biostudies-literatureBlom KAdobe, IncDeutsche Forschungsgemeinschaft (DFG)Welch Foundation (The Welch Foundation)Deutsche ForschungsgemeinschaftNSF | MPS | Division of ChemistryAlexander von Humboldt-StiftungNational Science Foundation (NSF)Welch FoundationNSF | MPS | Division of Chemistry (CHE)Alexander von Humboldt-Stiftung (AvH)National Science Foundatione2318333121https://www.ebi.ac.uk/biostudies/studies/S-EPMC11047069biostudies-literatureUnknown121(17)Many nonequilibrium, active processes are observed at a coarse-grained level, where different microscopic configurations are projected onto the same observable state. Such "lumped" observables display memory, and in many cases, the irreversible character of the underlying microscopic dynamics becomes blurred, e.g., when the projection hides dissipative cycles. As a result, the observations appear less irreversible, and it is very challenging to infer the degree of broken time-reversal symmetry. Here we show, contrary to intuition, that by ignoring parts of the already coarse-grained state space we may-via a process called milestoning-improve entropy-production estimates. We present diverse examples where milestoning systematically renders observations "closer to underlying microscopic dynaProceedings of the National Academy of Sciences of the United States of AmericaMilestoning estimators of dissipation in systems observed at a coarse resolution.PMC11047069n/a1955552Heisenberg Program grant GO 2762/4-1IIS 2212048F-1514Song KBlom KMakarov DEVouga EGodec AfalseMilestoning estimators of dissipation in systems observed at a coarse resolution.Many nonequilibrium, active processes are observed at a coarse-grained level, where different microscopic configurations are projected onto the same observable state. Such "lumped" observables display memory, and in many cases, the irreversible character of the underlying microscopic dynamics becomes blurred, e.g., when the projection hides dissipative cycles. As a result, the observations appear less irreversible, and it is very challenging to infer the degree of broken time-reversal symmetry. Here we show, contrary to intuition, that by ignoring parts of the already coarse-grained state space we may-via a process called milestoning-improve entropy-production estimates. We present diverse examples where milestoning systematically renders observations "closer to underlying microscopic dyna2024-01-01T00:00:00Z2024 Apr2025-04-04T11:05:19.053Z2025-04-04T11:05:19.053ZS-EPMC110470693862594910.1073/pnas.2318333121