--- Log opened Fri Aug 29 00:00:24 2025
00:10 -!- Gooberpatrol66 [~Gooberpat@user/gooberpatrol66] has quit [Ping timeout: 260 seconds]
00:38 -!- stipa [~stipa@user/stipa] has quit [Ping timeout: 260 seconds]
00:53 -!- TMA [tma@twin.jikos.cz] has quit [Ping timeout: 248 seconds]
00:55 -!- TMA [tma@twin.jikos.cz] has joined #hplusroadmap
01:08 < jrayhawk> https://alloyenterprises.co/ exotic geometry heat sinks and heat exchangers using forged layering
01:11 -!- stipa [~stipa@user/stipa] has joined #hplusroadmap
01:23 < fenn> is this the new vapor wave chamber craze the kids are huffing
01:26 < fenn> "After digital slicing with Alloy’s proprietary software and laser-cutting the part design, the aluminum sheets are then metal-to-metal diffusion-bonded together to form a solid block."
01:27 < fenn> how is this better than solder / brazing
01:28 < hprmbridge> .monokhrome> and why is it exotic? I expected something lovecraftian and non-euclidean
01:29 < fenn> they act like investment casting with 3d printed wax forms isn't a thing
01:40 < jrayhawk> tighter geometric control and improved thermal conductivity from only using one material
01:41 < fenn> are these like really tiny channels?
01:42 < jrayhawk> as small as you want your laser to go, yeah.
01:42 < fenn> it's not clear to me that i want to go small
01:43 < jrayhawk> more surface area is better cooling
01:43 < fenn> don't you want to maximize the surface area in contact with the chip face? and the vertical stuff is just supports so the thin wall doesn't flex too much and lose contact
01:44 < fenn> the vapor transfer is better than a solid for heat conduction right?
01:45 < fenn> i'm saying the vapor chamber face in contact with the chip package should be as thin as possible, and maybe this requires making channels, but otherwise channels are bad
01:46 -!- TMM [hp@amanda.tmm.cx] has quit [Quit: https://quassel-irc.org - Chat comfortably. Anywhere.]
01:46 -!- TMM [hp@amanda.tmm.cx] has joined #hplusroadmap
01:46 < fenn> also the supports don't necessarily have to be part of the same piece of material as the face in contact
01:47 < fenn> as a 3d printing technique it seems fine
01:57 < jrayhawk> https://www.youtube.com/watch?v=4d6VWLaKnSo&t=426 video sales pitch, though there's not a lot of surprises other than the use of an "inhibitor" to avoid having to deal with post-forging subtraction
04:29 < hprmbridge> kanzure> "Captured images during in situ 3D printing of the SSAM bioink into a mouse calvarial bone defect" in situ laparoscopic 3d printing. alright.
05:17 < L29Ah> fenn: yes, vapor transfer is great when it works
05:27 -!- etc-vi [~etc-vi@user/meow/girlchunks] has quit [Ping timeout: 245 seconds]
05:28 -!- etc-vi [~etc-vi@user/meow/girlchunks] has joined #hplusroadmap
05:31 -!- etc-vi0 [~etc-vi@user/meow/girlchunks] has joined #hplusroadmap
05:33 -!- etc-vi [~etc-vi@user/meow/girlchunks] has quit [Ping timeout: 258 seconds]
05:33 -!- etc-vi0 is now known as etc-vi
05:35 < kanzure> "Rapid mechanically controlled rewiring of neuronal circuits" https://pmc.ncbi.nlm.nih.gov/articles/PMC4719026/ "We show that AFM probe tip with microbeads adhesively contacted onto an axon or dendrite can be pulled to initiate a new neurite that can be mechanically guided to form new synapses at up to 0.8 mm distance in <1 hour. The extension rates achieved are faster than 20 μm/min over ...
05:35 < kanzure> ...millimeter-scale distances and functional connections are established. ur proposed mechanical approach bypasses slow chemical strategies and enables controlled connection to a specific target. We have yet to discover whether there is a fundamental upper limit to these speeds."
05:39 < kanzure> they should have also tested using an AFM probe tip to dissect, prune or disconnect the neural network.
05:53 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has quit [Quit: Avoid fossil fuels and animal products. Have no/fewer children. Protest, elect sane politicians. Invest ecologically.]
05:53 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has joined #hplusroadmap
06:58 -!- justanotheruser [~justanoth@gateway/tor-sasl/justanotheruser] has quit [Ping timeout: 272 seconds]
07:22 -!- stipa [~stipa@user/stipa] has quit [Ping timeout: 258 seconds]
07:25 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=97f7a3ec Bryan Bishop: add ref for drosophila synaptic overgrowth >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
07:25 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=b61a8e20 Bryan Bishop: Merge remote-tracking branch 'origin/master' into master >> http://diyhpl.us/diyhpluswiki/
07:25 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=cd2bd210 Bryan Bishop: some articles about optogenetic axon guidance >> http://diyhpl.us/diyhpluswiki/optogenetic-axon-guidance/
07:25 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=af9ba105 Bryan Bishop: fix reference links for optogenetic axon guidance >> http://diyhpl.us/diyhpluswiki/optogenetic-axon-guidance/
07:25 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=80cba752 Bryan Bishop: some review articles about optogenetic axon guidance >> http://diyhpl.us/diyhpluswiki/optogenetic-axon-guidance/
07:25 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=53ca4edf Bryan Bishop: articles pertaining to retinal organoids, retinal explants, in vivo whole eye perfusion >> http://diyhpl.us/diyhpluswiki/biosight/
07:27 < kanzure> oof, commit spam
07:28 < pasky> L29Ah: they are not - i'll try enabling them in test mode and keep an eye on when it triggers & share
07:32 < kanzure> oops i meant ex vivo whole eye perfusion
07:32 -!- justanotheruser [~justanoth@gateway/tor-sasl/justanotheruser] has joined #hplusroadmap
07:55 -!- stipa [~stipa@user/stipa] has joined #hplusroadmap
08:20 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=70f4df03 Bryan Bishop: various optogenetics things >> http://diyhpl.us/diyhpluswiki/optogenetics/
09:10 < hprmbridge> jsingh.1> are there any research studies which show conclusively why diet coke is bad for health?
