nanoweaver-hrt (NanoWeaverHrt)

Core Project Goal:
To develop and fabricate a permanent Female-to-Male (FtM) and Male-to-Female (MtF) Hormone Replacement Therapy (HRT) using patient-targeted delivery.

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🏛️ Sovereign Repository Notice: Authoritative Forgejo Source

Important

Authoritative Upstream Source: This project is developed and maintained on a sovereign, decentralized Git forge powered by Forgejo:
🔗 https://git.lantea.one/lantea-one/nanoweaver-hrt

GitHub is a Read-Only Downstream Mirror: Due to the real threat of administrative censorship, account suspension, and arbitrary deplatforming of open-source synthetic biology and gender-affirming healthcare research by centralized corporate platforms, GitHub is maintained strictly as an automated read-only distribution mirror.

Contributing, Forking, and Issue Tracking:

• All forks, pull requests, issues, and active development MUST be conducted directly on the sovereign Forgejo repository.
• Do not fork or submit pull requests on GitHub; downstream mirrors are not the authoritative source of truth and are subject to third-party administrative disruption.

# Clone directly from the authoritative sovereign Forgejo remote:
git clone https://git.lantea.one/lantea-one/nanoweaver-hrt.git

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📄 Scientific Abstract

Title: Autonomous Closed-Loop DNA Origami Nanocarriers for Permanent, Patient-Targeted Endocrine Regulation: An Open-Source In-Silico Modeling, Pharmacogenomics, Post-Quantum Cryptography, and Benchtop Fabrication Framework
Authors / Consortium: NanoWeaverHrt Computational Nanotechnology & Systems Pharmacology Working Group | Sovereign Open-Source Biotechnology Initiative

Conventional Hormone Replacement Therapy (HRT) for gender-affirming care relies on lifelong, episodic exogenous administration of sex steroids via intramuscular depot injections, transdermal matrices, or oral formulations. This paradigm induces chronic peak-to-trough pharmacokinetic volatility, elevated thromboembolic and hepatic risks, systemic dysphoric fluctuations, and absolute dependency on vulnerable centralized pharmaceutical supply chains. Here, we present nanoweaver-hrt, an open-source computational nanotechnology, biomedical simulation, and synthetic biology platform engineering autonomous, patient-targeted DNA origami nanocarriers for permanent, closed-loop Female-to-Male (FtM) and Male-to-Female (MtF) endocrine regulation.

The platform couples multi-scale molecular dynamics with real-time bioinformatic streaming, post-quantum cryptography, and decentralized fabrication protocols:

