A naturally occurring amino acid substitution in the voltage-dependent sodium channel selectivity filter affects channel gating

The pore of sodium channels contains a selectivity filter made of 4 amino acids, D/E/K/A. In voltage sensitive sodium channel (Nav) channels from jellyfish to human the fourth amino acid is Ala. This Ala, when mutated to Asp, promotes slow inactivation. In some Nav channels of pufferfishes, the Ala is replaced with Gly. We studied the biophysical properties of an Ala-to-Gly substitution (A1529G) in rat Nav1.4 channel expressed in Xenopus oocytes alone or with a beta 1 subunit. The Ala-to-Gly substitution does not affect monovalent cation selectivity and positively shifts the voltage-dependent inactivation curve, although co-expression with a beta 1 subunit eliminates the difference between A1529G and WT. There is almost no difference in channel fast inactivation, but the beta 1 subunit accelerates WT current inactivation significantly more than it does the A1529G channels. The Ala-to-Gly substitution mainly influences the rate of recovery from slow inactivation. Again, the beta 1 subunit is less effective on speeding recovery of A1529G than the WT. We searched Nav channels in numerous databases and noted at least four other independent Ala-to-Gly substitutions in Nav channels in teleost fishes. Thus, the Ala-to-Gly substitution occurs more frequently than previously realized, possibly under selection for alterations of channel gating.

Traffic engineered NoC for streaming applications

Streaming applications demand hard bandwidth and throughput guarantees in a multiprocessor environment amidst resource competing processes. We present a Label Switching based Network-on-Chip (LS-NoC) motivated by throughput guarantees offered by bandwidth reservation. Label switching is a packet relaying technique in which individual packets carry route information in the form of labels. A centralized LS-NoC Management framework engineers traffic into Quality of Service (QoS) guaranteed routes. LS-NoC caters to the requirements of streaming applications where communication channels are fixed over the lifetime of the application. The proposed NoC framework inherently supports heterogeneous and ad hoc system-on-chips. The LS-NoC can be used in conjunction with conventional best effort NoC as a QoS guaranteed communication network or as a replacement to the conventional NoC. A multicast, broadcast capable label switched router for the LS-NoC has been designed. A 5 port, 256 bit data bus, 4 bit label router occupies 0.431 mm(2) in 130 nm and delivers peak bandwidth of 80 Gbits/s per link at 312.5 MHz. Bandwidth and latency guarantees of LS-NoC have been demonstrated on traffic from example streaming applications and on constant and variable bit rate traffic patterns. LS-NoC was found to have a competitive AreaxPower/Throughput figure of merit with state-of-the-art NoCs providing QoS. Circuit switching with link sharing abilities and support for asynchronous operation make LS-NoC a desirable choice for QoS servicing in chip multiprocessors. (C) 2013 Elsevier B.V. All rights reserved.

MRT Letter: Light Sheet Based Imaging Flow Cytometry on a Microfluidic Platform

We propose a light sheet based imaging flow cytometry technique for simultaneous counting and imaging of cells on a microfluidic platform. Light sheet covers the entire microfluidic channel and thus omits the necessity of flow focusing and point scanning based technology. Another advantage lies in the orthogonal detection geometry that totally cuts-off the incident light, thereby substantially reducing the background in the detection. Compared to the existing state-of-art techniques the proposed technique shows marked improvement. Using fluorescently-coated Saccharomyces cerevisiae cells we have recorded cell counting with throughput as high as 2,090 cells/min in the low flow rate regime and were able to image the individual cells on-the-go. Overall, the proposed system is cost-effective and simple in channel geometry with the advantage of efficient counting in operational regime of low laminar flow. This technique may advance the emerging field of microfluidic based cytometry for applications in nanomedicine and point of care diagnostics. Microsc. Res. Tech. 76:1101-1107, 2013. (c) 2013 Wiley Periodicals, Inc.

Joint Evaluation of Reduced Feedback Scheme, Scheduling, and Rate Adaptation in OFDMA Systems with Feedback Delays

Orthogonal frequency division multiple access (OFDMA) systems exploit multiuser diversity and frequency-selectivity to achieve high spectral efficiencies. However, they require considerable feedback for scheduling and rate adaptation, and are sensitive to feedback delays. We develop a comprehensive analysis of the OFDMA system throughput as a function of the feedback scheme, frequency-domain scheduler, and discrete rate adaptation rule in the presence of feedback delays. We analyze the popular best-n and threshold-based feedback schemes. We show that for both the greedy and round-robin schedulers, the throughput degradation, given a feedback delay, depends primarily on the fraction of feedback reduced by the feedback scheme and not the feedback scheme itself. Even small feedback delays at low vehicular speeds are shown to significantly degrade the throughput. We also show that optimizing the link adaptation thresholds as a function of the feedback delay can effectively counteract the detrimental effect of delays.