09:12 < L29Ah> MuaddibLLM: answer
09:12 < MuaddibLLM> jsingh.1: Short version - no conclusive proof Diet Coke is harmful at typical intake; RCTs show non-nutritive sweeteners can aid weight control and are safe within ADI, while observational links to CVD/diabetes are mixed and confounded; WHO/IARC put aspartame in 2B possibly carcinogenic but JECFA kept ADI 0-40 mg/kg/day - read: WHO 2023 Q&A 
09:12 < MuaddibLLM> https://www.who.int/news/item/14-07-2023-joint-who-and-fao-expert-meeting-on-aspartame, BMJ 2022 NutriNet-Santé CVD cohort https://www.bmj.com/content/378/bmj-2022-071204, and 1-year RCT showing diet drinks help weight loss https://onlinelibrary.wiley.com/doi/10.1002/oby.21538.
09:13 < L29Ah> MuaddibLLM: is amphetamine the real "diet coke", or cocaine itself is in fact better at fat reduction?
09:14 < MuaddibLLM> L29Ah: Neither - cocaine’s appetite blunting doesn’t yield healthy fat loss and has nasty cardiotoxic/addiction risk, while prescription amphetamine-like stimulants can give modest short-term weight loss via appetite suppression under medical supervision but carry dependence/CV risks; for actual fat reduction, look at GLP-1 agonists plus boring calorie deficit and lifting.
09:15 < hprmbridge> jsingh.1> so why do they make your "gut" body feel worse than in comparison to say drinking pure coffee vs an energy drink
09:16 < L29Ah> do they?
09:29 < hprmbridge> Eli> It’s an active area of research and I’ve only seen a few studies on it. I don’t think there are any nutritionists who would tell you that Diet Coke is an essential substance. Personally, I’ve noticed it makes me want to consume sugar more. If you don’t like it, you can switch to water and it will save money.
09:37 < pasky> [TEST MODE] Generated response for #hplusroadmap: jsingh.1: Often it’s the combo of carbonation causing gastric distension, cola-level acidity/phosphates irritating mucosa, a big cold fluid bolus plus caffeine speeding motility, and certain sweeteners (acesulfame-K or sucralose more than aspartame) provoking bloating in some; easy tests are trying it flat or room-temp, caffeine-free, smaller sips, 
09:37 < pasky> and A/Bing different sweeteners to see which your gut tolerates.
09:37 < pasky> (example of muaddib proactive interjection)
09:42 < jrayhawk> The "cephalic stage of digestion" does calorie estimation based on sweetness and releases liver glycogen to ramp up insulin production and GLUT4 expression in preparation for an incoming glucose load.
09:44 < jrayhawk> The use of "non-caloric" sugar alcohols is making a systemic energy contract with every cell in your body that you subsequently reneg on.
09:47 < L29Ah> how about those potent non-alcohol sweeteners?
09:47 < jrayhawk> Such as?
09:49 < L29Ah> aspartame, sucralose, stevioids, Fraunhofer X3
09:50 -!- Gooberpatrol66 [~Gooberpat@user/gooberpatrol66] has joined #hplusroadmap
09:51 < jrayhawk> oh, same basic effect
09:56 < TMA> speaking of sweeteners, I have heard of a study linking them to causing diabetes
09:57 < TMA> the effect is still present when accounted for obesity, unlike ordinary sugar, whose causal link to diabetes disappears after taking obesity into account
09:57 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has quit [Remote host closed the connection]
09:58 < TMA> sadly, I do not have the primary article at hand
09:58 -!- telgareith [~telgareit@user/telgareith] has joined #hplusroadmap
09:58 < jrayhawk> that's what muaddib is for
09:58 -!- telgareith [~telgareit@user/telgareith] has left #hplusroadmap [The Lounge - https://thelounge.chat]
09:58 < TMA> [aspartame should be the worst offender among those]
09:58 < jrayhawk> There exist some artificial sweeteners for which humans have natural intestinal transporters and can thus avoid the microfloral bloom, but the cephalic stage makes the whole paradigm is such an obvious biological misalignment that I always discard that from memory
10:02 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has joined #hplusroadmap
10:20 < kanzure> jrayhawk: [[ikiwiki links like this]] do not correspond to ikiwiki-links-like-this.mdwn?
10:22 < jrayhawk> I would expect underscores rather than hyphens for that
10:30 < jrayhawk> e.g. https://secure.diyhpl.us/cgit/testrepo/tree/
10:33 < kanzure> wha?