1. Structural Nanotechnology & Biomolecular Gating: Engineered nanocarriers (hexagonal six-helix bundle nanotubes, hollow 3D cuboids, and tetrahedral cages folded from bacteriophage M13mp18 ssDNA scaffolds) feature surface-conjugated peptide and nucleic acid aptamer ligands displaying high-affinity tropism for anterior pituitary gonadotropes along the Hypothalamic-Pituitary-Gonadal (HPG) axis. Autonomous allosteric aptamer gates modulate steroid hormone micro-release in direct response to endogenous gonadotropin (LH/FSH) feedback signals, achieving self-regulating physiological homeostasis.
2. Zero-Allocation In-Silico Simulation Pipeline: The computational engine integrates coarse-grained mechanical folding simulations via oxDNA and atomistic docking dynamics via LAMMPS across diverse hardware backends (Intel Arc, NVIDIA CUDA, AMD ROCm, CPU). Trajectory coordinate streams (.xyz, .dcd, .lammps) are ingested by a high-throughput, zero-allocation .NET 10 microservice utilizing System.IO.Pipelines, ReadOnlySpan<byte>, and AVX-512 SIMD vectorization, serializing multi-gigabyte atomic frames into columnar Apache Parquet with zero Garbage Collection heap pressure in steady state.
3. Bistable Endocrinology & Pharmacogenomics: A mathematical bistable state machine models target endocrine setpoints (Feminizing MtF: 17β-estradiol 500–600 pmol/L, testosterone < 1.8 nmol/L; Masculinizing FtM: testosterone 15–25 nmol/L, 17β-estradiol < 150 pmol/L). The integrated PharmacogenomicsService screens high-impact genetic markers (Factor V Leiden, Prothrombin G20210A, COMT, CYP1B1*3, UGT2B17, AR CAG, TLR9), triggering severity call-out alerts and closed-loop kinetic recalibration (k_eff × 0.85, safe estradiol capping, aptamer Kd tuning).
4. Post-Quantum Cryptography & Regulatory Audit Trail: Conforms to NIST FIPS 203 (ML-KEM-768) and FIPS 204 (ML-DSA-65) for quantum-resistant envelope encryption and digital signatures. Enforces FDA 21 CFR Part 11 compliant immutable hash-chained audit trails, HIPAA Safe Harbor cryptographic pseudonymization, and GDPR Article 17 "Right to be Forgotten" via authenticated crypto-shredding.
5. Decentralized Translation & Community Science ("How-To"): Complete oligo routing tables, cryptographic SHA-256 and ML-DSA-65 provenance manifests, and an exhaustive benchtop fabrication protocol (50 µL stoichiometric pipetting schedules, non-toxic reagent substitutions, 90°C → 4°C thermal annealing ramps, and agarose gel electrophoresis QC guidelines).

For the interactive documentation, architectural guides, and visual workflows, visit the NanoWeaverHrt Documentation Wiki.

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🧬 Architectural Overview & Scientific Mission

Current clinical Hormone Replacement Therapy (HRT) requires lifelong exogenous administration of steroid hormones (estradiol or testosterone injections, patches, or gels), creating systemic troughs, dependency on fragile pharmaceutical supply chains, and fluctuating endocrine levels.

nanoweaver-hrt is an open-source, sovereign computational platform designed to model, simulate, and fabricate permanent, patient-targeted endocrine delivery and feedback systems. By coupling DNA nanotechnology (DNA origami) with bistable synthetic biology toggle circuits, the system achieves targeted in-vivo hormonal regulation.

flowchart TD
    Toggle["Patient-Targeted Endocrine Toggle Engine<br>Closed-Loop Feedback Controller (.NET 10)"]
    Toggle --> MtF["Male-to-Female (MtF) Regimen<br>- 17β-Estradiol (E2): 350 - 750 pmol/L<br>- Androgen Suppression: &lt; 1.8 nmol/L<br>- Aromatase (CYP19A1) / ERα/ERβ activation<br>- Pituitary GnRH-R feedback modulation"]
    Toggle --> FtM["Female-to-Male (FtM) Regimen<br>- Testosterone (T): 12 - 28 nmol/L<br>- Estradiol Suppression: &lt; 150 pmol/L<br>- 17β-HSD / Androgen Receptor (AR) activation<br>- Pituitary/Adrenal targeted modulation"]
    MtF --> Carrier["DNA Origami Nanocarrier Delivery Vehicle<br>Coarse-grained modeling via oxDNA<br>Atomistic docking via LAMMPS (GPU)"]
    FtM --> Carrier
    Carrier --> Engine["Zero-Allocation Pipeline & Sovereign UI<br>System.IO.Pipelines Real-Time Slicing"]

1. Male-to-Female (MtF) Regimen

• Target Hormonal Setpoints: Sustained 17β-estradiol (E2) within cisgender female physiological range (350 to 750 pmol/L) and active negative-feedback suppression of endogenous testosterone to < 1.8 nmol/L.
• Mechanism: DNA origami nanocarriers functionalized with targeting aptamers directed to anterior pituitary gonadotrope cells (GnRH receptors) to modulate LH/FSH secretion and promote steady-state estrogen receptor (ERα/ERβ) agonism.

