Assessment of classical scrapie infectivity in sheep embryos
Why this work is in the frame
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Bibliographic record
Abstract
Naturally scrapie infected VRQ/VRQ (n = 47) and ARR/ARR control (n = 11) Romanov sheep were super-ovulated and mated with matching genotype rams. Embryos were collected in dams 6 to 7 days after the oestrus and embryos were selected according to guidelines from the International Embryo Technology Society. A total of 267 transferable and 149 non-transferable embryos were collected in the VRQ/VRQ dams and 55 transferable and 23 non-transferable embryos were collected in ARR/ARR controls. The presence of prion seeding activity in non-transferable and transferable embryos from each dam was tested by Protein Misfolding Cyclic Amplification. After four amplification rounds, none of the reactions seeded with embryos displayed detectable levels of abnormal PrP. In contrast, Protein Misfolding Cyclic Amplification reactions seeded with a 10 -8 diluted 10% brainstem homogenate from a VRQ/VRQ infected dam were found to be PrP res positive. Among the 267 transferable VRQ/VRQ embryos, 204 embryos collected from 19 different VRQ/VRQ infected dams were inoculated to ovine PrP transgenic mice (tg338 mice) by intracerebral route. Nineteen embryos from two ARR/ARR dams were inoculated as controls. No clinical signs indicative of Transmissible Spongiform Encephalopathy and no PrP Sc accumulation were observed in any of the tg338 mice inoculated with embryos. Within the limit of the experiment (intrinsic sensitivity of the bioassay and Protein Misfolding Cyclic Amplification) these results indicate that the residual risk of the presence of detectable infectivity or positive seeding activity in transferable embryos from other VRQ/VRQ sheep that would be infected by the Langlade scrapie agent is lower than 1.79% and 1.37%, respectively (upper bound of the exact binomial 95% confidence interval).
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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