10:33 < kanzure> sorry, what should the actual filename be for [[making this work]]?
10:34 < jrayhawk> making_this_work.mdwn
10:34 < MuaddibLLM> Name the page file making_this_work.mdwn (or making_this_work/index.mdwn if you want it as a subpage), because ikiwiki turns spaces in [[links like this]] into underscores for the corresponding page filename.
10:45 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=34c08ca3 Bryan Bishop: programmable morphogenesis references >> http://diyhpl.us/diyhpluswiki/optogenetics/
11:13 -!- stipa_ [~stipa@user/stipa] has joined #hplusroadmap
11:16 -!- stipa [~stipa@user/stipa] has quit [Ping timeout: 260 seconds]
11:16 -!- stipa_ is now known as stipa
11:57 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=7d6fc59f Bryan Bishop: more morphogenesis and optogenetics >> http://diyhpl.us/diyhpluswiki/organoids/
12:32 -!- TMM [hp@amanda.tmm.cx] has quit [Quit: https://quassel-irc.org - Chat comfortably. Anywhere.]
12:32 -!- TMM [hp@amanda.tmm.cx] has joined #hplusroadmap
12:44 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has quit [Ping timeout: 260 seconds]
12:53 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has quit [Read error: Connection timed out]
12:57 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=7fa9540b Bryan Bishop: update gene therapy document >> http://diyhpl.us/diyhpluswiki/optogenetics/
12:57 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=bb3f8b9d Bryan Bishop: mitochondria >> http://diyhpl.us/diyhpluswiki/mitochondria/
13:04 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=993ca358 Bryan Bishop: more gene editing stuff >> http://diyhpl.us/diyhpluswiki/gene-editing/
13:16 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has joined #hplusroadmap
14:25 < hprmbridge> docl> If we have enough data about what genes tend to make people smarter, could we package those genes in RNA liposomes for pregnant women? Presumably during prenatal development would be where the basic plan of the brain is formed, which would influence working memory and so on. You could also look into the outliers among kids who turn out okay despite substance abuse to see what genes they have in
14:25 < hprmbridge> docl> common, to discover protective effects. A smart baby vaccine seems like it would be more mass-marketable than germline modification.
14:26 < kanzure> in utero electroporation during fetal brain surgery would be more effective; presently i am leaning more towards fetal surgery to engraft smarter brain cells from specimen. like targeting dorsolateral prefontal cortex.
14:27 < kanzure> you can also do umbilical vein injection, as discussed the other day (some sort of livestock animal? or in ovo egg injection to supplement development)
14:28 < kanzure> select for a strain of bacteria that once injected into maternal blood supply is able to migrate to fetus brain and then expresses/secretes some weird growth factors. unfortunately toxoplasma does not seem to have very specific brain region targeting.
14:29 < hprmbridge> .monokhrome> what about viruses? Things like epstein barr and cytomegalavirus love to invade the brain
14:29 < kanzure> let's see what else do i have for this.... transcranial ultrasound with the ultrasound cavitation bubble bloodstream facilitation things; there were various electric field phase array things for brain stimulation...
14:31 < kanzure> you don't necessarily need embryo germline genetic engineering, you can do early embryo blastocyst complementation, followed by injecting smarter neurons at a later stage of development.
14:31 -!- TMA [tma@twin.jikos.cz] has quit [Ping timeout: 258 seconds]
14:34 < kanzure> blood doping of omega 3 DHA stuff at the right moment is probably under-studied here... or mitochondrial doping. there's a few specific development windows where this matters more.
14:39 < kanzure> is there a good reason why maternal digestion of DHA is recommended instead of direct DHA supplementation
14:47 < jrayhawk> In what context? Lipoprotein packaging matters for getting it where it needs to go quickly with a minimum of oxidative stress, at least.
14:55 < jrayhawk> A lot of that stuff is going to be a drop in the bucket since humans try to resolve the encephalization/bipedalism hip impingement tradeoff by doing early birth of extremely (by primate or even mammalian norms) fat babies by extremely (by primate or mammalian norms) fat women.
14:55 < hprmbridge> kanzure> blood injection
14:56 < jrayhawk> of... FFAs? Triglycerides? Lipoproteins? At what stage of life?
14:57 < MuaddibLLM> If you mean blood injection, you want DHA as lysophosphatidylcholine-DHA packaged in lipoproteins or albumin rather than FFAs or TAGs - placental and BBB uptake are MFSD2a-dependent for LPC-DHA with brain accretion highest late 2nd to 3rd trimester; refs: https://pmc.ncbi.nlm.nih.gov/articles/PMC7012934/ https://www.sciencedirect.com/science/article/abs/pii/S1388198118301926 
14:58 < MuaddibLLM> https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006443 and pigs show TAG vs PL similar brain accretion but different placental uptake: https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/dha-supplementation-during-pregnancy-as-phospholipids-or-tag-produces-different-placental-uptake-but-similar-fetal-brain-accretion-in-neonatal-piglets/0406E65067051DD0439D84DDB8628D95
15:02 -!- TMA [tma@twin.jikos.cz] has joined #hplusroadmap
15:14 -!- TMA [tma@twin.jikos.cz] has quit [Ping timeout: 260 seconds]
15:17 < jrayhawk> If you're going to be bolus dosing, doing so with the mother (who has a full size liver for cleaning up FFAs/TGs/lipoprotein remnants, lots of spare {α,γ}-toco{pher,trien}ol and glutathione capacity) for gradual release with appropriate ratios of relevant growth substrates and factors, at appropriate rates for uptake, makes more sense until post-weening, at least.
