--- Log opened Wed Aug 14 00:00:22 2024
00:58 -!- dartmouthed [~blackunsp@li761-35.members.linode.com] has quit [Quit: ZNC 1.8.2 - https://znc.in]
00:59 -!- dartmouthed [~blackunsp@li761-35.members.linode.com] has joined #hplusroadmap
01:02 -!- mxz_ [~mxz@user/mxz] has quit [Ping timeout: 248 seconds]
01:04 -!- ike8 [e8f913dbdf@irc.cheogram.com] has quit [Ping timeout: 248 seconds]
01:19 -!- justanot1 [~justanoth@gateway/tor-sasl/justanotheruser] has quit [Remote host closed the connection]
01:21 -!- justanotheruser [~justanoth@gateway/tor-sasl/justanotheruser] has joined #hplusroadmap
01:22 -!- Netsplit *.net <-> *.split quits: FelixWeis__, SDr, s0ph1a, otoburb
01:34 -!- Netsplit over, joins: FelixWeis__, otoburb, s0ph1a, SDr
02:23 < fenn> i was thinking about BHT for reducing the damage to fats during cooking, and discovered that people take it as a supplement or drug
02:26 < fenn> steve fowkes (i've heard that name before!) wrote a book about using BHT for viral infections including chronic infections https://projectwellbeing.com/wp-content/uploads/2020/03/BHTbook-StevenWmFowkes-200302.pdf
03:06 -!- mxz_ [~mxz@user/mxz] has joined #hplusroadmap
04:17 < alethkit> Eli: dont really want to do genomic testing until I can do it locally on hardware
05:02 < hprmbridge> alonzoc> What's the current status of the mitochondrial theory of aging? Because I was reading a study on correlations between parental lifespan and their childs and the correlation seems to be strongest with the parent of the same sex. Going in I thought it'd probably correlate more strongly with the mother than the father for all children, especially if mitochondrial disfunction was the primary cause of
05:02 < hprmbridge> alonzoc> aging
05:04 < nsh> it's not just doing something by itself is it
05:05 < nsh> on no my mitrochondrium which is in no way existing in continuous complex interaction with the cell mediated by nuclear-DNA-resultant processes just up an expired. woe is me
05:09 < nsh> mDNA might for instance predispose one to relatively higher production of reactive oxygen but this might be compensated for as a result of material and/or paternal nDNA contributions
05:09 < nsh> +species
05:10 < nsh> i don't think you can infer anything from the lifespan correlations study at all, let alone in the context of specific theories of ageing-related processes or dysfunctions
05:12 < nsh> stress is also a major (extrinsic) component in these processes, and predisposition to stressors may correlate more strongly for societal reasons with the parent of the same sex
05:13 < hprmbridge> alonzoc> True, it just went against my expectations so was gonna ask here what the latest consensus is on the root cause of aging. Given aging is a degradation of a functional network and global properties of networks tend to be more strongly dependent on outlier connections (weakest, strongest,  most bridge-like, etc link) I'd expect aprori that if mitochondria was the weakest link in the system
05:13 < hprmbridge> alonzoc> mitochondrial differences would be the primary factor for aging
05:17 < hprmbridge> alonzoc> That last point is actually a really good one
05:29 < kanzure> strange to see this having a life of its own without me actively involved https://btctranscripts.com/
05:32 < fenn> there is no consensus on the root cause of aging
05:32 < hprmbridge> alonzoc> kanzure: The bitcoin community moved beyond using you as it's universal secretary?
05:32 < kanzure> well, i got too busy and stopped going to a bunch of conferences or doing transcripts
05:33 < kanzure> the site pays people to do transcripts
05:33 < kanzure> (and this wasn't built by me)
05:37 < hprmbridge> alonzoc> fenn: I know it kinda annoys me coming from a focus on CS and physics, Biological systems are insanely messy and complex. Every time I read about the immune system or the like in any great detail I get insanely confused
05:37 < kanzure> eventually human biology will need to be migrated to solid state alternatives or something that is not so impossibly hard to debug and fix
05:38 < kanzure> unfortunately, biological substrates are our current only programmable exponential self-replicators that we have access to
05:40 < kanzure> things like brain fixation (read as: physical fixation of human biological memory, personality, or skill) could be a stopgap measure
05:40 < hprmbridge> alonzoc> That is something I wish for lol. Atleast with complex codebases you can kinda crib away the complexity and mess due to human intentionality, plus the interactions are explicit and rigid.
05:41 < kanzure> see https://gnusha.org/logs/2022-12-14.log
05:41 < hprmbridge> alonzoc> time ref?
