Alzheimer Research Forum Live Discussion: Now you see them, now you don't: The amyloid channel hypothesis1
Bibliographic record
Abstract
In 1993, Arispe et al. [1] reported that Aβ formed ion channels, and proposed that channels could cause cellular pathology and toxicity.Abundant evidence now supports this view, including the facts that virtually all amyloids form channels and that Aβ can inhibit long-term potentiation (LTP), depolarize neurons, allow cytochrome C efflux from mitochondria [2], and kill cells.Channel formation readily explains most amyloid pathophysiology, including memory disturbance, calcium dysfunction, membrane depolarizations, increased reactive oxygen species (ROS), sensitivity to toxins, and apoptosis.Larry Nault: Bruce, do these channels have a hypothetical geometry?A pipe or a duct?Bounded by what?Bruce Kagan: Larry, Arispe and Guy proposed several possible models for the
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.016 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.004 | 0.001 |
| Scholarly communication | 0.006 | 0.006 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.017 | 0.013 |
| Insufficient payload (model declined to judge) | 0.162 | 0.075 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".