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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. Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter.

    Directory of Open Access Journals (Sweden)

    Tobias Åkerström

    Full Text Available BACKGROUND: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na(+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined. MATERIALS AND METHODS: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers. RESULTS: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%. Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005 and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005. DISCUSSION: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing

  3. 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.

  4. Cognitive FH Channel Selection for Bluetooth Network

    OpenAIRE

    Yi Peng; Qingzhi Du; Long Hua; Yubing Shao

    2013-01-01

    Bluetooth is a short-range wireless technology that operates in the 2.4GHz unlicensed ISM band, so it will inevitably encounter the interference from other wireless systems and other Bluetooth piconets. Because of the flexible, efficient and reliable spectrum access by adapting the radio’s operating characteristics to the real-time conditions of the environment, cognitive radio technology is apply in Bluetooth network. In this paper, a novel cognitive FH channel selection method which is buil...

  5. 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.

  6. Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels.

    Science.gov (United States)

    Kozai, Daisuke; Sakaguchi, Reiko; Ohwada, Tomohiko; Mori, Yasuo

    2015-01-01

    The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators. Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and discuss their modulatory mechanisms. PMID:26411770

  7. [Model of the selective calcium channel of characean algae].

    Science.gov (United States)

    Lunevskiĭ, V Z; Zherelova, O M; Aleksandrov, A A; Vinokurov, M G; Berestovskiĭ, G N

    1980-01-01

    The present work was intended to further investigate the selective filter of calcium channel on both a cell membrane and reconstructed channels. For the studies on cell membranes, an inhibitor of chloride channels was chosen (ethacrynic acid) to pass currents only through the calcium channels. On both the cells and reconstructed channels, permeability of ions of different crystal radii and valencies was investigated. The obtained results suggest that the channel represents a wide water pore with a diameter larger than 8 A into which ions go together with the nearest water shell. The values of the maximal currents are given by electrostatic interaction of the ions with the anion center of the channel. A phenomenological two-barrier model of the channel is given which describes the movement of all the ions studied. PMID:6251921

  8. DISTRIBUTION CHANNELS SELECTION USING PCA-DEA APPROACH

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    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.

  9. 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.

  10. 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.

  11. Synchronization in Strictly Bandlimited Frequency Selective Ultra-Wideband Channels

    CERN Document Server

    Böcherer, Georg

    2008-01-01

    The frequency selectivity of wireless communication channels can be characterized by the delay spread Ds of the channel impulse response. If the delay spread is small compared to the bandwidth W of the input signal, that is, Ds*W approximately equal to 1, the channel appears to be flat fading. For Ds*W >> 1, the channel appears to be frequency selective, which is usually the case for wideband signals. In the first case, small scale synchronization with a precision much higher than the sampling time T = 1/W is crucial. In this paper, it is shown by analytical means that this is different in the wideband regime. Here synchronization with a precision of T is sufficient and small scale synchronization cannot further increase the captured energy at the receiver. Simulation results show that this effect already occurs for W > 50MHz for the IEEE 802.15.4a channel model.

  12. 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

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

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    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.

  19. 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.

  20. 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.

  1. Noise masking reveals channels for second-order letters

    OpenAIRE

    Oruç, İpek; Landy, Michael S.; Pelli, Denis G.

    2005-01-01

    We investigate the channels underlying identification of second-order letters using a critical-band masking paradigm. We find that observers use a single 1–1.5 octave-wide channel for this task. This channel’s best spatial frequency (c/letter) did not change across different noise conditions (indicating the inability of observers to switch channels to improve signal-to-noise ratio) or across different letter sizes (indicating scale invariance), for a fixed carrier frequency (c/letter). Howeve...

  2. Self-organized models of selectivity in calcium channels

    International Nuclear Information System (INIS)

    The role of flexibility in the selectivity of calcium channels is studied using a simple model with two parameters that accounts for the selectivity of calcium (and sodium) channels in many ionic solutions of different compositions and concentrations using two parameters with unchanging values. We compare the distribution of side chains (oxygens) and cations (Na+ and Ca2+) and integrated quantities. We compare the occupancies of cations Ca2+/Na+ and linearized conductance of Na+. The distributions show a strong dependence on the locations of fixed side chains and the flexibility of the side chains. Holding the side chains fixed at certain predetermined locations in the selectivity filter distorts the distribution of Ca2+ and Na+ in the selectivity filter. However, integrated quantities—occupancy and normalized conductance—are much less sensitive. Our results show that some flexibility of side chains is necessary to avoid obstruction of the ionic pathway by oxygen ions in 'unfortunate' fixed positions. When oxygen ions are mobile, they adjust 'automatically' and move 'out of the way', so they can accommodate the permeable cations in the selectivity filter. Structure is the computed consequence of the forces in this model. The structures are self-organized, at their free energy minimum. The relationship of ions and side chains varies with an ionic solution. Monte Carlo simulations are particularly well suited to compute induced-fit, self-organized structures because the simulations yield an ensemble of structures near their free energy minimum. The exact location and mobility of oxygen ions has little effect on the selectivity behavior of calcium channels. Seemingly, nature has chosen a robust mechanism to control selectivity in calcium channels: the first-order determinant of selectivity is the density of charge in the selectivity filter. The density is determined by filter volume along with the charge and excluded volume of

  3. Modulation of mechanosensitive calcium-selective cation channels by temperature

    Science.gov (United States)

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

    1993-01-01

    Gating of associations of mechanosensitive Ca(2+)-selective cation co-channels in the plasmalemma of onion epidermis has a strong and unusual temperature dependence. Tension-dependent activity rises steeply as temperature is lowered from 25 degrees C to about 6 degrees C, but drops to a low level at about 5 degrees C. Under the conditions tested (with Mg2+ and K+ at the cytosolic face of outside-out membrane patches), promotion results both from more bursting at all observed linkage levels and from longer duration of bursts of co-channels linked as quadruplets and quintuplets. Co-channel conductance decreases linearly, but only modestly, with declining temperature. It is proposed that these and related mechanosensitive channels may participate in a variety of responses to temperature, including thermonasty, thermotropism, hydrotropism, and both cold damage and cold acclimation.

  4. 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.

  5. Antenna Subset Selection for Cyclic Prefix Assisted MIMO Wireless Communications over Frequency Selective Channels

    Directory of Open Access Journals (Sweden)

    T. Kaiser

    2008-04-01

    Full Text Available Antenna (subset selection techniques are feasible to reduce the hardware complexity of multiple-input multiple-output (MIMO systems, while keeping the benefits of higher-order MIMO systems. Many studies of antenna selection schemes are based on frequency-flat channel models, which are inconsistent to broadband MIMO systems employing spatial-multiplexing. In broadband MIMO systems aiming to provide high-data-rate links, the employed signal bandwidth is typically larger than the coherence bandwidth of the channel so that the channel will be of frequency selective nature. Within this contribution we provide an overview on joint transmitter- and receiver-side antenna subset selection methods for frequency selective channels and deploy them in MIMO orthogonal frequency division multiplexing (OFDM systems and MIMO single-carrier (SC systems employing frequency domain equalization (FDE.

  6. Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels.

    Science.gov (United States)

    Du, Yuzhe; Nomura, Yoshiko; Liu, Zhiqi; Huang, Zachary Y; Dong, Ke

    2009-12-01

    Tetrodotoxin (TTX) is a potent blocker of voltage-gated sodium channels, but not all sodium channels are equally sensitive to inhibition by TTX. The molecular basis of differential TTX sensitivity of mammalian sodium channels has been largely elucidated. In contrast, our knowledge about the sensitivity of invertebrate sodium channels to TTX remains poor, in part because of limited success in functional expression of these channels. In this study, we report the functional characterization in Xenopus oocytes of the first non-insect, invertebrate voltage-gated sodium channel from the varroa mite (Varroa destructor), an ecto-parasite of the honeybee. This arachnid sodium channel activates and inactivates rapidly with half-maximal activation at -18 mV and half-maximal fast inactivation at -29 mV. Interestingly, this arachnid channel showed surprising TTX resistance. TTX blocked this channel with an IC(50) of 1 microM. Subsequent site-directed mutagenesis revealed two residues, Thr-1674 and Ser-1967, in the pore-forming region of domains III and IV, respectively, which were responsible for the observed resistance to inhibition by TTX. Furthermore, sequence comparison and additional amino acid substitutions suggested that sequence polymorphisms at these two positions could be a widespread mechanism for modulating TTX sensitivity of sodium channels in diverse invertebrates. PMID:19828457

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Mechanosensory calcium-selective cation channels in epidermal cells

    Science.gov (United States)

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

    1993-01-01

    This paper explores the properties and likely functions of an epidermal Ca(2+)-selective cation channel complex activated by tension. As many as eight or nine linked or linkable equivalent conductance units or co-channels can open together. Open time for co-channel quadruplets and quintuplets tends to be relatively long with millimolar Mg2+ (but not millimolar Ca2+) at the cytosolic face of excised plasma membrane. Sensitivity to tension is regulated by transmembrane voltage and temperature. Under some circumstances channel activity is sychronized in rhythmic pulses. Certain lanthanides and a cytoskeleton-disturbing herbicide that inhibit gravitropic reception act on the channel system at low concentrations. Specifically, ethyl-N-phenylcarbamate promotes tension-dependent activity at micromolar levels. With moderate suction, Gd3+ provided at about 0.5 micromole at the extracellular face of the membrane promotes for several seconds but may then become inhibitory. Provision at 1-2 micromoles promotes and subsequently inhibits more vigorously (often abruptly and totally), and at high levels inhibits immediately. La3+, a poor gravitropic inhibitor, acts similarly but much more gradually and only at much higher concentrations. These properties, particularly these susceptibilities to modulation, indicate that in vivo the mechanosensitive channel must be mechanosensory and mechanoregulatory. It could serve to transduce the shear forces generated in the integrated wall-membrane-cytoskeleton system during turgor changes and cell expansion as well as transducing the stresses induced by gravity, touch and flexure. In so far as such transduction is modulated by voltage and temperature, the channels would also be sensors for these modalities as long as the wall-membrane-cytoskeleton system experiences mechanical stress.

  17. K(+) versus Na(+) ions in a K channel selectivity filter: a simulation study.

    OpenAIRE

    Shrivastava, Indira H.; Tieleman, D. Peter; Biggin, Philip C; Sansom, Mark S P

    2002-01-01

    Molecular dynamics simulations of a bacterial potassium channel (KcsA) embedded in a phospholipid bilayer reveal significant differences in interactions of the selectivity filter with K(+) compared with Na(+) ions. K(+) ions and water molecules within the filter undergo concerted single-file motion in which they translocate between adjacent sites within the filter on a nanosecond timescale. In contrast, Na(+) ions remain bound to sites within the filter and do not exhibit translocation on a n...

  18. Engineering Highly Potent and Selective Microproteins against Nav1.7 Sodium Channel for Treatment of Pain.

    Science.gov (United States)

    Shcherbatko, Anatoly; Rossi, Andrea; Foletti, Davide; Zhu, Guoyun; Bogin, Oren; Galindo Casas, Meritxell; Rickert, Mathias; Hasa-Moreno, Adela; Bartsevich, Victor; Crameri, Andreas; Steiner, Alexander R; Henningsen, Robert; Gill, Avinash; Pons, Jaume; Shelton, David L; Rajpal, Arvind; Strop, Pavel

    2016-07-01

    The prominent role of voltage-gated sodium channel 1.7 (Nav1.7) in nociception was revealed by remarkable human clinical and genetic evidence. Development of potent and subtype-selective inhibitors of this ion channel is crucial for obtaining therapeutically useful analgesic compounds. Microproteins isolated from animal venoms have been identified as promising therapeutic leads for ion channels, because they naturally evolved to be potent ion channel blockers. Here, we report the engineering of highly potent and selective inhibitors of the Nav1.7 channel based on tarantula ceratotoxin-1 (CcoTx1). We utilized a combination of directed evolution, saturation mutagenesis, chemical modification, and rational drug design to obtain higher potency and selectivity to the Nav1.7 channel. The resulting microproteins are highly potent (IC50 to Nav1.7 of 2.5 nm) and selective. We achieved 80- and 20-fold selectivity over the closely related Nav1.2 and Nav1.6 channels, respectively, and the IC50 on skeletal (Nav1.4) and cardiac (Nav1.5) sodium channels is above 3000 nm The lead molecules have the potential for future clinical development as novel therapeutics in the treatment of pain. PMID:27129258

  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

    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.

  2. 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.

  3. Biophysical characterization of the honeybee DSC1 orthologue reveals a novel voltage-dependent Ca2+ channel subfamily: CaV4.

    Science.gov (United States)

    Gosselin-Badaroudine, Pascal; Moreau, Adrien; Simard, Louis; Cens, Thierry; Rousset, Matthieu; Collet, Claude; Charnet, Pierre; Chahine, Mohamed

    2016-08-01

    Bilaterian voltage-gated Na(+) channels (NaV) evolved from voltage-gated Ca(2+) channels (CaV). The Drosophila melanogaster Na(+) channel 1 (DSC1), which features a D-E-E-A selectivity filter sequence that is intermediate between CaV and NaV channels, is evidence of this evolution. Phylogenetic analysis has classified DSC1 as a Ca(2+)-permeable Na(+) channel belonging to the NaV2 family because of its sequence similarity with NaV channels. This is despite insect NaV2 channels (DSC1 and its orthologue in Blatella germanica, BSC1) being more permeable to Ca(2+) than Na(+) In this study, we report the cloning and molecular characterization of the honeybee (Apis mellifera) DSC1 orthologue. We reveal several sequence variations caused by alternative splicing, RNA editing, and genomic variations. Using the Xenopus oocyte heterologous expression system and the two-microelectrode voltage-clamp technique, we find that the channel exhibits slow activation and inactivation kinetics, insensitivity to tetrodotoxin, and block by Cd(2+) and Zn(2+) These characteristics are reminiscent of CaV channels. We also show a strong selectivity for Ca(2+) and Ba(2+) ions, marginal permeability to Li(+), and impermeability to Mg(2+) and Na(+) ions. Based on current ion channel nomenclature, the D-E-E-A selectivity filter, and the properties we have uncovered, we propose that DSC1 homologues should be classified as CaV4 rather than NaV2. Indeed, channels that contain the D-E-E-A selectivity sequence are likely to feature the same properties as the honeybee's channel, namely slow activation and inactivation kinetics and strong selectivity for Ca(2+) ions. PMID:27432995

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

    OpenAIRE

    Young, Laura K.; Smithson, Hannah E.

    2014-01-01

    There is evidence that letter identification is mediated by only a narrow band of spatial frequencies and that the center frequency of the neural channel thought to underlie this selectivity is related to the size of the letters. When letters are spatially filtered (at a fixed size) the channel tuning characteristics change according to the properties of the spatial filter (Majaj et al., 2002). Optical aberrations in the eye act to spatially filter the image formed on the retina—their effect ...

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

    OpenAIRE

    Laura eYoung; Hannah eSmithson

    2014-01-01

    There is evidence that letter identification is mediated by only a narrow band of spatial frequencies and that the centre frequency of the neural channel thought to underlie this selectivity is related to the size of the letters. When letters are spatially filtered (at a fixed size) the channel tuning characteristics change according to the properties of the spatial filter (Majaj et al., 2002). Optical aberrations in the eye act to spatially filter the image formed on the retina - their effec...

  6. 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.

  7. Cognitive Radio Channel Selection Strategy Based on Experience-Weighted Attraction Learning

    OpenAIRE

    Qian Jiansheng; Sun Yong

    2013-01-01

    In this paper, an innovative proposed channel selection algorithm based on Experience-Weighted Attraction (EWA) learning allows Cognitive Radio (CR) to learn radio environment communication channel characteristics online. By accumulating the history channel experience, it can predict, select and change the current optimal communication channel, dynamic ensure the quality of communication links and finally reduce system communication outage probability. Validation and reliability have been str...

  8. 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.

  9. 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...

  10. Exome sequencing of ion channel genes reveals complex variant profiles confounding personal risk assessment in epilepsy

    Science.gov (United States)

    Klassen, Tara; Davis, Caleb; Goldman, Alica; Burgess, Dan; Chen, Tim; Wheeler, David; McPherson, John; Bourquin, Traci; Lewis, Lora; Villasana, Donna; Morgan, Margaret; Muzny, Donna; Gibbs, Richard; Noebels, Jeffrey

    2011-01-01

    Ion channel mutations are an important cause of rare Mendelian disorders affecting brain, heart, and other tissues. We performed parallel exome sequencing of 237 channel genes in a well characterized human sample, comparing variant profiles of unaffected individuals to those with the most common neuronal excitability disorder, sporadic idiopathic epilepsy. Rare missense variation in known Mendelian disease genes is prevalent in both groups at similar complexity, revealing that even deleterious ion channel mutations confer uncertain risk to an individual depending on the other variants with which they are combined. Our findings indicate that variant discovery via large scale sequencing efforts is only a first step in illuminating the complex allelic architecture underlying personal disease risk. We propose that in silico modeling of channel variation in realistic cell and network models will be crucial to future strategies assessing mutation profile pathogenicity and drug response in individuals with a broad spectrum of excitability disorders. PMID:21703448

  11. 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.

  12. Parallel Selection Revealed by Population Sequencing in Chicken.

    Science.gov (United States)

    Qanbari, Saber; Seidel, Michael; Strom, Tim-Mathias; Mayer, Klaus F X; Preisinger, Ruedi; Simianer, Henner

    2015-12-01

    Human-driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern chicken. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying genes relevant to domestication and improvement that ultimately may help to further genetically improve this economically important animal. We used whole genome sequence data from 50 hens of commercial white (WL) and brown (BL) egg-laying chicken along with pool sequences of three meat-type chicken to perform a systematic screening of past selection in modern chicken. Evidence of positive selection was investigated in two steps. First, we explored evidence of parallel fixation in regions with overlapping elevated allele frequencies in replicated populations of layers and broilers, suggestive of selection during domestication or preimprovement ages. We confirmed parallel fixation in BCDO2 and TSHR genes and found four candidates including AGTR2, a gene heavily involved in "Ascites" in commercial birds. Next, we explored differentiated loci between layers and broilers suggestive of selection during improvement in chicken. This analysis revealed evidence of parallel differentiation in genes relevant to appearance and production traits exemplified with the candidate gene OPG, implicated in Osteoporosis, a disorder related to overconsumption of calcium in egg-laying hens. Our results illustrate the potential for population genetic techniques to identify genomic regions relevant to the phenotypes of importance to breeders. PMID:26568375

  13. 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.

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

    Science.gov (United States)

    Young, Laura K; Smithson, Hannah E

    2014-01-01

    There is evidence that letter identification is mediated by only a narrow band of spatial frequencies and that the center frequency of the neural channel thought to underlie this selectivity is related to the size of the letters. When letters are spatially filtered (at a fixed size) the channel tuning characteristics change according to the properties of the spatial filter (Majaj et al., 2002). Optical aberrations in the eye act to spatially filter the image formed on the retina-their effect is generally to attenuate high frequencies more than low frequencies but often in a non-monotonic way. We might expect the change in the spatial frequency spectrum caused by the aberration to predict the shift in channel tuning observed for aberrated letters. We show that this is not the case. We used critical-band masking to estimate channel-tuning in the presence of three types of aberration-defocus, coma and secondary astigmatism. We found that the maximum masking was shifted to lower frequencies in the presence of an aberration and that this result was not simply predicted by the spatial-frequency-dependent degradation in image quality, assessed via metrics that have previously been shown to correlate well with performance loss in the presence of an aberration. We show that if image quality effects are taken into account (using visual Strehl metrics), the neural channel required to model the data is shifted to lower frequencies compared to the control (no-aberration) condition. Additionally, we show that when spurious resolution (caused by π phase shifts in the optical transfer function) in the image is masked, the channel tuning properties for aberrated letters are affected, suggesting that there may be interference between visual channels. Even in the presence of simulated aberrations, whose properties change from trial-to-trial, observers exhibit flexibility in selecting the spatial frequencies that support letter identification. PMID:25324794

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

    Directory of Open Access Journals (Sweden)

    Laura eYoung

    2014-09-01

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

  16. HERG channel (dys)function revealed by dynamic action potential clamp technique

    OpenAIRE

    Berecki, G; Zegers, J.G.; Verkerk, A.O.; Bhuiyan, Z.A.; Jonge, de, M.J.I.; Veldkamp, M.W.; Wilders, R; Ginneken, van, CJJM Kees

    2005-01-01

    The human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier potassium current (IKr). Per-Arnt-Sim domain mutations of the HERG channel are linked to type 2 long-QT syndrome. We studied wild-type and/or type 2 long-QT syndrome-associated mutant (R56Q) HERG current (IHERG) in HEK-293 cells, at both 23 and 36°C. Conventional voltage-clamp analysis revealed mutation-induced changes in channel kinetics. To assess functional implication(s) of the mutatio...

  17. 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

  18. Critical assessment of OmpF channel selectivity: merging information from different experimental protocols

    International Nuclear Information System (INIS)

    The ion selectivity of a channel can be quantified in several ways by using different experimental protocols. A wide, mesoscopic channel, the OmpF porin of the outer membrane of E. coli, serves as a case study for comparing and analysing several measures of the channel cation-anion permeability in chlorides of alkali metals (LiCl, NaCl, KCl, CsCl). We show how different insights can be gained and integrated to rationalize the global image of channel selectivity. To this end, reversal potential, channel conductance and bi-ionic potential (two different salts with a common anion on each side of the channel but with the same concentration) experiments are discussed in light of an electrodiffusion model based on the Poisson-Nernst-Planck formalism. Measurements and calculations based on the atomic crystal structure of the channel show that each protocol displays a particular balance between the different sources of selectivity.

  19. Sedimentary processes in Zenisu deep-sea channel revealed by side-scan imagery

    Science.gov (United States)

    Wu, Shiguo; Guo, Junhua; Hidekazu, Tokuyama

    2005-12-01

    Side-scan sonar data collected by Cruises 99-09 Leg 2 and 00-06 Leg 1 of R/V Yokosuka were used to reveal the sedimentary processes in Zenisu deep-sea channel. The middle and lower segments of the channel are rich in turbidite and other debrite deposits. By high-resolution imaging, three sedimentary processes were distinguished with distinct acoustic features. 1. Slumps and slides occur with contrasting backscatter, rough surface textures, blockings, and acoustic shadows at head walls. They are very extensive and often in lobate form downslope. 2. Debris flow has uniform, general medium backscatter, sometimes showing marbling/lineation in lobate form. 3. Turbidity current is characterized by low backscatter confined to the channel as acoustic signal is attenuated. Regional tectonics must be the dominating factor that controls deposition pattern in this area.

  20. Valence selectivity of the gramicidin channel: a molecular dynamics free energy perturbation study.

    OpenAIRE

    Roux, B

    1996-01-01

    The valence selectivity of the gramicidin channel is examined using computer simulations based on atomic models. The channel interior is modeled using a gramicidin-like periodic poly (L,D)-alanine beta-helix. Free energy perturbation calculations are performed to obtain the relative affinity of K+ and Cl- for the channel. It is observed that the interior of the gramicidin channel provides an energetically favorable interaction site for a cation but not for an anion. Relative to solvation in b...

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

    Energy Technology Data Exchange (ETDEWEB)

    Derebe, Mehabaw G.; Sauer, David B.; Zeng, Weizhong; Alam, Amer; Shi, Ning; Jiang, Youxing (UTSMC); (ETH Zurich)

    2015-11-30

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

  2. 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.

  3. Functional Expression of an Arachnid Sodium Channel Reveals Residues Responsible for Tetrodotoxin Resistance in Invertebrate Sodium Channels*

    OpenAIRE

    Du, Yuzhe; Nomura, Yoshiko; Liu, Zhiqi; Huang, Zachary Y.; Dong, Ke

    2009-01-01

    Tetrodotoxin (TTX) is a potent blocker of voltage-gated sodium channels, but not all sodium channels are equally sensitive to inhibition by TTX. The molecular basis of differential TTX sensitivity of mammalian sodium channels has been largely elucidated. In contrast, our knowledge about the sensitivity of invertebrate sodium channels to TTX remains poor, in part because of limited success in functional expression of these channels. In this study, we report the functional characterization in X...

  4. Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels

    OpenAIRE

    Li-Smerin, Yingying; Swartz, Kenton J.

    1998-01-01

    Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin and grammotoxin are two related protein toxins found in the venom of the Chilean Rose Tarantula, Phrixotrichus spatulata. Hanatoxin inhibits voltage-gated K+ channels and grammotoxin inhibits voltage-gated Ca2+ channels. Both toxins inhibit their respective channels by interfering with normal operation of the voltage-dependent gating mechanism. The sequenc...

  5. KCNQ Modulators Reveal a Key Role for KCNQ Potassium Channels in Regulating the Tone of Rat Pulmonary Artery Smooth Muscle

    OpenAIRE

    Joshi, Shreena; Sedivy, Vojtech; Hodyc, Daniel; Herget, Jan; Gurney, Alison M

    2009-01-01

    Potassium channels are central to the regulation of pulmonary vascular tone. The smooth muscle cells of pulmonary artery display a background K+ conductance with biophysical properties resembling those of KCNQ (KV7) potassium channels. Therefore, we investigated the expression and functional role of KCNQ channels in pulmonary artery. The effects of selective KCNQ channel modulators were investigated on K+ current and membrane potential in isolated pulmonary artery smoo...

  6. 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.

  7. Selection of marketing channels for the distribution of industrial enterprises’ innovative products

    Directory of Open Access Journals (Sweden)

    L.O. Syhyda

    2014-03-01

    Full Text Available The aim of the article. The aim of the study is to determine the stages by which it is possible to select among existing marketing channels of the enterprise ones that would be best to use in innovative products’ distribution. The results of the analysis. The author proposes stages by following which it is possible to choose marketing channels for the innovative products’ distribution at industrial enterprises. At the first stage of marketing channels’ selection diagnostics of marketing distribution policy actual state is held. It allows to identify shortcomings in the distribution system and to identify areas of its improvement in order to bring the finished products to customers in the best conditions. At the second stage the assessment of enterprise’s existing marketing channels is provided. The assessment helps to define marketing channels of the enterprise and the type of innovative products that can be distributed via them. The third stage provides the selection of the most relevant marketing channels among existing channels at the enterprise. Those channels are expected to spread innovative products. The selection is based on qualitative assessment. A qualitative assessment of the marketing channel of innovative products is made by following criterias: - target market of innovative product and market on which channel operates; - compliance of innovative product to the range of products which are distributed via the channel; - actions for advance of an innovative product; - willingness of participants in channel to distribute innovative product; - level of expenses for distribution of innovative product via the channel; - risk at distribution of innovative products in the channel. The last, fourth stage involves selection of management strategies for marketing channels of innovative product. Conclusions and directions of further researches. Thus, the proposed sequence of stages of innovative products’ marketing channels choice

  8. 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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Rene Raphemot

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

  11. 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

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Justin John Finnerty

    Full Text Available 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.

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

    OpenAIRE

    Yongmei Liu; Yuhua Sun; Junhua Hu

    2013-01-01

    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 channe...

  15. Structure and selectivity of novel ω-conotoxins and conus catus that target neuronal calcium channel subtypes

    International Nuclear Information System (INIS)

    Full text: ω-Conotoxins selective for N-type voltage-sensitive calcium channels have promising therapeutic applications in conditions such as pain and neurodegeneration following cerebral ischaemia. Here we report the discovery of novel conotoxins from the piscivorous snail Conus carus using 125I-GVIA binding to rat brain membrane to guide fractionation of crude venom, and cloning to identify the expressed gene products from the venom duct tissue. Four peptides were isolated and named ω-conotoxins CVIA-D (CVIA-D) on the basis of their pharmacology and structure. CVIA-D had varying extents of homology to other ω-conotoxins, with loop 4 of CVID showing significant sequence divergence. From binding studies in rat brain, the rank order of potency to displace 125I-GVIA from N-type calcium channel (CVID = GVIA=MVIIA > CVIA > CVIC = CVIB > MVIIC) was reversed at the P/Q-type calcium channel (defined by 125I-MVIIC). CVID was most selective for N-type vs P/Q-type calcium channels, being 1.5 to 2-orders of magnitude more selective than GVIA and MVIIA, respectively. CVIA-D each inhibited neurally-evoked contractions in rat vas deferens in a reversible manner, with potencies that correlated with their ability to inhibit 125I-GVIA binding. Compared with GVIA, CVID was a more potent inhibitor of central N-type calcium channels (α1,B-dexpressed in Xenopus oocytes) than of peripheral N-type calcium channels (rat vas deferens). 1H NMR studies revealed that CVID adopts a similar 3D fold to other ω-conotoxins. However, in contrast to GVIA, MVIIA or MVIIC, CVID has two hydrogen bonds that hold loops 2 and 4 proximal, a factor that may contribute to the enhanced ability of CVID to discriminate among neuronal calcium channels

  16. 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

    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...... stronger than water-protein interactions, except near a conserved, positively charged Arg residue. We find that variations of the protein electrostatic field through the channel, owing to preserved structural features, completely explain the bipolar orientation of water. This orientation persists despite...... water translocation in single. le and blocks proton transport. Furthermore, we find that for permeation of a cation, ion-protein electrostatic interactions are more unfavorable at the conserved NPA motifs than at the conserved Arg, suggesting that the major barrier against proton transport in aquaporins...

