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A hybrid of genetic algorithm and particle swarm optimization for recurrent network design.

An evolutionary recurrent network which automates the design of recurrent neural/fuzzy networks using a new evolutionary learning algorithm is proposed in this paper. This new evolutionary learning algorithm is based on a hybrid of genetic algorithm (GA) and particle swarm optimization (PSO), and is thus called HGAPSO. In HGAPSO, individuals in a new generation are created, not only by crossover and mutation operation as in GA, but also by PSO. The concept of elite strategy is adopted in HGAPSO, where the upper-half of the best-performing individuals in a population are regarded as elites. However, instead of being reproduced directly to the next generation, these elites are first enhanced. The group constituted by the elites is regarded as a swarm, and each elite corresponds to a particle within it. In this regard, the elites are enhanced by PSO, an operation which mimics the maturing phenomenon in nature. These enhanced elites constitute half of the population in the new generation, whereas the other half is generated by performing crossover and mutation operation on these enhanced elites. HGAPSO is applied to recurrent neural/fuzzy network design as follows. For recurrent neural network, a fully connected recurrent neural network is designed and applied to a temporal sequence production problem. For recurrent fuzzy network design, a Takagi-Sugeno-Kang-type recurrent fuzzy network is designed and applied to dynamic plant control. The performance of HGAPSO is compared to both GA and PSO in these recurrent networks design problems, demonstrating its superiority.

Journal Article↗

Contributions of NMDA receptors to network recruitment and rhythm generation in spinal cord cultures.

N-methyl-d-aspartic acid (NMDA) receptors are implicated in fictive locomotion; however, their precise role there is not clear. In cultures of dissociated cells from foetal rat spinal cord, synchronous bursting (but not fictive locomotion) can be induced by disinhibition, which is produced by blocking glycinergic and gamma-aminobutyric acid (GABA)A-dependent synaptic conductances. In this study, we investigate the role of NMDA-R in rhythm generation during disinhibition with multielectrode arrays and patch-clamp. We previously determined that bursting activity is generated by repetitive recruitment of a network through recurrent excitation. Blocking NMDA-R with d(-)-2-amino-5-phosphonopentanoic acid (APV) decreased the burst duration, suggesting a role of such receptors in the maintenance of high network activity during the bursts. In addition, APV reduced burst rate in about a third of the experiments, suggesting a contribution of NMDA-R in network recruitment. When (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA)/kainate receptors were blocked with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the presence of disinhibition, the burst rate was reduced and burst onset was slowed in two-thirds of the experiments. In the remaining experiments, bursting ceased completely with CNQX. Neither APV nor CNQX changed the spatial patterns of activity in the network, suggesting a co-operation of both receptors in rhythm generation. While NMDA alone was not able to create a rhythm, it accelerated bursting in the presence of disinhibition, made it more regular and slowed down network recruitment. These effects were most likely due to the depolarization of the interneurons in the network. We conclude that NMDA-R contribute to rhythm generation in spinal cultures by supporting recurrent excitation and network recruitment and by depolarizing the network.

2-Amino-5-phosphonovalerate↗

The maintenance of the endoplasmic reticulum network is regulated by p47, a cofactor of p97, through phosphorylation by cdc2 kinase.

The endoplasmic reticulum (ER) has a characteristic complex polygonal structure with hallmark three-way junctions in many types of cells. To investigate the mechanisms responsible for maintaining the ER network, we established ER disassembly and reassembly assays in semi-intact Chinese hamster ovary (CHO) cells that constitutively expressed heat shock protein-47 fused to the green fluorescent protein (GFP-HSP47) as an ER marker (the cells are referred to as CHO-HSP cells). Using these assays, we found that maintenance of the ER network required cytosol and adenosine triphosphate/guanosine 5'-triphosphate (ATP/GTP) hydrolysis, but not actin filaments or microtubules. We also showed that the ER network was disrupted upon addition of either N-ethylmaleimide-treated cytosol after washing semi-intact cells with high salt solution or mitotic cytosol in nocodazole-treated semi-intact CHO-HSP cells. The disrupted ER network induced by mitotic cytosol was reformed by the addition of interphase cytosol. In addition, we found that p47, a cofactor of p97, was essential for the maintenance of the ER network, and that phosphorylation of p47 by cdc2 kinase resulted in ER network disruption by mitotic cytosol. Taken together, these results imply that the maintenance of the ER network requires a membrane fusion process mediated by p97/p47, and that cell cycle-dependent morphological changes of the ER network are regulated through phosphorylation/dephosphorylation of p47.

