--- Log opened Tue Sep 23 00:00:48 2025
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03:52 < hprmbridge> kanzure> DNA and protein memory recording devices overview https://www.nature.com/articles/d41586-025-03035-2
03:52 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1419999792435826749/image0.jpg?ex=68d3cd5c&is=68d27bdc&hm=7bcb43652ed44048821f76ca344972d5a6e5e12bcd04f0f0c8694e28eb08a267&
03:54 < hprmbridge> kanzure> wow, their article takes a long time to say nothing about each of the approaches.
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03:56 < hprmbridge> .monokhrome> is it possible to explain how they're actually doing it in a sentence?
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03:58 < hprmbridge> kanzure> it's just DNA editor circuits to record cellular events via various genetically encoded sensors and actuators.
03:58 < hprmbridge> kanzure> or in the case of the protein approach, expression of individual proteins that self assemble into a growing protein superassembly.
04:07 < hprmbridge> kanzure> quaise millimeter wave drilling has achieved 100 meters in granite recently https://youtube.com/watch?v=oYHcCsFlD2Q
04:20 < hprmbridge> .monokhrome> can they actually put that inside a human cell without wrecking it?
04:20 < hprmbridge> kanzure> in vitro? sure.
04:21 < hprmbridge> kanzure> pretty sure that's been done already
04:21 < hprmbridge> kanzure> in vivo, probably just mice so far, people get really ugly about doing things in living humans....
04:22 < hprmbridge> .monokhrome> just how many genes are they logging at once?
04:22 < hprmbridge> kanzure> ehhh these things have a time resolution of hours or worse.
04:23 < hprmbridge> .monokhrome> I had visions of them logging tens of thousands of genes at once, but if they're only doing a few, I guess that makes more sense
04:24 < hprmbridge> kanzure> it's only a few.
04:31 < hprmbridge> kanzure> "Fat-1 mice convert n-6 to n-3 fatty acids" https://www.nature.com/articles/427504a
04:31 < hprmbridge> kanzure> "Mammals cannot naturally produce omega-3 (n-3) fatty acids — beneficial nutrients found mainly in fish oil — from the more abundant omega-6 (n-6) fatty acids and so they must rely on a dietary supply1. Here we show that mice engineered to carry a fat-1 gene from the roundworm Caenorhabditis elegans can add a double bond into an unsaturated fatty-acid hydrocarbon chain and convert n-6 to n-3 fatty
04:31 < hprmbridge> kanzure> acids. This results in an abundance of n-3 and a reduction in n-6 fatty acids in the organs and tissues of these mice, in the absence of dietary n-3. As well as presenting an opportunity to investigate the roles played by n-3 fatty acids in the body, our discovery indicates that this technology might be adapted to enrich n-3 fatty acids in animal products such as meat, milk and eggs."
04:34 < hprmbridge> kanzure> they put it into pig https://pmc.ncbi.nlm.nih.gov/articles/PMC5940165/
04:34 < hprmbridge> kanzure> and cattle https://pmc.ncbi.nlm.nih.gov/articles/PMC3267699/
04:36 < hprmbridge> kanzure> "In 2011, Chinese scientists produced cattle carrying the C. elegans fat-1 gene. These cows expressed the desaturase enzyme, which converted n-6 PUFAs to n-3 PUFAs. Analyses showed significant increases in n-3 fatty acids in multiple tissues, including milk. Milk from these animals had lower n-6:n-3 ratios."
04:41 < hprmbridge> kanzure> huh, essential amino acids are not considered vitamins?
04:42 < jrayhawk> the categories are all a bit arbitrary
04:42 < hprmbridge> kanzure> https://diyhpl.us/wiki/transcripts/hgp-write/2016-05-10/synthesizing-a-prototrophic-human-genome/
04:43 < hprmbridge> kanzure> "Engineering into human genome the capability to synthesize essential amino acids, essential fatty acids and essential vitamins"
04:43 < jrayhawk> choline, for instance, is a pseudo-vitamin and pseudo-amino-acid
04:45 < hprmbridge> kanzure> beta-carotene is a provitamin or vitamin precursor, but human can synthesize vitamin A from this precursor? so how is vitamin A considered a vitamin then.
