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At least 1,063 records · Page 59Linked to original sources

On the design of artificial auto-associative neuronal networks.

In this paper, we consider the problem of how to construct an artificial neuronal network such that it reproduces a given set of patterns in an exact manner. It turns out that the structure of the weight matrix of the network represents the structure of the set of patterns it is acting on, not the patterns themselves. Conditions are discussed under which the associative network memorizes a certain subset of these patterns. Our formal approach is based on the simple observation that neural networks are structured sets of neurons. By regarding recurrent neural networks as dynamical systems with symmetry, the category of G-sets and G-morphisms appears as a natural framework for evaluating their structure and functioning analytically.

Journal Article↗

Mechanisms for regulating synaptic efficiency in the visual cortex.

Brief epochs of pairing of low frequency synaptic activation and postsynaptic depolarization, in vitro, in supragranular neurons of nature guinea-pig visual cortex lead to a transient (20-60 min) synaptic potentiation. The process is due to a true up-regulation of excitatory synapse efficiency onto the activated neuron. The potentiation requires NMDA receptor activation and a postsynaptic calcium signal for induction and it is modifiable by endogenous nitric oxide (NO) production in the mature cortex. In the cortex of young animals (< PND 21), the pairing-induced potentiation is robust and depends on a postsynaptic calcium signal but it is independent of NMDA receptor activation and NO production. The ability of cortical synaptosomes to release endogenous glutamate is enhanced by NMDA receptor activation and this enhancement is NO-dependent. The NO signal, however, does not amplify the glutamate release of all synapses but only those that have activated voltage-gated calcium channels and were presumably more active at the time of the NO signal. Electrophysiological recordings from visual cortical neurons in anesthetized cats with local iontophoresis of compounds that inhibit or facilitate endogenous cortical NO production reveal the capacity for NO to modulate visual responses in vivo. NO appears to act in the intact cortex by amplifying signals of visual inputs that were co-active at the time of the NO production. The adult visual cortex is capable of dramatic alterations in synaptic efficiency over brief periods suggesting a dynamic cortical network. NMDA receptors and nitric oxide contribute to these processes.

Algorithms↗

A mathematical method for investigating dynamic behavior of an idiotype network of the immune system. The time minimum optimal control theory.

We proposed a mathematical method to investigate an integrated property of an idiotype immune network under the time minimum optimal control. The transient changes of amounts of B cell receptor bound antibodies and immune complex in the network system were expressed by detailed differential equations. The rate constant for binding the second Fab arm of antibody was set as a function of coulombic repulsive force to express the influence of redistribution of electrical charges in the ligand-receptor molecular complex. We proposed time minimum optimal control strategy as an organizing principle for rapid reactions of the immune system. Based on the rigorous mathematical foundations of the optimal control theory, we determined the differential equations for co-state variables for the state variables to compute the time minimum transient changes in the amount of the species. Biological parameters in the immune reactions were utilized from the reported experimental data. Numerical computation disclosed that influence of changes in a rate constant extended to all the species of the network. Changes in a rate constant in a different B cell system reinforced the collaborations among the idiotypes and lead them to set in motion the ejection of the antigen. Simulation of reported experimental data by the present method was successful. There were, however, some inevitable dissociations between reported experimental data and computed results. The present method will be available for evaluating the time minimum reaction of the immune network system.

Journal Article↗

Endocytosis and vesicle trafficking.

Several common themes have emerged from recent structural and functional studies of proteins involved in the formation of coated vesicles. For example, inositol polyphosphate lipid headgroups are bound specifically by a variety of different domains in ways appropriate to domain function. Another theme is the recognition of short sequence motifs in structureless regions of other coat components, allowing dynamic multicomponent networks to be established.

Binding Sites↗

Identification of the stimulated hemiretina in primary school children and adults based on left and right hemifield pattern reversal visual evoked potentials--a comparative study.

OBJECTIVES: The analysis of left and right hemifield pattern-reversal visual evoked potentials (PVEPs) in children and the identification of the stimulated hemiretina testing different identification procedures previously applied to adults. METHODS: Lateral hemifield PVEPs were recorded in 40 children (6-11 years) and 27 adults (25-40 years) from, at least, 19 standard electrodes. Two procedures were tested for the determination of the stimulated hemifield: firstly, the evaluation of the values of instantaneous frequency at the occipital electrodes at P100 latency (determined by the global field power), and secondly, the application of a generalised dynamic neural network (GDNN) using the PVEP time course at selected electrode positions as the external input. RESULTS: P100 latency as well as P100 amplitude over the contralateral occiput in children were significantly greater than in adults. Contrary to the behaviour in adults, instantaneous frequency is not a robust identifier of left and right hemiretina stimulation in children. The best identification performances were achieved when using group trained GDNNs with the bipolar difference signals of electrodes P3/P4 or T5/T6 as the external input. CONCLUSIONS: The PVEPs at electrodes P3/P4 and T5/T6 contain essential information for the determination of the stimulated hemifield. This should be further considered during the development of on-line procedures for automatic PVEP detection in future studies.

