Cl{sup -} channel, Ano1

    Energy Technology Data Exchange (ETDEWEB)

    Mazzone, Amelia; Eisenman, Seth T.; Strege, Peter R. [Enteric NeuroScience Program, Mayo Clinic, Rochester, MN (United States); Yao, Zhen [Laboratory of Molecular Genetics, UCSF, San Francisco, CA (United States); Ordog, Tamas; Gibbons, Simon J. [Enteric NeuroScience Program, Mayo Clinic, Rochester, MN (United States); Farrugia, Gianrico, E-mail: farrugia.gianrico@mayo.edu [Enteric NeuroScience Program, Mayo Clinic, Rochester, MN (United States)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer T16A{sub inh}-A01 blocked Ano1 currents in HEK cells expressing Ano1. Black-Right-Pointing-Pointer T16A{sub inh}-A01 reduced proliferation in ICC primary cultures and CFPAC-1 cell line. Black-Right-Pointing-Pointer T16A{sub inh}-A01 reduced proliferation of ICC in intact smooth muscle strips. -- Abstract: Background: Ion channels play important roles in regulation of cellular proliferation. Ano1 (TMEM16A) is a Ca{sup 2+}-activated Cl{sup -} channel expressed in several tumors and cell types. In the muscle layers of the gastrointestinal tract Ano1 is selectively expressed in interstitial cells of Cajal (ICC) and appears to be required for normal gastrointestinal slow wave electrical activity. However, Ano1 is expressed in all classes of ICC, including those that do not generate slow waves suggesting that Ano1 may have other functions. Indeed, a role for Ano1 in regulating proliferation of tumors and ICC has been recently suggested. Recently, a high-throughput screen identified a small molecule, T16A{sub inh}-A01 as a specific inhibitor of Ano1. Aim: To investigate the effect of the T16A{sub inh}-A01 inhibitor on proliferation in ICC and in the Ano1-expressing human pancreatic cancer cell line CFPAC-1. Methods: Inhibition of Ano1 was demonstrated by whole cell voltage clamp recordings of currents in cells transfected with full-length human Ano1. The effect of T16A{sub inh}-A01 on ICC proliferation was examined in situ in organotypic cultures of intact mouse small intestinal smooth muscle strips and in primary cell cultures prepared from these tissues. ICC were identified by Kit immunoreactivity. Proliferating ICC and CFPAC-1 cells were identified by immunoreactivity for the nuclear antigen Ki67 or EdU incorporation, respectively. Results: T16A{sub inh}-A01 inhibited Ca{sup 2+}-activated Cl{sup -} currents by 60% at 10 {mu}M in a voltage-independent fashion. Proliferation of ICC was significantly reduced in primary cultures

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

    Energy Technology Data Exchange (ETDEWEB)

    Na, Jonggeol; Jung, Ikhwan; Kshetrimayum, Krishnadash S.; Park, Seongho; Park, Chansaem; Han, Chonghun [Seoul National University, Seoul (Korea, Republic of)

    2014-12-15

    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

  5. The vertical distribution of selected trace metals and organic compounds in bottom materials of the proposed lower Columbia River export channel, Oregon, 1984

    Science.gov (United States)

    Fuhrer, Gregory J.; Horowitz, Arthur J.

    1989-01-01

    A proposal to deepen the lower Columbia River navigation channel in Oregon prompted a study of the vertical distribution of selected trace metals and organic compounds in bottom sediments. These data are needed to evaluate the effects of dredging and disposal operations. Elutriation testing of bottom material indicated chemical concentrations as large as 900 ug/L for barium, 6,500 ug/L for manganese, and 14 ug/L for nickel. The amount of oxygen present during elutriation testing of reduced bottom material was shown to have a negligble effect on manganese elutriate-test concentrations, but it did affect barium and iron concentrations. Sediment-associated organochlorine compounds detected in bottom-sediment core samples were as large as 0.1 ug/kg (micrograms/kilogram) for aldrin, 2.0 ug/kg for chlordane, 27 ug/kg for DDD, 5.0 ug/kg for DDE, 0.2 ug/kg for DDT, 0.2 ug/kg for dieldrin, 37 ug/kg for PCB 's 1.0 ug/kg for PCN 's and 1.0 ug/kg for heptachlor epoxide. Concentrations of cadmium, lead, and zinc in selected cores were found to exceed those of local basalts. Concentrations of cadmium, lead, and zinc were as large as 3.6 ug/g, 26 ug/g, and 210 ug/g respectively. Bottom-sediment concentrations of cadmium , chromium, copper, iron, and zinc associated with the less-than-100-micrometer size fraction are larger than those associated with the greater-than-100-micrometer fraction. (USGS)

  6. Performance analysis of selection diversity in Nakagami fading channel%选择式合并方法在Nakagami信道上的性能分析

    Institute of Scientific and Technical Information of China (English)

