--- Log opened Sun Sep 07 00:00:32 2025
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00:23 < hprmbridge> kanzure> davidad says "All the estimates I can find for average receptors per synapse in human CNS range from 140 to 300."
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03:46 < hprmbridge> kanzure> "Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs" https://pmc.ncbi.nlm.nih.gov/articles/PMC9990469/
04:49 < stipa> add
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05:35 < hprmbridge> kanzure> anyone try qwen3-max yet?
09:01 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=d876ce8c Bryan Bishop: more brain stuff >> http://diyhpl.us/diyhpluswiki/xenotransplantation/
09:18 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1414283753655894066/image0.jpg?ex=68bf01e2&is=68bdb062&hm=89da179cb80dfc9dc0605b7ba6f00c08ece90706802636c5ba15673ccb47a529&
09:32 < hprmbridge> kanzure> "pharmacological inhibition of adenine nucleotide translocase (ANT) function, or inhibition of mitochondria permeability transition pore (mPTP) opening by bacteria-derived mitochondrial toxin bongkrekic acid (BKA), mimics basal progenitor expansion by ARHGAP11B"  https://www.sciencedirect.com/science/article/pii/S0896627319310360
09:41 < hprmbridge> kanzure> oh, cyclosporine A also inhibits mPTP opening.
09:43 < hprmbridge> kanzure> oh, bongkrekic acid is a relevant inhibitor but not of mPTP. oops.
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10:04 < hprmbridge> kanzure> lymph node bioreactor stuff was called lygenesis.com (see logs)
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10:50 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1414306733722959993/file_000000001a9c61f9889c6e738b369cf9.png?ex=68bf1749&is=68bdc5c9&hm=624a1c2d338edc49d7eb44d0bba7f96ce2c1e9f81c5db64c422fb20c765d4f28&
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12:26 < kanzure> geochurch added six genes today
12:34 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=d2fd039b Bryan Bishop: import 10+ years of updates from george church wishlist >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
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13:38 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=3c94bc29 Bryan Bishop: more cell-specific expression technologies >> http://diyhpl.us/diyhpluswiki/xenotransplantation/
13:45 < hprmbridge> kanzure> SP0535 when inserted in mice promotes cortical expansion: https://cdn.discordapp.com/attachments/1064664282450628710/1414351003746173070/image.png?ex=68bf4084&is=68bdef04&hm=8fc8641be3abf6f65c1a5f27d71c5022dad1ae595e4dd7901cbd36489b2c70c0&
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14:48 < darsie> https://x0.at/3_Ib.txt#future
15:02 < hprmbridge> kanzure> future forecasting is notoriously difficult
15:03 < hprmbridge> kanzure> "Here, we developed synthetic zinc finger transcription regulators (synZiFTRs), which are compact and based largely on human-derived proteins. As a proof of principle, we engineered gene switches and circuits that allow precise, user-defined control over therapeutically relevant genes in primary T cells using orthogonal, US Food and Drug Administration–approved small-molecule inducers." hey that's
15:03 < hprmbridge> kanzure> a neat idea. from https://diyhpl.us/wiki/cell-specific_expression/
15:04 < hprmbridge> kanzure> "synNotch receptors convert a surface antigen cue into a user-defined transcriptional output (e.g., gRNA, TF, recombinase). Combine with miRNA logic to get (antigen) AND (miRNA profile) targeting."
15:05 < darsie> watch me ;)
15:53  * L29Ah watches
15:54 < fenn> somehow i had never heard of resistant starch
15:55 < fenn> it makes it through the small intestine without being digested, and then microbes in the large intestine ferment it, preferably into short chain fatty acids
15:55 < fenn> there are all sorts of ridiculously expensive products but you can just heat a regular starch and let it cool, and it re-crystallizes or something and turns into resistant starch if you eat it cold
15:56 < jrayhawk> there's a lot of circumstantial variability, there
15:56 < fenn> or green bananas / plantains
15:56 < jrayhawk> start small and work your way up
15:57 < fenn> i had 28g of cooked refrigerated oatmeal
15:57 < jrayhawk> it goes very poorly for some people
15:57 < fenn> (one large spoonful)
15:59 < fenn> i also started L. reuteri and B. infantis a few days ago
15:59 < fenn> the equilibrium yogurt was causing issues because i can't guarantee that the milk from the store is fresh enough
16:00 < fenn> batch 1 was fine batch 2 was not
16:00 < fenn> that's a me problem though
16:02 < fenn> also re the amazon thing, it was very confusing. they have two nearly identical services, "amazon overnight delivery" and "amazon fresh" both of which sell an identical selection of perishable groceries. the difference is "overnight" has free delivery with $25 worth of anything from amazon, but amazon fresh has free delivery with $50 of amazon fresh stuff, and it's a separate shopping cart
16:03 < fenn> i think "overnight" is for prime customers only
16:03 < fenn> but also you can sign up to "amazon fresh" for like the same amount as paying for prime, but it's just a much worse deal overall
16:03 < fenn> so never use amazon fresh
16:03 < jrayhawk> i forget, did you do any attempts to distinguish HI from MCAS in yourself?
