Transcriptional network dynamics in macrophage activation

Transcriptional regulatory networks govern cell differentiation and the cellular response to external stimuli. However, mammalian model systems have not yet been accessible for network analysis. Here, we present a genome-wide network analysis of the transcriptional regulation underlying the mouse macrophage response to bacterial lipopolysaccharide (LPS). Key to uncovering the network structure is our combination of time-series cap analysis of gene expression with in silico prediction of transcription factor binding sites. By integrating microarray and qPCR time-series expression data with a promoter analysis, we find dynamic subnetworks that describe how signaling pathways change dynamically during the progress of the macrophage LPS response, thus defining regulatory modules characteristic of the inflammatory response. In particular, our integrative analysis enabled us to suggest novel roles for the transcription factors ATF-3 and NRF-2 during the inflammatory response. We believe that our system approach presented here is applicable to understanding cellular differentiation in higher eukaryotes. (c) 2006 Elsevier Inc. All rights reserved.

GPNN: Power studies and applications of a neural network method for detecting gene-gene interactions in studies of human disease

Background: The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease. Results: We show that GPNN has high power to detect even relatively small genetic effects (2-3% heritability) in simulated data models involving two and three locus interactions. The limits of detection were reached under conditions with very small heritability (

Integrated power scheme simulator for human-system integration studies

We present a simulator of a hydropower company’s view of its scheme, and its broader market and network context, which has been developed to evaluate advanced displays for control room operations. Although simplified, the simulator captures all the main aspects of scheme operations. The simulator allows controlled studies to be performed that test the effectiveness of current vs advanced display concepts under normal vs unexpected operating conditions that can be scripted into the simulator.

The time dimension of neural network models

This review attempts to provide an insightful perspective on the role of time within neural network models and the use of neural networks for problems involving time. The most commonly used neural network models are defined and explained giving mention to important technical issues but avoiding great detail. The relationship between recurrent and feedforward networks is emphasised, along with the distinctions in their practical and theoretical abilities. Some practical examples are discussed to illustrate the major issues concerning the application of neural networks to data with various types of temporal structure, and finally some highlights of current research on the more difficult types of problems are presented.

Neural network-based wind vector retrieval from satellite scatterometer data

Obtaining wind vectors over the ocean is important for weather forecasting and ocean modelling. Several satellite systems used operationally by meteorological agencies utilise scatterometers to infer wind vectors over the oceans. In this paper we present the results of using novel neural network based techniques to estimate wind vectors from such data. The problem is partitioned into estimating wind speed and wind direction. Wind speed is modelled using a multi-layer perceptron (MLP) and a sum of squares error function. Wind direction is a periodic variable and a multi-valued function for a given set of inputs; a conventional MLP fails at this task, and so we model the full periodic probability density of direction conditioned on the satellite derived inputs using a Mixture Density Network (MDN) with periodic kernel functions. A committee of the resulting MDNs is shown to improve the results.

Word of mouth communication within online communities:conceptualizing the online social network

Word of mouth (WOM) communication is a major part of online consumer interactions, particularly within the environment of online communities. Nevertheless, existing (offline) theory may be inappropriate to describe online WOM and its influence on evaluation and purchase.The authors report the results of a two-stage study aimed at investigating online WOM: a set of in-depth qualitative interviews followed by a social network analysis of a single online community. Combined, the results provide strong evidence that individuals behave as if Web sites themselves are primary "actors" in online social networks and that online communities can act as a social proxy for individual identification. The authors offer a conceptualization of online social networks which takes the Web site into account as an actor, an initial exploration of the concept of a consumer-Web site relationship, and a conceptual model of the online interaction and information evaluation process. © 2007 Wiley Periodicals, Inc. and Direct Marketing Educational Foundation, Inc.

Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity

The loss of dopamine in idiopathic or animal models of Parkinson's disease induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurones. We sought to establish whether these firing patterns observed in vivo were preserved in slices taken from dopamine-depleted animals, thus establishing a role for the isolated subthalamic-globus pallidus complex in generating the pathological activity. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of dopamine as measured in striatum by high pressure liquid chromatography. Likewise, significant reductions in tyrosine hydroxylase immunostaining within the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in substantia nigra were observed. Compared with slices from intact mice, neurones in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of 4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABAA receptor antagonist picrotoxin caused no change in firing pattern. Bath application of dopamine significantly increased cell firing rate and regularized the pattern of activity in cells from slices from both MPTP-treated and control animals. Although the absolute change was more modest in control slices, the maximum dopamine effect in the two groups was comparable. Indeed, when taking into account the basal firing rate, no differences in the sensitivity to dopamine were observed between these two cohorts. Furthermore, pairs of subthalamic nucleus cells showed no correlated activity in slices from either control (21 pairs) or MPTP-treated animals (20 pairs). These results indicate that the isolated but interconnected subthalamic-globus pallidus network is not itself sufficient to generate the aberrant firing patterns in dopamine-depleted animals. More likely, inputs from other regions, such as the cortex, are needed to generate pathological oscillatory activity. © 2006 IBRO.

