---
vault_clearance: KETER
halo:
  classification: RESTRICTED
  confidence: HIGH
  front: "39_Project_MindWithBody — bounty board tracking the testable predictions of the unified Stage 0 mechanism (mechanical-shear-from-supply-chain-failure → LINC-mediated nuclear envelope tear → downstream 4-stage chain). Operationalizes the 11 predictions from MECHANISM_AND_DISEASE_MAP_2026-05-04.md §4.5 into actionable work."
  custodian: "Jixiang Leng"
  created: 2026-05-04
  wing: READY
  containment: "Operator-internal bounty board. Each bounty traces back to one or more predictions in MECHANISM_AND_DISEASE_MAP §4.5. Cai Lei deliverable critical-path is MWB-A1 + MWB-A2 + MWB-A3 + MWB-E1."
---

# 39_Project_MindWithBody — BOUNTY BOARD

> Bounties tracking the unified Stage 0 mechanism + load-vs-release HALO + cross-disease deployment. Each entry maps to: (a) which prediction in MECHANISM §4.5 it tests; (b) what data/compute is needed; (c) what unblocks downstream when it lands.

**ID prefix:** `MWB-` for MindWithBody. Tiers A through E by priority + scope.

**Status legend:** `OPEN` (not started) · `IN PROGRESS` (active work) · `BLOCKED` (waiting on dependency) · `READY` (scripts/infrastructure exist; operator self-service) · `SOLVED` (verified, OpenTimestamps anchored) · `DEFERRED` (postponed; see notes)

---

## Tier A — Critical-path testing of the unified Stage 0 mechanism (Cai Lei deliverable on this path)

| ID | Title | Status | Prediction tested | Time | Notes |
|---|---|---|---|---|---|
| **MWB-A1** | **Run Pineda 2024 motor cortex (Synapse syn51105515)** — UPPER_MN (Betz cells) load-vs-release per-cell-type evaluation; SENSORY (in Pineda not Yadav) check if any sensory population captured | READY (scripts at [`../10_Project_DiscordIntoSymphony/experiments/als_load_vs_release_2026-05-04/`](../10_Project_DiscordIntoSymphony/experiments/als_load_vs_release_2026-05-04/), bounty also tracked there as ALS-1) | **P11** (K_RG ACUTE TIGHTEN as unified single-cell readout) | 30 min operator + 10-15 min compute on personal laptop | If UPPER_MN shows LOAD_VS_RELEASE_CONFIRMED → unified mechanism validated at single-cell resolution on real human ALS data. **Cai Lei deliverable critical-path.** |
| **MWB-A2** | **Run Yadav 2023 lumbar spinal cord (GSE190442/GSE222322)** — LOWER_α-MN load-vs-release; SENSORY_NEURON as built-in negative control for motor-specificity | READY (scripts in 10/experiments/als_load_vs_release_2026-05-04/, also tracked as ALS-2 there) | **P11** + the negative-control half (sensory should NOT show pattern) | 30 min operator + 10 min compute | Combined with MWB-A1: between-dataset comparison (Pineda UPPER_MN vs Yadav LOWER_α-MN load scores) anchors the cytoskeletal-load-gradient prediction (P3+P4 from §1.2). **Anchors Cai Lei's clinical pattern (cervical>bulbar>lumbar) to mechanism.** |
| **MWB-A3** | **NEFL serum trajectory analysis on Cai Lei (specific patient)** — engagement-gated through AskHelpU; serial NEFL values + ALSFRS-R from his clinical record | BLOCKED on Cai Lei outreach | **P1** direct (NEFL trajectory tracks Stage 0 cytoskeletal-shear rate; slow progressors show lower trajectory) | 1 day operator if data accessible | Direct test of unified mechanism on the anchor patient case. If his NEFL trajectory is genuinely lower-slope than fast-progressor mean, the framework's prediction at the individual-patient level is validated. |
| **MWB-A4** | **NEFL/NEFH serum trajectory population analysis** — pull public ALS biomarker datasets with paired ALSFRS-R progression slope | OPEN (data identification needed) | **P1** at population scale | 2-3 days literature search + analysis | Datasets: Verde 2019 cohort, Benatar/Pulmonary BIONIC, Lu 2015 cohort. Test prediction that NEFL slope (not just snapshot) tracks repair capacity. |
| **MWB-A5** | **EV propagation efficiency analysis: fast-progressor vs slow-progressor CSF in iPSC-MN co-culture** | OPEN (collaborator-gated; equipment needed) | **P2** direct (fast-progressor EVs propagate cascade more efficiently) | 3-6 mo collaborator partnership | Sproviero lab has the framework; engagement question is whether a collaboration is possible. Per-cell-type evaluation of cascade triggering using `run_pineda_2024.py` evaluator architecture. |
| **MWB-A6** | **SOD1G93A and TDP-43 mouse Lamin B1 + LINC-complex immunostaining** — cross-cell-type analysis in spinal cord (alpha-MN vs gamma-MN vs sensory vs interneuron) | OPEN (mouse work; collaborator-gated) | **P8** (slow-progressor signature includes preserved Lamin B1) at tissue level + selective vulnerability gradient | 3-6 mo collaborator partnership | Predicts: alpha-MN show progressive Lamin B1 loss + LINC complex perturbation; sensory neurons spared at tissue level. |