Adenosine Triphosphatases↗

Elderly persons' social network and need for social support after their first myocardial infarction.

Social network and social support are phenomena suggested to be of importance to successful recovery from myocardial infarction. However, very few studies have been carried out, especially among the elderly, focusing on their social network and its ability to provide adequate support after myocardial infarction. The aim of this study was to examine elderly persons' social network and need for social support three months after their first myocardial infarction. The sample consisted of 128 persons between 65 and 94 years of age who answered a questionnaire. The results showed that the subjects, even the oldest ones, had an available social network and that they were satisfied with the support it provided. There was an increased need for social support after the myocardial infarction, especially for emotional support and appraisal, but also for instrumental aid and information. Despite these positive results indicating that elderly persons with myocardial infarction have a social network, whose members provide them with support, there may be a need for support also from persons outside this network. Assessment of social network characteristics and the need for social support as well as the provision of adequate information about additional support networks are important tasks for all health professionals.

Adaptation, Psychological↗

Social networks of women caregivers.

Social networks and the support that network members provide are important resources for family caregivers in sustaining their caregiving role. Caregivers' perceptions of support from family and friends have been linked to their health status (R. Kahn & T. Antonucci, 1980; I. Sandler & M. Barrera, 1984). The purpose of this study was to explore the social networks and types of perceived support described by women who are caregivers of cognitively impaired older adults. Content analysis was used to examine interview data from a longitudinal qualitative study of 20 women caregivers of cognitively impaired older persons. An important finding of this study was the identification of a typology of social networks of the women caregivers. The caregivers' perceptions of satisfaction with support received and experience of conflict with network members varied according to the characteristics of their social network. Those caregivers who belonged to diverse social networks reported high satisfaction with the support that they received and little or no conflict. Those caregivers with kin-dominated social networks reported little satisfaction with support received and a high degree of conflict.

Adult↗

Phoneme discrimination using connectionist networks.

The application of connectionist networks to speech recognition is assessed using a set of eight representative phonetic discrimination problems chose with respect to a theory of phonetics. A connectionist network model called the temporal flow model (TFM) is defined which represents temporal relationships using delay links and permits general patterns of connectivity. It is argued that the model has properties appropriate for time varying signals such as speech. Networks are trained using gradient descent methods of iterative nonlinear optimization to reduce the mean-squared error between the actual and the desired response of the output units. Separate network solutions are demonstrated for all eight phonetic discrimination problems for one male speaker. The network solutions are analyzed carefully and are shown in every case to make use of known acoustic phonetic cues. The network solutions vary in the degree to which they make use of context-dependent cues to achieve phoneme recognition. The network solutions were tested on data not used for training and achieved an average accuracy of 99.5%. It is concluded that acoustic phonetic speech recognition can be accomplished using connectionist networks.

Algorithms↗

The neural network classification of false killer whale (Pseudorca crassidens) vocalizations.

This study reports the use of unsupervised, self-organizing neural network to categorize the repertoire of false killer whale vocalizations. Self-organizing networks are capable of detecting patterns in their input and partitioning those patterns into categories without requiring that the number or types of categories be predefined. The inputs for the neural networks were two-dimensional characterization of false killer whale vocalization, where each vocalization was characterized by a sequence of short-time measurements of duty cycle and peak frequency. The first neural network used competitive learning, where units in a competitive layer distributed themselves to recognize frequently presented input vectors. This network resulted in classes representing typical patterns in the vocalizations. The second network was a Kohonen feature map which organized the outputs topologically, providing a graphical organization of pattern relationships. The networks performed well as measured by (1) the average correlation between the input vectors and the weight vectors for each category, and (2) the ability of the networks to classify novel vocalizations. The techniques used in this study could easily be applied to other species and facilitate the development of objective, comprehensive repertoire models.

Animals↗

Switching of a neuron from one network to another by sensory-induced changes in membrane properties.