05:41 < kanzure> 11:23 < kanzure> too many things go wrong with biology and it's too hard to predict/reason about, therefore the system should be upgraded to something that makes more sense to our primitive intellects
05:41 < kanzure> "... there is no source, the bytecode has multiple reentrent abstractions, is unstable and has a very low signal to noise ratio, the runtime is unbootstrappable, the execution is nondeterministic, it tries to randomly integrate and execute code from other computers... multiple reentrant and self-modifying abstractions. absolutely everything has subtle side effects."
05:41 < kanzure> https://groups.google.com/g/diybio/c/GxRTESzUWUI/m/IS-zLDlUu_YJ
05:43 < hprmbridge> alonzoc> Protein folding isn't to bad if that was everything. The main issue is the common media of the cytoplasm. A nano-factory where all molocules are confined to their transport belts is much nicer 😄
05:43 < kanzure> there are some biological mechanisms for spatial addressing like on cytoskeleton.. or maybe spatial addressing is the wrong way to say it. scaffolding of some kind at least.
05:44 < fenn> the endoplasmic reticulum is kinda like that conveyor belt you imagine
05:44 < fenn> also they tow bags of stuff around
05:44 < kanzure> story of my life
05:45 < kanzure> for aging in particular i continue to believe that germline intervention is where we can plausibly get the most bang for the buck
05:45 < hprmbridge> alonzoc> The energy landscape of the proteins in general is something like a spin funnel which makes everything fairly nice
05:45 < kanzure> spin funnel?
05:45 < hprmbridge> alonzoc> Oh wikipedia has it as folding funnel
05:45 < fenn> nobody's stopping you from germline interventioning yeast or flies
05:46 < kanzure> i don't have a good source that talks about how enzymatic activity of polymerase, ribosome, etc is like pushing stuff up an energy gradient and consuming local resources to do so.. something to help illustrate the point that these machines are fighting against entropy or something. maybe there's a reference out there.
05:46 < fenn> the problem is the anti-aging community thinks a 50% increase in lifespan is progress on solving aging
05:47 < hprmbridge> alonzoc> kanzure: https://www.researchgate.net/publication/221925547_Protein_Folding_Binding_and_Energy_Landscape_A_Synthesis figure 2 is what the energy landscape of protein folding looks like. The dimensionality is still high but biology evolved for energy landscapes which physics can solve quickly even if they are still non-convex
05:47 < kanzure> there are many problems in the anti-aging community, such as the fascination with supplements and small molecule interventions, short time horizons and a focus on current adults, a lack of regard for the enormity of the problem and how it might take 350 years to solve aging (it might also take less time!)
05:48 < kanzure> like, if we're living in a world where anti-aging tech really does take 200 more years of sustained current levels of biological research efforts, then we ought to be preparing the advocates for this so that nobody gives up in 50 years for all the false promises of anti-aging researchers
05:48 < kanzure> because it is more important that we solve aging in 200 years than not solving it at all
05:49 < kanzure> this is similar to the point i like to make that even if we can't solve adult anti-aging in time for current adults to be uhh anti-aged (or whatever), we should still be fairly thrilled about being able to get big gains for next-generation children that aren't yet born, because there's a fair chance we could be the last generation to die from aging which is a pretty good outcome in the scheme ...
05:49 < hprmbridge> alonzoc> Yeah the small molocule stuff is nice but I strongly doubt it'll actually provide a lifespan boost upto many hundred of years
05:49 < kanzure> ...of things from "aging is totally unsolvable" to "aging is completely solved for everyone currently living"
05:51 < fenn> alonzoc the OSMK stuff makes it seem like aging is just a continuation of the developmental program, but the program just doesn't lead anywhere
05:51 < kanzure> for the level of complexity and difficulty of the anti-aging problem, i do not see anti-aging advocates at the levels or depths of weirdness that i would expect someone to have, there's a lot of weird midwit stuff going on that needs to be ostracized
05:52 < fenn> you can't dump several billion dollars on an industry and expect thousands of geniuses to magically appear
05:52 < hprmbridge> alonzoc> fenn: Why don't you think the yamanaka factor stuff won't lead anywhere? the hype for the chemical cocktail paper makes me worried people will switch from looking at epigentic stuff to the search for a simple small molocule cocktail though
05:52 < kanzure> fenn: why not! that should exactly be our expectation!
05:53 < kanzure> and if they don't appear then we need to do the social pressure cooker chamber thing until we turn young people into those weirdo geniuses then
05:53 < kanzure> like why isn't the default assumption that anti-aging gets mostly solved by schloendorn whole body transplantation/replacement and physical biological memory fixation or brain 3d printing or something.
05:53 < fenn> alonzoc i mean the evolved biological program that turns single general purpose cells into many special purpose cells, that program doesn't lead anywhere after age 30-ish because you've either reproduced or not at that point
05:54 < kanzure> another weird way to solve anti-aging would be a long trajectory human breeding program for families of exceptionally long lived humans. this could take 500+ years and it still might beat out biological research approach to anti-aging.