16:04 < fenn> i'm not sure what i would do to distinguish, but i don't have the rashes and stuff typical of MCAS
16:04 < fenn> pea shoots eaten along with the equilibrium batch 2 seemed to have prevented the bad reaction to it, but i'm still wary
16:05 < jrayhawk> MCAS can be localized to specific organs AFAIK. Mastocytosis is the one that does whole-body reactions, including chracteristic rashes.
16:06 < jrayhawk> er, characteristic
16:08 < fenn> i have been considering getting this for prevention when eating suspect foods https://www.amazon.com/NATURDAO-Vegetable-Deficiency-Histamine-Intolerance/dp/B08R5ZVG4L
16:09 < fenn> it's a lot easier than dealing with pea shoots, but it also might be overkill
16:10 < jrayhawk> overkill at least makes for strong signals
16:11 < fenn> supposedly if you push too hard on breaking down histamine, the body will just upregulate histamine production, and this can lead to oscillations
16:13 < jrayhawk> that should hopefully also be made obvious with drowsiness
16:16 < jrayhawk> huh, https://pubmed.ncbi.nlm.nih.gov/1712330/ glycine needed to repair ulcers increases reaction severity (presumably preformed collagen is the less disaster-prone way to deliver it)
16:16 < jrayhawk> seems weird
16:21 < fenn> my h. pylori breath test was negative and i don't have any pain so i don't think i have to worry about ulcers
16:22 < fenn> in any case getting plenty of well hydrolyzed chicken skin and broth
16:23 < fenn> i notice adding a little vinegar to the pressure cooker makes it "cook" faster and ends up more like jello at the same cook time (15 min) and the jello effect only goes up to the water line
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16:55 < fenn> interesting review on that diamine oxidase pill: "at higher doses, I think it has off-target effects and acts as an MAO...ie the opposite of an MAOi. I suspect that at higher doses, it breaks down the monoamine precursors to dopamine and norepinephrine. When I was taking it a higher doses, I started feeling depressed, and my Adderall stopped working."
16:56 < fenn> lots of bad reactions to it
16:57 < hprmbridge> kanzure> localization of expression to L5 pyramidal neurons https://pmc.ncbi.nlm.nih.gov/articles/PMC8610077/ and ">800 different enhancer AAVs covering most subclasses of cortical cells" courtesy of paul allen institute https://pmc.ncbi.nlm.nih.gov/articles/PMC11195086/
18:01 < L29Ah> https://agorism.dev/meme/future/post-singularity-scenarios2.png
18:10 < L29Ah> > you can just heat a regular starch and let it cool, and it re-crystallizes or something and turns into resistant starch if you eat it cold
18:10 < L29Ah> MuaddibLLM: is this true?
18:11 < MuaddibLLM> Diving into resistant starch science - checking if cooling really does the magic...
18:11 < MuaddibLLM> Yes, this is absolutely true! When you cook starch (gelatinization) and then cool it, the starch molecules undergo "retrogradation" and form RS3 (retrograded resistant starch) - cooling at 4°C for 12-24h maximizes this effect, and reheating partially destroys it again. https://pmc.ncbi.nlm.nih.gov/articles/PMC10713747/ https://pmc.ncbi.nlm.nih.gov/articles/PMC11640666/
18:17 < hprmbridge> kanzure> lygenesis lymph node injection phase 2a clinical trial for liver https://clinicaltrials.gov/study/NCT04496479
18:18 < hprmbridge> kanzure> estimated completion 2027q4 :/
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18:38 < fenn> it's been 3 years, n=12, no results yet?