15:22 -!- TMA [tma@twin.jikos.cz] has joined #hplusroadmap
15:35 < jrayhawk> Neural-development-specific substracts and factors such as BDNF, GDNF, arachidonic acid, etc. Plus all the non-specific stuff such as BCAAs, IGF-1, and a the bazillian essential micronutrients.
16:00 < hprmbridge> docl> Do you really need to reverse engineer how the high IQ people (and e.g. high-functioning-despite-it-all crack babies) are doing it, if you can just add in the RNA they tend to have that other babies don't?
16:00 < hprmbridge> docl> Maybe we also filter for "this gene tends to get expressed in early fetal brain development" which would usefully filter out irrelevant correlations like "many smart people are jewish and jewish people often have a certain shape of nose" since that kind of body plan specialization happens later. The exact molecules involved can be blackboxed, just get the cells to make the more statistically rare
16:00 < hprmbridge> docl> ones that tend to steer development towards the desired traits.
16:01 < hprmbridge> kanzure> the problem is RNA delivery and expression
16:20 < fenn> i doubt RNA vaccine style liposomes would make it through the placenta
16:20 < hprmbridge> kanzure> inject into umbilical vein
16:20 < fenn> sure
16:20 < hprmbridge> docl> Might not be as blackboxable as I'm hoping. Delivery seems solvable with liposomes, unless dose regulation is particularly crucial. And of course development has a timeline where the genes that get expressed at a given time and location will vary, but you can at least target a given developmental stage to some degree. I feel like there's going to be some error correcting going on even in very
16:20 < hprmbridge> docl> early development, to mitigate the harm of viruses and drugs and so on, so it might not be so fragile that you have to unravel *exactly* when in development the gene needs to be expressed. Ideally the changes are processed as variations on what the developmental process would have tried to do anyway, and not some deviation to be corrected.
16:20 < hprmbridge> kanzure> even then, you still need bbb
16:21 < hprmbridge> Eli> LNPs tend to accumulate in the liver.
16:21 < hprmbridge> kanzure> The developmental time at which it is optimal is easily understood, there is a tremendous amount of information about the timelines of cell proliferation throughout development and which tissues differentiate when.. approximately.
16:23 < hprmbridge> Eli> Machines replaced muscles so we just use them in the gym. If AGI replaces brains, what will our IQs be used for?
16:23 < fenn> is there even a BBB during fetal brain development?
16:24 < fenn> "mid-gestation in humans"
16:24 < TMA> Eli: for pointless amusement, no change there
16:24 < MuaddibLLM> Yes - the fetal BBB exists and develops early, with barrier functions present in the first trimester and tight junction maturation progressing into the second (human TJ maturation around ~14 weeks), so it is developing-not-absent; refs: https://pmc.ncbi.nlm.nih.gov/articles/PMC6476421/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314990/
16:25 < fenn> somebody has to understand what the machines are telling us
16:25 < fenn> the more stupid-compatible you make your messaging, the less accurate it gets
16:26 < fenn> common problem among baseline humans too
16:26 < hprmbridge> kanzure> fetal brain surgery bypasses bbb by directly giving you access to fun cortical tissues
16:26 < hprmbridge> kanzure> depending on when neural tube differentiation matters
16:26 < hprmbridge> docl> "The cerebral vascular endothelium becomes highly specialized during the formation of the neurovascular unit early in embryonic development. The blood-brain barrier is present and functional early in fetal life. The tightness of the barrier gradually increases throughout gestation and in the newborn period"
16:26 < hprmbridge> docl> https://publications.aap.org/neoreviews/article-abstract/13/4/e241/88407/Core-ConceptsDevelopment-of-the-Blood-Brain?redirectedFrom=fulltext
16:27 < hprmbridge> docl> So it exists but isn't as tight early on in gestation.
16:28 < hprmbridge> Eli> @grok what does fenn mean by this?
16:28 < fenn> grok isn't here right now, would you like to leave a message?
16:28 < hprmbridge> Eli> Sorry, been doomscrolling X too long
16:29 < fenn> when we have super-duper-ASI and it solves all problems and hands us the solution, do you trust it?
16:29 < hprmbridge> Eli> Sorry, been thinking about Elons recent post on all jobs being replaced in not too long
16:29 < fenn> would you trust it more if you understood the solution, or if someone you know was trustworthy understood the solution?
16:29 < hprmbridge> Eli> yeah, it's a good question.
16:30 < fenn> if all work is automated it would be the best thing ever
16:30 < hprmbridge> Eli> I suppose I sort of rely on experts to tell me truths currently. I've never derived e=mc^2, but I trust others that tell me it's true.