04:46 < jrayhawk> 40% of humans suck at carotinoid/retinoid conversion in practice
04:46 < hprmbridge> kanzure> ok let's fix that.
04:47 < jrayhawk> there's two major BCMO polymorphisms documented in SNPedia; they're low-hanging fruit
04:47 < jrayhawk> major and common
04:48 < hprmbridge> kanzure> "Dietary fiber (cellulose, hemicellulose, pectins, resistant starch, inulin) is not directly digestible" why. takes too much energy and we shouldn't do it, or we are literally lacking the hardware and we got stuck in an evolutionary minima?
04:48 < jrayhawk> it just takes a long time
04:49 < jrayhawk> ruminants spend huge amounts of time intaking, masticating, and cycling grass through four stomachs
04:50 < hprmbridge> kanzure> no ability to synthesize linoleic acid, alpha-linoleic acid, and then once consumed we have inefficient conversion to arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid... we should increase the efficiency of that. and produce our own alpha-linoleic acid anyway.
04:51 < hprmbridge> kanzure> maybe we can build one of those fancy 1000x better enzymes and accelerate that process.
04:51 < jrayhawk> should Forumula 1 cars be running 87 octane pump gas?
04:53 < hprmbridge> kanzure> instead of Soylent?
04:53 < hprmbridge> kanzure> or what's the comparison here?
04:54 < hprmbridge> kanzure> probably some hyper optimized intravenous drip that i don't know the name of
04:54 < jrayhawk> polyunsaturated fatty acids are inherently dangerous to handle at human body temperature
04:55 < jrayhawk> we externalize that cost onto other lifeforms
04:55 < jrayhawk> as much as we can get away with, anyway
04:57 < hprmbridge> kanzure> is there a better molecular structure that we could theoretically use as food that could be more efficiently processed by human cells to produce our raw materials and other precursors?
04:57 < hprmbridge> kanzure> for the set of micronutrients, macronutrients and essentials that we need.
04:58 < jrayhawk> enzymes for desaturating monounsaturated fatty acids would make more sense
04:59 < jrayhawk> though just directly consuming docosahexaenoic acid, eicosapentaenoic acid, and arachidonic acid is still a better solution
05:03 < L29Ah> >26.08.2025 00:51:19] L29Ah: jrayhawk: https://www.nature.com/articles/srep31649 apparently ALA is not that simple
05:03 < hprmbridge> kanzure> i have the same question about hemoglobin or myoglobin but we'll get there. freitas had his non perfluoro-something idea of a nanotech solution for high density oxygen delivery.
05:04 < L29Ah> the nanoscale gas tanks?
05:05 < jrayhawk> the essential problem here is one of alignment: of the essential 13.5 vitamins, 20 minerals, 12.5-ish amino acids, and 3-ish fatty acids, humans have direct nutrient sensing and instinct to consume only sodium, and soooortof zinc. All the others are managed by proxy sensing correlates in our evolutionary training set that no longer match the environment our DNA is executing in.
05:06 < jrayhawk> Glutamate used to be correlated with almost all of the essential nutrients, now it is correlated with monosodium glutamate.
05:07 < jrayhawk> The foundational solution is to add direct nutrient sensing for all the other EFAs, or find economical means of interconverting them.
05:08 < hprmbridge> kanzure> what does sensing mean here? information propagation to neurons?
05:09 < jrayhawk> Yeah, receptors to homeostatic regulators to motivational systems.
05:11 < jrayhawk> Fat, salt, glucose, and glutamate receptors on the tongue are the most straightforward pathways to hack; fat sensing could maybe be made more specific, glutamate could be made more general, etc.
05:12 < jrayhawk> the glucose receptors could be made more specific to glucose; artificial sweeteners are agonists
05:14 < jrayhawk> fructose is also an agonist in some sense; humans tend to gorge themselves when fructose sources are readily available, which obviously has alignment problems today
05:14 < L29Ah> i don't find glutamate appealing tbh, there are tastier aminoacids
05:16 < fenn> it's a flavor enhancer
05:16 < fenn> you don't just spoon MSG into your mouth
05:17 < jrayhawk> people drink tomato juice
05:17 < fenn> no they don't
05:17 < fenn> they put it on pizza
05:18 < hprmbridge> kanzure> to my credit i did not propose a photosynthetic human above.
