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From First Principles

Lester Nare and Krishna Choudhary
From First Principles
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  • FFP EP. 15 | AI-Generated Genomes, Retinal Implants, and Palomar’s Mystery Lights Explained
    AI, Eyes, and the Sky — From Synthetic Genomes to Restored Vision and Cosmic MysteriesHosted by Lester Nare and Krishna Choudhary, this episode of From First Principles explores three cutting-edge breakthroughs connecting medicine, technology, and astronomy.Summary• AI for Oncology, Minus the Privacy Risk: University of Toronto researchers develop OncoGAN—a generative model that creates realistic synthetic cancer genomes to accelerate precision oncology while protecting patient data.• Restoring Sight: The PRIMA (PRIMAvera) trial in NEJM demonstrates how a wireless sub-retinal photovoltaic implant can restore central vision in people with advanced macular degeneration.• Revisiting Cosmic Transients: New analyses of Palomar’s POSS-I plates re-examine the “multi-point transients” with fresh alignment statistics and an innovative Earth’s-shadow control test.Show Notes• University of Toronto — OncoGAN / Synthetic Cancer Genomes (Cell Genomics)• NEJM — PRIMA (PRIMAvera) Wireless Sub-Retinal Implant Trial for Geographic Atrophy• Palomar POSS-I Plates — Multi-Point Transient Analysis (IOP PASP Paper)• Palomar Alignment vs Earth’s Shadow Control (Nature Scientific Reports 2025)
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  • FFP EP. 14 | Chen Ning Yang — The Man Who Unlocked Symmetry
    Hosted by Lester Nare and Krishna Choudhary, this episode tells the story of Nobel laureate Chen Ning Yang and how his ideas on symmetry and gauge theory transformed modern physics.Summary• Early Years & Mentorship: From China to Chicago — learning under Fermi and Chandrasekhar.• Parity Violation: How Yang & Lee overturned the mirror-symmetry assumption and changed physics forever.• Gauge Symmetry & Yang-Mills Fields: The foundation of the Standard Model of particle physics.• Legacy & Philosophy: Why Yang saw beauty as nature’s signature and symmetry as its language.Show Notes• Nobel Prize in Physics 1957 — Chen Ning Yang & Tsung-Dao Lee• Original Yang–Mills Paper (1954, Physical Review)• Madame Wu’s Parity Violation Experiment (1957)• Biography of Subrahmanyan Chandrasekhar (University of Chicago)
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  • FFP EP. 13 | Portable Muon Beams, Sodium Batteries, and the Secret to Long Life
    Aloha internet — Lester Nare and Krishna Choudhary return with three extraordinary research stories: portable muon beams, sodium-ion batteries, and the secret to long life.Summary• Lawrence Berkeley’s compact muon beam technology and its applications in archaeology, volcanology, and security.• UC San Diego + U Chicago’s solid-state sodium battery that rivals lithium in power but not in cost.• Tongji University’s naked mole rat DNA study uncovering a genetic pathway for longer, healthier life.Show NotesPortable Muon BeamNature News CoveragePhysical Review Accelerators and Beams PaperSodium Ion BatteriesScience Daily CoverageJoule Paper (2025)Naked Mole Rats & LongevityBBC CoverageScience Journal Paper
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  • FFP EP. 12 | From Princeton to the Nobel Prizes — How FFP Started + 2025 Nobel Recap
    After a packed week of Nobel Prize coverage, Lester and Krishna look back on how From First Principles began and why they built it as an “ESPN for Science.” They revisit 2025’s Medicine, Physics and Chemistry winners and discuss why fundamental research and immigration policy are core to America’s scientific edge.Quick note: this week’s episode is in vertical format because of a technical hiccup during recording — back to widescreen next week!SummaryOrigin Story — Two Princeton friends from different continents unite around a shared love of science and storytelling.The Mission — Creating an “ESPN for Science” that celebrates research and the people behind it.Nobel Follow-ups — Medicine (Tregs and non-immune roles), Physics (macroscopic quantum tunneling and quantum supremacy), Chemistry (MOFs and industrial scaling).Funding + Immigration — Why public research grants and curating global talent are vital to scientific leadership.Show NotesNobel Prize Press Release (2025 Medicine)Nobel Prize Press Release (2025 Physics)Nobel Prize Press Release (2025 Chemistry)Nature Genetics (2001) — FOXP3 Mutation Causes DysregulationNature (1999) — MOF-5 Discovery (Omar Yaghi et al.)Google Quantum AI Lab — Quantum Supremacy (Nature, 2019)
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  • FFP EP. 11 | From Cells to Circuits to Crystals — 2025 Nobel Prizes Unpacked
    Hosted by Lester Nare and Krishna Choudhary, this one-episode special brings all three 2025 Nobel Prizes in the sciences into a single listen: Medicine (immune tolerance and FOXP3), Physics (macroscopic quantum tunneling in superconducting circuits), and Chemistry (metal–organic frameworks and “new rooms for chemistry”).SummaryMedicine: Regulatory T cells and the FOXP3 gene that prevent autoimmune disease.Physics: Macroscopic quantum tunneling and energy quantization in electrical circuits — the bridge to today’s qubits.Chemistry: Metal–Organic Frameworks (MOFs) — modular porous crystals enabling CO₂ capture, water harvesting, and hydrogen storage.Show Notes Nobel Prize Press Release (2025 Medicine) Nature Genetics (2001) — FOXP3 mutation and IPEX link Nature Genetics (2001) — FOXP3 Mutation Causes Dysregulation Nature Genetics (2001) — FOXP3 Gene Cause IPEX Syndrome Science (2003) — FOXP3 function in regulatory T cells German Journal of Immunology (1995) — Sakaguchi’s first Treg paper Nobel Prize Press Release (2025 Physics) Physical Review Letters (1980s) — Macroscopic Quantum Tunneling Experiments (UC Berkeley) BCS Theory (1972 Nobel) — Bardeen, Cooper & Schrieffer, University of Illinois Josephson Effect (1973 Nobel) — Brian D. Josephson Google Quantum AI Lab — Quantum Supremacy Paper (Nature, 2019) Nobel Prize Press Release (2025 Chemistry) Nature (1999) — MOF-5 Discovery (Omar Yaghi et al.) Science (2003) — Reticular Chemistry Foundations Journal of the American Chemical Society (1989, 1990) — Richard Robson’s Early Frameworks Lawrence Berkeley National Laboratory — ChatMOF and AI-Assisted Materials Discovery
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About From First Principles

We break down the week’s biggest science headlines from first principles—because understanding the world shouldn’t require a PhD.
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