822 research outputs found
COSMOS: the COsmic-ray Soil Moisture Observing System
The newly-developed cosmic-ray method for measuring area-average soil moisture at the hectometer horizontal scale is being implemented in the COsmic-ray Soil Moisture Observing System (or the COSMOS). The stationary cosmic-ray soil moisture probe measures the neutrons that are generated by cosmic rays within air and soil and other materials, moderated by mainly hydrogen atoms located primarily in soil water, and emitted to the atmosphere where they mix instantaneously at a scale of hundreds of meters and whose density is inversely correlated with soil moisture. The COSMOS has already deployed more than 50 of the eventual 500 cosmic-ray probes, distributed mainly in the USA, each generating a time series of average soil moisture over its horizontal footprint, with similar networks coming into existence around the world. This paper is written to serve a community need to better understand this novel method and the COSMOS project. We describe the cosmic-ray soil moisture measurement method, the instrument and its calibration, the design, data processing and dissemination used in the COSMOS project, and give example time series of soil moisture obtained from COSMOS probes
Molecular composition of type VI collagen. Evidence for chain heterogeneity in mammalian tissues and cultured cells
Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics
When using mathematical models to make quantitative predictions for clinical or industrial use, it is important that predictions come with a reliable estimate of their accuracy (uncertainty quantification). Because models of complex biological systems are always large simplifications, model discrepancy arisesāmodels fail to perfectly recapitulate the true data generating process. This presents a particular challenge for making accurate predictions, and especially for accurately quantifying uncertainty in these predictions. Experimentalists and modellers must choose which experimental procedures (protocols) are used to produce data used to train models. We propose to characterise uncertainty owing to model discrepancy with an ensemble of parameter sets, each of which results from training to data from a different protocol. The variability in predictions from this ensemble provides an empirical estimate of predictive uncertainty owing to model discrepancy, even for unseen protocols. We use the example of electrophysiology experiments that investigate the properties of hERG potassium channels. Here, āinformation-richā protocols allow mathematical models to be trained using numerous short experiments performed on the same cell. In this case, we simulate data with one model and fit it with a different (discrepant) one. For any individual experimental protocol, parameter estimates vary little under repeated samples from the assumed additive independent Gaussian noise model. Yet parameter sets arising from the same model applied to different experiments conflictāhighlighting model discrepancy. Our methods will help select more suitable ion channel models for future studies, and will be widely applicable to a range of biological modelling problems
The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention
Background: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods: In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na+/K+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results: We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na+/K+ ATPase elicits SD. Elevated K+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions: Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory. Ā© 2022, The Author(s)
Cell-scale degradation of peritumoural extracellular matrix fibre network and its role within tissue-scale cancer invasion
Local cancer invasion of tissue is a complex, multiscale process which plays
an essential role in tumour progression. Occurring over many different temporal
and spatial scales, the first stage of invasion is the secretion of matrix
degrading enzymes (MDEs) by the cancer cells that consequently degrade the
surrounding extracellular matrix (ECM). This process is vital for creating
space in which the cancer cells can progress and it is driven by the activities
of specific matrix metalloproteinases (MMPs). In this paper, we consider the
key role of two MMPs by developing further the novel two-part multiscale model
introduced in [33] to better relate at micro-scale the two micro-scale
activities that were considered there, namely, the micro-dynamics concerning
the continuous rearrangement of the naturally oriented ECM fibres within the
bulk of the tumour and MDEs proteolytic micro-dynamics that take place in an
appropriate cell-scale neighbourhood of the tumour boundary. Focussing
primarily on the activities of the membrane-tethered MT1-MMP and the soluble
MMP-2 with the fibrous ECM phase, in this work we investigate the MT1-MMP/MMP-2
cascade and its overall effect on tumour progression. To that end, we will
propose a new multiscale modelling framework by considering the degradation of
the ECM fibres not only to take place at macro-scale in the bulk of the tumour
but also explicitly in the micro-scale neighbourhood of the tumour interface as
a consequence of the interactions with molecular fluxes of MDEs that exercise
their spatial dynamics at the invasive edge of the tumour
- ā¦