links 1/6/25: https://roamresearch.com/#/app/srcpublic/page/01-06-2025

• https://en.m.wikipedia.org/wiki/Ralph_Fiennes descended from Norman nobility
• https://meltingasphalt.com/wealth-the-toxic-byproduct/ nice essay on how (money) earnings generally represent your benefit to others while consumption spending is a cost to others
• https://mises.org/mises-daily/defending-miser not only is the "miser" who invests productively benefiting others, but so is the "hoarder" who takes money out of circulation to put under a mattress -- hoarders lower prices.
  • ehhh, shouldn't lowering prices and raising prices be seen as equally neutral in real terms?
• https://timmermanreport.com/2025/01/ai-needs-natural-language-to-give-structure-to-biology/ I'm sorry, you just named three discoveries in the latest table of contents of Science or Nature, and complained that biological "foundation models" can't come up with them, and that instead you need LLMs? what are you even thinking???
  • you are in a hurry to replace human thought at the highest levels, when there's a tremendous amount left to be done in developing AIs to replace tedious grunt work.
  • why??? why do you want to put the PI out of a job? There aren't that many PIs. why are you starting here? it's so backwards.
  • what they're actually doing at FutureHouse is pretty cool: "write an accurate and cited Wikipedia-style article for nearly every protein-coding gene in the human genome." I think accelerating lit review is a useful function of LLMs. there's a lot of information out there! using automation to synthesize it is a win!
  • but my god, man, why are you framing this as "I really want the machine to do all the thinking for me" rather than "I want everyone to have a research assistant in their pocket so they can more efficiently explore hypotheses with the context of the whole scientific literature." do you not like thinking and learning? do you wish you could quit or something???
• https://blog.samaltman.com/reflections
  • "We believe that, in 2025, we may see the first AI agents “join the workforce” and materially change the output of companies." Ok, this is a real prediction (that we can grade him on later) and it certainly seems technologically possible today -- it remains to be seen whether it'll be organizationally possible, useful in the first contexts where it's used, or whether it'll cause catastrophic errors.
    • if i had to guess, i think commercial AI agents will be launched by OpenAI, and their economic impact will be ambiguous, by end of 2025.
• https://parahumans.wordpress.com/ trying to read this, again, for the fourth? time.
  • not sure why I keep bouncing off this. it's recommended by friends, I'm excited by the promise of interesting conceptual things being done with the superhero-genre system, but my god there are many chapters of "boring"-to-me stuff (action scenes, description of city politics & class dynamics that doesn't feel true to life, etc)
• ketamine overdose risks:
  • https://pmc.ncbi.nlm.nih.gov/articles/PMC3168228/
    • typical recreational doses are 200-300 mg (orally) or 50-100mg IV, roughly 50x the effective IV dose for general anaesthesia.
  • https://www.psychiatrist.com/jcp/oral-ketamine-for-depression-practical-considerations/
    • similarly, oral ketamine for depression is given in doses ranging from 25mg to 300 mg
  • https://www.ncbi.nlm.nih.gov/books/NBK541087/ this StatPearls claims that the median lethal dose for a 70kg human is 678 mg, but references a study not cited
  • https://www.researchgate.net/profile/Robert-Gable/publication/8167013_Acute_Toxic_Effects_of_Club_Drugs/links/55d4419d08ae7fb244f59d58/Acute-Toxic-Effects-of-Club-Drugs.pdf
    • this is the Gable et al study mentioned in the StatPearls article
    • it mentions that the rodent LD50 for ketamine is 600 mg/kg, and divides by 10 (which is apparently a standard rule of thumb for converting between species) to get 4.2 g for a 70 kg human
    • they say a typical recreational dose is 175 mg, and so get a "safety ratio" (lethal dose/effective dose) of 25, safer than alcohol.
    • StatPearls may have misquoted this paper...I'm not sure where they're getting their 678 mg number.
  • if the lethal dose really is only about twice the effective dose, as in the StatPearls article, that's a very tight window.
    • for context:
      • the median lethal dose (LD50) of ethanol is the equivalent of about 25-40 standard drinks
      • the LD50 of aspirin is about 43 aspirin tablets
      • the LD50 of amphetamine is between 20-200 times a typical prescription ADHD dose
• https://www.youtube.com/watch?v=ouJrOQfkeok  how a Kite cell therapy (autologous) is manufactured (they ship your blood sample to a facility, and process/expand your cells in 5 days).
• https://docs.google.com/document/d/1-jBoSEVlryiX1IaSzV4vKuihDfm_LgXUznvSpl1T1kg/edit?tab=t.0#heading=h.vnjrknmu0cff
  • suicide note of a DeepMind researcher who took ketamine for depression, developed psychosis and then very severe depression unlike anything he'd experienced before; "the emergency alarm continues to strike blind panic and fear into my mind every second" for two years with no change.
• https://marginalrevolution.com/marginalrevolution/2025/01/simple-points-on-immigration.html Tyler Cowen remains pro-high-skilled immigration.
• https://impact-ops.notion.site/11c061ba6c7880b38073e8ddfb4f1db0?v=11c061ba6c788137aa62000c8aa8918b  an instruction manual for setting up a nonprofit.
  • having started a nonprofit myself and screwed some of this up, i want to endorse taking a lot of care with legal compliance and administrative processes.
    • an "ordinary" middle-class person, in their personal life, usually doesn't have to worry too much about accidentally breaking laws. a founder (of a nonprofit or small business) can ABSOLUTELY do illegal stuff by accident and get burned for it.
    • it's also very easy to accidentally be the kind of terrible boss you hear horror stories about...just screw up payroll!

• https://www.nature.com/articles/s41467-024-53922-x 

  • neuroblastoma and embryonic kidney cell lines exhibit the "massed-spaced" effect discovered in neurons by Hermann Ebbinghaus where a repeated spaced stimulus has a stronger response than a "massed" (clumped) stimulus, almost as though "learning" the difference between an event that recurs and a (potentially erroneous) one-off.
    • in non-neural cells, instead of looking at neuron firing we're looking at a particular cell signaling pathway engineered to carry a luciferase gene that glows when the CRE gene is transcribed.
    • The chemical TPA directly activates protein kinase C (PKC)
    • the chemical forskolin activated protein kinase A (PKA) via raising cAMP levels, which activate PKA
    • PKA and PKC both phosphorylate the transcription factor protein CREB1
    • CREB1 causes lots of genes, including our reported gene CRE, to be transcribed more
    • this pathway was selected to be similar to the way serotonin activates a signaling cascade during memory via PKA and PKC
  • people are sharing around popular articles claiming that this proves kidney cells have memory, but it really doesn't.
  • it proves that the mechanisms of neuronal memory have shared properties with cell signaling mechanisms present throughout the body, which is what you'd expect; neurons necessarily evolved as a variation on some other kind of cell.
  • now, understanding exactly how this works is interesting! but no, it doesn't mean you think with your kidneys.