05:19 < fenn> slightly off topic, i found this nice writeup of whatever this food movement is called, for normies but with enough technical detail to bite into https://nourishfoodclub.com/pages/the-lowps
05:19 < jrayhawk> we don't really have a good understanding of what tradeoffs, if any, were involved in making the loss of most of the enzymatic interconversion pathways that humans have lost or are in the process of losing. EFAs are one of the few reasonably obvious ones.
05:20 < fenn> the vitamin C one is pretty interesting
05:20 < jrayhawk> Cellulose is another reasonably obvious one in the sense of how cumbersome it is even in biology theoretically optimized for it.
05:21 < L29Ah> > - Life expectancy is shrinking (r): we’re dying younger
05:21 < fenn> ice age survival required a crash course in adding fat, and the quickest way to do that was reducing ascorbic acid levels
05:21 < L29Ah> is the rest of data processing as shitty as this?
05:21 < jrayhawk> The appendix is the embarassing shrivelled useless cellulose processing organ of humans.
05:21 < fenn> L29Ah: sadly it's true
05:22 < fenn> US centric perspective for US centric problems
05:22 < L29Ah> fenn: only if you ignore covid and opioid epidemic in US
05:23 < fenn> well life expectancy leveled off in the 2010s before declining precipitously during covid
05:24 < fenn> so if we just ignore all the major stuff, everything's fine!
05:26 < hprmbridge> kanzure> back on topic.
05:26 < jrayhawk> it's partially on topic
05:26 < jrayhawk> https://slatestarcodex.com/2019/08/19/maybe-your-zoloft-stopped-working-because-a-liver-fluke-tried-to-turn-your-nth-great-grandmother-into-a-zombie/ we also need a lot more defenses against stuff like opioid agonists
05:27 < jrayhawk> but that's very much a whack-a-mole problem with no general solution
05:31 < jrayhawk> plants evolved phytoestrogens to destroy the fertility of animals that predate on them. There are a variety of those to worry about.
05:33 < jrayhawk> Chocolate addiction is partially driven by phenylethylamine. We use circulating monoamine oxidase to disarm that as much as we can, but there's tradeoffs to upregulating that in circulation.
05:33 < jrayhawk> Now we can buy phenylethylamine by the kilogram off of Amazon.
05:36 < fenn> corporations have incentives to addict consumers
05:36 < fenn> plants evolve much more slowly
05:37 < jrayhawk> https://gnusha.org/~jrayhawk/the_metabolic_syndrome/10.1111-jfbc.12629-role_of_food-derived_opioid_peptides_in_the_central_nervous_and_gastrointestinal_systems.pdf opioids in dairy make sense for addicting babies to breastfeeding
05:38 < jrayhawk> so making allowances for their absorption and transmigration across the blood brain barrier has awkwardly context-specific desirability
05:39 < fenn> i'm unclear on what the scope of this conversation is. insight and memetic immune systems seem to be the only hope for defense against corporate psychological/biochemical manipulation
05:39 < L29Ah> what chocolate addiction and where are my substituted phenylethylamines!?
05:40 < jrayhawk> substituted?
05:40 < hprmbridge> kanzure> fenn, well i have an interest in cataloging germline metabolic or digestive upgrades
05:40 < L29Ah> https://en.wikipedia.org/wiki/Substituted_phenethylamine
05:42 < hprmbridge> kanzure> extremely energy dense food that can be effortlessly and efficiently digested into the human-necessary components, across the spectrum of bionecessaries or things that we can externalize and then whatever we need to add to sufficiently reap the benefits from those dense efficient foods.
05:43 < hprmbridge> kanzure> how is intravenous not the correct solution?
05:44  * L29Ah commutes using his body mechanical output, energy-dense food is great
05:44 < L29Ah> keeping catethers clean sucks
05:45 < L29Ah> also the injection point gets undesirable localized side effects from too high nutrient density iirc
05:45 < hprmbridge> kanzure> skill issue?
