DQIS — Register of Scientific Objections v13

Supplementary document to the DQIS framework (Zenodo DOI: 10.5281/zenodo.19855263). Register of scientific objections identified during preparation for academic validation of the DQIS framework — Distributed Quantum-Inspired Immune Surveillance. Version 13.0 (April 2026) — 15 objections addressed: O1 — Empirical grounding of parameter p_i — updated v13.0: full computational model for T-β p_i (O1.3): three models with increasing fidelity using published AFM distributions (8 tissue types, 500+ measurements) + DQIS AND-gate M/E architecture. Model 3 result: p_i = 0.004 (90% CI: 0.003–0.007, Monte Carlo 10,000 iterations, τ* = 0.85 kPa). T-β computationally on target; DQIS-3 timeline revised from 4–7 years engineering to 1–2 years in vitro validation. O2 — Statistical independence of channels — empirically validated on GSE72056; inter-group M/E pairs LTD ≈ 0, θ ≈ 0.17; balanced quorum eliminates intra-M hub vulnerability by construction. O3 — Selective pressure at population scale — O3-A structurally mitigated by Pattern Drift Sensor (v9.0); O3-B (global coordination) remains as long-term infrastructure requirement. O4 — Channel T-ε: reachability of p_i = 0.01 — histotype-dependent p_i; already on target for HER2+/EGFR-amplified tumors. O5 — DQIS-J: number of paediatric procedures — resolved v14.0: single massive-dose infusion, self-sustaining threshold effect, 1 paediatric day-hospital session. O6 — T-γ* temporal criterion vs T-cell contact time — resolved: NFAT-like biochemical integrator, 3–4 brief contacts to threshold. O7 — Clonal hematopoietic drift (CHIP) disrupts the 5-pool balance of DQIS-A — managed: pre-infusion conditioning + cfDNA clonal barcoding + selective iC9 reset. O8 — Progressive epigenetic silencing of transgenes — open: CTCF insulators + AAVS1 + HSC turnover as countermeasures; T-cell organoid validation required before Phase I. O9 — Balanced-quorum co-presence probability in the TME — resolved v12.0: transit-based model replaces static λ assumption; P_quorum ≥99.93% in all tumor phases; detection threshold N ~ 3×10³ cells. O10 — Bulk-derived correlations ρ_ij underestimate single-cell correlations — corrected v12.0: ρ_sc ≤ ρ_bulk for inter-group pairs (θ=0.17 is upper bound); sensitivity table replaced with correct k=3 Monte Carlo values from §6.2b (prior k=5 values from v11.0 were erroneous). O11 — Ci-VSP immunogenicity — resolved for Phase 0 PoC: no strong HLA-A*02:01 binders; PTEN cross-reactivity signal (H→Q mutation recommended before Phase I); partially open for Phase I. O12 — Sub-threshold dormant cells (CDICs) — managed: T-δ and T-ε cover structurally; O12-B identifies pregnancy as clinical contraindication for CDIC calibration mode. O13 — HLA silencing and NK missing self in DQIS-J — resolved: HLA-E in construct; pool self-sustaining at 3.5–6.7× N_threshold. O14 — Transferability of Penn Medicine data to immunocompetent children — partially resolved computationally: N_ss 5–9× above threshold in all plausible scenarios; preclinical validation recommended before Phase I. O15 — Brain reporter gap: chromogenic signal does not exit BBB — resolved v14.0: S_tm transmembrane isoform + hepatic S₂ paracrine cascade; blue urine signal in 11–24h from brain, without modification to clinical procedure. No open structural flaws. High-severity open items (O8, O14) require standard preclinical validation, not conceptual breakthroughs. Not a peer-reviewed publication. Prior art deposit. Contact: [email protected] documents: - DQIS Consolidated Framework (main document): https://zenodo.org/records/19877553 - Addendum I — Temporal Stratification of Tail Dependence Risk: https://zenodo.org/records/19877810