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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...

Design and validation of a semi-quantitative microneutralization assay for human Metapneumovirus A1 and B1 subtypes

This study presents a comprehensive overview of human Metapneumovirus (hMPV), an enveloped RNA virus identified in 2001. It details the virus's biological characteristics, epidemiological significance, and ongoing vaccine research efforts. hMPV is classified within the Pneumoviridae family and comprises two global genetic lineages, namely A and B. While the pathogenic mechanisms underlying hMPV infection remain inadequately understood, the structural proteins involved, particularly the Fusion (F) protein, are instrumental in mediating infection and modulating the immune response. The F protein is highly conserved and is regarded as the principal target for vaccine development, as it promotes the formation of neutralizing antibodies, a contrast to the more variable Glycoprotein G. From an epidemiological perspective, hMPV is widely distributed and predominantly impacts infants and young children, often resulting in severe respiratory illnesses. Despite the absence of a licensed va...

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