961 resultados para Calcium channel blockers


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In the present work, we experimentally study the flow of water over textured hydrophobic surfaces in a micro-channel. Shear stress measurements are done along with direct visualization of trapped air pockets on the hydrophobic surface. The trapped air pockets on such surfaces are known to be responsible for apparent slip at these surfaces and hence in significant drag reduction. In typical circumstances, the apparent slip reduces over time as seen, for example, from our shear stress measurements. This implies that the drag reduction will not be sustained. We have performed extensive visualizations of the trapped air pockets while varying flow parameters like the flow rate and the pressure. We present here direct visualizations that show that under some conditions, the air pockets can grow with time. The variation of the air pocket size with time is found to change qualitatively and quantitatively as the flow rate is varied. These measured changes in the air pocket size with time have a direct bearing on the sustainability of apparent slip in micro-channel flows.

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Key points center dot Active calcium signal propagation occurs when an initial calcium trigger elicits calcium release through endoplasmic reticulum (ER) receptors. A high concentration of the calcium trigger in thin-calibre dendrites would suppress release of calcium through hippocampal inositol trisphosphate receptors (InsP3Rs). center dot Could the high-density expression of A-type K+ channels in thin-calibre dendrites be a mechanism for inhibiting this suppression, thereby restoring the utility of the ER as a substrate for active calcium propagation? center dot Quantitative analyses involving experimentally constrained models reveal a bell-shaped dependence of calcium released through InsP3Rs on the A-type K+ channel density, during the propagation of a calcium wave. center dot A-type K+ channels regulated the relative contribution of ER calcium to the induction of synaptic plasticity in the presence of model metabotropic glutamate receptors. center dot These results identify a novel form of interaction between active dendrites and the ER membrane and suggest that A-type K+ channels are ideally placed for inhibiting the suppression of InsP3Rs in thin-calibre dendrites. Abstract The A-type potassium current has been implicated in the regulation of several physiological processes. Here, we explore a role for the A-type potassium current in regulating the release of calcium through inositol trisphosphate receptors (InsP3R) that reside on the endoplasmic reticulum (ER) of hippocampal pyramidal neurons. To do this, we constructed morphologically realistic, conductance-based models equipped with kinetic schemes that govern several calcium signalling modules and pathways, and constrained the distributions and properties of constitutive components by experimental measurements from these neurons. Employing these models, we establish a bell-shaped dependence of calcium release through InsP3Rs on the density ofA-type potassium channels, during the propagation of an intraneuronal calcium wave initiated through established protocols. Exploring the sensitivities of calcium wave initiation and propagation to several underlying parameters, we found that ER calcium release critically depends on dendritic diameter and that wave initiation occurred at branch points as a consequence of a high surface area to volume ratio of oblique dendrites. Furthermore, analogous to the role ofA-type potassium channels in regulating spike latency, we found that an increase in the density ofA-type potassium channels led to increases in the latency and the temporal spread of a propagating calcium wave. Next, we incorporated kinetic models for the metabotropic glutamate receptor (mGluR) signalling components and a calcium-controlled plasticity rule into our model and demonstrate thatthe presence of mGluRs induced a leftward shift in a BienenstockCooperMunro-like synaptic plasticity profile. Finally, we show that the A-type potassium current could regulate the relative contribution of ER calcium to synaptic plasticity induced either through 900 pulses of various stimulus frequencies or through theta burst stimulation. Our results establish a novel form of interaction between active dendrites and the ER membrane, uncovering a powerful mechanism that could regulate biophysical/biochemical signal integration and steer the spatiotemporal spread of signalling microdomains through changes in dendritic excitability.

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In plants, calcium-dependent protein kinases (CDPKs) are key intermediates in calcium-mediated signaling that couple changes in Ca2+ levels to a specific response. In the present study, we report the high-level soluble expression of calcium-dependent protein kinase1 from Cicer arietinum (CaCDPK1) in Escherichia coli. The expression of soluble CaCDPK1 was temperature dependent with a yield of 3-4 mg/l of bacterial culture. CaCDPK1 expressed as histidine-tag fusion protein was purified using Ni-NTA affinity chromatography till homogeneity. The recombinant CaCDPK1 protein exhibited both calcium-dependent autophosphorylation and substrate phosphorylation activities with a V (max) and K (m) value of 13.2 nmol/min/mg and 34.3 mu M, respectively, for histone III-S as substrate. Maximum autophosphorylation was seen only in the presence of calcium. Optimum temperature for autophosphorylation was found to be 37 A degrees C. The recombinant protein showed optimum pH range of 6-9. The role of autophosphorylation in substrate phosphorylation was investigated using histone III-S as exogenous substrate. Our results show that autophosphorylation happens before substrate phosphorylation and it happens via intra-molecular mechanism as the activity linearly depends on enzyme concentrations. Autophosphorylation enhances the kinase activity and reduces the lag phase of activation, and CaCDPK1 can utilize both ATP and GTP as phosphodonor but ATP is preferred than GTP.

