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Nature Communications Aug 2022Integration-to-threshold models of two-choice perceptual decision making have guided our understanding of human and animal behavior and neural processing. Although such...
Integration-to-threshold models of two-choice perceptual decision making have guided our understanding of human and animal behavior and neural processing. Although such models seem to extend naturally to multiple-choice decision making, consensus on a normative framework has yet to emerge, and hence the implications of threshold characteristics for multiple choices have only been partially explored. Here we consider sequential Bayesian inference and a conceptualisation of decision making as a particle diffusing in n-dimensions. We show by simulation that, within a parameterised subset of time-independent boundaries, the optimal decision boundaries comprise a degenerate family of nonlinear structures that jointly depend on the state of multiple accumulators and speed-accuracy trade-offs. This degeneracy is contrary to current 2-choice results where there is a single optimal threshold. Such boundaries support both stationary and collapsing thresholds as optimal strategies for decision-making, both of which result from stationary representations of nonlinear boundaries. Our findings point towards a normative theory of multiple-choice decision making, provide a characterisation of optimal decision thresholds under this framework, and inform the debate between stationary and dynamic decision boundaries for optimal decision making.
Topics: Animals; Bayes Theorem; Decision Making; Diffusion; Humans
PubMed: 36038538
DOI: 10.1038/s41467-022-32741-y -
Biophysical Journal Apr 2022Biochemical specificity is critical in enzyme function, evolution, and engineering. Here we employ an established kinetic model to dissect the effects of reactant...
Biochemical specificity is critical in enzyme function, evolution, and engineering. Here we employ an established kinetic model to dissect the effects of reactant geometry and diffusion on product formation speed and accuracy in the presence of cognate (correct) and near-cognate (incorrect) substrates. Using this steady-state model for spherical geometries, we find that, for distinct kinetic regimes, the speed and accuracy of the reactions are optimized on different regions of the geometric landscape. From this model we deduce that accuracy can be strongly dependent on reactant geometric properties even for chemically limited reactions. Notably, substrates with a specific geometry and reactivity can be discriminated by the enzyme with higher efficacy than others through purely diffusive effects. For similar cognate and near-cognate substrate geometries (as is the case for polymerases or the ribosome), we observe that speed and accuracy are maximized in opposing regions of the geometric landscape. We also show that, in relevant environments, diffusive effects on accuracy can be substantial even far from extreme kinetic conditions. Finally, we find how reactant chemical discrimination and diffusion can be related to simultaneously optimize steady-state flux and accuracy. These results highlight how diffusion and geometry can be employed to enhance reaction speed and discrimination, and similarly how they impose fundamental restraints on these quantities.
Topics: Diffusion; Kinetics; Ribosomes
PubMed: 35278424
DOI: 10.1016/j.bpj.2022.03.005 -
The Journal of General Physiology Oct 2023Osmosis is an important force in all living organisms, yet the molecular basis of osmosis is widely misunderstood as arising from diffusion of water across a membrane...
Osmosis is an important force in all living organisms, yet the molecular basis of osmosis is widely misunderstood as arising from diffusion of water across a membrane separating solutions of differing osmolarities, and hence different water concentrations. In 1923, Peter Debye proposed a physical model for a semipermeable membrane emphasizing the repulsive forces between solute molecules and membrane that prevent the solute from entering the membrane. His work was hardly noticed at the time and slipped out of view. We show that Debye's analysis of van 't Hoff's law for osmotic equilibrium also provides a consistent and plausible mechanism for osmotic flow. A difference in osmolyte concentrations in solutions separated by a semipermeable membrane leads to different pressures at the two water-membrane interfaces because the total repulsive force between solute molecules and the membrane is different at the two interfaces. Water is therefore driven through the membrane for exactly the same reason that pure water flows in response to an imposed hydrostatic pressure difference. In this paper, we present the Debye model in both equilibrium and flow conditions. We point out its applicability regardless of the nature of the membrane with examples ranging from the predominantly convective flow of water through synthetic membranes and capillary walls to the purely diffusive flow of independent water molecules through a lipid bilayer and the flow of a single-file column of water molecules in narrow protein channels.
Topics: Diffusion; Lipid Bilayers; Osmosis; Pressure; Water
PubMed: 37624228
DOI: 10.1085/jgp.202313332 -
Biophysical Journal Oct 2021Biophysical modeling of development started with Alan Turing. His two-morphogen reaction-diffusion model was a radical but powerful simplification. Despite its apparent... (Review)
Review
Biophysical modeling of development started with Alan Turing. His two-morphogen reaction-diffusion model was a radical but powerful simplification. Despite its apparent limitations, the model captured real developmental processes that only recently have been validated at the molecular level in many systems. The precision and robustness of reaction-diffusion patterning, despite boundary condition-dependence, remain active areas of investigation in developmental biology.