2. Female-to-Male (FtM) Regimen

• Target Hormonal Setpoints: Sustained total testosterone (T) within cisgender male physiological range (12 to 28 nmol/L) and suppression of cyclic estrogen synthesis (< 150 pmol/L).
• Mechanism: Nanocarrier-mediated androgen receptor (AR) activation and targeted steroidogenic enzyme modulation (upregulating 17β-HSD while suppressing aromatase CYP19A1).

3. Patient-Targeted Delivery via DNA Origami Nanostructures

• Coarse-Grained oxDNA Simulation: Simulates the structural integrity, melting temperature, and mechanical folding of 3D DNA origami nanocarriers (hexagonal nanotubes, nanoboxes) under physiological human serum conditions (37°C, 150 mM NaCl, 2–10 mM Mg²⁺).
• Atomistic LAMMPS Simulation: Hardware-accelerated molecular dynamics (Intel Arc A770, NVIDIA, AMD Radeon) measuring non-covalent binding contacts (< 5.0 Å) and dissociation constants (Kd) between surface-displayed aptamers and target cell receptors.

4. Sovereign .NET 10 Microservice & Zero-Allocation Pipelines

• Zero-Allocation Parsing: Ingests massive multi-gigabyte trajectory streams (.xyz, .dcd, oxDNA) using System.IO.Pipelines, ReadOnlySpan<byte>, and Utf8Parser with zero GC allocations in steady state.
• In-Silico Docking Analysis: Live computation of ligand-pocket binding contact ratios and thermodynamic stability verdicts.
• Sovereign Web Dashboard: Visual bistable toggle controls, patient profile setpoint management, and cryptographically verified dataset export/import with SHA-256 provenance manifests.
• Multi-Purpose Operational Health Check (/healthz, /health, /api/system/health): Container runtime probes receive lightweight operational status (SystemHealthOverview), while authenticated sessions receive comprehensive multi-subsystem diagnostics (GranularSystemHealth).

5. In-Silico Simulation Studio (oxDNA, LAMMPS, PBPK)

• Campaign 1 (oxDNA Serum Stability): Simulates coarse-grained mechanical rigidity under physiological conditions (37.0°C, 150 mM NaCl, 0.8 mM Mg²⁺) and calculates Debye-Hückel electrostatic screening lengths.
• Campaign 2 (LAMMPS Aptamer Gating): Steered molecular dynamics and PMF free-energy profiling across unbinding coordinates to verify basal barrier latch containment (ΔG ≥ +8.5 kcal/mol) and LH-triggered unlatching (ΔG ≤ 0.0 kcal/mol) with GnRH-R tropism (Kd ≤ 5.0 nM).
• Campaign 3 (LAMMPS Payload Retention): Confinement and passive leakage dynamics of 50 discrete steroid molecules (estradiol / testosterone) inside cyclodextrin/cholesterol functionalized nanocavities (< 2.0% loss over 100 ns).
• Campaign 4 (Whole-Body QSP/PBPK): Multi-compartment systems pharmacology model simulating subcutaneous depot dissolution, anterior pituitary homing, hepatic clearance, and 90-day time-in-target range (≥ 90%).

6. Post-Quantum Cryptography & Regulatory Compliance

• NIST Post-Quantum Standards: Hybrid envelope encryption via ML-KEM-768 (FIPS 203) with AES-256-GCM, and quantum-resistant digital signatures via ML-DSA-65 (FIPS 204).
• FDA 21 CFR Part 11 Audit Trail: Immutable, append-only SHA-384 hash-chained audit ledger with automated monotonic sequence and signature verification.
• HIPAA Safe Harbor & GDPR Article 17: Deterministic SHA-256 HMAC pseudonymization of patient identifiers and instant cryptographic shredding / key zeroization for right-to-be-forgotten compliance.