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Fast and efficient channel estimation is key to achieving high data rate performance in mobile and vehicular communication systems, where the channel is fast time-varying. To this end, this work proposes and optimizes channel-dependent training schemes for reciprocal Multiple-Input Multiple-Output (MIMO) channels with beamforming (BF) at the transmitter and receiver. First, assuming that Channel State Information (CSI) is available at the receiver, a channel-dependent Reverse Channel Training (RCT) signal is proposed that enables efficient estimation of the BF vector at the transmitter with a minimum training duration of only one symbol. In contrast, conventional orthogonal training requires a minimum training duration equal to the number of receive antennas. A tight approximation to the capacity lower bound on the system is derived, which is used as a performance metric to optimize the parameters of the RCT. Next, assuming that CSI is available at the transmitter, a channel-dependent forward-link training signal is proposed and its power and duration are optimized with respect to an approximate capacity lower bound. Monte Carlo simulations illustrate the significant performance improvement offered by the proposed channel-dependent training schemes over the existing channel-agnostic orthogonal training schemes.

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With the objective of investigating the direct conversion of inorganic carbonates such as CaCO3 to hydrocarbons, assisted by transition metal ions, we have carried out studies on CaCO3 in an intimate admixture with iron oxides (FeCaCO) with a wide range of Fe/Ca mole ratios (x), prepared by co-precipitation. The hydrogen reduction of FeCaCO at 673 K gives up to 23% yield of the hydrocarbons CH4, C2H4, C2H6 and C3H8, leaving solid iron residues in the form of iron metal, oxides and carbide particles. The yield of hydrocarbons increases with x and the conversion of hydrocarbons occurs through the formation of CO. While the total yield of hydrocarbons obtained by us is comparable to that in the Fischer-Tropsch synthesis, the selectivity for C-2-C-3 hydrocarbons reported here is noteworthy.

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A decode and forward protocol based Trellis Coded Modulation (TCM) scheme for the half-duplex relay channel, in a Rayleigh fading environment, is presented. The proposed scheme can achieve any spectral efficiency greater than or equal to one bit per channel use (bpcu). A near-ML decoder for the suggested TCM scheme is proposed. It is shown that the high Signal to Noise Ratio (SNR) performance of this near-ML decoder approaches the performance of the optimal ML decoder. Based on the derived Pair-wise Error Probability (PEP) bounds, design criteria to maximize the diversity and coding gains are obtained. Simulation results show a large gain in SNR for the proposed TCM scheme over uncoded communication as well as the direct transmission without the relay.

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Orthogonal frequency-division multiple access (OFDMA) systems divide the available bandwidth into orthogonal subchannels and exploit multiuser diversity and frequency selectivity to achieve high spectral efficiencies. However, they require a significant amount of channel state feedback for scheduling and rate adaptation and are sensitive to feedback delays. We develop a comprehensive analysis for OFDMA system throughput in the presence of feedback delays as a function of the feedback scheme, frequency-domain scheduler, and rate adaptation rule. Also derived are expressions for the outage probability, which captures the inability of a subchannel to successfully carry data due to the feedback scheme or feedback delays. Our model encompasses the popular best-n and threshold-based feedback schemes and the greedy, proportional fair, and round-robin schedulers that cover a wide range of throughput versus fairness tradeoff. It helps quantify the different robustness of the schedulers to feedback overhead and delays. Even at low vehicular speeds, it shows that small feedback delays markedly degrade the throughput and increase the outage probability. Further, given the feedback delay, the throughput degradation depends primarily on the feedback overhead and not on the feedback scheme itself. We also show how to optimize the rate adaptation thresholds as a function of feedback delay.