---

## Tier B — Data acquisition gaps (needed to enable Tier A or downstream tests)

| ID | Title | Status | Notes |
|---|---|---|---|
| **MWB-B1** | **Acquire serial NEFL biomarker data from public ALS cohorts (ALSFRS-R-anchored)** | OPEN | Verde 2019, Benatar 2018, Lu 2015 datasets. Determine which are publicly downloadable vs require DUA. |
| **MWB-B2** | **AskHelpU biobank UNC13A rs12608932 genotype + serial biomarker request** (engagement-gated; promote from existing Tier-4 ask in ALS_DATASETS_2026-05-04.md) | BLOCKED on Cai Lei outreach | This single SNP gates the lithium decision per existing memory note. The biobank likely has it; Cai Lei or his team can authorize access. **Specific first-message ask, not generic data request.** |
| **MWB-B3** | **DMD scRNA-seq cross-cell-type acquisition** — satellite cells + myofibers + cardiac muscle for cross-cell-type test of load-vs-release in muscle | OPEN | Caputo 2023, Cutler 2024 (satellite cell cluster), Naddaf 2024 IBM, Jiang 2024 FSHD per existing ALS_DATASETS reference. Tests P7 (DMD therapeutics inform ALS) by mapping the parallel mechanism in muscle tissue. |
| **MWB-B4** | **PD substantia nigra dataset survivable on operator-personal compute** — Kamath PD chunked-load OR alternative | BLOCKED on chunked-load patch (~50 lines) OR FW-I2 personal-billed GCP | Tracked in load-vs-release HALO as UR-1a / ALS-4 in 10. Resolves whether rotenone monotone-load was HVG-2000 artifact or real biological pattern. |
| **MWB-B5** | **Pineda 2024 BAM access (raw FASTQ via SRA PRJNA1073234) for Method 2 TE-storm quantification** | OPEN | Method 2 (lament discover0) needs raw reads for repeat-aware TE quantification independent of annotation. Required for full Stage 3 (TE storm) measurement on Cai Lei-relevant motor cortex data. |
| **MWB-B6** | **Long-COVID + post-viral cardiomyopathy scRNA-seq** for cross-disease 4-stage test | OPEN | RECOVER cohort, LCRI, PolyBio LCCI per existing ALS_DATASETS. HNW relevance: Bryan Johnson, Hannah Davis. |

