h06 log

2026-04-23

#6 mRNA Therapy: A → B. Mech 3→2. Hill-sensitivity sweep 125-pt grid (HILL_K × HILL_N × MAX_BOOST) shows per-OHC ROBUST (60% grid reaches tx_trough ≥ 2×) but cochlea-mean therapeutic ARCHITECTURALLY IMPOSSIBLE at LNP eff ≤ 20% for ANY Hill params — identity cochlea_mean ≤ 1 + eff·(max_boost-1) caps ceiling at 1.80× even at MAX_BOOST=5, OHC-targeted 20%. Reframes stack A+B as “B + marginal A” not synergistic. → STRC h06 Hill Sensitivity Sweep 2026-04-23
#6 mRNA Therapy post-audit partial fix: A held. STRC_HL_D + RBM24_HL_D reframed from ⚠ UNSOURCED to lit-anchored OOM estimates (Zhang 2012 Nature PMID 22246323 for stereocilia <10 %/day; Mauriac 2024 PNAS PMID 39320919 for GPSM2 t½ 9–10 d; Schwanhäusser 2011 Nature PMID 21593866 for proteome median 46h). Hill K_M/n/max_boost stay CIRCULAR FIT (no OHC splicing dose-response lit exists). #4 Strategy B inherits. → STRC h06 Parameter Provenance Audit 2026-04-23