Network approaches to drug discovery

Introduction: Advances in genomics technologies are providing a very large amount of data on genome-wide gene expression profiles, protein molecules and their interactions with other macromolecules and metabolites. Molecular interaction networks provide a useful way to capture this complex data and comprehend it. Networks are beginning to be used in drug discovery, in many steps of the modern discovery pipeline, with large-scale molecular networks being particularly useful for the understanding of the molecular basis of the disease. Areas covered: The authors discuss network approaches used for drug target discovery and lead identification in the drug discovery pipeline. By reconstructing networks of targets, drugs and drug candidates as well as gene expression profiles under normal and disease conditions, the paper illustrates how it is possible to find relationships between different diseases, find biomarkers, explore drug repurposing and study emergence of drug resistance. Furthermore, the authors also look at networks which address particular important aspects such as off-target effects, combination-targets, mechanism of drug action and drug safety. Expert opinion: The network approach represents another paradigm shift in drug discovery science. A network approach provides a fresh perspective of understanding important proteins in the context of their cellular environments, providing a rational basis for deriving useful strategies in drug design. Besides drug target identification and inferring mechanism of action, networks enable us to address new ideas that could prove to be extremely useful for new drug discovery, such as drug repositioning, drug synergy, polypharmacology and personalized medicine.

Interaction Signatures Stabilizing the NAD(P)-Binding Rossmann Fold: A Structure Network Approach

The fidelity of the folding pathways being encoded in the amino acid sequence is met with challenge in instances where proteins with no sequence homology, performing different functions and no apparent evolutionary linkage, adopt a similar fold. The problem stated otherwise is that a limited fold space is available to a repertoire of diverse sequences. The key question is what factors lead to the formation of a fold from diverse sequences. Here, with the NAD(P)-binding Rossmann fold domains as a case study and using the concepts of network theory, we have unveiled the consensus structural features that drive the formation of this fold. We have proposed a graph theoretic formalism to capture the structural details in terms of the conserved atomic interactions in global milieu, and hence extract the essential topological features from diverse sequences. A unified mathematical representation of the different structures together with a judicious concoction of several network parameters enabled us to probe into the structural features driving the adoption of the NAD(P)-binding Rossmann fold. The atomic interactions at key positions seem to be better conserved in proteins, as compared to the residues participating in these interactions. We propose a ``spatial motif'' and several ``fold specific hot spots'' that form the signature structural blueprints of the NAD(P)-binding Rossmann fold domain. Excellent agreement of our data with previous experimental and theoretical studies validates the robustness and validity of the approach. Additionally, comparison of our results with statistical coupling analysis (SCA) provides further support. The methodology proposed here is general and can be applied to similar problems of interest.

Smart Network Interface Selection for E-DTNs

We implement two energy models that accurately and comprehensively estimates the system energy cost and communication energy cost for using Bluetooth and Wi-Fi interfaces. The energy models running on a system is used to smartly pick the most energy optimal network interface so that data transfer between two end points is maximized.

A scalable network port scan detection system on FPGA

With ever increasing network speed, scalable and reliable detection of network port scans has become a major challenge. In this paper, we present a scalable and flexible architecture and a novel algorithm, to detect and block port scans in real time. The proposed architecture detects fast scanners as well as stealth scanners having large inter-probe periods. FPGA implementation of the proposed system gives an average throughput of 2 Gbps with a system clock frequency of 100 MHz on Xilinx Virtex-II Pro FPGA. Experimental results on real network trace show the effectiveness of the proposed system in detecting and blocking network scans with very low false positives and false negatives.

Smoothed functional and Quasi-Newton algorithms for routing in multi-stage queueing network with constraints

We consider the problem of optimal routing in a multi-stage network of queues with constraints on queue lengths. We develop three algorithms for probabilistic routing for this problem using only the total end-to-end delays. These algorithms use the smoothed functional (SF) approach to optimize the routing probabilities. In our model all the queues are assumed to have constraints on the average queue length. We also propose a novel quasi-Newton based SF algorithm. Policies like Join Shortest Queue or Least Work Left work only for unconstrained routing. Besides assuming knowledge of the queue length at all the queues. If the only information available is the expected end-to-end delay as with our case such policies cannot be used. We also give simulation results showing the performance of the SF algorithms for this problem.