Stationary scattering from a nonlinear network

Transmission through a complex network of nonlinear one-dimensional leads is discussed by extending the stationary scattering theory on quantum graphs to the nonlinear regime. We show that the existence of cycles inside the graph leads to a large number of sharp resonances that dominate scattering. The latter resonances are then shown to be extremely sensitive to the nonlinearity and display multistability and hysteresis. This work provides a framework for the study of light propagation in complex optical networks.

Outlier detection in scatterometer data:Neural network approaches

Satellite-borne scatterometers are used to measure backscattered micro-wave radiation from the ocean surface. This data may be used to infer surface wind vectors where no direct measurements exist. Inherent in this data are outliers owing to aberrations on the water surface and measurement errors within the equipment. We present two techniques for identifying outliers using neural networks; the outliers may then be removed to improve models derived from the data. Firstly the generative topographic mapping (GTM) is used to create a probability density model; data with low probability under the model may be classed as outliers. In the second part of the paper, a sensor model with input-dependent noise is used and outliers are identified based on their probability under this model. GTM was successfully modified to incorporate prior knowledge of the shape of the observation manifold; however, GTM could not learn the double skinned nature of the observation manifold. To learn this double skinned manifold necessitated the use of a sensor model which imposes strong constraints on the mapping. The results using GTM with a fixed noise level suggested the noise level may vary as a function of wind speed. This was confirmed by experiments using a sensor model with input-dependent noise, where the variation in noise is most sensitive to the wind speed input. Both models successfully identified gross outliers with the largest differences between models occurring at low wind speeds. © 2003 Elsevier Science Ltd. All rights reserved.

Neural network enhanced self tuning adaptive control application for non-linear control of dynamic systems

The main theme of research of this project concerns the study of neutral networks to control uncertain and non-linear control systems. This involves the control of continuous time, discrete time, hybrid and stochastic systems with input, state or output constraints by ensuring good performances. A great part of this project is devoted to the opening of frontiers between several mathematical and engineering approaches in order to tackle complex but very common non-linear control problems. The objectives are: 1. Design and develop procedures for neutral network enhanced self-tuning adaptive non-linear control systems; 2. To design, as a general procedure, neural network generalised minimum variance self-tuning controller for non-linear dynamic plants (Integration of neural network mapping with generalised minimum variance self-tuning controller strategies); 3. To develop a software package to evaluate control system performances using Matlab, Simulink and Neural Network toolbox. An adaptive control algorithm utilising a recurrent network as a model of a partial unknown non-linear plant with unmeasurable state is proposed. Appropriately, it appears that structured recurrent neural networks can provide conveniently parameterised dynamic models for many non-linear systems for use in adaptive control. Properties of static neural networks, which enabled successful design of stable adaptive control in the state feedback case, are also identified. A survey of the existing results is presented which puts them in a systematic framework showing their relation to classical self-tuning adaptive control application of neural control to a SISO/MIMO control. Simulation results demonstrate that the self-tuning design methods may be practically applicable to a reasonably large class of unknown linear and non-linear dynamic control systems.

The role of GABAergic modulation in motor function related neuronal network activity

At rest, the primary motor cortex (M1) exhibits spontaneous neuronal network oscillations in the beta (15–30 Hz) frequency range, mediated by inhibitory interneuron drive via GABA-A receptors. However, questions remain regarding the neuropharmacological basis of movement related oscillatory phenomena, such as movement related beta desynchronisation (MRBD), post-movement beta rebound (PMBR) and movement related gamma synchronisation (MRGS). To address this, we used magnetoencephalography (MEG) to study the movement related oscillatory changes in M1 cortex of eight healthy participants, following administration of the GABA-A modulator diazepam. Results demonstrate that, contrary to initial hypotheses, neither MRGS nor PMBR appear to be GABA-A dependent, whilst the MRBD is facilitated by increased GABAergic drive. These data demonstrate that while movement-related beta changes appear to be dependent upon spontaneous beta oscillations, they occur independently of one other. Crucially, MRBD is a GABA-A mediated process, offering a possible mechanism by which motor function may be modulated. However, in contrast, the transient increase in synchronous power observed in PMBR and MRGS appears to be generated by a non-GABA-A receptor mediated process; the elucidation of which may offer important insights into motor processes.