    陈云飞; 罗汉文; 宋文涛

    2001-01-01

    This paper proceeds an evaluation of selection diversity inNakagami fa ding channel according to the principle of maximum output level.Closed form expr ession of bit error rate is derived and compared with the principle of maximum s ignal noise ratio.Numerical result shows a slight deterioration but a great redu ction of complexity.%文根据最大输出电平准则,对选择式合并在Nakagami信道上的性能作了比以往理论分析更符合实际的评价,导出了误码率的闭式解,并与最大信噪比准则时作了比较。结果表明,采用最大输出电平准则时系统的性能稍有恶化,但实现的复杂度却大为降低。

  7. New Concept of PLC Modems: Multi-Carrier System for Frequency Selective Slow-Fading Channels Based on Layered SCCC Turbocodes

    Directory of Open Access Journals (Sweden)

    J. Zavrtalek

    2015-09-01

    Full Text Available The article introduces a novel concept of a PLC modem as a complement to the existing G3 and PRIME standards for communications using medium- or high-voltage overhead or cable lines. The proposed concept is based on the fact that the levels of impulse noise and frequency selectivity are lower on high-voltage lines than on low-voltage ones. Also, the demands for “cost-effective” circuitry design are not so crucial as in the case of modems for low-voltage level. In contract to these positive conditions, however, there is the need to overcome much longer distances and to take into account low SNR on the receiving side. With respect to the listed reasons, our concept makes use of MCM, instead of OFDM. The assumption of low SNR is compensated through the use of an efficient channel coding based on a serially concatenated turbo code. In addition, MCM offers lower latency and PAPR compared to OFDM. Therefore, when using MCM, it is possible to excite the line with higher power. The proposed concept has been verified during experimental transmission of testing data over a real, 5 km long, 22kV overhead line.

  8. Precise localization of the voltage-gated potassium channel subunits Kv3.1b and Kv3.3 revealed in the molecular layer of the rat cerebellar cortex by a pre-embedding immunogold method.

    Science.gov (United States)

    Puente, Nagore; Mendizabal-Zubiaga, Juan; Elezgarai, Izaskun; Reguero, Leire; Buceta, Ianire; Grandes, Pedro

    2010-10-01

    A proper motor activity relies on a correct cerebellar function. The Kv3.1 and Kv3.3 voltage-gated potassium channels are key proteins involved in cerebellar function and dysfunction, as the lack of these causes severe motor deficits. Both channel subunits are coexpressed in granule cells and are rapidly activated at relatively positive potentials to support the generation of fast action potentials. However, the contribution of each subunit to the molecular architecture of the parallel fibers, the granule cell axons, is so far unknown. The goal of this study was to elucidate the relative distribution of Kv3.1b and Kv3.3 in specific compartments of the rat parallel fibers by using a pre-embedding immunocytochemical method for electron microscopy. Numerous Kv3.1b and Kv3.3 silver-intensified gold particles were associated with membranes of parallel fiber synaptic terminals and their intervaricose segments. Kv3.1b was found in about 85% of parallel fiber synaptic terminals and in about 47% of their intervaricose portions. However, only 28% of intervaricosities and 23% of parallel fiber presynaptic boutons were Kv3.3 immunopositive. The analysis also revealed that 54% of Purkinje cell dendritic spines localized Kv3.3. Although both potassium channel subunits share localization in the same presynaptic parallel fiber compartments, the present results with the method used indicate that there are a higher percentage of parallel fibers labeled for Kv3.1b than for Kv3.3, and that the labeling intensity for each subunit is higher in specific subcompartments analyzed than in others.

  9. Comparative molecular field analysis using selectivity fields reveals residues in the third transmembrane helix of the serotonin transporter associated with substrate and antagonist recognition.

    Science.gov (United States)

    Walline, Crystal C; Nichols, David E; Carroll, F Ivy; Barker, Eric L

    2008-06-01

    The human serotonin transporter (hSERT) regulates the spatial and temporal actions of serotonin (5-HT) neurotransmission by removing 5-HT from the synapse. Previous studies have identified residues in the third transmembrane helix (TMH) that may be important for substrate translocation or antagonist recognition. We identified hSERT residues in TMH III that are divergent from Drosophila SERT and used species-scanning mutagenesis to generate reciprocal mutants. Transport inhibition assays suggest that the potency of substituted amphetamines was decreased for the hSERT mutants A169D, I172M, and S174M. In addition, there was a loss of potency for several antidepressants and 3-phenyltropane analogs for the I172M mutant. These results suggest that residues in TMH III may contribute to antagonist recognition. We carried out comparative molecular field analyses using selectivity fields to directly visualize the mutation-induced effects of antagonist potency for antidepressants, 3-phenyltropane analogs, and amphetamines. The hSERT I172M selectivity field analysis for the 3-phenyltropane analogs revealed that electrostatic interactions resulted in decreased potency. The amphetamine and antidepressant selectivity field analyses reveal the observed decreases in potencies for the hSERT I172M mutant are due to a change in tertiary structure of the hSERT protein and are not due to disruption of a direct binding site. Finally, the hSERT mutant A169D displayed altered kinetics for sodium binding, indicating that this residue may lie near the putative sodium binding site. A SERT homology model developed from the Aquifex aeolicus leucine transporter structure provides a structural context for further interpreting the results of the TMH III mutations.

  10. In Vitro Antibacterial Mechanism of Action of Crude Garlic (Allium sativum) Clove Extract on Selected Probiotic Bifidobacterium Species as Revealed by SEM, TEM, and SDS-PAGE Analysis.