A neuron that is an integral member of the pyloric neural network of the lobster stomatogastric nervous system leaves this network and instead fires exclusively with another stomatogastric nervous system network, the cardiac sac network, whenever the cardiac sac network is active. This switch is associated with the neuron losing, in a long-lasting fashion, regenerative oscillatory membrane properties that underlie its participation in the pyloric network. Functional membership of neurons in central networks is thus not fixed, and long-lasting neuromodulatory influences, controlled at least in part by sensory inputs, can switch neurons from one network to another.

Action Potentials↗

Robust identification of large genetic networks.

Temporal and spatial gene expression, together with the concentration of proteins and metabolites, is tightly controlled in the cell. This is possible thanks to complex regulatory networks between these different elements. The identification of these networks would be extremely valuable. We developed a novel algorithm to identify a large genetic network, as a set of linear differential equations, starting from measurements of gene expression at steady state following transcriptional perturbations. Experimentally, it is possible to overexpress each of the genes in the network using an episomal expression plasmid and measure the change in mRNA concentration of all the genes, following the perturbation. Computationally, we reduced the identification problem to a multiple linear regression, assuming that the network is sparse. We implemented a heuristic search method in order to apply the algorithm to large networks. The algorithm can correctly identify the network, even in the presence of large noise in the data, and can be used to predict the genes that directly mediate the action of a compound. Our novel approach is experimentally feasible and it is readily applicable to large genetic networks.

Algorithms↗

Control motifs for intracellular regulatory networks.

A number of technological innovations are yielding unprecedented data on the networks of biochemical, genetic, and biophysical reactions that underlie cellular behavior and failure. These networks are composed of hundreds to thousands of chemical species and structures, interacting via nonlinear and possibly stochastic physical processes. A central goal of modern biology is to optimally use the data on these networks to understand how their design leads to the observed cellular behaviors and failures. Ultimately, this knowledge should enable cellular engineers to redesign cellular processes to meet industrial needs (such as optimal natural product synthesis), aid in choosing the most effective targets for pharmaceuticals, and tailor treatment for individual genotypes. The size and complexity of these networks and the inevitable lack of complete data, however, makes reaching these goals extremely difficult. If it proves possible to modularize these networks into functional subnetworks, then these smaller networks may be amenable to direct analysis and might serve as regulatory motifs. These motifs, recurring elements of control, may help to deduce the structure and function of partially known networks and form the basis for fulfilling the goals described above. A number of approaches to identifying and analyzing control motifs in intracellular networks are reviewed.

Animals↗

Network analysis in public health: history, methods, and applications.

Network analysis is an approach to research that is uniquely suited to describing, exploring, and understanding structural and relational aspects of health. It is both a methodological tool and a theoretical paradigm that allows us to pose and answer important ecological questions in public health. In this review we trace the history of network analysis, provide a methodological overview of network techniques, and discuss where and how network analysis has been used in public health. We show how network analysis has its roots in mathematics, statistics, sociology, anthropology, psychology, biology, physics, and computer science. In public health, network analysis has been used to study primarily disease transmission, especially for HIV/AIDS and other sexually transmitted diseases; information transmission, particularly for diffusion of innovations; the role of social support and social capital; the influence of personal and social networks on health behavior; and the interorganizational structure of health systems. We conclude with future directions for network analysis in public health.

Behavioral Research↗

Recurrent networks of submucous neurons controlling intestinal secretion: a modeling study.

Secretomotor neurons, immunoreactive for vasoactive intestinal peptide (VIP), are important in controlling chloride secretion in the small intestine. These neurons form functional synapses with other submucosal VIP neurons and transmit via slow excitatory postsynaptic potentials (EPSPs). Thus they form a recurrent network with positive feedback. Intrinsic sensory neurons within the submucosa are also likely to form recurrent networks with positive feedback, provide substantial output to VIP neurons, and receive input from VIP neurons. If positive feedback within recurrent networks is sufficiently large, then neurons in the network respond to even small stimuli by firing at their maximum possible rate, even after the stimulus is removed. However, it is not clear whether such a mechanism operates within the recurrent networks of submucous neurons. We investigated this question by performing computer simulations of realistic models of VIP and intrinsic sensory neuron networks. In the expected range of electrophysiological properties, we found that activity in the VIP neuron network decayed slowly after cessation of a stimulus, indicating that positive feedback is not strong enough to support the uncontrolled firing state. The addition of intrinsic sensory neurons produced a low stable firing rate consistent with the common finding that basal secretory activity is, in part, neurogenic. Changing electrophysiological properties enables these recurrent networks to support the uncontrolled firing state, which may have implications with hypersecretion in the presence of enterotoxins such as cholera-toxin.