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Given the significant gains that relay-based cooperation promises, the practical problems of acquisition of channel state information (CSI) and the characterization and optimization of performance with imperfect CSI are receiving increasing attention. We develop novel and accurate expressions for the symbol error probability (SEP) for fixed-gain amplify-and-forward relaying when the destination acquires CSI using the time-efficient cascaded channel estimation (CCE) protocol. The CCE protocol saves time by making the destination directly estimate the product of the source-relay and relay-destination channel gains. For a single relay system, we first develop a novel SEP expression and a tight SEP upper bound. We then similarly analyze an opportunistic multi-relay system, in which both selection and coherent demodulation use imperfect estimates. A distinctive aspect of our approach is the use of as few simplifying approximations as possible, which results in new results that are accurate at signal-to-noise-ratios as low as 1 dB for single and multi-relay systems. Using insights gleaned from an asymptotic analysis, we also present a simple, closed-form, nearly-optimal solution for allocation of energy between pilot and data symbols at the source and relay(s).

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Novel composite cyclodextrin (CD)-CaCO3 spherical porous microparticles have been synthesized through Ca2+-CD complex formation, which influences the crystal growth of CaCO3. The CDs are entrapped and distributed uniformly in the matrix of CaCO3 microparticles during crystallization. The hydrophobic fluorescent molecules coumarin and Nile red (NR) are efficiently encapsulated into these composite CD-CaCO3 porous particles through supramolecular inclusion complexation between entrapped CDs and hydrophobic molecules. Thermogravimetric (TGA) and infrared spectroscopy (IR) analysis of composite CD-CaCO3 particles reveals the presence of large CDs and their strong interaction with calcium carbonate nanoparticles. The resulting composite CD-CaCO3 microparticles are utilized as sacrificial templates for preparation of CD-modified layer-by-layer (LbL) capsules. After dissolution of the carbonate core, CDs are retained in the interior of the capsules in a network fashion and assist in the encapsulation of hydrophobic molecules. The efficient encapsulation of the hydrophobic fluorescent dye, coumarin, was successfully demonstrated using CD-modified capsules. In vitro release of the encapsulated coumarin from the CD-CaCO3 and CD-modified capsules has been demonstrated.

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Most charge generation studies on organic solar cells focus on the conventional mode of photocurrent generation derived from light absorption in the electron donor component (so called channel I). In contrast, relatively little attention has been paid to the alternate generation pathway: light absorption in the electron acceptor followed by photo-induced hole transfer (channel II). By using the narrow optical gap polymer poly(3,6-dithieno3,2-b] thiophen-2-yl)-2,5-bis(2-octyldodecyl)-pyrrolo- 3,4-c]pyrrole-1,4-dione-5',5 `'-diyl-alt-4,8-bis(dodecyloxy) benzo1,2-b:4,5-b'] dithiophene-2,6-diyl with two complimentary fullerene absorbers; phenyl-C-61-butyric acid methyl ester, and phenyl-C-71-butyric acid methyl ester (70-PCBM), we have been able to quantify the photocurrent generated each of the mechanisms and find a significant fraction (>30%), which is derived in particular from 70-PCBM light absorption.

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We consider bounds for the capacity region of the Gaussian X channel (XC), a system consisting of two transmit-receive pairs, where each transmitter communicates with both the receivers. We first classify the XC into two classes, the strong XC and the mixed XC. In the strong XC, either the direct channels are stronger than the cross channels or vice-versa, whereas in the mixed XC, one of the direct channels is stronger than the corresponding cross channel and vice-versa. After this classification, we give outer bounds on the capacity region for each of the two classes. This is based on the idea that when one of the messages is eliminated from the XC, the rate region of the remaining three messages are enlarged. We make use of the Z channel, a system obtained by eliminating one message and its corresponding channel from the X channel, to bound the rate region of the remaining messages. The outer bound to the rate region of the remaining messages defines a subspace in R-+(4) and forms an outer bound to the capacity region of the XC. Thus, the outer bound to the capacity region of the XC is obtained as the intersection of the outer bounds to the four combinations of the rate triplets of the XC. Using these outer bounds on the capacity region of the XC, we derive new sum-rate outer bounds for both strong and mixed Gaussian XCs and compare them with those existing in literature. We show that the sum-rate outer bound for strong XC gives the sum-rate capacity in three out of the four sub-regions of the strong Gaussian XC capacity region. In case of mixed Gaussian XC, we recover the recent results in 11] which showed that the sum-rate capacity is achieved in two out of the three sub-regions of the mixed XC capacity region and give a simple alternate proof of the same.