    Science.gov (United States)

    Booyens, J; Labuschagne, M C; Thantsha, M S

    2014-06-01

    There has been much research on the effects of garlic (Allium sativum) on numerous pathogens, but very few, if any, studies on its effect on beneficial, probiotic bifidobacteria. We have recently shown that garlic exhibits antibacterial activity against bifidobacteria. The mechanism by which garlic kills bifidobacteria is yet to be elucidated. This study sought to determine the mechanism of action of garlic clove extract on selected Bifidobacterium species using scanning and transmission electron microscopy and SDS-PAGE analysis. SEM micrographs revealed unusual morphological changes such as cell elongation, cocci-shaped cells with cross-walls, and distorted cells with bulbous ends. With TEM, observed changes included among others, condensation of cytoplasmic material, disintegration of membranes, and loss of structural integrity. SDS-PAGE analysis did not reveal any differences in whole-cell protein profiles of untreated and garlic clove extract-treated cells. The current study is the first to reveal the mechanism of action of garlic clove extract on probiotic Bifidobacterium species. The results indicate that garlic affects these beneficial bacteria in a manner similar to that exhibited in pathogens. These results therefore further highlight that caution should be taken especially when using raw garlic and probiotic bifidobacteria simultaneously as viability of these bacteria could be reduced by allicin released upon crushing of garlic cloves, thereby limiting the health benefits that the consumer anticipate to gain from probiotics.

  11. Effects of a non-selective TRPC channel blocker, SKF-96365, on melittin-induced spontaneous persistent nociception and inflammatory pain hypersensitivity

    Institute of Scientific and Technical Information of China (English)

    Jing Ding; Jia-Rui Zhang; Yan Wang; Chun-Li Li; Dan Lu; Su-Min Guan; Jun Chen

    2012-01-01

    Objective Melittin is the main peptide in bee venom and causes both persistent spontaneous nociception and pain hypersensitivity.Our recent studies indicated that both transient receptor potential (TRP) vanilloid receptor 1 (TRPV1) and canonical TRPs (TRPCs) are involved in mediating the melittin-induced activation of different subpopulations of primary nociceptive cells.Here,we further determined whether TRPC channels are involved in melittin-induced inflammatory nociceptive responses in behavioral assays.Methods The anti-nociceptive and anti-hyperalgesic effects of localized peripheral administration of three doses of the non-selective TRPC antagonist,SKF-96365 (1-{β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenyl}-1H-imidazole hydrochloride),were evaluated in melittin tests.Pain-related behaviors were rated by counting the number of paw flinches,and measuring paw withdrawal thermal latency (s) and paw withdrawl mechanical threshold (g),over a 1-h time-course.Results Localized peripheral SKF-96365 given before melittin prevented,and given after melittin significantly suppressed,the melittin-evoked persistent spontaneous nociception.Pre-blockade and post-suppression of activation of primary nociceptive activity resulted in decreased hypersensitivity to both thermal and mechanical stimuli applied to the primary injury site of the ipsilateral hindpaw,despite dose-effect differences between thermal and mechanical hyperalgesia.However,local administration of SKF-96365 into the contralateral hindpaw had no significant effect on any pain-associated behaviors.In addition,SKF-96365 had no effect on baseline threshold for either thermal or mechanical sensitivity under normal conditions.Conclusion Besides TRPV1,SKF-96365-sensitive TRPC channels might also be involved in the pathophysiological processing of melittin-induced inflammatory pain and hypersensitivity.Therapeutically,SKF-96365 is equally effective in preventing primary thermal and mechanical hyperalgesia as well as

  12. Research on Channel Selection of Three-level Competitive Supply Chains%三级竞争供应链的渠道选择研究

    Institute of Scientific and Technical Information of China (English)

    魏玲; 姚锋敏

    2014-01-01

    The Nash equilibrium structure of three-level competitive supply chains is addressed under the background of inter-chain competition .The problem is modeled by nonlinear programming , Nash game theory , and Stackelberg game theory , respectively .Based on these models , optimal solutions are obtained under three scenarios:fully distributed structure , fully integrated structure , and hybrid structure in which one supply chain is integrated and the other is distributed .Then, channel selection for two three-level competitive supply chains is analyzed .In this way, the Nash equilibrium structure is obtained based on three different decision criteria: the profit maximization of manufacturer , profit maximization of channel , and profit maximization of supply chain system .Results show that the Nash equilibrium structure of three-level competitive supply chains depends on the coefficient of product substitution and the decision criteria . However , when the competition intensity between supply chains is strong , no matter what decision criteria is applied , the fully distributed structure is the Nash equilibrium structure of a supply chain .%在供应链链间竞争的背景下,研究三级竞争供应链的纳什均衡结构。利用非线性规划、纳什博弈和Stackel-berg博弈理论,分析了2条三级竞争供应链的渠道选择问题,求解了3种情景:全分布式结构;全一体化结构和混合结构(一条供应链为一体化,另一条为分布式)下的决策变量的最优解,并分别依据3种决策标准,即制造商利润最大化、渠道利润最大化和供应链系统利润最大化,分析了不同决策标准下供应链纳什均衡结构。研究表明,三级竞争供应链的纳什均衡结构,依赖于产品之间的替代系数及决策标准,并且当供应链链间的竞争强度较大时,无论何种决策准则下,全分布式结构均为供应链的纳什均衡结构。