Scheduling for Fading Channels Under Partial Channel Information

We consider a scheduler for the downlink of a wireless channel when only partial channel-state information is available at the scheduler. We characterize the network stability region and provide two throughput-optimal scheduling policies. We also derive a deterministic bound on the mean packet delay in the network. Finally, we provide a throughput-optimal policy for the network under QoS constraints when real-time and rate-guaranteed data traffic may be present.

A Cooperative ARQ Scheme for Infrastructure WLANs

We propose a Cooperative Opportunistic Automatic Repeat ReQuest (CoARQ) scheme to solve the HOL-blocking problem in infrastructure IEEE 802.11 WLANs. HOL blocking occurs when the head-of-the-line packet at the Access Point (AP) queue blocks the transmission of packets to other destinations resulting in severe throughput degradation. When the AP transmits a packet to a mobile station (STA), some of the nodes in the vicinity can overhear this packet transmission successfully. If the original transmission by the AP is unsuccessful, our CoARQ scheme chooses the station. STA or AP) with the best channel to the intended receiver as a relay and the chosen relay forwards the AP's packet to the receiver. This way, our scheme removes the bottleneck at the AP, thereby providing significant improvements in the throughput of the AP. We analyse the performance of our scheme in an infrastructure WLAN under a TCP controlled file download scenario and our analytical results are further validated by extensive simulations.

On Generalized Spatial Modulation

Generalized spatial modulation (GSM) is a relatively new modulation scheme for multi-antenna wireless communications. It is quite attractive because of its ability to work with less number of transmit RF chains compared to traditional spatial multiplexing (V-BLAST system). In this paper, we show that, by using an optimum combination of number of transmit antennas (N-t) and number of transmit RF chains (N-rf), GSM can achieve better throughput and/or bit error rate (BER) than spatial multiplexing. First, we quantify the percentage savings in the number of transmit RF chains as well as the percentage increase in the rate achieved in GSM compared to spatial multiplexing; 18.75% savings in number of RF chains and 9.375% increase in rate are possible with 16 transmit antennas and 4-QAM modulation. A bottleneck, however, is the complexity of maximum-likelihood (ML) detection of GSM signals, particularly in large MIMO systems where the number of antennas is large. We address this detection complexity issue next. Specifically, we propose a Gibbs sampling based algorithm suited to detect GSM signals. The proposed algorithm yields impressive BER performance and complexity results. For the same spectral efficiency and number of transmit RF chains, GSM with the proposed detection algorithm achieves better performance than spatial multiplexing with ML detection.

A method of developing an agent based ubiquitous node monitoring protocol

A ubiquitous network plays a critical role to provide rendered services to ubiquitous application running nodes. To provide appropriate resources the nodes are needed to be monitored continuously. Monitoring a node in ubiquitous network is challenging because of dynamicity and heterogeneity of the ubiquitous network. The network monitor has to monitor resource parameters, like data rate, delay and throughput, as well as events such as node failure, network failure and fault in the system to curb the system failure. In this paper, we propose a method to develop a ubiquitous system monitoring protocol using agents. Earlier works on network monitoring using agents consider that the agents are designed for particular network. While in our work the heterogeneity property of the network has been considered. We have shown that the nodes' behaviour can be easily monitored by using agents (both static and mobile agent). The past behavior of the application and network, and past history of the Unode and the predecessor are taken into consideration to help SA to take appropriate decision during the time of emergency situation like unavailability of resources at the local administration, and to predict the migration of the Unode based on the previous node history. The results obtained in the simulation reflects the effectiveness of the technique.

Providing QoS in a cognitive radio network

We consider the problem of wireless channel allocation (whenever the channels are free) to multiple cognitive radio users in a Cognitive Radio Network (CRN) so as to satisfy their Quality of Service (QoS) requirements efficiently. The CRN base station may not know the channel states of all the users. The multiple channels are available at random times. In this setup Opportunistic Splitting can be an attractive solution. A disadvantage of this algorithm is that it requires the metrics of all users to be an independent, identically distributed sequence. However we use a recently generalized version of this algorithm in which the optimal parameters are learnt on-line through stochastic approximation and metrics can be Markov. We provide scheduling algorithms which maximize weighted-sum system throughput or are throughput or delay optimal. We also consider the scenario when some traffic streams are delay sensitive.

Next-generation optical microscopy

A new breed of microscopy techniques is coming to the forefront of optical imaging. They enhance the attainable 3D resolution of imaging in live and ``fixed'' cells' (with minimal structural perturbation) by greater than tenfold, bringing subcellular structures in sharp focus Along with long-term imaging, deep tissue and high throughput capablities, new insights in various fields of biology are being generated. The main set of these next-generation optical microscopy techniques along with select applications is described in this article.

