References, gene accessions, and methods provenance

Every external anchor in this whitepaper is listed here with its grade and database accession: five master genes (NCBI), ten transducer-channel genes (NCBI/UniProt), the classical optics, tonotopy, gating-spring, Hopf, and canal-mechanics references, and the 2023–2026 root-cause-treatment literature. Substrate claims are reproduced in-simulation; clinical claims are cited at level.

This page is the provenance layer. The substrate claims graded [V] are reproduced by python repro/run_all.py; everything graded [L] is a measured input or an established result, listed below with its NCBI/UniProt accession or citation. Master-gene γ is computed from human promoter sequence by the SantaLucia nearest-neighbour method; effector-channel γ is owned by the DNA pipeline. References are listed for attribution, paraphrased, not quoted.

A grounded program should make its sources inspectable. This page collects every external anchor the whitepaper relies on, separated by grade, so a reader can check each input independently of the in-simulation results — the practice set out in the no-tuning method.

Master genes (γ measured from human promoter sequence) — [L]

γ = −mean(nearest-neighbour stacking ΔG37) over the human proximal promoter (TSS−2000..+500), by the SantaLucia 1998 nearest-neighbour method; never fitted, cached so it reproduces offline.

Master genes and their measured γ
gene	γ	node	accession
`PAX6`	1.511	eye_retina_optics	NCBI Gene 5080
`RAX`	1.4541	eye_photoreceptor	NCBI Gene 30062
`EYA1`	1.3638	cochlea_frequency_map	NCBI Gene 2138
`SOX2`	1.4573	inner_ear_haircell	NCBI Gene 6657
`TAS1R3`	1.5555	taste_chemodetection	NCBI Gene 83756; UniProt Q7RTX0

Transducer effector genes (γ owned by the DNA pipeline) — identity cited [L]

Transducer channel genes and accessions
gene	accession	role
`CNGA1`	NCBI Gene 1259; UniProt P29973	rod CNG channel α (cooperative gate)
`CNGB1`	NCBI Gene 1258; UniProt Q14028	rod CNG channel β
`TMC1`	NCBI Gene 117531; UniProt Q8TDI8	hair-cell MET pore
`PCDH15`	NCBI Gene 65217; UniProt Q96QU1	tip link (gating spring)
`CDH23`	NCBI Gene 64072; UniProt Q9H251	tip link (gating spring)
`SLC26A5` (prestin)	NCBI Gene 375611; UniProt P58743	outer-hair-cell somatic motor = Hopf active force
`TAS1R2`	NCBI Gene 80834; UniProt Q8TE23	sweet receptor subunit
`TRPM5`	NCBI Gene 29850; UniProt Q9NZQ8	downstream taste cation channel
`CNGA2`	NCBI Gene 1260; UniProt Q16280	olfactory CNG channel (rod superfamily)
`ADCY3`	NCBI Gene 109; UniProt O60266	adenylyl cyclase (cAMP generator)

Classical and physiological anchors — [L] → [V]/[V-arith]

DNA stacking thermodynamics — SantaLucia 1998, a unified view of nearest-neighbour DNA thermodynamics (PNAS 95:1460): the source of the γ method.
Cochlear place-map — Greenwood 1990, a cochlear frequency-position function (JASA 87:2592): the ~20 Hz–20 kHz human tonotopy reproduced in tonotopy.
Hair-cell gating spring — Howard & Hudspeth 1988; Corey & Hudspeth 1983; Markin & Hudspeth 1995; Martin, Mehta & Hudspeth 2000: the two-state MET switch and negative bundle stiffness.
Hopf critical cochlea — Camalet, Duke, Jülicher & Prost 2000; Eguíluz et al. 2000; Hudspeth, Jülicher & Martin 2010: the self-tuned critical oscillator and the cube-root used in the cochlear amplifier.
Phototransduction — Fesenko, Kolesnikov & Lyubarsky 1985 (Nature 313:310): cGMP-gated rod conductance, the basis of phototransduction.
Vestibular canal mechanics — Steinhausen 1933; Van Egmond, Groen & Jongkees 1949 (J Physiol 110:1); Jones & Milsum 1965: the torsion-pendulum and velocity storage in vestibular balance.
Ocular optics — the Gullstrand reduced/schematic eye and Hofstetter 1965 age–amplitude formula, reproduced in ocular optics.

Root-cause treatment literature (2023–2026)

AMD / geographic atrophy — pegcetacoplan (C3) and avacincaptad pegol (C5), both FDA 2023; slow lesion growth on an anatomic endpoint, with no functional visual-acuity gain yet (partial).
Myopia control — IMI consensus: low-dose atropine, peripheral-defocus optics, outdoor light (retinal dopamine), and repeated low-level 650 nm red light; RCT-supported ≥50% slowing, long-term safety still accruing.
Glaucoma — Rho-kinase (ROCK) inhibitors netarsudil and ripasudil/fasudil: restore trabecular outflow plus IOP-independent retinal-ganglion-cell neuroprotection.
Presbycusis / SNHL — OTOF gene therapy restored hearing in children (clinical, 2024); ATOH1 hair-cell regeneration remains immature for acquired loss (contested); NT-3/BDNF synapse repair preclinical.
Cataract — pharmacological chaperones / oxysterols: reports of reversal were not replicated (Daszynski et al. 2019), so efficacy is unproven and surgery remains standard (contested).
Diabetic retinopathy — glycemic control resets the systemic setpoint (root); anti-VEGF blocks the downstream neovascular attractor (complication).
BPPV — canalith repositioning (Epley / Semont): mechanically returns the otoconia at the source, an instrument-level root-cause fix.

Citation discipline. References are listed for attribution and are paraphrased, not quoted. The substrate claims graded [V] are the ones reproduced by the engine; the clinical and classical items graded [L] are cited inputs at their stated evidence level. Any anchor whose exact coordinates need re-confirmation before formal publication is tracked in IRREPRODUCIBILITY_LEDGER.md. Full machine-readable registry: literature/citations.json.