05:54 < fenn> there's no selection pressure to keep organisms healthy after reproduction
05:54 < kanzure> fenn and i both brought up selection pressure at the same time
05:55 < hprmbridge> alonzoc> kanzure: well there is a ramp up time to get more people into biotech as it needs training time. Like we had it with CS to some degree once bigtech got big you had a tidal wave of people going into tech. Now it's got a bit silly with lots of fairly shallow low skilled people doing CS because they wanna be the next zuckerberg
05:56 < kanzure> i might argue against biotech training, has it helped at all?
05:56 < kanzure> it's important to be able to get lab work done, but that's about it
05:57 < kanzure> my rant about 3d brain printing is unfortunately too hypothetical because human brain matter is too complex for 3d printing (how do you place long-range dendrites in 3d space while printing everything else)
05:57 < hprmbridge> alonzoc> Yeah, well a sufficient knowledge of genetics and biochem would be useful as well. The theory is important.
05:57 < hprmbridge> alonzoc> I would defo support a scheme outside of the university system for people to get accredited that they won't fuck shit up in a lab.
05:58 < fenn> kanzure instead of waiting 500 years you could do the same breeding program on flies and mice and then port the lessons learned to humans
05:58 < kanzure> maybe, but people still screw stuff up in the lab, and then it's days or weeks of repeating previous work or debugging anyway, like to find what weirdo contamination you caused, and a lot of the work is doing that debugging anyway
05:59 < kanzure> fenn: they did do that on flies, and uh.. i forget where we ended up with regards to lessons learned and applying those to humans. tudor might know.
05:59 < fenn> afaik there are no immortal flies yet
05:59 < hprmbridge> alonzoc> Actually I think you could accelerate it even further if you do IVF for mice you can do embryo selection. Sequence all the mice genomes and correlate with lifespan. You basically have a combinatoric bandit problem and it can accelerate your search.
06:00 < kanzure> well you won't get immortal flies... you will get flies that haven't died yet... not that i'm complaining.
06:01 < hprmbridge> alonzoc> True but a x2 increase in lifespan is sufficient for now. an extra 70 or so years to someones productive life span would buy time for a permanent solution
06:01 < fenn> "Drosophila melanogaster lifespan extension under the combined influence of dietary restriction, co-administration of berberine, fucoxanthin, and rapamycin, photodeprivation, and low-temperature conditions up to 185 days in w1118 strain and up to 213 days in long-lived E(z)/w mutants. The trade-off was found between longevity and locomotion. The transcriptome analysis showed an impact of
06:02 < fenn> epigenetic alterations, lipid metabolism, cellular respiration, nutrient sensing, immune response, and autophagy"
06:02 < fenn> "we studied the long-lived Enhancer of zeste (E(z)) mutant flies. E(z) is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2) with H3K27 trimethylation activity."
06:03 < fenn> so, slow down the program, slow down metabolism, mop up all the garbage
06:03 < fenn> https://www.nature.com/articles/s42003-022-03524-4
06:03 < hprmbridge> alonzoc> Has anyone seen anyone use modified homologous cells (mesenchymal stem cells or T-cells look good) as a vector for in vitro gene delivery?
06:03 < fenn> it could be that there are several root causes of aging
06:05 < kanzure> alonzoc: by this point you are familiar with my rants about adult gene therapy right?
06:05 < hprmbridge> alonzoc> which ones are these?
06:06 < kanzure> that you aren't going to deliver genetic upgrades to every cell in the body
06:06 < fenn> we can certainly afford to spend a lot of money on curing aging, since it will eliminate basically all medical expenses
06:07 < fenn> you don't have to hit every cell
06:08 < kanzure> aren't all the important stem cells you want to target the ones that are hardest to reach by virus?
06:08 < fenn> i suppose it depends on what you want to do
06:08 < fenn> i don't think mutational load matters much at all
06:09 < fenn> humans are full of mutations already from the start
06:09 < kanzure> you wanted to gene therapize the important cells but not necessarily all the cells
06:09 < fenn> why do stem cells matter
06:09 < hprmbridge> alonzoc> Well i'm more considering it for delivering the yamanaka factors. I do agree the optimal solution is to basically abandon the biological substrate alltogether replace the whole body with a nanotech based setup. Could prolly improve most metrics by 2 OOM, lots of biology is fairly close to thermodynamic limits but there is a fair bit of room to improve
06:10 < kanzure> fenn: you want the cells that make your other cells to be de-aged and targeted because.. uh. you don't want to die. have i misunderstood something?
06:10 < fenn> biology hasn't even touched nuclear reactions at all
06:10 < fenn> (unless you believe the stories about chickens transmuting silicon into calcium for the egg shells)
06:11 < hprmbridge> alonzoc> kanzure: I agree viral vectors a probably a fools errand for modifying an adult body. However the immune system tends to ignore mesenchymal stem cells in the tissues the differentiate into and they're quite mobile.