  13. 一种基于MIMO预编码的多径分离方法%Method of multi-path separation based on precoding over frequency selective MIMO channel

    Institute of Scientific and Technical Information of China (English)

    张艳语; 朱义君; 张水莲

    2012-01-01

    In frequency-selective MIMO channel,a null space based linear transceiver scheme based on precoding was proposed. Each data vector and corresponding decoding matrix are in the joint null space of other delay channel matrices. Frequency -selective MIMO channel is transformed into several spatially orthogonal flat matrix sub-channels.The precoding research over frequency flat channel is directly applicable to the selective channel, thoroughly removing up ISI problem of Z domain method with i-dentical computation. Simulation results show that the proposed algorithm is of better capacity and error performance.%针对选择性MIMO信道多经分离问题,提出了一种基于预编码的收发联合设计方案.该方案中的每路发射矢量及其解码矩阵处于其他时延信道的共同零空间,把选择性信道多径分离为空间正交的若干平坦子信道,从而使平坦信道的预编码研究成果可以直接应用于选择性MIMO信道,解决了传统Z域处理中未消除ISI的问题,复杂度为Z域方法的L(多径数目)倍.仿真结果表明,该算法具有较好容量性能和误码率性能.

  14. 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).

  15. K(v)7 channels: function, pharmacology and channel modulators.

    Science.gov (United States)

    Dalby-Brown, William; Hansen, Henrik H; Korsgaard, Mads P G; Mirza, Naheed; Olesen, Søren-P

    2006-01-01

    K(v)7 channels are unique among K(+) channels, since four out of the five channel subtypes have well-documented roles in the development of human diseases. They have distinct physiological functions in the heart and in the nervous system, which can be ascribed to their voltage-gating properties. The K(v)7 channels also lend themselves to pharmacological modulation, and synthetic openers as well as blockers of the channels, regulating neuronal excitability, have existed even before the K(v)7 channels were identified by cloning. In the present review we give an account on the focused efforts to develop selective modulators, openers as well as blockers, of the K(v)7 channel subtypes, which have been undertaken during recent years, along with a discussion of the K(v)7 ion channel physiology and therapeutic indications for modulators of the neuronal K(v)7 channels.

  16. 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.

  17. Analysis of the Distribution Channel Selection of Retailer Based on Electronic Commerce%电子商务环境下零售商分销渠道的选择

    Institute of Scientific and Technical Information of China (English)

    董志刚; 马骋

    2015-01-01

    For the distribution channel selection on E-business environment, we sutudy two classes of distribution channels including one manufacturer and one retailer. On one hand, the first class consists of only one traditional offline retail channel, and on the other hand, the second one includes online and offline dual-channels in the same price strategy. By means of stackelberg game and hotelling model, well-posedness conditions of distribution channels choices are characterized. The studies have shown that manufacturer actively promotes retailer to choose dual-channels. and the different channel costs have different impacts on retailer's strategy. In some sense, our research results are of some importance for retailer to choose different distribution channels.%针对电子商务环境下的产品分销渠道,研究了由一个制造商和一个零售商组成的供应链中零售商分销渠道的选择问题。运用主从博弈和Hotelling模型,分别建立了单一线下渠道模型和在同价策略下的双渠道模型,通过对模型的分析,给出了零售商选择不同分销渠道的条件。研究表明:制造商会积极促使零售商选择线上线下双渠道;构建线上渠道的运营成本会影响零售商的渠道选择。研究结果对零售商的渠道选择有一定的指导意义。

  18. Co-localisation of K(ir)4.1 and AQP4 in rat and human cochleae reveals a gap in water channel expression at the transduction sites of endocochlear K(+) recycling routes.

    Science.gov (United States)

    Eckhard, Andreas; Gleiser, Corinna; Rask-Andersen, Helge; Arnold, Heinz; Liu, Wei; Mack, Andreas; Müller, Marcus; Löwenheim, Hubert; Hirt, Bernhard

    2012-10-01

    Sensory transduction in the cochlea depends on perilymphatic-endolymphatic potassium (K(+)) recycling. It has been suggested that the epithelial supporting cells (SCs) of the cochlear duct may form the intracellular K(+) recycling pathway. Thus, they must be endowed with molecular mechanisms that facilitate K(+) uptake and release, along with concomitant osmotically driven water movements. As yet, no molecules have been described that would allow for volume-equilibrated transepithelial K(+) fluxes across the SCs. This study describes the subcellular co-localisation of the K(ir)4.1 K(+) channel (K(ir)4.1) and the aquaporin-4 water channel (AQP4) in SCs, on the basis of immunohistochemical double-labelling experiments in rat and human cochleae. The results of this study reveal the expression of K(ir)4.1 in the basal or basolateral membranes of the SCs in the sensory domain of the organ of Corti that are adjacent to hair cells and in the non-sensory domains of the inner and outer sulci that abut large extracellular fluid spaces. The SCs of the inner sulcus (interdental cells, inner sulcus cells) and the outer sulcus (Hensen's cells, outer sulcus cells) display the co-localisation of K(ir)4.1 and AQP4 expression. However, the SCs in the sensory domain of the organ of Corti reveal a gap in the expression of AQP4. The outer pillar cell is devoid of both K(ir)4.1 and AQP4. The subcellular co-localisation of K(ir)4.1 and AQP4 in the SCs of the cochlea described in this study resembles that of the astroglia of the central nervous system and the glial Mueller cells in the retina.