Topics: Computational Biology; Diffusion; Models, Biological
PubMed: 34480925
DOI: 10.1016/j.bpj.2021.08.041 -
International Journal of Molecular... Nov 2023Using the framework of a continuous diffusion model based on the Smoluchowski equation, we analyze particle dynamics in the confinement of a transmembrane nanopore. We... (Review)
Review
Using the framework of a continuous diffusion model based on the Smoluchowski equation, we analyze particle dynamics in the confinement of a transmembrane nanopore. We briefly review existing analytical results to highlight consequences of interactions between the channel nanopore and the translocating particles. These interactions are described within a minimalistic approach by lumping together multiple physical forces acting on the particle in the pore into a one-dimensional potential of mean force. Such radical simplification allows us to obtain transparent analytical results, often in a simple algebraic form. While most of our findings are quite intuitive, some of them may seem unexpected and even surprising at first glance. The focus is on five examples: (i) attractive interactions between the particles and the nanopore create a potential well and thus cause the particles to spend more time in the pore but, nevertheless, increase their net flux; (ii) if the potential well-describing particle-pore interaction occupies only a part of the pore length, the mean translocation time is a non-monotonic function of the well length, first increasing and then decreasing with the length; (iii) when a rectangular potential well occupies the entire nanopore, the mean particle residence time in the pore is independent of the particle diffusivity inside the pore and depends only on its diffusivity in the bulk; (iv) although in the presence of a potential bias applied to the nanopore the "downhill" particle flux is higher than the "uphill" one, the mean translocation times and their distributions are identical, i.e., independent of the translocation direction; and (v) fast spontaneous gating affects nanopore selectivity when its characteristic time is comparable to that of the particle transport through the pore.
Topics: Nanopores; Diffusion
PubMed: 37958906
DOI: 10.3390/ijms242115923 -
Journal of Mathematical Biology Nov 2023Malignant gliomas are notoriously invasive, a major impediment against their successful treatment. This invasive growth has motivated the use of predictive partial...
Malignant gliomas are notoriously invasive, a major impediment against their successful treatment. This invasive growth has motivated the use of predictive partial differential equation models, formulated at varying levels of detail, and including (i) "proliferation-infiltration" models, (ii) "go-or-grow" models, and (iii) anisotropic diffusion models. Often, these models use macroscopic observations of a diffuse tumour interface to motivate a phenomenological description of invasion, rather than performing a detailed and mechanistic modelling of glioma cell invasion processes. Here we close this gap. Based on experiments that support an important role played by long cellular protrusions, termed tumour microtubes, we formulate a new model for microtube-driven glioma invasion. In particular, we model a population of tumour cells that extend tissue-infiltrating microtubes. Mitosis leads to new nuclei that migrate along the microtubes and settle elsewhere. A combination of steady state analysis and numerical simulation is employed to show that the model can predict an expanding tumour, with travelling wave solutions led by microtube dynamics. A sequence of scaling arguments allows us reduce the detailed model into simpler formulations, including models falling into each of the general classes (i), (ii), and (iii) above. This analysis allows us to clearly identify the assumptions under which these various models can be a posteriori justified in the context of microtube-driven glioma invasion. Numerical simulations are used to compare the various model classes and we discuss their advantages and disadvantages.
Topics: Humans; Glioma; Anisotropy; Computer Simulation; Diffusion; Travel
PubMed: 38015257
DOI: 10.1007/s00285-023-02025-0 -
PloS One 2023A variety of approaches to reducing the environmental impact of food production and consumption are being explored including technological solutions, such as food...
A variety of approaches to reducing the environmental impact of food production and consumption are being explored including technological solutions, such as food produced via biotechnological processes. However, the development of these technologies requires significant upfront investment and consumer acceptance is not guaranteed. The purpose of this research is to develop a system dynamics model to forecast demand, under multiple marketing and quality scenarios, for foods produced via novel technologies, using cellular agriculture as a case study. The model considers consumer heterogeneity, product awareness, word of mouth marketing (WOM), in-store marketing options, pricing options and product utility to estimate diffusion rates and market penetration. To our knowledge, there is no demand forecasting model available for food produced via novel technologies which relies on purchase intention data and incorporates all these factors. Therefore, this research closes a critical gap for that industry. Ultimately, the model shows that price and the consumers' utility for the product drives the final demand regardless of marketing scenario. Further, the rate of diffusion was highest when product samples are provided in store for all scenarios except when product utility is low and the product price is high. Model results suggest that market saturation was reached within the 32-week trial period when the price of the cellular agriculture product was the same as a traditional product but not when the price was double that of traditional meat. Given the lack of available trial data, the model scenarios should be considered a prior probability which should be refined as more data becomes available.