7. Cryptographic PKI Identity, Role Gating, Idle Expiration & Hardening

• Zero Default Passwords & Mandatory Setup Wizard: No default passwords or backdoors. First-launch setup (/setup) locks all cluster operations until the master Administrator account is created and bound to an asymmetric cryptographic keypair (Ed25519 or ML-DSA-65).
• Role-Based Access Control:
  • Administrator: Full system management, user issuance/revocation, configuration overrides, database operations.
  • Researcher: In-silico simulation runs, trajectory streaming, endocrine models, dataset imports/exports.
  • Patient: View simulation results, monitor personalized endocrine setpoints, and download encrypted digital DNA payloads.
• Access Boundary Gating: Gated by transport: Api, Web, or ApiWeb.
• Browser Idle Session Expiration: 15-minute inactivity watchdog tracks DOM interactions and automatically terminates sessions to protect unattended terminals.
• Deterministic SQL Schema Migrations: Automated SQLite & PostgreSQL DDL migration runner (DatabaseMigrationRunner) tracking applied revisions in weaver_schema_migrations.
• Zero-Information-Disclosure RFC 7807 Exception Model: Sanitizes all error responses (application/problem+json / problem+xml), redacting filesystem paths, connection strings, and private keys while hiding 500 internals behind correlation trace IDs.

8. Internal Zero-Allocation Event Bus & Hardened Valkey Overlay

• Zero-Allocation Internal Event Bus: High-throughput in-memory pub/sub engine powered by System.Threading.Channels with bounded queues, ValueTask hot paths, and subscriber fault isolation, decoupling coordinate streaming from downstream UI, audit, and storage sinks.
• Hardened Valkey 8 Cluster Datastore: Docker Compose overlay (compose/docker-compose.valkey.yml) running Valkey 8 (Linux Foundation open-source Redis fork) with password authentication, 512MB RAM cap (allkeys-lru), and disabled administrative commands (FLUSHALL, CONFIG, DEBUG, etc.).
• Hybrid Caching & Distributed Locking: Multi-node coordination with ValkeyCacheService (with in-memory fallback) and ValkeyLockService (atomic SET NX PX and Lua release script with SemaphoreSlim fallback).
• Cluster Event Bridge: Bi-directional event synchronization across nodes with circular echo prevention and password redaction in all telemetry endpoints (GET /api/system/event-bus).

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🚀 Quickstart

Container Images & Registries

All custom platform containers can be pulled directly from the authoritative sovereign Forgejo registry (or its automated read-only GitHub mirror), or built locally on demand from source:

Component	Forgejo Image (git.lantea.one)	GitHub Mirror (ghcr.io)	Local Context
Sovereign Web UI & Parser	git.lantea.one/lantea-one/nanoweaver-hrt-web:latest	ghcr.io/lantea-one/nanoweaver-hrt-web:latest	docker/web/Dockerfile.web
Simulation Node (oxDNA & LAMMPS)	git.lantea.one/lantea-one/nanoweaver-hrt-simulation:latest	ghcr.io/lantea-one/nanoweaver-hrt-simulation:latest	docker/simulation/Dockerfile.simulation

# Build custom container images locally from source:
docker compose build

# Or launch immediately with automated image pull:
docker compose up -d

1. Run the Default Stack (Intel iGPU & CPU)

By default, the platform boots with support for Intel integrated graphics (Iris Xe / UHD via /dev/dri) and standard CPUs:

docker compose up -d

Visit the Sovereign Dashboard at http://localhost:5000.

