--- Log opened Fri Jan 10 00:00:44 2025
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09:57 < kanzure> we should probalby try to stop ralph merkle from following through on his "freeze by" date. wasn't that targeted for 2025?
10:09 < AlonzoC> He had a freeze by date?
10:14 < AlonzoC> If he is a cryonics true believer I suspect the best counter argument to a freeze by date would be appealing to his utility if he continues working now.
10:14 < AlonzoC> Vitrification may preserve all the information in his brain but you need to ensure the future (1) wishes to resurrect you and (2) is one you want to wake up in.
10:14 < AlonzoC> If the singularity is within his lifetime he doesn't need to go into deep freeze.
10:14 < AlonzoC> While if he does freeze and we get a negative FOOM or whatever yud worries about these days he won't wake up nor will he wish to.
10:14 < AlonzoC> So it would be best to continue alive so you can act to ensure your future condition which you can't while frozen.
10:16 < L29Ah> maybe he is going to live by the dewar from now on
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12:30 < hprmbridge> heathal> https://www.biorxiv.org/content/10.1101/2024.12.16.628684v1
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12:33 < fruitishealthy> hello
12:33 < fruitishealthy> is aniracetam the best nootropic?
12:34 < AlonzoC> heathal: Saw the microscope thing on my news feed, once I got some space i'm defo gonna have a go.
12:37 < AlonzoC> Doesn't look to useful tho compared to other actual microscopes
12:40 < AlonzoC> fruitishealthy: i'm not very knowledgeable on nootropics but the general consensus afaik is small molocule interventions aren't that good.
12:40 < L29Ah> i wonder if it is better than $20 aliexpress microscopes
12:41 < L29Ah> i have one but i don't have any nice patterns to compare it, and it really needs a robot to focus it reliably
12:41 < AlonzoC> Probably better cheap microscopes are usually fairly bad ime
12:41 < L29Ah> (attach it to a 3d printer head for example)
13:00 < fruitishealthy> AlonzoC what do you mean by that?
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13:12 < AlonzoC> That supplementation and small molocules may allow you to reach your phenotypic maxima for mental performance it won't raise you far beyond you existing baseline.
13:12 < AlonzoC> Atleast I haven't seen any good evidence for small molecule drugs and suplements having effects meaningfully beyond what healthy diet and exercise would do.
13:12 < AlonzoC> Others disagree but i'm of the opinion the brain operates fairly close to optimal given design constraints and any meaningful improvement would involve structural changes not just poking all receptors of a specific type with a small molocule or increasing the availbity of specific amino-acids 
13:13 < AlonzoC> kanzure is more knowledgable than me though
13:25 < hprmbridge> Eli> @jrayhawk I was thinking about the teleological reason that the body seems to have more ldl than necessary. I read a paper showing that ldl declined significantly during the acute phase response. Those with a high pathogen burden had a decrease in ldl by like 50%. A case of antagonistic pleiotropy?
13:29 < hprmbridge> Eli> There’s no such thing as best nootropic. Genetics are not uniform. It’s impossible to predict what will have the greatest impact on phenotypic maxima.
13:35 < L29Ah> hygiene, broadly speaking, is the best nootropic
13:38 < AlonzoC> L29Ah: And a daily coffee can't forget that :D
13:38 < L29Ah> that's more individual
13:39 < L29Ah> twitchiness and restlessness are counterproductive for plenty of tasks
13:40 < AlonzoC> I've had some good results with L-theanine along with my coffee but I was never very twitchy tbh
13:41 < AlonzoC> Only twitchiness I got was from sleep deprivation (the best anti-nootropic practice short of neurotoxins I swear)
13:42 < AlonzoC> s/of neurotoxins/of ingesting neurotoxins/
13:45 < jrayhawk> Eli: serum LDL count is not the thing to think in terms of; it's a poor proxy for production, clearance, and residence time.
13:47 < jrayhawk> LDL concentration should be expected to go down if tissues suddenly undergo a bunch of oxidative stress and need to do membrane repair or modify homeoviscosity in response to, say, body temperature rising by five degrees Fahrenheit.
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13:51 < jrayhawk> Production and clearance can both increase in absolute terms while serum concentration decreases.
13:57 < jrayhawk> You do get some weird stuff like the older ApoE4 gene generating a neuroinflammatory ApoB cleavage pattern while the newer ApoE2 cleavage pattern is innocuous; it is likely ApoE4 was signalling genetic/environment misalignment during the C3-to-C4 arboreal-to-grassland transition.
13:58 < jrayhawk> "you are in a weird place eating weird food; best be on guard for weird pathogens"
14:08 < jrayhawk> re: nootropics: caffeine purines are plausibly a substitute for co-evolved neolithic gout purines. dopaminergics/norepinephrinergics are almost certainly a substitute for regular acute existential psychological stresses (hunting, war, etc.).
14:09 < jrayhawk> adderal can make you as attentive to tax paperwork as you would be to hand-to-hand combat.
