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.

Incentive Compatible Influence Maximization in Social Networks with Application to Viral Marketing

Information diffusion and influence maximization are important and extensively studied problems in social networks. Various models and algorithms have been proposed in the literature in the context of the influence maximization problem. A crucial assumption in all these studies is that the influence probabilities are known to the social planner. This assumption is unrealistic since the influence probabilities are usually private information of the individual agents and strategic agents may not reveal them truthfully. Moreover, the influence probabilities could vary significantly with the type of the information flowing in the network and the time at which the information is propagating in the network. In this paper, we use a mechanism design approach to elicit influence probabilities truthfully from the agents. Our main contribution is to design a scoring rule based mechanism in the context of the influencer-influencee model. In particular, we show the incentive compatibility of the mechanisms and propose a reverse weighted scoring rule based mechanism as an appropriate mechanism to use.

Dynamic mechanism design for markets with strategic resources

The assignment of tasks to multiple resources becomes an interesting game theoretic problem, when both the task owner and the resources are strategic. In the classical, nonstrategic setting, where the states of the tasks and resources are observable by the controller, this problem is that of finding an optimal policy for a Markov decision process (MDP). When the states are held by strategic agents, the problem of an efficient task allocation extends beyond that of solving an MDP and becomes that of designing a mechanism. Motivated by this fact, we propose a general mechanism which decides on an allocation rule for the tasks and resources and a payment rule to incentivize agents' participation and truthful reports. In contrast to related dynamic strategic control problems studied in recent literature, the problem studied here has interdependent values: the benefit of an allocation to the task owner is not simply a function of the characteristics of the task itself and the allocation, but also of the state of the resources. We introduce a dynamic extension of Mezzetti's two phase mechanism for interdependent valuations. In this changed setting, the proposed dynamic mechanism is efficient, within period ex-post incentive compatible, and within period ex-post individually rational.

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.

Assessment of the Relationships Among Design Methods, Design Activities, and Creativity

This paper presents an experimental study that was conducted to compare the results obtained from using different design methods (brainstorming (BR), functional analysis (FA), and SCAMPER) in design processes. The objectives of this work are twofold. The first was to determine whether there are any differences in the length of time devoted to the different types of activities that are carried out in the design process, depending on the method that is employed; in other words, whether the design methods that are used make a difference in the profile of time spent across the design activities. The second objective was to analyze whether there is any kind of relationship between the time spent on design process activities and the degree of creativity in the solutions that are obtained. Creativity evaluation has been done by means of the degree of novelty and the level of resolution of the designed solutions using creative product semantic scale (CPSS) questionnaire. The results show that there are significant differences between the amounts of time devoted to activities related to understanding the problem and the typology of the design method, intuitive or logical, that are used. While the amount of time spent on analyzing the problem is very small in intuitive methods, such as brainstorming and SCAMPER (around 8-9% of the time), with logical methods like functional analysis practically half the time is devoted to analyzing the problem. Also, it has been found that the amount of time spent in each design phase has an influence on the results in terms of creativity, but results are not enough strong to define in which measure are they affected. This paper offers new data and results on the distinct benefits to be obtained from applying design methods. DOI: 10.1115/1.4007362]

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.

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.

An efficient hybrid approach for design of automotive wheel bearings

Wheel bearings play a crucial role in the mobility of a vehicle by minimizing motive power loss and providing stability in cornering maneuvers. Detailed engineering analysis of a wheel bearing subsystem under dynamic conditions poses enormous challenges due to the nonlinearity of the problem caused by multiple factional contacts between rotating and stationary parts and difficulties in prediction of dynamic loads that wheels are subject to. Commonly used design methodologies are based on equivalent static analysis of ball or roller bearings in which the latter elements may even be represented with springs. In the present study, an advanced hybrid approach is suggested for realistic dynamic analysis of wheel bearings by combining lumped parameter and finite element modeling techniques. A validated lumped parameter representation serves as an efficient tool for the prediction of radial wheel load due to ground reaction which is then used in detailed finite element analysis that automatically accounts for contact forces in an explicit formulation.