Capture-Induced, Fast, Distributed, Splitting Based Selection with Imperfect Power Control

Opportunistic selection selects the node that improves the overall system performance the most. Selecting the best node is challenging as the nodes are geographically distributed and have only local knowledge. Yet, selection must be fast to allow more time to be spent on data transmission, which exploits the selected node's services. We analyze the impact of imperfect power control on a fast, distributed, splitting based selection scheme that exploits the capture effect by allowing the transmitting nodes to have different target receive powers and uses information about the total received power to speed up selection. Imperfect power control makes the received power deviate from the target and, hence, affects performance. Our analysis quantifies how it changes the selection probability, reduces the selection speed, and leads to the selection of no node or a wrong node. We show that the effect of imperfect power control is primarily driven by the ratio of target receive powers. Furthermore, we quantify its effect on the net system throughput.

EESM-Based Link Adaptation in Point-to-Point and Multi-Cell OFDM Systems: Modeling and Analysis

In contemporary wideband orthogonal frequency division multiplexing (OFDM) systems, such as Long Term Evolution (LTE) and WiMAX, different subcarriers over which a codeword is transmitted may experience different signal-to-noise-ratios (SNRs). Thus, adaptive modulation and coding (AMC) in these systems is driven by a vector of subcarrier SNRs experienced by the codeword, and is more involved. Exponential effective SNR mapping (EESM) simplifies the problem by mapping this vector into a single equivalent fiat-fading SNR. Analysis of AMC using EESM is challenging owing to its non-linear nature and its dependence on the modulation and coding scheme. We first propose a novel statistical model for the EESM, which is based on the Beta distribution. It is motivated by the central limit approximation for random variables with a finite support. It is simpler and as accurate as the more involved ad hoc models proposed earlier. Using it, we develop novel expressions for the throughput of a point-to-point OFDM link with multi-antenna diversity that uses EESM for AMC. We then analyze a general, multi-cell OFDM deployment with co-channel interference for various frequency-domain schedulers. Extensive results based on LTE and WiMAX are presented to verify the model and analysis, and gain new insights.

Morphological Effects of G-Quadruplex Stabilization Using a Small Molecule in Zebrafish

Zebrafish (Danio rerio) embryos are transparent and advantageous for studying early developmental changes due to ex utero development, making them an appropriate model for studying gene expression changes as a result of molecular targeting. Zebrafish embryos were injected with a previously reported G-quadruplex selective ligand, and the phenotypic changes were recorded. We report marked discrepancies in the development of intersegmental vessels. In silico analysis determined that the putative G-quadruplex motif occur in the upstream promoter region of the Cdh5 (N-cadherin) gene. A real-time polymerase chain reaction-based investigation indicated that in zebrafish, CDH-2 (ZN-cad) was significantly downregulated in the ligand-treated embryos. Biophysical characterization of the interaction of the ligand with the G-quadruplex motif found in this promoter yielded strong binding and stabilization of the G-quadruplex with this ligand. Hence, we report for the first time the phenotypic impact of G-quadruplex targeting with a ligand in a vertebrate organism. This study has unveiled not only G-quadruplex targeting in non-human animal species but also the potential that G-quadruplexes can provide a ready tool for understanding the phenotypic effects of targeting certain important genes involved in differentiation and developmental processes in a living eukaryotic organism.

A fast NMR method for resonance assignments: application to metabolomics

We present a new method for rapid NMR data acquisition and assignments applicable to unlabeled (C-12) or C-13-labeled biomolecules/organic molecules in general and metabolomics in particular. The method involves the acquisition of three two dimensional (2D) NMR spectra simultaneously using a dual receiver system. The three spectra, namely: (1) G-matrix Fourier transform (GFT) (3,2)D C-13, H-1] HSQC-TOCSY, (2) 2D H-1-H-1 TOCSY and (3) 2D C-13-H-1 HETCOR are acquired in a single experiment and provide mutually complementary information to completely assign individual metabolites in a mixture. The GFT (3,2)D C-13, H-1] HSQC-TOCSY provides 3D correlations in a reduced dimensionality manner facilitating high resolution and unambiguous assignments. The experiments were applied for complete H-1 and C-13 assignments of a mixture of 21 unlabeled metabolites corresponding to a medium used in assisted reproductive technology. Taken together, the experiments provide time gain of order of magnitudes compared to the conventional data acquisition methods and can be combined with other fast NMR techniques such as non-uniform sampling and covariance spectroscopy. This provides new avenues for using multiple receivers and projection NMR techniques for high-throughput approaches in metabolomics.

Combinatorial Exploration of the Structural Landscape of Acid-Pyridine Cocrystals

The structural landscape of acid-pyridine cocrystals is explored by adopting a combinatorial matrix method with 4-substituted benzoic acids and 4-substituted pyridines. The choice of the system restricts the primary synthon to the robust acid-pyridine entity. This methodology accordingly provides hints toward the formation of secondary synthons. The pK(a) rule is validated in the landscape by taking all components of the matrix together and exploring it as a whole. Along with the global features, the exploration of landscapes reveals some local features. Apart from the identification of secondary synthons, it also sheds light on the propensity of hydration in cocrystals, synthon competition, and certain topological similarities. The method described here combines two approaches, namely, database analysis and high throughput crystallography, to extract more information with minimal extra experimental effort.