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Record W4413939187 · doi:10.1101/2025.08.31.673412

Excitability as a Design Principle in the Immune System

2025· preprint· en· W4413939187 on OpenAlex
Yael Lebel, Uri Alon

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldEngineering
TopicArtificial Immune Systems Applications
Canadian institutionsnot available
FundersH2020 European Research CouncilAzrieli FoundationWeizmann Institute of ScienceEuropean Commission
KeywordsImmune systemMedicineImmunology

Abstract

fetched live from OpenAlex

Growing knowledge in immunology has outpaced the development of unifying concepts that explain how molecular circuits generate immune goals-strong response to pathogens, self-tolerance, and prevention of collateral damage. Here, we propose that excitability, a concept from dynamical systems, provides these goals in diverse contexts. An excitable system produces a large response pulse when stimulus crosses a threshold and then shuts itself down, followed by a refractory period. We mathematically screen thousands of cytokine and cell circuits to identify the handful that can show excitability. Of these, a single robust circuit is Pareto optimal for speed and strength-an effector that induces itself and induces its inhibitor. This circuit appears dozens of times in the human immune network, whereas the suboptimal circuits do not. It explains data on severe acute respiratory syndrome coronavirus 2, autoimmune flares, and tumor immunity and suggests therapeutic targets. Excitability may unite our understanding of immune circuits.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.240
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.018
GPT teacher head0.233
Teacher spread0.215 · 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