  17. Molecular and functional characterization of Bemisia tabaci aquaporins reveals the water channel diversity of hemipteran insects.

    Science.gov (United States)

    Van Ekert, Evelien; Chauvigné, François; Finn, Roderick Nigel; Mathew, Lolita G; Hull, J Joe; Cerdà, Joan; Fabrick, Jeffrey A

    2016-10-01

    The Middle East-Asia Minor 1 (MEAM1) whitefly, Bemisia tabaci (Gennadius) is an economically important pest of food, fiber, and ornamental crops. This pest has evolved a number of adaptations to overcome physiological challenges, including 1) the ability to regulate osmotic stress between gut lumen and hemolymph after imbibing large quantities of a low nitrogen, sugar-rich liquid diet; 2) the ability to avoid or prevent dehydration and desiccation, particularly during egg hatching and molting; and 3) to be adapted for survival at elevated temperatures. One superfamily of proteins involved in the maintenance of fluid homeostasis in many organisms includes the aquaporins, which are integral membrane channel proteins that aid in the rapid flux of water and other small solutes across biological membranes. Here, we show that B. tabaci has eight aquaporins (BtAqps), of which seven belong to the classical aquaporin 4-related grade of channels, including Bib, Drip, Prip, and Eglps and one that belongs to the unorthodox grade of aquaporin 12-like channels. B. tabaci has further expanded its repertoire of water channels through the expression of three BtDrip2 amino-terminal splice variants, while other hemipteran species express amino- or carboxyl-terminal isoforms of Drip, Prip, and Eglps. Each BtAqp has unique transcript expression profiles, cellular localization, and/or substrate preference. Our phylogenetic and functional data reveal that hemipteran insects lost the classical glp genes, but have compensated for this by duplicating the eglp genes early in their evolution to comprise at least three separate clades of glycerol transporters. PMID:27491441

  18. Selection of marketing channels for the distribution of industrial enterprises’ innovative products

    OpenAIRE

    L.O. Syhyda

    2014-01-01

    The aim of the article. The aim of the study is to determine the stages by which it is possible to select among existing marketing channels of the enterprise ones that would be best to use in innovative products’ distribution. The results of the analysis. The author proposes stages by following which it is possible to choose marketing channels for the innovative products’ distribution at industrial enterprises. At the first stage of marketing channels’ selection diagnostics of marketing...

  19. Proactive Relay Selection with Joint Impact of Hardware Impairment and Co-channel Interference

    OpenAIRE

    Duy, Tran Trung; Duong, Trung Q.; da Costa, Daniel Benevides; Bao, Vo Ngyugen Quoc; Elkashlan, Maged

    2015-01-01

    In this paper, we investigate the end-to-end performance of dual-hop proactive decode-and-forward relaying networks with Nth best relay selection in the presence of two practical deleterious effects: i) hardware impairment and ii) cochannel interference. In particular, we derive new exact and asymptotic closed-form expressions for the outage probability and average channel capacity of Nth best partial and opportunistic relay selection schemes over Rayleigh fading channels. Insightful discussi...

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

    OpenAIRE

    Tripathi, S; Hladky, S B

    1998-01-01

    Streaming potentials have been measured for gramicidin channels with a new method employing ion-selective microelectrodes. It is shown that ideally ion-selective electrodes placed at the membrane surface record the true streaming potential. Using this method for ion concentrations below 100 mM, approximately seven water molecules are transported whenever a sodium, potassium, or cesium ion, passes through the channel. This new method confirms earlier measurements (Rosenberg, P.A., and A. Finke...

  1. 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.

  2. 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.

  3. MIMO-DFE BASED SPACE-TIME RECEIVER OVER FREQUENCY SELECTIVE CHANNELS WITH LIMITED ERROR PROPAGATION

    Institute of Scientific and Technical Information of China (English)

    Shen Liyun; Hu Bo

    2005-01-01

    MIMO-DFE(Multiple-Input-Multiple-Output Decision Feedback Equalizer) based receiver architectures are researched recently to detect signals in BLAST(Bell laboratories LAyered Space-Time) over frequency-selective channels. Due to their recursive structure, these receivers may suffer from error propagation which results in an overall mean square error degradation. An MIMO-DFE based BLAST receiver with limited error propagation to combat frequencyselective channel is proposed, which employs both norm constraint on feedback filter taps and soft decision device. Simulation results show that the proposed receiver outperforms conventional ones in various frequency selective channels.

  4. 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.

  5. 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

    2016-04-01

    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.

  6. Enhancement of transport selectivity through nano-channels by non-specific competition.

    Directory of Open Access Journals (Sweden)

    Anton Zilman

    2010-06-01

    Full Text Available The functioning of living cells requires efficient and selective transport of materials into and out of the cell, and between different cellular compartments. Much of this transport occurs through nano-scale channels that do not require large scale molecular re-arrangements (such as transition from a 'closed' to an 'open' state and do not require a direct input of metabolic energy during transport. Nevertheless, these 'always open' channels are highly selective and pass only their cognate molecules, while efficiently excluding all others; indeed, these channels can efficiently transport specific molecules even in the presence of a vast excess of non-specific molecules. Such biological transporters have inspired the creation of artificial nano-channels. These channels can be used as nano-molecular sorters, and can also serve as testbeds for examining modes of biological transport. In this paper, we propose a simple kinetic mechanism that explains how the selectivity of such 'always open' channels can be based on the exclusion of non-specific molecules by specific ones, due to the competition for limited space inside the channel. The predictions of the theory account for the behavior of the nuclear pore complex and of artificial nanopores that mimic its function. This theory provides the basis for future work aimed at understanding the selectivity of various biological transport phenomena.

  7. Unique Inner Pore Properties of BK Channels Revealed by Quaternary Ammonium Block

    OpenAIRE

    Li, Weiyan; Aldrich, Richard W.

    2004-01-01

    Potassium channels have a very wide distribution of single-channel conductance, with BK type Ca2+-activated K+ channels having by far the largest. Even though crystallographic views of K+ channel pores have become available, the structural basis underlying BK channels' large conductance has not been completely understood. In this study we use intracellularly applied quaternary ammonium compounds to probe the pore of BK channels. We show that molecules as large as decyltriethylammonium (C10) a...

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2016-01-01

    Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group. PMID:27584582

  11. 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

  12. 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.

  13. 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.

  14. 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)

  15. Genomic signatures reveal geographic adaption and human selection in cattle

    Science.gov (United States)

    We investigated geographic adaptation and human selection using high-density SNP data of five diverse cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-k...

  16. 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.

  17. 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

  18. Selectivity of a Singly Permeating Ion in Nonselective NaK Channel: Combined QM and MD Based Investigations.

    Science.gov (United States)

    Sadhu, Biswajit; Sundararajan, Mahesh; Bandyopadhyay, Tusar

    2015-10-01

    Ion channels, such as potassium channels are known to discriminate ions to achieve remarkable selective transportation of K(+) over Na(+) through the membrane. The recently reported NaK ion channel, on the contrary, seems to be an exception, as it is observed to permeate most of the group IA alkali metal cations and hence is suggested to be nonselective in nature. However, does that correspond to a complete annihilation of selectivity inside the selectivity filter (SF) of the channel? What is the origin of such nonselectivity/selectivity, if any? The present computational study is an extensive multiscale modeling approach to find the probable answers to these intriguing questions. Here, we have used density functional theory (DFT) based calculations using a realistic truncated model of SF from the crystal structures of the NaK ion channel to evaluate the binding of various alkali metal ions (Na(+), K(+) and Cs(+)), free from "contamination" due to the absence any other "rivalry" cations, in its different binding sites. Among all of the possible binding sites, a vestibule is noticed to be nonselective and seen to act as a probable binding site only in the presence of multiple ions. Binding sites S3 and S4 are found to be selective for K(+) and Na(+), respectively. As an important observation, we find that calculations on oversimplified models using an isolated ion binding site may lead to an erroneous selectivity trend as it neglects the synergetics of consecutive binding sites on the final outcome. Energy decomposition analysis revealed ion-dipole electrostatics as the major contributing interaction in metal-bound binding sites. Our investigations find that although NaK is permeable to monovalent alkali metal ions, strongly "site specific" selectivity does exist at the three well-defined noncontiguous binding sites of the SF. Different important physicomechanical parameters (such as ligating environment, synergistic influence of binding sites, and topological

  19. 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.

  20. 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...

  1. Discovery of novel tetrahydroisoquinoline derivatives as orally active N-type calcium channel blockers with high selectivity for hERG potassium channels.

    Science.gov (United States)

    Ogiyama, Takashi; Inoue, Makoto; Honda, Shugo; Yamada, Hiroyoshi; Watanabe, Toshihiro; Gotoh, Takayasu; Kiso, Tetsuo; Koakutsu, Akiko; Kakimoto, Shuichiro; Shishikura, Jun-ichi

    2014-12-15

    N-type calcium channels represent a promising target for the treatment of neuropathic pain. The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration. We identified tetrahydroisoquinoline derivative 1a as a novel potent N-type calcium channel blocker. However, this compound also exhibited potent inhibitory activity against hERG channels. Structural optimizations led to identification of (1S)-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-{[(1-hydroxycyclohexyl)methyl]amino}ethanone ((S)-1h), which exhibited high selectivity for hERG channels while retaining potency for N-type calcium channel inhibition. (S)-1h went on to demonstrate in vivo efficacy as an orally available N-type calcium channel blocker in a rat spinal nerve ligation model of neuropathic pain. PMID:25456079

  2. 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.

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

    Science.gov (United States)

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

    1993-01-01

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

  4. 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.

  5. 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.

  6. Autocrine-Based Selection of Drugs That Target Ion Channels from Combinatorial Venom Peptide Libraries.

    Science.gov (United States)

    Zhang, Hongkai; Du, Mingjuan; Xie, Jia; Liu, Xiao; Sun, Jingying; Wang, Wei; Xin, Xiu; Possani, Lourival D; Yea, Kyungmoo; Lerner, Richard A

    2016-08-01

    Animal venoms represent a rich source of pharmacologically active peptides that interact with ion channels. However, a challenge to discovering drugs remains because of the slow pace at which venom peptides are discovered and refined. An efficient autocrine-based high-throughput selection system was developed to discover and refine venom peptides that target ion channels. The utility of this system was demonstrated by the discovery of novel Kv1.3 channel blockers from a natural venom peptide library that was formatted for autocrine-based selection. We also engineered a Kv1.3 blocker peptide (ShK) derived from sea anemone to generate a subtype-selective Kv1.3 blocker with a long half-life in vivo. PMID:27197631

  7. 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%.

  8. 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.

  9. 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).

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating.

    Science.gov (United States)

    Matthies, Doreen; Dalmas, Olivier; Borgnia, Mario J; Dominik, Pawel K; Merk, Alan; Rao, Prashant; Reddy, Bharat G; Islam, Shahidul; Bartesaghi, Alberto; Perozo, Eduardo; Subramaniam, Sriram

    2016-02-11

    CorA, the major Mg(2+) uptake system in prokaryotes, is gated by intracellular Mg(2+) (KD ∼ 1-2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg(2+)-bound and Mg(2+)-free conditions, but EPR spectroscopic studies reveal large Mg(2+)-driven quaternary conformational changes. Here, we determined cryo-EM structures of CorA in the Mg(2+)-bound closed conformation and in two open Mg(2+)-free states at resolutions of 3.8, 7.1, and 7.1 Å, respectively. In the absence of bound Mg(2+), four of the five subunits are displaced to variable extents (∼ 10-25 Å) by hinge-like motions as large as ∼ 35° at the stalk helix. The transition between a single 5-fold symmetric closed state and an ensemble of low Mg(2+), open, asymmetric conformational states is, thus, the key structural signature of CorA gating. This mechanism is likely to apply to other structurally similar divalent ion channels. PMID:26871634

  16. 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.

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Baconguis, Isabelle; Gouaux, Eric [Oregon HSU

    2012-07-29

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

  19. 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

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

    Directory of Open Access Journals (Sweden)

    Leandro Zúñiga

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

  1. Selection of fuel channels for Thermal Power Measurement in 700 MWe Indian PHWR by evolutionary algorithm

    International Nuclear Information System (INIS)

    Highlights: ► Thermal Power Monitoring System is used for on-line estimation of reactor bulk power and zone powers in PHWRs. ► This requires making best choice of 44 fuel channels out of 392 to be instrumented for measurement of flow and temperature. ► This constrained optimization problem is solved by Estimation of Distribution Algorithm. ► With the designed TPMS, bulk power and zone power can be predicted with an accuracy of 0.5% and 2% respectively. - Abstract: This paper presents studies on the design of Thermal Power Monitoring System (TPMS) for the forthcoming 700 MWe Indian Pressurized Heavy Water Reactor (PHWR). This reactor contains total 392 horizontal fuel channels. Each channel contains clustered natural Uranium fuel along with associated heavy water coolant placed inside a pressure tube. The coolant in different fuel channels is physically and thermally isolated from each other inside the core. It is necessary to select 44 fuel channels (out of 392) for keeping instrumentation to measure flow and temperature of coolant. The reactor is logically divided into 7 radial zones each containing certain number of fuel channels. The selection of instrumented channels is to be made such that power measured by them in terms of per unit basis represents the true zone-wise and global powers fairly accurately. This should be possible for a large number of reactor configurations that can occur because of the movement of reactivity devices in the core. Such a study is useful to make the TPMS more accurate means to measure the reactor bulk power and zone powers. The choice of 44 channels is an optimization problem in which the error in zonal and global power prediction is to be minimized. There are several constraints on the selection of instrumented channels. Therefore, a constrained combinatorial optimization problem has to be solved. An evolutionary technique based on Estimation of Distribution Algorithm (EDA) is used for this purpose. A suitable pattern of

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

    Energy Technology Data Exchange (ETDEWEB)

    Agah, Shaghayegh [Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005-1892 (United States); Pasquali, Matteo [Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005-1892 (United States); Department of Chemistry, Rice University, Houston, Texas 77005-1892 (United States); Kolomeisky, Anatoly B., E-mail: tolya@rice.edu [Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005-1892 (United States); Department of Chemistry, Rice University, Houston, Texas 77005-1892 (United States); Center for Theoretical Biological Physics, Rice University, Houston, Texas, 77005 (United States)

    2015-01-28

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

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Gating motions in voltage-gated potassium channels revealed by coarse-grained molecular dynamics simulations

    NARCIS (Netherlands)

    Treptow, W.; Marrink, S.J.; Tarek, M.

    2008-01-01

    Voltage-gated potassium (Kv) channels are ubiquitous transmembrane proteins involved in electric signaling of excitable tissues. A fundamental property of these channels is the ability to open or close in response to changes in the membrane potential. To date, their structure-based activation mechan

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Selecting the best performing online marketing communication channels to an international start-up Eve

    OpenAIRE

    Karatsevidis, Konstantinos

    2016-01-01

    In today’s technologically advanced world online marketers are constantly faced with ever-growing challenges of running successful marketing campaigns. The problem that most of digital marketers face is the overwhelming amount of marketing tools and channels available to them. “How to select which channel to focus on?”, “Should we invest in viral marketing or social media ads?”, “What’s the next big thing in marketing?” Those are the questions marketers face every day. This Bachelor...

  12. 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. PMID:27490364

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  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

    2014-10-01

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

    Science.gov (United States)

    Wu, Fei; Minteer, Shelley

    2015-02-01

    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.

  19. Efficient Relay Selection Scheme for Delay-Limited Non-Orthogonal Hybrid-ARQ Relay Channels

    CERN Document Server

    Maham, Behrouz; Debbah, Merouane

    2012-01-01

    We consider a half-duplex wireless relay network with hybrid-automatic retransmission request (HARQ) and Rayleigh fading channels. In this paper, we analyze the outage probability of the multi-relay delay-limited HARQ system with opportunistic relaying scheme in decode-and-forward mode, in which the \\emph{best} relay is selected to transmit the source's regenerated signal. A simple and distributed relay selection strategy is proposed for multi-relay HARQ channels. Then, we utilize the non-orthogonal cooperative transmission between the source and selected relay for retransmitting of the source data toward the destination if needed, using space-time codes or beamforming techniques. We analyze the performance of the system. We first derive the cumulative density function (CDF) and probability density function (PDF) of the selected relay HARQ channels. Then, the CDF and PDF are used to determine the outage probability in the $l$-th round of HARQ. The outage probability is required to compute the throughput-delay...

  20. 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.

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

    DEFF Research Database (Denmark)

    Wickelmaier, Florian; Choisel, Sylvain

    2005-01-01

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

  2. 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.

  3. Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body.

    Science.gov (United States)

    Kang, Dawon; Wang, Jiaju; Hogan, James O; Vennekens, Rudi; Freichel, Marc; White, Carl; Kim, Donghee

    2014-05-01

    The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K(+) current and causes cell depolarization, Ca(2+) influx via voltage-dependent Ca(2+) channels and a rise in intracellular [Ca(2+)] ([Ca(2+)]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K(+) channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K(+), Na(+) and Cs(+) but not to Cl(-) or Ca(2+). The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca(2+) channel with FPL64176 activated the 20 pS channel when 1 mm Ca(2+) was present in the external solution. Ca(2+) (10 μm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca(2+)]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be -28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K(+) conductance and then activates a Na(+)-permeable, non-selective cation channel via depolarization-induced rise in [Ca(2+)]i. Our results suggest that inhibition of K(+) efflux and stimulation of Na(+) influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia.

  4. 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...

  5. 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.

  6. 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...

  7. 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 ...

  8. A general method for selecting quantum channel for bidirectional controlled state teleportation and other schemes of controlled quantum communication

    Science.gov (United States)

    Thapliyal, Kishore; Verma, Amit; Pathak, Anirban

    2015-12-01

    Recently, a large number of protocols for bidirectional controlled state teleportation (BCST) have been proposed using n-qubit entangled states (nin {5,6,7}) as quantum channel. Here, we propose a general method of selecting multiqubit (n>4) quantum channels suitable for BCST and show that all the channels used in the existing protocols of BCST can be obtained using the proposed method. Further, it is shown that the quantum channels used in the existing protocols of BCST form only a negligibly small subset of the set of all the quantum channels that can be constructed using the proposed method to implement BCST. It is also noted that all these quantum channels are also suitable for controlled bidirectional remote state preparation. Following the same logic, methods for selecting quantum channels for other controlled quantum communication tasks, such as controlled bidirectional joint remote state preparation and controlled quantum dialogue, are also provided.

  9. Keeping active channels in their place: membrane phosphoinositides regulate TRPM channel activity in a compartment-selective manner.

    Science.gov (United States)

    Braun, Andrew P

    2012-01-01

    We have long appreciated that the controlled movement of ions and solutes across the cell surface or plasma membrane affects every aspect of cell function, ranging from membrane excitability to metabolism to secretion, and is also critical for the long-term maintenance of cell viability. Studies examining these physiological transport processes have revealed a vast array of ion channels, transporters and ATPase-driven pumps that underlie these transmembrane ionic movements and how acquired or genetic disruption of these processes are linked to disease. More recently, it has become evident that the ongoing function of intracellular organelles and subcellular compartments also depends heavily on the controlled movement of ions to establish distinct pH or ionic environments. However, limited experimental access to these subcellular domains/structures has hampered scientific progress in this area, due in large part to the difficulty of applying proven functional assays, such as patch clamp and radiotracer methodologies, to these specialized membrane locations. Using both functional and immune-labeling assays, we now know that the types and complement of channels, transporters and pumps located within intracellular membranes and organelles often differ from those present on the plasma membrane. Moreover, it appears that this differential distribution is due to the presence of discrete tags/signals present within these transport proteins that dictate their sorting/trafficking to spatially discrete membrane compartments, where they may also interact with scaffolding proteins that help maintain their localization. Such targeting signals may thus operate in a manner analogous to the way a postal code is used to direct the delivery of a letter. PMID:23151432

  10. 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.

  11. 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.

  12. 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.

  13. An embryo of protocells: The capsule of graphene with selective ion channels

    OpenAIRE

    Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; Shi, Keliang; Xu, Youwen; Mingliang, Zhang; Liu, Bo; Qiu, Hongdeng

    2015-01-01

    The synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactiv...

  14. 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.

  15. Performance and Improvement of MCS Selection with Channel Quality Estimation Errors for HSDPA

    Institute of Scientific and Technical Information of China (English)

    JIA Min-li; KUANG Jing-ming; WAN Lei; FEI Ze-song

    2006-01-01

    The throughput performance of modulation and coding schemes (MCS) selection with channel quality estimation errors (CQEE) is analyzed for high-speed downlink packet access (HSDPA). To reduce the loss of throughput caused by CQEE, the robust MCS selection method and adaptive MCS switching scheme are proposed. In addition, automatic repeat request (ARQ) scheme is used to improve the block error rat e (BLER) performance. Simulation results show that the proposed methods decrease the throughput loss resulted from CQEE efficiently and BLER performance gets better with ARQ scheme.

  16. Fractionation of a Herbal Antidiarrheal Medicine Reveals Eugenol as an Inhibitor of Ca2+-Activated Cl− Channel TMEM16A

    OpenAIRE

    Zhen Yao; Wan Namkung; Ko, Eun A; Jinhong Park; Lukmanee Tradtrantip; Verkman, A.S.

    2012-01-01

    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...

  17. Control of the Selectivity of the Aquaporin Water Channel Family by Global Orientational Tuning

    Science.gov (United States)

    Tajkhorshid, Emad; Nollert, Peter; Jensen, Morten Ø.; Miercke, Larry J. W.; O'Connell, Joseph; Stroud, Robert M.; Schulten, Klaus

    2002-04-01

    Aquaporins are transmembrane channels found in cell membranes of all life forms. We examine their apparently paradoxical property, facilitation of efficient permeation of water while excluding protons, which is of critical importance to preserving the electrochemical potential across the cell membrane. We have determined the structure of the Escherichia coli aquaglyceroporin GlpF with bound water, in native (2.7 angstroms) and in W48F/F200T mutant (2.1 angstroms) forms, and carried out 12-nanosecond molecular dynamics simulations that define the spatial and temporal probability distribution and orientation of a single file of seven to nine water molecules inside the channel. Two conserved asparagines force a central water molecule to serve strictly as a hydrogen bond donor to its neighboring water molecules. Assisted by the electrostatic potential generated by two half-membrane spanning loops, this dictates opposite orientations of water molecules in the two halves of the channel, and thus prevents the formation of a ``proton wire,'' while permitting rapid water diffusion. Both simulations and observations revealed a more regular distribution of channel water and an increased water permeability for the W48F/F200T mutant.

  18. 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.

  19. The structure of phospholamban pentamer reveals a channel-like architecture in membranes

    OpenAIRE

    Oxenoid, Kirill; Chou, James J.

    2005-01-01

    Contraction and relaxation of heart muscle cells is regulated by cycling of calcium between cytoplasm and sarcoplasmic reticulum. Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. Since PLN was discovered ≈30 years ago, extensive studies have aimed to explain how it influences calcium pumps and to determine whether it acts as an ion channel. We have determin...

  20. 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...

  1. ERGODIC CAPACITY FORMULA OF MIMO-OFDM SYSTEMS UNDER CORRELATED FREQUENCY SELECTIVE RAYLEIGH FADING CHANNELS

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    An explicit formula for the ergodic capacity of Orthogonal Frequency Division Multiplexing (OFDM)-based Multiple-Input Multiple-Output (MIMO) systems under correlated frequency selective Rayleigh channels is derived, by simplifying the channel response matrix in frequency domain into the so-called Kronecker model composed of three kinds of correlations, i.e. multipath tap gain correlation and spatial fading correlations at both transmitter and receiver. The derived formula is very simple and convenient for one to estimate the effects of all three kinds of correlations on MIMO-OFDM capacity. If taps are independent, there is a very simple expression for the ergodic capacity. In case of tap correlation, the capacity formula could be further given in an integral expression. The validity of the new formula is verified and the effects of correlations, delay spread as well as the number of subcarriers on the ergodic capacity are evaluated via Monte Carlo simulations.

  2. 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.

  3. Structure of the voltage-gated K⁺ channel Eag1 reveals an alternative voltage sensing mechanism.

    Science.gov (United States)

    Whicher, Jonathan R; MacKinnon, Roderick

    2016-08-12

    Voltage-gated potassium (K(v)) channels are gated by the movement of the transmembrane voltage sensor, which is coupled, through the helical S4-S5 linker, to the potassium pore. We determined the single-particle cryo-electron microscopy structure of mammalian K(v)10.1, or Eag1, bound to the channel inhibitor calmodulin, at 3.78 angstrom resolution. Unlike previous K(v) structures, the S4-S5 linker of Eag1 is a five-residue loop and the transmembrane segments are not domain swapped, which suggest an alternative mechanism of voltage-dependent gating. Additionally, the structure and position of the S4-S5 linker allow calmodulin to bind to the intracellular domains and to close the potassium pore, independent of voltage-sensor position. The structure reveals an alternative gating mechanism for K(v) channels and provides a template to further understand the gating properties of Eag1 and related channels. PMID:27516594

  4. Robust fetal QRS detection from noninvasive abdominal electrocardiogram based on channel selection and simultaneous multichannel processing.

    Science.gov (United States)

    Ghaffari, Ali; Mollakazemi, Mohammad Javad; Atyabi, Seyyed Abbas; Niknazar, Mohammad

    2015-12-01

    The purpose of this study is to provide a new method for detecting fetal QRS complexes from non-invasive fetal electrocardiogram (fECG) signal. Despite most of the current fECG processing methods which are based on separation of fECG from maternal ECG (mECG), in this study, fetal heart rate (FHR) can be extracted with high accuracy without separation of fECG from mECG. Furthermore, in this new approach thoracic channels are not necessary. These two aspects have reduced the required computational operations. Consequently, the proposed approach can be efficiently applied to different real-time healthcare and medical devices. In this work, a new method is presented for selecting the best channel which carries strongest fECG. Each channel is scored based on two criteria of noise distribution and good fetal heartbeat visibility. Another important aspect of this study is the simultaneous and combinatorial use of available fECG channels via the priority given by their scores. A combination of geometric features and wavelet-based techniques was adopted to extract FHR. Based on fetal geometric features, fECG signals were divided into three categories, and different strategies were employed to analyze each category. The method was validated using three datasets including Noninvasive fetal ECG database, DaISy and PhysioNet/Computing in Cardiology Challenge 2013. Finally, the obtained results were compared with other studies. The adopted strategies such as multi-resolution analysis, not separating fECG and mECG, intelligent channels scoring and using them simultaneously are the factors that caused the promising performance of the method. PMID:26462679

  5. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels

    Science.gov (United States)

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-01-01

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1–KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4–S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

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

    Science.gov (United States)

    Yao, Zhen; Namkung, Wan; Ko, Eun A; Park, Jinhong; Tradtrantip, Lukmanee; Verkman, A S

    2012-01-01

    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. PMID:22666439

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. An embryo of protocells: The capsule of graphene with selective ion channels

    Science.gov (United States)

    Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; Shi, Keliang; Xu, Youwen; Mingliang, Zhang; Liu, Bo; Qiu, Hongdeng; Liu, Jie; Wu, Wangsuo; Wang, Xiaoli; Wenzhen, An

    2015-05-01

    The synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into a secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused 84Kr25+, has a high selectivity for permeation of the monovalent metal ions ( Rb+ > K+ > Cs+ > Na+ > Li+, based on permeation concentration), but does not allow Cl- go through. It is similar to K+ channels, which would cause an influx of K+ into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life.

  13. 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.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Yue Huang

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

  16. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Revealing the activation pathway for TMEM16A chloride channels from macroscopic currents and kinetic models.

    Science.gov (United States)

    Contreras-Vite, Juan A; Cruz-Rangel, Silvia; De Jesús-Pérez, José J; Figueroa, Iván A Aréchiga; Rodríguez-Menchaca, Aldo A; Pérez-Cornejo, Patricia; Hartzell, H Criss; Arreola, Jorge

    2016-07-01

    TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca(2+)]i), membrane depolarization, extracellular Cl(-) or permeant anions and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations. (a) TMEM16A is activated by voltage in the absence of intracellular Ca(2+). (b) The Cl(-) conductance is decreased after reducing extracellular Cl(-) concentration ([Cl(-)]o). (c) ICl is regulated by physiological concentrations of [Cl(-)]o. (d) In cells dialyzed with 0.2 μM [Ca(2+)]i, Cl(-) has a bimodal effect: at [Cl(-)]o kinetics. To explain the contribution of Vm, Ca(2+) and Cl(-) to gating, we developed a 12-state Markov chain model. This model explains TMEM16A activation as a sequential, direct, and Vm-dependent binding of two Ca(2+) ions coupled to a Vm-dependent binding of an external Cl(-) ion, with Vm-dependent transitions between states. Our model predicts that extracellular Cl(-) does not alter the apparent Ca(2+) affinity of TMEM16A, which we corroborated experimentally. Rather, extracellular Cl(-) acts by stabilizing the open configuration induced by Ca(2+) and by contributing to the Vm dependence of activation. PMID:27138167

  19. 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...

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Assimi Abdel-Nasser

    2009-01-01

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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sandvig, K.; Olsnes, S.

