Flux balance analysis of biological systems: applications and challenges

Systems level modelling and simulations of biological processes are proving to be invaluable in obtaining a quantitative and dynamic perspective of various aspects of cellular function. In particular, constraint-based analyses of metabolic networks have gained considerable popularity for simulating cellular metabolism, of which flux balance analysis (FBA), is most widely used. Unlike mechanistic simulations that depend on accurate kinetic data, which are scarcely available, FBA is based on the principle of conservation of mass in a network, which utilizes the stoichiometric matrix and a biologically relevant objective function to identify optimal reaction flux distributions. FBA has been used to analyse genome-scale reconstructions of several organisms; it has also been used to analyse the effect of perturbations, such as gene deletions or drug inhibitions in silico. This article reviews the usefulness of FBA as a tool for gaining biological insights, advances in methodology enabling integration of regulatory information and thermodynamic constraints, and finally addresses the challenges that lie ahead. Various use scenarios and biological insights obtained from FBA, and applications in fields such metabolic engineering and drug target identification, are also discussed. Genome-scale constraint-based models have an immense potential for building and testing hypotheses, as well as to guide experimentation.

New insights from a fixed-point analysis of single cell IEEE 802.11 WLANs

We study a fixed-point formalization of the well-known analysis of Bianchi. We provide a significant simplification and generalization of the analysis. In this more general framework, the fixed-point solution and performance measures resulting from it are studied. Uniqueness of the fixed point is established. Simple and general throughput formulas are provided. It is shown that the throughput of any flow will be bounded by the one with the smallest transmission rate. The aggregate throughput is bounded by the reciprocal of the harmonic mean of the transmission rates. In an asymptotic regime with a large number of nodes, explicit formulas for the collision probability, the aggregate attempt rate, and the aggregate throughput are provided. The results from the analysis are compared with ns2 simulations and also with an exact Markov model of the backoff process. It is shown how the saturated network analysis can be used to obtain TCP transfer throughputs in some cases.

Comparative analysis of thermophilic and mesophilic proteins using Protein Energy Networks

Background: Thermophilic proteins sustain themselves and function at higher temperatures. Despite their structural and functional similarities with their mesophilic homologues, they show enhanced stability. Various comparative studies at genomic, protein sequence and structure levels, and experimental works highlight the different factors and dominant interacting forces contributing to this increased stability. Methods: In this comparative structure based study, we have used interaction energies between amino acids, to generate structure networks called as Protein Energy Networks (PENs). These PENs are used to compute network, sub-graph, and node specific parameters. These parameters are then compared between the thermophile-mesophile homologues. Results: The results show an increased number of clusters and low energy cliques in thermophiles as the main contributing factors for their enhanced stability. Further more, we see an increase in the number of hubs in thermophiles. We also observe no community of electrostatic cliques forming in PENs. Conclusion: In this study we were able to take an energy based network approach, to identify the factors responsible for enhanced stability of thermophiles, by comparative analysis. We were able to point out that the sub-graph parameters are the prominent contributing factors. The thermophiles have a better-packed hydrophobic core. We have also discussed how thermophiles, although increasing stability through higher connectivity retains conformational flexibility, from a cliques and communities perspective.

Comparative analysis of thermophilic and mesophilic proteins using Protein Energy Networks

Background: Thermophilic proteins sustain themselves and function at higher temperatures. Despite their structural and functional similarities with their mesophilic homologues, they show enhanced stability. Various comparative studies at genomic, protein sequence and structure levels, and experimental works highlight the different factors and dominant interacting forces contributing to this increased stability. Methods: In this comparative structure based study, we have used interaction energies between amino acids, to generate structure networks called as Protein Energy Networks (PENs). These PENs are used to compute network, sub-graph, and node specific parameters. These parameters are then compared between the thermophile-mesophile homologues. Results: The results show an increased number of clusters and low energy cliques in thermophiles as the main contributing factors for their enhanced stability. Further more, we see an increase in the number of hubs in thermophiles. We also observe no community of electrostatic cliques forming in PENs. Conclusion: In this study we were able to take an energy based network approach, to identify the factors responsible for enhanced stability of thermophiles, by comparative analysis. We were able to point out that the sub-graph parameters are the prominent contributing factors. The thermophiles have a better-packed hydrophobic core. We have also discussed how thermophiles, although increasing stability through higher connectivity retains conformational flexibility, from a cliques and communities perspective.

