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PubMed1992

A network thermodynamic model of the concentrating properties of the rabbit/rat kidney in the steady state using the electronic network simulation program SPICE.

A model for the simulation of the diluting and concentrating properties of the rabbit and rat kidney is developed. Translation of the physical model into an electronic one brings the model into a form that can be handled by the electronic network simulation program SPICE. The steady state responses of both kidneys to various inputs are calculated under certain conditions.

Animals↗
PubMed2006

New species in evolving networks--stochastic theory of sensitive networks and applications on the metaphorical level.

In this paper we develop a theory to describe stochastic influences on the fate of new species with non-linear growth rates in evolutionary processes. We develop a theoretical framework based on notions of species, network, innovation, competition, survival and fitness. We introduce a stochastic picture describing the role of fluctuations in the survival of new species in non-linear systems. In particular we consider the fate of new species with non-linear growth. As an application of the general model framework we consider the fate of 'rare species' in early biological evolution. We show that hypercycle systems do not represent the end of the evolutionary process as they may evolve further in small niches. This has implications for different types of applications ranging from biological systems on one level to socio-technological systems on a more metaphoric level.

Biological Evolution↗
PubMed2006

From gene networks underlying sex determination and gonadal differentiation to the development of neural networks regulating sociosexual behavior.

Genes are not expressed in isolation any more than social behavior has meaning outside of society. Both are in dynamic flux with the immediate environment that the gene/individual finds itself, which in turn establishes the timing, pattern, and conditions of expression. This means that complex behaviors and their genetic underpinnings should be viewed as a cumulative process, or as the result of experiences up to that point in time and, at the same time, as setting the stage for what will follow. The evidence indicates that as experiences accumulate throughout life, early experiences shape how genes/individuals will respond to later experiences, whereas later experiences modify the effects of these earlier experiences. A method of graphically representing and analyzing change in gene and neural networks is presented. Results from several animal model systems will be described to illustrate these methods. First, we will consider the phenomenon of temperature-dependent sex determination in reptiles. We will illustrate how the experience of a particular temperature during a sensitive period of embryogenesis sculpts not only the patterns of expression of genes involved in sex determination and gonadal differentiation but also the morphological, physiological, neuroendocrine, and behavioral traits of the adult phenotype. The second model system concerns the effects of the sex ratio in the litter in rats, and the genotype ratio in the litter of transgenic mice, on the nature and frequency of maternal care and how this in turn influences the patterns of activation of identified neural circuits subserving the offspring's sociosexual behavior when it is an adult.

Animals↗
PubMed2006

A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa possesses two N-acyl-homoserine lactone quorum-sensing systems that regulate large, overlapping sets of genes. Recent global transcriptome and proteome analyses provided a wealth of information about the identity of the regulated genes, N-acyl-homoserine lactone signal specificity, timing of induction, and environmental effects on gene expression. Quorum-sensing gene expression in P. aeruginosa is also embedded in a highly interconnected network of other regulatory systems with a high potential for integrating and responding to multiple environmental signals. Such epigenetic complexity may constitute the basis for the exceptional adaptability of P. aeruginosa to diverse environments.

4-Butyrolactone↗
PubMed1988

Network thermodynamic analysis and stimulation of isotonic solute-coupled volume flow in leaky epithelia: an example of the use of network theory to provide the qualitative aspects of a complex system and its verification by stimulation.

A network thermodynamic model was developed to provide insights into the nature of isotonic solute-coupled volume flow in "leaky" epithelia, where the transepithelial volume flow is assumed to be primarily through the cellular pathway. The coupled flows of solute and volume at each membrane in this four membrane model are described by the practical phenomenological equations as developed by Kedem & Katchalsky (1958). The model contains one permeable non-electrolyte solute (s) and a fixed amount of an impermeable non-electrolyte (i) inside the cell. The cell is assumed to be capable of volume regulation under the steady-state experimental conditions simulated. A solute-pump, located in the basolateral membrane, uses feedback regulation to adjust Cs in the cell in order to maintain cell volume at or near control levels in all simulations. Model behavior is, in general, very consistent with experimental observations with respect to tonicity and magnitude of volume flow over a wide range of experimental conditions. Examination of the parameter space suggests the following important features when isotonic solute-coupled volume flow moves primarily through the cellular pathway: (1) the apical membrane reflection coefficient must be less than that of the basolateral membrane; (2) the basement membrane reflection coefficient must be small; (3) the apical membrane solute permeability and reflection coefficient are the two most "sensitive" parameters and need to vary in an inverse manner in order to maintain isotonicity when both solute and volume flows increase; and (4) relationships (1) and (3) above imply the need for at least two separate solute pathways in the apical membrane, one that is shared with volume flow and one that is not.

Biological Transport↗
PubMed2002

Synthesis and properties of amphiphilic networks 2: a differential scanning calorimetric study of poly(dodecyl methacrylate-stat-2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate) networks and adhesion and spreading of dermal fibroblasts on these materials.