    1988-09-05

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

  8. 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.

  9. 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. PMID:25084457

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

    Directory of Open Access Journals (Sweden)

    Giuseppe Federico Amodeo

    Full Text Available 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.

  11. 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.

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

    OpenAIRE

    B.Sabarigiri; D.Suganyadevi

    2014-01-01

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

  13. 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.

  14. 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

  15. Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection.

    Science.gov (United States)

    Lenz, Tobias L; Spirin, Victor; Jordan, Daniel M; Sunyaev, Shamil R

    2016-10-01

    Deleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are maintained at considerable frequencies. Here, we test the hypothesis that balancing selection may counteract purifying selection in neighboring regions and thus maintain deleterious variants at higher frequency than expected from their detrimental fitness effect. We first show in realistic simulations that balancing selection reduces the density of polymorphic sites surrounding a locus under balancing selection, but at the same time markedly increases the population frequency of the remaining variants, including even substantially deleterious alleles. To test the predictions of our simulations empirically, we then use whole-exome sequencing data from 6,500 human individuals and focus on the most established example for balancing selection in the human genome, the major histocompatibility complex (MHC). Our analysis shows an elevated frequency of putatively deleterious coding variants in nonhuman leukocyte antigen (non-HLA) genes localized in the MHC region. The mean frequency of these variants declined with physical distance from the classical HLA genes, indicating dependency on genetic linkage. These results reveal an indirect cost of the genetic diversity maintained by balancing selection, which has hitherto been perceived as mostly advantageous, and have implications both for the evolution of recombination and also for the epidemiology of various MHC-associated diseases. PMID:27436009

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Genomic signatures reveal new evidences for selection of important traits in domestic cattle.

    Science.gov (United States)

    Xu, Lingyang; Bickhart, Derek M; Cole, John B; Schroeder, Steven G; Song, Jiuzhou; Tassell, Curtis P Van; Sonstegard, Tad S; Liu, George E

    2015-03-01

    We investigated diverse genomic selections using high-density single nucleotide polymorphism data of five distinct cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-known genes such as KIT, MC1R, ASIP, GHR, LCORL, NCAPG, WIF1, and ABCA12, we found evidence for a variety of novel and less-known genes under selection in cattle, such as LAP3, SAR1B, LRIG3, FGF5, and NUDCD3. Selective sweeps near LAP3 were then validated by next-generation sequencing. Genome-wide association analysis involving 26,362 Holsteins confirmed that LAP3 and SAR1B were related to milk production traits, suggesting that our candidate regions were likely functional. In addition, haplotype network analyses further revealed distinct selective pressures and evolution patterns across these five cattle breeds. Our results provided a glimpse into diverse genomic selection during cattle domestication, breed formation, and recent genetic improvement. These findings will facilitate genome-assisted breeding to improve animal production and health. PMID:25431480

  1. Picture-word interference reveals inhibitory effects of syllable frequency on lexical selection.

    Science.gov (United States)

    Farrell, Meagan T; Abrams, Lise

    2014-01-01

    While previous research has shown that high syllable frequency can facilitate speech production at the level of phonological/phonetic encoding, little is known about its influence on prephonological processes, specifically lexical selection. The current study used a picture-word interference (PWI) task to (a) shed light on the stages of lexical access where syllable frequency is relevant, and (b) inform as to whether lexical selection is accomplished via competition among activated word options. Participants named pictures whose names had high-frequency (HF) and low-frequency (LF) first syllables while ignoring phonologically related (same first syllable) or unrelated distractor words that were presented simultaneously. Word frequency was also manipulated, as half of the targets were HF words, and half were LF words. Results revealed inhibitory syllable frequency effects in all conditions, such that targets with HF first syllables were named more slowly than targets with LF first syllables. However, inhibitory syllable frequency effects were exacerbated in conditions thought to reflect heightened lexical competition, specifically in the presence of phonologically related distractors and for targets with low word frequency. These findings reveal novel evidence for first-syllable frequency effects on lexical selection and offer further support for models proposing delays at lexical selection due to activation of nontarget competitors. PMID:23931573

  2. 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.

  3. 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.

  4. 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.

  5. Transcriptome Display During Testicular Differentiation of Channel Catfish (Ictalurus punctatus) as Revealed by RNA-Seq Analysis.

    Science.gov (United States)

    Zeng, Qifan; Liu, Shikai; Yao, Jun; Zhang, Yu; Yuan, Zihao; Jiang, Chen; Chen, Ailu; Fu, Qiang; Su, Baofeng; Dunham, Rex; Liu, Zhanjiang

    2016-07-01

    Channel catfish (Ictalurus punctatus) has been recognized as a dominant freshwater aquaculture species in the United States. It is also a suitable model for studying the mechanisms of sex determination and differentiation because of its sexual plasticity and exhibition of both genetic and environmental sex determination. The testicular differentiation in male channel catfish normally starts between 90 and 102 days postfertilization (dpf), while the ovarian differentiation starts early from 19 dpf. As such, efforts to better understand the postponed testicular development at the molecular level are needed. Toward that end, we conducted transcriptomic comparison of gene expression of male and female gonads at 90, 100, and 110 dpf using high-throughput RNA-Seq. Transcriptomic profiles of male gonads on 90 and 100 dpf exhibited high similarities except for a small number of significantly up-regulated genes that were involved in development of germ cell-supporting somatic cells, while drastic changes were observed during 100-110 dpf, with a group of highly up-regulated genes that were involved in germ cells development, including nanog and pou5f1 Transcriptomic comparison between testes and ovaries identified male-preferential genes, such as gsdf, cxcl12, as well as other cytokines mediated the development of the gonad into a testis. Co-expression analysis revealed highly correlated genes and potential pathways underlying germ cell differentiation and spermatogonia stem cell development. The candidate genes and pathways identified in this study set the foundation for further studies on sex determination and differentiation in catfish as well as other teleosts. PMID:27307075

  6. 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...

  7. 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

    . METHODS: Cardiac biopsies were analyzed to investigate the expression level of the most prominent cardiac ion channels, with special focus on SK channels, in the equine heart. Subcellular distribution of SK isoform 2 (SK2) was assessed by immunohistochemistry and confocal microscopy......, and ventricular depolarization and repolarization times. RESULTS: Analysis revealed equivalent mRNA transcript levels of the 3 SK channel isoforms in atria compared to ventricles. Immunohistochemistry and confocal microscopy displayed a widespread distribution of SK2 in both atrial and ventricular cardiomyocytes...

  8. Quantitative analysis of the water occupancy around the selectivity filter of a K+ channel in different gating modes

    OpenAIRE

    Weingarth, Markus; van der Cruijsen, Elwin A. W.; Ostmeyer, Jared; Lievestro, Sylke; Roux, Benoît; Baldus, Marc

    2014-01-01

    Recovery in K+ channels, i.e., the transition from the inactivated non-conductive selectivity filter conformation towards the conductive conformation, occurs on a timescale of the order of seconds, which is astonishingly long, given that the structural differences among the filter conformations are faint (< 1 Å). Computational studies and electrophysiological measurements suggested that buried water molecules bound behind the selectivity filter are at the origin of the slowness of recovery in...

  9. Quantitative analysis of the water occupancy around the selectivity filter of a K+ channel in different gating modes

    NARCIS (Netherlands)

    Weingarth, Markus; Van Der Cruijsen, Elwin A W; Ostmeyer, Jared; Lievestro, Sylke; Roux, Benoiît; Baldus, Marc

    2014-01-01

    Recovery in K+ channels, that is, the transition from the inactivated nonconductive selectivity filter conformation toward the conductive conformation, occurs on a time scale of the order of seconds, which is astonishingly long, given that the structural differences among the filter conformations ar

  10. Frequency-selective fading statistics of shallow-water acoustic communication channel with a few multipaths

    Science.gov (United States)

    Bae, Minja; Park, Jihyun; Kim, Jongju; Xue, Dandan; Park, Kyu-Chil; Yoon, Jong Rak

    2016-07-01

    The bit error rate of an underwater acoustic communication system is related to multipath fading statistics, which determine the signal-to-noise ratio. The amplitude and delay of each path depend on sea surface roughness, propagation medium properties, and source-to-receiver range as a function of frequency. Therefore, received signals will show frequency-dependent fading. A shallow-water acoustic communication channel generally shows a few strong multipaths that interfere with each other and the resulting interference affects the fading statistics model. In this study, frequency-selective fading statistics are modeled on the basis of the phasor representation of the complex path amplitude. The fading statistics distribution is parameterized by the frequency-dependent constructive or destructive interference of multipaths. At a 16 m depth with a muddy bottom, a wave height of 0.2 m, and source-to-receiver ranges of 100 and 400 m, fading statistics tend to show a Rayleigh distribution at a destructive interference frequency, but a Rice distribution at a constructive interference frequency. The theoretical fading statistics well matched the experimental ones.

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

    International Nuclear Information System (INIS)

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

  12. Characterization of the first honeybee Ca²⁺ channel subunit reveals two novel species- and splicing-specific modes of regulation of channel inactivation.

    Science.gov (United States)

    Cens, Thierry; Rousset, Matthieu; Collet, Claude; Raymond, Valérie; Démares, Fabien; Quintavalle, Annabelle; Bellis, Michel; Le Conte, Yves; Chahine, Mohamed; Charnet, Pierre

    2013-07-01

    The honeybee is a model system to study learning and memory, and Ca(2+) signals play a key role in these processes. We have cloned, expressed, and characterized the first honeybee Ca(2+) channel subunit. We identified two splice variants of the Apis CaVβ Ca(2+) channel subunit (Am-CaVβ) and demonstrated expression in muscle and neurons. Although AmCaVβ shares with vertebrate CaVβ subunits the SH3 and GK domains, it beholds a unique N terminus that is alternatively spliced in the first exon to produce a long (a) and short (b) variant. When expressed with the CaV2 channels both, AmCaVβa and AmCaVβb, increase current amplitude, shift the voltage-sensitivity of the channel, and slow channel inactivation as the vertebrate CaVβ2a subunit does. However, as opposed to CaVβ2a, slow inactivation induced by Am-CaVβa was insensitive to palmitoylation but displayed a unique PI3K sensitivity. Inactivation produced by the b variant was PI3K-insensitive but staurosporine/H89-sensitive. Deletion of the first exon suppressed the sensitivity to PI3K inhibitors, staurosporine, or H89. Recording of Ba(2+) currents in Apis neurons or muscle cells evidenced a sensitivity to PI3K inhibitors and H89, suggesting that both AmCaVβ variants may be important to couple cell signaling to Ca(2+) entry in vivo. Functional interactions with phospho-inositide and identification of phosphorylation sites in AmCaVβa and AmCaVβb N termini, respectively, suggest that AmCaVβ splicing promoted two novel and alternative modes of regulation of channel activity with specific signaling pathways. This is the first description of a splicing-dependent kinase switch in the regulation of Ca(2+) channel activity by CaVβ subunit. PMID:23588376

  13. 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.

  14. A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels.

    Science.gov (United States)

    Furtado, Milena B; Wilmanns, Julia C; Chandran, Anjana; Tonta, Mary; Biben, Christine; Eichenlaub, Michael; Coleman, Harold A; Berger, Silke; Bouveret, Romaric; Singh, Reena; Harvey, Richard P; Ramialison, Mirana; Pearson, James T; Parkington, Helena C; Rosenthal, Nadia A; Costa, Mauro W

    2016-01-01

    Nkx2-5 is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5 gene dysfunction is the most common abnormality found in patients. Here we describe a novel mouse model and subsequent implications of Nkx2-5 loss for aspects of myocardial electrical activity. In this work we have engineered a new Nkx2-5 conditional knockout mouse in which flox sites flank the entire Nkx2-5 locus, and validated this line for the study of heart development, differentiation and disease using a full deletion strategy. While our homozygous knockout mice show typical embryonic malformations previously described for the lack of the Nkx2-5 gene, hearts of heterozygous adult mice show moderate morphological and functional abnormalities that are sufficient to sustain blood supply demands under homeostatic conditions. This study further reveals intriguing aspects of Nkx2-5 function in the control of cardiac electrical activity. Using a combination of mouse genetics, biochemistry, molecular and cell biology, we demonstrate that Nkx2-5 regulates the gene encoding Kcnh2 channel and others, shedding light on potential mechanisms generating electrical abnormalities observed in patients bearing NKX2-5 dysfunction and opening opportunities to the study of novel therapeutic targets for anti-arrhythmogenic therapies. PMID:26897459

  15. Microevolution of nematode miRNAs reveals diverse modes of selection.

    Science.gov (United States)

    Jovelin, Richard; Cutter, Asher D

    2014-01-01

    Micro-RNA (miRNA) genes encode abundant small regulatory RNAs that play key roles during development and in homeostasis by fine tuning and buffering gene expression. This layer of regulatory control over transcriptional networks is preserved by selection across deep evolutionary time, yet selection pressures on individual miRNA genes in contemporary populations remain poorly characterized in any organism. Here, we quantify nucleotide variability for 129 miRNAs in the genome of the nematode Caenorhabditis remanei to understand the microevolution of this important class of regulatory genes. Our analysis of three population samples and C. remanei's sister species revealed ongoing natural selection that constrains evolution of all sequence domains within miRNA hairpins. We also show that new miRNAs evolve faster than older miRNAs but that selection nevertheless favors their persistence. Despite the ongoing importance of purging of new mutations, we discover a trove of >400 natural miRNA sequence variants that include single nucleotide polymorphisms in seed motifs, indels that ablate miRNA functional domains, and origination of new miRNAs by duplication. Moreover, we demonstrate substantial nucleotide divergence of pre-miRNA hairpin alleles between populations and sister species. These findings from the first global survey of miRNA microevolution in Caenorhabditis support the idea that changes in gene expression, mediated through divergence in miRNA regulation, can contribute to phenotypic novelty and adaptation to specific environments in the present day as well as the distant past. PMID:25355809

  16. 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.

  17. 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.

  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. 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.

  20. Selection an Optimal Control Channel for STATCOM-Based Stabilizers to Damp Inter-Area Oscillation

    Directory of Open Access Journals (Sweden)

    A. Samanfar

    2014-01-01

    Full Text Available In static synchronous compensator (STATCOM a controllable AC voltage is generated by a voltage-source converter. There are two control channels for controlling of magnitude and phase of the voltage. When these devices are used for damping inter-are oscillations in multi-machine power systems, a damping stabilizer can be applied for both channels. In this paper, a method by quadratic mathematical programming has been presented to design of the damping stabilizer. By this method, the effect of the stabilizer in both control channels of the STATCOM on damping of inter-area oscillations has been assessed. Obtained results on a 2-area 4-machine power system shows that a STATCOM-based stabilizer in the phase control channel is more effective for damping inter-area oscillations than that of the magnitude control channel.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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. PMID:25616853

  6. Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes.

    Science.gov (United States)

    Wu, I; Shin, S C; Cao, Y; Bender, I K; Jafari, N; Feng, G; Lin, S; Cidlowski, J A; Schleimer, R P; Lu, N Z

    2013-01-01

    Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expressing the GR-A, -B, or -C, but not the GR-D, isoform. cDNA microarray analyses of cells sensitive (GR-C3) and insensitive (GR-D3) to DEX revealed glucocorticoid-induced proapoptotic transcriptomes. Genes that were regulated by the proapoptotic GR-C3, but not by the GR-D3, isoform likely contributed to glucocorticoid-induced apoptosis. The identified genes include those that are directly involved in apoptosis and those that facilitate cell killing. Chromatin immunoprecipitation assays demonstrated that distinct chromatin modification abilities may underlie the distinct functions of GR isoforms. Interestingly, all GR isoforms, including the GR-D3 isoform, suppressed mitogen-stimulated cytokines. Furthermore, the GR-C isoforms were selectively upregulated in mitogen-activated primary T cells and DEX treatment induced GR-C target genes in activated T cells. Cell-specific expressions and functions of GR isoforms may help to explain the tissue- and individual-selective actions of glucocorticoids and may provide a basis for developing improved glucocorticoids. PMID:23303127

  7. Mobile eye tracking reveals little evidence for age differences in attentional selection for mood regulation.

    Science.gov (United States)

    Isaacowitz, Derek M; Livingstone, Kimberly M; Harris, Julia A; Marcotte, Stacy L

    2015-04-01

    Two studies are reported representing the first use of mobile eye tracking to study emotion regulation across adulthood. Past research on age differences in attentional deployment using stationary eye tracking has revealed older adults show relatively more positive looking and seem to benefit more moodwise from this looking pattern, compared with younger adults. However, these past studies have greatly constrained the stimuli participants can look at, despite real-world settings providing numerous possibilities for what we choose to look at. The authors therefore used mobile eye tracking to study age differences in attentional selection, as indicated by fixation patterns to stimuli of different valence freely chosen by the participant. In contrast to stationary eye-tracking studies of attentional deployment, Study 1 showed that younger and older individuals generally selected similar proportions of valenced stimuli, and attentional selection had similar effects on mood across age groups. Study 2 replicated this pattern with an adult life span sample including middle-aged individuals. Emotion regulation-relevant attention may thus differ depending on whether stimuli are freely chosen or not. (PsycINFO Database Record PMID:25527965

  8. Adaptive antenna selection and Tx/Rx beamforming for large-scale MIMO systems in 60 GHz channels

    Directory of Open Access Journals (Sweden)

    Prasad Narayan

    2011-01-01

    Full Text Available Abstract We consider a large-scale MIMO system operating in the 60 GHz band employing beamforming for high-speed data transmission. We assume that the number of RF chains is smaller than the number of antennas, which motivates the use of antenna selection to exploit the beamforming gain afforded by the large-scale antenna array. However, the system constraint that at the receiver, only a linear combination of the receive antenna outputs is available, which together with the large dimension of the MIMO system makes it challenging to devise an efficient antenna selection algorithm. By exploiting the strong line-of-sight property of the 60 GHz channels, we propose an iterative antenna selection algorithm based on discrete stochastic approximation that can quickly lock onto a near-optimal antenna subset. Moreover, given a selected antenna subset, we propose an adaptive transmit and receive beamforming algorithm based on the stochastic gradient method that makes use of a low-rate feedback channel to inform the transmitter about the selected beams. Simulation results show that both the proposed antenna selection and the adaptive beamforming techniques exhibit fast convergence and near-optimal performance.

  9. 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.

  10. 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

  11. Contribution of the respiratory network to rhythm and motor output revealed by modulation of GIRK channels, somatostatin and neurokinin-1 receptors.

    Science.gov (United States)

    Montandon, Gaspard; Liu, Hattie; Horner, Richard L

    2016-01-01

    Breathing is generated by a respiratory network in the brainstem. At its core, a population of neurons expressing neurokinin-1 receptors (NK1R) and the peptide somatostatin (SST) form the preBötzinger Complex (preBötC), a site essential for the generation of breathing. PreBötC interneurons generate rhythm and follower neurons shape motor outputs by activating upper airway respiratory muscles. Since NK1R-expressing preBötC neurons are preferentially inhibited by μ-opioid receptors via activation of GIRK channels, NK1R stimulation may also involve GIRK channels. Hence, we identify the contribution of GIRK channels to rhythm, motor output and respiratory modulation by NK1Rs and SST. In adult rats, GIRK channels were identified in NK1R-expressing preBötC cells. Their activation decreased breathing rate and genioglossus muscle activity, an important upper airway muscle. NK1R activation increased rhythmic breathing and genioglossus muscle activity in wild-type mice, but not in mice lacking GIRK2 subunits (GIRK2(-/-)). Conversely, SST decreased rhythmic breathing via SST2 receptors, reduced genioglossus muscle activity likely through SST4 receptors, but did not involve GIRK channels. In summary, NK1R stimulation of rhythm and motor output involved GIRK channels, whereas SST inhibited rhythm and motor output via two SST receptor subtypes, therefore revealing separate circuits mediating rhythm and motor output. PMID:27599866

  12. 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.

  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; 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.

  14. 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.

  15. Miiuy croaker hepcidin gene and comparative analyses reveal evidence for positive selection.

    Directory of Open Access Journals (Sweden)

    Tianjun Xu

    Full Text Available Hepcidin antimicrobial peptide (HAMP is a small cysteine-rich peptide and a key molecule of the innate immune system against bacterial infections. Molecular cloning and genomic characterization of HAMP gene in the miiuy croaker (Miichthys miiuy were reported in this study. The miiuy croaker HAMP was predicted to encode a prepropeptide of 99 amino acids, a tentative RX(K/RR cleavage motif and eight characteristic cysteine residues were also identified. The gene organization is also similar to corresponding genes in mammals and fish consisting of three exons and two introns. Sequence polymorphism analysis showed that only two different sequences were identified and encoded two proteins in six individuals. As reported for most other species, the expression level was highest in liver and an up-regulation of transcription was seen in spleen, intestine and kidney examined at 24 h after injection of pathogenic bacteria, Vibrio anguillarum, the expression pattern implied that miiuy croaker HAMP is an important component of the first line defense against invading pathogens. In addition, we report on the underlying mechanism that maintains sequences diversity among fish and mammalian species, respectively. A series of site-model tests implemented in the CODEML program revealed that moderate positive Darwinian selection is likely to cause the molecular evolution in the fish HAMP2 genes and it also showed that the fish HAMP1 genes and HAMP2 genes under different selection pressures.

  16. Discrete-Time Block Models for Transmission Line Channels: Static and Doubly Selective Cases

    CERN Document Server

    Galli, Stefano

    2011-01-01

    Most methodologies for modeling Transmission Line (TL) based channels define the input-output relationship in the frequency domain (FD) and handle the TL resorting to a two-port network (2PN) formalism. These techniques have not yet been formally mapped into a discrete-time (DT) block model, which is useful to simulate and estimate the channel response as well as to design optimal precoding strategies. TL methods also fall short when they are applied to Time Varying (TV) systems, such as the power line channel. The objective of this paper is to establish if and how one can introduce a DT block model for the Power Line Channel. We prove that it is possible to use Lifting and Trailing Zeros (L&TZ) techniques to derive a DT block model that maps the TL-based input-output description directly in the time domain (TD) block channel model. More specifically, we find an interesting relationship between the elements of an ABCD matrix, defined in the FD, and filtering kernels that allow an elegant representation of...

  17. Allosteric modulators of the hERG K(+) channel: radioligand binding assays reveal allosteric characteristics of dofetilide analogs.

    Science.gov (United States)

    Yu, Zhiyi; Klaasse, Elisabeth; Heitman, Laura H; Ijzerman, Adriaan P

    2014-01-01

    Drugs that block the cardiac K(+) channel encoded by the human ether-à-go-go gene (hERG) have been associated with QT interval prolongation leading to proarrhythmia, and in some cases, sudden cardiac death. Because of special structural features of the hERG K(+) channel, it has become a promiscuous target that interacts with pharmaceuticals of widely varying chemical structures and a reason for concern in the pharmaceutical industry. The structural diversity suggests that multiple binding sites are available on the channel with possible allosteric interactions between them. In the present study, three reference compounds and nine compounds of a previously disclosed series were evaluated for their allosteric effects on the binding of [(3)H]astemizole and [(3)H]dofetilide to the hERG K(+) channel. LUF6200 was identified as an allosteric inhibitor in dissociation assays with both radioligands, yielding similar EC50 values in the low micromolar range. However, potassium ions increased the binding of the two radioligands in a concentration-dependent manner, and their EC50 values were not significantly different, indicating that potassium ions behaved as allosteric enhancers. Furthermore, addition of potassium ions resulted in a concentration-dependent leftward shift of the LUF6200 response curve, suggesting positive cooperativity and distinct allosteric sites for them. In conclusion, our investigations provide evidence for allosteric modulation of the hERG K(+) channel, which is discussed in the light of findings on other ion channels. PMID:24200993

  18. 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.

  19. 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.).

  20. 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.

  1. 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.

  2. 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

  3. Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel.

    Science.gov (United States)

    Murray, Justin K; Ligutti, Joseph; Liu, Dong; Zou, Anruo; Poppe, Leszek; Li, Hongyan; Andrews, Kristin L; Moyer, Bryan D; McDonough, Stefan I; Favreau, Philippe; Stöcklin, Reto; Miranda, Les P

    2015-03-12

    NaV1.7 is a voltage-gated sodium ion channel implicated by human genetic evidence as a therapeutic target for the treatment of pain. Screening fractionated venom from the tarantula Grammostola porteri led to the identification of a 34-residue peptide, termed GpTx-1, with potent activity on NaV1.7 (IC50 = 10 nM) and promising selectivity against key NaV subtypes (20× and 1000× over NaV1.4 and NaV1.5, respectively). NMR structural analysis of the chemically synthesized three disulfide peptide was consistent with an inhibitory cystine knot motif. Alanine scanning of GpTx-1 revealed that residues Trp(29), Lys(31), and Phe(34) near the C-terminus are critical for potent NaV1.7 antagonist activity. Substitution of Ala for Phe at position 5 conferred 300-fold selectivity against NaV1.4. A structure-guided campaign afforded additive improvements in potency and NaV subtype selectivity, culminating in the design of [Ala5,Phe6,Leu26,Arg28]GpTx-1 with a NaV1.7 IC50 value of 1.6 nM and >1000× selectivity against NaV1.4 and NaV1.5. PMID:25658507

  4. Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments.

    Science.gov (United States)

    Wichgers Schreur, Paul J; Kortekaas, Jeroen

    2016-08-01

    The bunyavirus genome comprises a small (S), medium (M), and large (L) RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization (FISH), the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus (RVFV) genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process. PMID:27548280

  5. 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...

  6. 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...

  7. Control of the selectivity of the aquaporin water channel family by global orientational tuning

    DEFF Research Database (Denmark)

    Jensen, Morten Østergaard; Tajkhorshid, E.; Nollert, P.;

    2002-01-01

    and orientation of a single file of seven to nine water molecules inside the channel. Two conserved asparagines force a central water molecule to serve strictly as a hydrogen bond donor to its neighboring water molecules. Assisted by the electrostatic potential generated by two half-membrane spanning loops......Aquaporins are transmembrane channels found in cell membranes of all life forms. We examine their apparently paradoxical property, facilitation of efficient permeation of water while excluding protons, which is of critical importance to preserving the electrochemical potential across the cell...... membrane. We have determined the structure of the Escherichia coli aquaglyceroporin GlpF with bound water, in native (2.7 angstroms) and in W48F/F200T mutant (2.1 angstroms) forms, and carried out 12-nanosecond molecular dynamics simulations that define the spatial and temporal probability distribution...

  8. 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.

  9. Ion slowing down and charge exchange at small impact parameters selected by channeling: superdensity effects

    OpenAIRE

    L'Hoir, A.; Adoui, A.; Barrué, F.; Billebaud, A.; Bosch, F.; Bräuning-Demian, A.; Bräuning, H.; Cassimi, A.; Chevallier, M.; C. Cohen; Dauvergne, D; Demonchy, C.E.; Giot, L.; Kirsch, R.; Gumberidze, A

    2005-01-01

    In two experiments performed with 20-30 MeV/u highly charged heavy ions (Pb56+, U91+) channeled through thin silicon crystals, we observed the original features of superdensity, associated to the glancing collisions with atomic rows undergone by part of the incident projectiles. In particular the very high collision rate yields a quite specific charge exchange regime, that leads to a higher ionization probability than in random conditions. X-ray measurements show that electrons captured in ou...

  10. 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.

  11. Resource-Based and Institutional Perspectives on Export Channel Selection and Export Performance

    OpenAIRE

    He, X; Brouthers, K. D.; Filatotchev, I.

    2012-01-01

    Exporting is a critically important strategy for firms to grow, yet research in this area has tended to ignore how firms can leverage resource-based capabilities to improve export performance. Building on the resource-based view and institutional theory, the authors develop a novel perspective to explain how a firm can improve export performance by aligning its export channel with its level of market orientation capabilities, contingent on the institutional distance between home and export ma...

  12. 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

  13. Multi-Feedback Interference Cancellation Algorithms for OFDM Systems over Doubly-Selective Channels

    Directory of Open Access Journals (Sweden)

    Peng Li

    2015-07-01

    Full Text Available Orthogonal frequency-division multiplexing (OFDM systems over rapidly time varying channels may suffer from significant inter-carrier interference (ICI, which destroys the orthogonality between subcarriers and degrades the detection performance. Without sufficient ICI suppression, OFDM systems usually experience an error floor. According to the approximate matched filter bound (AMFB, the error floor in a coded OFDM system is not irreducible. In this work, we introduce novel multiple feedback matched filter (MBMF-based ICI cancellation receivers. Based on the output of a novel MBMF scheme, the approach employs a multiple ICI cancellation strategy with or without signal-to-interference-plus-noise-ratio (SINR ordering. The developed schemes can significantly improve the performance and remove the error floor with a negligible complexity increase. Given the multiple cancellation approach, we compare the SINR performance of the MBMF outputs with that employing single feedback and show that the SINR performance with multiple cancellation candidates is improved over that with a single one at practical SNR values. Additionally, for time-varying channels, we exploit partial fast Fourier transform (PFFT by splitting one OFDM symbol into multiple segments; the channel state is separately estimated by least-squares (LS methods without inserting more pilots. Simulation results demonstrate the superiority of the proposed methods over serial and block equalizers and the robustness to the Doppler effects compared to conventional single-segment method.