Efficient Regular Expression Pattern Matching for Network Intrusion Detection Systems using Modified Word-based Automata

Network Intrusion Detection Systems (NIDS) intercept the traffic at an organization's network periphery to thwart intrusion attempts. Signature-based NIDS compares the intercepted packets against its database of known vulnerabilities and malware signatures to detect such cyber attacks. These signatures are represented using Regular Expressions (REs) and strings. Regular Expressions, because of their higher expressive power, are preferred over simple strings to write these signatures. We present Cascaded Automata Architecture to perform memory efficient Regular Expression pattern matching using existing string matching solutions. The proposed architecture performs two stage Regular Expression pattern matching. We replace the substring and character class components of the Regular Expression with new symbols. We address the challenges involved in this approach. We augment the Word-based Automata, obtained from the re-written Regular Expressions, with counter-based states and length bound transitions to perform Regular Expression pattern matching. We evaluated our architecture on Regular Expressions taken from Snort rulesets. We were able to reduce the number of automata states between 50% to 85%. Additionally, we could reduce the number of transitions by a factor of 3 leading to further reduction in the memory requirements.

Duty cycling and power management with a network of energy harvesting sensors

In this paper, we study duty cycling and power management in a network of energy harvesting sensor (EHS) nodes. We consider a one-hop network, where K EHS nodes send data to a destination over a wireless fading channel. The goal is to find the optimum duty cycling and power scheduling across the nodes that maximizes the average sum data rate, subject to energy neutrality at each node. We adopt a two-stage approach to simplify the problem. In the inner stage, we solve the problem of optimal duty cycling of the nodes, subject to the short-term power constraint set by the outer stage. The outer stage sets the short-term power constraints on the inner stage to maximize the long-term expected sum data rate, subject to long-term energy neutrality at each node. Albeit suboptimal, our solutions turn out to have a surprisingly simple form: the duty cycle allotted to each node by the inner stage is simply the fractional allotted power of that node relative to the total allotted power. The sum power allotted is a clipped version of the sum harvested power across all the nodes. The average sum throughput thus ultimately depends only on the sum harvested power and its statistics. We illustrate the performance improvement offered by the proposed solution compared to other naive schemes via Monte-Carlo simulations.

Multi-port network modeling for fractal shape microstrip antenna

In this paper we demonstrate the use of multi-port network modeling to analyze one such antenna with fractal shaped parts. Based on simulation and experimental studies, it has been demonstrated that model can accurately predict the input characteristics of antennas with Minkowski geometry replacing a side micro strip square ring.

Generalized bidirectional multi-pair multi-antennawireless network coding

In this paper, we focus on increasing the throughput and diversity of network coded MIMO transmissions in bidirectional multi-pair wireless relay networks. All nodes have multi-antenna capability. Pairs of nodes want to exchange messages via a relay having multi-antenna and encoding/decoding capability. Nodes transmit their messages to the relay in the first (MAC) phase. The relay decodes all the messages and XORs them and broadcasts the XORed message in the second (BC) phase. We develop a generalized framework for bidirectional multi-pair multi-antenna wireless network coding, which models different MIMO transmission schemes including spatial multiplexing (V-BLAST), orthogonal STBC (OSTBC), and non-orthogonal STBC (NO-STBC) in a unified way. Enhanced throughputs are achieved by allowing all nodes to simultaneously transmit at their full rate. High diversity orders are achieved through the use of NO-STBCs, characterized by full rate and full transmit diversity. We evaluate and compare the performance of VBLAST, OSTBC, and NO-STBC schemes in one-dimensional 1-pair linear network (one pair of nodes and a relay) and two-dimensional 2-pair `cross' network (two pairs of nodes and a relay).

