MEDEAS: a new modeling framework integrating global biophysical and socioeconomic constraints

Producción CientíficaA diversity of integrated assessment models (IAMs) coexists due to the different approaches developed to deal with the complex interactions, high uncertainties and knowledge gaps within the environment and human societies. This paper describes the open-source MEDEAS modeling framework, which has been developed with the aim of informing decision-making to achieve the transition to sustainable energy systems with a focus on biophysical, economic, social and technological restrictions and tackling some of the limitations identified in the current IAMs. MEDEAS models include the following relevant characteristics: representation of biophysical constraints to energy availability; modeling of the mineral and energy investments for the energy transition, allowing a dynamic assessment of the potential mineral scarcities and computation of the net energy available to society; consistent representation of climate change damages with climate assessments by natural scientists; integration of detailed sectoral economic structure (input–output analysis) within a system dynamics approach; energy shifts driven by physical scarcity; and a rich set of socioeconomic and environmental impact indicators. The potentialities and novel insights that this framework brings are illustrated by the simulation of four variants of current trends with the MEDEAS-world model: the consideration of alternative plausible assumptions and methods, combined with the feedback-rich structure of the model, reveal dynamics and implications absent in classical models. Our results suggest that the continuation of current trends will drive significant biophysical scarcities and impacts which will most likely derive in regionalization (priority to security concerns and trade barriers), conflict, and ultimately, a severe global crisis which may lead to the collapse of our modern civilization. Despite depicting a much more worrying future than conventional projections of current trends, we however believe it is a more realistic counterfactual scenario that will allow the design of improved alternative sustainable pathways in future work.Ministerio de Economía, Industria y Competitividad (Project CO2017-85110-R)Ministerio de Economía, Industria y Competitividad (Project JCI-2016–28833)MEDEAS project, funded by the European Union’s Horizon2020 research and innovation programme under grant agree-ment no. 691287.LOCOMOTION project, funded by the EuropeanUnion’s Horizon 2020 research and innovation programmeunder grant agreement no. 82110

Partial inhibition of human neutrophil activation by FK-506 at supratherapeutic concentrations

The macrolide, FK-506, is a potent and effective inhibitor of lymphocyte activation. We studied the effects of FK-506 on human neutrophil activation induced by chemoattractants and by various substances which circumvent receptor stimulation. After preincubation for 5 min at 37 degrees C, FK-506 (1 microM) inhibited N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe)- or platelet-activating factor-induced superoxide production in neutrophils by about 30%. At therapeutic concentrations (0.1-1 nM) FK-506 was ineffective. FK-506 did not inhibit exocytosis and rises in cytosolic Ca2+ concentration [Ca2+]i mediated by these stimuli, and it did not at all inhibit neutrophil activation induced by C5a, leukotriene B4 and 4 beta-phorbol 12-myristate 13-acetate. FK-506 (1 microM) inhibited A23187-induced exocytosis by about 35%, but A23187-induced superoxide production was unaffected. After preincubation for 5 min at 37 degrees C, FK-506 inhibited fMet-Leu-Phe-induced superoxide production in dibutyryl cAMP-differentiated HL-60 cells by about 20%; preincubation with the drug for 24 h did not result in inhibition of superoxide production. FK-506 did not inhibit agonist-binding to formyl peptide receptors and fMet-Leu-Phe-stimulated GTP hydrolysis of heterotrimeric regulatory guanine nucleotide-binding proteins (G-proteins) in membranes from dibutyryl cAMP-differentiated HL-60 cells. FK-506 did not change steady-state and differential polarized phase fluorescence in HL-60 membranes using 1,6-diphenylhexa-1,3,5-triene and 12-(9-anthroyloxy)-stearate as probes. Our results show that FK-506 at supratherapeutic concentrations partially inhibits neutrophil activation. Inhibition by FK-506 of fMet-Leu-Phe-induced superoxide production is rapid in onset and is not due to inhibition of agonist-binding to receptors, interference with G-proteins or protein kinase C, reduction of rises in [Ca2+]i or alteration in physical membrane state

In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles

Fluorescence imaging is one of the most versatile and widely used visualization methods in biomedical research. However, tissue autofluorescence is a major obstacle confounding interpretation of in vivo fluorescence images. The unusually long emission lifetime (5-13 mu s) of photoluminescent porous silicon nanoparticles can allow the time-gated imaging of tissues in vivo, completely eliminating shorter-lived (<10 ns) emission signals from organic chromophores or tissue autofluorescence. Here using a conventional animal imaging system not optimized for such long-lived excited states, we demonstrate improvement of signal to background contrast ratio by 450-fold in vitro and by 420-fold in vivo when imaging porous silicon nanoparticles. Time-gated imaging of porous silicon nanoparticles accumulated in a human ovarian cancer xenograft following intravenous injection is demonstrated in a live mouse. The potential for multiplexing of images in the time domain by using separate porous silicon nanoparticles engineered with different excited state lifetimes is discussed