MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Online Monitoring Technical Basis and Analysis Framework for Large Power Transformers; Interim Report for FY 2012

The Light Water Reactor Sustainability program at Idaho National Laboratory (INL) is actively conducting research to develop and demonstrate online monitoring (OLM) capabilities for active components in existing Nuclear Power Plants. A pilot project is currently underway to apply OLM to Generator Step-Up Transformers (GSUs) and Emergency Diesel Generators (EDGs). INL and the Electric Power Research Institute (EPRI) are working jointly to implement the pilot project. The EPRI Fleet-Wide Prognostic and Health Management (FW-PHM) Software Suite will be used to implement monitoring in conjunction with utility partners: the Shearon Harris Nuclear Generating Station (owned by Duke Energy for GSUs, and Braidwood Generating Station (owned by Exelon Corporation) for EDGs. This report presents monitoring techniques, fault signatures, and diagnostic and prognostic models for GSUs. GSUs are main transformers that are directly connected to generators, stepping up the voltage from the generator output voltage to the highest transmission voltages for supplying electricity to the transmission grid. Technical experts from Shearon Harris are assisting INL and EPRI in identifying critical faults and defining fault signatures associated with each fault. The resulting diagnostic models will be implemented in the FW-PHM Software Suite and tested using data from Shearon-Harris. Parallel research on EDGs is being conducted, and will be reported in an interim report during the first quarter of fiscal year 2013

Guidance for Deployment of Mobile Technologies for Nuclear Power Plant Field Workers

This report is a guidance document prepared for the benefit of commercial nuclear power plants’ (NPPs) supporting organizations and personnel who are considering or undertaking deployment of mobile technology for the purpose of improving human performance and plant status control (PSC) for field workers in an NPP setting. This document especially is directed at NPP business managers, Electric Power Research Institute, Institute of Nuclear Power Operations, and other non-Information Technology personnel. This information is not intended to replace basic project management practices or reiterate these processes, but is to support decision-making, planning, and preparation of a business case

Перспективи розвитку експортоорієнтованої стратегії підприємств

Рассмотрен вопрос стратегического развития экспортноориентрованной политики предприятий. Раскрыты перспективы развития международных торговых отношений Украины.Розглянуто питання стратегічного розвитку експортноорієнтовної політики підприємств. Розкрито перспективи розвитку міжнародних торгівельних відносин України

Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides

Pseudomonads are cosmopolitan microorganisms able to produce a wide array of specialized metabolites. These molecules allow Pseudomonas to scavenge nutrients, sense population density and enhance or inhibit growth of competing microorganisms. However, these valuable metabolites are typically characterized one-molecule–one-microbe at a time, instead of being inventoried in large numbers. To index and map the diversity of molecules detected from these organisms, 260 strains of ecologically diverse origins were subjected to mass-spectrometry-based molecular networking. Molecular networking not only enables dereplication of molecules, but also sheds light on their structural relationships. Moreover, it accelerates the discovery of new molecules. Here, by indexing the Pseudomonas specialized metabolome, we report the molecular-networking-based discovery of four molecules and their evolutionary relationships: a poaeamide analogue and a molecular subfamily of cyclic lipopeptides, bananamides 1, 2 and 3. Analysis of their biosynthetic gene cluster shows that it constitutes a distinct evolutionary branch of the Pseudomonas cyclic lipopeptides. Through analysis of an additional 370 extracts of wheat-associated Pseudomonas, we demonstrate how the detailed knowledge from our reference index can be efficiently propagated to annotate complex metabolomic data from other studies, akin to the way in which newly generated genomic information can be compared to data from public databases

Online Monitoring Technical Basis and Analysis Framework for Large Power Transformers; Interim Report for FY 2012

The Light Water Reactor Sustainability program at Idaho National Laboratory (INL) is actively conducting research to develop and demonstrate online monitoring (OLM) capabilities for active components in existing Nuclear Power Plants. A pilot project is currently underway to apply OLM to Generator Step-Up Transformers (GSUs) and Emergency Diesel Generators (EDGs). INL and the Electric Power Research Institute (EPRI) are working jointly to implement the pilot project. The EPRI Fleet-Wide Prognostic and Health Management (FW-PHM) Software Suite will be used to implement monitoring in conjunction with utility partners: the Shearon Harris Nuclear Generating Station (owned by Duke Energy for GSUs, and Braidwood Generating Station (owned by Exelon Corporation) for EDGs. This report presents monitoring techniques, fault signatures, and diagnostic and prognostic models for GSUs. GSUs are main transformers that are directly connected to generators, stepping up the voltage from the generator output voltage to the highest transmission voltages for supplying electricity to the transmission grid. Technical experts from Shearon Harris are assisting INL and EPRI in identifying critical faults and defining fault signatures associated with each fault. The resulting diagnostic models will be implemented in the FW-PHM Software Suite and tested using data from Shearon-Harris. Parallel research on EDGs is being conducted, and will be reported in an interim report during the first quarter of fiscal year 2013

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening

Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin's Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover a functional asymmetry within the heart of cohesin's highly conserved ABC-like ATPase machinery and find that both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around the sister chromatids by counteracting an activity associated with one of cohesin's two ATPase sites. Tight regulation of DNA entrapment and release by the cohesin complex is crucial for its multiple cellular functions. Elbatsh et al. find that cohesin's release from DNA requires an activity associated with one of its ATPase sites, whereas both sites control cohesin's loading onto DNA

The Impossibility of a Perfectly Competitive Labor Market

Using the institutional theory of transaction cost, I demonstrate that the assumptions of the competitive labor market model are internally contradictory and lead to the conclusion that on purely theoretical grounds a perfectly competitive labor market is a logical impossibility. By extension, the familiar diagram of wage determination by supply and demand is also a logical impossibility and the neoclassical labor demand curve is not a well-defined construct. The reason is that the perfectly competitive market model presumes zero transaction cost and with zero transaction cost all labor is hired as independent contractors, implying multi-person firms, the employment relationship, and labor market disappear. With positive transaction cost, on the other hand, employment contracts are incomplete and the labor supply curve to the firm is upward sloping, again causing the labor demand curve to be ill-defined. As a result, theory suggests that wage rates are always and everywhere an amalgam of an administered and bargained price. Working Paper 06-0