Compound delivery / Source audit with conditional calculations
See assay and PK eligibility results
MOTS-c persistence claims depend on what the assay measures
Signal-to-detection-limit scale separation is not true concentration or universal assay failure. One steady-state immunoreactive measurement does not identify intact-parent half-life or oral availability; donor-linked repair data remain unavailable.
{
"status": "Source-data unavailability qualified; authorized pivot to primary analytical specificity and PK intake",
"inputs_sha256_lf_text": "0a22838bfeac0f27d19b0c0ce6715f532ad74816f17f02d0ab1e6062242eea0e",
"hash_convention": "UTF-8 text after universal-newline normalization to LF",
"MSC_units": {
"human_donors": 12,
"recipient_mice": 36,
"combined_independent_sample_size": null,
"histology_field_n_can_replace_mouse_n": false,
"donor_linkage": {
"numerical_donor_linked_metabolism_repair_reanalysis_eligible": false,
"missing": [
"numeric_metabolic_values",
"numeric_repair_values",
"stable_individual_donor_ids",
"culture_to_donor_crosswalk",
"recipient_to_donor_crosswalk",
"endpoint_unit_hierarchy_resolved"
],
"effect_or_correlation_estimate": null
}
},
"analytical_scale_comparison": {
"reported_LLOD_ng_per_mL": 0.1,
"reported_ELISA_signal_range_ng_per_mL": [
45.9,
218.5
],
"reported_ELISA_signal_to_LLOD_scale_ratio_range": [
458.99999999999994,
2185.0
],
"n_reference_subjects": 20,
"individual_paired_concentrations_available": false,
"true_intact_parent_concentrations": null,
"assay_bias_or_cross_reactivity_estimate": null,
"universal_ELISA_failure_inferred": false,
"interpretation": "Reported immunoassay-signal/LCMS-detection-limit scale separation only; not a true concentration bound, specificity proof, calibration slope, or PK parameter."
},
"steady_state_identity": {
"expression": "C_ss = F * R / CL",
"scope": "Simple linear steady-state parent mass balance; R is administered parent input rate, F its systemic fraction, C_ss its exogenous intact-parent increment with endogenous contribution resolved.",
"half_life_expression": "t_half = ln(2) * V / CL",
"half_life_scope": "One-compartment linear disposition (or appropriate terminal distribution volume); neither V nor terminal slope follows from one steady-state immunoreactive concentration.",
"K14Q_reported_apparent_clearance_slowing_factor": 2.6,
"variant_specific_plasma_calibration_preserved": true,
"interpretation": "Variant-specific calibration corrects lower assay sensitivity and is real evidence. It does not resolve intact molecular species, every product's cross-reactivity, endogenous baseline, input F or a decay half-life. Knoop's different commercial assay does not universally invalidate it.",
"new_native_clearance_or_half_life_estimate": null
},
"pk_eligibility": [
{
"case_id": "MSC_cell_pretreatment",
"context": "cell_pretreatment",
"reported_timepoint_count": 0,
"finite_interval_parent_AUC_intake_eligible": false,
"terminal_half_life_intake_eligible": false,
"absolute_parent_clearance_from_AUC_intake_eligible": false,
"absolute_oral_F_intake_eligible": false,
"missing_for_AUC": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs"
],
"missing_for_terminal_half_life": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"sufficient_terminal_phase_sampling"
],
"missing_for_absolute_clearance_from_AUC": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"systemic_input_fraction_known",
"administered_parent_amount_known",
"complete_parent_AUC_or_qualified_extrapolation"
],
"missing_for_oral_F": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"paired_oral_iv_parent_auc_available",
"dose_normalization_known",
"route_comparison_context_qualified",
"both_routes_complete_parent_AUC_or_qualified_extrapolation"
],
"numerical_AUC_half_life_clearance_or_F": null,
"gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate."
},
{
"case_id": "Knoop_endogenous_reference",
"context": "endogenous_observation",
"reported_timepoint_count": 0,
"finite_interval_parent_AUC_intake_eligible": false,
"terminal_half_life_intake_eligible": false,
"absolute_parent_clearance_from_AUC_intake_eligible": false,
"absolute_oral_F_intake_eligible": false,
"missing_for_AUC": [
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs"
],
"missing_for_terminal_half_life": [
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"sufficient_terminal_phase_sampling"
],
"missing_for_absolute_clearance_from_AUC": [
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"systemic_input_fraction_known",
"administered_parent_amount_known",
"complete_parent_AUC_or_qualified_extrapolation"
],
"missing_for_oral_F": [
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"paired_oral_iv_parent_auc_available",
"dose_normalization_known",
"route_comparison_context_qualified",
"both_routes_complete_parent_AUC_or_qualified_extrapolation"
],
"numerical_AUC_half_life_clearance_or_F": null,
"gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate."
},
{
"case_id": "Knoop_storage_caption",
"context": "sample_storage",
"reported_timepoint_count": 0,
"finite_interval_parent_AUC_intake_eligible": false,
"terminal_half_life_intake_eligible": false,
"absolute_parent_clearance_from_AUC_intake_eligible": false,
"absolute_oral_F_intake_eligible": false,
"missing_for_AUC": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs"
],
"missing_for_terminal_half_life": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"sufficient_terminal_phase_sampling"
],
"missing_for_absolute_clearance_from_AUC": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"systemic_input_fraction_known",
"administered_parent_amount_known",
"complete_parent_AUC_or_qualified_extrapolation"
],
"missing_for_oral_F": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"administered_systemic_route_known",
"serial_concentration_time_data",
"in_vivo_systemic_administration_context",
"at_least_two_quantified_concentration_time_pairs",
"paired_oral_iv_parent_auc_available",
"dose_normalization_known",
"route_comparison_context_qualified",
"both_routes_complete_parent_AUC_or_qualified_extrapolation"
],
"numerical_AUC_half_life_clearance_or_F": null,
"gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate."
},
{
"case_id": "K14Q_pump_ELISA",
"context": "steady_state_extravascular_infusion",
"reported_timepoint_count": 1,
"finite_interval_parent_AUC_intake_eligible": false,
"terminal_half_life_intake_eligible": false,
"absolute_parent_clearance_from_AUC_intake_eligible": false,
"absolute_oral_F_intake_eligible": false,
"missing_for_AUC": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"serial_concentration_time_data",
"at_least_two_quantified_concentration_time_pairs"
],
"missing_for_terminal_half_life": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"serial_concentration_time_data",
"at_least_two_quantified_concentration_time_pairs",
"sufficient_terminal_phase_sampling"
],
"missing_for_absolute_clearance_from_AUC": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"serial_concentration_time_data",
"at_least_two_quantified_concentration_time_pairs",
"systemic_input_fraction_known",
"administered_parent_amount_known",
"complete_parent_AUC_or_qualified_extrapolation"
],
"missing_for_oral_F": [
"source_reports_parent_specific_detection",
"source_reports_quantitative_matrix_assay_validation",
"baseline_or_endogenous_component_resolved",
"serial_concentration_time_data",
"at_least_two_quantified_concentration_time_pairs",
"paired_oral_iv_parent_auc_available",
"dose_normalization_known",
"route_comparison_context_qualified",
"both_routes_complete_parent_AUC_or_qualified_extrapolation"
],
"numerical_AUC_half_life_clearance_or_F": null,
"gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate."
}
],
"eligible_numerical_parent_pk_datasets": 0,
"oral_F_assigned": null,
"delivery_or_analogue_functional_rank": null,
"source_observations_digitized_or_synthesized": false
}