Network-error correcting codes using small fields

Recently, Ebrahimi and Fragouli proposed an algorithm to construct scalar network codes using small fields (and vector network codes of small lengths) satisfying multicast constraints in a given single-source, acyclic network. The contribution of this paper is two fold. Primarily, we extend the scalar network coding algorithm of Ebrahimi and Fragouli (henceforth referred to as the EF algorithm) to block network-error correction. Existing construction algorithms of block network-error correcting codes require a rather large field size, which grows with the size of the network and the number of sinks, and thereby can be prohibitive in large networks. We give an algorithm which, starting from a given network-error correcting code, can obtain another network code using a small field, with the same error correcting capability as the original code. Our secondary contribution is to improve the EF Algorithm itself. The major step in the EF algorithm is to find a least degree irreducible polynomial which is coprime to another large degree polynomial. We suggest an alternate method to compute this coprime polynomial, which is faster than the brute force method in the work of Ebrahimi and Fragouli.

A dynamic topology management in a hybrid wireless superstore network

with the development of large scale wireless networks, there has been short comings and limitations in traditional network topology management systems. In this paper, an adaptive algorithm is proposed to maintain topology of hybrid wireless superstore network by considering the transactions and individual network load. The adaptations include to choose the best network connection for the response, and to perform network Connection switching when network situation changes. At the same time, in terms of the design for topology management systems, aiming at intelligence, real-time, the study makes a step-by-step argument and research on the overall topology management scheme. Architecture for the adaptive topology management of hybrid wireless networking resources is available to user’s mobile device. Simulation results describes that the new scheme has outperformed the original topology management and it is simpler than the original rate borrowing scheme.

Performance analysis of data and voice connections in a cognitive radio network

We study the performance of cognitive (secondary) users in a cognitive radio network which uses a channel whenever the primary users are not using the channel. The usage of the channel by the primary users is modelled by an ON-OFF renewal process. The cognitive users may be transmitting data using TCP connections and voice traffic. The voice traffic is given priority over the data traffic. We theoretically compute the mean delay of TCP and voice packets and also the mean throughput of the different TCP connections. We compare the theoretical results with simulations.

Network congestion management by fuzzy inference using virtual flows

Effective network overload alleviation is very much essential in order to maintain security and integrity from the operational viewpoint of deregulated power systems. This paper aims at developing a methodology to reschedule the active power generation from the sources in order to manage the network congestion under normal/contingency conditions. An effective method has been proposed using fuzzy rule based inference system. Using virtual flows concept, which provides partial contributions/counter flows in the network elements is used as a basis in the proposed method to manage network congestions to the possible extent. The proposed method is illustrated on a sample 6 bus test system and on modified IEEE 39 bus system.

A novel space cloth using resistor grid network for radar absorbers in stealth applications

We report novel resistor grid network based space cloth for application in single and multi layer radar absorbers. The space cloth is analyzed and relations are derived for the sheet resistance in terms of the resistor in the grid network. Design curves are drawn using MATLAB and the space cloth is analyzed using HFSS™ software in a Salisbury screen for S, C and X bands. Next, prediction and simulation results for a three layer Jaumann absorber using square grid resistor network with a Radar Cross Section Reduction (RCSR) of -15 dB over C, X and Ku bands is reported. The simulation results are encouraging and have led to the fabrication of prototype broadband radar absorber and experimental work is under progress.

Performance analysis of adaptive physical layer network coding for wireless two-way relaying

The performance analysis of adaptive physical layer network-coded two-way relaying scenario is presented which employs two phases: Multiple access (MA) phase and Broadcast (BC) phase. The deep channel fade conditions which occur at the relay referred as the singular fade states fall in the following two classes: (i) removable and (ii) non-removable singular fade states. With every singular fade state, we associate an error probability that the relay transmits a wrong network-coded symbol during the BC phase. It is shown that adaptive network coding provides a coding gain over fixed network coding, by making the error probabilities associated with the removable singular fade states contributing to the average Symbol Error Rate (SER) fall as SNR-2 instead of SNR-1. A high SNR upper-bound on the average end-to-end SER for the adaptive network coding scheme is derived, for a Rician fading scenario, which is found to be tight through simulations. Specifically, it is shown that for the adaptive network coding scheme, the probability that the relay node transmits a wrong network-coded symbol is upper-bounded by twice the average SER of a point-to-point fading channel, at high SNR. Also, it is shown that in a Rician fading scenario, it suffices to remove the effect of only those singular fade states which contribute dominantly to the average SER.