SYBEL-KRONOS: Sentetik Biyolojik Devreler ve Hücresel Bilgi İşlem için Açık Matris Protokolü

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1. Verfasser: Muzaffer enes yünlü
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Veröffentlicht: Zenodo 2026
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author Muzaffer enes yünlü
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contents <p>SYBEL-KRONOS V2.0 – Synthetic Biology Circuits for Cellular Decision-Making (Defensive Publication / Prior Art)</p> <p> </p> <p>Published by: Muzaffer Enes Yünlü</p> <p>License: CC BY-NC-SA 4.0</p> <p>Legal status: Publicly available technical document – constitutes prior art under patent law</p> <p> </p> <p>---</p> <p> </p> <p>What is this document?</p> <p> </p> <p>This document describes three concrete synthetic biology circuits that enable living cells to make logical decisions.</p> <p> </p> <p>Each circuit reads specific biomarkers, applies AND/OR logic, and produces a therapeutic output (insulin, IL-10, or apoptosis).</p> <p> </p> <p>Purpose: To prevent others from patenting these circuits and keep them in the public domain.</p> <p> </p> <p>---</p> <p> </p> <p>Scope – 3 Concrete Circuits</p> <p> </p> <p>Circuit Condition Inputs Logic Output Cell Line</p> <p>1 Type 2 Diabetes Glucose > 180 mg/dL, Insulin < 0.5 ng/mL AND Insulin HEK293</p> <p>2 Chronic Inflammation IL-6 > 50 pg/mL, TNF-α > 20 pg/mL OR IL-10 Jurkat (T cell)</p> <p>3 DNA Damage ROS > 0.1 μM, p53 < 0.5 ng/mL AND Apoptosis (CASP3) HeLa</p> <p> </p> <p>Concrete Measurement Methods (with Catalog Numbers)</p> <p> </p> <p>· Glucose: Abbott Freestyle Libre (fluorescence sensor)</p> <p>· Insulin / IL-6 / TNF-α / p53: ELISA (Mercodia, R&D Systems)</p> <p>· ROS: Amplex Red (Thermo Fisher A12222)</p> <p> </p> <p>---</p> <p> </p> <p>Memory Mechanisms (3 examples)</p> <p> </p> <p>1. Permanent silencing via DNA methylation (Tet-On + DNMT3a, doxycycline-triggered)</p> <p>2. Flip-Flop circuit (Set-Reset, IPTG / glucose)</p> <p>3. Long-term silencing via CRISPRi (dCAS9-KRAB, doxycycline-triggered)</p> <p> </p> <p>---</p> <p> </p> <p>Kill-Switch Integration (4 layers, inherited from APROS-V9.2)</p> <p> </p> <p>Layer Mechanism Trigger</p> <p>1 Degron (FKBP12-F36V + dTAG-13) Time > 24 hours</p> <p>2 Tissue-specific miRNA Wrong tissue (miR-122/1/124/142)</p> <p>3 CRISPRi (dCAS9-KRAB) Unwanted expression</p> <p>4 Intracellular sensor p53 > λ1, ROS > λ2, ATP < λ3</p> <p> </p> <p>Condition: ANY trigger TRUE → circuit halts, apoptosis begins</p> <p> </p> <p>---</p> <p> </p> <p>What is covered as prior art?</p> <p> </p> <p>· The 3 circuits + 3 memory mechanisms + 4 kill-switch layers above</p> <p>· Obvious variations (under KSR v. Teleflex, 2007):</p> <p>  · ±20% change in threshold values</p> <p>  · Routine optimization (dose-response)</p> <p>  · Transfer to similar cell lines (HEK293 → HEK293T / HeLa; Jurkat → primary T cells)</p> <p>  · Changing trigger doses</p> <p> </p> <p>Total covered configurations: ~24 variations (mathematically bounded, no exaggeration)</p> <p> </p> <p>---</p> <p> </p> <p>What is NOT covered?</p> <p> </p> <p>· Biomarker combinations other than the 3 circuits above</p> <p>· Different logic gates (NAND, NOR, XOR, etc.)</p> <p>· The full 256-biomarker list (only 6 have measurement methods)</p> <p>· Any efficacy claims (e.g., “this circuit cures cancer”) – only “if X then Y” is defined</p> <p>· Kill-switch layers outside APROS</p> <p> </p> <p>---</p> <p> </p> <p>Who is this for?</p> <p> </p> <p>· Patent offices (prior art search)</p> <p>· Synthetic biologists, molecular biologists, bioengineers</p> <p>· Cell therapy companies</p> <p>· Open science advocates</p> <p> </p> <p>---</p> <p> </p> <p>How to cite?</p> <p> </p> <p>Yünlü, M. E. (2026). SYBEL-KRONOS V2.0: Defensive Publication and Prior Art Document – Synthetic Biology Circuits. Zenodo.</p> <p>(Original concept: April 5, 2026; this version: April 14, 2026)</p> <p> </p> <p>---</p> <p> </p> <p>Not / Note:</p> <p>Bu dokümanda tanımlanmayan hiçbir şey için prior art iddiasında bulunulmaz.</p> <p>No prior art is claimed for anything not explicitly defined in this document.</p> <p> </p> <p>---</p>