Action Potentials↗

Shear stress is not sufficient to control growth of vascular networks: a model study.

Local vessel wall shear stress is considered to be important for vessel growth. This study is a theoretical investigation of how this mechanism contributes to the structure of a vascular network. The analyses and simulations were performed on vascular networks of increasing complexity, ranging from single-vessel resistance to large hexagonal networks. These networks were perfused by constant-flow sources, constant-pressure sources, or pressure sources with internal resistances. The mathematical foundation of the local endothelial shear stress and vessel wall adaptation was as follows: delta d/delta t = K*(tau-tau desired)*d, where d is vessel diameter, tau desired is desired shear stress, and K is a growth factor. Single vessels and networks with vessels in series developed stable optimal diameters when perfused at constant flow or with a constant-pressure source with internal resistance. However, when constant-pressure perfusion was applied, these vessels developed ever-increasing diameters or completely regressed. In networks with two vessels in parallel, only one; vessel attained an optimal diameter and the other regressed, irrespective of the nature of the perfusion source. Finally, large hexagonal networks regressed to a single vessel when perfused with a pressure source with internal resistance. The behavior was independent of variation in parameters, although the adaptation rate and the diameter of the final vessel were altered. Similar conclusions hold for models of vascular trees. We conclude that the effect of shear stress on vascular diameter alone does not lead to stable network structures, and additional factor(s) must be present.

Adaptation, Physiological↗

Three-dimensional reconstructed glomerular capillary network: blood flow distribution and local filtration.

We developed a mathematical model to simulate blood flow and filtration in individual capillary segments of a glomerular network reconstructed from a normal Munich-Wistar (MW) rat. Three-dimensional geometric reconstruction was obtained by semithin serial sections (1 micron) of one glomerulus after perfusion fixation of kidney. Photomicrographs of each section were digitized and processed, using a computer-based image-analysis system, to derive the topological organization of the capillary network and mean diameter and length of individual capillary segments. Blood flow rate in capillary segments was calculated using a theoretical model that considers apparent viscosity of blood in small capillaries as a function of local rheological parameters, partition of cells at bifurcations, and local filtration dependent on transmembrane hydraulic and oncotic pressure gradients along the network. In accord with previous observations, the topological organization of the capillary network disclosed a three-lobular structure. The ultrafiltration coefficient (Kf) calculated for the euvolemic MW rat with the present network approach was compared with that derived from a theoretical model that assumes identical capillaries in parallel. The latter model is shown to underestimate Kf, particularly under conditions in which filtration pressure equilibrium is approached. Calculation of local blood flow and filtration along the network indicates a heterogeneous distribution of these parameters and that some parts of the capillary network operate at filtration pressure equilibrium even if the overall network operates at filtration disequilibrium.

Animals↗

Distributed amine modulation of graded chemical transmission in the pyloric network of the lobster stomatogastric ganglion.

