Non-equilibrium transitions in multiscale systems with a bifurcating slow manifold

Noise-induced transitions between metastable fixed points in systems evolving on multiple time scales are analyzed in situations where the time scale separation gives rise to a slow manifold with bifurcation. This analysis is performed within the realm of large deviation theory. It is shown that these non-equilibrium transitions make use of a reaction channel created by the bifurcation structure of the slow manifold, leading to vastly increased transition rates. Several examples are used to illustrate these findings, including an insect outbreak model, a system modeling phase separation in the presence of evaporation, and a system modeling transitions in active matter self-assembly. The last example involves a spatially extended system modeled by a stochastic partial differential equation

ECONOMIC CYCLES AND THE THERMODYNAMIC UNCERTAINTY RELATIONS

In the century and a half since Maxwell first conjured his “finite being” which Lord Kelvin subsequently dubbed a “daemon”, researchers have explored the connections between non-equilibrium thermodynamics, entropy, and information theory. In recent years various Thermodynamic Uncertainty Relations (TURs) have been derived to inform upon the relationship between the entropy production and the precision possible in thermodynamic machines and processes. In this paper the recently derived TURs are applied to a hypothetical thermodynamic economy. The TURs define the lower bound on the total entropy production of the economy. Changes in the economy’s entropy production rate have important consequences for the stability of the economic systems, the growth of inflation and play a central role in the evolution of the business cycle. This new perspective has important implications for policy makers, researchers, and other economic actors

Excellentia Eminentia Effectio

"In these pages you will learn about the fascinating research endeavors that each of our faculty members is undertaking. We have divided their research into the broad categories of health, sustainability, information, and systems. While we recognize the imperfect nature of categorizing research that, by its very nature may be interdisciplinary or transdisciplinary, we nonetheless believe it will be helpful as a way to see the depth and breadth of our research endeavors within each grouping. As you read the profiles on these pages, I know you will begin to appreciate that, taken as a whole, the research spectrum at Columbia Engineering is exceptional and that, as our professors go about their work, they are at the cusp of making breakthroughs that will have a major impact on the way we live our lives today and tomorrow.

Entropy mediated organization of E.coli chromosome in fast growth conditions

Recent experiments have been able to visualise chromosome organization in fast-growing E.coli cells. However, the mechanism underlying the spatio-temporal organization remains poorly understood. We propose that the DNA adopts a specific polymer topology as it goes through its cell cycle. We establish that the emergent entropic forces between polymer segments of the DNA-polymer with modified topology, leads to chromosome organization as seen in-vivo. We employ computer simulations of a replicating bead spring model of a polymer in a cylinder to investigate the problem. Our simulation of the overlapping cell cycles not only show successful segregation, but also reproduces the evolution of the spatial organization of the chromosomes as observed in experiments. This manuscript in addition to our previous work on slowly growing bacterial cells, shows that our topology-based model can explain the organization of chromosomes in all growth conditions

Thermal Characteristics and Safety Aspects of Lithium-Ion Batteries: An In-Depth Review

This paper provides an overview of the significance of precise thermal analysis in the context of lithium-ion battery systems. It underscores the requirement for additional research to create efficient methodologies for modeling and controlling thermal properties, with the ultimate goal of enhancing both the safety and performance of Li-ion batteries. The interaction between temperature regulation and lithium-ion batteries is pivotal due to the intrinsic heat generation within these energy storage systems. A profound understanding of the thermal behaviors exhibited by lithium-ion batteries, along with the implementation of advanced temperature control strategies for battery packs, remains a critical pursuit. Utilizing tailored models to dissect the thermal dynamics of lithium-ion batteries significantly enhances our comprehension of their thermal management across a wide range of operational scenarios. This comprehensive review systematically explores diverse research endeavors that employ simulations and models to unravel intricate thermal characteristics, behavioral nuances, and potential runaway incidents associated with lithium-ion batteries. The primary objective of this review is to underscore the effectiveness of employed characterization methodologies and emphasize the pivotal roles that key parameters—specifically, current rate and temperature—play in shaping thermal dynamics. Notably, the enhancement of thermal design systems is often more feasible than direct alterations to the lithium-ion battery designs themselves. As a result, this thermal review primarily focuses on the realm of thermal systems. The synthesized insights offer a panoramic overview of research findings, with a deeper understanding requiring consultation of specific published studies and their corresponding modeling endeavors

The quantum revolution in enzymatic chemistry: combining quantum and classical mechanics to understand biochemical processes