  14. 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.

  15. 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.

  16. 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

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

    DEFF Research Database (Denmark)

    Wickelmaier, Florian Maria; Choisel, Sylvain

    2005-01-01

    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 of the......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, their...... 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....

  18. Scheduling algorithm to select $k$ optimal programme slots in television channels: A graph theoretic approach

    OpenAIRE

    Pal, Madhumangal; Pal, Anita

    2014-01-01

    In this paper, it is shown that all programmes of all television channels can be modelled as an interval graph. The programme slots are taken as the vertices of the graph and if the time duration of two {programme slots} have non-empty intersection, the corresponding vertices are considered to be connected by an edge. The number of viewers of a programme is taken as the weight of the vertex. A set of programmes that are mutually exclusive in respect of time scheduling is called a session. We ...

  19. 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

  20. Cycle Time Reduction in Injection Molding Process by Selection of Robust Cooling Channel Design

    OpenAIRE

    Muhammad Khan; S. Kamran Afaq; Nizar Ullah Khan; Saboor Ahmad

    2014-01-01

    Cycle time of a part in injection molding process is very important as the rate of production and the quality of the parts produced depend on it, whereas the cycle time of a part can be reduced by reducing the cooling time which can only be achieved by the uniform temperature distribution in the molded part which helps in quick dissipation of heat. Conformal cooling channel design is the solution to the problem which basically “conforms” to the shape of cavity in the molds. This paper describ...

  1. L-type Ca2+ channel sparklets revealed by TIRF microscopy in mouse urinary bladder smooth muscle.

    Science.gov (United States)

    Sidaway, Peter; Teramoto, Noriyoshi

    2014-01-01

    Calcium is a ubiquitous second messenger in urinary bladder smooth muscle (UBSM). In this study, small discrete elevations of intracellular Ca(2+), referred to as Ca(2+) sparklets have been detected in an intact detrusor smooth muscle electrical syncytium using a TIRF microscopy Ca(2+) imaging approach. Sparklets were virtually abolished by the removal of extracellular Ca(2+) (0.035 ± 0.01 vs. 0.23 ± 0.07 Hz/mm(2); Pmembrane. Ca(2+) sparklets were inhibited by the calcium channel inhibitors R-(+)-Bay K 8644 (1 μM) (0.034 ± 0.02 vs. 0.21 ± 0.08 Hz/mm(2); PCPA (10 μM), there was no apparent change in the overall frequency of Ca(2+) sparklets, although the sparklet frequencies of each UBSM became statistically independent of each other (Spearman's rank correlation 0.2, P>0.05), implying that Ca(2+) store mediated signals regulate Ca(2+) sparklets. Under control conditions, inhibition of store operated Ca(2+) entry using ML-9 (100 μM) had no significant effect. Amplitudes of Ca(2+) sparklets were unaffected by any agonists or antagonists, suggesting that these signals are quantal events arising from activation of a single channel, or complex of channels. The effects of CPA and ML-9 suggest that Ca(2+) sparklets regulate events in the cell membrane, and contribute to cytosolic and sarcoplasmic Ca(2+) concentrations. PMID:24699670

  2. Punishment-Induced Behavioral and Neurophysiological Variability Reveals Dopamine-Dependent Selection of Kinematic Movement Parameters

    OpenAIRE

    Galea, J. M.; Ruge, D.; Buijink, A.; Bestmann, S.; Rothwell, J. C.

    2013-01-01

    Action selection describes the high-level process which selects between competing movements. In animals, behavioural variability is critical for the motor exploration required to select the action which optimizes reward and minimizes cost/punishment, and is guided by dopamine (DA). The aim of this study was to test in humans whether low-level movement parameters are affected by punishment and reward in ways similar to high-level action selection. Moreover, we addressed the proposed dependence...

  3. CRSN轻量级信道选择算法%CRSN Lightweight Channel Selection Algorithm

    Institute of Scientific and Technical Information of China (English)

    傅宇; 余强; 余娜; 赵石真

    2015-01-01

    近年对认知无线电动态频谱接入技术研究基本上分为两类:频谱感知和基于概率预测,频谱感知直接获取物理层状态信息能更加准确,然而由于其算法一般较为复杂,能耗较高。提出一种轻量级算法,综合考虑信道及链路状态信息用以进行信道决策,仿真表明该算法在保持较低能耗的前提下提高系统的吞吐量,降低网络延迟。%In recent years, research on cognitive radio dynamic spectrum access technology is basically divided into two categories:spectrum sensing and probabilistic forecasting, spectrum sensing direct access to the physical layer status information is more accurate, because of their algorithm is generally more complex, higher energy consumption. Proposes a lightweight algorithm, considering the channel and link state information for decision-channel, simulation shows that the algorithm increases the throughput of the system reduces network latency under the premise of maintaining low power consumption.

  4. Analysis of maximal-ratio of transmitting/receiving antenna selection with perfect and partial channel information

    Institute of Scientific and Technical Information of China (English)

    Xiao XIAO; Guangxi ZHU; Lin ZHOU; Desheng WANG; Li LI

    2008-01-01

    To improve system performance and reduce the complexity and cost of receiver hardware, we investi-gated a new multiple-input multiple-output (MIMO) scheme combining maximal-ratio transmitting and receiver antenna selection (MRT/RAS). In this scheme, a single receiving antenna, which maximizes the signal-to-noise ratio (SNR) at the receiver, is selected for demodulation. The closed-form outage probability and the bit error rate (BER) of the MRT/RAS system are both presented. The simulation demonstrates that the MRT/ RAS scheme can achieve a full diversity order as if all the receiving antennas were used. It is shown that the MRT/RAS scheme outperforms some more complex space-time codes of the same spectral efficiency. The ana-lytical results are verified by simulation. In the end, we also analyze the MRT/RAS system based on partial chan-nel information.

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

    OpenAIRE

    Yuanliu Xu; Jiancheng Shi; Jinyang Du

    2015-01-01

    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....

  6. 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.

  7. 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.

  8. Elaborate cellulosome architecture of Acetivibrio cellulolyticus revealed by selective screening of cohesin–dockerin interactions

    Directory of Open Access Journals (Sweden)

    Yuval Hamberg

    2014-10-01

    Full Text Available Cellulosic waste represents a significant and underutilized carbon source for the biofuel industry. Owing to the recalcitrance of crystalline cellulose to enzymatic degradation, it is necessary to design economical methods of liberating the fermentable sugars required for bioethanol production. One route towards unlocking the potential of cellulosic waste lies in a highly complex class of molecular machines, the cellulosomes. Secreted mainly by anaerobic bacteria, cellulosomes are structurally diverse, cell surface-bound protein assemblies that can contain dozens of catalytic components. The key feature of the cellulosome is its modularity, facilitated by the ultra-high affinity cohesin–dockerin interaction. Due to the enormous number of cohesin and dockerin modules found in a typical cellulolytic organism, a major bottleneck in understanding the biology of cellulosomics is the purification of each cohesin- and dockerin-containing component, prior to analyses of their interaction. As opposed to previous approaches, the present study utilized proteins contained in unpurified whole-cell extracts. This strategy was made possible due to an experimental design that allowed for the relevant proteins to be “purified” via targeted affinity interactions as a function of the binding assay. The approach thus represents a new strategy, appropriate for future medium- to high-throughput screening of whole genomes, to determine the interactions between cohesins and dockerins. We have selected the cellulosome of Acetivibrio cellulolyticus for this work due to its exceptionally complex cellulosome systems and intriguing diversity of its cellulosomal modular components. Containing 41 cohesins and 143 dockerins, A. cellulolyticus has one of the largest number of potential cohesin–dockerin interactions of any organism, and contains unusual and novel cellulosomal features. We have surveyed a representative library of cohesin and dockerin modules spanning the

  9. 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.

  10. 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.

  11. Structure of a Bacterial Virus DNA-Injection Protein Complex Reveals a Decameric Assembly with a Constricted Molecular Channel.

    Directory of Open Access Journals (Sweden)

    Haiyan Zhao

    Full Text Available The multi-layered cell envelope structure of Gram-negative bacteria represents significant physical and chemical barriers for short-tailed phages to inject phage DNA into the host cytoplasm. Here we show that a DNA-injection protein of bacteriophage Sf6, gp12, forms a 465-kDa, decameric assembly in vitro. The electron microscopic structure of the gp12 assembly shows a ~150-Å, mushroom-like architecture consisting of a crown domain and a tube-like domain, which embraces a 25-Å-wide channel that could precisely accommodate dsDNA. The constricted channel suggests that gp12 mediates rapid, uni-directional injection of phage DNA into host cells by providing a molecular conduit for DNA translocation. The assembly exhibits a 10-fold symmetry, which may be a common feature among DNA-injection proteins of P22-like phages and may suggest a symmetry mismatch with respect to the 6-fold symmetric phage tail. The gp12 monomer is highly flexible in solution, supporting a mechanism for translocation of the protein through the conduit of the phage tail toward the host cell envelope, where it assembles into a DNA-injection device.

  12. L-type Ca2+ channel sparklets revealed by TIRF microscopy in mouse urinary bladder smooth muscle.

    Directory of Open Access Journals (Sweden)

    Peter Sidaway

    Full Text Available Calcium is a ubiquitous second messenger in urinary bladder smooth muscle (UBSM. In this study, small discrete elevations of intracellular Ca(2+, referred to as Ca(2+ sparklets have been detected in an intact detrusor smooth muscle electrical syncytium using a TIRF microscopy Ca(2+ imaging approach. Sparklets were virtually abolished by the removal of extracellular Ca(2+ (0.035 ± 0.01 vs. 0.23 ± 0.07 Hz/mm(2; P0.05, implying that Ca(2+ store mediated signals regulate Ca(2+ sparklets. Under control conditions, inhibition of store operated Ca(2+ entry using ML-9 (100 μM had no significant effect. Amplitudes of Ca(2+ sparklets were unaffected by any agonists or antagonists, suggesting that these signals are quantal events arising from activation of a single channel, or complex of channels. The effects of CPA and ML-9 suggest that Ca(2+ sparklets regulate events in the cell membrane, and contribute to cytosolic and sarcoplasmic Ca(2+ concentrations.

  13. Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity

    NARCIS (Netherlands)

    Fawcett, Tim W.; Kuijper, Bram; Weissing, Franz J.; Pen, Ido

    2011-01-01

    Female choice is a powerful selective force, driving the elaboration of conspicuous male ornaments. This process of sexual selection has profound implications for many life-history decisions, including sex allocation. For example, females with attractive partners should produce more sons, because th

  14. 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.

  15. Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia.

    Science.gov (United States)

    Conforti, L; Millhorn, D E

    1997-07-15

    1. Electrophysiological (single-channel patch clamp) and molecular biological experiments (reverse transcriptase-polymerase chain reaction) were performed to attempt to identify the O2-sensitive K+ channel in rat phaeochromocytoma (PC12) cells. 2. Four types of K+ channels were recorded in PC12 cells: a small-conductance K+ channel (14 pS), a calcium-activated K+ channel (KCa; 102 pS) and two K+ channels with similar conductance (20 pS). These last two channels differed in their time-dependent inactivation: one was a slow-inactivating channel, while the other belonged to the family of fast transient K+ channels. 3. The slow-inactivating 20 pS K+ channel was inhibited by hypoxia. Exposure to hypoxia produced a 50% reduction in channel activity (number of active channels in the patch x open probability). Hypoxia had no effect on the 20 pS transient K+ channels, whereas reduced O2 stimulated the KCa channels. 4. The genes encoding the alpha-subunits of slow-inactivating K+ channels for two members of the Shaker subfamily of K+ channels (Kv1.2 and Kv1.3) together with the Kv2.1, Kv3.1 and Kv3.2 channel genes were identified in PC12 cells. 5. The expression of the Shaker Kv1.2, but none of the other K+ channel genes, increased in cells exposed to prolonged hypoxia (18 h). The same cells were more responsive to a subsequent exposure to hypoxia (35% inhibition of K+ current measured in whole-cell voltage clamp) compared with the cells maintained in normoxia (19% inhibition). 6. These results indicate that the O2-sensitive K+ channel in PC12 cells is a 20 pS slow-inactivating K+ channel that is upregulated by hypoxia. This channel appears to belong to the Shaker subfamily of voltage-gated K+ channels. PMID:9263911

  16. Relay selection for multiple access relay channel with decode-forward and analog network coding

    CERN Document Server

    Hassan, Ahmed Hassan M; Huang, Benxiong; Eisa, Edriss; Azhar, Muhammad

    2012-01-01

    This paper presents a relay selection for decode-and-forward based on network coding (DF-NC) and analog-NC protocols in general scheme of cellular network system. In the propose scheme the two source node simultaneously transmit their own information to all the relays as well as the destination node, and then, a single relay i.e. best with a minimum symbol error rate (SER) will be selected to forward the new version of the received signal. Simulation results show that, the DF-NC scheme with considerable performance has exactness over analog-NC scheme. To improve the system performance, optimal power allocation between the two sources and the best relay is determined based on the asymptotic SER. By increasing the number of relays node, the optimum power allocation achieve better performance than asymptotic SER.

  17. Perceptual load manipulation reveals sensitivity of the face-selective N170 to attention.

    Science.gov (United States)

    Mohamed, Tarik N; Neumann, Markus F; Schweinberger, Stefan R

    2009-05-27

    It has been controversial whether the face-sensitive N170 is affected by selective attention. We manipulated attention sensu Lavie's perceptual load theory to short (200 ms) presentations of task-irrelevant unfamiliar faces or houses, while participants identified superimposed target letters 'X' versus 'N'. These targets were strings of either six identical (low load) or six different letters (high load). Under low load, we found a prominent face-selective N170 response. Under high load, however, we not only observed a dramatic reduction of the face N170 but also an unexpected enhancement of the house N170, such that face selectivity was almost completely lost. We conclude that the early stages of face processing indexed by the N170 strongly depend on selective attention. PMID:19369907

  18. 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.

  19. 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.

  20. Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

    Science.gov (United States)

    Petersen, Jessica L.; Mickelson, James R.; Rendahl, Aaron K.; Valberg, Stephanie J.; Andersson, Lisa S.; Axelsson, Jeanette; Bailey, Ernie; Bannasch, Danika; Binns, Matthew M.; Borges, Alexandre S.; Brama, Pieter; da Câmara Machado, Artur; Capomaccio, Stefano; Cappelli, Katia; Cothran, E. Gus; Distl, Ottmar; Fox-Clipsham, Laura; Graves, Kathryn T.; Guérin, Gérard; Haase, Bianca; Hasegawa, Telhisa; Hemmann, Karin; Hill, Emmeline W.; Leeb, Tosso; Lindgren, Gabriella; Lohi, Hannes; Lopes, Maria Susana; McGivney, Beatrice A.; Mikko, Sofia; Orr, Nicholas; Penedo, M. Cecilia T.; Piercy, Richard J.; Raekallio, Marja; Rieder, Stefan; Røed, Knut H.; Swinburne, June; Tozaki, Teruaki; Vaudin, Mark; Wade, Claire M.; McCue, Molly E.

    2013-01-01

    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 FST-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. PMID:23349635

  1. Experimental selection reveals a trade-off between fecundity and lifespan in the coliphage Qß

    OpenAIRE

    García-Villada, Libertad; Drake, John W.

    2013-01-01

    Understanding virus evolution is key for improving ways to counteract virus-borne diseases. Results from comparative analyses have previously suggested a trade-off between fecundity and lifespan for viruses that infect the bacterium Escherichia coli (i.e. for coliphages), which, if confirmed, would define a particular constraint on the evolution of virus fecundity. Here, the occurrence of such a trade-off is investigated through a selection experiment using the coliphage Qß. Selection was app...

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

    Directory of Open Access Journals (Sweden)

    Vaze Rahul

    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.

  3. Development of selective blockers for Ca2+-activated Cl- channel using Xenopus laevis oocytes with an improved drug screening strategy

    Directory of Open Access Journals (Sweden)

    Oh Soo-Jin

    2008-10-01

    Full Text Available Abstract Background Ca2+-activated Cl- channels (CaCCs participate in many important physiological processes. However, the lack of effective and selective blockers has hindered the study of these channels, mostly due to the lack of good assay system. Here, we have developed a reliable drug screening method for better blockers of CaCCs, using the endogeneous CaCCs in Xenopus laevis oocytes and two-electrode voltage-clamp (TEVC technique. Results Oocytes were prepared with a treatment of Ca2+ ionophore, which was followed by a treatment of thapsigargin which depletes Ca2+ stores to eliminate any contribution of Ca2+ release. TEVC was performed with micropipette containing chelerythrine to prevent PKC dependent run-up or run-down. Under these conditions, Ca2+-activated Cl- currents induced by bath application of Ca2+ to oocytes showed stable peak amplitude when repetitively activated, allowing us to test several concentrations of a test compound from one oocyte. Inhibitory activities of commercially available blockers and synthesized anthranilic acid derivatives were tested using this method. As a result, newly synthesized N-(4-trifluoromethylphenylanthranilic acid with trifluoromethyl group (-CF3 at para position on the benzene ring showed the lowest IC50. Conclusion Our results provide an optimal drug screening strategy suitable for high throughput screening, and propose N-(4-trifluoromethylphenylanthranilic acid as an improved CaCC blocker.

  4. 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.

  5. 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.

  6. 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. PMID:27262660

  7. 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.

  8. 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.

  9. Multi-agent Q-Learning of Channel Selection in Multi-user Cognitive Radio Systems: A Two by Two Case

    OpenAIRE

    Li, Husheng

    2009-01-01

    Resource allocation is an important issue in cognitive radio systems. It can be done by carrying out negotiation among secondary users. However, significant overhead may be incurred by the negotiation since the negotiation needs to be done frequently due to the rapid change of primary users' activity. In this paper, a channel selection scheme without negotiation is considered for multi-user and multi-channel cognitive radio systems. To avoid collision incurred by non-coordination, each user s...

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Meaning Making: What Reflective Essays Reveal about Biology Students' Conceptions about Natural Selection

    Science.gov (United States)

    Balgopal, Meena M.; Montplaisir, Lisa M.

    2011-01-01

    The process of reflective writing can play a central role in making meaning as learners process new information and connect it to prior knowledge. An examination of the written discourse can therefore be revealing of learners' cognitive understanding and affective (beliefs, feelings, motivation to learn) responses to concepts. Despite reflective…

  15. Some remarks on the selection of exit channels in the theoretical description of dissociative recombination

    Directory of Open Access Journals (Sweden)

    Guberman Steven L.

    2015-01-01

    Full Text Available The need for the careful selection of dissociative routes for inclusion in the theoretical calculation of accurate dissociative recombination (DR cross sections and rate constants is discussed. For total energies corresponding to the sum of the “free” electron energy plus the ion vibrational energy, all neutral diabatic curves that fall between or near the turning points of the highest Rydberg vibrational levels with the same electronic symmetry need to be included in the calculation. This is especially the case if there are several dissociative routes of the same electronic symmetry that satisfy this criterion. Also, care must be exercised in the exclusion of dissociative routes having relatively small electron capture widths. Examples from theoretical studies of the dissociative recombination (DR of N2+ are used as illustrations.

  16. 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

  17. 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

  18. 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

  19. A clickable neurosteroid photolabel reveals selective Golgi compartmentalization with preferential impact on proximal inhibition.

    Science.gov (United States)

    Jiang, Xiaoping; Shu, Hong-Jin; Krishnan, Kathiresan; Qian, Mingxing; Taylor, Amanda A; Covey, Douglas F; Zorumski, Charles F; Mennerick, Steven

    2016-09-01

    Anesthetic, GABA-active neurosteroids potently augment GABAA receptor function, leading to important behavioral consequences. Neurosteroids and their synthetic analogues are also models for a wide variety of cell-permeant neuroactive compounds. Cell permeation and compartmentalization raise the possibility that these compounds' actions are influenced by their cellular partitioning, but these contributions are not typically considered experimentally or therapeutically. To examine the interplay between cellular accumulation and pharmacodynamics of neurosteroids, we synthesized a novel chemical biology analogue (bio-active, clickable photolabel) of GABA-active neurosteroids. We discovered that the analogue selectively photo-labels neuronal Golgi in rat hippocampal neurons. The active analogue's selective distribution was distinct from endogenous cholesterol and not completely shared by some non-GABA active, neurosteroid-like analogues. On the other hand, the distribution was not enantioselective and did not require energy, in contrast to other recent precedents from the literature. We demonstrate that the soma-selective accumulation can act as a sink or source for steroid actions at plasma-membrane GABA receptors, altering steady-state and time course of effects at somatic GABAA receptors relative to dendritic receptors. Our results suggest a novel mechanism for compartment-selective drug actions at plasma-membrane receptors. PMID:27114255

  20. Genome-wide view of genetic diversity reveals paths of selection and cultivar differentiation in peach domestication.

    Science.gov (United States)

    Akagi, Takashi; Hanada, Toshio; Yaegaki, Hideaki; Gradziel, Thomas M; Tao, Ryutaro

    2016-06-01

    Domestication and cultivar differentiation are requisite processes for establishing cultivated crops. These processes inherently involve substantial changes in population structure, including those from artificial selection of key genes. In this study, accessions of peach (Prunus persica) and its wild relatives were analysed genome-wide to identify changes in genetic structures and gene selections associated with their differentiation. Analysis of genome-wide informative single-nucleotide polymorphism loci revealed distinct changes in genetic structures and delineations among domesticated peach and its wild relatives and among peach landraces and modern fruit (F) and modern ornamental (O-A) cultivars. Indications of distinct changes in linkage disequilibrium extension/decay and of strong population bottlenecks or inbreeding were identified. Site frequency spectrum- and extended haplotype homozygosity-based evaluation of genome-wide genetic diversities supported selective sweeps distinguishing the domesticated peach from its wild relatives and each F/O-A cluster from the landrace clusters. The regions with strong selective sweeps harboured promising candidates for genes subjected to selection. Further sequence-based evaluation further defined the candidates and revealed their characteristics. All results suggest opportunities for identifying critical genes associated with each differentiation by analysing genome-wide genetic diversity in currently established populations. This approach obviates the special development of genetic populations, which is particularly difficult for long-lived tree crops. PMID:27085183

  1. 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.

  2. Isolation, synthesis and characterization of ω-TRTX-Cc1a, a novel tarantula venom peptide that selectively targets L-type Cav channels.

    Science.gov (United States)

    Klint, Julie K; Berecki, Géza; Durek, Thomas; Mobli, Mehdi; Knapp, Oliver; King, Glenn F; Adams, David J; Alewood, Paul F; Rash, Lachlan D

    2014-05-15

    Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba(2+) currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC50) values of 825nM and 2.24μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV channels but did not affect low voltage-activated T-type CaV channels. Cc1a exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1-E5) or C-terminus (ΔW35-V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type CaV channels. PMID:24561180

  3. A trait-based approach reveals the feeding selectivity of a small endangered Mediterranean fish.

    Science.gov (United States)

    Rodríguez-Lozano, Pablo; Verkaik, Iraima; Maceda-Veiga, Alberto; Monroy, Mario; de Sostoa, Adolf; Rieradevall, Maria; Prat, Narcís

    2016-05-01

    Functional traits are growing in popularity in modern ecology, but feeding studies remain primarily rooted in a taxonomic-based perspective. However, consumers do not have any reason to select their prey using a taxonomic criterion, and prey assemblages are variable in space and time, which makes taxon-based studies assemblage-specific. To illustrate the benefits of the trait-based approach to assessing food choice, we studied the feeding ecology of the endangered freshwater fish Barbus meridionalis. We hypothesized that B. meridionalis is a selective predator which food choice depends on several prey morphological and behavioral traits, and thus, its top-down pressure may lead to changes in the functional composition of in-stream macroinvertebrate communities. Feeding selectivity was inferred by comparing taxonomic and functional composition (13 traits) between ingested and free-living potential prey using the Jacob's electivity index. Our results showed that the fish diet was influenced by 10 of the 13 traits tested. Barbus meridionalis preferred prey with a potential size of 5-10 mm, with a medium-high drift tendency, and that drift during daylight. Potential prey with no body flexibility, conical shape, concealment traits (presence of nets and/or cases, or patterned coloration), and high aggregation tendency had a low predation risk. Similarly, surface swimmers and interstitial taxa were low vulnerable to predation. Feeding selectivity altered the functional composition of the macroinvertebrate communities. Fish absence favored taxa with weak aggregation tendency, weak flexibility, and a relatively large size (10-20 mm of potential size). Besides, predatory invertebrates may increase in fish absence. In conclusion, our study shows that the incorporation of the trait-based approach in diet studies is a promising avenue to improve our mechanistic understanding of predator-prey interactions and to help predict the ecological outcomes of predator invasions and

  4. Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes

    OpenAIRE

    Wu, I; Shin, S. C.; Cao, Y; Bender, I K; N Jafari; Feng, G.; Lin, S.; Cidlowski, J. A.; Schleimer, R. P.; Lu, N Z

    2013-01-01

    Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expres...

  5. Selection on Human Genes as Revealed by Comparisons to Chimpanzee cDNA

    OpenAIRE

    Hellmann, Ines; Zöllner, Sebastian; Enard, Wolfgang; Ebersberger , Ingo; Nickel, Birgit; Pääbo, Svante

    2003-01-01

    To better understand the evolutionary forces that affect human genes, we sequenced 5055 expressed sequence tags from the chimpanzee and compared them to their human counterparts. In conjunction with intergenic chimpanzee DNA sequences and data on human single-nucleotide polymorphisms in the genes studied, this allows us to gauge the extent to which selection affects human genes at a genome-wide scale. The comparison to intergenic DNA sequences indicates that about 39% of silent sites in prote...

  6. 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.

  7. Channel selection and pricing with channel preference dependent demand%需求与渠道偏好相关下渠道选择和定价研究

    Institute of Scientific and Technical Information of China (English)

    王志宏; 张小翠

    2011-01-01

    建立了由一个制造商和一个零售商组成的双渠道供应链模型,考虑了市场需求与消费者渠道偏好相关时,制造商的定价和渠道设计选择问题.分别讨论了供应链制造商集中控制和分散控制两种控制模式下制造商采取以下三种不同渠道策略时在定价、需求和收益方面的差异:只有传统渠道、只有电子渠道、双渠道.分析发现双渠道的有效性取决于消费者属性和渠道成本两大因素.双渠道不影响制造商的定价,并刺激了新的市场需求,提高了制造商和供应链的利润.同时双渠道降低了分散控制下零售商的定价及需求,造成了零售商的利润亏损.最后通过算例仿真,验证了结论的正确性.%We develop a dual-channel supply chain model with a single manufacturer and retailer,considering channel selection and pricing strategy with consumers' channel preference dependent demand.Manufacturers have three different distribution options:(1) only a retail channel,(2) only a e-tail channel,(3) dual-channel.We compare the differences in pricing and demand as well as profit of dual-channel with other distribution strategies both in the condition of a integrated supply chain and non-integrated supply chain.It is found that the effectiveness of dual-channel depends on consumer attributes and channel costs.Dual-channel strategy will not affect the pricing of the manufacturer,and will stimulate new demands,so it will improve the profits of the supply chain and the manufacturer.Meanwhile,dual-channel will cut down the price and demand of retail channel in a non-integrated supply chain,so it will reduce retailer's profit.At last,we illustrate our analytical results with some examples,and the proposed conclusions are validated.

  8. Complex Selection on Human Polyadenylation Signals Revealed by Polymorphism and Divergence Data

    Science.gov (United States)

    Kainov, Yaroslav A.; Aushev, Vasily N.; Naumenko, Sergey A.; Tchevkina, Elena M.; Bazykin, Georgii A.

    2016-01-01

    Polyadenylation is a step of mRNA processing which is crucial for its expression and stability. The major polyadenylation signal (PAS) represents a nucleotide hexamer that adheres to the AATAAA consensus sequence. Over a half of human genes have multiple cleavage and polyadenylation sites, resulting in a great diversity of transcripts differing in function, stability, and translational activity. Here, we use available whole-genome human polymorphism data together with data on interspecies divergence to study the patterns of selection acting on PAS hexamers. Common variants of PAS hexamers are depleted of single nucleotide polymorphisms (SNPs), and SNPs within PAS hexamers have a reduced derived allele frequency (DAF) and increased conservation, indicating prevalent negative selection; at the same time, the SNPs that “improve” the PAS (i.e., those leading to higher cleavage efficiency) have increased DAF, compared to those that “impair” it. SNPs are rarer at PAS of “unique” polyadenylation sites (one site per gene); among alternative polyadenylation sites, at the distal PAS and at exonic PAS. Similar trends were observed in DAFs and divergence between species of placental mammals. Thus, selection permits PAS mutations mainly at redundant and/or weakly functional PAS. Nevertheless, a fraction of the SNPs at PAS hexamers likely affect gene functions; in particular, some of the observed SNPs are associated with disease. PMID:27324920

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

    Science.gov (United States)

    Takacs-Vesbach, Cristina; Inskeep, William P; Jay, Zackary J; Herrgard, Markus J; Rusch, Douglas B; Tringe, Susannah G; Kozubal, Mark A; Hamamura, Natsuko; Macur, Richard E; Fouke, Bruce W; Reysenbach, Anna-Louise; McDermott, Timothy R; Jennings, Ryan deM; Hengartner, Nicolas W; Xie, Gary

    2013-01-01

    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 circum-neutral pH (6.5-7.8) sites containing dissolved sulfide were dominated by Sulfurihydrogenibium spp. (Hydrogenothermaceae). Thermocrinis (Aquificaceae) populations were found primarily in the circum-neutral 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.