Design and analysis of rate aware ad hoc 802.11 networks

802.11 WLANs are characterized by high bit error rate and frequent changes in network topology. The key feature that distinguishes WLANs from wired networks is the multi-rate transmission capability, which helps to accommodate a wide range of channel conditions. This has a significant impact on higher layers such as routing and transport levels. While many WLAN products provide rate control at the hardware level to adapt to the channel conditions, some chipsets like Atheros do not have support for automatic rate control. We first present a design and implementation of an FER-based automatic rate control state machine, which utilizes the statistics available at the device driver to find the optimal rate. The results show that the proposed rate switching mechanism adapts quite fast to the channel conditions. The hop count metric used by current routing protocols has proven itself for single rate networks. But it fails to take into account other important factors in a multi-rate network environment. We propose transmission time as a better path quality metric to guide routing decisions. It incorporates the effects of contention for the channel, the air time to send the data and the asymmetry of links. In this paper, we present a new design for a multi-rate mechanism as well as a new routing metric that is responsive to the rate. We address the issues involved in using transmission time as a metric and presents a comparison of the performance of different metrics for dynamic routing.

Protein Hydration and Water Structure: X-ray Analysis of a Closely Packed Protein Crystal with Very Low Solvent Content

Low-humidity monoclinic lysozyme, resulting from a water-mediated transformation, has one of the lowest solvent contents (22% by volume) observed in a protein crystal. Its structure has been solved by the molecular replacement method and refined to an R value of 0.175 for 7684 observed reflections in the 10–1.75 Å resolution shell. 90% of the solvent in the well ordered crystals could be located. Favourable sites of hydration on the protein surface include side chains with multiple hydrogen-bonding centres, and regions between short hydrophilic side chains and the main-chain CO or NH groups of the same or nearby residues. Major secondary structural features are not disrupted by hydration. However, the free CO groups at the C terminii and, to a lesser extent, the NH groups at the N terminii of helices provide favourable sites for water interactions, as do reverse turns and regions which connect β-structure and helices. The hydration shell consists of discontinuous networks of water molecules, the maximum number of molecules in a network being ten. The substrate-binding cleft is heavily hydrated, as is the main loop region which is stabilized by water interactions. The protein molecules are close packed in the crystals with a molecular coordination number of 14. Arginyl residues are extensively involved in intermolecular hydrogen bonds and water bridges. The water molecules in the crystal are organized into discrete clusters. A distinctive feature of the clusters is the frequent occurrence of three-membered rings. The protein molecules undergo substantial rearrangement during the transformation from the native to the low-humidity form. The main-chain conformations in the two forms are nearly the same, but differences exist in the side-chain conformation. The differences are particularly pronounced in relation to Trp 62 and Trp 63. The shift in Trp 62 is especially interesting as it is also known to move during inhibitor binding.

Monte Carlo simulation of network formation based on structural fragments in epoxy-anhydride systems

A method combining the Monte Carlo technique and the simple fragment approach has been developed for simulating network formation in amine-catalysed epoxy-anhydride systems. The method affords a detailed insight into the nature and composition of the network, showing the distribution of various fragments. It has been used to characterize the network formation in the reaction of the diglycidyl ester of isophthalic acid with hexahydrophthalic anhydride, catalysed by benzyldimethylamine. Pre-gel properties like number and weight distributions and average molecular weights have been calculated as a function of epoxy conversion, leading to a prediction of the gel-point conversion. Analysis of the simulated network further yields other characteristic properties such as concentration of crosslink points, distribution and concentration of elastically active chains, average molecular weight between crosslinks, sol content and mass fraction of pendent chains. A comparison has been made of the properties obtained through simulation with those predicted by the fragment approach alone, which, however, gives only average properties. The Monte Carlo simulation results clearly show that loops and other cyclic structures occur in the gel. This may account for the differences observed between the results of the simulation and the fragment model in the post-gel phase. Copyright (C) 1996 Elsevier Science Ltd.

Performance analysis of wavelength/time codes with and without hard-limiter

Fiber-optic CDMA technology is well suited for high speed local-area-networks (LANs) as it has good salient features. In this paper, we model the wavelength/time multiple-pulses-per-row (W/T MPR) FO-CDMA network channel, as a Z channel. We compare the performances of W/T MPR code with and without hard-limiter and show that significant performance improvement can be achieved by using hard-limiters in the receivers. In broadcast channels, MAI is the dominant source of noise. Hence the performance analysis is carried out considering only MAI and other receiver noises are neglected.

An Empirical Analysis of Heterogeneity in IEEE 802.11 MAC Protocol Implementations and its Implications

Wireless LAN (WLAN) market consists of IEEE 802.11 MAC standard conformant devices (e.g., access points (APs), client adapters) from multiple vendors. Certain third party certifications such as those specified by the Wi-Fi alliance have been widely used by vendors to ensure basic conformance to the 802.11 standard, thus leading to the expectation that the available devices exhibit identical MAC level behavior. In this paper, however, we present what we believe to be the first ever set of experimental results that highlight the fact that WLAN devices from different vendors in the market can have heterogeneous MAC level behavior. Specifically, we demonstrate with examples and data that in certain cases, devices may not be conformant with the 802.11 standard while in other cases, they may differ in significant details that are not a part of mandatory specifications of the standard. We argue that heterogeneous MAC implementations can adversely impact WLAN operations leading to unfair bandwidth allocation, potential break-down of related MAC functionality and difficulties in provisioning the capacity of a WLAN. However, on the positive side, MAC level heterogeneity can be useful in applications such as vendor/model level device fingerprinting.