This paper reflects the authors' personal journey in applying quantum chemistry methods to understand one of the most important processes in nature: enzymatic catalysis. The integration of quantum mechanics with biomolecular simulations represents one of the most significant advances in computational enzymology over the past few decades. This approach has revolutionized our understanding of enzyme function and catalytic mechanisms, and has provided powerful tools for enzyme design and optimization. Combined quantum mechanics/molecular mechanics (QM/MM) methods have transformed theoretical studies of enzymatic reactions from qualitative descriptions to quantitative predictions, capable of guiding experimental work with unprecedented accuracy

Dagstuhl News January - December 2011

"Dagstuhl News" is a publication edited especially for the members of the Foundation "Informatikzentrum Schloss Dagstuhl" to thank them for their support. The News give a summary of the scientific work being done in Dagstuhl. Each Dagstuhl Seminar is presented by a small abstract describing the contents and scientific highlights of the seminar as well as the perspectives or challenges of the research topic

Mechanistic Studies of HIV-1 Capsid Maturation and Nuclear Entry Using Multiscale Coarse-Grained Simulations

During HIV-1 maturation, CA can self-assemble into a wide range of capsid morphologies made of ~175-250 hexamers and 12 pentamers. Most recently, the cellular polyanion inositol hexakisphosphate (IP6) has been demonstrated to facilitate conical capsid formation by coordinating a ring of arginine residues within the central cavity of capsid hexamers and pentamers. However, the precise kinetic interplay of events during IP6 and CA co-assembly is unclear. In the first project, we use Coarse-grained Molecular Dynamics (CGMD) simulations to elucidate the underlying molecular mechanism of capsid formation, including the crucial role played by IP6. We show that IP6, in relatively small quantities at first, promotes curvature generation by trapping pentameric defects in the growing lattice and shifts assembly behavior towards kinetically favored outcomes. Our analysis also suggests that IP6 can stabilize metastable capsid intermediates and can induce structural pleomorphism in mature capsids. Relatedly, A structural switch comprising the Thr-Val-Gly-Gly (TVGG) motif either assumes a disordered coil or a helix conformation to regulate hexamer or pentamer assembly, respectively. Both IP6 binding and TVGG coil-to-helix transition are essential for pentamer formation. However, the correlation between IP6 binding at the pore and mechanistic details of coil-to-helix transition in pentamer have not been elucidated. Using extensive all-atom molecular dynamics simulations and structural analysis, we demonstrate that IP6 binding at the pore triggers a network of interactions downstream. IP6 imparts structural order at the central ring, which results in multiple kinetically controlled events leading to the coil-to-helix conformational change of the TVGG motif. IP6 facilitates the helix-to-coil transition by allowing the formation of intermediate conformations. Our results identify the key kinetic role of IP6 in pentamer formation, which facilitates the capsid assembly. These results also may point to new druggable targets to prevent intact HIV-1 core formation. For example, small molecule Lenacapavir (LEN) has been proposed to disrupt capsid morphogenesis by occupying the FG-binding pocket located between neighboring CA subunits. As LEN and IP6 interact with overlapping structural elements, they can compete to influence the assembly pathway and outcomes. Using coarse-grained molecular simulations, we examined capsid assembly across varying IP6 and LEN conditions. Our results reveal a concentration-dependent shift in assembly outcomes: LEN accelerates hexamer assembly and reduces pentamer incorporation, leading to malformed, multilayered, or incomplete capsids. Simulations including the viral RNP further show that LEN-treated capsids frequently fail to encapsidate the RNA genome, indicating impaired maturation. Our calculations confirm that LEN impairs the formation of high-curvature regions necessary for closure, supporting a model of off-pathway assembly as a mechanism of viral inhibition. Building on these findings, we developed a bottom-up coarse-grained modeling framework to investigate the interaction of the HIV-1 capsid with host factors during nuclear entry. We constructed and simulated CG models of the capsid in complex with cyclophilin A, Nup358, and Nup153. Our results reveal that while moderate levels of CypA binding stabilize the capsid, excessive CypA coating induces asymmetric strain and structural collapse, particularly at the narrow tip. Simulations of Nup358 domains captured known structural features such as the S-shaped N-terminal solenoid and the oligomerization-driven filament formation via the OE domain. We further modeled Nup153-mediated interactions at the nuclear basket and observed multivalent FG-pocket binding and weak Nup153 self-association, suggesting a possible role in directional capsid translocation and mesh formation. These findings provide a unified view of HIV-1 capsid behavior across multiple stages of viral replication, from self-assembly to nuclear import. The integrative modeling approach presented here lays a foundation for future investigations into viral uncoating, host restriction and antiviral design targeting capsid-host interactions