Topics: Meat; Agriculture; Biotechnology; Diffusion; Industry
PubMed: 37639442
DOI: 10.1371/journal.pone.0290169 -
Magnetic Resonance Imaging Apr 2021Cytological features such as cell size and intracellular morphology provide fundamental information on cell status and hence may provide specific information on changes... (Review)
Review
Cytological features such as cell size and intracellular morphology provide fundamental information on cell status and hence may provide specific information on changes that arise within biological tissues. Such information is usually obtained by invasive biopsy in current clinical practice, which suffers several well-known disadvantages. Recently, novel MRI methods such as IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) have been developed for direct measurements of mean cell size non-invasively. The IMPULSED protocol is based on using temporal diffusion spectroscopy (TDS) to combine measurements of water diffusion over a wide range of diffusion times to probe cellular microstructure over varying length scales. IMPULSED has been shown to provide rapid, robust, and reliable mapping of mean cell size and is suitable for clinical imaging. More recently, cell size distributions have also been derived by appropriate analyses of data acquired with IMPULSED or similar sequences, which thus provides MRI-cytometry. This review summarizes the basic principles, practical implementations, validations, and example applications of MR cell size imaging based on TDS and demonstrates how cytometric information can be used in various applications. In addition, the limitations and potential future directions of MR cytometry are identified including the diagnosis of nonalcoholic steatohepatitis of the liver and the assessment of treatment response of cancers.
Topics: Cell Size; Diffusion; Humans; Magnetic Resonance Imaging; Spectrum Analysis
PubMed: 33338562
DOI: 10.1016/j.mri.2020.12.010 -
NeuroImage Oct 2023Spatial attention is often described as a mental spotlight that enhances information processing at the attended location. Using fMRI, we investigated background...
Spatial attention is often described as a mental spotlight that enhances information processing at the attended location. Using fMRI, we investigated background connectivity between the pulvinar and V1 in relation to focused versus diffused attention allocation, in weak and strong crowding contexts. Our findings revealed that focused attention led to enhanced correlations between the pulvinar and V1. Notably, this modulation was initiated by the pulvinar, and the strength of the modulation was dependent on the saliency of the target. These findings suggest that the pulvinar initiates information reweighting to V1, which underlies attentional selection in cluttered scenes.
Topics: Humans; Pulvinar; Cognition; Diffusion
PubMed: 37619793
DOI: 10.1016/j.neuroimage.2023.120341 -
Comparative Biochemistry and... Mar 2021The capillary bed constitutes the obligatory pathway for almost all oxygen (O) and substrate molecules as they pass from blood to individual cells. As the largest organ,... (Review)
Review
The capillary bed constitutes the obligatory pathway for almost all oxygen (O) and substrate molecules as they pass from blood to individual cells. As the largest organ, by mass, skeletal muscle contains a prodigious surface area of capillaries that have a critical role in metabolic homeostasis and must support energetic requirements that increase as much as 100-fold from rest to maximal exercise. In 1919 Krogh's 3 papers, published in the Journal of Physiology, brilliantly conflated measurements of muscle capillary function at rest and during contractions with Agner K. Erlang's mathematical model of O diffusion. These papers single-handedly changed the perception of capillaries from passive vessels serving at the mercy of their upstream arterioles into actively contracting vessels that were recruited during exercise to elevate blood-myocyte O flux. Although seminal features of Krogh's model have not withstood the test of time and subsequent technological developments, Krogh is credited with helping found the field of muscle microcirculation and appreciating the role of the capillary bed and muscle O diffusing capacity in facilitating blood-myocyte O flux. Today, thanks in large part to Krogh, it is recognized that comprehending the role of the microcirculation, as it supports perfusive and diffusive O conductances, is fundamental to understanding skeletal muscle plasticity with exercise training and resolving the mechanistic bases by which major pathologies including heart failure and diabetes cripple exercise tolerance and cerebrovascular dysfunction predicates impaired executive function.
Topics: Animals; Capillaries; Diffusion; Humans; Muscle Cells; Muscles; Oxygen
PubMed: 33242636
DOI: 10.1016/j.cbpa.2020.110852