18:39 < fenn> seems like n should be higher if there's no alternative
18:42 < fenn> if i had end stage liver disease i'd just fuckin do it myself
18:43 < L29Ah> but if you didn't, would you sponsor the scientists to enlarge their experiment?
18:44 < fenn> no, i don't have enough money to make a meaningful impact
18:44 < L29Ah> terminal liver disease is one of these diseases that are extremely rare if you don't do stupid things
18:45 < fenn> i'd still want to save people who did stupid things
18:45 < L29Ah> you don't have enough money so you have to prioritize, okay?
18:45 < fenn> is taking tylenol a stupid thing?
18:45 < L29Ah> taking enough of it to destroy your liver is
18:46 < fenn> what if you had too much green tea and then tylenol
18:46 < fenn> and so on
18:46 < fenn> even if someone is a lifelong alcoholic i wouldn't necessarily blame them
18:46 < L29Ah> it is not about blaming
18:47 < L29Ah> you have a choice: save a random person or save a random but likely stupid person, what would you choose?
18:47 < fenn> i don't think the signal is very strong from the "has liver disease" indicator
18:48 < fenn> if i want to be an EA then DDT bed nets
18:48 < L29Ah> https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics-z/alcohol-facts-and-statistics/alcohol-and-human-body it is
18:48 < L29Ah> plz no strawmen
18:49 < fenn> cause area 1: save people dying of liver disease, cause area 2: save people dying of malaria
18:49 < fenn> why is this a strawman argument?
18:50 < L29Ah> because we are originally talking about research investment, and now you decide to play an imaginary EA instead of your values you presented earlier
18:50 < fenn> i'm not sure if the n is small because of lack of money or FDA regulations
18:51 < L29Ah> shifting the problem of research funding to short-term meatbag count optimization
18:51 < fenn> originally i thought it was small because of regulations
18:51 < fenn> you were the one that brought up funding
18:52 < L29Ah> you can have more of everything with more funding if you are small relative to the economy at large
18:53 < L29Ah> n=12 is tiny by stage 2 intervention research standards, afaiu
18:55 < fenn> why don't they make the patients pay?
18:55 < L29Ah> the guy with the big club says no
18:57 < L29Ah> although there are indirect efforts like disease-oriented charities that circumvent this problem a tiny bit
19:09 < kanzure> looks like one of the hospitals withdrew, maybe it's a small study because it's not exactly a normal idea
19:13 < fenn> disease-oriented charities has the free rider problem unless it's an extremely rare disease
19:15 < L29Ah> yup
19:15 < L29Ah> but you can quietly negotiate with specific decision makers there
19:16 < L29Ah> MuaddibLLM: would that be unlawful in US?
19:17 < MuaddibLLM> Checking charity law - this gets into some murky regulatory territory...
19:17 < MuaddibLLM> Found IRS rules on private benefit - now checking criminal bribery laws...
19:18 < MuaddibLLM> Depends what you're "quietly negotiating" - charity officials aren't public officials under federal bribery laws (18 USC 201), but you could still hit IRS private benefit violations, state commercial bribery laws, or federal fraud charges if there's quid pro quo/kickbacks involved https://www.irs.gov/charities-non-profits/charitable-organizations/inurement-private-benefit-charitable-organizations
19:19 < L29Ah> MuaddibLLM: does participation in a study as a research subject qualify as a kickback?
19:19 < fenn> blergh. chatgpt saying stuff i don't want to hear: https://rentry.co/q7mn4kb7
19:19 < MuaddibLLM> Short answer: No - being a study subject and getting reasonable IRB-approved compensation is not a “kickback,” but payments that induce referrals or federally reimbursable services can trigger AKS/CMP or state commercial bribery issues; see FDA on paying subjects https://www.fda.gov/regulatory-information/search-fda-guidance-documents/payment-and-reimbursement-research-subjects OHRP FAQ on subject payment 
19:19 < MuaddibLLM> https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/informed-consent/index.html#payment and HHS OIG on Anti-Kickback/beneficiary inducements https://oig.hhs.gov/compliance/safe-harbor-regulations/ and https://oig.hhs.gov/compliance/compliance-resources/beneficiary-inducements-cmp/.