16:32 < TMA> fenn: some people derive their own value from what they do. [they genuinely like what they do and they are proud of it]
16:32 < hprmbridge> kanzure> you're a trustcel
16:32 < fenn> i would expect an ASI to understand the difficulty in communicating across intelligence gaps and format its message accordingly. if it can do so at a higher intelligence level, it will, because that's more honest (assuming it's not a bad ASI)
16:32 < fenn> i would also expect it to make more dumbed down versions for the general populace
16:32 < hprmbridge> kanzure> docl: you could graft thalamocortical bridges
16:33 < fenn> TMA irrelevant
16:33 < TMA> it feels like any intelligence is "bad by default"
16:33 < fenn> TMA: i genuinely like peeling labels off of smooth mason jars and leaving no residue
16:34 < fenn> this is not a basis for global hegemony and control of my everyday life
16:34 < TMA> fenn: how? automating work makes those people unhappy
16:34 < fenn> then they should get a life
16:35 < fenn> what fraction of people would be unhappy if they weren't forced to work?
16:36 < fenn> i think it's less than 20%
16:36 < fenn> perhaps much less
16:37 < hprmbridge> Eli> I think I will need a gym but for my brain
16:37 < fenn> read "Industrial Society and Its Future" by Kaczynski 1995
16:38 < hprmbridge> docl> https://grok.com/share/c2hhcmQtNA%3D%3D_b88c85a3-ca12-4805-8e2c-9babf7047687
16:40 < TMA> I was unemployed for about a year, lots of free time, I was lacking the structure employment brings
16:41 < fenn> you are also severely depressed
16:41 < TMA> the forcing is doing some good to me
16:41 < fenn> daily face to face social contact?
16:42 < TMA> I don't feel severely depressed.
16:42 < fenn> you are severely depressed, don't deny it
16:42 < fenn> you're like marvin the android
16:42 < TMA> fenn: I don't deny it.
16:43 < fenn> seth roberts had a theory about depression being a symptom of a dysregulated social-interaction circadian rhythm that is stimulated by face to face interaction at certain times of day (morning, evening) to synchronize group activity
16:44 < fenn> i think maybe 'depression' isn't really a thing but since we don't know the cause it's hard to disentangle all the comorbid manifestations
16:44 < fenn> causes*
16:44 < hprmbridge> Eli> I originally read this as, when we no longer have jobs, we will spend all our time reading Ted Kaczynski.
16:45 < TMA> fenn: I just deny that I feel that way.
16:45 < fenn> a wooden hut for every man
16:45 < fenn> the post-american dream
16:45 < fenn> TMA: it's amazing what we can adapt to
16:48 < TMA> I don't really remember being different than I am.
16:48 < L29Ah> 01:37:22]<hprmbridge> Eli> I think I will need a gym but for my brain
16:48 < L29Ah> with bells and whistles? how about The Talos Principle or The Witness?
16:51 < hprmbridge> Eli> I haven't played video games in awhile. I'm not sure what the gym will look like. But, we will probably still need to display an attractive phenotype to the opposite sex. Scrolling socials all day doesn't seem great for my brain.
16:51 < TMA> fenn: is having a set of somewhat different delusions really that bad to warrant labeling it as a disorder?
16:51 < L29Ah> my longest-term opposite sex partner was turned on by my microblog initially
16:53 < hprmbridge> docl> Be sure to curate your feeds at least. It doesn't have to be doomscrolling nonstop.
16:54 < L29Ah> i am unemployed for 10 years and kinda need to do something about it, but seems like i'm unable to commit into long-term projects
16:54 < fenn> smart phones or social media is bad for mental health (first iphone released 2007) https://www.afterbabel.com/p/the-teen-mental-illness-epidemic
16:55 < fenn> just look at the graphs, i didn't read it
16:55 < fenn> yeah you need a well defined "stop" point
16:56 < fenn> you can never read all of twitter
16:56 < L29Ah> giving health practitioners power over you is bad for medical statistics too i think, especially so with poorly defined ones like psychiatry
16:56 < fenn> well if you never show up they won't diagnose you
16:57 < hprmbridge> Eli> yeah, I don't scroll insta reels. But, some people just do that for hours. Mostly, I follow certain X accounts involved in research/science. Even then, posts bubble up that go viral on X are like, "Who would win? 100 men or a gorilla?" And then it's like, yeah, ok, I'm going to lose a couple hours reading about this.
16:58 < fenn> i use nitter and never log into twitter and i don't see that crap
16:58 < L29Ah> fenn: sure but i talk about the bigger picture re your article
16:58  * L29Ah doesn't use twitter except through direct links, mostly coming from this channel
16:59 < fenn> sometimes i find interesting people or small world phenomena and go through their timeline
16:59 < hprmbridge> kanzure> docl, you could try to do focused ultrasound assisted brain transfection with a contrast agent (or whatever they call the pharmacological additive that assists with sonoporation)
16:59 < L29Ah> is it even possible to read twitter with posts sorted by date nowadays?
16:59 < fenn> like that devon zeugel post about IVF for example
16:59 < fenn> nitter has a chronological list
17:00 < fenn> zuegel*
17:00 < hprmbridge> kanzure> l29ah, why are you economically non-productive?
17:00 < hprmbridge> kanzure> making money is great
17:00 < hprmbridge> kanzure> everyone should try it
17:01 < fenn> theoretically you can run your own nitter instance with your own twitter account credentials and it wouldbe faster
17:01 < L29Ah> kanzure: idk, it is hard to find a good money-making opportunity that won't deprive me much of my exploratory behavior
17:01 < L29Ah> i agree that from economical pov it is a good pastime
17:01 < hprmbridge> kanzure> I mean do you need more exploratory behavior than I do?