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spellingShingle SYBEL-KRONOS: Sentetik Biyolojik Devreler ve Hücresel Bilgi İşlem için Açık Matris Protokolü
Muzaffer enes yünlü
<p>SYBEL-KRONOS V2.0 – Synthetic Biology Circuits for Cellular Decision-Making (Defensive Publication / Prior Art)</p> <p> </p> <p>Published by: Muzaffer Enes Yünlü</p> <p>License: CC BY-NC-SA 4.0</p> <p>Legal status: Publicly available technical document – constitutes prior art under patent law</p> <p> </p> <p>---</p> <p> </p> <p>What is this document?</p> <p> </p> <p>This document describes three concrete synthetic biology circuits that enable living cells to make logical decisions.</p> <p> </p> <p>Each circuit reads specific biomarkers, applies AND/OR logic, and produces a therapeutic output (insulin, IL-10, or apoptosis).</p> <p> </p> <p>Purpose: To prevent others from patenting these circuits and keep them in the public domain.</p> <p> </p> <p>---</p> <p> </p> <p>Scope – 3 Concrete Circuits</p> <p> </p> <p>Circuit Condition Inputs Logic Output Cell Line</p> <p>1 Type 2 Diabetes Glucose > 180 mg/dL, Insulin < 0.5 ng/mL AND Insulin HEK293</p> <p>2 Chronic Inflammation IL-6 > 50 pg/mL, TNF-α > 20 pg/mL OR IL-10 Jurkat (T cell)</p> <p>3 DNA Damage ROS > 0.1 μM, p53 < 0.5 ng/mL AND Apoptosis (CASP3) HeLa</p> <p> </p> <p>Concrete Measurement Methods (with Catalog Numbers)</p> <p> </p> <p>· Glucose: Abbott Freestyle Libre (fluorescence sensor)</p> <p>· Insulin / IL-6 / TNF-α / p53: ELISA (Mercodia, R&D Systems)</p> <p>· ROS: Amplex Red (Thermo Fisher A12222)</p> <p> </p> <p>---</p> <p> </p> <p>Memory Mechanisms (3 examples)</p> <p> </p> <p>1. Permanent silencing via DNA methylation (Tet-On + DNMT3a, doxycycline-triggered)</p> <p>2. Flip-Flop circuit (Set-Reset, IPTG / glucose)</p> <p>3. Long-term silencing via CRISPRi (dCAS9-KRAB, doxycycline-triggered)</p> <p> </p> <p>---</p> <p> </p> <p>Kill-Switch Integration (4 layers, inherited from APROS-V9.2)</p> <p> </p> <p>Layer Mechanism Trigger</p> <p>1 Degron (FKBP12-F36V + dTAG-13) Time > 24 hours</p> <p>2 Tissue-specific miRNA Wrong tissue (miR-122/1/124/142)</p> <p>3 CRISPRi (dCAS9-KRAB) Unwanted expression</p> <p>4 Intracellular sensor p53 > λ1, ROS > λ2, ATP < λ3</p> <p> </p> <p>Condition: ANY trigger TRUE → circuit halts, apoptosis begins</p> <p> </p> <p>---</p> <p> </p> <p>What is covered as prior art?</p> <p> </p> <p>· The 3 circuits + 3 memory mechanisms + 4 kill-switch layers above</p> <p>· Obvious variations (under KSR v. Teleflex, 2007):</p> <p>  · ±20% change in threshold values</p> <p>  · Routine optimization (dose-response)</p> <p>  · Transfer to similar cell lines (HEK293 → HEK293T / HeLa; Jurkat → primary T cells)</p> <p>  · Changing trigger doses</p> <p> </p> <p>Total covered configurations: ~24 variations (mathematically bounded, no exaggeration)</p> <p> </p> <p>---</p> <p> </p> <p>What is NOT covered?</p> <p> </p> <p>· Biomarker combinations other than the 3 circuits above</p> <p>· Different logic gates (NAND, NOR, XOR, etc.)</p> <p>· The full 256-biomarker list (only 6 have measurement methods)</p> <p>· Any efficacy claims (e.g., “this circuit cures cancer”) – only “if X then Y” is defined</p> <p>· Kill-switch layers outside APROS</p> <p> </p> <p>---</p> <p> </p> <p>Who is this for?</p> <p> </p> <p>· Patent offices (prior art search)</p> <p>· Synthetic biologists, molecular biologists, bioengineers</p> <p>· Cell therapy companies</p> <p>· Open science advocates</p> <p> </p> <p>---</p> <p> </p> <p>How to cite?</p> <p> </p> <p>Yünlü, M. E. (2026). SYBEL-KRONOS V2.0: Defensive Publication and Prior Art Document – Synthetic Biology Circuits. Zenodo.</p> <p>(Original concept: April 5, 2026; this version: April 14, 2026)</p> <p> </p> <p>---</p> <p> </p> <p>Not / Note:</p> <p>Bu dokümanda tanımlanmayan hiçbir şey için prior art iddiasında bulunulmaz.</p> <p>No prior art is claimed for anything not explicitly defined in this document.</p> <p> </p> <p>---</p>
title SYBEL-KRONOS: Sentetik Biyolojik Devreler ve Hücresel Bilgi İşlem için Açık Matris Protokolü
url https://doi.org/10.5281/zenodo.19592444