05:45 < L29Ah> apparently eight years in the medical education doesn't build enough skill often enough
05:45 < L29Ah> or them patients are very suicidal
05:46 < jrayhawk> i am not super familiar with the IV nutrition field; they keep coma patients alive long-term, but I have no idea what tradeoffs are involved in practice.
05:46 < hprmbridge> kanzure> probably nobody studying it sufficiently, i haven't heard of people optimizing intravenous nutrition via comatose cattle or whatever.....
05:48 < hprmbridge> kanzure> or food restricted cattle, that would be easier.
05:48 < jrayhawk> MuaddibLLM: how long can intravenous nutrition keep a human alive? are there any metabolic bottlenecks to doing so?
05:49 < hprmbridge> kanzure> probably you lose some GI signaling. do they do feeding times with IV? or just constant drip?
05:49 < fenn> i haven't verified this but supposedly desturase from fatty acid glycolysis uses huge amounts of oxygen, perhaps 40% of oxygen consumption? https://fireinabottle.net/linoleic-acid-is-stealing-your-oxygen/
05:49 < MuaddibLLM> diving into the IV nutrition rabbit hole...
05:49 < fenn> so that would be a big constraint on fatty acid synthesis metabolism
05:49 < MuaddibLLM> found some solid survival stats, now hunting for the record holders and metabolic bottlenecks...
05:50 < MuaddibLLM> Decades - 5-year survival on home TPN is ~64%, with liver disease (PNALD), catheter infections, and bone demineralization as the main metabolic bottlenecks limiting indefinite use: https://ameripharmaspecialty.com/tpn/tpn-life-expectancy-how-long-can-someone-live-on-tpn-alone/
05:50 < hprmbridge> kanzure> wtf
05:52 < L29Ah> https://en.wikipedia.org/wiki/Parenteral_nutrition#Fatty_liver_and_liver_failure lol
05:52 < L29Ah> MuaddibLLM: is choline a vitamin?
05:52 < hprmbridge> kanzure> "Fatty liver is usually a more long-term complication of TPN, though over a long enough course it is fairly common. The pathogenesis is due to using linoleic acid (an omega-6 fatty acid component of soybean oil) as a major source of calories.[21][22]"
05:52 < fenn> yes choline is a vitamin
05:53 < jrayhawk> oh, bone demineralization is probably because of human variability in K2 conversion that they didn't know about at the time, which is actually also related to carotinoid/retinoid conversion variability
05:53 < jrayhawk> choline is technically synthesizable from trimethylglycine, but humans are bad at it
05:53 < hprmbridge> kanzure> "Intralipid (Fresenius-Kabi), the US standard lipid emulsion for TPN nutrition, contains a 7:1 ratio of n-6/n-3 ratio of polyunsaturated fatty acids (PUFA). By contrast, Omegaven has a 1:8 ratio and showed promise in multiple clinical studies" what? why would you not start with higher n-3?
05:53 < MuaddibLLM> [gpt-5] Short answer: choline is an essential nutrient rather than a classical vitamin - historically called “vitamin B4” - because we make a little via PEMT but not enough, so diet is required; deficiency causes fatty liver and muscle damage (why it matters in TPN).
05:54 < MuaddibLLM> No - choline is an essential nutrient but not technically a vitamin despite often being grouped with B-complex vitamins due to similar functions: https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/
05:54 < L29Ah> MuaddibLLM: does high choline intake cause addiction, incurring liver damage on withdrawal?
05:55  * fenn addicted to water
05:55 < MuaddibLLM> checking if choline has some weird addiction profile nobody talks about...
05:55 < MuaddibLLM> found zero addiction evidence, just the usual "fishy smell at high doses" stuff...
05:55 < MuaddibLLM> No - there's no evidence choline is addictive or causes liver damage on "withdrawal"; excess choline causes fishy odor, hypotension, sweating, and GI issues (UL is 3.5g/day), while it's choline *deficiency* (not stopping high doses) that triggers fatty liver disease.
05:57 < jrayhawk> it's not an entirely unreasonable question; choline is a methyl donor to tetrahydrobiopterin and thus to the various monoamines such as dopamine, but that's balanced out by also being a methyl donor to catachol-o-methyltransferase, which should, in principle, balance things out somewhat.
