Hemodynamic Homeostasis · §2 · γ = −mean(NN stacking ΔG₃₇, SantaLucia 1998)

Node identities grounded in real DNA: master-gene γ from nearest-neighbour thermodynamics

Each control node is grounded in real DNA, not assigned by hand. Its master gene’s stacking parameter γ = −mean(nearest-neighbour ΔG₃₇, SantaLucia 1998) is measured from the actual human promoter. SIX2 (kidney) gives γ = 1.5556, reproducing the locked DNA atlas exactly; REN (renin) gives γ = 1.3634 on the identical pipeline. Measured [V], never fitted.

The pressure loop is built on genomically grounded node identities. Each master gene’s nearest-neighbour stacking parameter γ is computed from its real human proximal-promoter sequence (SantaLucia 1998 ΔG₃₇): SIX2 = 1.5556 (gc 0.6381) reproduces the locked DNA atlas bit-for-bit, and REN = 1.3634 (gc 0.4746) is measured on the same convention — a measured input, never a fitted one [V].

Why genomic grounding matters

The credibility of a physiological loop model rests on where its node identities come from. Here they come from the genome. Rather than naming “the kidney” or “the RAAS gland” by convenience, each control node is anchored to a specific master gene, and that gene’s sequence-level identity is quantified by a single deterministic number measured from its DNA — the nearest-neighbour stacking parameter γ. This is the same first-principles DNA interpretation used across the VP framework, applied here so that the pressure loop inherits identities that are grounded in physics, not stipulated.

The measurement: nearest-neighbour stacking ΔG₃₇

The grounding quantity is γ = −mean(nearest-neighbour stacking free energy ΔG₃₇) over the proximal-promoter window, using the SantaLucia-1998 unified 16-doublet parameters. The window is the gene’s proximal promoter (transcription start site −2000 to +500 in the gene’s orientation), taken from the exact NCBI gene-model 5′ end; it is 2501 bp long. Because nearest-neighbour stacking ΔG₃₇ is reverse-complement invariant, γ (and the GC fraction) depend only on the genomic window, not on which strand is read — the value is an intrinsic property of the locus.

Validation, then measurement — the honesty gate

The pipeline is not trusted on assertion; it must first reproduce a locked value exactly. Run on the kidney nephron-progenitor master SIX2 (NC_000002.12, chromosome 2), it returns γ = 1.5556 and GC = 0.6381 over the 2501 bp window — reproducing the locked DNA-atlas value bit-for-bit with no fitting. Only after that gate passes is the renin master REN (NC_000001.11, chromosome 1, TSS 204166337, cross-checked against the Ensembl canonical transcript ENST00000272190) measured on the identical convention, giving γ = 1.3634 and GC = 0.4746. REN is therefore a measured input, computed by the same rule that reproduces SIX2, never a number chosen to fit the loop.

What is grounded, and what stays single-sourced

The two pressure-control master genes that carry a discrete master — the kidney volume integrator (SIX2) and the renin–angiotensin endocrine node (REN) — are both genomically grounded and measured in this package, with their promoter sequences cached so the values reproduce offline bit-for-bit. The remaining nodes (the baroreflex arc and the vascular-tone effector) are circuit/diffuse rather than single-master, so they are cited from the sibling packages rather than assigned a single gene. The canonical derivation of organ identity and developmental order remains the DNA volume’s, by design (one source of truth); this package’s contribution is to re-measure the relevant master-gene γ in-package and to build the multi-organ pressure loop, its sensory layer and its disease dynamics on those grounded identities.

Developmental order from the same numbers

The same γ values also order the nodes: the developmental-order readout is γ-ascending over the measured masters, so the identities and their sequence are read off one consistent genomic measurement rather than two unrelated assumptions. This is the sense in which the simulation is grounded in DNA emergence: the objects it circulates are tied, through γ, to the real sequences that specify them.