14:12 < jrayhawk> https://darktka.github.io/focus.png
14:14 < jrayhawk> antidepressants may be a substitute for regular social feedback
14:14 < AlonzoC> Saw the graph before but i'm impressed the LSD microdose is so far up there
14:15 < AlonzoC> wouldn't apriori guess it would have an effect above nicotine 
14:15 < fruitishealthy> thank you all for your time
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14:16 < AlonzoC> no problem also check out the wiki
14:16 < AlonzoC> https://diyhpl.us/wiki/
14:19 < L29Ah> AlonzoC: it is a subjective scale, and psychedelics affect perception strongly, so i wouldn't rely on that too much
14:20 < AlonzoC> Ahh, well it atleast says it's worth looking at
14:20 < hprmbridge> Eli> LSD is always the one that stands out in these charts. You wonder how much of it is placebo, due to the psychoactive effects, and how much of it is real. There is some recent evidence that the the primary MOA of antidepressents, LSD, ketamine, etc ... all has to do with the TrkB receptor. They are all upstream of this receptor which has an impact on BDNF. It's currently being studied.
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14:22 < jrayhawk> it was a fad around that time, so suspicion is warrented
14:24 < AlonzoC> Yeah LSD microdosing was a whole thing for a while iirc. Did any good data come out of it?
14:24 < AlonzoC> or just a fad?
14:26 < L29Ah> AlonzoC: there was the self-blinding studio a few years ago, and iirc the result is near placebo
14:26 < L29Ah> *study
14:27 < hprmbridge> Eli> The data is supposed to be in that chart.
14:29 < hprmbridge> Eli> I think it's difficult to study this stuff because LSD is schedule 1.
14:29 < superkuh> Anyone have a working libgen url? Or remember the .onion?
14:29 < hprmbridge> Eli> So, a bunch of n=1s is our best knowledge.
14:30 < L29Ah> superkuh: https://libgen.gs/
14:30 < L29Ah> Eli: the mentioned study had over 100 participants
14:30 < hprmbridge> Eli> I would be furious if you used any of the capability of the following link to allow poor people to have access to scientific knowledge: https://annas-archive.org/
14:30 < superkuh> Thanks!
14:31 < hprmbridge> Eli> Post it.
14:32 < AlonzoC> Allowing poor people and those without priestly authority from a approved institution accessing scientific knowledge?
14:33 < hprmbridge> Eli> Sorry. I was being a little facetious. Technically, it's illegal.
14:33 < AlonzoC> How heretical yudowsky shall drone strike your PC for contributing to existential risk
14:33 < hprmbridge> Eli>  https://cdn.discordapp.com/attachments/1064664282450628710/1327405020295200789/all_my_homies_hate_closed_access.jpg?ex=6782f1c2&is=6781a042&hm=7aa332404a3aa441802624e66ecb0db0367a281d00ae035607624a35569d9921&
14:34 < L29Ah> https://elifesciences.org/articles/62878
14:47 < hprmbridge> Eli> I love that they did this. However, I'd like to see more robust studies. My prior is that people who are suffering depression might experience significant improvement in cognition. I'd also like to see more control over the dose. This study didn't verify that the subjects were actually consuming LSD.
14:47 < hprmbridge> Eli>
14:47 < hprmbridge> Eli> "A key limitation of the present study is the lack of verification of the nature, purity, and dosage of the psychedelic substance used for microdosing. Psilocybin-containing mushrooms were used by 23% of the sample, 14% used legal LSD analogues (such as 1P-LSD), whereas 62% sourced their substance from the black market, mostly LSD (61%)."
14:49 < hprmbridge> Eli> I totally forgot 1P-LSD is unscheduled. 😆
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14:51 < AlonzoC> Huh, didn't know about that (1P-LSD being unscheduled). Not a thing in the UK given the broadness of our laws
14:51 < hprmbridge> Eli> I feel like I remember seeing Google ads fo 1p-lsd.
14:52 < AlonzoC> I know Mescaline is legal here not sure how that works in light of the Psychoactive Substances Act 2016i
14:54 < hprmbridge> Eli> Our ancestors would have overthrown the government by now.
14:55 < AlonzoC> tell me about it..
14:56 < AlonzoC> Gotta love the ratchet of government power creep
14:56 < AlonzoC> And it's simultaneous complete lack of competence
14:58 < hprmbridge> Eli> Yeah, It's incredible. Chemists come up with new stuff every year and the government pays their people to outlaw it every year. Forever wars are guaranteed job security.
14:59 < hprmbridge> Eli> The FDA is just the enforcement arm of a narcocartel
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15:07 < L29Ah> curiously, most recent psychedelics studies seem to come from UK
15:19 < hprmbridge> Eli> There seems to be some progress. MAPS is a non-profit trying to do clinical trials to get psychedelics approved. The p values on psychedelics are unbelievable.
15:19 < hprmbridge> Eli> I recently saw Rick Perry is trying to get Ibogaine off the schedule 1 list. Incredible that there is such a thing as scheduled drugs to begin with. I have no understanding how something like that is legal.
