STRC h05 Ca Oscillation — Parameter Provenance Audit 2026-04-25
Second audit extending STRC h05 Parameter Provenance Audit 2026-04-23. The 2026-04-23 audit removed 4 phantom citations from scripts and flagged ⚠ rows. This pass completes the literature retrieval for all retrievable parameters, identifies one additional phantom (PMID 21458670 for CaMKII), confirms 3 STRC parameters as permanently unmeasured, and creates 7 paper notes.
PHANTOM resolution — high priority (3 + 1 bonus)
PHANTOM 1: “Sharma 2018” — STRC mRNA t½
Resolution: NOT MEASURED — value retracted from model as primary measurement.
Exhaustive literature search finds no paper by any author named Sharma from 2018 measuring STRC mRNA stability or half-life. No primary paper measuring STRC mRNA t½ in any cell type exists in PubMed or bioRxiv as of 2026-04-25. The parameter STRC_MRNA_DECAY_S = 1e-4 (t½ ~2 h) and k_mRNA_deg = 0.0004 (t½ ~30 min) in the two scripts are both unsourced calibration parameters. Scripts already carry # ⚠ UNSOURCED comments from 2026-04-23 audit; no additional script changes needed. Literature table updated to reflect “NOT MEASURED.”
PHANTOM 2: STRC protein t½ — no source
Resolution: NOT MEASURED — value retracted from model as primary measurement.
No primary paper measures STRC protein half-life in OHCs or any mammalian system. The 38 h (pivot) vs 30-day (rbm24) values are 20× apart. Both are unsourced. No proteomics paper with STRC turnover data found. Scripts already carry # ⚠ UNSOURCED / # ⚠ fitted comments. Literature table updated.
PHANTOM 3: “Krey 2015” — STRC copy number 15,000/OHC
Resolution: NOT MEASURED — value retracted from model as primary measurement.
Krey et al. 2015 is Wilmarth et al. Scientific Data (PMID 25977827) — stereocilia proteome from mouse cochlea. STRC is not quantified in that dataset. No published proteomics paper (including mass spectrometry surveys of stereocilia) quantifies STRC copy number per OHC. The target_protein = 15,000 is a model calibration set-point with no empirical basis. Scripts carry # ⚠ UNSOURCED comment from 2026-04-23. Literature table updated.
BONUS PHANTOM 4: “Chao 2011 Cell PMID 21458670” — CaMKII
Resolution: PHANTOM — PMID 21458670 is a completely different paper.
PMID 21458670 resolves to: Edlich F et al. “Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol.” Cell 2011;145(1):104-16. This is an apoptosis paper with zero CaMKII content. The correct CaMKII paper is Chao LH et al. “A mechanism for tunable autoinhibition in the structure of a human Ca2+/calmodulin-dependent kinase II holoenzyme.” Cell 2011;146(5):732-45. PMID: 21884935. Paper note created: 2011-chao-camkii-holoenzyme-structure. Scripts corrected in ca_oscillation_rbm24_ode.py.
New finding from Chao 2011 (PMID 21884935): CaM EC50 for full holoenzyme activation = 6.0 µM (short linker, Hill n=2.1). Model Kd_CaMKII = 1 µM is ~6× lower — a model choice, not a measurement for the OHC isoform. Flagged in scripts.
Additional citation corrections (not full phantoms but wrong papers)
“Mammano 1999 Pflugers Arch” → CORRECTED
Mammano 1999 (PMID 10436049, J Neurosci) = “ATP-Induced Ca2+ release in cochlear outer hair cells: localization of an IP3-gated Ca2+ store.” This is not a PMCA kinetics paper. The correct sources for k_extrusion are:
- Yamoah et al. 1998 J Neurosci (PMID 9425003) — PMCA density + functional necessity
- Beurg et al. 2010 J Neurophysiol (PMID 20427623) — max extrusion 3.7 fmol/s, τ ~50 ms
Paper notes created for both. Scripts updated.
”Müller et al. 2002” buffer ratio → CORRECTED
No Müller 2002 paper on OHC calcium buffering found in any search. The correct primary source is Hackney et al. 2005 J Neurosci (PMID 16120789): oncomodulin 2-3 mM + calbindin 15-230 µM in rat OHC = ~5-6 mM total Ca2+-binding sites; OHC buffer is 110× that of IHC. Paper note created: 2005-hackney-calcium-buffering-proteins.
”Houslay 2010” PDE4 kinetics → CORRECTED
No Houslay primary paper from 2010 on PDE4 kinetics identified. Closest: Houslay & Adams 2003 Biochem J (PMID 12444918) — a review with no original kinetics. For primary Km measurement: Owens et al. 1997 Biochem J (PMID 9337850): Km = 4.8 µM for full-length PDE4A. Model PDE4_KM_NM = 4000 nM (4 µM) is consistent. PDE4 Vmax remains a model-fitted parameter with no primary source. Paper notes created for both.
”Lumpkin 2001” wrong year → CORRECTED
Paper is from 1998: Lumpkin & Hudspeth J Neurosci 1998 (PMID 9698322). Scripts updated in both models.
”Fettiplace 2017” wrong year in n_channels comment → CORRECTED
Fettiplace & Kim 2014 Physiol Rev (PMID 24987009). n_channels ~134 is consistent with 2 channels per tip link × 60-100 stereocilia per OHC (per Fettiplace 2014). Script updated.