Adult↗

The transitional ER localization mechanism of Pichia pastoris Sec12.

COPII vesicles assemble at ER subdomains called transitional ER (tER) sites, but the mechanism that generates tER sites is unknown. To study tER biogenesis, we analyzed the transmembrane protein Sec12, which initiates COPII vesicle formation. Sec12 is concentrated at discrete tER sites in the budding yeast Pichia pastoris. We find that P. pastoris Sec12 exchanges rapidly between tER sites and the general ER. The tER localization of Sec12 is saturable and is mediated by interaction of the Sec12 cytosolic domain with a partner component. This interaction apparently requires oligomerization of the Sec12 lumenal domain. Redistribution of P. pastoris Sec12 to the general ER does not perturb the localization of downstream tER components, suggesting that Sec12 and other COPII proteins associate with a tER scaffold. These results provide evidence that tER sites form by a network of dynamic associations at the cytosolic face of the ER.

COP-Coated Vesicles↗

Bicontinuous microemulsions as media for electrochemical studies.

Biocontinuous microemulsions of didodecyldimethylammonium bromide (DDAB)/dodecane/water were explored as media for voltammetric reductions and oxidations of ruthenium(III) hexaammine, ferrocyanide, ferrocene, cob(II)alamin, and several polycyclic aromatic hydrocarbons (PAHs). These clear microemulsions are conductive and are believed to contain a dynamic extended network of interconnected water tubules. Agreement of simulated and experimental voltammetric data shows that electrochemical theory for homogeneous media is followed to a good approximation in DDAB microemulsions. Diffusion of electroactive solutes did not reflect the high bulk viscosities of the microemulsions. Non-polar molecules and ions diffuse as if they were in neat oil or aqueous media, respectively, and voltammograms with good signal to noise ratio are obtained. Reductions of PAHs in the microemulsions occurred by an ECE-type pathway, with nearly reversible one-electron reductions achieved at high scan rates.

Electrochemistry↗

Dynamic stability of signal transduction networks depending on downstream and upstream specificity of protein kinases.

Mathematical methods are used for explaining the structural design of signal transduction networks, e.g. MAP kinase cascades, which control cell proliferation, differentiation or apoptosis. Taking into account protein kinases and phosphatases the interrelation between the topology of signaling networks and the stability of their ground state are analysed. It is shown that the stability is closely related to the system's dimension and to the number of cycles within the network. Systems with a higher number of kinases and/or cycles tend to be more unstable. In contrast to that increasing phosphatase activity stabilises the ground state.

Animals↗

Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane).

One key challenge in regenerating vital organs is the survival of transplanted cells. To meet their metabolic requirements, transport by diffusion is insufficient, and a convective pathway, i.e., a vasculature, is required. Our laboratory pioneered the concept of engineering a vasculature using microfabrication in silicon and Pyrex. Here we report the extension of this concept and the development of a methodology to create an endothelialized network with a vascular geometry in a biocompatible polymer, poly(dimethyl siloxane) (PDMS). High-resolution PDMS templates were produced by replica-molding from micromachined silicon wafers. Closed channels were formed by bonding the patterned PDMS templates to flat PDMS sheets using an oxygen plasma. Human microvascular endothelial cells (HMEC-1) were cultured for 2 weeks in PDMS networks under dynamic flow. The HMEC-1 cells proliferated well in these confined geometries (channel widths ranging from 35 mum to 5 mm) and became confluent after four days. The HMEC-1 cells lined the channels as a monolayer and expressed markers for CD31 and von Willebrand factor (vWF). These results demonstrate that endothelial cells can be cultured in confined geometries, which is an important step towards developing an in vitro vasculature for tissue-engineered organs.

Biocompatible Materials↗

Expression dynamics of a cellular metabolic network.

Toward the goal of understanding system properties of biological networks, we investigate the global and local regulation of gene expression in the Saccharomyces cerevisiae metabolic network. Our results demonstrate predominance of local gene regulation in metabolism. Metabolic genes display significant coexpression on distances smaller than the average network distance, a behavior supported by the distribution of transcription factor binding sites in the metabolic network and genome context associations. Positive gene coexpression decreases monotonically with distance in the network, while negative coexpression is strongest at intermediate network distances. We show that basic topological motifs of the metabolic network exhibit statistically significant differences in coexpression behavior.

Binding Sites↗

Nonlinear dynamics of ice-wedge networks and resulting sensitivity to severe cooling events.