A series of amphiphilic networks was prepared by radical copolymerisation of dodecyl methacrylate, 2,3-propandiol-1-methacrylate and ethandiol dimethacrylate. DSC studies on these materials, swollen in water. revealed that only materials containing more than 27 wt% of water displayed melting endotherms due to the melting of ice-like structures of water (freezing water). In materials that did produce a melting endotherm the peak was generally bimodal. Changing thermal history and heating rate did not effect the shape of the two peaks, nor the relative contribution of each peak to the total endothermic response. These observations and the narrow peak width of the low temperature endotherm suggested that the bimodality was an artefact of the DSC experiment and may be due to the promotion of the glass transition once a fraction of the water has frozen. The morphology of transformed human dermal fibroblasts grown on these materials was then examined by scanning electron microscopy. Compositions that contained only non-freezing water were found to allow cell adhesion and spreading. Cells with well-spread morphologies were obtained on materials containing small fractions of freezing water and dodecyl methacrylate. These fibroblasts displayed surface features such as microvilli and filapodia. However, all compositions of poly(2,3-propandiol-1-methacrylate-co-ethandiol dimethacrylate) (i.e. hydrogels that do not contain dodecyl methacrylate repeat units) were poor substrates for cell growth and examination of these materials showed that very few cells had adhered and those that did were highly rounded.

Biocompatible Materials↗
PubMed2003

From gene networks to brain networks.

The brain's structural organization is so complex that 2,500 years of analysis leaves pervasive uncertainty about (i) the identity of its basic parts (regions with their neuronal cell types and pathways interconnecting them), (ii) nomenclature, (iii) systematic classification of the parts with respect to topographic relationships and functional systems and (iv) the reliability of the connectional data itself. Here we present a prototype knowledge management system (http://brancusi.usc.edu/bkms/) for analyzing the architecture of brain networks in a systematic, interactive and extendable way. It supports alternative interpretations and models, is based on fully referenced and annotated data and can interact with genomic and functional knowledge management systems through web services protocols.

Animals↗
PubMed2005

Protein interactions and fluctuations in a proteomic network using an elastic network model.

A set of protein conformations are analyzed by normal mode analysis. An elastic network model is used to obtain fluctuation and cooperativity of residues with low amplitude fluctuations across different species. Slow modes that are associated with the function of proteins have common features among different protein structures. We show that the degree of flexibility of the protein is important for proteins to interact with other proteins and as the species gets more complex its proteins become more flexible. In the complex organism, higher cooperativity arises due to protein structure and connectivity.

Animals↗
PubMed2005

Multidisciplinary perspectives on core networking skills. A study of skills: and associated training needs, for professionals working in managed clinical networks.

Possessing a wide mix of non-clinical competences is important for professionals involved in managed clinical networks (MCNs). Skills that stand out are related to interpersonal issues, problem solving, decision-making, and managing change. Interprofessional and interorganizational collaboration is important in health care generally and is not confined to MCNs. Skills are likely to have relevance in wider contexts. Training needs identified for professionals in MCNs relate to skills associated with working in challenging situations, including: 'managing change,' 'conflict resolution,' and 'negotiation.' Limited generalizations about profession-specific skills and training needs can be made. However, it is more appropriate to identify skills needed for the specific role(s) an individual is asked to perform, and to investigate if there are performance gaps between skills and competencies.

Attitude of Health Personnel↗
PubMed1983

A multifunction network of computers in a large pathology department. Integration of word processing, data base management, and general purpose computing using network principles.

We report the strategies for design and implementation of a system of compatible mini- and microcomputers intended to improve efficiency of data handling and research in several clinical and academic divisions of a large university hospital department of Pathology. A dedicated, preprogrammed, multiuser, word processing computer and small standalone word processing stations connected to a general purpose minicomputer, using standard network protocols for communication, permit virtually error-free movement of data between computers doing functionally distinct tasks of word processing, data base management, and general scientific computing. User programming is minimized and is done in a simple, well-known, high-level language. We show that cost, thruput, speed, document volume, document size, revision cycle frequency, data base size, and frequency of use are important design criteria and that existing staff can be trained easily to operate the systems.

Computers↗
PubMed2004

Simulating genetic networks made easy: network construction with simple building blocks.

UNLABELLED: We present SIM-plex, a genetic network simulator with a very intuitive interface in which a user can easily specify interactions as simple 'if-then' statements. The simulator is based on the mathematical model of Piecewise Linear Differential Equations (PLDEs). With PLDEs, genetic interactions are approximated as acting in a switch-like manner. AVAILABILITY: The Java program, examples and a tutorial are available at http://www.psb.ugent.be/cbd/ CONTACT: {stcru,makui}@psb.ugent.be

Algorithms↗
PubMed2000

Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model.