  10. 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.

  11. A Novel Binding Mode Reveals Two Distinct Classes of NMDA Receptor GluN2B-selective Antagonists.

    Science.gov (United States)

    Stroebel, David; Buhl, Derek L; Knafels, John D; Chanda, Pranab K; Green, Michael; Sciabola, Simone; Mony, Laetitia; Paoletti, Pierre; Pandit, Jayvardhan

    2016-05-01

    N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels that play key roles in brain physiology and pathology. Because numerous pathologic conditions involve NMDAR overactivation, subunit-selective antagonists hold strong therapeutic potential, although clinical successes remain limited. Among the most promising NMDAR-targeting drugs are allosteric inhibitors of GluN2B-containing receptors. Since the discovery of ifenprodil, a range of GluN2B-selective compounds with strikingly different structural motifs have been identified. This molecular diversity raises the possibility of distinct binding sites, although supporting data are lacking. Using X-ray crystallography, we show that EVT-101, a GluN2B antagonist structurally unrelated to the classic phenylethanolamine pharmacophore, binds at the same GluN1/GluN2B dimer interface as ifenprodil but adopts a remarkably different binding mode involving a distinct subcavity and receptor interactions. Mutagenesis experiments demonstrate that this novel binding site is physiologically relevant. Moreover, in silico docking unveils that GluN2B-selective antagonists broadly divide into two distinct classes according to binding pose. These data widen the allosteric and pharmacological landscape of NMDARs and offer a renewed structural framework for designing next-generation GluN2B antagonists with therapeutic value for brain disorders. PMID:26912815

  12. Breeding signature of combining ability improvement revealed by a genomic variation map from recurrent selection population in Brassica napus

    Science.gov (United States)

    Zhao, Xinwang; Li, Bao; Zhang, Ka; Hu, Kaining; Yi, Bin; Wen, Jing; Ma, Chaozhi; Shen, Jinxiong; Fu, Tingdong; Tu, Jinxing

    2016-01-01

    Combining ability is crucial for parent selection in crop hybrid breeding. The present investigation and results had revealed the underlying genetic factors which might contribute in adequate combining ability, further assisting in enhancing heterosis and stability. Here, we conducted a large-scale analysis of genomic variation in order to define genomic regions affecting the combining ability in recurrent selection population of rapeseed. A population of 175 individuals was genotyped with the Brassica60K SNP chip. 525 hybrids were assembled with three different testers and used to evaluate the general combining ability (GCA) in three environments. By detecting the changes of the genomic variation, we identified 376 potential genome regions, spanning 3.03% of rapeseed genome which provided QTL-level resolution on potentially selected variants. More than 96% of these regions were located in the C subgenome, indicating that C subgenome had sustained stronger selection pressure in the breeding program than the A subgenome. In addition, a high level of linkage disequilibrium in rapeseed genome was detected, suggesting that marker-assisted selection for the population improvement might be easily implemented. This study outlines the evidence for high GCA on a genomic level and provided underlying molecular mechanism for recurrent selection improvement in B. napus. PMID:27412721

  13. Breeding signature of combining ability improvement revealed by a genomic variation map from recurrent selection population in Brassica napus.

    Science.gov (United States)

    Zhao, Xinwang; Li, Bao; Zhang, Ka; Hu, Kaining; Yi, Bin; Wen, Jing; Ma, Chaozhi; Shen, Jinxiong; Fu, Tingdong; Tu, Jinxing

    2016-01-01

    Combining ability is crucial for parent selection in crop hybrid breeding. The present investigation and results had revealed the underlying genetic factors which might contribute in adequate combining ability, further assisting in enhancing heterosis and stability. Here, we conducted a large-scale analysis of genomic variation in order to define genomic regions affecting the combining ability in recurrent selection population of rapeseed. A population of 175 individuals was genotyped with the Brassica60K SNP chip. 525 hybrids were assembled with three different testers and used to evaluate the general combining ability (GCA) in three environments. By detecting the changes of the genomic variation, we identified 376 potential genome regions, spanning 3.03% of rapeseed genome which provided QTL-level resolution on potentially selected variants. More than 96% of these regions were located in the C subgenome, indicating that C subgenome had sustained stronger selection pressure in the breeding program than the A subgenome. In addition, a high level of linkage disequilibrium in rapeseed genome was detected, suggesting that marker-assisted selection for the population improvement might be easily implemented. This study outlines the evidence for high GCA on a genomic level and provided underlying molecular mechanism for recurrent selection improvement in B. napus. PMID:27412721

  14. Subtype-selective activation of K(v)7 channels by AaTXKβ₂₋₆₄, a novel toxin variant from the Androctonus australis scorpion venom.

    Science.gov (United States)

    Landoulsi, Zied; Miceli, Francesco; Palmese, Angelo; Amoresano, Angela; Marino, Gennaro; El Ayeb, Mohamed; Taglialatela, Maurizio; Benkhalifa, Rym

    2013-11-01

    K(v)7.4 channel subunits are expressed in central auditory pathways and in inner ear sensory hair cells and skeletal and smooth muscle cells. Openers of K(v)7.4 channels have been suggested to improve hearing loss, systemic or pulmonary arterial hypertension, urinary incontinence, gastrointestinal and neuropsychiatric diseases, and skeletal muscle disorders. Scorpion venoms are a large source of peptides active on K⁺ channels. Therefore, we have optimized a combined purification/screening procedure to identify specific modulator(s) of K(v)7.4 channels from the venom of the North African scorpion Androctonus australis (Aa). We report the isolation and functional characterization of AaTXKβ₂₋₆₄, a novel variant of AaTXKβ₁₋₆₄, in a high-performance liquid chromatography fraction from Aa venom (named P8), which acts as the first peptide activator of K(v)7.4 channels. In particular, in both Xenopus oocytes and mammalian Chinese hamster ovary cells, AaTXKβ₂₋₆₄, but not AaTXKβ₁₋₆₄, hyperpolarized the threshold voltage of current activation and increased the maximal currents of heterologously expressed K(v)7.4 channels. AaTXKβ₂₋₆₄ also activated K(v)7.3, K(v)7.2/3, and K(v)7.5/3 channels, whereas homomeric K(v)1.1, K(v)7.1, and K(v)7.2 channels were unaffected. We anticipate that these results may prove useful in unraveling the novel biologic roles of AaTXKβ₂₋₆₄-sensitive K(v)7 channels and developing novel pharmacologic tools that allow subtype-selective targeting of K(v)7 channels. PMID:24019223

  15. [3H]TA-3090, a selective benzothiazepine-type calcium channel receptor antagonist: In vitro characterization

    International Nuclear Information System (INIS)

    Binding of the new benzothiazepine calcium channel blocker, (+)-(2S,3S)-3-acetoxy-8-chloro-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2- (4- methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one maleate, [3H]TA-3090, was characterized and its specificity for rat myocardial benzothiazepine receptors described. Scatchard plots and nonlinear regression analysis of specific [3H]TA-3090 binding best fit a one-site binding model (Kd = 8.8 +/- 2.7 nM, Bmax = 132 +/- 38 fmol/mg protein). Kinetically derived affinity constants were in close agreement (Kd = 7.86 nM) with those obtained from analysis of equilibrium binding data. In comparison, under identical conditions [3H]diltiazem exhibited a Kd of 38 nM and Bmax, 106 fmol/mg protein. Specific binding was saturable, reversible and stereoselective (d-cis-TA-3090 Ki = 14 nM; 1-cis-TA-3090 Ki = 2700 nM). Competitions for [3H]TA-3090 binding were conducted with nifedipine, propranolol, prazosin, quinuclidinyl benzilate, verapamil and yohimbine. Only the calcium channel blockers nifedipine and verapamil inhibited specific [3H]TA-3090 binding. Nifedipine could maximally inhibit only 52% of specifically bound [3H]TA-3090 at 10 microM. In contrast, however, 10 microM verapamil completely inhibited specific radioligand binding (Ki = 93 +/- 28 nM) but with six times less efficacy than TA-3090. Thus, these data demonstrate that [3H]TA-3090 is a potent radioligand selective for the benzothiazepine binding site and is consistent with the hypothesis that [3H]TA-3090 interacts with a myocardial benzothiazepine receptor site

  16. 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.

  17. 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.

  18. Splicing reporter mice revealed the evolutionally conserved switching mechanism of tissue-specific alternative exon selection.

    Directory of Open Access Journals (Sweden)

    Akihide Takeuchi

    Full Text Available Since alternative splicing of pre-mRNAs is essential for generating tissue-specific diversity in proteome, elucidating its regulatory mechanism is indispensable to understand developmental process or tissue-specific functions. We have been focusing on tissue-specific regulation of mutually exclusive selection of alternative exons because this implies the typical molecular mechanism of alternative splicing regulation and also can be good examples to elicit general rule of "splice code". So far, mutually exclusive splicing regulation has been explained by the outcome from the balance of multiple regulators that enhance or repress either of alternative exons discretely. However, this "balance" model is open to questions of how to ensure the selection of only one appropriate exon out of several candidates and how to switch them. To answer these questions, we generated an original bichromatic fluorescent splicing reporter system for mammals using fibroblast growth factor-receptor 2 (FGFR2 gene as model. By using this splicing reporter, we demonstrated that FGFR2 gene is regulated by the "switch-like" mechanism, in which key regulators modify the ordered splice-site recognition of two mutually exclusive exons, eventually ensure single exon selection and their distinct switching. Also this finding elucidated the evolutionally conserved "splice code," in which combination of tissue-specific and broadly expressed RNA binding proteins regulate alternative splicing of specific gene in a tissue-specific manner. These findings provide the significant cue to understand how a number of spliced genes are regulated in various tissue-specific manners by a limited number of regulators, eventually to understand developmental process or tissue-specific functions.

  19. Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis

    Directory of Open Access Journals (Sweden)

    Kalyan S. Chakrabarti

    2016-01-01

    Full Text Available Molecular recognition plays a central role in biology, and protein dynamics has been acknowledged to be important in this process. However, it is highly debated whether conformational changes happen before ligand binding to produce a binding-competent state (conformational selection or are caused in response to ligand binding (induced fit. Proposals for both mechanisms in protein/protein recognition have been primarily based on structural arguments. However, the distinction between them is a question of the probabilities of going via these two opposing pathways. Here, we present a direct demonstration of exclusive conformational selection in protein/protein recognition by measuring the flux for rhodopsin kinase binding to its regulator recoverin, an important molecular recognition in the vision system. Using nuclear magnetic resonance (NMR spectroscopy, stopped-flow kinetics, and isothermal titration calorimetry, we show that recoverin populates a minor conformation in solution that exposes a hydrophobic binding pocket responsible for binding rhodopsin kinase. Protein dynamics in free recoverin limits the overall rate of binding.

  20. Single molecule imaging reveals differences in microtubule track selection between Kinesin motors.

    Directory of Open Access Journals (Sweden)

    Dawen Cai

    2009-10-01

    Full Text Available Cells generate diverse microtubule populations by polymerization of a common alpha/beta-tubulin building block. How microtubule associated proteins translate microtubule heterogeneity into specific cellular functions is not clear. We evaluated the ability of kinesin motors involved in vesicle transport to read microtubule heterogeneity by using single molecule imaging in live cells. We show that individual Kinesin-1 motors move preferentially on a subset of microtubules in COS cells, identified as the stable microtubules marked by post-translational modifications. In contrast, individual Kinesin-2 (KIF17 and Kinesin-3 (KIF1A motors do not select subsets of microtubules. Surprisingly, KIF17 and KIF1A motors that overtake the plus ends of growing microtubules do not fall off but rather track with the growing tip. Selection of microtubule tracks restricts Kinesin-1 transport of VSVG vesicles to stable microtubules in COS cells whereas KIF17 transport of Kv1.5 vesicles is not restricted to specific microtubules in HL-1 myocytes. These results indicate that kinesin families can be distinguished by their ability to recognize microtubule heterogeneity. Furthermore, this property enables kinesin motors to segregate membrane trafficking events between stable and dynamic microtubule populations.

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

    Science.gov (United States)

    Wolfowicz, Iliona; Baumgarten, Sebastian; Voss, Philipp A; Hambleton, Elizabeth A; Voolstra, Christian R; Hatta, Masayuki; Guse, Annika

    2016-01-01

    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. PMID:27582179

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

    Science.gov (United States)

    Wolfowicz, Iliona; Baumgarten, Sebastian; Voss, Philipp A.; Hambleton, Elizabeth A.; Voolstra, Christian R.; Hatta, Masayuki; Guse, Annika

    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.

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

    Science.gov (United States)

    Wolfowicz, Iliona; Baumgarten, Sebastian; Voss, Philipp A.; Hambleton, Elizabeth A.; Voolstra, Christian R.; Hatta, Masayuki; Guse, Annika

    2016-01-01

    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. PMID:27582179

  4. 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 (Plinear 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.

  5. 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.

  6. 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.

  7. The molecular physiology of CRAC channels

    Science.gov (United States)

    Prakriya, Murali

    2011-01-01

    Summary The Ca2+release-activated Ca2+ (CRAC) channel is a highly Ca2+-selective store-operated channel expressed in T cells, mast cells, and various other tissues. CRAC channels regulate critical cellular processes such as gene expression, motility, and the secretion of inflammatory mediators. The identification of Orai1, a key subunit of the CRAC channel pore, and STIM1, the endoplasmic reticulum (ER) Ca2+ sensor, have provided the tools to illuminate the mechanisms of regulation and the pore properties of CRAC channels. Recent evidence indicates that the activation of CRAC channels by store depletion involves a coordinated series of steps, which include the redistributions of STIM1 and Orai1, direct physical interactions between these proteins, and conformational changes in Orai1, culminating in channel activation. Additional studies have revealed that the high Ca2+ selectivity of CRAC channels arises from the presence of an intrapore Ca2+ binding site, the properties of which are finely honed to occlude the permeation of the much more prevalent Na+. Structure-function studies have led to the identification of the potential pore-binding sites for Ca2+, providing a firm framework for understanding the mechanisms of selectivity and gating of the CRAC channel. This review summarizes recent progress in understanding the mechanisms of CRAC channel activation, pore properties, and modulation. PMID:19754891

  8. Structures of the PutA peripheral membrane flavoenzyme reveal a dynamic substrate-channeling tunnel and the quinone-binding site.

    Science.gov (United States)

    Singh, Harkewal; Arentson, Benjamin W; Becker, Donald F; Tanner, John J

    2014-03-01

    Proline utilization A (PutA) proteins are bifunctional peripheral membrane flavoenzymes that catalyze the oxidation of L-proline to L-glutamate by the sequential activities of proline dehydrogenase and aldehyde dehydrogenase domains. Located at the inner membrane of Gram-negative bacteria, PutAs play a major role in energy metabolism by coupling the oxidation of proline imported from the environment to the reduction of membrane-associated quinones. Here, we report seven crystal structures of the 1,004-residue PutA from Geobacter sulfurreducens, along with determination of the protein oligomeric state by small-angle X-ray scattering and kinetic characterization of substrate channeling and quinone reduction. The structures reveal an elaborate and dynamic tunnel system featuring a 75-Å-long tunnel that links the two active sites and six smaller tunnels that connect the main tunnel to the bulk medium. The locations of these tunnels and their responses to ligand binding and flavin reduction suggest hypotheses about how proline, water, and quinones enter the tunnel system and where L-glutamate exits. Kinetic measurements show that glutamate production from proline occurs without a lag phase, consistent with substrate channeling and implying that the observed tunnel is functionally relevant. Furthermore, the structure of reduced PutA complexed with menadione bisulfite reveals the elusive quinone-binding site. The benzoquinone binds within 4.0 Å of the flavin si face, consistent with direct electron transfer. The location of the quinone site implies that the concave surface of the PutA dimer approaches the membrane. Altogether, these results provide insight into how PutAs couple proline oxidation to quinone reduction. PMID:24550478

  9. 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.

  10. Degenerate in vitro genetic selection reveals mutations that diminish alfalfa mosaic virus RNA replication without affecting coat protein binding.

    Science.gov (United States)

    Rocheleau, Gail; Petrillo, Jessica; Guogas, Laura; Gehrke, Lee

    2004-08-01

    The alfalfa mosaic virus (AMV) RNAs are infectious only in the presence of the viral coat protein; however, the mechanisms describing coat protein's role during replication are disputed. We reasoned that mechanistic details might be revealed by identifying RNA mutations in the 3'-terminal coat protein binding domain that increased or decreased RNA replication without affecting coat protein binding. Degenerate (doped) in vitro genetic selection, based on a pool of randomized 39-mers, was used to select 30 variant RNAs that bound coat protein with high affinity. AUGC sequences that are conserved among AMV and ilarvirus RNAs were among the invariant nucleotides in the selected RNAs. Five representative clones were analyzed in functional assays, revealing diminished viral RNA expression resulting from apparent defects in replication and/or translation. These data identify a set of mutations, including G-U wobble pairs and nucleotide mismatches in the 5' hairpin, which affect viral RNA functions without significant impact on coat protein binding. Because the mutations associated with diminished function were scattered over the 3'-terminal nucleotides, we considered the possibility that RNA conformational changes rather than disruption of a precise motif might limit activity. Native polyacrylamide gel electrophoresis experiments showed that the 3' RNA conformation was indeed altered by nucleotide substitutions. One interpretation of the data is that coat protein binding to the AUGC sequences determines the orientation of the 3' hairpins relative to one another, while local structural features within these hairpins are also critical determinants of functional activity. PMID:15254175

  11. Triclosan Resistome from Metagenome Reveals Diverse Enoyl Acyl Carrier Protein Reductases and Selective Enrichment of Triclosan Resistance Genes.

    Science.gov (United States)

    Khan, Raees; Kong, Hyun Gi; Jung, Yong-Hoon; Choi, Jinhee; Baek, Kwang-Yeol; Hwang, Eul Chul; Lee, Seon-Woo

    2016-01-01

    Triclosan (TCS) is a widely used antimicrobial agent and TCS resistance is considered to have evolved in diverse organisms with extensive use of TCS, but distribution of TCS resistance has not been well characterized. Functional screening of the soil metagenome in this study has revealed that a variety of target enoyl acyl carrier protein reductases (ENR) homologues are responsible for the majority of TCS resistance. Diverse ENRs similar to 7-α-hydroxysteroid dehydrogenase (7-α-HSDH), FabG, or the unusual YX7K-type ENR conferred extreme tolerance to TCS. The TCS-refractory 7-α HSDH-like ENR and the TCS-resistant YX7K-type ENR seem to be prevalent in human pathogenic bacteria, suggesting that a selective enrichment occurred in pathogenic bacteria in soil. Additionally, resistance to multiple antibiotics was found to be mediated by antibiotic resistance genes that co-localize with TCS resistance determinants. Further comparative analysis of ENRs from 13 different environments has revealed a huge diversity of both prototypic and metagenomic TCS-resistant ENRs, in addition to a selective enrichment of TCS-resistant specific ENRs in presumably TCS-contaminated environments with reduced ENR diversity. Our results suggest that long-term extensive use of TCS can lead to the selective emergence of TCS-resistant bacterial pathogens, possibly with additional resistance to multiple antibiotics, in natural environments. PMID:27577999

  12. Triclosan Resistome from Metagenome Reveals Diverse Enoyl Acyl Carrier Protein Reductases and Selective Enrichment of Triclosan Resistance Genes

    Science.gov (United States)

    Khan, Raees; Kong, Hyun Gi; Jung, Yong-Hoon; Choi, Jinhee; Baek, Kwang-Yeol; Hwang, Eul Chul; Lee, Seon-Woo

    2016-01-01

    Triclosan (TCS) is a widely used antimicrobial agent and TCS resistance is considered to have evolved in diverse organisms with extensive use of TCS, but distribution of TCS resistance has not been well characterized. Functional screening of the soil metagenome in this study has revealed that a variety of target enoyl acyl carrier protein reductases (ENR) homologues are responsible for the majority of TCS resistance. Diverse ENRs similar to 7-α-hydroxysteroid dehydrogenase (7-α-HSDH), FabG, or the unusual YX7K-type ENR conferred extreme tolerance to TCS. The TCS-refractory 7-α HSDH-like ENR and the TCS-resistant YX7K-type ENR seem to be prevalent in human pathogenic bacteria, suggesting that a selective enrichment occurred in pathogenic bacteria in soil. Additionally, resistance to multiple antibiotics was found to be mediated by antibiotic resistance genes that co-localize with TCS resistance determinants. Further comparative analysis of ENRs from 13 different environments has revealed a huge diversity of both prototypic and metagenomic TCS-resistant ENRs, in addition to a selective enrichment of TCS-resistant specific ENRs in presumably TCS-contaminated environments with reduced ENR diversity. Our results suggest that long-term extensive use of TCS can lead to the selective emergence of TCS-resistant bacterial pathogens, possibly with additional resistance to multiple antibiotics, in natural environments. PMID:27577999

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  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. 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.

  19. 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.

  20. 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. PMID:27100102

  1. 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.

  2. The Earliest Ion Channels

    Science.gov (United States)

    Pohorille, A.; Wilson, M. A.; Wei, C.

    2009-12-01

    Supplying protocells with ions required assistance from channels spanning their membrane walls. The earliest channels were most likely short proteins that formed transmembrane helical bundles surrounding a water-filled pore. These simple aggregates were capable of transporting ions with efficiencies comparable to those of complex, contemporary ion channels. Channels with wide pores exhibited little ion selectivity but also imposed only modest constraints on amino acid sequences of channel-forming proteins. Channels with small pores could have been selective but also might have required a more precisely defined sequence of amino acids. In contrast to modern channels, their protocellular ancestors had only limited capabilities to regulate ion flux. It is postulated that subsequent evolution of ion channels progressed primarily to acquire precise regulation, and not high efficiency or selectivity. It is further proposed that channels and the surrounding membranes co-evolved.

  3. 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.

  4. 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.

  5. Optimal Selection of Sensing Channel in Cognitive Radio Network%认知无线电中感知信道的优化选择方法

    Institute of Scientific and Technical Information of China (English)

    叶军; 朱琦

    2012-01-01

    Spectrum sensing has been identified as a key requirement for dynamic spectrum allocation in cognitive radio network(CRN). Based on energy detection,this paper proposed an optimization method for channel selection in multi-user and multi-channel scenario. This method maximizes the normalized throughput that can be obtained by a CR user sensing a primary user's channel. The improved Hungarian algorithm is adopted to select the optimal channel for CR users. Simulation results show that the proposed optimization method can improve the overall normalized throughput comparing with the random channel selection method.%在认知无线电中,频谱感知是实现频谱动态接入的重要前提和核心环节,文中在多用户多信道环境下基于能量检测提出了一种感知信道优化选择的方法.该方法从最大化一个次用户感知一个主用户信道能获得的归一化吞吐量出发,在目标检测概率限制下,提出了基于改进的匈牙利算法进行感知信道选择的最优方法.仿真结果表明,与感知信道随机选择方法相比较,文中提出的方法可以大大提高整个次用户网络的归一化吞吐量.

  6. 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...

  7. 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...

  8. 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

  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)

    Mu, Xingjiang; Pridgeon, Julia W; Klesius, Phillip H

    2013-11-01

    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 re-infection as tester. Of the 96 clones isolated from the SSH library, 28 unique expressed sequence tags (ESTs) were obtained, of which eight were confirmed to be slightly but significantly (P CXCL-10); 4) signaling proteins (cadherin EGF LAG seven-pass G-type receptor 1, very large inducible GTPase 1, arginine deiminase type 2, lymphokine-activated killer T-cell originated protein kinase); 5) lysozyme (lysozyme c). Overall, the total 27 genes (8 ESTs plus the 19 selected genes) were significantly (P < 0.001) more induced by the first infection. Peaked expression of lysozyme c and serum lysozyme activity after the first infection were seen at 24 hpi, whereas that after the re-infection were seen at 12 hpi, suggesting that both innate and adaptive immunity were involved in the defense against the re-infection of A. hydrophila. PMID:24036330

  10. 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.

  11. Limited selection of sodium channel blocking toxin-producing bacteria from paralytic shellfish toxin-contaminated mussels (Aulacomya ater).

    Science.gov (United States)

    Vásquez, Mónica; Grüttner, Carol; Möeller, Blanca; Moore, Edward R B

    2002-01-01

    Paralytic shellfish toxins (PSTs) are sodium channel blocking (SCB) toxins, produced by cyanobacteria, as well as by marine dinoflagellates and their associated bacteria, and cause serious health and economic concern worldwide. In a previous study, approximately 70% of the bacteria enriched from PST-contaminated shellfish tissue and isolated on marine agar medium were observed to produce SCB toxins. In the study reported here, the high percentage of cultivable toxigenic bacteria is demonstrated to be obtained through a marked selection on marine agar medium. The cultivable as well as the total bacterial diversity associated with PST-contaminated shellfish collected from the Magallanes region in the south of Chile has been analysed. Approximately 80% of bacterial isolates, analysed by restriction analysis of PCR amplified ribosomal DNA (i.e., ARDRA fingerprinting), were limited to only two genotypic OTUs (operational taxonomic unit). Sequence determination and analysis of the 16S rDNA from representative isolates of both OTUs established them to be closely related to species of the Psychrobacter genus of the gamma-subclass of the Proteobacteria. The total bacterial diversity in the shellfish was further analysed, using a cultivation-independent strategy of extraction of total DNA from contaminated tissue, PCR-amplification of bacterial 16S rRNA genes, cloning of the PCR products and analysis of the cloned 16S rDNA sequence types by fingerprinting and sequencing. Only 2% of the cloned sequence types corresponded to species of the Psychrobacter genus. The 16S rDNA sequence types detected clustered with species of the y-Proteobacteria subclass, the Cytophaga-Flexibacter-Bacteroides (CFB), the Fusobacteria and the Firmicutes phyla. The level of diversity observed within the libraries of cloned 16S rDNA was markedly greater than that observed among isolates obtained through marine agar enrichment cultures from the same shellfish tissue. Additionally the predominant

  12. 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.

  13. 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.

  14. The role of negative selection in protein evolution revealed through the energetics of the native state ensemble.

    Science.gov (United States)

    Hoffmann, Jordan; Wrabl, James O; Hilser, Vincent J

    2016-04-01

    Knowing the determinants of conformational specificity is essential for understanding protein structure, stability, and fold evolution. To address this issue, a novel statistical measure of energetic compatibility between sequence and structure was developed using an experimentally validated model of the energetics of the native state ensemble. This approach successfully matched sequences from a diverse subset of the human proteome to their respective folds. Unexpectedly, significant energetic compatibility between ostensibly unrelated sequences and structures was also observed. Interrogation of these matches revealed a general framework for understanding the origins of conformational specificity within a proteome: specificity is a complex function of both the ability of a sequence to adopt folds other than the native, and ability of a fold to accommodate sequences other than the native. The regional variation in energetic compatibility indicates that the compatibility is dominated by incompatibility of sequence for alternative fold segments, suggesting that evolution of protein sequences has involved substantial negative selection, with certain segments serving as "gatekeepers" that presumably prevent alternative structures. Beyond these global trends, a size dependence exists in the degree to which the energetic compatibility is determined from negative selection, with smaller proteins displaying more negative selection. This partially explains how short sequences can adopt unique folds, despite the higher probability in shorter proteins for small numbers of mutations to increase compatibility with other folds. In providing evolutionary ground rules for the thermodynamic relationship between sequence and fold, this framework imparts valuable insight for rational design of unique folds or fold switches. Proteins 2016; 84:435-447. © 2016 Wiley Periodicals, Inc. PMID:26800099

  15. Single relay selection in multi-access relay channel%多接入中继信道中的单中继选择

    Institute of Scientific and Technical Information of China (English)

    宋沈煜; 陈文

    2012-01-01

    It has been shown that cooperative relay selection schemes promise gains in robustness and energy-efficiency in wireless relaying networks. This paper considers multi-access relay channel (MARC) with 2 sources, N relays and 1 destination, where the half-duplexing relays perform non-regenerative network coding for the received signals from the two sources. Taking the direct links into consideration, it develops new single relay selection schemes based on best worst channel selection scheme, best signal-to-noise ratio selection scheme and best harmonic mean selection. The simulation results show that they outperform the existing schemes.%研究表明,协作中继选择能提高无线中继网络的鲁棒性和能效.文中研究一个多接入中继信道,包含2个信源,N个中继和1个信宿.中继节点为半双工,对两个信源的信号采用非再生的网络编码.考虑直接链路,基于最佳最差信道、最佳信噪比和最佳调和平均选择,提出新的选择策略.仿真结果表明其在性能上优于原有策略.

  16. Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator

    Science.gov (United States)

    Mattmann, Margrith E.; Yu, Haibo; Lin, Zhihong; Xu, Kaiping; Huang, Xiaofang; Long, Shunyou; Wu, Meng; McManus, Owen B.; Engers, Darren W.; Le, Uyen M.; Li, Min; Lindsley, Craig W.; Hopkins, Corey R.

