Fluorescence recovery after photobleaching (FRAP) is now widely used to investigate binding interactions in live cells. Although various idealized solutions have been identified for the reaction-diffusion equations that govern FRAP, there has been no comprehensive analysis or systematic approach to serve as a guide for extracting binding information from an arbitrary FRAP curve. Here we present a complete solution to the FRAP reaction-diffusion equations for either single or multiple independent binding interactions, and then relate our solution to the various idealized cases. This yields a coherent approach to extract binding information from FRAP data which we have applied to the question of transcription factor mobility in the nucleus. We show that within the nucleus, the glucocorticoid receptor is transiently bound to a single state, with each molecule binding on average 65 sites per second. This rapid sampling is likely to be important in finding a specific promoter target sequence. Further we show that this predominant binding state is not the nuclear matrix, as some studies have suggested. We illustrate how our analysis provides several self-consistency checks on a FRAP fit. We also define constraints on what can be estimated from FRAP data, show that diffusion should play a key role in many FRAP recoveries, and provide tools to test its contribution. Overall our approach establishes a more general framework to assess the role of diffusion, the number of binding states, and the binding constants underlying a FRAP recovery.
We consider the equation in question on the interval 0 g x 5 1 having Neumann boundary conditions, with f ( u ) = F'(u), where F is a double well energy density with equal minima at u = 1. The only stable states of the system are patternless constant solutions. But given two-phase initial data, a pattern of interfacial layers typically forms far out of equilibrium. The ensuing nonlinear relaxation process is extremely slow: patterns persist for exponentially long times proportional to exp( A , / / € ) , where A: = F"(+l) and I is the minimum distance between layers. Physically. a tiny potential jump across a layer drives its motion.We prove the existence and persistence of these metastable patterns, and characterise accurately the equations governing their motion. The point of view is reminiscent of center manifold theory: a manifold parametrising slowly evolving states is introduced, a neighbourhood is shown to be normally attracting, and the parallel flow is characterised to high relative accuracy. Proofs involve a detailed study of the Dirichlet problem, spectral gap analysis, and energy estimates.
This paper is the first in a series to address questions of qualitative behaviour, stability and rigorous passage to a continuum limit for solitary waves in one-dimensional non-integrable lattices with the Hamiltonianwith a generic nearest-neighbour potential V . Here we establish that for speeds close to sonic, unique single-pulse waves exist and the profiles are governed by a continuum limit valid on all length scales, not just the scales suggested by formal asymptotic analysis. More precisely, if the deviation of the speed c from the speed of sound c s = √ V (0) is c s ε 2 /24 then as ε → 0 the renormalized displacement profile (1/ε 2 )r c (•/ε) of the unique single-pulse wave with speed c, q j +1 (t) − q j (t) = r c (j − ct), is shown to converge uniformly to the soliton solution of a KdV equation containing derivatives of the potential as coefficients, −r x + r xxx + 12(V (0)/V (0)) r r x = 0. Proofs involve (a) a new and natural framework for passing to a continuum limit in which the above KdV travelling-wave equation emerges as a fixed point of a renormalization process, (b) careful singular perturbation analysis of lattice Fourier multipliers and (c) a new Harnack inequality for nonlinear differential-difference equations.
We consider the approach to self-similarity (or dynamical scaling) in Smoluchowski's equations of coagulation for the solvable kernels K(x, y) = 2, x + y and xy. In addition to the known self-similar solutions with exponential tails, there are one-parameter families of solutions with algebraic decay, whose form is related to heavy-tailed distributions well-known in probability theory. For K = 2 the size distribution is Mittag-Leffler, and for K = x + y and K = xy it is a power-law rescaling of a maximally skewed α-stable Lévy distribution. We characterize completely the domains of attraction of all self-similar solutions under weak convergence of measures. Our results are analogous to the classical characterization of stable distributions in probability theory. The proofs are simple, relying on the Laplace transform and a fundamental rigidity lemma for scaling limits.
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