1. In the pyloric network of the lobster stomatogastric ganglion, graded synapses organize the network output. The amines dopamine (DA), serotonin, and octopamine each elicit a distinctive motor pattern from a quiescent pyloric network. We have examined the effects of these amines on the graded synaptic strengths between the six major types of neurons of this network to understand how amine modulation of synaptic strength contributes to the amine-induced motor patterns. Here we tested amine affects at 10 different graded chemical synapses of the pyloric network. We show that each amine has a statistically different spectrum of distributed effects across the network synapses. 2. Under our control conditions (isolated pairs of neurons, removal of modulatory input), most of the graded chemical synapses were weak and some synapses were nonfunctional. The output synapses of the ventricular dilator (VD) neuron were significantly stronger than the other synapses. 3. DA altered the synaptic strength of every graded chemical synapse. This amine strengthened the weak chemical output synapses of the anterior burster (AB), lateral pyloric (LP), and pyloric constrictor (PY) neurons and weakened (and in some cases abolished) the strong chemical output synapses of the VD neuron. The AB-->inferior cardiac neuron (IC) and PY-->IC graded chemical synapses were nonfunctional under our control conditions; DA activated these silent synapses. 4. Serotonin enhanced the AB's output chemical synapses but weakened all the other graded chemical synapses examined. Octopamine's effects were much weaker than those of the other two amines. It enhanced the AB-->LP synapse and the LP's output synapses and weakly strengthened the AB-->PY, VD-->LP, and VD-->PY synapses. 5. The amines alter the input resistance of many of the pyloric neurons, and this could contribute to the observed changes in synaptic strength by altering passive current flow between input and output sites in the cells. However, the input resistance changes were relatively small compared with the changes in synaptic strength and cannot alone account for the synaptic modulation. In some cases the sign of the input resistance change was inconsistent with the change in synaptic strength. Thus the amines appear to modify synaptic transmission directly in this system. 6. This study completes our description of amine effects on all the graded synapses of the pyloric network. We summarize our present and earlier work to show that modulators can reconfigure the entire synaptic organization of a neural network by acting at many distributed synaptic sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

High-betweenness proteins in the yeast protein interaction network.

Structural features found in biomolecular networks that are absent in random networks produced by simple algorithms can provide insight into the function and evolution of cell regulatory networks. Here we analyze "betweenness" of network nodes, a graph theoretical centrality measure, in the yeast protein interaction network. Proteins that have high betweenness, but low connectivity (degree), were found to be abundant in the yeast proteome. This finding is not explained by algorithms proposed to explain the scale-free property of protein interaction networks, where low-connectivity proteins also have low betweenness. These data suggest the existence of some modular organization of the network, and that the high-betweenness, low-connectivity proteins may act as important links between these modules. We found that proteins with high betweenness are more likely to be essential and that evolutionary age of proteins is positively correlated with betweenness. By comparing different models of genome evolution that generate scale-free networks, we show that rewiring of interactions via mutation is an important factor in the production of such proteins. The evolutionary and functional significance of these observations are discussed.

Journal Article↗

An integrative genomics approach to the reconstruction of gene networks in segregating populations.

The reconstruction of genetic networks in mammalian systems is one of the primary goals in biological research, especially as such reconstructions relate to elucidating not only common, polygenic human diseases, but living systems more generally. Here we propose a novel gene network reconstruction algorithm, derived from classic Bayesian network methods, that utilizes naturally occurring genetic variations as a source of perturbations to elucidate the network. This algorithm incorporates relative transcript abundance and genotypic data from segregating populations by employing a generalized scoring function of maximum likelihood commonly used in Bayesian network reconstruction problems. The utility of this novel algorithm is demonstrated via application to liver gene expression data from a segregating mouse population. We demonstrate that the network derived from these data using our novel network reconstruction algorithm is able to capture causal associations between genes that result in increased predictive power, compared to more classically reconstructed networks derived from the same data.

11-beta-Hydroxysteroid Dehydrogenases↗

Changes in the vascular network of the oral epithelium and reduced enamel epithelium during tooth eruption.

The purpose of this study was to examine the vascular network beneath the reduced enamel epithelium (REE) and oral epithelium (OE) during tooth eruption. Using the corrosive-resin casting method, vascular resin casts were prepared from premolar and molar teeth of the dog and examined by scanning electron microscopy. The vascular network beneath the REE is arranged in two layers, an inner layer consisting of a dense capillary network and an outer layer composed primarily of arterioles and venules. Throughout tooth eruption, the configuration of the vessels of the inner layer is continually changing from a network of capillary loops to a fishnet pattern, whereas the arrangement of the vessels of the outer layer remains fairly constant. When the crown emerges into the oral cavity, leakage of resin from the vessels provides evidence of increased vascular permeability, suggesting the presence of inflammation within the marginal gingiva. When root development is nearly complete, the vascular network adjacent to the REE becomes continuous with that of the OE. The inner margin of the free gingiva receives its blood supply from this network, and the vessels of this network also give off branches which anastomose with the capillary network of the periodontal ligament.

Animals↗