Research Note 07 · Published May 2026
Defensive publication of 1,908,879 sequence-distinct allosteric peptide modulator candidates targeting the MT1 and MT2 melatonin receptors, dedicated to the public domain as prior art under 35 U.S.C. §102 and analogous foreign-jurisdiction novelty provisions (EU, UK, JP, CN). 35,198 unique linear backbones × 90 form-variant chemistries spanning seven chemistry families (lipidation, PEGylation, glycosylation, Fc fusion, prodrug, glucuronidation, macrocyclization). Three-tier disclosure architecture: 100 Tier 1 deep-dossier candidates with 15-section per-candidate HTML, 1,000 Tier 2 table-form stubs, 1,907,779 Tier 3 manifest-only entries plus a WIPO Standard ST.26 Sequence Listing at the unique-backbone level for examiner-side BLAST searchability. The universal-protocol package satisfies §102 enablement under the In re Wands factors with eight family-level synthesis protocols and three form-variant-independent characterization protocols (radioligand-displacement binding assay, cAMP HTRF functional readout with Christopoulos-Kenakin allosteric cooperativity discrimination, RP-HPLC + ESI-MS + AAA QC). Bundle SHA-256 anchored to Bitcoin via OpenTimestamps.
disclosure landing · Zenodo deposit and full bundle in the archive
Research Note 06 · Published May 2026
A public reference catalog of 84 aging-dysregulated human miRNAs with integrated dossiers covering López-Otín hallmark mapping, centenarian-signature classification across six independent cohort studies, predicted target footprint, GTEx v8 tissue exposure, mouse and rat ortholog mapping, SenMayo SASP overlay, top fifteen HIGH-tier predicted targets, and freedom-to-operate clearance across six antisense modulator chemistries against a 5,596-patent corpus. Twenty-five candidates pass the canonical antisense chemistry without HIGH or MEDIUM patent encumbrance and are publishable at canonical specificity. Six SASP-axis candidates clear at canonical chemistry as a senolytic discovery panel. Hero candidate miR-130a-3p hits all three independent evidence axes simultaneously: SASP-axis, centenarian-preserved, and IP-clean canonical.
catalog landing · Zenodo deposit and full bundle in the archive
Research Note 05 · Published April 2026
A closed-form multi-region human miRNA target binding affinity atlas across 3'UTR, 5'UTR, and CDS, with computational m6A modulation flag. 2,656 mature human miRNAs (miRBase v22) by 19,542 canonical human protein-coding transcripts (GENCODE v47); 153,160,752 (miRNA, transcript, region) predictions in a single SQLite database. The CDS pipeline validates against an n=25 literature panel; the 5'UTR pipeline validates against an n=18 scanning + n=2 cap-proximity literature panel; the 3'UTR pipeline validates at Pearson R = 0.847 against single-molecule kinetics and AUC = 0.9339 multi-site against TarBase v9. CLIP-seq concordance bench reports median top-100 enrichment 2.83× across n=602 miRNAs; the drug-design demonstration recovers 37/37 published on-target genes across five clinical-stage miRNA therapeutics.
dataset landing · Zenodo deposit and full bundle in the archive
Research Note 04 · Published April 2026
The GLP-1 family is the most commercially valuable peptide drug class in modern pharmaceuticals. Approved members (semaglutide, liraglutide, tirzepatide, dulaglutide, exenatide) and clinical-stage molecules (retatrutide, cotadutide, survodutide, mazdutide, cagrilintide) collectively underpin a market exceeding USD 100 billion in projected annual sales. The originator IP estate is concentrated and weakly differentiated at the sequence level: most claims rest on small substitution patterns around a conserved central scaffold, and the extant patent corpus does not adequately disclose the full sequence space surrounding each approved peptide. This drop publishes 3,800 novel sequence-distinct analogs across five structural classes as public-domain prior art under 35 U.S.C. §102. 82 candidates are immediately bench-ready (Kd ≤ 1 nM at primary target, required dose ≤ 100 mg/week at PIONEER-1 anchor); a single Tier A candidate is bench-validatable for approximately USD 7-12k and 2-3 weeks of parallel synthesis-and-assay work.
disclosure landing · Zenodo deposit and full bundle in the archive
Research Note 03 · Published April 2026
Rybelsus is oral semaglutide at about one-percent bioavailability. The same absorption ceiling applies to the full metabolic-peptide class at three-to-five-kilodalton molecular weight: liraglutide, tirzepatide, exenatide, cagrilintide, retatrutide, survodutide. Ninety-nine percent of every swallowed dose is wasted, and that ratio sets the retail-price floor across the category. This drop publishes an integrated multi-mechanism oral tablet at class level, covering all seven clinically relevant peptides simultaneously, with predicted human bioavailability four to fourteen percent theoretical, two to fourteen times Rybelsus.
approx. 28 min read · technical disclosure, PDF, and Zenodo DOI in the archive
Research Note 02 · Published April 2026
A Starship-class Mars departure burn requires the receiver vehicle to aggregate close to its full 1500-ton methalox load in low Earth orbit across a multi-flight tanker campaign. Ship-to-ship cryogenic transfer at this scale has not flown. The aggregation campaign raises six coupled cryogenic fluid-management problems, each absent from SpaceX's public patent record. This note works each pain point from first principles and publishes the integrated six-subsystem architecture as a §102 defensive publication.
approx. 22 min read · technical disclosure, PDF, and Zenodo DOI in the archive
Research Note 01 · Published April 2026
The first deployed cohort of Bloom's solid-oxide stacks fell well short of the ten-year service-life expectation. Three mechanisms on the cathode side degrade the cell at once, and industry mitigation addresses only the most visible. This note works each mechanism from first principles and specifies a graded-microstructure cathode architecture that suppresses all three with minimal changes to the existing co-fire process flow.
approx. 20 min read · technical disclosure, PDF, and Zenodo DOI in the archive