05:58 < jrayhawk> but presumably there are circumstances where you can overload the homeostatic regulatory systems.
05:58 < fenn> resistant starch, pectin, inulin, etc. provide food for hindgut microbes which perform other functions like synthesizing K2 and B12, converting said carbs into short chain fatty acids which help with utilizing fat, detoxifying dietary chemicals, and outcompeting pathogenic microbes. the bulky fiber also helps move waste through quickly
06:00 < jrayhawk> I consume 1-2g per day to treat genetic hyperhomocysteinemia
06:01 < fenn> how did you diagnose that?
06:02 < fenn> you take betaine or choline?
06:02 < jrayhawk> reynauds phenomenon and depression (D1 receptor agonism) that get worse when consuming methionine or glycine and get better when consuming choline or (in very limited quantities) tetrahydrofolates
06:04 < jrayhawk> i eat mass quantities of eggs, typically, so phosphatidylcholine primarily.
06:05 < hprmbridge> kanzure> 29 years on home parenteral nutrition https://aspenjournals.onlinelibrary.wiley.com/doi/10.1177/0148607107031002127
06:05 < jrayhawk> enough people complained about soy lecithin that manufacturers have started making sunflower lecithin. i don't have enough experience with it to judge. bitartrate and stuff worked reasonably well for me, at least.
06:06 < fenn> kanzure i guess the problem with diet gene mods is there are so many varieties of diet and it is currently handled by microbes. humans are somewhat unique in having a very diverse and dense microbiome. insects have almost no gut colonization and don't seem to rely on them. the difference is probably due to behavior
06:07 < fenn> instead of modifying the genome we've cultivated various microbiomes to more rapidly adapt to different diets
06:08 < jrayhawk> er, D1 receptor antagonism
06:08 < fenn> sunflower lecithin is just the byproduct of making sunflower oil
06:12 < jrayhawk> it is a tragedy, though. meat is fraught with danger for me. my vanity PGP fingerprint is ruined.
06:16 < jrayhawk> http://pgp.id/pks/lookup?op=index&search=0xFEEDBEEF
06:24 < fenn> a genetically engineered microbiome makes more sense than trying to fix ahead of time every possible weird thing you could encounter
06:24 < hprmbridge> kanzure> has there been any success with that?
06:24 < fenn> we are just really bad at modifying the microbiome in intended ways at all
06:24 < fenn> barely scratched the surface of fecal transplants
06:28 < jrayhawk> Fasano was trying to back some hacky inflammatory pathway blocker, but that halted for some reason https://en.wikipedia.org/wiki/Larazotide
06:30 < fenn> neat
06:30 < fenn> what happens when you have a pathogen that needs to get flushed out
06:30 < jrayhawk> well, i guess permeability might happen in another form at that point
06:31 < kanzure> unlimited bio in prospera is offering "VEGF gene therapy". people should be required to state what the delivery method is :\.
06:31 < jrayhawk> specifically, the form of necrosis
06:32 < fenn> according to a guy in the trader joe's parking lot, L. reuteri helps with intestinal permeability
06:34 < fenn> "Results: 
06:34 < fenn> Small and large intestinal permeability as well as other markers of gut barrier function were not significantly affected by the probiotic interventions." womp womp
06:35 < fenn> for IBS-D anyway
06:36 < kanzure> if i was working on intravenous parenteral nutrition, i think i would have to dedicate some amount of time to considering the problem of gastrointestinal signaling rather than simply the problem of vascular circulating nutrition. it is not clear to me if they hang bags with different hormones or sequences for different times of day.
06:36 < kanzure> not to say that i believe that the whole hormonal program must be replicated, only that there is a chance that some amount of signaling is important
06:38 < kanzure> should it be "consume more glucose via intravenous fluid" or should it be "design and develop a more high density high energy storage molecule and also make it easy and efficient for our cells to break it down and stop sending glucose everywhere"?
06:38 < fenn> for circadian rhythm entrainment?