Topology optimization-based design of a compliant aircraft compliant aircraft wing for morphing leading and trailing edges

In this paper, we present a methodology for designing a compliant aircraft wing, which can morph from a given airfoil shape to another given shape under the actuation of internal forces and can offer sufficient stiffness in both configurations under the respective aerodynamic loads. The least square error in displacements, Fourier descriptors, geometric moments, and moment invariants are studied to compare candidate shapes and to pose the optimization problem. Their relative merits and demerits are discussed in this paper. The `frame finite element ground structure' approach is used for topology optimization and the resulting solutions are converted to continuum solutions. The introduction of a notch-like feature is the key to the success of the design. It not only gives a good match for the target morphed shape for the leading and trailing edges but also minimizes the extension of the flexible skin that is to be put on the airfoil frame. Even though linear small-displacement elastic analysis is used in optimization, the obtained designs are analysed for large displacement behavior. The methodology developed here is not restricted to aircraft wings; it can be used to solve any shape-morphing requirement in flexible structures and compliant mechanisms.

Design and Analysis of an Acknowledgment-Aware Asynchronous MPR MAC Protocol for Distributed WLANs

Multi-packet reception (MPR) promises significant throughput gains in wireless local area networks (WLANs) by allowing nodes to transmit even in the presence of ongoing transmissions in the medium. However, the medium access control (MAC) layer must now be redesigned to facilitate rather than discourage - these overlapping transmissions. We investigate asynchronous MPR MAC protocols, which successfully accomplish this by controlling the node behavior based on the number of ongoing transmissions in the channel. The protocols use the backoff timer mechanism of the distributed coordination function, which makes them practically appealing. We first highlight a unique problem of acknowledgment delays, which arises in asynchronous MPR, and investigate a solution that modifies the medium access rules to reduce these delays and increase system throughput in the single receiver scenario. We develop a general renewal-theoretic fixed-point analysis that leads to expressions for the saturation throughput, packet dropping probability, and average head-of-line packet delay. We also model and analyze the practical scenario in which nodes may incorrectly estimate the number of ongoing transmissions.

Wireless Network Coding for MIMO Two-Way Relaying

The design of modulation schemes for the physical layer network-coded two-way MIMO relaying scenario is considered, with the denoise-and-forward protocol which employs two phases: Multiple Access phase and Broadcast phase. It is shown that for MIMO two-way relaying, the minimum distance of the effective constellation at the relay becomes zero when all the rows of the channel fade coefficient matrix belong to a finite number of vector subspaces referred to as the singular fade subspaces. The singular fade subspaces can be classified into two kinds based on whether their harmful effects can be removed or not: (i) the removable and (ii) the non-removable singular fade subspaces. It is shown that network coding maps obtained by the completion of appropriate partially filled Latin Rectangles can remove the harmful effects of all the removable singular fade subspaces. For 2(lambda)-PSK signal set, the removable and non-removable singular fade subspaces are characterized and, it is shown that the number of non-removable singular fade subspaces is a small fraction of the total number of singular fade subspaces and this fraction tends to zero as the constellation size tends to infinity. The Latin Rectangles for the case when the end nodes use different number of antennas are shown to be obtainable from the Latin Squares for the case when they use the same number of antennas. Also, the network coding maps which remove all the removable singular singular fade subspaces are shown to be obtainable from a small set of Latin Squares. The removal of all the singular fade subspaces by properly choosing the network coding map, provides a gain of 5.5 dB over the conventional Exclusive-OR network coding, in a Rayleigh fading scenario with 2 antennas at the end nodes and one antenna at the relay node, for 4-PSK signal set.

Guided Ultrasonic Wave Propagation through Inaccessible Damage in a Folded Plate using Sensor-Actuator Network

Rapid diagnostics and virtual imaging of damages in complex structures like folded plate can help reduce the inspection time for guided wave based NDE and integrated SHM. Folded plate or box structure is one of the major structural components for increasing the structural strength. Damage in the folded plate, mostly in the form of surface breaking cracks in the inaccessible zone is a usual problem in aerospace structures. One side of the folded plate is attached (either riveted or bonded) to adjacent structure which is not accessible for immediate inspection. The sensor-actuator network in the form of a circular array is placed on the accessible side of the folded plate. In the present work, a circular array is employed for scanning the entire folded plate type structure for damage diagnosis and wave field visualization of entire structural panel. The method employs guided wave with relatively low frequency bandwidth of 100-300 kHz. Change in the response signal with respect to a baseline signal is used to construct a quantitative relationship with damage size parameters. Detecting damage in the folded plate by using this technique has significant potential for off-line and on-line SHM technologies. By employing this technique, surface breaking cracks on inaccessible face of the folded plate are detected without disassembly of structure in a realistic environment.