Single-neuron recordings from behaving primates have established a link between working memory processes and information-specific neuronal persistent activity in the prefrontal cortex. Using a network model endowed with a columnar architecture and based on the physiological properties of cortical neurons and synapses, we have examined the synaptic mechanisms of selective persistent activity underlying spatial working memory in the prefrontal cortex. Our model reproduces the phenomenology of the oculomotor delayed-response experiment of Funahashi et al. (S. Funahashi, C.J. Bruce and P.S. Goldman-Rakic, Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol 61:331-349, 1989). To observe stable spontaneous and persistent activity, we find that recurrent synaptic excitation should be primarily mediated by NMDA receptors, and that overall recurrent synaptic interactions should be dominated by inhibition. Isodirectional tuning of adjacent pyramidal cells and interneurons can be accounted for by a structured pyramid-to-interneuron connectivity. Robust memory storage against random drift of the tuned persistent activity and against distractors (intervening stimuli during the delay period) may be enhanced by neuromodulation of recurrent synapses. Experimentally testable predictions concerning the neural basis of working memory are discussed.

Animals↗
PubMed2006

Network growth models and genetic regulatory networks.

We study a class of growth algorithms for directed graphs that are candidate models for the evolution of genetic regulatory networks. The algorithms involve partial duplication of nodes and their links, together with the innovation of new links, allowing for the possibility that input and output links from a newly created node may have different probabilities of survival. We find some counterintuitive trends as the parameters are varied, including the broadening of the in-degree distribution when the probability for retaining input links is decreased. We also find that both the scaling of transcription factors with genome size and the measured degree distributions for genes in yeast can be reproduced by the growth algorithm if and only if a special seed is used to initiate the process.

Animals↗
PubMed2005

Function of the cytochrome bc1-aa3 branch of the respiratory network in mycobacteria and network adaptation occurring in response to its disruption.

The aerobic electron transport chain in Mycobacterium smegmatis can terminate in one of three possible terminal oxidase complexes. The structure and function of the electron transport pathway leading from the menaquinol-menaquinone pool to the cytochrome bc1 complex and terminating in the aa3-type cytochrome c oxidase was characterized. M. smegmatis strains with mutations in the bc1 complex and in subunit II of cyctochome c oxidase were found to be profoundly growth impaired, confirming the importance of this respiratory pathway for mycobacterial growth under aerobic conditions. Disruption of this pathway resulted in an adaptation of the respiratory network that is characterized by a marked up-regulation of cydAB, which encodes the bioenergetically less efficient and microaerobically induced cytochrome bd-type menaquinol oxidase that is required for the growth of M. smegmatis under O2-limiting conditions. Further insights into the adaptation of this organism to rerouting of the electron flux through the branch terminating in the bd-type oxidase were revealed by expression profiling of the bc1-deficient mutant strain using a partial-genome microarray of M. smegmatis that is enriched in essential genes. Although the expression profile was indicative of an increase in the reduced state of the respiratory chain, blockage of the bc1-aa3 pathway did not induce the sentinel genes of M. smegmatis that are induced by oxygen starvation and are regulated by the DosR two-component regulator.

Electron Transport↗
PubMed2004

4th meeting of the EU research network EUROME: from the identification of genes and cellular networks in murine models of arthritis to novel therapeutic intervention strategies in rheumatoid arthritis, London, UK, 9 March 2004.

Rheumatoid arthritis (RA) is a common human disease with a prevalence of about 1% in most parts of the world. At the time of symptom onset it is difficult to predict the severity of subsequent disease course. After 2 years joint erosions are seen in most patients, and most patients become clinically disabled within 20 years. A recent meeting at the Kennedy Institute of Rheumatology (Imperial College, London) brought together representatives from several European centres of excellence, to discuss research funded by the EU Framework 5 Quality of Life Programme. This research network combines gene and protein expression profiling with different animal models of RA to identify cells, genes and pathways contributing to arthritis initiation, progression and chronicity. The studies discussed highlight the reality that collaboration between different research groups is the basis of groundbreaking research and, it is hoped, eventual new therapies for RA.

Angiogenesis Inhibitors↗
PubMed2004

A network-based system to improve care for schizophrenia: the Medical Informatics Network Tool (MINT).

The Medical Informatics Network Tool (MINT) is a software system that supports the management of care for chronic illness. It is designed to improve clinical information, facilitate teamwork, and allow management of health care quality. MINT includes a browser interface for entry and organization of data and preparation of real-time reports. It includes personal computer-based applications that interact with clinicians. MINT is being used in a project to improve the treatment of schizophrenia. At each patient visit, a nurse briefly assesses symptoms, side effects, and other key problems and enters this information into MINT. When the physician subsequently opens the patient's electronic medical record, a window appears with the assessment information, a messaging interface, and access to treatment guidelines. Clinicians and managers receive reports regarding the quality of patients' treatment. To date, MINT has been used with more than 165 patients and 29 psychiatrists and has supported practices that are consistent with improvements in the quality of care.

Decision Support Systems, Clinical↗