Evidence that interaction between conserved residues in transmembrane helices 2, 3, and 7 are crucial for human VPAC1 receptor activation

The VPAC(1) receptor belongs to family B of G protein-coupled receptors (GPCR-B) and is activated upon binding of the vasoactive intestinal peptide (VIP). Despite the recent determination of the structure of the N terminus of several members of this receptor family, little is known about the structure of the transmembrane (TM) region and about the molecular mechanisms leading to activation. In the present study, we designed a new structural model of the TM domain and combined it with experimental mutagenesis experiments to investigate the interaction network that governs ligand binding and receptor activation. Our results suggest that this network involves the cluster of residues Arg(188) in TM2, Gln(380) in TM7, and Asn(229) in TM3. This cluster is expected to be altered upon VIP binding, because Arg(188) has been shown previously to interact with Asp(3) of VIP. Several point mutations at positions 188, 229, and 380 were experimentally characterized and were shown to severely affect VIP binding and/or VIP-mediated cAMP production. Double mutants built from reciprocal residue exchanges exhibit strong cooperative or anticooperative effects, thereby indicating the spatial proximity of residues Arg(188), Gln(380), and Asn(229). Because these residues are highly conserved in the GPCR-B family, they can moreover be expected to have a general role in mediating function.

Multi-criteria logistics distribution network design using SAS/OR

This paper explores the use of the optimization procedures in SAS/OR software with application to the contemporary logistics distribution network design using an integrated multiple criteria decision making approach. Unlike the traditional optimization techniques, the proposed approach, combining analytic hierarchy process (AHP) and goal programming (GP), considers both quantitative and qualitative factors. In the integrated approach, AHP is used to determine the relative importance weightings or priorities of alternative warehouses with respect to both deliverer oriented and customer oriented criteria. Then, a GP model incorporating the constraints of system, resource, and AHP priority is formulated to select the best set of warehouses without exceeding the limited available resources. To facilitate the use of integrated multiple criteria decision making approach by SAS users, an ORMCDM code was implemented in the SAS programming language. The SAS macro developed in this paper selects the chosen variables from a SAS data file and constructs sets of linear programming models based on the selected GP model. An example is given to illustrate how one could use the code to design the logistics distribution network.

The throughput order of multicast traffics with physical-layer network coding in random wireless ad hoc networks

This paper attempts to address the effectiveness of physical-layer network coding (PNC) on the throughput improvement for multi-hop multicast in random wireless ad hoc networks (WAHNs). We prove that the per session throughput order with PNC is tightly bounded as T((nvmR (n))-1) if m = O(R-2 (n)), where n is the total number of nodes, R(n) is the communication range, and m is the number of destinations for each multicast session. We also show that per-session throughput order with PNC is tight bounded as T(n-1), when m = O(R-2(n)). The results of this paper imply that PNC cannot improve the throughput order of multicast in random WAHNs, which is different from the intuition that PNC may improve the throughput order as it allows simultaneous signal access and combination.

Practical network coding for two way relay channels in LTE networks

In this paper, the implementation aspects and constraints of the simplest network coding (NC) schemes for a two-way relay channel (TWRC) composed of a user equipment (mobile terminal), an LTE relay station (RS) and an LTE base station (eNB) are considered in order to assess the usefulness of the NC in more realistic scenarios. The information exchange rate gain (IERG), the energy reduction gain (ERG) and the resource utilization gain (RUG) of the NC schemes with and without subcarrier division duplexing (SDD) are obtained by computer simulations. The usefulness of the NC schemes are evaluated for varying traffic load levels, the geographical distances between the nodes, the RS transmit powers, and the maximum numbers of retransmissions. Simulation results show that the NC schemes with and without SDD, have the throughput gains 0.5% and 25%, the ERGs 7 - 12% and 16 - 25%, and the RUGs 0.5 - 3.2%, respectively. It is found that the NC can provide performance gains also for the users at the cell edge. Furthermore, the ERGs of the NC increase with the transmit power of the relay while the ERGs of the NC remain the same even when the maximum number of retransmissions is reduced.