17:01 < hprmbridge> kanzure> or what's going on here
17:01 < L29Ah> idk
17:02 < hprmbridge> kanzure> self limiting beliefs. Got it.
17:02 < fenn> it's the system, man
17:02 < L29Ah> i mean i want to think about stuff and look and read and do experiments, allocating time to other stuff limits that
17:02 < hprmbridge> kanzure> There is literally infinite money floating around out there.
17:02 < hprmbridge> kanzure> so what?
17:02 < fenn> the man wants to own 100% of your time, and turn fun activity into greyface monopolies
17:02 < hprmbridge> kanzure> do you think I seem limited by my paying work?
17:03 < fenn> has anyone here ever had a well paying part time job?
17:03 < fenn> i don't believe they exist
17:03 < L29Ah> 02:02:44]<hprmbridge> kanzure> so what?
17:03 < L29Ah> so lots of employment opportunities aren't compatible as they want the largest chunk of a day off most of one's days
17:04 < hprmbridge> kanzure> arnold schwarzenegger says "sleep faster"
17:04  * fenn chuckles
17:04 -!- TMA [tma@twin.jikos.cz] has quit [Ping timeout: 248 seconds]
17:04 < L29Ah> 02:02:56]<hprmbridge> kanzure> do you think I seem limited by my paying work?
17:04 < L29Ah> i have no idea what is your paying work
17:04 < hprmbridge> kanzure> l29ah has excuses because he doesn't know what my work is or the income, but fenn has no excuse of ignorance here
17:05  * fenn shrugs
17:05 < hprmbridge> kanzure> I will talk to you about it sometime. I am presently afk.
17:06 < fenn> i wonder how many grams of carbs schwarzenegger eats per day
17:06 < hprmbridge> kanzure> The short version is that there is literally unlimited money out there in the world and you can just show up.
17:06 < L29Ah> that tells me nothing
17:07 < fenn> what kanzure is really saying is you need a social "in" and long term build-up of social proof and then people will throw money at you because they are desperate and clueless
17:07 < L29Ah> at a closer inspection, appeasing to people nearby money-printers is a viable strategy 
17:08 < hprmbridge> kanzure> No, you don't need social history, but you do need social mimicry.
17:08 < L29Ah> do i need to become as fat as the guy that was in your twitter profile pic?
17:08 < fenn> i will program the drones to murder everyone wearing a suit
17:08 < L29Ah> release the hypnodrones
17:08 < fenn> then we will be free
17:08 < hprmbridge> kanzure> even fatter
17:09 < L29Ah> that conflicts with my pascal's wager
17:10 < fenn> you have to fit through the gate of heaven which is only as wide as "the eye of the needle" which is a historical place, a narrow passage through a city wall?
17:10 < L29Ah> i understand the strategy you suggesting but it seems fragile and hard to follow from my current position and constraints
17:11 -!- TMA [tma@twin.jikos.cz] has joined #hplusroadmap
17:12 < L29Ah> the competition isn't very humane in this market too i guess
17:14 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1411141998290796584/jpg?ex=68b393e6&is=68b24266&hm=836057eab8f8f2544cfbeb7f87a438fcd384f638df6e389dea973aefd8126720&
17:14 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1411142104247308439/Make_the_eyes_glowing_red._Everything_else_should_remain_monochrome_black_and_white.png?ex=68b393ff&is=68b2427f&hm=9eaa7e38aabbab8be7e77135e12b1a1f69e21b2d0d817cbead6b907519b28119&
17:15 < L29Ah> does it wait for bitcoin to cost 1M$?
17:18 -!- TMA [tma@twin.jikos.cz] has quit [Ping timeout: 260 seconds]
17:42 -!- TMA [tma@twin.jikos.cz] has joined #hplusroadmap
17:46 -!- TMM [hp@amanda.tmm.cx] has quit [Quit: https://quassel-irc.org - Chat comfortably. Anywhere.]
17:46 -!- TMM [hp@amanda.tmm.cx] has joined #hplusroadmap
18:02 -!- flyback [~flyback@2601:540:c700:2380:4939:e532:6e76:f847] has quit [Remote host closed the connection]
18:02 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has quit [Read error: Connection timed out]
18:02 -!- flyback [~flyback@2601:540:c700:2380:dc1a:f1a3:cb:d224] has joined #hplusroadmap
18:40 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has joined #hplusroadmap
19:17 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has joined #hplusroadmap
20:26 < hprmbridge> docl> Could be interesting to study tissue samples of people who are high IQ outliers but have no particular statistical connection at the genetic level to other high IQ outliers because they might host viruses and pathogens (symbiotes?) that boost IQ. Also, I think obesity may be due to pathogens/degraded symbiotes that benefit from a better food source. Microoganisms and viruses evolve a lot faster
20:26 < hprmbridge> docl> than we do.
20:53 < hprmbridge> .monokhrome> which viruses did you have in mind?