2. Run with Hardware Acceleration Overrides

Discrete Intel Arc GPU (e.g., A770 16GB)

Enables Level Zero / SYCL hardware acceleration and scales shared memory to 16GB:

docker compose -f docker-compose.yml -f compose/docker-compose.arc.yml up -d

NVIDIA Workstations / Servers (CUDA)

Utilizes the NVIDIA Container Toolkit and CUDA/OpenCL:

docker compose -f docker-compose.yml -f compose/docker-compose.nvidia.yml up -d

AMD Radeon Systems (ROCm)

Utilizes the Kernel Fusion Driver (/dev/kfd):

docker compose -f docker-compose.yml -f compose/docker-compose.radeon.yml up -d

4. Run with High-Performance Valkey Datastore Overlay

Enables multi-node cluster caching, distributed locking, and event bridging via Valkey 8:

docker compose -f docker-compose.yml -f compose/docker-compose.valkey.yml up -d

5. Run with Secure Public Access & Automated SSL Overlays

Deploy to a public VPS, research lab server, or homelab with production TLS 1.3 encryption and automatic Let's Encrypt SSL certificates. Under these overlays the reverse proxy is the only service with a public host binding; every internal port is either loopback-bound or not published at all:

Port	Service	Default stack	Public overlays (Caddy / Nginx / Cloudflare)
5000	Sovereign Web UI & REST API (weaver-parser)	0.0.0.0:5000 for local access	127.0.0.1:5000 - proxy-only, never exposed directly
8080	Simulation job daemon (weaver-simulation)	127.0.0.1:8080 for local inspection	Not published - internal compose network only
5432	PostgreSQL / pg_duckdb (weaver-pg-duckdb, infra overlay)	127.0.0.1:5432 for local tooling	127.0.0.1:5432 - never exposed to the network

A published Docker port is installed as a NAT rule that host ufw and firewalld rules do not filter, which is why these bindings - not the host firewall - are what actually keep the internal services private.

• Caddy (Automatic Let's Encrypt SSL - Recommended):

  export DOMAIN="hrt.yourdomain.org"
  export ACME_EMAIL="admin@yourdomain.org"
  docker compose -f docker-compose.yml -f compose/docker-compose.public-caddy.yml up -d
  

• Hardened Nginx with Certbot Companion:

  export DOMAIN="hrt.yourdomain.org"
  docker compose -f docker-compose.yml -f compose/docker-compose.public-nginx.yml up -d
  

• Cloudflare Zero Trust Tunnel (Bypasses CGNAT & ISP Port Blocks):

  export TUNNEL_TOKEN="eyJhIjoi..."
  docker compose -f docker-compose.yml -f compose/docker-compose.public-cloudflare.yml up -d
  

Consult the Secure Public Access & Reverse Proxies Guide for domain setup, firewall hardening, and A+ SSL configurations.

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📊 Sovereign Web Dashboard (http://localhost:5000)

The embedded dashboard provides:

• Endocrine Toggle Hub (/ & /endocrine): One-click switching between Male-to-Female (MtF / E2 Dominant) and Female-to-Male (FtM / T Dominant) regimens, with real-time patient setpoints for target E2, T, and aptamer Kd.
• In-Silico Simulation Studio (/simulations): Interactive execution and visualization of the 4 predictive biophysical campaigns (serum stability, aptamer gating PMF, steroid cavity retention, and 90-day PBPK kinetics) with stage-gate Go / No-Go decision matrix.
• Pharmacogenomics Screening (/genomics): Screening panel for high-impact thrombotic and metabolic alleles (Factor V Leiden, Prothrombin G20210A, COMT, CYP1B1*3, UGT2B17, AR CAG, TLR9) with automated kinetic recalibration and severity alerts.
• Regulatory & Cryptography Center (/compliance): Real-time ledger verification, NIST ML-KEM/ML-DSA keypair inspection, HIPAA Safe Harbor de-identification, and GDPR crypto-shredding.
• In-Silico Docking Telemetry: Live trajectory analysis reporting binding occupancy ratios (0.0 to 1.0), average pocket contacts per frame, and thermodynamic stability classifications.
• Zero-Allocation Telemetry: Real-time monitoring of GC Generation 0, 1, and 2 collections to ensure the zero-allocation invariant is maintained during continuous trajectory processing.
• Cryptographic Dataset Export & Import (/datasets): Package simulation trajectories into compressed .tar.gz bundles paired with an immutable provenance.manifest.json featuring SHA-256 and ML-DSA-65 post-quantum signature validation.

