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A system responding to a stochastic driving signal can be interpreted as computing, by means of its dynamics, an implicit model of the environmental variables. The system's state retains information about past environmental fluctuations, and a fraction of this information is predictive of future ones. The remaining nonpredictive information reflects model(More)
Several distinct computational approaches have recently been implemented to represent conformational heterogeneity from X-ray crystallography datasets that are averaged in time and space. As these modeling methods mature, newly discovered alternative conformations are being used to derive functional protein mechanisms. Room temperature X-ray data collection(More)
A fundamental problem in modern thermodynamics is how a molecular-scale machine performs useful work, while operating away from thermal equilibrium without excessive dissipation. To this end, we derive a friction tensor that induces a Riemannian manifold on the space of thermodynamic states. Within the linear-response regime, this metric structure controls(More)
Three generations of a kindred comprising 50 individuals are described in which recurrent intrahepatic cholestasis of pregnancy has occurred with high frequency. A uniform expression and complete penetrance of the trait in the women of a limited "affected" portion of the kindred (6 affected of 10 women), along with the direct parent-to-child inheritance(More)
We have measured the bending elasticity of short double-stranded DNA (dsDNA) chains through small-angle x-ray scattering from solutions of dsDNA-linked dimers of gold nanoparticles. This method, which does not require exertion of external forces or binding to a substrate, reports on the equilibrium distribution of bending fluctuations, not just an average(More)
Many interesting divergence measures between conjugate ensembles of nonequilibrium trajectories can be experimentally determined from the work distribution of the process. Herein, we review the statistical and physical significance of several of these measures, in particular the relative entropy (dissipation), Jeffreys divergence (hysteresis),(More)
Electrophorescing biopolymers across nanopores modulates the ionic current through the pore, revealing the polymer's diameter, length, and conformation. The rapidity of polymer translocation ( approximately 30,000 bp/ms) in this geometry greatly limits the information that can be obtained for each base. Here we show that the translocation speed of(More)
Stem cells occupy variable environments where they must distinguish stochastic fluctuations from developmental cues. Here, we use optogenetics to investigate how the pluripotency network in embryonic stem (ES) cells achieves a robust response to differentiation cues but not to gene expression fluctuations. We engineered ES cells in which we could(More)
Knowledge of the mechanical properties of double-stranded DNA (dsDNA) is essential to understand the role of dsDNA looping in gene regulation and the mechanochemistry of molecular machines that operate on dsDNA. Here, we use a newly developed tool, force sensors with optical readout, to measure the forces inside short, strained loops composed of both dsDNA(More)
A deeper understanding of nonequilibrium phenomena is needed to reveal the principles governing natural and synthetic molecular machines. Recent work has shown that when a thermodynamic system is driven from equilibrium then, in the linear response regime, the space of controllable parameters has a Riemannian geometry induced by a generalized friction(More)