---

## Tier C — Mechanism-bridge investigations (literature passes + framework integration)

| ID | Title | Status | Prediction supported | Time |
|---|---|---|---|---|
| **MWB-C1** | **Literature pass on Lamin B1 / LINC complex stabilizers as therapeutic candidates** — small molecules, peptides, gene therapy | OPEN | **P4** | 2-3 days |
| **MWB-C2** | **Literature pass on calcium-buffer-mimetic strategies** — parvalbumin overexpression, calbindin-D28k therapy, calmodulin modulators | OPEN | **P3** + extension to combined intervention | 2-3 days |
| **MWB-C3** | **Literature pass on cytoskeletal-load-modulating drugs in ALS** — mexiletine (Weiss 2016), riluzole mechanism, Nav1.7 blockers | OPEN | **P5+P6** mechanism support | 2-3 days |
| **MWB-C4** | **Literature pass on DMD therapeutics translatable to ALS** — utrophin upregulation, micro-dystrophin, exon-skipping ASOs | OPEN | **P7** direct | 3-5 days; **HIGH VALUE — could surface translational opportunities ahead of standard ALS pipeline** |
| **MWB-C5** | **Literature pass on hypothermia / Q10 modulation in motor neuron degeneration** — cold-induced reductions in fasciculation; whole-body cooling for neuroprotection precedent | OPEN | **P5** | 2-3 days |
| **MWB-C6** | **Literature pass on EV-mediated propagation in ALS** — Sproviero series, Banack 2020, Feiler 2015, Iguchi 2016 | OPEN | **P2 + P9** mechanism support | 2-3 days |
| **MWB-C7** | **Literature pass on Phase 3 ALS trial failures organized by mechanism layer** — which trials targeted which stage; which failed; can the failure pattern be re-explained by the unified mechanism (each was treating a downstream stage rather than Stage 0)? | OPEN | Indirect — establishes why fragmented account couldn't predict failures | 3-5 days; high value for the publishable narrative |
| **MWB-C8** | **Literature pass on selective vulnerability — six fragmented hypotheses with their best supporting and contradicting papers** | OPEN | Establishes the §1.2 collapse rigorously with citations | 3-5 days |

---

## Tier D — Operator framework integration (HALO development)

| ID | Title | Status | Notes |
|---|---|---|---|
| **MWB-D1** | **Add Stage 0 (mechanical-shear primary mechanism) to MECHANISM_AND_DISEASE_MAP** | DONE 2026-05-04 | Rewritten in §1.1, §1.2, §1.3, §1.4. The 4-stage chain became 5-stage with Stage 0 added upstream. |
| **MWB-D2** | **Write HALO_UNIFIED_STAGE_0_MECHANISM_2026-05-04.md** — standalone HALO consolidating the synthesis (separate from MECHANISM doc which is the practical experimental design + cross-disease map) | OPEN | The standalone HALO would be the canonical statement of the synthesis for cross-vault citation. Currently the synthesis is embedded in MECHANISM §1; promoting to a HALO makes it cite-able from other projects (28 recycler, 33 GoldenHair, 35 splicing, etc.). |
| **MWB-D3** | **Cross-link Stage 0 to load-vs-release HALO + 33 collagen-mimetic Trojan HALO + 28 recycler hypothesis + tau-as-AMP work** | PARTIAL | Already cross-linked in MECHANISM §1.4 and HALO_LOAD_VS_RELEASE. Could be more comprehensive — need single cross-link map showing all the projects whose work feeds into the unified mechanism. |
| **MWB-D4** | **Cross-link operator's body-state observations** — cold-induced motor slowing as in-vivo demonstration of Q10 effect (P5 mechanism support); sub-40 RHR as substrate-resilience marker | OPEN | This bridges the operator's personal data (07_Project_Command OPERATOR_CONTEXT) to the mechanism. The cold-slowing observation is genuinely novel-in-context — operator has felt-sense data the field doesn't have access to. |
| **MWB-D5** | **Update DMD_EQ_ALS_THESIS_2026-05-04.md to reference the unified Stage 0 mechanism** explicitly — both diseases are loss-of-structural-protective-protein → membrane/envelope tear → Ca²⁺ flood → cell death → fibrosis | OPEN | Already conceptually aligned; needs explicit cross-reference + the unified-mechanism framing carried into the DMD doc. |
| **MWB-D6** | **Update RETROTRANSPOSON_ACCESS_MAP_2026-05-04.md** to reflect that retrotransposon storm is downstream of Stage 0 (was treated as parallel to the 4-stage chain previously) | OPEN | Light edit — change framing from "parallel signal" to "Stage 3 downstream of mechanical primary lesion." |