06:11 < fenn> kanzure you can just turn any cell into "a stem cell" with yamanaka factors
06:11 < kanzure> if you want turbo-cancer sure
06:12 < fenn> have you missed the whole partial reprogramming thing somehow?
06:12 < hprmbridge> alonzoc> Yeah but application of a subset just resets the cells to a more youthful stage in their own life
06:12 < fenn> you can revert to any previous point on the differentiation tree
06:13 < fenn> it's not precise enough yet, depends on timing and concentration
06:14 < kanzure> alonzoc: is that equivalent to aubrey's whole body stem cell rejuvenation? i guess not because you're not fixing the stem cell niches, you're proposing instead to constantly be injecting and delivering fresh stem cells to all tissues at whatever appropriate rates?
06:14 < fenn> eventually we will develop sensing methods to regulate the reprogramming activity and have closed loop control over the amount of reverting
06:15 < fenn> i want to say demethylation but i think it's more than that
06:15 < hprmbridge> yashgaroth> in vivo though?
06:16 < fenn> yes as part of the gene therapy payload, probably implemented as a genetic regulatory network
06:16 < fenn> i mean the thing you're modifying is already a bunch of genetic regulatory elements
06:17 < hprmbridge> alonzoc> kanzure: Nah I'm more thinking that you could homologous cells as trojan horses for multiplex gene-editing or delivery of theraputic agents. Modified T-Cells for cancer therapy are immunogenic but for tissues like muscle, bone, etc  mesenchymal stem cells have an immunosurpressive effect. You "just" have reprogrammed mesenchymal stem cells wander the tissue hitting cells with the partial yamanaka
06:17 < hprmbridge> alonzoc> factors (you also want some mechanism to stop a cell being "fixed" multiple times during a therapy).
06:18 < fenn> if 99% of your cells die eventually that's fine. eventualy in 200 years we can go in and do DNA surgery to fix the accumulated mutations one at a time
06:19 < hprmbridge> alonzoc> The "replace everything thesesus style" might work with cloned stem cells but for neural tissue that might not work. You defo need to be more careful rejuvenating the brain
06:19 < fenn> i don't know
06:20 < hprmbridge> alonzoc> However, the single cell gene editing capabilities we have now are far from sufficient to reprogram human cells to do complex jobs beyond "go attack that cancer please" as far as I can tell
06:20 < fenn> dreams might refresh forgotten memories and teach the new neurons the old stuff without having to actually experience it again
06:21 < hprmbridge> alonzoc> fenn: defo need to do it very incrementally if you theseus the brain
06:21 < fenn> yes
06:21 < hprmbridge> alonzoc> yash is prolly gonna tell me my idea is dumb and probably not possible now /hj
06:21 < hprmbridge> yashgaroth> "...is typing"
06:21 < hprmbridge> alonzoc> why i'm worried
06:22 < hprmbridge> yashgaroth> stem cell rejuv falls apart w/ neurons because yeah in most tissues you can just ablate all the "bad" cells and reactivate/replace stem cells. Neurons you've gotta go cell by cell or risk forgetting how to breathe or talk
06:23 < hprmbridge> alonzoc> Tbh I doubt there will ever be a "magic pill" I expect it to be like rejuv from     Peter F. Hamilton's Commonwealth Saga
06:24 < fenn> or you might learn more optimal ways of breathing or talking that use less neural activity, by training a minimal additional population of new neurons
06:24 < fenn> not important for breathing but maybe relevant for high signal to noise ratio talking
06:26 < fenn> counterintuitively, high intelligence and psychedelic experience both involve less neural activity than average
06:26 < hprmbridge> yashgaroth> also yamanaka factors don't just gradually walk cells back along differentiation, we don't really know how it works. Or if it works/helps in otherwise-healthy animals. If you can deliver the OSK to enough cells to matter (including the magical genetic circuits that prevent mass teratomas or toxicity) then you've already solved biology. Hence why everyone's fucking around with small molecules to
06:26 < hprmbridge> yashgaroth> reactivate them instead, which has its own issues of dosage and regulation
06:27 < kanzure> reactivate what instead?
06:27 < fenn> according to the lottery ticket hypothesis of how neural networks do useful world modeling, most of the neurons are just kinda there, and randomly a small subset of them just happen to match how the world is structured and do useful modeling
06:27 < hprmbridge> yashgaroth> yamanaka factors, OSK(M)
06:28 < kanzure> fenn: i'm familiar with yamanaka factors and dedifferentiation but i was under the impression that we tried it in mice and the mice aren't healthy from just that
06:29 < fenn> it's all pretty new
06:30 < fenn> hm apparently i don't have any of this bookmarked
06:31 < fenn> .t https://www.nature.com/articles/s41586-020-2975-4
06:31 < saxo> Reprogramming to recover youthful epigenetic information and restore vision | Nature
06:31 < hprmbridge> alonzoc> fenn: I don't know of any evidence that biological neural nets have the lottery ticket hypothesis. We know ANNs do but the "dead" neurons in a representation would probably be pruned if it was biological and replaced by more neurons. There is also the fact that larger ANNs learn faster which the lottery ticket hypothesis explains partially but I suspect it's more likely that it's due to the
06:31 < hprmbridge> alonzoc> network acting as a fused ensemble of sub-networks which allows faster learning overall.