Computer-Aided Reliability Analysis of Complicated Networks

A computer-aided procedure is described for analyzing the reliability of complicated networks. This procedure breaks down a network into small subnetworks whose reliability can be more readily calculated. The subnetworks which are searched for are those with only two nodes; this allows the original network to be considerably simplified.

Computer-Aided Reliability Analysis of Complicated Networks

A computer-aided procedure is described for analyzing the reliability of complicated networks. This procedure breaks down a network into small subnetworks whose reliability can be more readily calculated. The subnetworks which are searched for are those with only two nodes; this allows the original network to be considerably simplified.

Topological analysis of general linear networks

A new method of network analysis, a generalization in several different senses of existing methods and applicable to all networks for which a branch-admittance (or impedance) matrix can be formed, is presented. The treatment of network determinants is very general and essentially four terminal rather than three terminal, and leads to simple expressions based on trees of a simple graph associated with the network and matrix, and involving products of low-order, usually(2 times 2)determinants of tree-branch admittances, in addition to tree-branch products as in existing methods. By comparison with existing methods, the total number of trees and of tree pairs is usually considerably reduced, and this fact, together with an easy method of tree-pair sign determination which is also presented, makes the new method simpler in general. The method can be very easily adapted, by the use of infinite parameters, to accommodate ideal transformers, operational amplifiers, and other forms of network constraint; in fact, is thought to be applicable to all linear networks.

Switching and fault transient analysis of 765 kV transmission systems

The analysis of electromagnetic transients arising in EHV/UHV power networks gives necessary information about the possible stresses on the different network components, which will determine their proper design, limits of operation as well as their pertinent protection strategies. This paper describes the transient analysis of 765 kV EHV transmission system which is a typical expansion in Indian power grid system. Considering various conditions, switching transient and fault transient studies are carried out. A FORTRAN version of EMTP is developed, to study a practical example, then a comparison with the results available in the literature is made.

Causality analysis of groundwater dynamics based on a Vector Autoregressive model in the semi-arid basin of Gundal (South India)

Causal relationships existing between observed levels of groundwater in a semi-arid sub-basin of the Kabini River basin (Karnataka state, India) are investigated in this study. A Vector Auto Regressive model is used for this purpose. Its structure is built on an upstream/downstream interaction network based on observed hydro-physical properties. Exogenous climatic forcing is used as an input based on cumulated rainfall departure. Optimal models are obtained thanks to a trial approach and are used as a proxy of the dynamics to derive causal networks. It appears to be an interesting tool for analysing the causal relationships existing inside the basin. The causal network reveals 3 main regions: the Northeastern part of the Gundal basin is closely coupled to the outlet dynamics. The Northwestern part is mainly controlled by the climatic forcing and only marginally linked to the outlet dynamic. Finally, the upper part of the basin plays as a forcing rather than a coupling with the lower part of the basin allowing for a separate analysis of this local behaviour. The analysis also reveals differential time scales at work inside the basin when comparing upstream oriented with downstream oriented causalities. In the upper part of the basin, time delays are close to 2 months in the upward direction and lower than 1 month in the downward direction. These time scales are likely to be good indicators of the hydraulic response time of the basin which is a parameter usually difficult to estimate practically. This suggests that, at the sub-basin scale, intra-annual time scales would be more relevant scales for analysing or modelling tropical basin dynamics in hard rock (granitic and gneissic) aquifers ubiquitous in south India. (c) 2012 Elsevier B.V. All rights reserved.

Analysis of MAC protocols with correlation receiver for optical CDMA networks – part I

In this paper optical code-division multiple-access (O-CDMA) packet network is considered. Two types of random access protocols are proposed for packet transmission. In protocol 1, all distinct codes and in protocol 2, distinct codes as well as shifted versions of all these codes are used. O-CDMA network performance using optical orthogonal codes (OOCs) 1-D and twodimensional (2-D) wavelength/time single-pulse-per-row (W/TSPR) codes are analyzed. The main advantage of using 2-D codes instead of one-dimensional (1-D) codes is to reduce the errors due to multiple access interference among different users. In this paper, correlation receiver is considered in the analysis. Using analytical model, we compute and compare packet-success probability for 1-D and 2-D codes in an O-CDMA network and the analysis shows improved performance with 2-D codes as compared to 1-D codes.