Decision spine
Frames the controlling thesis, evidence status, buyer implications, and research-use limits.
Rare Diseases
Zemi Dossier
Research-use only
Mitochondrial Medicine Permanence Ladder
A decision package on mitochondrial medicine as a permanence-matching problem across transfer, shift, edit, replacement, and organelle-level strategy.
Decision this dossier helps answer
Which mitochondrial programs need transient support, durable shift, editing, replacement, or avoidance based on heteroplasmy and tissue constraints?
Problem this dossier solves
Mitochondria are a permanence problem before they are a platform category.
The dossier frames mitochondrial medicine around how long the intervention must persist and where correction must reside. It helps buyers match transfer, modulation, editing, or replacement to the disease biology rather than to platform excitement.
What is moving: current field evidence and platform activity
What is unresolved: decision-grade proof, endpoint logic, and failure modes
What Zemi solves: evidence-gated next-study strategy
Full decision package
100-page research report plus 37-sheet Evidence & Decision Workbook
Buy now
$3,500$5,500Launch price
Controlling thesis
Mitochondria are a permanence problem before they are a platform category.
The dossier frames mitochondrial medicine around how long the intervention must persist and where correction must reside. It helps buyers match transfer, modulation, editing, or replacement to the disease biology rather than to platform excitement.
A Zemi Dossier turns uncertain emerging research into a decision package: what is known, what is inferred, what is hypothetical, what would falsify the thesis, and what should be built, funded, avoided, monitored, or validated next.
Research report preview
First 30 pages of the actual Mitochondrial Medicine Permanence Ladder research report.
The public page shows the real document style, density, evidence posture, and decision framing before a buyer requests access to the full Zemi Dossier package.
Research report
The research report is the argument. It is not the whole product.
The PDF research report is the structured argument: field status, evidence maturity, buyer implications, falsifiable hypotheses, power-calculated next studies, strategic recommendations, limitations, and traceability posture.
Inspectable infrastructure
Pairs the report with claim ledgers, evidence tables, power rows, audit surfaces, and decision tools.
Executable next studies
Links hypotheses to endpoint logic, assumptions, sample-size logic, budget, and timeline planning.
Research report table of contents
Public TOC generated from the source report.
The full research report is delivered as a licensed PDF. This table shows the decision structure without publishing the full product.
| Section | What it covers | Buyer value |
|---|---|---|
| Decision Brief Read This First | Turns the report into immediate buyer triage: what matters now, what is still uncertain, and what to do next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Contents | Shows the report structure and where to inspect the argument, evidence, workbook logic, and limits. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Executive Summary | Condenses the dossier thesis, evidence posture, buyer implications, and next-study priorities. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Scope and Evidence Integrity | Defines the evidence window, source boundaries, research-use limits, and labeling discipline. | Lets the buyer audit support strength before relying on the package. |
| Why the bright lines and scope fences are load-bearing, not boilerplate | Defines the evidence window, source boundaries, research-use limits, and labeling discipline. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The count reconciliation, stated so it cannot be hand-waved | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Decision Snapshot Overview | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Buy Build Wait Avoid | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Buyer Decision Matrix | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Source Quality Dashboard | Shows how strong the source base is and where conclusions depend on indirect or thinner support. | Lets the buyer audit support strength before relying on the package. |
| Why the re-grade matters, and what it does not claim | Links claims to source support so users can separate what is known, inferred, and hypothetical. | Lets the buyer audit support strength before relying on the package. |
| The Set Point Permanence Ladder Model | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The model in one sentence | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The set-point is a vector, not a number | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The value equation: a product over a sum | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The three rungs, matched to durability | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The eight through-lines (candidate discoveries, each grounded against June-2026 evidence) | Frames the field's June 2026 state, active programs, research fronts, and timing signals. | Lets the buyer audit support strength before relying on the package. |
| The keystone: the Permanence-Match Classifier (PMC) | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| What would falsify the model | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The four denominator blockers, as engineering parameters | Defines the populations, measurements, or comparison bases needed to interpret evidence without overgeneralizing. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The threshold vector, formally | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The classifier in practice: reading three real profiles | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Why a product over a sum, and not a weighted sum | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The assay panel as the model's sensory organ | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The wash-out arithmetic that defines Durability-Mismatch | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The Permanence Match Classifier | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Current Signal Refresh 2025 2026 | Frames the field's June 2026 state, active programs, research fronts, and timing signals. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Reading the window as a coherent move, not a list of events | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The forward read into 2027-2028 | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Cross Domain Synthesis | Shows how separate research signals converge, diverge, or interact across domains, mechanisms, or study layers. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The synthesis claims, carried one level deeper | Defines the governing argument and the evidence gates that would support or falsify it. | Lets the buyer audit support strength before relying on the package. |
| The remaining synthesis claims, and what each commits the field to | Defines the governing argument and the evidence gates that would support or falsify it. | Lets the buyer audit support strength before relying on the package. |
| The synthesis, as a single claim | Defines the governing argument and the evidence gates that would support or falsify it. | Lets the buyer audit support strength before relying on the package. |
| A bioenergetic theory of immune aging (referenced, not re-litigated) | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| The fourth axis, mapped onto the nuclear permanence spectrum | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Evidence Maturity Matrix | Links claims to source support so users can separate what is known, inferred, and hypothetical. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
Evidence & Decision Workbook
The workbook is the decision engine.