06:31 < hprmbridge> yashgaroth> good ol' sinclair
06:32 < fenn> alonzoc the neurons dont get pruned but the synapses do
06:32 < hprmbridge> alonzoc> Point
06:33 < fenn> maybe re-rolling that simulated annealing step with a partially frozen subnetwork will result in a better final system
06:33 < fenn> like that short story "Understand"
06:34 < fenn> the narrator drowned or something and lost a lot of brain matter, then they gave him drugs to re-grow the lost tissue
06:37 < fenn> i guess my ideal brain refresh program is something like: kill 10% of least active neurons, do neural regrowth, let synapses form, do a lot of dreaming and dredging up old memories, wait 10 years, repeat
06:37 < hprmbridge> alonzoc> The notion that neural nets are a point estimate of the true model (which lies in the same class) kinda breaks down when they're massively overcomplete. A lot of the maths from statistical learning theory is really just not the case. Even the best approach I know of "Singular learning theory" which handles the singular nature of the parameter space still relies on the assumption of realisability
06:37 < hprmbridge> alonzoc> and is only partially talking into account what massive overcompleteness of the parameter space really "means".
06:37 < hprmbridge> alonzoc> This archive of ntoes is interesting on this http://therisingsea.org/notes/metauni/ and is https://arxiv.org/pdf/2010.11560 a good intro
06:38 < hprmbridge> alonzoc> for the notes `dlt*.pdf` and `slt*.pdf` are what you wanna read
06:38  * fenn sees the word 'category' and nopes out
06:39 < hprmbridge> alonzoc> The maths they use is more algebraic geometry and calculus along with stuff from statistical physics
06:40 < fenn> there's this LLM merge technique which explicitly recognizes that multiple valid circuits exist simultaneously, and throws out most of the useful ones in order to make space for other functionality
06:40 < fenn> .t https://arxiv.org/abs/2311.03099
06:40 < saxo> [2311.03099] Language Models are Super Mario: Absorbing Abilities from Homologous Models as a Free Lunch
06:40 < hprmbridge> alonzoc> It's interesting stuff but very niche there are like two? univeristies with groups doing research on it which really annoys me I wish there was a research team in the UK working on it
06:41 < fenn> https://github.com/yule-BUAA/MergeLM this page has the ugly diagram with the functionality guys that will eventually make sense
06:42 < hprmbridge> alonzoc> I'll move of the topic of SLT but the really meaty note is dlt3.pdf section 3 inspired an experiment I'm tinkering with atm
06:43 < hprmbridge> alonzoc> oh wait section 3 and 4
06:44 < fenn> the yoga of universality classes
06:47 < fenn> i have no idea what any of this means, sorry
06:50 < hprmbridge> alonzoc> Pity. Anyways the primary result SLT has come to so far is that the standard low order expansion of generalisation error is actually wrong for any hierarchical model like a neural net or gaussian mixture model. Generalisation error does not scale with dimensionality but with the "RLCT" which can be thought of as a "local dimensionality" which in neural nets is a lot lower than the actual parameter
06:50 < hprmbridge> alonzoc> count
06:52 < hprmbridge> alonzoc> RLCT (real log canonical threshold) is a pita to compute and whole papers are about computing it for even simple toy models
06:53 -!- darsie [~darsie@84-112-12-36.cable.dynamic.surfer.at] has quit [Remote host closed the connection]
06:54 -!- darsie [~darsie@84-112-12-36.cable.dynamic.surfer.at] has joined #hplusroadmap
06:55 < hprmbridge> alonzoc> But there are ways to estimate it in more practical models. Like *all good* (sarcasm) AI research there is a alignmentforum post about it https://www.alignmentforum.org/posts/jvGqQGDrYzZM4MyaN/growth-and-form-in-a-toy-model-of-superposition
06:56 < fenn> this polygon stuff look familiar from https://transformer-circuits.pub/2022/toy_model/index.html
06:59 < fenn> with enough parameters you don't actually need any of that overloading of neurons
06:59 < fenn> polygons are how you pack more information into the same number of neurons
07:00 < hprmbridge> alonzoc> True the point is you want to do that because such models are likely to generalise better a single layer network with exponentially many neurons is universal after all
07:00 < fenn> and/or more redundancy i suppose
07:02 < hprmbridge> alonzoc> I really need to get my hands on a box filled with GPUs at some point... numerical experiments are necessary and take *forever*
07:05 < fenn> runpod is a thing
07:06 < fenn> vast.ai is even cheaper 
07:07 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has quit [Read error: Connection timed out]
07:08 < hprmbridge> alonzoc> I'll have to give them a try. I still want a local cluster at some point. The prices look really good tho
07:17 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has joined #hplusroadmap
09:22 < docl> perhaps you could have a graphene nanoribbon ticker tape to replace dna with. you need a reader molecule that can find the address and transmit signals to your rna synthesizer reliably. C12/C13 isotopes could encode the data.