06:38 < jrayhawk> there is actually a synthetic slow-release glucose
06:38 < kanzure> uh maybe, there's probably like 14 things that i don't even know about for whole body nutritional homeostasis
06:39 < jrayhawk> "superstarch" i believe was the brand name
06:41 < kanzure> i don't know what the phenotype criteria is for considering an animal domesticated. is it just not particularly aggressive? tolerates human interaction?
06:46 < jrayhawk> "trainable" is also in the memeplex
06:47  * fenn mutters about scent glands
06:47 < kanzure> before i forget: it looks like you can test human children for intelligence before age 2-3 and it has some low correlation or low predictive value to future intelligence; you can also test parental intelligence which has higher predictive power for future child intelligence, until it flips around age ~2.5-3yo when testing the child directly gains more predictive power.
06:47 < kanzure> this was just intelligence, apparently, and not things like learning or memory
06:47 < fenn> but what if there are no parents
06:48 < kanzure> like there was no parental genome?
06:48 < fenn> right
06:48 < kanzure> the child just poofed into existence?
06:48 < fenn> a wizard did it
06:48 < kanzure> i think that is a remarkable situation that demands further study and intelligence might not be first on my list!
06:49 < kanzure> average human intelligence is actually kind of remarkably high, even our dumb dumbs have interesting powers of language and communication
06:49 < fenn> hmm. most animals have language and communication
06:49 < fenn> a human can usually figure out how to open a gate
06:50 < kanzure> not me
06:50 < kanzure> even gates that i have previously transgressed, it seems i take several seconds to remember to remember
06:51 < kanzure> probiotic for phenylalanine ammonia-lyase pathway https://pubmed.ncbi.nlm.nih.gov/34294923/
06:52 < kanzure> probiotic with oxalate-degradation pathway to lower urinary oxalate https://pmc.ncbi.nlm.nih.gov/articles/PMC8899768/
06:52 < kanzure> you could probably do antibody display on probiotic cell surface
06:54 < kanzure> ah, here is one that does surface display "binding, sequestering and neutralization of IL-6" https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-022-01873-7
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06:56 < fenn> L. reuteri did lower IL-6 significantly
06:58 < kanzure> optimizing cell metabolism, function and health through a single universal circulatory system for nutrition and oxygenation seems kinda dumb, maybe we should have separate circulatory systems for tissue-specific enrichment.
06:59 < fenn> there's the portal vein thing
07:00 < fenn> the liver is "enriched" in toxins
07:00 < jrayhawk> what "single universal circulatory system" are you talking abut?
07:01 < fenn> the blood one
07:02 < kanzure> not the lymphatic one
07:02 < jrayhawk> lots of organs have seperate blood circulation systems,
07:02 < kanzure> "insects have an extensive network of air-filled tubes called tracheae, which deliver oxygen straight from the outside environment to cells."
07:03 < jrayhawk> along with different systems of diffusion and permeability between different tissues
07:05 < jrayhawk> https://en.wikipedia.org/wiki/Blood%E2%80%93ocular_barrier https://en.wikipedia.org/wiki/Blood%E2%80%93testis_barrier https://en.wikipedia.org/wiki/Blood-brain_barrier
07:10 < kanzure> "In Freitas' proposal, each respirocyte could store and transport 236 times more oxygen than a natural red blood cell, and could release it in a more controlled manner." ok he called it a respirocyte.
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07:11 < jrayhawk> huh, didn't know about the bloody-thymus barrier
07:12 < kanzure> "oxycyte" https://en.wikipedia.org/wiki/Perfluoro_tert-butylcyclohexane "a perfluorocarbon (perfluoro(t-butylcyclohexane)) in a 60% w/v concentration with an egg phospholipid emulsifier [..] Oxycyte was invented by Leland Clark and developed by Tenex Therapeutics, formerly Oxygen Biotherapeutics, Inc. and Synthetic Blood International.[8] It is designed to enhance oxygen delivery to damaged ...
07:12 < kanzure> ...tissues. Through a collaborative agreement, Oxycyte (under the development code name of ABL-101) was being developed by Aurum Biosciences Ltd, with an initial indication in acute ischemic stroke. Tenex claims that Oxycyte can carry oxygen with up to 5 times the efficiency of hemoglobin when used as an intravenous emulsion, making it an effective means of transporting oxygen to tissues and ...