  19. A novel TCR transgenic model reveals that negative selection involves an immediate, Bim-dependent pathway and a delayed, Bim-independent pathway.

    Directory of Open Access Journals (Sweden)

    Damian Kovalovsky

    Full Text Available A complete understanding of negative selection has been elusive due to the rapid apoptosis and clearance of thymocytes in vivo. We report a TCR transgenic model in which expression of the TCR during differentiation occurs only after V(DJ-like recombination. TCR expression from this transgene closely mimics expression of the endogenous TCRalpha locus allowing for development that is similar to wild type thymocytes. This model allowed us to characterize the phenotypic changes that occurred after TCR-mediated signaling in self-reactive thymocytes prior to their deletion in a highly physiological setting. Self-reactive thymocytes were identified as being immature, activated and CD4(loCD8(lo. These cells had upregulated markers of negative selection and were apoptotic. Elimination of Bim reduced the apoptosis of self-reactive thymocytes, but it did not rescue their differentiation and the cells remained at the immature CD4(loCD8(lo stage of development. These cells upregulate Nur77 and do not contribute to the peripheral T cell repertoire in vivo. Remarkably, development past the CD4(loCD8(lo stage was possible once the cells were removed from the negatively selecting thymic environment. In vitro development of these cells occurred despite their maintenance of high intracellular levels of Nur77. Therefore, in vivo, negatively selected Bim-deficient thymocytes are eliminated after prolonged developmental arrest via a Bim-independent pathway that is dependent on the thymic microenvironment. These data newly reveal a layering of immediate, Bim-dependent, and delayed Bim-independent pathways that both contribute to elimination of self-reactive thymocytes in vivo.

  20. Strategies for sustainable channel relations in mobile telecom sector

    Directory of Open Access Journals (Sweden)

    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.

  1. TRP channels in schistosomes

    Directory of Open Access Journals (Sweden)

    Swarna Bais

    2016-12-01

    Full Text Available Praziquantel (PZQ is effectively the only drug currently available for treatment and control of schistosomiasis, a disease affecting hundreds of millions of people worldwide. Many anthelmintics, likely including PZQ, target ion channels, membrane protein complexes essential for normal functioning of the neuromusculature and other tissues. Despite this fact, only a few classes of parasitic helminth ion channels have been assessed for their pharmacological properties or for their roles in parasite physiology. One such overlooked group of ion channels is the transient receptor potential (TRP channel superfamily. TRP channels share a common core structure, but are widely diverse in their activation mechanisms and ion selectivity. They are critical to transducing sensory signals, responding to a wide range of external stimuli. They are also involved in other functions, such as regulating intracellular calcium and organellar ion homeostasis and trafficking. Here, we review current literature on parasitic helminth TRP channels, focusing on those in schistosomes. We discuss the likely roles of these channels in sensory and locomotor activity, including the possible significance of a class of TRP channels (TRPV that is absent in schistosomes. We also focus on evidence indicating that at least one schistosome TRP channel (SmTRPA has atypical, TRPV1-like pharmacological sensitivities that could potentially be exploited for future therapeutic targeting.

  2. Independent stratum formation on the avian sex chromosomes reveals inter-chromosomal gene conversion and predominance of purifying selection on the W chromosome.

    Science.gov (United States)

    Wright, Alison E; Harrison, Peter W; Montgomery, Stephen H; Pointer, Marie A; Mank, Judith E

    2014-11-01

    We used a comparative approach spanning three species and 90 million years to study the evolutionary history of the avian sex chromosomes. Using whole transcriptomes, we assembled the largest cross-species dataset of W-linked coding content to date. Our results show that recombination suppression in large portions of the avian sex chromosomes has evolved independently, and that long-term sex chromosome divergence is consistent with repeated and independent inversions spreading progressively to restrict recombination. In contrast, over short-term periods we observe heterogeneous and locus-specific divergence. We also uncover four instances of gene conversion between both highly diverged and recently evolved gametologs, suggesting a complex mosaic of recombination suppression across the sex chromosomes. Lastly, evidence from 16 gametologs reveal that the W chromosome is evolving with a significant contribution of purifying selection, consistent with previous findings that W-linked genes play an important role in encoding sex-specific fitness.