09:46  * nsh updates a list
09:48 < nsh> why not a tiny slab of granite and a tiny chisel while we're incorporating ridiculously archaic human inventions into scales alien to their already dubious utility
10:35 -!- _flood [flooded@gateway/vpn/protonvpn/flood/x-43489060] has quit [Ping timeout: 252 seconds]
10:45 < kanzure> docl: what problem is that solving? it would still spew out proteins and peptides and create hard-to-debug hard-to-reason-about spaghetti inside cells.
10:46 < kanzure> https://www.esd.whs.mil/Portals/54/Documents/FOID/Reading%20Room/Science_and_Technology/16-F-1333_%20DOC_02_LENR_Briefing.pdf
11:25 < kanzure> "a selection scheme for superconductivity based on microcalorimetry, that you would do in IIRC an organic solute that overlaps in liquid state with high-temp superconductors"
11:28 < kanzure> .g "church of sequence space"
11:28 < saxo> https://twitter.com/Kemmishtree/status/1806835827827486769
11:32 < kanzure> "Evolution is smarter than any of us. This is why I'm obsessed with sequence space. This is why it's more important than outer space. I'm tired of the refrain I've heard more than once that directed evolution must go hand-in-hand with careful scaffolding and computational strategies and that there's really no way to get from non-active to active without a lot of clever guidance. Bollocks! ...
11:32 < kanzure> ...Unleash the genius idiocy of evolution and put your ego aside."
11:34 < kanzure> from https://www.science.org/content/blog-post/evolving-enzymes-let-em-rip
11:34 < kanzure> "So they're not ready to turn off the software just yet. But you have to wonder - if there were some way to run the random-mutation process more quickly, and reduce the time and effort of the mutation/screening/selection loop, computational design might well end up playing a much smaller role. (See here for more thoughts on this). Enzymes are capable of things that we would never think of ...
11:34 < kanzure> ...ourselves, and we should always give them the chance to surprise us when we can."
11:35 < kanzure> or rather, from https://web.archive.org/web/20131009084546/https://pipeline.corante.com/archives/2013/07/31/evolving_enzymes_let_em_rip.php
11:37 < alethkit> Eli: Nutrigenetics seems to be a field, and not a company? I could not find any on DDG.
11:52 -!- flooded [flooded@gateway/vpn/protonvpn/flood/x-43489060] has joined #hplusroadmap
12:31 < hprmbridge> Eli> Yes, it’s a field that you can get degrees in. It’s newish due to the fact that cheap genetic sequencing for humans hasn’t been around long.
12:36 < hprmbridge> Eli> My current belief is that we evolved to die. Why do rats live a few years? Humans live 120 years? And immortal jellyfish don’t die?
12:36 < hprmbridge> Eli>
12:36 < hprmbridge> Eli> Why would evolution have us stop having babies at a certain age? Even if we believe it’s due to antagonistic pleitropy, then we have to ask why antagonistic pleitropy occurs when it does? It’s due to humans evolving to maximize their objective function given constraints in the system. If a turtle can live to hundreds of years of age, why not a human? We evolved to die.
12:39 < hprmbridge> Eli> Also, should we have a discord bot that warns us when David Sinclair articles pop up?
12:48 < docl> kanzure: the synthetic nucleus would just spew mRNA and ribosomes like a natural nucleus does. you could micromanage every cell in a body though. empirical-test any novel stuff in teensy microchimeric chunks you can revert to normal at any point. you'd also use optical signals that directly substitute for chemomechanistic ones and provide location-tracking for all cells.
12:52 < TMA> Eli: my current understanding is that there is no selection presure on not dying (there is little gain from living longer when your children are capable of producing more offspring)
12:52 < docl> isotope ratio based storage in graphene nanoribbon is denser than dna, so that carves room you could use for redundancy for rna expressing mechanisms
12:56 < docl> kanzure: replacing the proteins with spiroligomer or other building block based stereochemical systems is easy enough to bootstrap to if you control the nucleus. you can use gradual revertable microchimeristic mods.