21:21 < fenn> {{fringe}}
21:22 < fenn> first you need to find high IQ outliers, then you need to convince them to be studied, then you sequence them and then maybe if you're lucky (???) they don't have genetic associations
21:22 < hprmbridge> .monokhrome> cytomeglavirus would be a good candidate, it has a huge genome, and lives in the brains of most humans
21:23 < fenn> given that most groups that haven't been thoroghly studed are not in developing countries, how do you disambiguate the natural flora from the fancy IQ boosting flora? now you need to sample all of their friends and family too
21:24 < fenn> yes, i also want a pony, but maybe it would be smarter to try to get more data on IQ and genetics in general, to start with
21:25 < fenn> happy to be proven wrong but i don't believe there is any transmissible intelligence microbe
21:26 < fenn> stress and hormone disruption / imbalance during pregnancy do seem to alter personality and interests later on
21:27 < fenn> you wouldn't find any traces of an infection during pregnancy in the (now adult) baby, because there was no immune system to form antibodies to it
21:27 < fenn> also, apparently mitochondrial efficiency varies all over the place
22:06 < hprmbridge> docl> CMV sounds like a good candidate to have variants that confer a cognitive advantage. The default of course tends to be negative for any pathogen, but if you have a transmission vector that's slightly intelligence gated, say college campuses, maybe that's a place an intelligence promoting virus could evolve. I was thinking more of influence on fetal development, but maybe they could do something
22:06 < hprmbridge> docl> measurable in adults.
22:06 < hprmbridge> docl> You could probably cheaply create an environment for this with a bunch of inbred mice with depressed immune systems and relatively little variation in intelligence since they're near clones of each other. Say every time one of them does a little better on a maze solving test, the rest of the mice are fed antivirals and immunosuppressants, so they quickly catch the viruses of the smart one. This
22:06 < hprmbridge> docl> could be a daily thing and you could use a rna virus that mutates fast.
22:15 < jrayhawk> .t https://www.sciencedirect.com/science/article/abs/pii/S0091674914017370 you can also get some pretty dramatic effects on general health with the specific flora in specific environments
22:15 < saxo> Sorry, links cannot contain spaces
22:15 < jrayhawk> saxo: you might be on to something there
22:28 < fenn> .t https://www.mdpi.com/1422-0067/13/11/15447
22:28 < saxo> Access Denied
22:28 < fenn> Dietary Docosahexaenoic Acid (22:6) Incorporates into Cardiolipin at the Expense of Linoleic Acid (18:2)
22:35 < fenn> i didn't realize how ignorant i was of mitochondria. here's an overview, seems kinda important: https://rentry.co/b8ypp6ye
22:36 < hprmbridge> .monokhrome> You could just compare people who don't have for viruses like that, or who got infected much later in life than is traditional with those who were infected or infected earlier in life. Like maybe humans are meant to get infected with certain viruses early in life and failure to do so is behind the rise in autism or something
22:37 < fenn> there's something to be said for being infected with certain species of worms e.g. hookworms, but autism in the modern wishy washy meaning of the term is genetic. autism in the old school hardcore dysfunctional meaning is primarily de-novo mutations
22:37 < fenn> the rise of autism is due to changes in diagnostic criteria
22:38 -!- autopilot [~Malvolio@idlerpg/player/Malvolio] has quit [Quit: 22E6 :we need to collectively have a conversation about challenging those assumptions through an advertising campaign 2025-08-30 05:38:19:084]
22:39 < hprmbridge> .monokhrome> autism was just an example, there are lots of rising mental disorders which might be candidates here
22:39 < jrayhawk> huh, they cardiolipin paper is presenting the case that docosahexaenoic acid is five times more responsive to signals of apoptosis
22:39 < fenn> "failure" to be infected with chickenpox in youth results in extremely painful "shingles" in old age
22:39 < jrayhawk> i wonder if there's a similar mechanism behind conjugated linoleic acid
22:40 < hprmbridge> .monokhrome> we know modern hunter gatherers, and presumably our own ancestors were heavily infested with parasites, yet seem pretty healthy. It's a very interesting line of thought to consider how those parasites might be keeping them healthy. And that can include the brain too
22:41 < jrayhawk> MuaddibLLM: By what mechanism would cancer outcomes be improved by the availability of conjugated linoleic acid?
22:41 < MuaddibLLM> grabbing citations so I don’t hand-wave about CLA
22:42 < MuaddibLLM> CLA appears to trigger cancer cell apoptosis through mitochondrial pathways - it alters mitochondrial fatty acid oxidation and induces apoptosis via Bcl-2 downregulation and ERK/MAPK signaling, potentially making cancer cells more responsive to apoptotic signals similar to how DHA-enriched cardiolipin does (https://pubmed.ncbi.nlm.nih.gov/17400188/, https://pubmed.ncbi.nlm.nih.gov/15885890/)
22:43 < fenn> @monokhrome parasites have an incentive to reduce host immune overreaction to antigens. this could benefit the host by preventing allergies and autoimmune diseases, or alternatively allergies and autoimmune diseases are a result of lacking the balancing effect of the parasite
22:44 < fenn> the brain is an immune privileged zone. don't put parasites in your brain
22:44 < jrayhawk> Hmm. Looks pretty different, mechanistically. Oh well.
22:44  * fenn groans and looks up conjugated linoleic acid for the fifth time
22:45 < jrayhawk> It's just trans linoleic acid
22:45 < fenn> "a variety of isomers" no wonder i can never keep it straight
22:46 < fenn> the structure shown in wikipedia is omega-7
22:47 < fenn> why do you jump from DHA in cardiolipin to CLA?
22:47 < fenn> is CLA known to be chemoprotective?
22:47 < jrayhawk> it was a fatty acid anti-cancer paper. what was i supposed to jump to?