  3. 网络直销型制造商开辟新渠道模式选择分析%Analysis of new channel mode selection for Internet direct manufacturer

    Institute of Scientific and Technical Information of China (English)

    曾伟

    2015-01-01

    文章从网络直销型制造商的角度研究了其开辟新渠道模式选择的问题。假设制造商已经拥有一条网络直销渠道,分别研究了制造商Stackelberg、零售商Stackelberg和双方Nash均衡3种不同权力结构下的双渠道定价策略;进一步讨论了制造商开辟新渠道需要满足的条件,分析了条件的改变对各方利润的影响。结果表明,制造商可以通过改变渠道投入力度来进行渠道模式选择。在渠道选择上应坚持“一主一辅”的原则,即以网络直销渠道为主,开辟零售渠道作为补充;或只保留很少部分的网络直销渠道,转为以零售渠道销售为主。而投入力度相当将会造成内耗,损失各方利益。%New channel mode selection problems are studied from the Internet direct manufacturer ’ s point of view .Assuming that the manufacturer already has an Internet direct distribution channel ,the dual‐channel pricing strategies are given under three different power structures ,namely manufacturer Stackelberg ,retailer Stackelberg and Nash equilibrium between the two parties .The conditions to add new channel for manufacturer are discussed and the influence of the change of conditions on the parties is analyzed .T he results show that the manufacturer can change the channel model selection by inten‐sity of input .T he manufacturer should insist on the principle of “one primary ,one secondary”,i .e . either mainly taking Internet direct channel and retail channel as complementary or mainly taking re‐tail channel and keeping only very small part of Internet direct channel as a supplement .But equiva‐lent intensity of input may cause internal friction and damage the profits of all members .

  4. Facilitation of ß-cell K(ATP) channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac.

    Science.gov (United States)

    Leech, Colin A; Dzhura, Igor; Chepurny, Oleg G; Schwede, Frank; Genieser, Hans-G; Holz, George G

    2010-01-01

    Clinical studies demonstrate that combined administration of sulfonylureas with exenatide can induce hypoglycemia in type 2 diabetic subjects. Whereas sulfonylureas inhibit ß-cell K(ATP) channels by binding to the sulfonylurea receptor-1 (SUR1), exenatide binds to the GLP-1 receptor, stimulates ß-cell cAMP production and activates both PKA and Epac. In this study, we hypothesized that the adverse in vivo interaction of sulfonylureas and exenatide to produce hypoglycemia might be explained by Epac-mediated facilitation of K(ATP) channel sulfonylurea sensitivity. We now report that the inhibitory action of a sulfonylurea (tolbutamide) at K(ATP) channels was facilitated by 2’-O-Me-cAMP, a selective activator of Epac. Thus, under conditions of excised patch recording, the dose-response relationship describing the inhibitory action of tolbutamide at human ß-cell or rat INS-1 cell K(ATP) channels was left-shifted in the presence of 2’-O-Me-cAMP, and this effect was abolished in INS-1 cells expressing a dominant-negative Epac2. Using an acetoxymethyl ester prodrug of an Epac-selective cAMP analog (8-pCP T-2’-O-Me-cAMP-AM), the synergistic interaction of an Epac activator and tolbutamide to depolarize INS-1 cells and to raise [Ca²(+)](i) was also measured. This effect of 8-pCP T-2’-O-Me-cAMP-AM correlated with its ability to stimulate phosphatidylinositol 4,5-bisphosphate hydrolysis that might contribute to the changes in K(ATP) channel sulfonylurea-sensitivity reported here. On the basis of such findings, we propose that the adverse interaction of sulfonylureas and exenatide to induce hypoglycemia involves at least in part, a functional interaction of these two compounds to close K(ATP) channels, to depolarize ß-cells and to promote insulin secretion.

  5. Compressive sensing based Bayesian sparse channel estimation for OFDM communication systems: high performance and low complexity.

    Science.gov (United States)

    Gui, Guan; 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.

  6. HCN Channels and Heart Rate

    Directory of Open Access Journals (Sweden)

    Ilaria Dentamaro

    2012-04-01

    Full Text Available Hyperpolarization and Cyclic Nucleotide (HCN -gated channels represent the molecular correlates of the “funny” pacemaker current (If, a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

  7. A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus.

    Science.gov (United States)

    Corzo, Gerardo; Papp, Ferenc; Varga, Zoltan; Barraza, Omar; Espino-Solis, Pavel G; Rodríguez de la Vega, Ricardo C; Gaspar, Rezso; Panyi, Gyorgy; Possani, Lourival D

    2008-10-30

    A novel potassium channel blocker peptide was purified from the venom of the scorpion Centruroides suffusus suffusus by high-performance liquid chromatography and its amino acid sequence was completed by Edman degradation and mass spectrometry analysis. It contains 38 amino acid residues with a molecular weight of 4000.3Da, tightly folded by three disulfide bridges. This peptide, named Css20, was shown to block preferentially the currents of the voltage-dependent K+-channels Kv1.2 and Kv1.3. It did not affect several other ion channels tested at 10 nM concentration. Concentration-response curves of Css20 yielded an IC50 of 1.3 and 7.2 nM for Kv1.2- and Kv1.3-channels, respectively. Interestingly, despite the similar affinities for the two channels the association and dissociation rates of the toxin were much slower for Kv1.2, implying that different interactions may be involved in binding to the two channel types; an implication further supported by in silico docking analyses. Based on the primary structure of Css20, the systematic nomenclature proposed for this toxin is alpha-KTx 2.13.