Patterns of subsurface wedges of ice that form along cooling-induced tension fractures, expressed at the ground surface by ridges or troughs spaced 10 30 m apart, are ubiquitous in polar lowlands. Fossilized ice wedges, which are widespread at lower latitudes, have been used to infer the duration and mean temperature of cold periods within Proterozoic and Quaternary climates, and recent climate trends have been inferred from fracture frequency in active ice wedges. Here we present simulations from a numerical model for the evolution of ice-wedge networks over a range of climate scenarios, based on the interactions between thermal tensile stress, fracture and ice wedges. We find that short-lived periods of severe cooling permanently alter the spacing between ice wedges as well as their fracture frequency. This affects the rate at which the widths of ice wedges increase as well as the network's response to subsequent climate change. We conclude that wedge spacing and width in ice-wedge networks mainly reflect infrequent episodes of rapidly falling ground temperatures rather than mean conditions.

Journal Article↗

Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration.

Recognition molecules of the immunoglobulin superfamily have important roles in neuronal interactions during ontogeny, including migration, survival, axon guidance and synaptic targeting. Their downstream signal transduction events specify whether a cell changes its place of residence or projects axons and dendrites to targets in the brain, allowing the construction of a dynamic neural network. A wealth of recent discoveries shows that cell adhesion molecules interact with attractant and repellent guidance receptors to control growth cone and cell motility in a coordinate fashion. We focus on the best-studied subclasses, the neural cell adhesion molecule NCAM and the L1 family of adhesion molecules, which share important structural and functional features. We have chosen these paradigmatic molecules and their interactions with other recognition molecules as instructive for elucidating the mechanisms by which other recognition molecules may guide cell interactions during development or modify their function as a result of injury, learning and memory.

Animals↗

Organelle inheritance in plant cell division: the actin cytoskeleton is required for unbiased inheritance of chloroplasts, mitochondria and endoplasmic reticulum in dividing protoplasts.

Nuclear inheritance is highly ordered, ensuring stringent, unbiased partitioning of chromosomes before cell division. In plants, however, little is known about the analogous cellular processes that might ensure unbiased inheritance of non-nuclear organelles, either in meristematic cell divisions or those induced during the acquisition of totipotency. We have investigated organelle redistribution and inheritance mechanisms during cell division in cultured tobacco mesophyll protoplasts. Quantitative analysis of organelle repositioning observed by autofluorescence of chloroplasts or green fluorescent protein (GFP), targeted to mitochondria or endoplasmic reticulum (ER), demonstrated that these organelles redistribute in an ordered manner before division. Treating protoplasts with cytoskeleton-disrupting drugs showed that redistribution depended on actin filaments (AFs), but not on microtubules (MTs), and furthermore, that an intact actin cytoskeleton was required to achieve unbiased organelle inheritance. Labelling the actin cytoskeleton with a novel GFP-fusion protein revealed a highly dynamic actin network, with local reorganisation of this network itself, appearing to contribute substantially to repositioning of chloroplasts and mitochondria. Our observations show that each organelle exploits a different strategy of redistribution to ensure unbiased partitioning. We conclude that inheritance of chloroplasts, mitochondria and ER in totipotent plant cells is an ordered process, requiring complex interactions with the actin cytoskeleton.

Actins↗

Fast intracellular motion in the living cell by video rate reflection confocal laser scanning microscopy.

Fast intracellular motion (FIM) was first revealed by back scattered light (BSL) imaging in video rate confocal scanning laser microscopy (VRCSLM), beyond the limits of spatial and temporal resolution obtainable with conventional optical microscopy. BSL imaging enabled visualisation of intra and extracellular motion with resolution in space down to 0.2 microm and in time to 1/25th of a second. Mapping the cell space at 0.2 microm x 0.2 microm (XY = in instantaneous best focal plane) x 0.5 microm (Z = height/depth, optic axis direction) volume steps revealed a communication layer above the known contact layer and an integrated dynamic spatial network (IDSN) towards the cell centre. FIM was originally observed as localised quasichaotic dancing (dithering) or reflecting patches/spots in the cell centre, faster in the darker nuclear space. Later, a second type of FIM was recognised which differed by the presence of a varied proportion of centrifugal and centripetal directional movements and/or jumping of patches/spots in the cell centre and outside the nuclear space. The first type is characteristic for cells in slightly adverse conditions while the second type has so far only been found in eutrophic cells. Temporal speeding up and coarsening of FIM, followed by slowing and eventually cessation at cell death, was found on exposure to strong stressors. It was concluded that the state of FIM provides instantaneous information about individual cell reactions to actual treatment and about cell survival. A putative switch between the first and second type FIM could be considered as an indicator of timing of cellular processes. The significance of FIM for the biology of the cell is seen in the rapid assessment of the condition of an individual live cell investigated by combination of various methods. Requirements for further development of this approach are outlined.