    2012-01-01

    A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (>100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. PMID:22910039

  17. 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.

  18. Voltage-gated proton channels.

    Science.gov (United States)

    Decoursey, Thomas E

    2012-04-01

    Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely, the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance approximately 10(3) times smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn(2+) (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B-lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H(+) for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens.

  19. 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

  20. 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

  1. Evolutionary adaptation of the amino acid and codon usage of the mosquito sodium channel following insecticide selection in the field mosquitoes.

    Directory of Open Access Journals (Sweden)

    Qiang Xu

    Full Text Available Target site insensitivity resulting from point mutations within the voltage-gated sodium channel of the insect nervous system is known to be of primary importance in the development of resistance to pyrethroid insecticides. This study shifts current research paradigms by conducting, for the first time, a global analysis of all the naturally occurring mutations, both nonsynonymous and synonymous mutations, as well as mutation combinations in the entire mosquito sodium channel of Culex quinquefasciatus and analyzing their evolutionary and heritable feature and roles in insecticide resistance. Through a systematic analysis of comparing nucleotide polymorphisms in the entire sodium channel cDNAs of individuals between susceptible and resistant mosquito strains, between field parental mosquitoes and their permethrin selected offspring, and among different mosquito groups categorized by their levels of tolerance to specific permethrin concentrations within and among the mosquito strains of the field parental strains and their permethrin selected offspring, 3 nonsynonymous (A(109S, L(982F, and W(1573R and 6 synonymous (L(852, G(891, A(1241, D(1245, P(1249, and G(1733 mutations were identified. The co-existence of all 9 mutations, both nonsynonymous and synonymous, and their homozygousity were found to be important factors for high levels of resistance. Our study, for the first time, provide a strong case demonstrating the co-existence of both nonsynonymous and synonymous mutations in the sodium channel of resistant mosquitoes in response to insecticide resistance and the inheritance of these mutations in the offspring of field mosquito strains following insecticide selection.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Reductions in Susceptibility of Channel Catfish (Ictalutus punctatus) to Enteric Septicemia of Catfish (ESC) Through Two Generations of Selection

    Science.gov (United States)

    Improvement of disease resistance in aquaculture species through selective breeding has had some success. At the USDA-ARS Catfish Genetics Research Unit, Stoneville, MS, a multitrait selection index was utilized to select for growth, carcass yield, and resistance to enteric septicemia of catfish (...

  7. 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.

  8. Channels selection in the retail banking sector: relationship between the factors influencing the usage and the perceived service quality

    OpenAIRE

    Júnior, Luciana de Oliveira Santos

    2011-01-01

    Mestrado em Marketing Quality is regarded as one of the main objectives to achieve in a successful organization, where the corporate policy is defined around of how to stay efficient while achieving the quality requirements defined by the consumer. Thus, companies in the banking sector are concentrating their efforts to achieve excellence, beginning with the service channels, which represent the point of contact with their clients. This dissertation aims to deepen the study on the use o...

  9. 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.

  10. Gramicidin Channels: Versatile Tools

    Science.gov (United States)

    Andersen, Olaf S.; Koeppe, Roger E., II; Roux, Benoît

    Gramicidin channels are miniproteins in which two tryptophan-rich subunits associate by means of transbilayer dimerization to form the conducting channels. That is, in contrast to other ion channels, gramicidin channels do not open and close; they appear and disappear. Each subunit in the bilayer-spanning channel is tied to the bilayer/solution interface through hydrogen bonds that involve the indole NH groups as donors andwater or the phospholipid backbone as acceptors. The channel's permeability characteristics are well-defined: gramicidin channels are selective for monovalent cations, with no measurable permeability to anions or polyvalent cations; ions and water move through a pore whose wall is formed by the peptide backbone; and the single-channel conductance and cation selectivity vary when the amino acid sequence is varied, even though the permeating ions make no contact with the amino acid side chains. Given the plethora of available experimental information—for not only the wild-type channels but also for channels formed by amino acid-substituted gramicidin analogues—gramicidin channels continue to provide important insights into the microphysics of ion permeation through bilayer-spanning channels. For similar reasons, gramicidin channels constitute a system of choice for evaluating computational strategies for obtaining mechanistic insights into ion permeation through the more complex channels formed by integral membrane proteins.

  11. 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.

  12. Coordination Numbers of K+ and Na+ Ions Inside the Selectivity Filter of the KcsA Potassium Channel: Insights from First Principles Molecular Dynamics

    OpenAIRE

    Bucher, Denis; Guidoni, Leonardo; Carloni, Paolo; Rothlisberger, Ursula

    2010-01-01

    Quantum mechanics/molecular mechanics (QM/MM) Car-Parrinello simulations were performed to estimate the coordination numbers of K+ and Na+ ions in the selectivity filter of the KcsA channel, and in water. At the DFT/BLYP level, K+ ions were found to display an average coordination number of 6.6 in the filter, and 6.2 in water. Na+ ions displayed an average coordination number of 5.2 in the filter, and 5.0 in water. A comparison was made with the average coordination numbers obtained from usin...

  13. NOTE: Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

    Science.gov (United States)

    Duncan, L.; Shelmerdine, H.; Hughes, M. P.; Coley, H. M.; Hübner, Y.; Labeed, F. H.

    2008-01-01

    Dielectrophoresis (DEP)—the motion of particles in non-uniform AC fields—has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K+ and Ca2+ levels were extremely similar between sensitive and resistant lines, levels of Cl- were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function.

  14. Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, L [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Shelmerdine, H [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Hughes, M P [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Coley, H M [Postgraduate Medical School, University of Surrey, Guildford GU27XH (United Kingdom); Huebner, Y [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Labeed, F H [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom)

    2008-01-21

    Dielectrophoresis (DEP)-the motion of particles in non-uniform AC fields-has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K{sup +} and Ca{sup 2+} levels were extremely similar between sensitive and resistant lines, levels of Cl{sup -} were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function. (note)

  15. High overlap of CNVs and selection signatures revealed by varLD analyses of taurine and zebu cattle

    Science.gov (United States)

    Selection Signatures (SS) assessed through analysis of genomic data are being widely studied to discover population specific regions selected via artificial or natural selection. Different methodologies have been proposed for these analyses, each having specific limitations as to the age of the sele...

  16. Control of the Aquaporin-4 Channel Water Permeability by Structural Dynamics of Aromatic/Arginine Selectivity Filter Residues.

    Science.gov (United States)

    Kitchen, Philip; Conner, Alex C

    2015-11-17

    The aquaporins (AQPs) make up a family of integral membrane proteins that control cellular water flow. Gating of the water channel by conformational changes induced by phosphorylation or protein-protein interactions is an established regulatory mechanism for AQPs. Recent in silico and crystallographic analyses of the structural biology of AQPs suggest that the rate of water flow can also be controlled by small movements of single-amino acid side chains lining the water pore. Here we use measurements of the membrane water permeability of mammalian cells expressing AQP4 mutants to provide the first in vitro evidence in support of this hypothesis. PMID:26512424

  17. Atrial-selective prolongation of refractory period with AVE0118 is due principally to inhibition of sodium channel activity

    OpenAIRE

    Burashnikov, Alexander; Barajas-Martinez, Hector; Hu, Dan; Nof, Eyal; Blazek, Jonathan; Antzelevitch, Charles

    2012-01-01

    AVE0118’s action to prolong effective refractory period (ERP) in atria but not ventricles is thought to be due to its inhibition of IKur. However, in non-remodeled atria, AVE0118 prolongs ERP but not action potential duration (APD70-90), which can be explained with inhibition of sodium, but not potassium channel current. ERP, APD, and the maximum rate of rise of the AP upstroke (Vmax) were measured in canine isolated coronary-perfused right atrial and in superfused ventricular tissue preparat...

  18. Commensurate CO2 Capture, and Shape Selectivity for HCCH over H2CCH2, in Zigzag Channels of a Robust Cu(I)(CN)(L) Metal-Organic Framework.

    Science.gov (United States)

    Miller, Reece G; Southon, Peter D; Kepert, Cameron J; Brooker, Sally

    2016-06-20

    A novel copper(I) metal-organic framework (MOF), {[Cu(I)2(py-pzpypz)2(μ-CN)2]·MeCN}n (1·MeCN), with an unusual topology is shown to be robust, retaining crystallinity during desolvation to give 1, which has also been structurally characterized [py-pzpypz is 4-(4-pyridyl)-2,5-dipyrazylpyridine)]. Zigzag-shaped channels, which in 1·MeCN were occupied by disordered MeCN molecules, run along the c axis of 1, resulting in a significant solvent-accessible void space (9.6% of the unit cell volume). These tight zigzags, bordered by (Cu(I)CN)n chains, make 1 an ideal candidate for investigations into shape-based selectivity. MOF 1 shows a moderate enthalpy of adsorption for binding CO2 (-32 kJ mol(-1) at moderate loadings), which results in a good selectivity for CO2 over N2 of 4.8:1 under real-world operating conditions of a 15:85 CO2/N2 mixture at 1 bar. Furthermore, 1 was investigated for shape-based selectivity of small hydrocarbons, revealing preferential uptake of linear acetylene gas over ethylene and methane, partially due to kinetic trapping of the guests with larger kinetic diameters. PMID:27258550

  19. A Quantitative Model of the GIRK1/2 Channel Reveals That Its Basal and Evoked Activities Are Controlled by Unequal Stoichiometry of Gα and Gβγ.

    Science.gov (United States)

    Yakubovich, Daniel; Berlin, Shai; Kahanovitch, Uri; Rubinstein, Moran; Farhy-Tselnicker, Isabella; Styr, Boaz; Keren-Raifman, Tal; Dessauer, Carmen W; Dascal, Nathan

    2015-11-01

    G protein-gated K+ channels (GIRK; Kir3), activated by Gβγ subunits derived from Gi/o proteins, regulate heartbeat and neuronal excitability and plasticity. Both neurotransmitter-evoked (Ievoked) and neurotransmitter-independent basal (Ibasal) GIRK activities are physiologically important, but mechanisms of Ibasal and its relation to Ievoked are unclear. We have previously shown for heterologously expressed neuronal GIRK1/2, and now show for native GIRK in hippocampal neurons, that Ibasal and Ievoked are interrelated: the extent of activation by neurotransmitter (activation index, Ra) is inversely related to Ibasal. To unveil the underlying mechanisms, we have developed a quantitative model of GIRK1/2 function. We characterized single-channel and macroscopic GIRK1/2 currents, and surface densities of GIRK1/2 and Gβγ expressed in Xenopus oocytes. Based on experimental results, we constructed a mathematical model of GIRK1/2 activity under steady-state conditions before and after activation by neurotransmitter. Our model accurately recapitulates Ibasal and Ievoked in Xenopus oocytes, HEK293 cells and hippocampal neurons; correctly predicts the dose-dependent activation of GIRK1/2 by coexpressed Gβγ and fully accounts for the inverse Ibasal-Ra correlation. Modeling indicates that, under all conditions and at different channel expression levels, between 3 and 4 Gβγ dimers are available for each GIRK1/2 channel. In contrast, available Gαi/o decreases from ~2 to less than one Gα per channel as GIRK1/2's density increases. The persistent Gβγ/channel (but not Gα/channel) ratio support a strong association of GIRK1/2 with Gβγ, consistent with recruitment to the cell surface of Gβγ, but not Gα, by GIRK1/2. Our analysis suggests a maximal stoichiometry of 4 Gβγ but only 2 Gαi/o per one GIRK1/2 channel. The unique, unequal association of GIRK1/2 with G protein subunits, and the cooperative nature of GIRK gating by Gβγ, underlie the complex pattern of

  20. A Quantitative Model of the GIRK1/2 Channel Reveals That Its Basal and Evoked Activities Are Controlled by Unequal Stoichiometry of Gα and Gβγ.

    Directory of Open Access Journals (Sweden)

    Daniel Yakubovich

    2015-11-01

    Full Text Available G protein-gated K+ channels (GIRK; Kir3, activated by Gβγ subunits derived from Gi/o proteins, regulate heartbeat and neuronal excitability and plasticity. Both neurotransmitter-evoked (Ievoked and neurotransmitter-independent basal (Ibasal GIRK activities are physiologically important, but mechanisms of Ibasal and its relation to Ievoked are unclear. We have previously shown for heterologously expressed neuronal GIRK1/2, and now show for native GIRK in hippocampal neurons, that Ibasal and Ievoked are interrelated: the extent of activation by neurotransmitter (activation index, Ra is inversely related to Ibasal. To unveil the underlying mechanisms, we have developed a quantitative model of GIRK1/2 function. We characterized single-channel and macroscopic GIRK1/2 currents, and surface densities of GIRK1/2 and Gβγ expressed in Xenopus oocytes. Based on experimental results, we constructed a mathematical model of GIRK1/2 activity under steady-state conditions before and after activation by neurotransmitter. Our model accurately recapitulates Ibasal and Ievoked in Xenopus oocytes, HEK293 cells and hippocampal neurons; correctly predicts the dose-dependent activation of GIRK1/2 by coexpressed Gβγ and fully accounts for the inverse Ibasal-Ra correlation. Modeling indicates that, under all conditions and at different channel expression levels, between 3 and 4 Gβγ dimers are available for each GIRK1/2 channel. In contrast, available Gαi/o decreases from ~2 to less than one Gα per channel as GIRK1/2's density increases. The persistent Gβγ/channel (but not Gα/channel ratio support a strong association of GIRK1/2 with Gβγ, consistent with recruitment to the cell surface of Gβγ, but not Gα, by GIRK1/2. Our analysis suggests a maximal stoichiometry of 4 Gβγ but only 2 Gαi/o per one GIRK1/2 channel. The unique, unequal association of GIRK1/2 with G protein subunits, and the cooperative nature of GIRK gating by Gβγ, underlie the complex

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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)

    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 identifiedCYPs genes through in silico analysis using EST, RNA-Seq and genome databases of channel catfish.Phylogenetic ...

  7. 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.

  8. 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...

  9. 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

  10. Evidences of early to late fluid migration from an upper Miocene turbiditic channel revealed by 3D seismic coupled to geochemical sampling within seafloor pockmarks, Lower Congo Basin

    Energy Technology Data Exchange (ETDEWEB)

    Gay, A. [Challenger Division for Seafloor Processes, National Oceanography Centre of Southampton, Southampton (United Kingdom); Lopez, M.; Seranne, M. [Laboratoire Dynamique de la Lithosphere, Universite Montpellier 2, Montpellier (France); Cochonat, P. [Laboratoire Environnements Sedimentaires, Departement Geosciences Marines, IFREMER, Brest (France); Levache, D.; Sermondadaz, G. [TOTAL, Pau (France)

    2006-04-15

    Using high quality 3D seismic data within the Lower Congo Basin (LCB), we have identified pockmarks that are aligned above the sinuous belt of a buried turbiditic palaeo-channel, 1000m beneath the seafloor. Geochemical analyses on cores (GC traces), taken in the centre of four of these pockmarks along this channel, show no clear evidence for migrated oil. But, some features of the GC traces, including elevated baselines (UCM>34{mu}g/g) and a broad molecular weight range of n-alkanes with little odd-even preference, may be interpreted as indicating the presence of thermogenic hydrocarbons in the cores. Seismic profiles show that these pockmarks developed above two main features representative of pore fluid escape during early compaction: (1) closely spaced normal faults affecting the upper 0-800ms TWT of the sedimentary column. This highly faulted interval (HFI) appears as a hexagonal network in plane view, which is characteristic of a volumetrical contraction of sediments in response to pore fluid escape. (2) Buried palaeo-pockmarks and their underlying chimneys seem to be rooted at the channel-levee interface. The chimneys developed during early stages of burial and are now connected to the HFI. This study shows that the buried turbiditic channel now concentrates thermogenic fluids that can migrate through early chimneys and polygonal faults to reach the seafloor within some pockmarks. Using a multidisciplinary approach within the Lower Congo Basin, combining 3D seismic data and geochemical analyses on cores, we trace the fluid history from early compaction expelling pore fluids to later migration of thermogenic hydrocarbons. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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.

  13. 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 .

  14. Genome-wide candidate regions for selective sweeps revealed through massive parallel sequencing of DNA across ten turkey populations

    OpenAIRE

    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 breeding is critical for understanding the dynamics of genomic change in these species. Intense selective breeding and population bottlenecks are expected to leave signatures in the genome of domesticate...

  15. 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.

  16. Contrasting epidemic histories reveal pathogen-mediated balancing selection on class II MHC diversity in a wild songbird.

    Directory of Open Access Journals (Sweden)

    Dana M Hawley

    Full Text Available The extent to which pathogens maintain the extraordinary polymorphism at vertebrate Major Histocompatibility Complex (MHC genes via balancing selection has intrigued evolutionary biologists for over half a century, but direct tests remain challenging. Here we examine whether a well-characterized epidemic of Mycoplasmal conjunctivitis resulted in balancing selection on class II MHC in a wild songbird host, the house finch (Carpodacus mexicanus. First, we confirmed the potential for pathogen-mediated balancing selection by experimentally demonstrating that house finches with intermediate to high multi-locus MHC diversity are more resistant to challenge with Mycoplasma gallisepticum. Second, we documented sequence and diversity-based signatures of pathogen-mediated balancing selection at class II MHC in exposed host populations that were absent in unexposed, control populations across an equivalent time period. Multi-locus MHC diversity significantly increased in exposed host populations following the epidemic despite initial compromised diversity levels from a recent introduction bottleneck in the exposed host range. We did not observe equivalent changes in allelic diversity or heterozygosity across eight neutral microsatellite loci, suggesting that the observations reflect selection rather than neutral demographic processes. Our results indicate that a virulent pathogen can exert sufficient balancing selection on class II MHC to rescue compromised levels of genetic variation for host resistance in a recently bottlenecked population. These results provide evidence for Haldane's long-standing hypothesis that pathogens directly contribute to the maintenance of the tremendous levels of genetic variation detected in natural populations of vertebrates.

  17. 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.

  18. Long-term maintenance of channel distribution in a central pattern generator neuron by neuromodulatory inputs revealed by decentralization in organ culture.

    Science.gov (United States)

    Mizrahi, A; Dickinson, P S; Kloppenburg, P; Fénelon, V; Baro, D J; Harris-Warrick, R M; Meyrand, P; Simmers, J

    2001-09-15

    Organotypic cultures of the lobster (Homarus gammarus) stomatogastric nervous system (STNS) were used to assess changes in membrane properties of neurons of the pyloric motor pattern-generating network in the long-term absence of neuromodulatory inputs to the stomatogastric ganglion (STG). Specifically, we investigated decentralization-induced changes in the distribution and density of the transient outward current, I(A), which is encoded within the STG by the shal gene and plays an important role in shaping rhythmic bursting of pyloric neurons. Using an antibody against lobster shal K(+) channels, we found shal immunoreactivity in the membranes of neuritic processes, but not somata, of STG neurons in 5 d cultured STNS with intact modulatory inputs. However, in 5 d decentralized STG, shal immunoreactivity was still seen in primary neurites but was likewise present in a subset of STG somata. Among the neurons displaying this altered shal localization was the pyloric dilator (PD) neuron, which remained rhythmically active in 5 d decentralized STG. Two-electrode voltage clamp was used to compare I(A) in synaptically isolated PD neurons in long-term decentralized STG and nondecentralized controls. Although the voltage dependence and kinetics of I(A) changed little with decentralization, the maximal conductance of I(A) in PD neurons increased by 43.4%. This increase was consistent with the decentralization-induced increase in shal protein expression, indicating an alteration in the density and distribution of functional A-channels. Our results suggest that, in addition to the short-term regulation of network function, modulatory inputs may also play a role, either directly or indirectly, in controlling channel number and distribution, thereby maintaining the biophysical character of neuronal targets on a long-term basis. PMID:11549743

  19. Tetrahydroisoquinoline-Derived Urea and 2,5-Diketopiperazine Derivatives as Selective Antagonists of the Transient Receptor Potential Melastatin 8 (TRPM8) Channel Receptor and Antiprostate Cancer Agents.

    Science.gov (United States)

    De Petrocellis, Luciano; Arroyo, Francisco J; Orlando, Pierangelo; Schiano Moriello, Aniello; Vitale, Rosa Maria; Amodeo, Pietro; Sánchez, Aránzazu; Roncero, Cesáreo; Bianchini, Giulia; Martín, M Antonia; López-Alvarado, Pilar; Menéndez, J Carlos

    2016-06-23

    Tetrahydroisoquinoline derivatives containing embedded urea functions were identified as selective TRPM8 channel receptor antagonists. Structure-activity relationships were investigated, with the following conclusions: (a) The urea function and the tetrahydroisoquinoline system are necessary for activity. (b) Bis(1-aryl-6,7dimethoxy-1,2,3,4-tetrahydroisoquinolyl)ureas are more active than compounds containing one tetrahydroisoquinoline ring and than an open phenetylamine ureide. (c) Trans compounds are more active than their cis isomers. (d) Aryl substituents are better than alkyls at the isoquinoline C-1 position. (e) Electron-withdrawing substituents lead to higher activities. The most potent compound is the 4-F derivative, with IC50 in the 10(-8) M range and selectivities around 1000:1 for most other TRP receptors. Selected compounds were found to be active in reducing the growth of LNCaP prostate cancer cells. TRPM8 inhibition reduces proliferation in the tumor cells tested but not in nontumor prostate cells, suggesting that the activity against prostate cancer is linked to TRPM8 inhibition. PMID:27232526

  20. 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.

  1. 政府干涉下闭环供应链的回收渠道选择策略%Recycling Channel Selection Strategy of Closed-loop Supply Chain under Government Intervention

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In order to improve the recovery efficiency , recycling channel selection of closed-loop supply chain under government intervention is studied .Closed-loop supply chain decision models are established under single recycling channel ( the manufacturer ) , single recycling channel ( the retailer ) and mixed re-cycling channel .Then strategies for choosing recycling channel are studied respectively from the perspec -tives of consumers , the government , the manufacturer , the retailer and the whole supply chain .The re-sults show that the retailer always wants to participate in recycling and that from the other four perspec -tives, with recycling channel selection mainly affected by recycling competing intensity , government inter-vention has little effect on recycling channel selection .The results can be used as a reference for the gov-ernment's environmental policy and macro-control policy , recycling channel selection for the members of the closed-loop supply chain and consumers .%为了提高回收效率,在政府对制造商的回收行为进行干涉下建立了制造商回收、零售商回收和混合回收决策模型,分别从消费者、政府、制造商、零售商和供应链整体五个角度研究了回收渠道的选择策略。结果表明,零售商总是希望参与回收;从其他四个角度来看,回收渠道选择主要受回收渠道竞争强度的影响,政府干涉对渠道选择影响不大。

  2. Voltage-Gated Proton Channels

    OpenAIRE

    DeCoursey, Thomas E.

    2008-01-01

    Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dime...

  3. 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.

  4. 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

    )tropane, or for 3,4-methylenedioxymethamphetamine (MDMA). Analysis of six hSERT/bSERT chimeras and subsequent species-scanning mutagenesis of each isoform revealed methionine-180, tyrosine-495, and phenylalanine-513 to be responsible for the increase in citalopram and paroxetine potencies at hSERT and methionine...

  5. C. elegans TRP channels.

    Science.gov (United States)

    Xiao, Rui; Xu, X Z Shawn

    2011-01-01

    Transient receptor potential (TRP) channels represent a superfamily of cation channels found in all eukaryotes. The C. elegans genome encodes seventeen TRP channels covering all of the seven TRP subfamilies. Genetic analyses in C. elegans have implicated TRP channels in a wide spectrum of behavioral and physiological processes, ranging from sensory transduction (e.g. chemosensation, touch sensation, proprioception and osmosensation) to fertilization, drug dependence, organelle biogenesis, apoptosis, gene expression, and neurotransmitter/hormone release. Many C. elegans TRP channels share similar activation and regulatory mechanisms with their vertebrate counterparts. Studies in C. elegans have also revealed some previously unrecognized functions and regulatory mechanisms of TRP channels. C. elegans represents an excellent genetic model organism for the study of function and regulation of TRP channels in vivo. PMID:21290304

  6. 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

  7. 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

  8. 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.

  9. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential

    OpenAIRE

    Pal, Chandan; Bengtsson-Palme, Johan; Kristiansson, Erik; Larsson, D. G. Joakim

    2015-01-01

    Background Antibacterial biocides and metals can co-select for antibiotic resistance when bacteria harbour resistance or tolerance genes towards both types of compounds. Despite numerous case studies, systematic and quantitative data on co-occurrence of such genes on plasmids and chromosomes is lacking, as is knowledge on environments and bacterial taxa that tend to carry resistance genes to such compounds. This effectively prevents identification of risk scenarios. Therefore, we aimed to ide...

  10. ARTIFICIAL SELECTION ON RELATIVE BRAIN SIZE REVEALS A POSITIVE GENETIC CORRELATION BETWEEN BRAIN SIZE AND PROACTIVE PERSONALITY IN THE GUPPY

    OpenAIRE

    Kotrschal, Alexander; Lievens, Eva J.P.; Dahlbom, Josefin; Bundsen, Andreas; Semenova, Svetlana; Sundvik, Maria; Maklakov, Alexei A.; Winberg, Svante; Panula, Pertti; Kolm, Niclas

    2014-01-01

    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 li...

  11. 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.

  12. Selection for cuticular melanism reveals immune function and life-history trade-offs in Spodoptera littoralis

    OpenAIRE

    Cotter, S. C.; Myatt, J. P.; Benskin, C. M. H.; Wilson, K.

    2008-01-01

    Several insect species show an increase in cuticular melanism in response to high densities. In some species, there is evidence that this melanism is correlated with an up-regulation of certain immune system components, particularly phenoloxidase (PO) activity, and with the down-regulation of lysozyme activity, suggesting a trade-off between the two traits. As melanism has a genetic component, we selected both melanic and nonmelanic lines of the phase-polyphenic lepidopteran, Spodoptera litto...

  13. Paired neuron recordings in the prefrontal and inferotemporal cortices reveal that spatial selection precedes object identification during visual search

    OpenAIRE

    Monosov, Ilya E.; David L Sheinberg; Thompson, Kirk G.

    2010-01-01

    We addressed the question of how we locate and identify objects in complex natural environments by simultaneously recording single neurons from two brain regions that play different roles in this familiar activity—the frontal eye field (FEF), an area in the prefrontal cortex that is involved in visual spatial selection, and the inferotemporal cortex (IT), which is involved in object recognition—in monkeys performing a covert visual search task. Although the monkeys reported object identity, n...

  14. Discovery of the surface polarity gradient on iridescent Morpho butterfly scales reveals a mechanism of their selective vapor response.

    Science.gov (United States)

    Potyrailo, Radislav A; Starkey, Timothy A; Vukusic, Peter; Ghiradella, Helen; Vasudev, Milana; Bunning, Timothy; Naik, Rajesh R; Tang, Zhexiong; Larsen, Michael; Deng, Tao; Zhong, Sheng; Palacios, Manuel; Grande, James C; Zorn, Gilad; Goddard, Gregory; Zalubovsky, Sergey

    2013-09-24

    For almost a century, the iridescence of tropical Morpho butterfly scales has been known to originate from 3D vertical ridge structures of stacked periodic layers of cuticle separated by air gaps. Here we describe a biological pattern of surface functionality that we have found in these photonic structures. This pattern is a gradient of surface polarity of the ridge structures that runs from their polar tops to their less-polar bottoms. This finding shows a biological pattern design that could stimulate numerous technological applications ranging from photonic security tags to self-cleaning surfaces, gas separators, protective clothing, sensors, and many others. As an important first step, this biomaterial property and our knowledge of its basis has allowed us to unveil a general mechanism of selective vapor response observed in the photonic Morpho nanostructures. This mechanism of selective vapor response brings a multivariable perspective for sensing, where selectivity is achieved within a single chemically graded nanostructured sensing unit, rather than from an array of separate sensors. PMID:24019497

  15. 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

    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...... 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...

  16. Distinct transport selectivity of two structural subclasses of the nodulin-like intrinsic protein family of plant aquaglyceroporin channels.