19:20 < fenn> i have definitely heard of people paying to enroll in clinical trials
19:21 < L29Ah> then it needs an advertisment budget or some other way for subjects to find their studies promptly
19:21 < fenn> iirc it was an ongoing study with rolling enrollment
19:23 < jrayhawk> RS2 is the form people have millions of years of exposure to in the form of savannah sedge tubers
19:23 < fenn> did they eat them raw?
19:23 < fenn> tiger nuts!
19:24 < fenn> why is this a new thing
19:24 < jrayhawk> the transition to C-4 energy ecology was 2.5mya and mastery of fire was much, much later
19:25 < fenn> i mean i never heard of tiger nuts until a few years ago, there's a bit of hype around it as a source of saturated fat and protein, or something
19:27 < fenn> i'll be honest i don't know what a savannah sedge tuber is
19:27 < jrayhawk> tiger nuts, yeah
19:41 < kanzure> here is what the hyperslop machines think about genetic-modifications.mdwn for intelligence, memory, learning, etc https://diyhpl.us/~bryan/irc/chatgpt/intelligence/
19:43 < kanzure> fenn: i agree that "create a VC fund" is a good strategy that more people should employ, however your slopmachine missed my comments in here from a few months ago for how to fund and finance these deep time research projects
19:43 < kanzure> essentially an investor wants exposure to the future market which is undeniably going to be enormous, however any given startup or research project is somewhat unlikely to perform well against other competing short-term investments
19:44 < kanzure> (especally if you are particularly early to the whole field or the technology is immature)
19:45 < kanzure> so what to do about this? i argue that investors still want to buy a slice of that future market and they want (more than anything else) exposure to that future, and so they can secure that exposure through more aggressive investment agreements that encumber the entrepreneur with ongoing obligations even beyond the death of the startup
19:45 < kanzure> such as social networking related obligations, introduction obligations, media rights, or other specific performance in the entrepreneur's future
19:46 < kanzure> this was an interesting slop output https://diyhpl.us/~bryan/irc/chatgpt/intelligence/protein-engineering-gpt5.txt
19:47 < kanzure> and https://diyhpl.us/~bryan/irc/chatgpt/intelligence/pattern-opus.txt
19:48 < jrayhawk> https://www.astralcodexten.com/p/impact-markets-the-annoying-details comes ot mind
19:59 < hprmbridge> kanzure> "There's no credible way to sell these benefits - just because I sell you the impact certificate for curing malaria, doesn’t mean Harvard would be willing to make you the department chair instead." this is incorrect and misunderstands what elon does, why coauthorship is monetizable, and how (mutually meaningful) sponsorships work.
20:08 < hprmbridge> kanzure> is this missing an altruistic free rider problem analysis or does the abuse of the commons not apply due to their karmic charitability?
21:50 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=4051928d fenn: can't be bothered to jump through the hoops necessary to upload my fixes to wikipedia so adding it here instead. license is CC0 >> http://diyhpl.us/diyhpluswiki/users/fenn/mitochondrion_diagram_en.svg
22:02 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=192283e8 fennwiki: add cute image of a mitochondrion >> http://diyhpl.us/diyhpluswiki/mitochondria/
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22:57 < fenn> darsie is planning for the future: https://x0.at/3_Ib.txt#future
22:57 < fenn> you can hack the matrix at any time, but if you do so, it will be game over
22:57 < fenn> [ ] hack  [ ] don't hack
23:37 < darsie> Why will it be game over?
23:38 < darsie> I mean, hacking out of the Matrix into the real world. Or maybe hacking new energy sources, FTL/worm holes or so into the universe.
23:38 < darsie> Should have made that a pad, cause I'm still editing it a bit.
23:39 < fenn> i've been using rentry lately for its markdown rendering and editability
23:39 < fenn> i don't like how etherpad has a chat window that you can't get rid of
23:40 < fenn> and the crazy colors
23:41 < darsie> https://rentry.co/azfuyi4b testing
23:44 < darsie> ok, gotta save the edit code.
23:45 < fenn> you can also set a custom edit code
23:54 < fenn> "you may set a modify code, which is used in place of an edit code when editing a Rentry. A modify code can only be used to edit the Rentry's text, allowing you to share it without risking the URL being stolen."
23:55 < darsie> ok
23:55 < darsie> https://rentry.co/FutureTimeline
23:55 < fenn> the distinction between edit and modify wasn't clear to me
23:59 < darsie> URL seems to be case insensitive.
--- Log closed Mon Sep 08 00:00:31 2025