Animals↗

Phenotypic and dynamical transitions in model genetic networks. I. Emergence of patterns and genotype-phenotype relationships.

Genotype-phenotype interactions during the evolution of form in multicellular organisms is a complex problem but one that can be aided by computational approaches. We present here a framework within which developmental patterns and their underlying genetic networks can be simulated. Gene networks were chosen to reflect realistic regulatory circuits, including positive and negative feedback control, and the exchange of a subset of gene products between cells, or within a syncytium. Some of these networks generate stable spatial patterns of a subset of their molecular constituents, and can be assigned to categories (e.g., "emergent" or "hierarchic") based on the topology of molecular circuitry. These categories roughly correspond to what has been discussed in the literature as "self-organizing" and "programmed" processes of development. The capability of such networks to form patterns of repeating stripes was studied in network ensembles in which parameters of gene-gene interaction were caused to vary in a manner analogous to genetic mutation. The evolution under mutational change of individual representative networks of each category was also simulated. We have found that patterns with few stripes (< or =3) are most likely to originate in the form of a hierarchic network, whereas those with greater numbers of stripes (> or =4) originate most readily as emergent networks. However, regardless of how many stripes it contains, once a pattern is established, there appears to be an evolutionary tendency for emergent mechanisms to be replaced by hierarchic mechanisms. These results have potential significance for the understanding of genotype-phenotype relationships in the evolution of metazoan form.

Biological Evolution↗

Phenotypic and dynamical transitions in model genetic networks. II. Application to the evolution of segmentation mechanisms.

Knowledge of the genetic control of segmentation in Drosophila has made insect segmentation a paradigmatic case in the study of the evolution of developmental mechanisms. In Drosophila, the patterns of expression of segmentation genes are established simultaneously in all segments by a complex set of interactions between transcriptional factors that diffuse in a syncytium occupying the whole embryo. Such mechanisms cannot act in short germ-band insects where segments appear sequentially from a cellularized posterior proliferative zone. Here, we compare mechanisms of segmentation in different organisms and discuss how the transition between the different types of segmentation can be explained by small and progressive changes in the underlying gene networks. The recent discovery of a temporal oscillation in expression during somitogenesis of vertebrate homologs of the pair-rule gene hairy enhances the plausibility of an earlier proposal that the evolutionary origin of both the short- and long germ-band modes of segmentation was an oscillatory genetic network (Newman 1993). An implication of this scenario is that the self-organizing, pattern-forming system embodied in an oscillatory network operating in the context of a syncytium (i.e., a reaction-diffusion system)-which is hypothesized to have originated the simultaneous mode of segmentation-must have been replaced by the genetic hierarchy seen in modern-day Drosophila over the course of evolution. As demonstrated by the simulations in the accompanying article, the tendency for "emergent" genetic networks, associated with self-organizing processes, to be replaced through natural selection with hierarchical networks is discussed in relation to the evolution of segmentation.

Animals↗

A class of cellular automata modeling winnerless competition.

Neural units introduced by Rabinovich et al. ("Sensory coding with dynamically competitive networks," UCSD and CIT, February 1999) motivate a class of cellular automata (CA) where spatio-temporal encoding is feasible. The spatio-temporal information capacity of a CA is estimated by the information capacity of the attractor set, which happens to be finitely specified. Two-dimensional CA are studied in detail. An example is given for which the attractor is not a subshift. (c) 2002 American Institute of Physics.

Journal Article↗

Forces generated during actin-based propulsion: a direct measurement by micromanipulation.

Dynamic actin networks generate forces for numerous types of movements such as lamellipodia protrusion or the motion of endocytic vesicles. The actin-based propulsive movement of Listeria monocytogenes or of functionalized microspheres have been extensively used as model systems to identify the biochemical components that are necessary for actin-based motility. However, quantitative force measurements are required to elucidate the mechanism of force generation, which is still under debate. To directly probe the forces generated in the process of actin-based propulsion, we developed a micromanipulation experiment. A comet growing from a coated polystyrene bead is held by a micropipette while the bead is attached to a force probe, by using a specially designed "flexible handle." This system allows us to apply both pulling and pushing external forces up to a few nanonewtons. By pulling the actin tail away from the bead at high speed, we estimate the elastic modulus of the gel and measure the force necessary to detach the tail from the bead. By applying a constant force in the range of -1.7 to 4.3 nN, the force-velocity relation is established. We find that the relation is linear for pulling forces and decays more weakly for pushing forces. This behavior is explained by using a dimensional elastic analysis.

Actins↗