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Record W3001344158 · doi:10.1073/pnas.1909196117

Selectivity filter modalities and rapid inactivation of the hERG1 channel

2020· article· en· W3001344158 on OpenAlexafffund
Williams E. Miranda, Kevin R. DeMarco, Jiqing Guo, Henry J. Duff, Igor Vorobyov, Colleen E. Clancy, Sergei Y. Noskov

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2020
Typearticle
Languageen
FieldMedicine
TopicCardiac electrophysiology and arrhythmias
Canadian institutionsLibin Cardiovascular Institute of AlbertaUniversity of Calgary
FundersCommon FundCanadian Institutes of Health ResearchGovernment of CanadaNational Institutes of HealthNational Heart, Lung, and Blood InstituteUniversity of California, DavisAlberta InnovatesKillam TrustsNational Institute of General Medical SciencesAmerican Heart Association
KeywordsSelectivityFilter (signal processing)BiophysicsPermeationFrequency selectivityChannel (broadcasting)RepolarizationChemistryMembraneBiologyElectrophysiologyBiochemistryComputer scienceNeuroscienceElectronic engineeringEngineeringTelecommunications

Abstract

fetched live from OpenAlex

Significance The familial mutations impacting repolarization K + currents conducted by the hERG1 channel are significant determinants of arrhythmogenicity. Here, we show how the arrhythmogenic gain-of-function mutation (N629D) in the pore domain impairs channel selectivity and inactivation by shifting complex conformational equilibria between the conductive and nonconductive states of the selectivity filter and by impacting filter modalities. This study highlights notable differences in the permeation and inactivation dynamics in a human channel that displays a nonconventional selectivity filter.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
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 head0.041
GPT teacher head0.281
Teacher spread0.240 · 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 designBench or experimental
Domainnot available
GenreEmpirical

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

Citations52
Published2020
Admission routes2
Has abstractyes

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