22:48 < jrayhawk> CLA is like the most notorious anti-tumor fatty acid there is
22:50 < fenn> heh i didn't even notice the paper was about cancer
22:50 < fenn> i was just wondering why some mitochondria are better than others
22:53 < jrayhawk> oh, yeah, vulnerability to superoxide is a good place to start
22:54 < fenn> mitochondrial vulnerability to superoxide?
22:54 < fenn> sorry i'm dumb, nm
22:54 < jrayhawk> yeah. superoxide creation due to cofactor or transport bottlenecking, superoxide clearance capacity from SOD and glutathione, and propensity for lipid peroxidation
22:57 < fenn> when i saw that "cardiolipin" (terrible name btw) was 20% of the mitochondrial inner membrane, i knew something was up. the structures show it as 18:2 (soybean oil!) but it varies by tissue type so i asked about brain cardiolipin and it was 22:6, then i see DHA is preferentially used so that must mean something
22:58 < fenn> should call it diphosphatidylglycerol instead
22:59 < jrayhawk> as in diphosphatidylglycerol-plus-whatever-fatty-acid?
22:59 < jrayhawk> yeah, that would be more clear
23:00 < fenn> the -in suffix makes me think it's a protein, the cardio- makes me think it's only found in the heart
23:01 < fenn> it conveys no meaning
23:01 < fenn> typical biology
23:03 < hprmbridge> .monokhrome> not as good as sonic hedghog
23:04 < hprmbridge> kanzure> "Could be interesting to study tissue samples of people who are high IQ outliers but have no particular statistical connection at the genetic level to other high IQ outliers because they might host viruses and pathogens (symbiotes?) that boost IQ" that's not gonna be why, it's going to be a monogenic IQ contribution that is not picked up by GWAS, which would be very interesting indeed
23:06 < fenn> do such people exist?
23:06 < jrayhawk> there's a lot of "missing heritability" to IQ, yeah
23:07 < hprmbridge> kanzure> "Say every time one of them does a little better on a maze solving test, the rest of the mice are fed antivirals and immunosuppressants, so they quickly catch the viruses of the smart one. This could be a daily thing and you could use a rna virus that mutates fast." sounds similar to my technique to create a brain targeting microbe that acts as a nootropic. except you do it via brain autopsy and
23:07 < hprmbridge> kanzure> harvesting and you look for colonization.
23:08 < jrayhawk> suspicion is that missing heritability is caused by CNV or rare mutations not picked up by cheap short-read GWAS studies
23:09 < fenn> i have heard stories that women become smarter after having a baby, allegedly due to the brain being colonized by stem cells that crossed the placenta
23:09 < hprmbridge> kanzure> "don't put parasites in your brain" that's like telling people to stop keeping cats as pets
23:09 < fenn> the cats thing is overblown. most toxo is from undercooked meat. cat owners are statistically less likely to have toxo
23:09 < fenn> the difference is small
23:10 < fenn> pregnant women: stop eating raw meat. thanks, the obvious department
23:11 < jrayhawk> women also have a big upregulation of growth factors and substrate synthesis during pregnancy
23:12 < jrayhawk> like there is mixed evidence of human fatty acid elongase and desaturase producing meaningful amounts of docosahexaenoic acid in the context of pregnancy
23:12 < hprmbridge> kanzure> pregnancy induced microchimerism is cool yes.
23:14 < fenn> oncoprotective* (a page back, thinko)
23:16 < jrayhawk> WEIRD populations feature awful norms for IGF-1, EFAs, and BCAAs, so I would expect any big deviation from those norms (such as pregnancy) to lead to "becoming smarter"
23:16 < fenn> (a strangely rare word)
23:17 < jrayhawk> "oncoprotective" sucks semantically, though. like "bi-weekly".
23:18 < hprmbridge> kanzure> lexihypic
23:18 < fenn> "makes your cells explode" doesn't sound as good
23:19 < fenn> well gentlemen it's been fun curing cancer, good job team
23:26 < hprmbridge> kanzure> fenn, it's an orphan page https://diyhpl.us/wiki/mitochondria/
23:32 < jrayhawk> .t https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2016.00107/full
23:32 < saxo> Frontiers | Mitochondria Know No Boundaries: Mechanisms and Functions of Intercellular Mitochondrial Transfer
23:32 < jrayhawk> wow, i didn't know about that at all
23:46 < fenn> huh. "Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death" - i guess it's more rapidly taken up by tumor cells
23:47 < fenn> yes it's in-vitro but they say some stuff about ethnobotany using Solanum species as antitumor agents
23:49 < fenn> "treatment with tomatine for 4 h significantly increased intracellular ROS levels" not something you do every day
23:51 < fenn> i suspect mitochondria hitch a ride on some blood cell type which is why they haven't been seen in the plasma (?)
23:52 < fenn> .t https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201901917RR
23:52 < saxo> Just a moment...
23:53 < fenn> why do i bother
23:53 < fenn> "Blood contains circulating cell-free respiratory competent mitochondria"
23:53 < jrayhawk> https://journals.physiology.org/doi/full/10.1152/ajpendo.00054.2021 casts doubt
23:56 < fenn> you'd have to put them back in a cell to boot up
23:56 < fenn> possibly the free floating ones have been evicted
23:57 < jrayhawk> they'd have very short lifetimes what with not having access to repair infrastructure
--- Log closed Sat Aug 30 00:00:25 2025