  8. Transcriptome Analysis of the Central and Peripheral Nervous Systems of the Spider Cupiennius salei Reveals Multiple Putative Cys-Loop Ligand Gated Ion Channel Subunits and an Acetylcholine Binding Protein.

    Directory of Open Access Journals (Sweden)

    Päivi H Torkkeli

    Full Text Available Invertebrates possess a diverse collection of pentameric Cys-loop ligand gated ion channel (LGIC receptors whose molecular structures, evolution and relationships to mammalian counterparts have been intensely investigated in several clinically and agriculturally important species. These receptors are targets for a variety of control agents that may also harm beneficial species. However, little is known about Cys-loop receptors in spiders, which are important natural predators of insects. We assembled de novo transcriptomes from the central and peripheral nervous systems of the Central American wandering spider Cupiennius salei, a model species for neurophysiological, behavioral and developmental studies. We found 15 Cys-loop receptor subunits that are expected to form anion or cation permeable channels, plus a putative acetylcholine binding protein (AChBP that has only previously been reported in molluscs and one annelid. We used phylogenetic and sequence analysis to compare the spider subunits to homologous receptors in other species and predicted the 3D structures of each protein using the I-Tasser server. The quality of homology models improved with increasing sequence identity to the available high-resolution templates. We found that C. salei has orthologous γ-aminobutyric acid (GABA, GluCl, pHCl, HisCl and nAChα LGIC subunits to other arthropods, but some subgroups are specific to arachnids, or only to spiders. C. salei sequences were phylogenetically closest to gene fragments from the social spider, Stegodyphus mimosarum, indicating high conservation within the Araneomorphae suborder of spiders. C. salei sequences had similar ligand binding and transmembrane regions to other invertebrate and vertebrate LGICs. They also had motifs associated with high sensitivity to insecticides and antiparasitic agents such as fipronil, dieldrin and ivermectin. Development of truly selective control agents for pest species will require information about

  9. Revealing mechanisms of selective, concentration-dependent potentials of 4-hydroxy-2-nonenal to induce apoptosis in cancer cells through inactivation of membrane-associated catalase.

    Science.gov (United States)

    Bauer, Georg; Zarkovic, Neven

    2015-04-01

    Tumor cells generate extracellular superoxide anions and are protected against superoxide anion-mediated intercellular apoptosis-inducing signaling by the expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a versatile second messenger generated during lipid peroxidation, has been shown to induce apoptosis selectively in malignant cells. The findings described in this paper reveal the strong, concentration-dependent potential of 4-HNE to specifically inactivate extracellular catalase of tumor cells both indirectly and directly and to consequently trigger apoptosis in malignant cells through superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4-HNE caused apoptosis selectively in NOX1-expressing tumor cells through inactivation of their membrane-associated catalase, thus reactivating subsequent intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 µM and higher directly inactivated membrane-associated catalase of tumor cells, whereas at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on initial singlet oxygen formation through H2O2 and peroxynitrite interaction. Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased superoxide anion generation by NOX1 and amplification of singlet oxygen generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4-HNE and singlet oxygen cooperate in complex autoamplificatory loops during this process. The finding of these novel anticancer pathways may be useful for understanding the role of 4-HNE in the control of malignant cells and for the optimization of ROS-dependent therapeutic approaches including antioxidant treatments.

  10. Multi-species sequence comparison reveals dynamic evolution of the elastin gene that has involved purifying selection and lineage-specific insertions/deletions

    Directory of Open Access Journals (Sweden)

    Green Eric D

    2004-05-01

    Full Text Available Abstract Background The elastin gene (ELN is implicated as a factor in both supravalvular aortic stenosis (SVAS and Williams Beuren Syndrome (WBS, two diseases involving pronounced complications in mental or physical development. Although the complete spectrum of functional roles of the processed gene product remains to be established, these roles are inferred to be analogous in human and mouse. This view is supported by genomic sequence comparison, in which there are no large-scale differences in the ~1.8 Mb sequence block encompassing the common region deleted in WBS, with the exception of an overall reversed physical orientation between human and mouse. Results Conserved synteny around ELN does not translate to a high level of conservation in the gene itself. In fact, ELN orthologs in mammals show more sequence divergence than expected for a gene with a critical role in development. The pattern of divergence is non-conventional due to an unusually high ratio of gaps to substitutions. Specifically, multi-sequence alignments of eight mammalian sequences reveal numerous non-aligning regions caused by species-specific insertions and deletions, in spite of the fact that the vast majority of aligning sites appear to be conserved and undergoing purifying selection. Conclusions The pattern of lineage-specific, in-frame insertions/deletions in the coding exons of ELN orthologous genes is unusual and has led to unique features of the gene in each lineage. These differences may indicate that the gene has a slightly different functional mechanism in mammalian lineages, or that the corresponding regions are functionally inert. Identified regions that undergo purifying selection reflect a functional importance associated with evolutionary pressure to retain those features.

  11. An overview of historical channel adjustment and selected hydraulic values in the Lower Sabine and Lower Brazos River Basins, Texas and Louisiana

    Science.gov (United States)

    Heitmuller, Franklin T.; Greene, Lauren E.; John D. Gordon, John D.