12:57 < docl> just replacing the major metabolic pathways would probably be a huge deal, as you're clearing out space in the cell that you can then devote to other stuff
13:20 < docl> also I sort of suspect actin filaments and microtubules could be replaced as structural and signalling components, would be another way to clear more space for other stuff. you could leave the neurons alone for this purpose, but no reason you can't make other cells more durable and spacious with some substitutions here and there. you can replace mitosis with more centralized factory systems the size of 
13:20 < docl> a grain of rice. make small cells that travel around and anchor and specialize where needed.
14:22 < hprmbridge> Eli> Why? Why don’t humans keep having babies? Even when old?
14:23 < docl> disease, starvation, predation, murder, etc
14:24 < docl> i.e. they don't get old often enough to influence evolution to prevent aging later
14:25 < docl> which is of course not the case any more, we tend to live far past the reproductive window and die primarily of aging. so our genes are currently under selective pressure to extend that window
14:50 < TMA> except they are not.
14:52 < TMA> those that live longer are selected against. the first world with its longest life expectancies is also the group with the least fertility 
14:54 < TMA> and even when you look closer on the internal differences in fertility, the most fertile subgroups tend to be the shortest lived ones
14:56 < hprmbridge> kanzure> "Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins" https://www.science.org/doi/10.1126/science.ado3290
14:56 < hprmbridge> kanzure> 45,000 amino acids
14:57 < TMA> for example figure 2 of https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-022-13656-1 
15:17 -!- TMM [hp@amanda.tmm.cx] has quit [Quit: https://quassel-irc.org - Chat comfortably. Anywhere.]
15:18 -!- TMM [hp@amanda.tmm.cx] has joined #hplusroadmap
15:53 < docl> having kids in your 40s is a workaround for the college career induced delay for women. so late menopause is being selected for in some populations.
15:59 < fenn> the DoD doesn't need to invest "heavily" into LENR they just need to fund anyone at all, so that at least the basic foundational science work gets done
15:59 < fenn> zero funding for 30 years in a climate of fear and shame and you obviously won't make a lot of progress
16:00 < fenn> DoD is probably the ones running the disinfo campaign to start with, so no surprise they don't want to publicly fund it
16:00 < hprmbridge> kanzure> what, acoustic cavitation fusion stuff?
16:00 < fenn> that's not LENR is it?
16:01 < fenn> just a funny way of making high temperature and density
16:01 < hprmbridge> kanzure> don't look at me, i'm a tourist in this area
16:02 < hprmbridge> kanzure> https://projecthailmary.fandom.com/wiki/Astrophage
16:02 < hprmbridge> kanzure> "If I was writing a science fiction story and wanted this to sound plausible, I'd posit an organelle that underwent cavitation and produced muons, which then bind to free protons and catalyze fusion reactions. The producing muons from cavitation thing is a total hand-wave though."
16:03 < hprmbridge> kanzure> anyway, microbial fuel cells have already been optimized to hell and back and someone would have noticed by now maybe if there was any special physics they could hijack
16:04 < hprmbridge> kanzure> or maybe explored wrong part of sequence space......
16:04 < hprmbridge> kanzure> don't have to understand how it works as long as it does the thing!
16:05 < fenn> yeah you need much higher particle energies to produce muons
16:06 < hprmbridge> alonzoc> I really enjoyed project hail mary but the astrophage are also smaller than the wavelengths they absorb to turn into energy
16:07 < hprmbridge> alonzoc> one sec gotta check the details I might be the wavelength they emit or home in on
16:08 < fenn> @Eli there's no value in knowing right away when an anti-aging article comes out
16:09 < fenn> every time i've been around a news bot, it has been annoying
16:10 < hprmbridge> alonzoc> yeah news bots usualy just spam you with articles which are either not interesting or end up a dud in a weeks time
16:11 < hprmbridge> alonzoc> Oh yeah it was the whole super crosssectionality bit that was the deus ex machina that explain how they could interact with wavelengths much larger and trap neutrinos etc
16:13 < hprmbridge> alonzoc> The two magic physics twists that make the book work. Super cross sectionality, and the neutrino being a majorana fermion (which is within the realm of possibility)
16:14 < hprmbridge> alonzoc> It'd be really neat if neutrinos were majorana particles
16:16 < hprmbridge> kanzure> well, the astrophage concept isn't the only biological idea
16:17 < hprmbridge> alonzoc> Oh there are the spider things yeah I was more looking at the changes to physics needed for the story
16:38 < hprmbridge> kanzure> if you were needing to make a fusion reactor bacteria, you wouldn't also want to have to make it an interstellar extremophile too...
