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Progress in modeling dynamic systems for sustainable development.

ABSTRACT: This Perspective evaluates recent progress in modeling nature-society systems to inform sustainable development. We argue that recent work has begun to address longstanding and often-cited challenges in bringing modeling to bear on problems of sustainable development. For each of four stages of modeling practice-defining purpose, selecting components, analyzing interactions, and assessing interventions-we highlight examples of dynamical modeling methods and advances in their application that have improved understanding and begun to inform action. Because many of these methods and associated advances have focused on particular sectors and places, their potential to inform key open questions in the field of sustainability science is often underappreciated. We discuss how application of such methods helps researchers interested in harnessing insights into specific sectors and locations to address human well-being, focus on sustainability-relevant timescales, and attend to power differentials among actors. In parallel, application of these modeling methods is helping to advance theory of nature-society systems by enhancing the uptake and utility of frameworks, clarifying key concepts through more rigorous definitions, and informing development of archetypes that can assist hypothesis development and testing. We conclude by suggesting ways to further leverage emerging modeling methods in the context of sustainability science.

SUBMITTER: Selin NE

PROVIDER: S-EPMC10556647 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Progress in modeling dynamic systems for sustainable development.

Selin Noelle E NE Giang Amanda A Clark William C WC

Proceedings of the National Academy of Sciences of the United States of America 20230926 40

This Perspective evaluates recent progress in modeling nature-society systems to inform sustainable development. We argue that recent work has begun to address longstanding and often-cited challenges in bringing modeling to bear on problems of sustainable development. For each of four stages of modeling practice-defining purpose, selecting components, analyzing interactions, and assessing interventions-we highlight examples of dynamical modeling methods and advances in their application that hav ...[more]

PMID: 37751553

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Project description:Accurate prediction of metabolism is a significant outstanding challenge in toxicology. The best predictions are based on experimental data from in vitro systems using primary hepatocytes. The predictivity of the primary hepatocyte-based culture systems, however, is still limited due to well-known phenotypic instability and rapid decline of metabolic competence within a few hours. Dynamic flow bioreactors for three-dimensional cell cultures are thought to be better at recapitulating tissue microenvironments and show potential to improve in vivo extrapolations of chemical or drug toxicity based on in vitro test results. These more physiologically relevant culture systems hold potential for extending metabolic competence of primary hepatocyte cultures as well. In this investigation, we used computational fluid dynamics to determine the optimal design of a flow-based hepatocyte culture system for evaluating chemical metabolism in vitro. The main design goals were (1) minimization of shear stress experienced by the cells to maximize viability, (2) rapid establishment of a uniform distribution of test compound in the chamber, and (3) delivery of sufficient oxygen to cells to support aerobic respiration. Two commercially available flow devices - RealBio® and QuasiVivo® (QV) - and a custom developed fluidized bed bioreactor were simulated, and turbulence, flow characteristics, test compound distribution, oxygen distribution, and cellular oxygen consumption were analyzed. Experimental results from the bioreactors were used to validate the simulation results. Our results indicate that maintaining adequate oxygen supply is the most important factor to the long-term viability of liver bioreactor cultures. Cell density and system flow patterns were the major determinants of local oxygen concentrations. The experimental results closely corresponded to the in silico predictions. Of the three bioreactors examined in this study, we were able to optimize the experimental conditions for long-term hepatocyte cell culture using the QV bioreactor. This system facilitated the use of low system volumes coupled with higher flow rates. This design supports cellular respiration by increasing oxygen concentrations in the vicinity of the cells and facilitates long-term kinetic studies of low clearance test compounds. These two goals were achieved while simultaneously keeping the shear stress experienced by the cells within acceptable limits.

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Dataset Information

Progress in modeling dynamic systems for sustainable development.

Publications

Progress in modeling dynamic systems for sustainable development.

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