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Record W4388851828 · doi:10.1101/2023.11.20.567244

Statistical Methods for Microrheology of Airway Mucus with Extreme Heterogeneity

2023· preprint· en· W4388851828 on OpenAlexfundno aff
Neall Caughman, Micah Papanikolas, Matthew R. Markovetz, Ronit Freeman, David B. Hill, M. Gregory Forest, Martin Lysy

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldMedicine
TopicCystic Fibrosis Research Advances
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of CanadaDirectorate for Computer and Information Science and EngineeringAlfred P. Sloan FoundationNational Institutes of HealthNational Science Foundation
KeywordsMucusHomogeneity (statistics)MucinMicrorheologyBiological systemCluster analysisRheologyBrownian motionMathematicsArtificial intelligencePattern recognition (psychology)StatisticsMaterials scienceComputer scienceChemistryBiology

Abstract

fetched live from OpenAlex

Abstract The mucus lining of the human airway epithelium contains two gel-forming mucins, MUC5B and MUC5AC. During progression of cystic fibrosis (CF), mucus hyper-concentrates as its mucin ratio changes, coinciding with formation of insoluble, dense mucus flakes. We explore rheological heterogeneity of this pathology with reconstituted mucus matching three stages of CF progression and particle-tracking of 200 nm and 1 micron diameter beads. We introduce statistical data analysis methods specific to low signal-to-noise data within flakes. Each bead time series is decomposed into: (i) a fractional Brownian motion (fBm) classifier of the pure time-series signal ; (ii) high-frequency static and dynamic noise; and (iii) low-frequency deterministic drift. Subsequent analysis focuses on the denoised fBm classifier ensemble from each mucus sample and bead diameter. Every ensemble fails a homogeneity test, compelling clustering methods to assess levels of heterogeneity. The first binary level detects beads within vs. outside flakes. A second binary level detects within-flake bead signals that can vs. cannot be disentangled from the experimental noise floor. We show all denoised ensembles, within- and outside-flakes, fail a homogeneity test, compelling additional clustering; next, all clusters with sufficient data fail a homogeneity test. These levels of heterogeneity are consistent with outcomes from a stochastic phase-separation process, and dictate applying the generalized Stokes-Einstein relation to each bead per cluster per sample, then frequency-domain averaging to assess rheological heterogeneity. Flakes exhibit a spectrum of gel-like and sol-like domains, outside-flake solutions a spectrum of sol-like domains, painting a rheological signature of the phase-separation process underlying flake-burdened mucus.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.017
metaresearch head score (Gemma)0.043
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.017
Threshold uncertainty score0.088

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0170.043
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0040.002
Science and technology studies0.0010.002
Scholarly communication0.0020.001
Open science0.0020.002
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.053
GPT teacher head0.351
Teacher spread0.298 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreMethods

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2023
Admission routes1
Has abstractyes

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