⚠ rows converted to ✅ this pass
| Row | Parameter | New status |
|---|---|---|
| Apical compartment volume | V_apex ~50 fL | ✅ Lumpkin & Hudspeth 1998 PMID 9698322 |
| Resting [Ca2+] | 20-310 nM | ✅ Lumpkin & Hudspeth 1998 PMID 9698322 |
| Ca2+ buffer capacity | 100-1000× | ✅ Hackney 2005 PMID 16120789 |
| PMCA extrusion rate | k ~30 /s | ✅ Yamoah 1998 PMID 9425003 + Beurg 2010 PMID 20427623 (as model estimate) |
| PDE4 Km | ~4 µM | ✅ Owens 1997 PMID 9337850 (4.8 µM direct measurement) |
| CaMKII EC50/Kd | ~6 µM | ✅ Chao 2011 PMID 21884935 (EC50 6 µM for short-linker holoenzyme) |
Paper notes created (7 total this pass)
- 1998-lumpkin-hudspeth-stereocilia-calcium-regulation (PMID 9698322)
- 1998-yamoah-pmca-stereocilia-extrusion (PMID 9425003)
- 2010-beurg-calcium-balance-ohc (PMID 20427623)
- 2005-hackney-calcium-buffering-proteins (PMID 16120789)
- 2011-chao-camkii-holoenzyme-structure (PMID 21884935)
- 2003-houslay-adams-pde4-review (PMID 12444918)
- 1997-owens-pde4a-kinetics (PMID 9337850)
Remaining ⚠ / ❌ blockers
| Parameter | Status | Reason |
|---|---|---|
| STRC mRNA t½ | ⚠ NOT MEASURED | No primary literature exists. Scripts carry WARNING comment. |
| STRC protein t½ | ⚠ NOT MEASURED | No primary literature exists. Cross-script inconsistency remains. |
| STRC copy number/OHC | ⚠ NOT MEASURED | No proteomics paper quantifies STRC/OHC. |
| AC1 Vmax (cell-normalized) | ⚠ model choice | 30-60× above membrane-prep value; justified as volume normalisation |
| PDE4 Vmax | ⚠ no primary | Fitted model parameter; no OHC-specific source |
| CaMKII k_auto | ⚠ not measured | Fitted; Chao 2011 is structural only |
| CREB dephos k | ⚠ mismatch | 2-4× faster than Gonzalez & Montminy 1989; no OHC source |
| CRE half-saturation K_half | ⚠ unverified | ”Cha 2010” PMID not confirmed; no alternative found |
| k_mRNA_deg (STRC) | ⚠ 4× cross-script mismatch | Both unsourced; no primary data |
| k_prot_deg (STRC) | ⚠ 20× cross-script mismatch | Both unsourced; no primary data |
Wet-lab gates needed to resolve STRC kinetic parameters:
- STRC mRNA stability: actinomycin D chase in OHC line (HEI-OC1 or primary mouse OHC)
- STRC protein t½: cycloheximide chase + immunofluorescence in OHC
- STRC copy number: single-cell proteomics (SciPlex or similar) in sorted OHC
Model-script corrections summary
| File | Lines changed | What |
|---|---|---|
ca_oscillation_rbm24_ode.py | n_channels comment | ”Fettiplace 2017” → “Fettiplace & Kim 2014 PMID 24987009” |
ca_oscillation_rbm24_ode.py | f_Ca comment | ”Lumpkin 2001” → “Beurg 2006” |
ca_oscillation_rbm24_ode.py | buffer_ratio comment | Added “Hackney 2005”; removed phantom “Müller 2002” |
ca_oscillation_rbm24_ode.py | V_apex comment | ”Lumpkin 2001” → “Lumpkin & Hudspeth 1998 PMID 9698322” |
ca_oscillation_rbm24_ode.py | k_extrusion comment | Corrected “Mammano 1999” → “Yamoah 1998 + Beurg 2010” |
ca_oscillation_rbm24_ode.py | Kd_CaMKII block | PMID 21458670 (phantom) → PMID 21884935; added WARNING |
ca_oscillation_ac1_creb_pivot.py | K_EXTRUSION_S comment | Corrected “Mammano 1999 Pflugers Arch” attribution |
ca_oscillation_ac1_creb_pivot.py | V_APEX_L comment | ”Lumpkin 2001” → “Lumpkin & Hudspeth 1998 PMID 9698322” |
ca_oscillation_ac1_creb_pivot.py | PDE4 comment | ”Houslay 2010” phantom → “Owens 1997 PMID 9337850”; added WARNING |
lit_audit state
lit_audit: partial (see blockers above)
Rationale for partial not fixed:
- 3 STRC parameters (mRNA t½, protein t½, copy number) have NO primary literature. Cannot be resolved by literature retrieval — require wet-lab measurement.
- “Cha 2010” CRE half-saturation PMID remains unconfirmed.
- PDE4 Vmax and CaMKII k_auto remain model-fitted.
fixed would be premature. These are fundamental model parameters with no empirical basis; they are retracted from primary-measurement status and documented as model calibration set-points.
Ranking delta
| Axis | Pre-audit | Post-audit | Reason |
|---|---|---|---|
| Mech | 3 | 3 | Topological result unchanged; phantom resolution did not change mechanism sketch |
| Deliv | 4 | 4 | Acoustic delivery unchanged |
| Misha-fit | 2 | 2 | Unchanged |
Tier: A (unchanged). This audit closes known phantom debt and improves citation integrity. The 3 STRC kinetic parameters remain unmeasured — this is now explicit and documented, not hidden. The hypothesis’s scientific weakness remains Misha-fit (2), not computational fidelity.
Connections
[part-of]STRC Hypothesis Ranking[part-of]STRC Cross-Hypothesis Parameter Audit 2026-04-23[see-also]STRC Calcium Oscillation Acoustic Therapy[see-also]calcium-oscillation[about]Misha