---

## Tier E — Cai Lei-specific deliverables (engagement-gated)

| ID | Title | Status | Notes |
|---|---|---|---|
| **MWB-E1** | **Cai Lei first-message update with unified mechanism context** — replace the per-stage explanation with the integrated Stage 0 mechanism + load-vs-release prediction + DMD parallel + specific NEFL trajectory ask | BLOCKED on MWB-A1 + MWB-A2 results | Once Pineda + Yadav verdicts land, the first-message becomes substantive ("we tested the framework on real ALS motor neurons; here's what we found") rather than speculative. |
| **MWB-E2** | **Cai Lei UNC13A rs12608932 genotype request** (escalated from Tier-4 ask in ALS_DATASETS to specific first-message ask) | BLOCKED on first-message draft | Single SNP gates lithium decision per existing memory note. AskHelpU biobank has it. Specific operator-actionable request. |
| **MWB-E3** | **Slow-progressor stratification analysis using unified mechanism criteria** — apply MWB-A1+A2 verdict logic to Cai Lei's specific cellular profile if accessible (his iPSC-MN line if banked, or his serum biomarker trajectory) | BLOCKED on AskHelpU partnership + sample availability | If AskHelpU has banked iPSC-MN from him, this becomes a per-patient framework deployment. The mechanism predicts his cellular profile should match slow-progressor signature on cytoskeletal-robustness + calcium-buffer + repair-capacity axes. |
| **MWB-E4** | **Cai Lei Phase II memo template populated with results** — once MWB-A1+A2+A3 land, write the actual deployable memo | BLOCKED on prerequisite bounties | Template exists in [`../10_Project_DiscordIntoSymphony/experiments/als_load_vs_release_2026-05-04/PINEDA_YADAV_RUNBOOK.md`](../10_Project_DiscordIntoSymphony/experiments/als_load_vs_release_2026-05-04/PINEDA_YADAV_RUNBOOK.md) §6. Adapt to whichever verdict came back. |

---

## Tier F — Publishable cross-disease atlas (longer-arc; HNW patient-founder portfolio activation)

| ID | Title | Status | Notes |
|---|---|---|---|
| **MWB-F1** | **Run `mind_with_body_4stage` (now 5stage) pipeline on 7-disease cohort** — cancer + ALS + DMD + IBM + lupus + long-COVID + MS | OPEN (~5-7 days compute on existing fleet) | Per existing operator priorities §6.2. Output: cross-disease 5-stage matrix. Tests P11 (K_RG ACUTE TIGHTEN as unified single-cell readout) at cross-disease scale. |
| **MWB-F2** | **Cross-disease comparison analysis** — identify which stages are conserved (predicted: 0-3) vs disease-specific overlay (predicted: 4) | BLOCKED on MWB-F1 | Tests cross-disease prediction in MECHANISM §4. |
| **MWB-F3** | **Write up cross-disease atlas as preprint OR provisional patent #4 (multi-disease 5-stage cellular failure mode + sequential combination therapy logic)** | BLOCKED on MWB-F1+F2; counsel review | Per MECHANISM §5 strategic implications. **HIGH VALUE — broadest patent claim.** |

---

## Critical paths

**Cai Lei deliverable:** MWB-A1 → MWB-A2 → MWB-E1 → MWB-E2. Total: ~2 days of operator work + ~1 hour compute (operator self-service via runbook).

