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- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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- Donges, Jonathan F., et al.
(författare)
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Earth system modeling with endogenous and dynamic human societies : the copan
- 2020
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 11:2, s. 395-413
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of Earth system dynamics in the Anthropocene requires explicitly taking into account the increasing magnitude of processes operating in human societies, their cultures, economies and technosphere and their growing feedback entanglement with those in the physical, chemical and biological systems of the planet. However, current state-of-the-art Earth system models do not represent dynamic human societies and their feedback interactions with the biogeophysical Earth system and macroeconomic integrated assessment models typically do so only with limited scope. This paper (i) proposes design principles for constructing world-Earth models (WEMs) for Earth system analysis of the Anthropocene, i.e., models of social (world)-ecological (Earth) coevolution on up to planetary scales, and (ii) presents the copan:CORE open simulation modeling framework for developing, composing and analyzing such WEMs based on the proposed principles. The framework provides a modular structure to flexibly construct and study WEMs. These can contain biophysical (e.g., carbon cycle dynamics), socio-metabolic or economic (e.g., economic growth or energy system changes), and sociocultural processes (e.g., voting on climate policies or changing social norms) and their feedback interactions, and they are based on elementary entity types, e.g., grid cells and social systems. Thereby, copan:CORE enables the epistemic flexibility needed for contributions towards Earth system analysis of the Anthropocene given the large diversity of competing theories and methodologies used for describing socio-metabolic or economic and sociocultural processes in the Earth system by various fields and schools of thought. To illustrate the capabilities of the framework, we present an exemplary and highly stylized WEM implemented in copan:CORE that illustrates how endogenizing sociocultural processes and feedbacks such as voting on climate policies based on socially learned environmental awareness could fundamentally change macroscopic model outcomes.
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- Kok, Gautam, et al.
(författare)
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Treatment of ARS deficiencies with specific amino acids
- 2021
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600. ; 23:11, s. 2202-2207
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Recessive cytosolic aminoacyl-tRNA synthetase (ARS) deficiencies are severe multiorgan diseases, with limited treatment options. By loading transfer RNAs (tRNAs) with their cognate amino acids, ARS are essential for protein translation. However, it remains unknown why ARS deficiencies lead to specific symptoms, especially early life and during infections. We set out to increase pathophysiological insight and improve therapeutic possibilities. Methods: In fibroblasts from patients with isoleucyl-RS (IARS), leucyl-RS (LARS), phenylalanyl-RS-beta-subunit (FARSB), and seryl-RS (SARS) deficiencies, we investigated aminoacylation activity, thermostability, and sensitivity to ARS-specific amino acid concentrations, and developed personalized treatments. Results: Aminoacylation activity was reduced in all patients, and further diminished at 38.5/40 °C (PLARS and PFARSB), consistent with infectious deteriorations. With lower cognate amino acid concentrations, patient fibroblast growth was severely affected. To prevent local and/or temporal deficiencies, we treated patients with corresponding amino acids (follow-up: 1/2–2 2/3rd years), and intensified treatment during infections. All patients showed beneficial treatment effects, most strikingly in growth (without tube feeding), head circumference, development, coping with infections, and oxygen dependency. Conclusion: For these four ARS deficiencies, we observed a common disease mechanism of episodic insufficient aminoacylation to meet translational demands and illustrate the power of amino acid supplementation for the expanding ARS patient group. Moreover, we provide a strategy for personalized preclinical functional evaluation.
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