170 research outputs found

    Policitemia vera en un perro : su diagnóstico y su tratamiento

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    En este artículo presentamos un caso clínico de policitemia vera (eritrocitosis) canina con un nivel de eritropoyetina en suero normal. Fue diagnosticado y tratado mediante flebotomías repetidas, en un primer momento y con hidroxyurea posteriormente

    Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

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    <p>Abstract</p> <p>Background</p> <p>Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization.</p> <p>Results</p> <p>Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity.</p> <p>Conclusions</p> <p>Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.</p

    Wave Propagation Through Non-Uniform Plasma

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    Increased energy demand has led to plans for building many new dams in the western Amazon, mostly in the Andean region. Historical data and mechanistic scenarios are used to examine potential impacts above and below six of the largest dams planned for the region, including reductions in downstream sediment and nutrient supplies, changes in downstream flood pulse, changes in upstream and downstream fish yields, reservoir siltation, greenhouse gas emissions and mercury contamination. Together, these six dams are predicted to reduce the supply of sediments, phosphorus and nitrogen from the Andean region by 69, 67 and 57% and to the entire Amazon basin by 64, 51 and 23%, respectively. These large reductions in sediment and nutrient supplies will have major impacts on channel geomorphology, floodplain fertility and aquatic productivity. These effects will be greatest near the dams and extend to the lowland floodplains. Attenuation of the downstream flood pulse is expected to alter the survival, phenology and growth of floodplain vegetation and reduce fish yields below the dams. Reservoir filling times due to siltation are predicted to vary from 106-6240 years, affecting the storage performance of some dams. Total CO2 equivalent carbon emission from 4 Andean dams was expected to average 10 Tg y-1 during the first 30 years of operation, resulting in a MegaWatt weighted Carbon Emission Factor of 0.139 tons C MWhr-1. Mercury contamination in fish and local human populations is expected to increase both above and below the dams creating significant health risks. Reservoir fish yields will compensate some downstream losses, but increased mercury contamination could offset these benefits

    Review of existing and operable observing systems and sensors

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    Deliverable 1.4 is aimed at identification of existing and operable observing systems and sensors which are relevant to COMMON SENSE objectives. Report aggregates information on existing observing initiatives, programmes, systems, platforms and sensors. The Report includes: • inventory of previous and current EU funded projects. Some of the them, even if started before 2007, were aimed at activities which are relevant or in line with those stemming from MSFD in 2008. The ‘granulation’ of the contents and objectives of the projects varies from sensors development through observation methodologies to monitoring strategies, • inventory of research infrastructure in Europe. It starts from an attempt to define of Marine Research Infrastructure, as there is not a single definition of Research Infrastructure (RI) or of Marine Research Infrastructure (MRI), and there are different ways to categorise them. The chapter gives the categorization of the MRI, together with detailed description and examples of MRI – research platforms, marine data systems, research sites and laboratories with respect of four MSFD descriptors relevant to COMMON SENSE project, • two chapters on Research Programs and Infrastructure Networks; the pan-European initiatives aimed at cooperation and efficient use of infrastructural resources for marine observation and monitoring and data exchange are analysed. The detailed description of observing sensors and system are presented as well as frameworks for cooperation, • information on platforms (research vessels) available to the Project for testing developed sensors and systems. Platforms are available and operating in all three regions of interest to the project (Mediterranean, North Sea, Baltic), • annexed detailed description of two world-wide observation networks and systems. These systems are excellent examples of added value offered by integrated systems of ocean observation (from data to knowledge) and how they work in practice. Report concludes that it is seen a shortage of new classes of sensors to fulfil the emerging monitoring needs. Sensors proposed to be developed by COMMON SENSE project shall answer to the needs stemmed from introduction of MSFD and GES descriptors

    In silico pathway reconstruction: Iron-sulfur cluster biogenesis in Saccharomyces cerevisiae

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    BACKGROUND: Current advances in genomics, proteomics and other areas of molecular biology make the identification and reconstruction of novel pathways an emerging area of great interest. One such class of pathways is involved in the biogenesis of Iron-Sulfur Clusters (ISC). RESULTS: Our goal is the development of a new approach based on the use and combination of mathematical, theoretical and computational methods to identify the topology of a target network. In this approach, mathematical models play a central role for the evaluation of the alternative network structures that arise from literature data-mining, phylogenetic profiling, structural methods, and human curation. As a test case, we reconstruct the topology of the reaction and regulatory network for the mitochondrial ISC biogenesis pathway in S. cerevisiae. Predictions regarding how proteins act in ISC biogenesis are validated by comparison with published experimental results. For example, the predicted role of Arh1 and Yah1 and some of the interactions we predict for Grx5 both matches experimental evidence. A putative role for frataxin in directly regulating mitochondrial iron import is discarded from our analysis, which agrees with also published experimental results. Additionally, we propose a number of experiments for testing other predictions and further improve the identification of the network structure. CONCLUSION: We propose and apply an iterative in silico procedure for predictive reconstruction of the network topology of metabolic pathways. The procedure combines structural bioinformatics tools and mathematical modeling techniques that allow the reconstruction of biochemical networks. Using the Iron Sulfur cluster biogenesis in S. cerevisiae as a test case we indicate how this procedure can be used to analyze and validate the network model against experimental results. Critical evaluation of the obtained results through this procedure allows devising new wet lab experiments to confirm its predictions or provide alternative explanations for further improving the models

    Analysis of relevant technical issues and deficiencies of the existing sensors and related initiatives currently set and working in marine environment. New generation technologies for cost-effective sensors

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    The last decade has seen significant growth in the field of sensor networks, which are currently collecting large amounts of environmental data. This data needs to be collected, processed, stored and made available for analysis and interpretation in a manner which is meaningful and accessible to end users and stakeholders with a range of requirements, including government agencies, environmental agencies, the research community, industry users and the public. The COMMONSENSE project aims to develop and provide cost-effective, multi-functional innovative sensors to perform reliable in-situ measurements in the marine environment. The sensors will be easily usable across several platforms, and will focus on key parameters including eutrophication, heavy metal contaminants, marine litter (microplastics) and underwater noise descriptors of the MSFD. The aims of Tasks 2.1 and 2.2 which comprise the work of this deliverable are: • To obtain a comprehensive understanding and an up-to-date state of the art of existing sensors. • To provide a working basis on “new generation” technologies in order to develop cost-effective sensors suitable for large-scale production. This deliverable will consist of an analysis of state-of-the-art solutions for the different sensors and data platforms related with COMMONSENSE project. An analysis of relevant technical issues and deficiencies of existing sensors and related initiatives currently set and working in marine environment will be performed. Existing solutions will be studied to determine the main limitations to be considered during novel sensor developments in further WP’s. Objectives & Rationale The objectives of deliverable 2.1 are: • To create a solid and robust basis for finding cheaper and innovative ways of gathering data. This is preparatory for the activities in other WPs: for WP4 (Transversal Sensor development and Sensor Integration), for WP(5-8) (Novel Sensors) to develop cost-effective sensors suitable for large-scale production, reducing costs of data collection (compared to commercially available sensors), increasing data access availability for WP9 (Field testing) when the deployment of new sensors will be drawn and then realized

    Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

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    <p>Abstract</p> <p>Background</p> <p>Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements.</p> <p>Results</p> <p>We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer-approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in <it>Saccharomyces cerevisiae</it>. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast <it>Saccharomyces cerevisiae </it>to heat shock</p> <p>Conclusion</p> <p>Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.</p

    Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

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    Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics. © 2022 The Author(s
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