Developmental signaling pathways needed to evolve to be robust against environmental fluctuations. In this issue, Shimizu et al. reveal a complex system of interacting endocytic pathways that help to maintain consistent levels of Notch activity across a range of temperatures.

Simulated tempering (ST) is an established Markov Chain Monte Carlo (MCMC) methodology for sampling from a multimodal density π(θ). The technique involves introducing an auxiliary variable k taking values in a finite subset of [0, 1] and indexing a set of tempered distributions, say π k (θ) ∝ π(θ) k. Small values of k encourage better mixing, but samples from π are only obtained when the joint ...

We introduce an enhanced sampling simulation technique based on continuous tempering, i.e., on continuously varying the temperature of the system under investigation. Our approach is mathematically straightforward, being based on an extended Hamiltonian formulation in which an auxiliary degree of freedom, determining the effective temperature, is coupled to the physical system. The physical sys...