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Why Biological Systems Suddenly Change State: An Intuitive Guide to Freidlin–Wentzell Theory

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  Stochasticity is ubiquitous in biology and neuroscience, manifesting in various forms, including ion channel noise, synaptic variability, gene regulatory fluctuations, noisy population dynamics, and more. Many biological systems spend long periods in a stable “state” and only rarely transition to another state due to noise. For instance, a neuron typically remains inactive but may occasionally trigger a spontaneous spike. Similarly, a gene can switch from the OFF state to the ON state due to rare bursts of transcription factors. Cells can also transition out of metabolic or epigenetic states, populations might shift between different ecological equilibria, and a viral infection can fluctuate between phases of control and uncontrollability. Freidlin–Wentzell theory provides a mathematically rigorous framework to study these phenomena when noise is small but nonzero . It tells you, firstly, h ow likely rare transitions are,    secondly,   h ow fast they occ...

MULTICOLLINEARITY IN LINEAR MODELS

1. Introduction One of the fundamental assumptions of the general linear model 1) y = X β + u where u is a vector of zero-mean and uncorrelated stochastic errors,  is that the data matrix X of order n * k has rank k, that is, the explanatory variables are not linearly dependent. This is because the least squares solution 2)  b = ( X ' X ) -1 X ' y   requires the inversion of X ' X , which, however, would not be possible if the rank of X is <k (because X becomes singular). If  some or all of the explanatory variables are perfectly collinear, then  the system 1)  is said to be affected by " extreme"  multicollinearity .   Problems in the   calculation of the solution 2) can emerge even when the collinearity among the variables is not perfect. the main effects of collinearity are [ 1 ]: Lowered precision of the estimates t hat makes it difficult, if not impossible, to separate the relative influences of ...

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