A locked public preview of selected workbook-derived sheets: sheet structure, decision modules, power rows, traceability, and audit posture. Licensed buyers receive the full workbook files.
Read-only workbook preview with clipped values and no formulas. Licensed buyers receive the full Evidence & Decision Workbook with editable assumptions and working files.
Workbook inventory
Delivered workbook sheets.
Full inventories belong on dossier pages, not the homepage. Sheet names below are extracted from the actual workbook file.
| # | Workbook sheet | What it does |
|---|---|---|
| 1 | 1. Workbook Guide | Navigation layer for using the workbook, understanding sheet roles, and following the decision package. Public preview exposes Evidence directness, 0 Direct / 64 Adjacent / 7. fields and clipped entries such as Source-support verdicts, 45 SUPPORTS_EXACTLY /. |
| 2 | 2. Claim Ledger | Claim-by-claim ledger showing verdicts, source support, inference status, and decision relevance. Public preview exposes claim_id, claim_text, report_section, report_page fields and clipped entries such as F1, Barth syndrome transplant-free., Key Findings;. |
| 3 | 3. Evidence Table | Evidence-verification surface for checking sources, support quality, and the audit trail. Public preview exposes Identifier, Title (verified), Journal, Year fields and clipped entries such as PMID:42070974, Survival and Clinical Progression in., Not reported. |
| 4 | 4. Source-Support Verdicts | Independent check on whether key claims are actually supported by cited sources. Public preview exposes UNCLEAR, 5, 0, Re-anchored or flagged (e.g.. fields and clipped entries such as CONTRADICTS, Source contradicts a claim, None found. |
| 5 | 5. Source-Quality Summary | Summary of source strength, gaps, and areas where conclusions depend on weaker evidence. Public preview exposes Metric, Fresh (value-based, this analysis), Superseded (source strict screen) fields and clipped entries such as High-quality primary/review,. |
| 6 | 6. Base-Agreement Ledger | Evidence-verification surface for checking sources, support quality, and the audit trail. Public preview exposes Base claim / program, Base claim text, Currency-check source, Latest June-2026 finding fields and clipped entries such as F1, Barth syndrome. |
| 7 | 7. Cross-Study Merge Map | Workbook surface supporting a specific evidence, decision, study-planning, or release-control workflow. Public preview exposes Cluster (shared id), Consolidated finding, merged_claim_ids (source UUIDs -., Consolidated framing fields and clipped entries such. |
| 8 | 8. Permanence-Ladder Rung Track | Workbook surface supporting a specific evidence, decision, study-planning, or release-control workflow. Public preview exposes Lesion class, Matched lever (rung), Durability class, Binding blocker fields and clipped entries such as Point-mutation (high. |
| 9 | 9. Heteroplasmy - Set-Point Tra | Segments the field by relevant biology so buyer decisions are not overgeneralized. Public preview exposes Parameter, Value, Tissue / context, Source fields and clipped entries such as Within-muscle threshold, complex I., 13.8%, m.3243A>G muscle. |
| 10 | 10. Transfer-Transplant Asset T | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes Asset / program, Type, Source / sourcing, Indication / organ fields and clipped entries such as McCully / Boston Children's MT, Autologous. |
| 11 | 11. Editing Off-Target-Germline | Captures failure modes and constraints that could invalidate or narrow a program. Public preview exposes Editor / advance, Off-target performance, Germline coupling, Source fields and clipped entries such as DddA11 (activity-enhanced), OFF-TARGET + embryonic. |
| 12 | 12. Allogeneic-Immune (DAMP) Tr | Segments the field by relevant biology so buyer decisions are not overgeneralized. Public preview exposes DAMP / mechanism, Effect, Mitigation, Source fields and clipped entries such as Circulating mtDNA -> TLR9, aggravates post-ischemic recovery, TLR9. |
