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 pᵢ — updated v13. 0: full computational model for T-β pᵢ (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: pᵢ = 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 pᵢ = 0. 01 — histotype-dependent pᵢ; 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; Pquorum ≥99. 93% in all tumor phases; detection threshold N ~ 3×10³ cells. O10 — Bulk-derived correlations ρᵢj underestimate single-cell correlations — corrected v12. 0: ρₛc ≤ ρbulk 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× Nₜhreshold. O14 — Transferability of Penn Medicine data to immunocompetent children — partially resolved computationally: Nₛs 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: Sₜm 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: dqis. research@proton. meRelated documents: - DQIS Consolidated Framework (main document): https: //zenodo. org/records/19877553 - Addendum I — Temporal Stratification of Tail Dependence Risk: https: //zenodo. org/records/19877810
DQIS Research Group (Thu,) studied this question.