    Science.gov (United States)

    Wallace, Ian S; Roberts, Daniel M

    2005-12-27

    Major intrinsic proteins (MIPs) are a diverse class of integral membrane proteins that facilitate the transport of water and some small solutes across cellular membranes. X-ray structures of MIPs indicate that a tetrad of residues (the ar/R region) form a narrow pore constriction that constitutes the selectivity filter. In comparison with mammalian and microbial species, plants have a greater number and diversity of MIPs with greater than 30 genes encoding four phylogenetic subfamilies with eight different classes of ar/R sequences. The nodulin 26-like intrinsic protein (NIP) subfamily in Arabidopsis can be subdivided into two ar/R subgroups: the NIP subgroup I, which resembles the archetype of the family, soybean nodulin 26, and the NIP subgroup II, which is represented by the Arabidopsis protein AtNIP6;1. These two NIPs differ principally by the substitution of a conserved alanine (NIP subgroup II) for a conserved tryptophan (NIP subgroup I) in the helix 2 position (H2) of the ar/R filter. A comparison of the water and solute tranport properties of the two proteins was performed by expression in Xenopus laevis oocytes. Nodulin 26 is an aquaglyceroporin with a modest osmotic water permeability (P(f)) and the ability to transport uncharged solutes such as glycerol and formamide. In constrast, AtNIP6;1 showed no measurable water permeability but transported glycerol, formamide, as well as larger solutes that were impermeable to nodulin 26. By site-directed mutagenesis, we show that the H2 position is the crucial determinant that confers these transport behaviors. A comparison of the NIPs and tonoplast-intrinsic proteins (TIP) shows that the H2 residue can predict the transport profile for water and glycerol with histidine found in TIP-like aquaporins, tryptophan found in aquaglyceroporins (NIP I), and alanine found in water-impermeable glyceroporins (AtNIP6;1). PMID:16363796

  17. A comparative proteomic analysis of the simple amino acid repeat distributions in Plasmodia reveals lineage specific amino acid selection.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available BACKGROUND: Microsatellites have been used extensively in the field of comparative genomics. By studying microsatellites in coding regions we have a simple model of how genotypic changes undergo selection as they are directly expressed in the phenotype as altered proteins. The simplest of these tandem repeats in coding regions are the tri-nucleotide repeats which produce a repeat of a single amino acid when translated into proteins. Tri-nucleotide repeats are often disease associated, and are also known to be unstable to both expansion and contraction. This makes them sensitive markers for studying proteome evolution, in closely related species. RESULTS: The evolutionary history of the family of malarial causing parasites Plasmodia is complex because of the life-cycle of the organism, where it interacts with a number of different hosts and goes through a series of tissue specific stages. This study shows that the divergence between the primate and rodent malarial parasites has resulted in a lineage specific change in the simple amino acid repeat distribution that is correlated to A-T content. The paper also shows that this altered use of amino acids in SAARs is consistent with the repeat distributions being under selective pressure. CONCLUSIONS: The study shows that simple amino acid repeat distributions can be used to group related species and to examine their phylogenetic relationships. This study also shows that an outgroup species with a similar A-T content can be distinguished based only on the amino acid usage in repeats, and suggest that this might be a useful feature for proteome clustering. The lineage specific use of amino acids in repeat regions suggests that comparative studies of SAAR distributions between proteomes gives an insight into the mechanisms of expansion and the selective pressures acting on the organism.

  18. 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

    of Atlantic cod (Gadus morhua) studied over an 80-year period. Screening of >1000 gene-associated single-nucleotide polymorphisms (SNPs) identified 77 loci that showed highly elevated levels of differentiation, likely as an effect of directional selection, in either time, space or both. Exploratory analysis...... the 1928 to 1960 period showed almost complete stability during later decades. The contrasting microevolutionary trajectories among populations resulted in sequential shifts in spatial outliers, with no locus maintaining elevated spatial differentiation throughout the study period. Simulations of migration...

  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. PMID:27381649

  20. Comparative genomics of chemosensory protein genes reveals rapid evolution and positive selection in ant-specific duplicates.

    Science.gov (United States)

    Kulmuni, J; Wurm, Y; Pamilo, P

    2013-06-01

    Gene duplications can have a major role in adaptation, and gene families underlying chemosensation are particularly interesting due to their essential role in chemical recognition of mates, predators and food resources. Social insects add yet another dimension to the study of chemosensory genomics, as the key components of their social life rely on chemical communication. Still, chemosensory gene families are little studied in social insects. Here we annotated chemosensory protein (CSP) genes from seven ant genomes and studied their evolution. The number of functional CSP genes ranges from 11 to 21 depending on species, and the estimated rates of gene birth and death indicate high turnover of genes. Ant CSP genes include seven conservative orthologous groups present in all the ants, and a group of genes that has expanded independently in different ant lineages. Interestingly, the expanded group of genes has a differing mode of evolution from the orthologous groups. The expanded group shows rapid evolution as indicated by a high dN/dS (nonsynonymous to synonymous changes) ratio, several sites under positive selection and many pseudogenes, whereas the genes in the seven orthologous groups evolve slowly under purifying selection and include only one pseudogene. These results show that adaptive changes have played a role in ant CSP evolution. The expanded group of ant-specific genes is phylogenetically close to a conservative orthologous group CSP7, which includes genes known to be involved in ant nestmate recognition, raising an interesting possibility that the expanded CSPs function in ant chemical communication. PMID:23403962

  1. 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.

  2. 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. PMID:27483397

  3. Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection.

    Science.gov (United States)

    Pandey, Rajesh; Bhattacharya, Aniket; Bhardwaj, Vivek; Jha, Vineet; Mandal, Amit K; Mukerji, Mitali

    2016-01-01

    Primate-specific Alus harbor different regulatory features, including miRNA targets. In this study, we provide evidence for miRNA-mediated modulation of transcript isoform levels during heat-shock response through exaptation of Alu-miRNA sites in mature mRNA. We performed genome-wide expression profiling coupled with functional validation of miRNA target sites within exonized Alus, and analyzed conservation of these targets across primates. We observed that two miRNAs (miR-15a-3p and miR-302d-3p) elevated in stress response, target RAD1, GTSE1, NR2C1, FKBP9 and UBE2I exclusively within Alu. These genes map onto the p53 regulatory network. Ectopic overexpression of miR-15a-3p downregulates GTSE1 and RAD1 at the protein level and enhances cell survival. This Alu-mediated fine-tuning seems to be unique to humans as evident from the absence of orthologous sites in other primate lineages. We further analyzed signatures of selection on Alu-miRNA targets in the genome, using 1000 Genomes Phase-I data. We found that 198 out of 3177 Alu-exonized genes exhibit signatures of selection within Alu-miRNA sites, with 60 of them containing SNPs supported by multiple evidences (global-FST > 0.3, pair-wise-FST > 0.5, Fay-Wu's H  2.0, high ΔDAF) and implicated in p53 network. We propose that by affecting multiple genes, Alu-miRNA interactions have the potential to facilitate population-level adaptations in response to environmental challenges. PMID:27586304

  4. 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.

  5. RFI channels

    Science.gov (United States)

    Mceliece, R. J.

    1980-01-01

    A class of channel models is presented which exhibit varying burst error severity much like channels encountered in practice. An information-theoretic analysis of these channel models is made, and conclusions are drawn that may aid in the design of coded communication systems for realistic noisy channels.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Pricing Models of Closed-Loop Supply Chain and Decisions on Collecting Channel Selection%闭环供应链定价模型与回收渠道选择决策

    Institute of Scientific and Technical Information of China (English)

    洪宪培; 王宗军; 赵丹

    2012-01-01

    利用Stackelberg博弈理论考察了具有直接销售渠道和间接销售渠道的闭环供应链的定价以及制造商回收渠道的选择等问题,构建了3种不同回收渠道下的闭环供应链模型.研究发现:①当间接销售渠道销售产品的市场份额在不同范围内取值时,批发价格和直接销售渠道的销售价格呈现出不同的关系 ;②当3种回收渠道的回收成本相同时,制造商回收渠道的效率更高 ;③影响回收渠道选择的主要因素与制造商所获利润的大小有关,当3种回收渠道的回收成本相同与不同时,制造商会根据自己所获利润的大小,选取不同的回牧渠道对废旧品进行回收.%This paper studies the pricing of the closed-loop supply chain with direct and indirect distribution channel and the selection of collecting channel by Stackelberg game theory. Closed-loop supply chain models under three different collecting channels are constructed. The results show: (1) The wholesale price and the selling price in direct distribution channel exhibit different relationships, when the choice of the number in certain range with market share of indirect distribution channel;(2) The efficiency of the manufacturer's collecting channel is higher when the collecting cost are the same in three collecting channels; (3)The main factor that influence the selection of the collecting channel is relevant to the manufacturer' s profit. According to the condition of the collecting cost under three collecting channels, the manufacturer selects different collecting channel deciding on its profit.

  12. 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

  13. 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)

  14. 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.

  15. Structure and orientation of two voltage-dependent anion-selective channel isoforms. An attenuated total reflection fourier-transform infrared spectroscopy study.

    Science.gov (United States)

    Abrecht, H; Goormaghtigh, E; Ruysschaert, J M; Homble, F

    2000-12-29

    Two VDAC (voltage-dependent anion-selective channel) isoforms were purified from seed cotyledons of Phaseolus vulgaris by chromatofocusing chromatography. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was used to study the structural properties of the two isoforms reconstituted in a mixture of asolectin and 5% stigmasterol. The IR spectra of the two VDAC isoforms were highly similar indicating 50 to 53% anti-parallel beta-sheet. The orientation of the beta-strands relative to the barrel axis was calculated from the experimentally obtained dichroic ratios of the amide I beta-sheet component and the amide II band. Comparing the IR spectra of the reconstituted VDAC isoforms with the IR spectra of the bacterial porin OmpF, for which a high resolution structure is available, provided evidence for a general structural organization of the VDAC isoforms similar to that of bacterial porins. Hydrogen-deuterium exchange measurements indicated that the exchange of the amide protons occurs to a higher extent in the two VDAC isoforms than in the OmpF porin.

  16. 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.

  17. 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.

  18. 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

    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。%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 .

  19. 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

  20. 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).

  1. Role of Calcium-activated Potassium Channels in Atrial Fibrillation Pathophysiology and Therapy.

    Science.gov (United States)

    Diness, Jonas G; Bentzen, Bo H; Sørensen, Ulrik S; Grunnet, Morten

    2015-11-01

    Small-conductance Ca(2+)-activated potassium (SK) channels are relative newcomers within the field of cardiac electrophysiology. In recent years, an increased focus has been given to these channels because they might constitute a relatively atrial-selective target. This review will give a general introduction to SK channels followed by their proposed function in the heart under normal and pathophysiological conditions. It is revealed how antiarrhythmic effects can be obtained by SK channel inhibition in a number of species in situations of atrial fibrillation. On the contrary, the beneficial effects of SK channel inhibition in situations of heart failure are questionable and still needs investigation. The understanding of cardiac SK channels is rapidly increasing these years, and it is hoped that this will clarify whether SK channel inhibition has potential as a new anti-atrial fibrillation principle. PMID:25830485

  2. Role of Calcium-activated Potassium Channels in Atrial Fibrillation Pathophysiology and Therapy.

    Science.gov (United States)

    Diness, Jonas G; Bentzen, Bo H; Sørensen, Ulrik S; Grunnet, Morten

    2015-11-01

    Small-conductance Ca(2+)-activated potassium (SK) channels are relative newcomers within the field of cardiac electrophysiology. In recent years, an increased focus has been given to these channels because they might constitute a relatively atrial-selective target. This review will give a general introduction to SK channels followed by their proposed function in the heart under normal and pathophysiological conditions. It is revealed how antiarrhythmic effects can be obtained by SK channel inhibition in a number of species in situations of atrial fibrillation. On the contrary, the beneficial effects of SK channel inhibition in situations of heart failure are questionable and still needs investigation. The understanding of cardiac SK channels is rapidly increasing these years, and it is hoped that this will clarify whether SK channel inhibition has potential as a new anti-atrial fibrillation principle.

  3. 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。

  4. 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.

  5. 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 .

  6. 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.

  7. Evolutionary game model on the channel selection of the supply and the demand parties%供需双方渠道选择行为的演化博弈模型

    Institute of Scientific and Technical Information of China (English)

    马慧; 杨德礼; 陈大鹏

    2011-01-01

    电子商务的发展给供需双方带来了机遇,同时也使其面临渠道选择的困惑。从供需双方渠道选择问题入手,针对其策略选择的有限理性特点,利用演化博弈方法,设计了供应链供需双方渠道选择过程的演化博弈模型,分别得到供应方选择双分销渠道和需求方选择网络渠道的复制动态方程,分析了在消费者剩余和供应方的期望利润等不同因素的影响下双方的行为演化和演化稳定策略并提出了相应建议。%The development of electronic business brings chances to both the supply and the demand parties. However,at the same time, both parties face the puzzle in channel selection, Base on the situation,the problem of channel selection is discussed by evolutionary game method according to the bounded rationality characteristics of both parties when make decisions. The evolutionary game model is designed in the process of channel selection. Futhermore, the replicator dynamics equation is achieved under the case of the supply part in dual-channel and the demand party in network channel. The behavior evolution and evolutionary stabilization strategy are analyzed under the influence of consumer's surplus and the expect profit.Finally,some proposals for both parties are present according to the analysis results.

  8. 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.

  9. 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. PMID:24983012

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

    Directory of Open Access Journals (Sweden)

    Guan Gui

    2014-01-01

    Full Text Available 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.

  11. Channel Change in 2007 at Selected Sites on the Marias River, Montana, Following a 2006 High-Flow Release from Tiber Dam

    Science.gov (United States)

    Auble, Gregor T.; Bowen, Zachary H.

    2009-01-01

    In June 2006, an opportunistic high-flow release was made from Tiber Dam on the Marias River in Montana to investigate possible alternatives for partially restoring the river's natural flow pattern and variability. At two sites along the river, we measured channel geometry in 2006 before and after the high-flow release to evaluate channel change and alteration of physical habitat. Here we provide data from a resurvey of those sites, conducted in August 2007.

  12. Evolutionary Adaptation of the Amino Acid and Codon Usage of the Mosquito Sodium Channel following Insecticide Selection in the Field Mosquitoes

    OpenAIRE

    Qiang Xu; Lee Zhang; Ting Li; Lan Zhang; Lin He; Ke Dong; Nannan Liu

    2012-01-01

    Target site insensitivity resulting from point mutations within the voltage-gated sodium channel of the insect nervous system is known to be of primary importance in the development of resistance to pyrethroid insecticides. This study shifts current research paradigms by conducting, for the first time, a global analysis of all the naturally occurring mutations, both nonsynonymous and synonymous mutations, as well as mutation combinations in the entire mosquito sodium channel of Culex quinquef...

  13. Morphological and genetic analyses reveal a cryptic species complex in the echinoid Echinocardium cordatum and rule out a stabilizing selection explanation.

    Science.gov (United States)

    Egea, E; David, B; Choné, T; Laurin, B; Féral, J P; Chenuil, A

    2016-01-01

    Preliminary analyses revealed the presence of at least five mitochondrial clades within the widespread sea urchin Echinocardium cordatum (Spatangoida). In this study, we analyzed the genetic (two mitochondrial and two nuclear sequence loci) and morphological characteristics (20 indices) from worldwide samples of this taxon to establish the species limits, morphological diversity and differentiation. Co-occurring spatangoid species were also analyzed with mitochondrial DNA. The nuclear sequences confirm that mitochondrial lineages correspond to true genetic entities and reveal that two clades (named A and B1) hybridize in their sympatry area, although a more closely related pair of clades (B1 and B2), whose distributions widely overlap, does not display hybridization. The morphology of all E. cordatum clade pairs was significantly differentiated, but no morphological diagnostic character was evidenced. By contrast, other spatangoid species pairs that diverged more recently than the E. cordatum clades display clear diagnostic characters. Morphological diversity thus appears responsible for the absence of diagnostic characters, ruling out stabilizing selection, a classical explanation for cryptic species. Alternative classical explanations are (i) environmental plasticity or (ii) a high diversity of genes determining morphology, maintained by varying environmental conditions. We suggest a new hypothesis that the observed morphological diversity is selectively neutral and reflects high effective population sizes in the E. cordatum complex. It is supported by the higher abundance of this taxon compared with other taxa, a trend for the genetic and morphological diversity to be correlated in Europe, and the higher genetic and morphological diversities found in clades of E cordatum (except B1) than in other spatangoid samples in Europe. However, the Pacific clades do not confirm these trends. PMID:26265259

  14. 基于动态频谱博弈约束机制的认知无线网络信道选择算法%Cognitive radio network channel selection algorithm based on dynamic spectrum game binding mechanism

    Institute of Scientific and Technical Information of China (English)

    王思秀; 郭文强; 阿布都热合曼·卡的尔

    2015-01-01

    For the problem that cognitive wireless network channel access,to reduce interference between the channels au-thorized by the primary user of the second user,and increase the efficiency of channel utilization,this paper proposed a cogni-tive radio network channel selection algorithm based on dynamic spectrum game binding mechanism.First of all,it proposed a game constraint mechanism to analyze secondary users in the use of spectrum resources as well as the cost to harvest the bene-fits,constraints derived function spectrum allocation game,the spectral time selected by the user can be utilized as much as possible and to produce benefits improve the utilization of spectrum resources.Secondly,in order to choose a better access channel,channel selection method based on channel utilization,packet loss rate,power situation of these three performance indicators to select authorized idle channel.Simulation and comparison of experimental results show that the algorithm based on time series prediction method compared to the competition and cooperative spectrum access based method to reduce the delay in channel access interference and improve with better results on the channel utilization.%针对认知无线网络的信道接入问题,为减少在授权信道上次用户与主用户之间的互相干扰,并提高信道利用效率,提出一种基于动态频谱博弈约束机制的认知无线网络信道选择算法。首先提出一种博弈约束机制,分析次用户在利用频谱资源时所付出的成本以及所收获的效益,得出频谱分配博弈的约束函数,使次用户所选择的频谱能够尽可能地被利用并产生效益,提高频谱资源的利用率。为了选择更好的接入信道,采用基于信道利用率、丢包率、功率情况这三种性能指标的信道选择方法来选择授权的空闲信道。实验仿真及对比结果表明,该算法相比基于时间序列预测方法和基于竞争协作频谱接入方法

  15. 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

  16. 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.

  17. 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.

  18. Functional Insights from Glutamate Receptor Ion Channel Structures

    Science.gov (United States)

    Kumar, Janesh; Mayer, Mark L.

    2014-01-01

    X-ray crystal structures for the soluble amino terminal and ligand binding domains of glutamate receptor ion channels, combined with a 3.6 Å resolution structure of the full length AMPA receptor GluA2 homotetramer, provide unique insights into the mechanisms of iGluR assembly and function. Increasingly sophisticated biochemical, computational and electrophysiological experiments are beginning to reveal the mechanism of action of partial agonists, and yield new models for the mechanism of action of allosteric modulators. Newly identified NMDA receptor ligands acting at novel sites offer hope for development of subtype selective modulators. Many issues remain unsolved, including the role of the ATD in AMPA receptor signaling, and the mechanisms by which auxiliary proteins regulate receptor activity. The structural basis for ion permeation and ion channel block also remain areas of uncertainty, and despite substantial progress, molecular dynamics simulations have yet to reveal how binding of glutamate opens the ion channel pore. PMID:22974439

  19. Insect sodium channels and insecticide resistance

    OpenAIRE

    Dong, Ke

    2007-01-01

    Voltage-gated sodium channels are essential for the generation and propagation of action potentials (i.e., electrical impulses) in excitable cells. Although most of our knowledge about sodium channels is derived from decades of studies of mammalian isoforms, research on insect sodium channels is revealing both common and unique aspects of sodium channel biology. In particular, our understanding of the molecular dynamics and pharmacology of insect sodium channels has advanced greatly in recent...

  20. Molecular dynamics of CYP2D6 polymorphisms in the absence and presence of a mechanism-based inactivator reveals changes in local flexibility and dominant substrate access channels.

    Directory of Open Access Journals (Sweden)

    Parker W de Waal

    Full Text Available Cytochrome P450 enzymes (CYPs represent an important enzyme superfamily involved in metabolism of many endogenous and exogenous small molecules. CYP2D6 is responsible for ∼ 15% of CYP-mediated drug metabolism and exhibits large phenotypic diversity within CYPs with over 100 different allelic variants. Many of these variants lead to functional changes in enzyme activity and substrate selectivity. Herein, a molecular dynamics comparative analysis of four different variants of CYP2D6 was performed. The comparative analysis included simulations with and without SCH 66712, a ligand that is also a mechanism-based inactivator, in order to investigate the possible structural basis of CYP2D6 inactivation. Analysis of protein stability highlighted significantly altered flexibility in both proximal and distal residues from the variant residues. In the absence of SCH 66712, *34, *17-2, and *17-3 displayed more flexibility than *1, and *53 displayed more rigidity. SCH 66712 binding reversed flexibility in *17-2 and *17-3, through *53 remained largely rigid. Throughout simulations with docked SCH 66712, ligand orientation within the heme-binding pocket was consistent with previously identified sites of metabolism and measured binding energies. Subsequent tunnel analysis of substrate access, egress, and solvent channels displayed varied bottle-neck radii. Taken together, our results indicate that SCH 66712 should inactivate these allelic variants, although varied flexibility and substrate binding-pocket accessibility may alter its interaction abilities.

  1. Structure and Mechanism of a Pentameric Formate Channel

    Energy Technology Data Exchange (ETDEWEB)

    Waight, A.; Love, J; Wang, D

    2010-01-01

    Formate transport across the inner membrane is a critical step in anaerobic bacterial respiration. Members of the formate/nitrite transport protein family function to shuttle substrate across the cytoplasmic membrane. In bacterial pathogens, the nitrite transport protein is involved in protecting bacteria from peroxynitrite released by host macrophages. We have determined the 2.13-{angstrom} structure of the formate channel FocA from Vibrio cholerae, which reveals a pentamer in which each monomer possesses its own substrate translocation pore. Unexpectedly, the fold of the FocA monomer resembles that found in water and glycerol channels. The selectivity filter in FocA consists of a cytoplasmic slit and a central constriction ring. A 2.5-{angstrom} high-formate structure shows two formate ions bound to the cytoplasmic slit via both hydrogen bonding and van der Waals interactions, providing a structural basis for the substrate selectivity of the channel.

  2. Single-step selection of drug resistant Acinetobacter baylyi ADP1 mutants reveals a functional redundancy in the recruitment of multidrug efflux systems.

    Directory of Open Access Journals (Sweden)

    Anthony J Brzoska

    Full Text Available Members of the genus Acinetobacter have been the focus recent attention due to both their clinical significance and application to molecular biology. The soil commensal bacterium Acinetobacter baylyi ADP1 has been proposed as a model system for molecular and genetic studies, whereas in a clinical environment, Acinetobacter spp. are of increasing importance due to their propensity to cause serious and intractable systemic infections. Clinically, a major factor in the success of Acinetobacter spp. as opportunistic pathogens can be attributed to their ability to rapidly evolve resistance to common antimicrobial compounds. Whole genome sequencing of clinical and environmental Acinetobacter spp. isolates has revealed the presence of numerous multidrug transporters within the core and accessory genomes, suggesting that efflux is an important host defense response in this genus. In this work, we used the drug-susceptible organism A. baylyi ADP1 as a model for studies into the evolution of efflux mediated resistance in genus Acinetobacter, due to the high level of conservation of efflux determinants across four diverse Acinetobacter strains, including clinical isolates. A single exposure of therapeutic concentrations of chloramphenicol to populations of A. baylyi ADP1 cells produced five individual colonies displaying multidrug resistance. The major facilitator superfamily pump craA was upregulated in one mutant strain, whereas the resistance nodulation division pump adeJ was upregulated in the remaining four. Within the adeJ upregulated population, two different levels of adeJ mRNA transcription were observed, suggesting at least three separate mutations were selected after single-step exposure to chloramphenicol. In the craA upregulated strain, a T to G substitution 12 nt upstream of the craA translation initiation codon was observed. Subsequent mRNA stability analyses using this strain revealed that the half-life of mutant craA mRNA was significantly

  3. 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.

  4. Multi-ion conduction bands in a simple model of calcium ion channels

    International Nuclear Information System (INIS)

    We report self-consistent Brownian dynamics simulations of a simple electrostatic model of the selectivity filters (SF) of calcium ion channels. They reveal regular structure in the conductance and selectivity as functions of the fixed negative charge Qf at the SF. With increasing Qf, there are distinct regions of high conductance (conduction bands) M0, M1, M2 separated by regions of almost zero-conductance (stop-bands). Two of these conduction bands, M1 and M2, are related to the saturated calcium occupancies of P = 1 and P = 2, respectively and demonstrate self-sustained conductivity. Despite the model's limitations, its M1 and M2 bands show high calcium selectivity and prominent anomalous mole fraction effects and can be identified with the L-type and RyR calcium channels. The non-selective band M0 can be identified with a non-selective cation channel, or with OmpF porin. (paper)

  5. On Data and Parameter Estimation Using the Variational Bayesian EM-algorithm for Block-fading Frequency-selective MIMO Channels

    DEFF Research Database (Denmark)

    Christensen, Lars P.B.; Larsen, Jan

    2006-01-01

    A general Variational Bayesian framework for iterative data and parameter estimation for coherent detection is introduced as a generalization of the EM-algorithm. Explicit solutions are given for MIMO channel estimation with Gaussian prior and noise covariance estimation with inverse-Wishart prio...

  6. 2-aminoethoxydiphenyl borate or lanthanum potentiates transient receptor potential-like channels in rat CA1 hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Fengpeng Sun; Tian-ming Gao

    2010-01-01

    Expression of transient receptor potential(TRP)channels is widespread with transcripts distributed throughout the brain.All TRP channel subunits are activated following phospholipase C activation and form cation-selective ion channels.Previous studies examining the existence of TRP channels in hippocampal CA1 pyramidal neurons were based on cultured neurons.Therefore,their relevance for living tissue remains unclear.In the present study,patch-clamp recordings were conducted from CA1 pyramidal neurons in hippocampal slices from 7-day-old rats.Whole-cell currents were obtained from CA1 hippocampal neurons with potentiation effects of 2-aminoethoxydiphenyl borate and lanthanum,revealing that recorded experimental currents were characteristic TRP-like channel currents.Identification of rat hippocampal mRNA transcripts of TRPC4,TRPC5,TRPV1,TRPV2,and TRPV3 channels further verified the expression of characteristic TRP-like channels on rat CA1hippocampal neurons.

  7. Research on selecting the sale channel model of the information goods%信息产品销售渠道模式选择研究

    Institute of Scientific and Technical Information of China (English)

    刘志勇; 李敏强; 寇纪淞

    2013-01-01

    The information goods manufacturer can distribute their products through many kinds of channels, e.g. online direct sale and traditional retail marketing. The retailer pays a manufacturer based on two common payment schemes, the Fixed-fee policy and the Per-copy policy. Which channel and sell model is preferable for the manufacture? The product quality, the price, and the customer acceptance for direct channel are the decisive factors. Through analyzing the decision behaviors of the manufacture, retailer and consumer, the model of maximizing the manufacture's profit is presented in the presence of both direct and retail channel. Based on the comparison among different channels, the paper shows that when the valuation for the information goods has a uniform distribution, the manufacture prefers the Fixed-fee policy through the direct sale channel, whereas the Per-copy policy is preferable through dual-channel. The best sale channel strategy is to distribute the high-quality version through the direct sale channel and the low-quality version through the retailing channel for the manufacturer.%信息产品供应商在销售产品时有多种渠道可以选择,可以通过在线直销,也可以通过传统的零售渠道方式.而在零售模式下,供应商可以与零售商之间采用Fixed-fee协议或Per-copy协议.供应商在面临这些不同的销售渠道和销售方式时,产品质量、销售价格以及消费者对直销渠道的接受程度等因素决定了最终的选择方式.通过对供应商、零售商和消费者的决策行为进行分析,给出了供应商通过直销渠道和零售渠道销售产品下的收益最优化模型,并对结果进行了比较.研究表明当消费者对产品评价值服从均匀分布的情况时,零售渠道下采用Fixed-fee模式有利于供应商,而在双重渠道下,供应商采用Per-copy模式更有利.而且当供应商采用直销渠道销售高质量产品,由零售渠道销售较低质量产品时,供应商能获得最大收益.

  8. Multi-ion conduction bands in a simple model of calcium ion channels

    CERN Document Server

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

    2012-01-01

    We report self-consistent Brownian dynamics simulations of a simple electrostatic model of the selectivity filters (SF) of calcium ion channels. They reveal regular structure in the conductance and selectivity as functions of the fixed negative charge Qf at the SF. This structure comprises distinct regions of high conductance (conduction bands) M0, M1, M2 separated by regions of zero-conductance (stop-bands). Two of these conduction bands, M1 and M2, demonstrate high calcium selectivity and prominent anomalous mole fraction effects and can be identified with the L-type and RyR calcium channels.

  9. Quantification of uncoupling protein 2 reveals its main expression in immune cells and selective up-regulation during T-cell proliferation.

    Directory of Open Access Journals (Sweden)

    Anne Rupprecht

    Full Text Available Uncoupling protein 2 (UCP2 is an inner mitochondrial membrane protein. Although the protein was discovered in 1997, its function and even its tissue distribution are still under debate. Here we present a quantitative analysis of mRNA and protein expression in various mice tissues, revealing that UCP2 is mainly expressed in organs and cells associated with the immune system. Although the UCP2 gene is present in the brain, as demonstrated using quantitative RT-PCR, the protein was not detectable in neurons under physiological conditions. Instead, we could detect UCP2 in microglia, which act in the immune defense of the central nervous system. In lymphocytes, activation led to a ten-fold increase of UCP2 protein expression simultaneously to the increase in levels of other mitochondrial proteins, whereas lymphocyte re-stimulation resulted in the selective increase of UCP2. The highest detected level of UCP2 expression in stimulated T-cells (0.54 ng/(µg total cellular protein was approximately 200 times lower than the level of UCP1 in brown adipose tissue from room temperature acclimated mice. Both the UCP2 expression pattern and the time course of up-regulation in stimulated T-cells imply UCP2's involvement in the immune response, probably by controlling the metabolism during cell proliferation.

