Transient Receptor Potential Channels of the Melastatin Family and Ischemic Responses of Central Neurons
Why this work is in the frame
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Bibliographic record
Abstract
The excitotoxic theory of stroke, which implicated N-methyl-d-aspartate (NMDA) receptors as mediators of excessive Ca(2+) entry and neuronal death, generated a great deal of enthusiasm for the prospect of using NMDA receptor antagonists to prevent the associated brain injury. Unfortunately, these receptor antagonists failed to provide effective treatments for human stroke. In part, the failure is likely a consequence of having to administer these drugs within a very short therapeutic window after stroke and to the intolerable psychomimetic side effects associated with their use. However, new possibilities for therapeutic intervention are revealing themselves as our understanding of excitotoxicity evolves. We now recognize that ischemia and Ca(2+) toxicity in central neurons can be attributed to a variety of mechanisms recruited downstream of NMDA receptor activation. These include the activation of Ca(2+)-permeable transient receptor potential channels of the melastatin family. The more-delayed activation of these channels offers the tantalizing possibility that drugs targeting selected members of this family may possess a wider therapeutic window for preventing the debilitating consequences after stroke onset.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it