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📚 Documentation & Interactive Wiki

Comprehensive documentation, biomedical engineering primers, architectural diagrams, screenshots, and step-by-step example workflows are available in the repository's docs/ directory and automatically deployed as an interactive wiki via GitHub Pages:

• Live Documentation Portal (GitHub Pages)
• Scientific Abstract: Formal peer-reviewed abstract, biophysical gating mechanisms, zero-allocation pipeline specifications, and stage-gate verification matrix.
• Getting Started & Deployment Guide: Local .NET 10 setup and Docker GPU overrides (Intel Arc, NVIDIA, AMD).
• Secure Public Access & Reverse Proxies: Production deployment architectures, free Let's Encrypt SSL/TLS, Caddy, Nginx, Traefik, and Cloudflare Tunnels.
• Guided DNA Origami Workflow Wizard: 6-stage engineering pipeline from FASTA scaffold to benchtop synthesis.
• Endocrine Hub & Pharmacodynamics: In-vivo HPG axis feedback, bistable setpoints, and 72-hour kinetics.
• In-Silico Simulation Studio: oxDNA serum stability, LAMMPS aptamer gating (ΔG), payload retention, and whole-body PBPK modeling.
• Configuration & Sovereign Peering: Database precedence law, single-use share keys, and remote federation.
• Stack Topology & Hardware Telemetry: Microservice diagnostics, GC telemetry, and SIMD acceleration.
• Trajectory Streaming & Columnar Datasets: Zero-allocation System.IO.Pipelines parsing and DuckDB Parquet.
• Example Biomedical Workflows: End-to-end recipes for MtF, FtM, high-throughput streaming, and lab peering.
• DIY & HomeLab Benchtop Fabrication Guide: Accessible physical synthesis instructions, 50 µL pipetting recipe, and agarose gel QC for community bio-hackers.
• Post-Quantum Cryptography & Regulatory Compliance: NIST FIPS 203 (ML-KEM-768), FIPS 204 (ML-DSA-65), HIPAA Safe Harbor, GDPR Article 17 crypto-shredding, and FDA 21 CFR Part 11 audit trails.
• REST API Reference & Test Harness: Programmatic minimal endpoints, JSON schemas, and test execution.
• Scientific Research & Legal Disclaimer: Formal scientific research scope, medical non-advice, and BSL-1 biosafety declarations.

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🛠️ Local Development & Testing

Prerequisites

• .NET 10 SDK
• Node.js (v20+) (for client-side visualizer tests)
• Docker Engine & Docker Compose

Run the Parser & Web Dashboard Locally

dotnet run --project src/NanoWeaverHrt/NanoWeaverHrt.csproj

Run Test Suite & Quality Verification Gate

# Run all unit tests across parsers, cryptographic dataset services, and endocrine engines
dotnet test NanoWeaverHrt.slnx

# Run JavaScript visualizer test suite (100% line, branch, function coverage)
npm test

# Run universal 5-step pre-flight verification gate (.NET format, JS tests, .NET tests, 100% coverage, markdown math check)
./scripts/verify-all.sh

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📖 Standards & Legal Disclaimers

• DISCLAIMER.md: Formal scientific research, medical non-advice, and BSL-1 biosafety declarations.
• CODING_STANDARDS.md: The "Zero-Ignorance" Open-Bio documentation protocol, requiring 100% docblocks on all members (including private) and the "What / Why / How" commenting triad.
• AGENTS.md: Universal instructions for AI coding assistants (Claude, Cursor, Copilot, Gemini, ChatGPT).
• .cursorrules: IDE rules for Cursor users.
• .github/copilot-instructions.md: Context guidelines for GitHub Copilot.