  10. Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging

    Science.gov (United States)

    Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Ma, Tian-Hsiang; Lin, Yi-Chun; Lo, Szecheng J.; Chang, Ta-Chau

    2016-08-01

    Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm‑1) and lipid (~2845 cm‑1) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans.

  11. Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging

    Science.gov (United States)

    Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Ma, Tian-Hsiang; Lin, Yi-Chun; Lo, Szecheng J.; Chang, Ta-Chau

    2016-08-01

    Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm-1) and lipid (~2845 cm-1) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans.

  12. Crystal Structure of a Thermostable Alanine Racemase from Thermoanaerobacter tengcongensis MB4 Reveals the Role of Gln360 in Substrate Selection.

    Directory of Open Access Journals (Sweden)

    Xiaoliang Sun

    Full Text Available Pyridoxal 5'-phosphate (PLP dependent alanine racemase catalyzes racemization of L-Ala to D-Ala, a key component of the peptidoglycan network in bacterial cell wall. It has been extensively studied as an important antimicrobial drug target due to its restriction in eukaryotes. However, many marketed alanine racemase inhibitors also act on eukaryotic PLP-dependent enzymes and cause side effects. A thermostable alanine racemase (AlrTt from Thermoanaerobacter tengcongensis MB4 contains an evolutionarily non-conserved residue Gln360 in inner layer of the substrate entryway, which is supposed to be a key determinant in substrate specificity. Here we determined the crystal structure of AlrTt in complex with L-Ala at 2.7 Å resolution, and investigated the role of Gln360 by saturation mutagenesis and kinetic analysis. Compared to typical bacterial alanine racemase, presence of Gln360 and conformational changes of active site residues disrupted the hydrogen bonding interactions necessary for proper PLP immobilization, and decreased both the substrate affinity and turnover number of AlrTt. However, it could be complemented by introduction of hydrophobic amino acids at Gln360, through steric blocking and interactions with a hydrophobic patch near active site pocket. These observations explained the low racemase activity of AlrTt, revealed the essential role of Gln360 in substrate selection, and its preference for hydrophobic amino acids especially Tyr in bacterial alanine racemization. Our work will contribute new insights into the alanine racemization mechanism for antimicrobial drug development.

  13. Ion channels and the transduction of light signals

    Science.gov (United States)

    Spalding, E. P.; Evans, M. L. (Principal Investigator)

    2000-01-01

    Studies of biological light-sensing mechanisms are revealing important roles for ion channels. Photosensory transduction in plants is no exception. In this article, the evidence that ion channels perform such signal-transducing functions in the complex array of mechanisms that bring about plant photomorphogenesis will be reviewed and discussed. The examples selected for discussion range from light-gradient detection in unicellular algae to the photocontrol of stem growth in Arabidopsis. Also included is some discussion of the technical aspects of studies that combine electrophysiology and photobiology.

  14. An ERG channel inhibitor from the scorpion Buthus eupeus

    DEFF Research Database (Denmark)

    Korolkova, Y.V.; Kozlov, S.A.; Lipkin, A.V.;

    2001-01-01

    the cloning, expression, and selectivity of BeKm-1. A full-length cDNA of 365 nucleotides encoding the precursor of BeKm-1 was isolated using the rapid amplification of cDNA ends polymerase chain reaction technique from mRNA obtained from scorpion telsons. Sequence analysis of the cDNA revealed......, KCNQ4 channels, and minimal effect on rELK1. Thus, BeKm-1 was shown to be a novel specific blocker of hERG1 potassium channels....

  15. WSN Doubly Selective Channel Feature Matching Algorithm in Complex Application Environment%复杂应用环境下WSN双选信道特征配准算法

    Institute of Scientific and Technical Information of China (English)

    王云良; 刘贤锋

    2015-01-01

    无线传感器网络(WSN)在复杂应用环境下的双选信道特征配准算法研究,是对WSN数据管理的关键技术,WSN在数据发送中要经历时间和频率的双选择性衰落,为了在接收端被正确地接收,需要进行特征配准设计。传统方法采用普勒域单信道配准方法,特征配准效果不好。提出一种基于时延-多普勒域的时间和频率双选信道特征配准算法,满足复杂应用环境下的WSN数据管理需求。在线自适应调整信道配准控制误差,动态实时捕获信道传输数据,实现节点自适应优化分布,通过信道模型构建,对WSN进行时延-多普勒域表征,采用双选信道估计方法实现特征配准。仿真结果表明,该算法在复杂应用环境下,根据不同的调制信号,在不同带内信噪比下能实现对WSN的双选信道特征配准,准确率高于传统算法,抗噪性能较好,提高WSN的数据管理和调度能力,展示了本文算法的优越性能。%Wireless sensor network (WSN) of doubly selective channel feature matching algorithm in complex application environment is the key technology of WSN data management, doubly selective WSN to experience time and frequency in da⁃ta transmitting fading, in order to be correctly receive the signal, need for feature matching design. The traditional method used the Doppler domain single channel matching method, and feature registration effect is not good. A time and frequency doubly selective channel feature matching algorithm of time delay-Doppler domain is proposed for WSN data management, it meets the needs of complex application environment. Online adaptive adjustment channel registration error is controlled, dynamic real-time capture channel transmission data, realize node adaptive optimization distribution, through the construc⁃tion of channel models, delay Doppler domain characterization of WSN is estimated, feature matching using the doubly se

  16. Exploring the Dynamics of the TWIK-1 Channel.

    Science.gov (United States)

    Oakes, Victoria; Furini, Simone; Pryde, David; Domene, Carmen

    2016-08-23

    Potassium channels in the two-pore domain family (K2P) have various structural attributes that differ from those of other K(+) channels, including a dimeric assembly constituted of nonidentical domains and an expansive extracellular cap. Crystallization of the prototypical K2P channel, TWIK-1, finally revealed the structure of these characteristics in atomic detail, allowing computational studies to be undertaken. In this study, we performed molecular-dynamics simulations for a cumulative time of ∼1 μs to discern the mechanism of ion transport throughout TWIK-1. We observed the free passage of ions beneath the extracellular cap and identified multiple high-occupancy sites in close proximity to charged residues on the protein surface. Despite the overall topological similarity of the x-ray structure of the selectivity filter to other K(+) channels, the structure diverges significantly in molecular-dynamics simulations as a consequence of nonconserved residues in both pore domains contributing to the selectivity filter (T118 and L228). The behavior of such residues has been linked to channel inactivation and the phenomenon of dynamic selectivity, where TWIK-1 displays robust Na(+) inward flux in response to subphysiological K(+) concentrations. PMID:27558721

  17. A BDT optimization study and assessment of deep learning in selecting VBF events in the $H\\to ZZ^{*}\\to4l$ channel

    CERN Document Server

    Morningstar, Alan

    2015-01-01

    Since the discovery of the Higgs boson in 2012, the most recently confirmed and final piece of the Standard Model has been rigorously studied in various production modes and decay channels. However, Run 1 of the LHC did not yield sufficient statistics to resolve production modes in the $H\\to ZZ^{*}\\to4l$ channel. Current and future runs of the LHC will offer sufficient data to do so, thus machine learning techniques used to separate the two most frequent Higgs boson production modes - gluon fusion and vector boson fusion - were studied and the findings are presented in this report. An optimization of boosted decision trees trained on $\\sqrt{s}=\\text{8 TeV}$ ATLAS Monte Carlo data is presented. The feasibility of improving classification efficiency by using deep neural networks is also studied and detailed below.

  18. High-resolution GPS tracking reveals habitat selection and the potential for long-distance seed dispersal by Madagascan flying foxes Pteropus rufus

    Directory of Open Access Journals (Sweden)

    Ryszard Oleksy

    2015-01-01

    Full Text Available Long-distance seed dispersal can be important for the regeneration of forested habitats, especially in regions where deforestation has been severe. Old World fruit bats (Pteropodidae have considerable potential for long-distance seed dispersal. We studied the movement patterns and feeding behaviour of the endemic Madagascan flying fox Pteropus rufus, in Berenty Reserve, southeast Madagascar. Between July and September 2012 (the dry season nine males and six females were tagged with customised GPS loggers which recorded fixes every 2.5 min between 18.00 and 06.00 h. The combined home range of all of the tagged bats during 86 nights exceeded 58,000 ha. Females had larger home ranges and core foraging areas and foraged over longer distances (average 28.1 km; median 26.7 km than males (average 15.4 km; median 9.5 km. Because the study was conducted during the gestation period, the increased energy requirements of females may explain their greater mean foraging area. Compositional analysis revealed that bats show strong preferences for overgrown sisal (Agave sisalana plantations (a mix of shrub, trees and sisal plants and remnant riverside forest patches. Sisal nectar and pollen were abundant food sources during the tracking period and this probably contributed to the selective use of overgrown sisal plantations. The bats also ate large quantities of figs (Ficus grevei during the study, and dispersed seeds of this important pioneer species. The bats flew at an average speed of 9.13 m/s, perhaps to optimise gliding performance. The study confirms that P. rufus has the potential to be a long-distance seed disperser, and is able to fly over a large area, often crossing cleared parts of its habitat. It potentially plays an important role in the regeneration of threatened forest habitats in this biodiversity hotspot.

  19. Crystal Structure of a Thermostable Alanine Racemase from Thermoanaerobacter tengcongensis MB4 Reveals the Role of Gln360 in Substrate Selection

    Science.gov (United States)

    Wang, Xiaoyan; Xu, Shujing; Ju, Jiansong; Xu, Xiaoling

    2015-01-01

    Pyridoxal 5’-phosphate (PLP) dependent alanine racemase catalyzes racemization of L-Ala to D-Ala, a key component of the peptidoglycan network in bacterial cell wall. It has been extensively studied as an important antimicrobial drug target due to its restriction in eukaryotes. However, many marketed alanine racemase inhibitors also act on eukaryotic PLP-dependent enzymes and cause side effects. A thermostable alanine racemase (AlrTt) from Thermoanaerobacter tengcongensis MB4 contains an evolutionarily non-conserved residue Gln360 in inner layer of the substrate entryway, which is supposed to be a key determinant in substrate specificity. Here we determined the crystal structure of AlrTt in complex with L-Ala at 2.7 Å resolution, and investigated the role of Gln360 by saturation mutagenesis and kinetic analysis. Compared to typical bacterial alanine racemase, presence of Gln360 and conformational changes of active site residues disrupted the hydrogen bonding interactions necessary for proper PLP immobilization, and decreased both the substrate affinity and turnover number of AlrTt. However, it could be complemented by introduction of hydrophobic amino acids at Gln360, through steric blocking and interactions with a hydrophobic patch near active site pocket. These observations explained the low racemase activity of AlrTt, revealed the essential role of Gln360 in substrate selection, and its preference for hydrophobic amino acids especially Tyr in bacterial alanine racemization. Our work will contribute new insights into the alanine racemization mechanism for antimicrobial drug development. PMID:26218070

  20. Transcriptome-wide N⁶-methyladenosine profiling of rice callus and leaf reveals the presence of tissue-specific competitors involved in selective mRNA modification.

    Science.gov (United States)

    Li, Yuli; Wang, Xiliang; Li, Cuiping; Hu, Songnian; Yu, Jun; Song, Shuhui

    2014-01-01

    N(6)-methyladenosine (m(6)A) is the most prevalent internal modification present in mRNAs of all higher eukaryotes. With the development of MeRIP-seq technique, in-depth identification of mRNAs with m(6)A modification becomes feasible. Here we present a transcriptome-wide m(6)A modification profiling effort for rice transcriptomes of differentiated callus and leaf, which yields 8,138 and 14,253 m(6)A-modified genes, respectively. The m(6)A peak (m(6)A-modified nucleotide position on mRNAs) distribution exhibits preference toward both translation termination and initiation sites. The m(6)A peak enrichment is negatively correlated with gene expression and weakly positively correlated with certain gene features, such as exon length and number. By comparing m(6)A-modified genes between the 2 samples, we define 1,792 and 6,508 tissue-specific m(6)A-modified genes (TSMGs) in callus and leaf, respectively. Among which, 626 and 5,509 TSMGs are actively expressed in both tissues but are selectively m(6)A-modified (SMGs) only in one of the 2 tissues. Further analyses reveal characteristics of SMGs: (1) Most SMGs are differentially expressed between callus and leaf. (2) Two conserved RNA-binding motifs, predicted to be recognized by PUM and RNP4F, are significantly over-represented in SMGs. (3) GO enrichment analysis shows that SMGs in callus mainly participate in transcription regulator/factor activity whereas SMGs in leaf are mainly involved in plastid and thylakoid. Our results suggest the presence of tissue-specific competitors involved in SMGs. These findings provide a resource for plant RNA epitranscriptomic studies and further enlarge our knowledge on the function of RNA m(6)A modification.

  1. TRESK potassium channel in human T lymphoblasts

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-03

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

  2. Performance Analysis of Multi-user Multi Input Multi Output- Interleave-Division Multiple-Access System Employing Turbo Coding 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 multi-user Multi Input Multi Output (MIMO assisted interleave based multiple-access system. In IDMA, different interleavers are used to distinguish users as against different signature sequence in a conventional code-Division Multiple-Access (CDMA scheme. Approach: The basic principle of IDMA is that the interleaver is unique for the users. Results: In this study, we consider that Interleavers are generated independently and randomly. Also the IDMA technique is extended to multi user MIMO IDMA with multi-user detection. At the receiver, OSIC detector is realized using ZF for frequency fading channel to combat MAI and MUI problem. The performance of the system is analyzed for different channel conditions using extensive simulation runs based on Monte Carlo simulation trials. Conclusion: It is shown that the IDMA scheme can achieve near single user performance in situations with very large numbers of users while maintaining very low receiver complexity. It is discerned from the computer simulation results that IDMA outperforms CDMA in frequency selective channel for high load conditions.

  3. Effects of a 2006 High-Flow Release from Tiber Dam on Channel Morphology at Selected Sites on the Marias River, Montana

    Science.gov (United States)

    Auble, Gregor T.; Bowen, Zachary H.

    2008-01-01

    In June 2006, an opportunistic high-flow release was made from Tiber Dam on the Marias River in Mont., to investigate possible alternatives for partially restoring the river's natural flow pattern and variability. At two sites along the river, we measured channel geometry before and after the high-flow release to evaluate channel change and alteration of physical habitat. Streamflow downstream from Tiber Dam has been stabilized by reduction of high flows and augmentation of low flows. This has produced flood-control benefits as well as some possible adverse environmental effects downstream from the dam. The 2006 high-flow release resulted in a downstream hydrograph with high flows of above-average magnitude in the post-dam flow regime of the Marias River. Timing of the peak and the declining limb of the release hydrograph were very similar to a historical, unregulated hydrograph of the Marias River. Furthermore, the high flow produced many of the qualitative elements of ecologically important physical processes that can be diminished or lost due to flow stabilization downstream from a dam. Typically dry back channels were occupied by flowing water. Islands were inundated, resulting in vegetation removal and sediment accretion that produced new disturbance patches of bare, moist substrate. Cut banks were eroded, and large woody debris was added to the river and redistributed. Flood-plain surfaces were inundated, producing substantial increases in wetted perimeter and spatially distinctive patterns of deposition associated with natural levee formation. The scale of the 2006 high flow - in terms of peak magnitude and the lateral extent of bottomland influenced by inundation or lateral channel movement - was roughly an order of magnitude smaller than the scale of an infrequent high flow in the pre-dam regime. Overall extent and composition of riparian vegetation will continue to change under a scaled-down, post-dam flow regime. For example, the importance of the non

  4. A Proposal for Mapping Historic Irrigation Channels to Reveal Insights into Agro-Climatic Systems: A Case Study in Upper Austria. GI_Forum 2013 – Creating the GISociety|

    OpenAIRE

    Neuwirth, Christian; Eisank, Clemens; D'Oleire-Oltmanns, Sebastian

    2016-01-01

    Recently, the remains of two historic irrigation channels were re-discovered in the Upper Austrian municipality of Regau. Since the current average precipitation in the region is sufficient to sustain a productive agricultural land use, the irrigation channels raise several questions related to climate variability. To verify different hypotheses such as the construction as a response to a changing climate or the assumed purpose of grassland irrigation, potential coherences are discussed. In a...

  5. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  6. Language Planning, Channel Management, and ESP.

    Science.gov (United States)

    Kennedy, Chris

    Channel management, a concept developed in marketing to refer to the process by which a product is moved from production to consumption, uses a channel of distribution operating at several levels, each responsible for one or more of the activities of moving the product forward to the consumer. The function of channel management is to select the…

  7. Partial QoS-Aware Opportunistic Relay Selection Over Two-Hop Channels: End-to-End Performance Under Spectrum-Sharing Requirements

    KAUST Repository

    Yuli Yang,

    2014-10-01

    In this paper, we propose a partial quality-of-service (QoS)-oriented relay selection scheme with a decode-and-forward (DF) relaying protocol, to reduce the feedback amount required for relay selection. In the proposed scheme, the activated relay is the one with the maximum signal-to-noise power ratio (SNR) in the second hop among those whose packet loss rates (PLRs) in the first hop achieve a predetermined QoS level. For the purpose of evaluating the performance of the proposed scheme, we exploit it with transmission constraints imposed on the transmit power budget and interference to other users. By analyzing the statistics of received SNRs in the first and second hops, we obtain the end-to-end PLR of this scheme in closed form under the considered scenario. Moreover, to compare the proposed scheme with popular relay selection schemes, we also derive the closed-form PLR expressions for partial relay selection (PRS) and opportunistic relay selection (ORS) criteria in the same scenario under study. Illustrative numerical results demonstrate the accuracy of our derivations and substantiate that the proposed relay selection scheme is a promising alternative with respect to the tradeoff between performance and complexity.

  8. Optimum Selection Strategy on Selling Channels Based on Ant Colony Algorithm%基于蚁群算法的产品销售渠道优选策略

    Institute of Scientific and Technical Information of China (English)

    王越超; 李毅

    2011-01-01

    Ant colony algorithm has strong ability to find optimal solutions, it can be used for optimization selection of product distribution channels problem. When the information of potential profits which a new product will make in certain selling locations is gathered, ant colony algorithm can be used to obtain the highest sales revenue, if the sales channels and marketing expenses cap are known. The flow chart based on ant colony algorithm was presented. And finally it was proved by case analysis that,ant colony optimization algorithm has effectiveness and good convergence speed,when it is used for the issue of selling channels selection.%鉴于蚁群算法具有较强的发现优选解的能力,将其用于产品销售渠道的优选问题中.当企业收集到某种新产品在可能销售地点的销售收益时,可以利用蚁群算法,求得在已知产品销售渠道和销售支出费用上限的约束条件下的最大销售收益.提出了基于蚁群算法的问题流程图,以实例分析证明了蚁群算法在产品销售渠道优选问题上,具有一定的有效性和较快的收敛速度.

  9. Mitochondrial Ion Channels

    Science.gov (United States)

    O’Rourke, Brian

    2009-01-01

    In work spanning more than a century, mitochondria have been recognized for their multifunctional roles in metabolism, energy transduction, ion transport, inheritance, signaling, and cell death. Foremost among these tasks is the continuous production of ATP through oxidative phosphorylation, which requires a large electrochemical driving force for protons across the mitochondrial inner membrane. This process requires a membrane with relatively low permeability to ions to minimize energy dissipation. However, a wealth of evidence now indicates that both selective and nonselective ion channels are present in the mitochondrial inner membrane, along with several known channels on the outer membrane. Some of these channels are active under physiological conditions, and others may be activated under pathophysiological conditions to act as the major determinants of cell life and death. This review summarizes research on mitochondrial ion channels and efforts to identify their molecular correlates. Except in a few cases, our understanding of the structure of mitochondrial ion channels is limited, indicating the need for focused discovery in this area. PMID:17059356

  10. Dynamics and consequences of water level fluctuations of selected lakes in the catchment of the Ostrowo-Gopło Channel

    Directory of Open Access Journals (Sweden)

    Piasecki Adam

    2014-12-01

    Full Text Available The article discusses water level fluctuations in lakes and the associated changes in the lake surface and water resources in the years 1992-2011. On the basis of detailed field studies carried out in the hydrological year 2011, short-term and dynamic changes in the lakes’ hydrology were determined. Changes in hydrological lake types were evoked by unexpected hydro-meteorological situations, in particular high precipitation totals and sudden thaws in winter. The main symptom of the lake type change was the restoration, after nearly 10 years, of channels connecting the lakes. In addition, a strong interdependence was recorded in the difference between evaporation and precipitation, as well as the mean annual ranges of lake water levels in the years 1992-2010

  11. Brands & Channels

    Institute of Scientific and Technical Information of China (English)

    Alice Yang

    2009-01-01

    @@ "Brands" and "Channels" are the two most important things in Ku-Hai Chen's eyes when doing business with Main-land China. Ku-Hai Chen, Executive Director of the International Trade Institute of Taiwan External Trade Development Council (TAITRA), flies frequently between Chinese Taipei and Mainland China, and was in Beijing earlier this month for his seminar.

  12. 基于学习策略的动态频谱接入信道选择及系统性能%Learning-based channel selection and system performance of dynamic spectrum access

    Institute of Scientific and Technical Information of China (English)

    叶芝慧; 冯奇; 王健

    2012-01-01

    To improve the performances of packet loss rate and throughput in cognitive radio network , an approach for learning-based dynamic spectrum access is put forward for spectrum sensing. A channel selection scheme is proposed under the condition that the priori information of primary user is known. Based on the idle and busy state statistical properties of the primary user signal, secondary user performs sensing on the objective licensed channel in accordance with the vacancy state probability in descending order, and then accesses to the first channel detected to be idle. For the fixed rate and variable rate services, the performances of packet loss rate and throughput of cognitive radio network are analyzed. As for the channel selection scheme in the case of the unknown priori information to the secondary user, the system performances are influenced by the mean probability of error prediction. Simulation results show that the proposed dynamic spectrum access scheme based on learning and prediction achieves better performances in packet loss rate and throughput than the random spectrum sensing. Learning-based channel selection of dynamic spectrum access can exploit spectrum holes efficiently and improve the channel utilization in cognitive radio systems.%为了提高认知无线网络的丢包率和吞吐量性能,运用基于学习策略的动态频谱接入方法感知授权信道.在已知主用户先验信息的条件下,认知用户根据主用户信号忙闲的统计特性,按照空闲状态概率从高到低的顺序依次对目标授权信道进行频谱感知,并接入第1个检测到的空闲信道.针对固定速率和可变速率2种业务类型,分别考察了认知无线网络的丢包率和吞吐量性能.在未知主用户先验统计特性的条件下,认知用户的平均错误预测概率直接影响着系统性能.仿真结果表明,与随机频谱感知性能相比,基于机器学习和预测的频谱感知的丢包率和吞吐量性能均有所

  13. Blocking the passage: C60 geometrically clogs K(+) channels.

    Science.gov (United States)

    Calvaresi, Matteo; Furini, Simone; Domene, Carmen; Bottoni, Andrea; Zerbetto, Francesco

    2015-05-26

    Classical molecular dynamics (MD) simulations combined with docking calculations, potential of mean force estimates with the umbrella sampling method, and molecular mechanic/Poisson-Boltzmann surface area (MM-PBSA) energy calculations reveal that C60 may block K(+) channels with two mechanisms: a low affinity blockage from the extracellular side, and an open-channel block from the intracellular side. The presence of a low affinity binding-site at the extracellular entrance of the channel is in agreement with the experimental results showing a fast and reversible block without use-dependence, from the extracellular compartment. Our simulation protocol suggests the existence of another binding site for C60 located in the channel cavity at the intracellular entrance of the selectivity filter. The escape barrier from this binding site is ∼21 kcal/mol making the corresponding kinetic rate of the order of minutes. The analysis of the change in solvent accessible surface area upon C60 binding shows that binding at this site is governed purely by shape complementarity, and that the molecular determinants of binding are conserved in the entire family of K(+) channels. The presence of this high-affinity binding site conserved among different K(+) channels may have serious implications for the toxicity of carbon nanomaterials. PMID:25873341

  14. Ion-Responsive Channels of Zwitterion-Carbon Nanotube Membrane for Rapid Water Permeation and Ultrahigh Mono-/Multivalent Ion Selectivity.

    Science.gov (United States)

    Liu, Tian-Yin; Yuan, Hao-Ge; Li, Qian; Tang, Yuan-Hui; Zhang, Qiang; Qian, Weizhong; Van der Bruggen, Bart; Wang, Xiaolin

    2015-07-28

    The rational combination of polymer matrix and nanostructured building blocks leads to the formation of composite membranes with unexpected capability of selectivity of monovalent electrolytes and water, which affords the feasibility to effeciently remove harmful ions and neutral molecules from the environment of concentrated salines. However, the multivalent ion rejection in salined water of routine nanocomposite membranes was less than 98% when ion strength is high, resulting in a poor ion selectivity far below the acceptable value. In this contribution, the ion-responsive membrane with zwitterion-carbon nanotube (ZCNT) entrances at the surface and nanochannels inside membrane has been proposed to obtain ultrahigh multivalent ion rejection. The mean effective pore diameter of ZCNT membrane was dedicated tuned from 1.24 to 0.54 nm with the rise in Na2SO4 concentration from 0 to 70 mol m(-3) as contrary to the conventional rejection drop in carbon nanotube (CNT) membrane. The ultrahigh selective permeabilities of monovalent anions against divalent anions of 93 and against glucose of 5.5 were obtained on ZCNT membrane, while such selectivities were only 20 and 1.6 for the pristine CNT membrane, respectively. The ZCNT membranes have potential applications in treatment of salined water with general NaCl concentration from 100 to 600 mol m(-3), which are widely applicable in desalination, food, and biological separation processes. PMID:26153719

  15. Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Stephenson Diane T

    2011-05-01

    doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms. Conclusions We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.

  16. Crystal structure of the epithelial calcium channel TRPV6.

    Science.gov (United States)

    Saotome, Kei; Singh, Appu K; Yelshanskaya, Maria V; Sobolevsky, Alexander I

    2016-06-23

    Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels. Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K(+) channel-like transmembrane domain, Ca(2+) selectivity is determined by direct coordination of Ca(2+) by a ring of aspartate side chains in the selectivity filter. On the basis of crystallographically identified cation-binding sites at the pore axis and extracellular vestibule, we propose a Ca(2+) permeation mechanism. Our results provide a structural foundation for understanding the regulation of epithelial Ca(2+) uptake and its role in pathophysiology. PMID:27296226

  17. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

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

    2004-01-01

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

  18. Single-Channel Recording of Ligand-Gated Ion Channels.

    Science.gov (United States)

    Plested, Andrew J R

    2016-01-01

    Single-channel recordings reveal the microscopic properties of individual ligand-gated ion channels. Such recordings contain much more information than measurements of ensemble behavior and can yield structural and functional information about the receptors that participate in fast synaptic transmission in the brain. With a little care, a standard patch-clamp electrophysiology setup can be adapted for single-channel recording in a matter of hours. Thenceforth, it is a realistic aim to record single-molecule activity with microsecond resolution from arbitrary cell types, including cell lines and neurons. PMID:27480725

  19. The non-selective cation-permeable channel TRPC3 is a tetrahedron with a cap on the large cytoplasmic end.

    Science.gov (United States)

    Mio, Kazuhiro; Ogura, Toshihiko; Hara, Yuji; Mori, Yasuo; Sato, Chikara

    2005-08-01

    TRPC3 plays important roles in neuronal differentiation and immune cell maturation by mediating the cationic current in response to phospholipase C activation, Ca2+ depletion, and diacylglycerol stimulation. Here, we purified the TRPC3 channel using a glycosylated tetramer and observed the structure using electron microscopy. Negatively stained specimens demonstrate homogeneous protein particles containing an internal cavity-like structure. These particle images were picked up by automated pick-up programs, aligned, and classified by the growing neural gas network method. Similarly oriented projections were averaged to decrease the signal-to-noise ratio. The averaged images progress from the top view to the side views, which are representative of their raw images. The top view confirmed the hypothesis of a four-domain structure, and the side view demonstrates a large cytoplasmic domain with a capped structure at the bottom, which is near a predicted locus of ion release. The total image of the protein is a blunt-edged trapezoid of 200 x 200 x 235 A. This large dimension of TRPC3 is also supported by the Stokes radius (92 A) obtained from gel filtration chromatography. PMID:15964551

  20. Strategy research for the channel selection of releasing commercial information through Internet%商务信息网络发布的渠道选择策略研究

    Institute of Scientific and Technical Information of China (English)

    王秦; 敖静海; 陈道志

    2012-01-01

    商务信息的网络发布可以提升商务信息的扩散范围、停留时间、表现形式、延伸效果和穿透能力,并且可以能动地进行信息跟踪,实现信息的有效沟通和交流,信息发布的效果十分明显。本文在分析网络发布渠道特点的基础上,提出商务信息网络发布渠道的选择策略,最后对商务信息网络发布的策略进行了一定的研究。%Web publishing of commercial information could improve commercial information’s expansion scope,elapsed time,expression form,extension effect and penetrating power,and actively trace information,so to communicate and exchange information effectively.The effect of releasing information is too distinctive.In this paper,based on the analyzing the characters of the main Internet releasing channels,the strategy for channel selection is presented about releasing commercial information.Finally,it is researched about the strategy for Internet distribution of commercial information.