| 13 | 13. Trial - Catalyst Tracker | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes NCT, Title, Sponsor, Status / phase fields and clipped entries such as NCT07531251, Phase 3b/4, Randomized,., Stealth BioTherapeutics Inc.. |
| 14 | 14. Safety - Failure-Mode Track | Captures failure modes and constraints that could invalidate or narrow a program. Public preview exposes Hazard, Rung, Denominator term, Mitigation / readout fields and clipped entries such as Off-target mtDNA editing, Edit, Off-Target/Germline-Tax. |
| 15 | 15. PMC Input Template | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Lesion class (CODE 1-6), 1=point-mutation,., (enter on sheet 16) fields and clipped entries such as Heteroplasmy margin (0-3), distance above. |
| 16 | 16. PMC Feature Score & Output | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Source directness (evidence base), Adjacent / Inferential - 0 Direct. fields and clipped entries such as Matched lever, Transfuse, Second-best lever. |
| 17 | 17. PMC Decision Rules | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Lesion code, Lesion class, Matched lever, Required next experiment fields and clipped entries such as point-mutation, Edit (DdCBE/TALED),. |
| 18 | 18. PMC Minimum Assay Panel | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Assay / readout, Tier, Measures, Source / note fields and clipped entries such as Heteroplasmy fraction (ddPCR/NGS), Required, mutant mtDNA load. |
| 19 | 19. PMC Archetype Cards | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Archetype profile, Lesion code, Margin, Durability fields and clipped entries such as NARP/MELAS high-heteroplasmy point., Edit,. |
| 20 | 20. PMC Validation Log | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes component, scenario_id, profile, input_vector_or_protocol fields and clipped entries such as Protocol, F1, all lesion classes. |
| 21 | 21. PMC Traceability Map | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes finding, lever, model_factor, evidence_id fields and clipped entries such as F1, Small-molecule, set-point. |
| 22 | 22. Hypotheses Ledger | Maps hypotheses to evidence state, falsification logic, endpoints, and next-study design. Public preview exposes ID, Tier, Axis, Primary endpoint fields and clipped entries such as F1, Flagship, Heteroplasmy-threshold x durability.. |
| 23 | 23. Next Studies + Gates | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Study / gate, Family, Tests, Links fields and clipped entries such as 1. PMC validation cohort, Model, lever-matched vs default on.. |
| 24 | 24. Competitive Landscape | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes company, asset / platform, modality, target / indication fields and clipped entries such as Stealth BioTherapeutics, FORZINITY (elamipretide),. |
| 25 | 25. Verification - Search Log | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes Base-Agreement adjudication, per-claim currency verdict +., 79 rows; 67 confirmed-current, 6. fields and clipped entries such as. |
| 26 | 26. Excluded + Salvage | Disposition log for rejected, bounded, or quarantined claims so they do not leak into the decision thesis. Public preview exposes Item, Bucket, Reason / source, Disposition / note fields and clipped entries such as Excluded 14 — NIH grant., offtopic,. |
| 27 | 27. Quarantine Register | Disposition log for rejected, bounded, or quarantined claims so they do not leak into the decision thesis. Public preview exposes NIH:R00HL168312-04, grant, Cardiac lactate metabolism; MCT4., NIH RePORTER grant abstract; no. fields and clipped entries such. |
| 28 | 28. Power Calculations | Power-calculation layer for assumptions, endpoint logic, computed sample sizes, and sensitivity checks. Public preview exposes hypothesis_id, study_id, endpoint, test_type fields and clipped entries such as F1, S1-PMC, Functional-responder, lever-matched.. |