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We consider the MIMO X channel (XC), a system consisting of two transmit-receive pairs, where each transmitter communicates with both the receivers. Both the transmitters and receivers are equipped with multiple antennas. First, we derive an upper bound on the sum-rate capacity of the MIMO XC under individual power constraint at each transmitter. The sum-rate capacity of the two-user multiple access channel (MAC) that results when receiver cooperation is assumed forms an upper bound on the sum-rate capacity of the MIMO XC. We tighten this bound by considering noise correlation between the receivers and deriving the worst noise covariance matrix. It is shown that the worst noise covariance matrix is a saddle-point of a zero-sum, two-player convex-concave game, which is solved through a primal-dual interior point method that solves the maximization and the minimization parts of the problem simultaneously. Next, we propose an achievable scheme which employs dirty paper coding at the transmitters and successive decoding at the receivers. We show that the derived upper bound is close to the achievable region of the proposed scheme at low to medium SNRs.

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A dynamical instability is observed in experimental studies on micro-channels of rectangular cross-section with smallest dimension 100 and 160 mu m in which one of the walls is made of soft gel. There is a spontaneous transition from an ordered, laminar flow to a chaotic and highly mixed flow state when the Reynolds number increases beyond a critical value. The critical Reynolds number, which decreases as the elasticity modulus of the soft wall is reduced, is as low as 200 for the softest wall used here (in contrast to 1200 for a rigid-walled channel) The instability onset is observed by the breakup of a dye-stream introduced in the centre of the micro-channel, as well as the onset of wall oscillations due to laser scattering from fluorescent beads embedded in the wall of the channel. The mixing time across a channel of width 1.5 mm, measured by dye-stream and outlet conductance experiments, is smaller by a factor of 10(5) than that for a laminar flow. The increased mixing rate comes at very little cost, because the pressure drop (energy requirement to drive the flow) increases continuously and modestly at transition. The deformed shape is reconstructed numerically, and computational fluid dynamics (CFD) simulations are carried out to obtain the pressure gradient and the velocity fields for different flow rates. The pressure difference across the channel predicted by simulations is in agreement with the experiments (within experimental errors) for flow rates where the dye stream is laminar, but the experimental pressure difference is higher than the simulation prediction after dye-stream breakup. A linear stability analysis is carried out using the parallel-flow approximation, in which the wall is modelled as a neo-Hookean elastic solid, and the simulation results for the mean velocity and pressure gradient from the CFD simulations are used as inputs. The stability analysis accurately predicts the Reynolds number (based on flow rate) at which an instability is observed in the dye stream, and it also predicts that the instability first takes place at the downstream converging section of the channel, and not at the upstream diverging section. The stability analysis also indicates that the destabilization is due to the modification of the flow and the local pressure gradient due to the wall deformation; if we assume a parabolic velocity profile with the pressure gradient given by the plane Poiseuille law, the flow is always found to be stable.

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Among the mu-conotoxins that block vertebrate voltage-gated sodium channels (VGSCs), some have been shown to be potent analgesics following systemic administration in mice. We have determined the solution structure of a new representative of this family, mu-BuIIIB, and established its disulfide connectivities by direct mass spectrometric collision induced dissociation fragmentation of the peptide with disulfides intact The major oxidative folding product adopts a 1-4/2-5/3-6 pattern with the following disulfide bridges: Cys5-Cys17, Cys6-Cys23, and Cys13-Cys24. The solution structure reveals that the unique N-terminal extension in mu-BuIIIB, which is also present in mu-BuIIIA and mu-BuIIIC but absent in other mu-conotoxins, forms part of a short a-helix encompassing Glu3 to Asn8. This helix is packed against the rest of the toxin and stabilized by the Cys5-Cys17 and Cys6-Cys23 disulfide bonds. As such, the side chain of Val1 is located close to the aromatic rings of Trp16 and His20, which are located on the canonical helix that displays several residues found to be essential for VGSC blockade in related mu-conotoxins. Mutations of residues 2 and 3 in the N-terminal extension enhanced the potency of mu-BuIIIB for Na(v)1.3. One analogue, D-Ala2]BuIIIB, showed a 40-fold increase, making it the most potent peptide blocker of this channel characterized to date and thus a useful new tool with which to characterize this channel. On the basis of previous results for related mu-conotoxins, the dramatic effects of mutations at the N-terminus were unanticipated and suggest that further gains in potency might be achieved by additional modifications of this region.