FASIMU: flexible software for flux-balance computation series in large metabolic networks

<p>Abstract</p> <p>Background</p> <p>Flux-balance analysis based on linear optimization is widely used to compute metabolic fluxes in large metabolic networks and gains increasingly importance in network curation and structural analysis. Thus, a computational tool flexible enough to realize a wide variety of FBA algorithms and able to handle batch series of flux-balance optimizations is of great benefit.</p> <p>Results</p> <p>We present FASIMU, a command line oriented software for the computation of flux distributions using a variety of the most common FBA algorithms, including the first available implementation of (i) weighted flux minimization, (ii) fitness maximization for partially inhibited enzymes, and (iii) of the concentration-based thermodynamic feasibility constraint. It allows batch computation with varying objectives and constraints suited for network pruning, leak analysis, flux-variability analysis, and systematic probing of metabolic objectives for network curation. Input and output supports SBML. FASIMU can work with free (lp_solve and GLPK) or commercial solvers (CPLEX, LINDO). A new plugin (faBiNA) for BiNA allows to conveniently visualize calculated flux distributions. The platform-independent program is an open-source project, freely available under GNU public license at <url>http://www.bioinformatics.org/fasimu</url> including manual, tutorial, and plugins.</p> <p>Conclusions</p> <p>We present a flux-balance optimization program whose main merits are the implementation of thermodynamics as a constraint, batch series of computations, free availability of sources, choice on various external solvers, and the flexibility on metabolic objectives and constraints.</p

Logistics management of late product individualisation -- application in the automotive industry

Global markets and the increasing demand of customers for individual products lead to a steady rise of product variants. Especially high quality goods on highly competitive markets like automobiles must meet customer's demands. The opportunity to configure a car according to ones' preferences leads to an unmanageable number of variants. Manufacturers' strategies to handle this problem reduce the offered component-combinations, but barely succeed in reducing the production-complexity. The approach of the late product individualisation (LPI) meets this problem. The complexity of the production is reduced without limiting the customer's choice to a small number of variants. The production process is relieved from customisation activities while these operations are relocated to further processes of the supply chain. The approach of LPI will be described and how it causes new challenges for the supply chain. Analytic instruments are presented which help to detect reasonable components of a product that should be individualised.analytical hierarchy process, AHP, efficiency analysis, LPI, late product individualisation, supply chain management, SCM, automotive logistics, automobile industry, production complexity, customisation,

Pathological glutamatergic neurotransmission in Gilles de la Tourette Syndrome

Gilles de la Tourette syndrome (GTS) is a hereditary, neuropsychiatric movement disorder with reported abnormalities in the neurotransmission of dopamine and γ- aminobutyric acid (GABA). Spatially focalized alterations in excitatory, inhibitory and modulatory neurochemical ratios within functional subdivisions of the basal ganglia, may lead to the expression of diverse motor and non-motor features as manifested in GTS. Current treatment strategies are often unsatisfactory thus provoking the need for further elucidation of the underlying pathophysiology. In view of (a) the close synergy exhibited by excitatory, inhibitory and modulatory neurotransmitter systems; (b) the crucial role played by glutamate (Glu) in tonic/phasic dopaminergic signalling; and (c) the interdependent metabolic relationship exhibited between Glu and GABA via glutamine (Gln); we postulated that glutamatergic signalling is related to the pathophysiology of GTS. As such, we examined the neurochemical profile of cortico-striato-thalamo-cortical regions in 37 well-characterized, drug-free adult patients and 36 age/gender-matched healthy controls via magnetic resonance spectroscopy at 3T. To interrogate the influence of treatment on metabolite concentrations, spectral data was acquired from 15 patients undergoing a four-week treatment with aripiprazole. Test-retest reliability measurements in 23 controls indicated high repeatability of voxel localization and metabolite quantitation. We report significant reductions in striatal concentrations of Gln, Glu+Gln (Glx) and the Gln:Glu ratio and thalamic concentrations of Glx in GTS in comparison to controls. On-treatment patients exhibited no significant metabolite differences when compared to controls but significant increases in striatal Glu and Glx and trends for increases in striatal Gln and thalamic Glx compared to baseline measurements. Multiple regression analysis revealed a significant negative correlation between (a) striatal Gln and actual tic severity and (b) thalamic Glu and pre-monitory urges. Our results indicate that patients with GTS exhibit an abnormality in the flux of metabolites in the GABA-Glu-Gln cycle, thus implying perturbations in astrocytic- neuronal coupling systems that maintain the subtle balance between excitatory and inhibitory neurotransmission within subcortical nuclei

Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is a hereditary, neuropsychiatric movement disorder with reported abnormalities in the neurotransmission of dopamine and γ- aminobutyric acid (GABA). Spatially focalized alterations in excitatory, inhibitory and modulatory neurochemical ratios within functional subdivisions of the basal ganglia, may lead to the expression of diverse motor and non-motor features as manifested in GTS. Current treatment strategies are often unsatisfactory thus provoking the need for further elucidation of the underlying pathophysiology. In view of (a) the close synergy exhibited by excitatory, inhibitory and modulatory neurotransmitter systems; (b) the crucial role played by glutamate (Glu) in tonic/phasic dopaminergic signalling; and (c) the interdependent metabolic relationship exhibited between Glu and GABA via glutamine (Gln); we postulated that glutamatergic signalling is related to the pathophysiology of GTS. As such, we examined the neurochemical profile of cortico-striato-thalamo-cortical regions in 37 well-characterized, drug-free adult patients and 36 age/gender-matched healthy controls via magnetic resonance spectroscopy at 3T. To interrogate the influence of treatment on metabolite concentrations, spectral data was acquired from 15 patients undergoing a four-week treatment with aripiprazole. Test-retest reliability measurements in 23 controls indicated high repeatability of voxel localization and metabolite quantitation. We report significant reductions in striatal concentrations of Gln, Glu+Gln (Glx) and the Gln:Glu ratio and thalamic concentrations of Glx in GTS in comparison to controls. On-treatment patients exhibited no significant metabolite differences when compared to controls but significant increases in striatal Glu and Glx and trends for increases in striatal Gln and thalamic Glx compared to baseline measurements. Multiple regression analysis revealed a significant negative correlation between (a) striatal Gln and actual tic severity and (b) thalamic Glu and pre-monitory urges. Our results indicate that patients with GTS exhibit an abnormality in the flux of metabolites in the GABA-Glu-Gln cycle, thus implying perturbations in astrocytic- neuronal coupling systems that maintain the subtle balance between excitatory and inhibitory neurotransmission within subcortical nuclei

Pathological glutamatergic neurotransmission in Gilles de la Tourette Syndrome

We hypothesized that glutamatergic signalling is related to pathophysiology of Gilles de la Tourette syndrome (GTS) and investigated glutamatergic metabolism within cortico-striatal regions using 1H-MRS at baseline and during treatment. Absolute metabolite concentrations were calculated with the consideration of voxel compartmentation following frequency and phase drift correction in the time domain. GTS patients exhibited reductions in striatal and thalamic [Glx], which were normalized with treatment and were correlated with clinical severity parameters. Our results implicate glutamatergic metabolism in GTS pathophysiology and indicate a possibly dysfunctional astrocytic-neuronal coupling system, which would have profound effects on the dopaminergic modulation of cortico-striatal input