| 29 | 29. Score Basis | Explains how scores or ratings were assigned so the decision instrument can be inspected. Public preview exposes Fresh citation grade, Moderate / Low, journal tier x design x. fields and clipped entries such as Directness, Adjacent / Inferential, 0 Direct. |
| 30 | 30. Figure Source Map | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes figure_id, figure_title, figure_family, section_anchor fields and clipped entries such as Figure 5, Citation re-grade across the 71. |
| 31 | 31. Figure Attempt Ledger | Figure and numeric reproduction log for validating calculations, chart inputs, or displayed values. Public preview exposes attempt_id, figure_family, attempt_method, backend fields and clipped entries such as fig01_grade_recalibration,. |
| 32 | 32. Traceability Certificate | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes claim_id, report_section, report_page, claim_text fields and clipped entries such as F1, Key Findings; Regulatory, section anchor: Key. |
| 33 | 33. Version Registry | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes version_item, date, detail, status fields and clipped entries such as v1.0 Dossier (report + workbook +., 2026-06-13, Initial premium. |
| 34 | 34. Audit Issues Log | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes audit_item, date, detail, status fields and clipped entries such as Evaluator warning 1 (merge clusters), 2026-06-13, 5 clusters. |
| 35 | 35. Figure Numeric Value Map | Figure and numeric reproduction log for validating calculations, chart inputs, or displayed values. Public preview exposes figure_id, file, plotted_element, value fields and clipped entries such as Figure 5, fig01_grade_recalibration.png, source strict High. |
| 36 | 36. Grok Provenance Ledger | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes figure_id, final_file, original_prompt_or_prompt_pointer, prompt_source_script fields and clipped entries such as Figure 1,. |
| 37 | 37. Currentness Maintenance | Monitoring surface for emerging signals, update triggers, and evidence changes that could alter the decision. Public preview exposes cadence, source_surface, exact_query_or_source, trigger_for_update fields and clipped entries such as 60 days, PubMed / NCBI. |
Power-calculated next studies
Power calculations are the execution bridge.
Power calculations are planning-grade research calculations for endpoint logic, assumptions, sample size, budget, and timeline. They do not prove hypotheses or constitute clinical protocol.
| Hypothesis | Primary endpoint | Test | Effect | α | Power | Computed n | Design n |
|---|---|---|---|---|---|---|---|
| F1 | Functional-responder, lever-matched vs default | Two-proportion (pooled) | 0.55 | 0.05 | 0.80 | 61 | 72 |
| F1b | Held-out classifier AUC vs baseline | AUC (Hanley-McNeil, external) | 0.8 | 0.05 | 0.80 | 176 | 176 |
| F2 | Cross-organ ATP recovery, transfusion vs vehicle | Two-sample means | 0.6 | 0.05 | 0.80 | 44 | 52 |
| F3 | Distance-to-threshold high vs low functional benefit | Two-sample means (Cohen d) | 0.5 | 0.05 | 0.80 | 63 | 63 |
| F4 | Editors passing off-target/germline gate | Two-proportion (pooled) | 0.9 | 0.05 | 0.80 | 20 | 24 |
Release audit discipline
Audit posture is part of the product.
Public pages do not publish exact audit scores. They should state the release discipline, revision posture, and limitations without implying peer review or validated clinical guidance.
Research-use decision package
Not medical advice, clinical guidance, investment advice, or a clinical protocol.
Known / inferred / hypothetical
The package separates cited evidence from inference and frontier hypothesis generation.
Audit-gated and revision-controlled
Adversarial audit checks source support, formulas, figures, limitations, and release readiness.
Buy this dossier
Full decision package — 100-page report + 37-sheet workbook
Buy now
- Decision research report (100 pages, PDF)
- Evidence & Decision Workbook (37 sheets, .xlsx) — claims, source-support verdicts, power calculations, traceability, and audit log
- Live, editable power-calculated next studies
$3,500$5,500Launch price