**Unified mechanism validation at single-cell resolution:** MWB-A1 + MWB-A2. Independent of Cai Lei outreach. Direct test of P11.

**Publishable cross-disease atlas:** MWB-F1 → MWB-F2 → MWB-F3. ~2-4 weeks compute + 4-6 weeks writing + counsel review. Activates HNW patient-founder pipeline at platform-thesis scale rather than per-disease.

**HNW patient-founder portfolio activation:** MWB-A1+A2 (validates framework) → MWB-F1+F2 (validates cross-disease) → individual outreach per disease (Cai Lei ALS, Sid Sijbrandij osteosarcoma, Chip Wilson FSHD, Selena Gomez lupus, Christina Applegate MS, Vallabh+Minikel prion, Bryan Johnson long-COVID, etc.).

---

## Cross-references

- **MECHANISM doc:** [MECHANISM_AND_DISEASE_MAP_2026-05-04.md](MECHANISM_AND_DISEASE_MAP_2026-05-04.md) §4.5 testable predictions list
- **Load-vs-release HALO:** [HALO_LOAD_VS_RELEASE_TRAJECTORY_2026-05-04.md](HALO_LOAD_VS_RELEASE_TRAJECTORY_2026-05-04.md) — the single-cell-resolution measurement of Stage 0 vulnerability
- **DMD parallel:** [DMD_EQ_ALS_THESIS_2026-05-04.md](DMD_EQ_ALS_THESIS_2026-05-04.md) — same Stage 0 mechanism in muscle
- **ALS dataset map:** [ALS_DATASETS_2026-05-04.md](ALS_DATASETS_2026-05-04.md) — Tier 0 through Tier 4 access tiers
- **Inhouse toolkit speeds:** [INHOUSE_TOOLKIT_SPEED_ASSESSMENT_2026-05-04.md](INHOUSE_TOOLKIT_SPEED_ASSESSMENT_2026-05-04.md) — Cai Lei 24-48 hour ETA basis
- **Tool inventory:** [TOOL_INVENTORY_2026-05-04.md](TOOL_INVENTORY_2026-05-04.md) — ~240 tools available
- **Literature aggregation:** [BOOK.md](BOOK.md) — citations supporting the 11 predictions
- **External-experiment dir** (where the actual scripts live): [../10_Project_DiscordIntoSymphony/experiments/als_load_vs_release_2026-05-04/](../10_Project_DiscordIntoSymphony/experiments/als_load_vs_release_2026-05-04/) — also has bounties tracked there as ALS-1 through ALS-6 (cross-linked above)
- **Collagen-mimetic Trojan HALO** (engineering layer): [../33_Project_GoldenHair/HALO_COLLAGEN_MIMETIC_TROJAN_2026-05-04.md](../33_Project_GoldenHair/HALO_COLLAGEN_MIMETIC_TROJAN_2026-05-04.md)
- **Recycler hypothesis** (downstream Stage 4 explanation): [../28_Project_RedFromTheGrave/theory/](../28_Project_RedFromTheGrave/theory/)
- **Operator substrate context** (P5+P6 anchoring data): [../07_Project_Command/OPERATOR_CONTEXT.md](../07_Project_Command/OPERATOR_CONTEXT.md)

---

## Provenance

Created 2026-05-04 by Claude (this session) immediately after rewriting MECHANISM_AND_DISEASE_MAP §1 to add Stage 0. Operator direction: *"Log your bounties in 39 for what we need to investigate then aggregate the literature on this into the book for 39."* Anchored to OpenTimestamps on save. The 39 project did not previously have a BOUNTY_BOARD per the standard project-triad pattern (BOUNTY_BOARD + WORLDLINE + FORM + BOOK). This file fills that slot.