16:45 < docl> The Reefs of Space had fusion bacteria
16:46 < docl> https://www.solarsystemheritage.com/reefs-of-space.html
16:52 < docl> the same trilogy that had the sapient stars thing. apparently it was based on hoyle's steady state universe notion. I didn't catch the point of that (hydrogen is abundant enough IRL) but nicoll's review says the idea was the universe could then be old enough for less plausible life forms. https://jamesdavisnicoll.com/review/flawed-but-intriguing
17:37 < hprmbridge> alonzoc> kanzure: Also the solution to the problem is much simpler than sending a starship to the home system. Just build a beacon in space that pretends to be Venus and siphon off the astrophage.
17:37 < hprmbridge> alonzoc> You only need to get the replication coefficient below 1. The astrophage wasn't gonna be a problem unless it grew exponentially. And astrophage gives you the fuel needed to do all the cool shit in space
17:56 < hprmbridge> kanzure> colonize icebergs as new land mass https://x.com/lsparrish/status/1823879513396404259
18:23 -!- Gooberpatrol66 [~Gooberpat@user/gooberpatrol66] has quit [Quit: Konversation terminated!]
18:24 -!- flyback [~flyback@2601:540:c781:7f90:b969:14d:4c44:f5ed] has quit [Ping timeout: 260 seconds]
18:28 -!- Gooberpatrol66 [~Gooberpat@user/gooberpatrol66] has joined #hplusroadmap
18:52 -!- flyback [~flyback@c-73-236-61-245.hsd1.pa.comcast.net] has joined #hplusroadmap
19:18 -!- darsie [~darsie@84-112-12-36.cable.dynamic.surfer.at] has quit [Ping timeout: 244 seconds]
20:55 -!- mxz__ [~mxz@user/mxz] has joined #hplusroadmap
20:56 -!- mxz_ [~mxz@user/mxz] has quit [Ping timeout: 245 seconds]
20:56 -!- mxz [~mxz@user/mxz] has quit [Ping timeout: 264 seconds]
20:56 -!- mxz__ is now known as mxz
22:03 -!- TMA [tma@twin.jikos.cz] has quit [Ping timeout: 244 seconds]
22:17 -!- TMA [tma@twin.jikos.cz] has joined #hplusroadmap
22:19 -!- gl00ten [~gl00ten@193.147.150.204] has joined #hplusroadmap
22:22 -!- gl00ten [~gl00ten@193.147.150.204] has quit [Remote host closed the connection]
22:24 -!- gl00ten [~gl00ten@193.147.150.204] has joined #hplusroadmap
22:27 -!- TMA [tma@twin.jikos.cz] has quit [Ping timeout: 276 seconds]
22:34 -!- TMA [tma@twin.jikos.cz] has joined #hplusroadmap
22:40 < fenn> "turtle can live to hundreds of years of age, why not a human?" turtles and naked mole rats have a slower metabolism
22:42 < fenn> "Why don’t humans keep having babies? Even when old?" because females run out of gametes, which are protected from mutation by not replicating. not a very satisfying reason i know
22:43 < fenn> isn't there evidence of like 80 year old paleolithic humans? was that a fluke, and earlier ancestors didn't live so long?
22:45 < fenn> 'humans didn't live long enough to reproduce at old ages' does not seem like a good reason either. it's sort of circular; humans (and other animals) died of predation when older because of aging, not because of lack of experience or wisdom
23:02 -!- mxz_ [~mxz@user/mxz] has joined #hplusroadmap
23:07 < docl> no, I mean that evolution can't measure 'lives longer in the counterfactual where the organism didn't die' since it lacks foresight/imagination
23:08 < docl> dying of predation before aging sets in makes it tough to evolve antiaging mechanisms
23:10 < hprmbridge> kanzure> these are very old arguments and surely someone else has written them up
23:15 < hprmbridge> Eli> The bot wouldn’t be to release Sinclair articles. It would be to warn people they are Sinclair articles when someone posts one in the discord. Was being a little facetious
23:20 < hprmbridge> Eli> Only 6 mammals go through menopause. mtDNA mutations are extremely concerning for sure.
23:23 < hprmbridge> Eli> I don’t think that’s the only correlated variable. Also, evolution controls metabolism.
23:23 < hprmbridge> Eli>
23:23 < hprmbridge> Eli> Men can have children until they die. There should be some pressure for increased lifespan. Not all of our ancestors died at age 40.
23:25 < fenn> agreed
23:28 < hprmbridge> Eli> It’s good and important to look at the genetic and biochemical reasons for aging. But we probably need to zoom out and also look at the evolutionary reasons for aging and how populations and individuals interact with their ecosystem to explain why humans and other organisms have very specific shelf lifes and different lifespans even among the same organism in different environments.
23:28 < hprmbridge> Eli> Probably could have used some more periods in that sentence 😵
23:39 -!- TMM [hp@amanda.tmm.cx] has quit [Quit: https://quassel-irc.org - Chat comfortably. Anywhere.]
23:40 -!- TMM [hp@amanda.tmm.cx] has joined #hplusroadmap
--- Log closed Thu Aug 15 00:00:23 2024