    2010-01-01

    The Sabine and Brazos are alluvial rivers; alluvial rivers are dynamic systems that adjust their geometry in response to changes in streamflow (discharge) and sediment load. In fluvial geomorphology, the term 'channel adjustment' refers to river channel changes in three geometric dimensions: (1) channel slope (profile); (2) the outline or shape, such as meandering or braided, projected on a horizontal plane (planform); and (3) cross-sectional form (shape). The primary objective of the study was to investigate how the channel morphology of these rivers has changed in response to reservoirs and other anthropogenic disturbances that have altered streamflow and sediment load. The results of this study are expected to aid ecological assessments in the lower Sabine River and lower Brazos River Basins for the Texas Instream Flow Program. Starting in the 1920s, several dams have been constructed on the Sabine and Brazos Rivers and their tributaries, and numerous bridges have been built and sometimes replaced multiple times, which have changed the natural flow regime and reduced or altered sediment loads downstream. Changes in channel geometry over time can reduce channel conveyance and thus streamflow, which can have adverse ecological effects. Channel attributes including cross-section form, channel slope, and planform change were evaluated to learn how each river's morphology changed over many years in response to natural and anthropogenic disturbances. Climate has large influence on the hydrologic regimes of the lower Sabine and lower Brazos River Basins. Equally important as climate in controlling the hydrologic regime of the two river systems are numerous reservoirs that regulate downstream flow releases. The hydrologic regimes of the two rivers and their tributaries reflect the combined influences of climate, flow regulation, and drainage area. Historical and contemporary cross-sectional channel geometries at 15 streamflow-gaging stations in the lower Sabine and

  12. Chick RGS2L demonstrates concentration-dependent selectivity for pertussis toxin-sensitive and -insensitive pathways that inhibit L-type Ca2+ channels.

    Science.gov (United States)

    Tosetti, Patrizia; Parente, Valeria; Taglietti, Vanni; Dunlap, Kathleen; Toselli, Mauro

    2003-05-15

    In neuronal cells, the influx of Ca2+ ions through voltage-dependent L-type calcium (L) channels couples excitation to multiple cellular functions. In addition to voltage, several neurotransmitters, hormones and cytokines regulate L channel gating via binding to G-protein-coupled receptors. Intracellular molecules that modify G-protein activity - such as regulator of G-protein-signalling (RGS) proteins - are therefore potential candidates for regulating Ca2+ influx through L channels. Here we show that a novel RGS2 splice variant from chick dorsal root ganglion (DRG) neurons, RGS2L, reduces bradykinin (BK)-mediated inhibition of neuronal L channels and accelerates recovery from inhibition. Chick RGS2 reduces the inhibition mediated by both the pertussis toxin (PTX)-sensitive (Gi/o-coupled) and the PTX-insensitive (presumably Gq/11-coupled) pathways. However, we demonstrate for the first time in a living cell that the extent of coupling to each pathway varies with RGS2L concentration. A low concentration of recombinant chick RGS2L (10 nM) preferentially reduces the inhibition mediated by the PTX-insensitive pathway, whereas a 100-fold higher concentration attenuates both PTX-sensitive- and PTX-insensitive-mediated components equally. Our data suggest that factors promoting RGS2L gene induction may regulate Ca2+ influx through L channels by recruiting low-affinity interactions with Gi/o that are absent at basal RGS2L levels.

  13. 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.

  14. MIMO Multiple Access Channel with an Arbitrarily Varying Eavesdropper

    CERN Document Server

    He, Xiang; Yener, Aylin

    2012-01-01

    A two-transmitter Gaussian multiple access wiretap channel with multiple antennas at each of the nodes is investigated. The channel matrices at the legitimate terminals are fixed and revealed to all the terminals, whereas the channel matrix of the eavesdropper is arbitrarily varying and only known to the eavesdropper. The secrecy degrees of freedom (s.d.o.f.) region under a strong secrecy constraint is characterized. A transmission scheme that orthogonalizes the transmit signals of the two users at the intended receiver and uses a single-user wiretap code is shown to be sufficient to achieve the s.d.o.f. region. The converse involves establishing an upper bound on a weighted-sum-rate expression. This is accomplished by using induction, where at each step one combines the secrecy and multiple-access constraints associated with an adversary eavesdropping a carefully selected group of sub-channels.

  15. VARIABLE-RATE MULTIUSER DIVERSITY IN CORRELATED MIMO CHANNEL VIA VIRTUAL CHANNEL REPRESENTATION

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper studies the multiuser diversity with constellation selection based on a virtual representation of realistic Multiple Input Multiple Output (MIMO) correlated channels. To realize multiuser diversity in slow fading channels, random beamforming is adopted. Random beamforming matrix exploiting virtual channel representation is constructed, which can match the channel matrix of the desired user better. Simultaneously, adaptive coded modulation is applied to each sub-channel of the selected user to improve the system performance further.

  16. Crystal structure and biochemical investigations reveal novel mode of substrate selectivity and illuminate substrate inhibition and allostericity in a subfamily of Xaa-Pro dipeptidases.

    Science.gov (United States)

    Are, Venkat N; Kumar, A