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15:28 < L29Ah> "think of the children"
15:29 < L29Ah> even ethanol was banned for some time in "the land of liberty"
15:29  * L29Ah blames christianity and statism
15:39 < darsie> L29Ah: Maybe not as rocket fuel.
15:46 < L29Ah> darsie: sure you can use it as rocket fuel, just become a business, get a license and get checked by state officials for its compliance, and pay for all that
15:47 < L29Ah> the schedule 1 research license in UK is a few thousands pounds and you need to renew it every year or so, iirc
15:49 < L29Ah> and then you'll have the pain of actually obtaining the substances (or buying an additional license to manufacture them and doing that in a compliant way)
15:49 < L29Ah> legally
16:00 < darsie> L29Ah: I just meant during the 'prohibition'.
16:04 < L29Ah> me too
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17:30 < juri_> just promise me one thing: after the singularity, you will build the ancestor simulator, and data recover me.
17:32 < fenn> so say we all
17:32 < fenn> better don't die
18:41 < hprmbridge> kanzure> can someone on a computer review and merge https://github.com/kanzure/diyhpluswiki/pull/244
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20:20 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=ad225446 Brian Muhia: Update molecular-manufacturing.mdwn >> 
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21:01 < NewtonTrendy> why does everything i say come accross as the most evil verison of it possible after a few seconds?
21:31 < fenn> because you have social media poisoning and/or schizophrenia, or the listener does
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21:35 < hprmbridge> lordkek__> Kanzure Can we talk in DM?
21:42 < hprmbridge> kanzure> no
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21:42 < hprmbridge> lordkek__> Can we talk here?
21:45 < hprmbridge> kanzure> what do you need?
21:48 < hprmbridge> lordkek__> I first sent an email to the bitcoin-security mailing list suggesting the problem. Next I have two thoughts to #hplusroudmap
21:49 < hprmbridge> kanzure> i don't receive those emails
21:50 < hprmbridge> lordkek__> Can I forward to your gmail?
21:57 < hprmbridge> lordkek__> To #hplusroudmap, one on nanotechnology and the other on longevity. These are ideas that I need to discuss a little bit because nanotechnology is not that much explored yet.
21:57 < hprmbridge> lordkek__>
21:57 < hprmbridge> lordkek__> Of course My goal is to work on these things with other people.. for the benefit of #hplusroudmap and the development of other ideas
21:58 < hprmbridge> kanzure> sure, present your ideas
22:25 < hprmbridge> lordkek__> The process of one-electron exchange in cells
22:25 < hprmbridge> lordkek__>
22:25 < hprmbridge> lordkek__> This exchange involves the donation or acceptance of electrons, which helps restore balance, repair cellular components, and sustain energy production.
22:25 < hprmbridge> lordkek__>
22:25 < hprmbridge> lordkek__> A key concept is the role of single-electron transfers in cellular damage and repair, restoring normal function.
22:25 < hprmbridge> lordkek__>
22:25 < hprmbridge> lordkek__> Oxygen plays a vital role in this system as the final electron acceptor in the electron transport chain (ETC). When oxygen is unavailable, the flow of electrons through the ETC is halted, preventing protons from being effectively pumped across the membrane. This disruption compromises cellular respiration and energy production, leading to SUFFUCATION at the cellular level.
22:31 < hprmbridge> lordkek__> With bitcoin I wanted to talk about the possibility of this bug which is simply about
22:31 < hprmbridge> lordkek__> malicious data that can influence the state or behavior of nodes by altering their stack or internal memory not relying on hashing.
22:46 < hprmbridge> Eli> New paper dropped: https://www.nature.com/articles/s41586-024-08300-4
22:46 < hprmbridge> Eli>  https://cdn.discordapp.com/attachments/1064664282450628710/1327529001501069362/IMG_1564.jpg?ex=6783653a&is=678213ba&hm=c41f147c0e6bc7162b39a987322e38a2cf9a68b7ae1f7ec91306486aad601fdb&
22:47 < hprmbridge> lordkek__> Nano sublimation energy storage
22:47 < hprmbridge> lordkek__>
22:47 < hprmbridge> lordkek__> A nano battery charging by "FREEZING" the simple ions and cations and the transformation described as Sub. Diffusion reaction
22:47 < hprmbridge> lordkek__>
22:47 < hprmbridge> lordkek__> battery would have an almost infinite lifespan because the energy is stored in a stable, antifreeze state, avoiding the common pitfalls of aging that affect conventional batteries.
22:47 < hprmbridge> lordkek__>
22:47 < hprmbridge> lordkek__> https://x.com/mike_argot/status/1851996661939077262?s=46
22:49 < hprmbridge> Eli> Not completely sure how they calculated the % reduction for everything. Going from homozygous apoe4 to homozygous apoe2 would reduce Alzheimer’s risk by like 12x or something like that.
22:51 < hprmbridge> Eli> The island of dr Moreau with 2025 biotech would unironically be a great film. Hollywood hasn’t caught up
--- Log closed Sat Jan 11 00:00:44 2025