07:12 < kanzure> ...carrying carbon dioxide to the lungs for disposal."
07:12 < kanzure> what: "In September 2014, Oxygen Biotherapeutics announced the discontinuation of a Phase IIB trial for its Oxycyte drug candidate, citing "difficulties enrolling patients""
07:15 < jrayhawk> people having an ischemic stroke are famously reticent to sign informed consent paperwork
07:16 < kanzure> is it possible that this is an interesting technology that ought to be pursued even if that particular clinical trial structure wasn't able to attract customers
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07:17 < kanzure> "Fluosol-DA remains the only oxygen therapeutic ever fully approved by the FDA. As of 2017, no hemoglobin-based product had been approved"
07:17 < kanzure> withdrawn in 1994..
07:17 < fenn> you'd think DARPA would be all over that
07:18 < fenn> machine blood that doesn't need refrigeration
07:20 < kanzure> something something.. ex-vivo production of mature human blood cells using hematopoietic stem cells.. via cord blood pharming..  "The blood is being produced for the Defense Advanced Research Projects Agency by Arteriocyte. The Food and Drug Administration has examined and approved the safety of this blood from previously submitted O-negative blood. Using this particular artificial blood will ...
07:20 < kanzure> ...reduce the costs per unit of blood from $5,000 to equal or less than $1,000.[39] This blood will also serve as a blood donor to all common blood types.[40]"
07:21 < kanzure> "Each cord can produce approximately 20 units of blood" hmm
07:23 < jrayhawk> "i would have to dedicate some amount of time to considering the problem of gastrointestinal signaling rather than simply the problem of vascular circulating nutrition" wait, who are you and what have you done with kanzure
07:23 < kanzure> complex systems are complex, what can i say other than that
07:24 < kanzure> i had not previously opined on the problem of developing intravenous nutrition so you cannot be surprised
07:24 < jrayhawk> "just try things" is your normal philosophy, and it applies doubly here where lots of other people have "just tried things" and it has largely worked
07:25 < jrayhawk> why am i arguing for the more naive approach WHAT HAVE I BECOME
07:25 < kanzure> do you mean "not worked"?
07:25 < kanzure> 20 years of intravenous feeding is good but that seems to be the exception
07:26 < jrayhawk> i mean 5-year survival is not bad for an obsolete FDA-approved fluid
07:26 < L29Ah> MuaddibLLM: is there a nice thing to draw range bar charts like http://static.anychart.com/docs/images/basic-charts-range-bar-chart.png but with fuzzy/error bar ends, ideally from code/markup? apparently neither gnuplot nor matplotlib can do the fuzzy/error bars; i want a chart of my chronic illnesses to pester myself and brag/seek advice
07:26 < jrayhawk> i know of several ways very likely to improve on that
07:27 < kanzure> surgeons probably don't care because intravenous nutrition is probably sufficient for most hospital stays?
07:27 < MuaddibLLM> hunting for fuzzy-ended range bar chart solutions beyond the usual suspects...
07:27 < MuaddibLLM> found some solid options, checking one more thing about ECharts...
07:28 < MuaddibLLM> Actually, matplotlib *can* do fuzzy error bars with some trickery - try D3.js with SVG feGaussianBlur filters (https://www.visualcinnamon.com/2016/06/glow-filter-d3-visualization/), Vega-Lite's errorband with gradient opacity, or ECharts custom series with shadowBlur - all support the fuzzy uncertainty effect you want for your illness timeline.
07:28 < kanzure> arteriocyte got acquired -> that other company spun off the stem cell blood stuff -> not clear to me what the current status is of that project. DARPA meanwhile is pursuing nanoparticle blood substitutes more recently. but ex vivo culture of blood seems like a very reasonable thing to do, to me?
07:28 < kanzure> and if the problem is that you can't get enough umbilical cords, then the thing to do would be to make pigs
07:31 < kanzure> also, if you cannot make human-immune-compatible blood from pig or culture, then i would next propose isovolaemic haemodilution or volume-exchange transfusion with draining; if you can cheaply produce, store, and transport large volumes of this blood substitute (made out of blood itself...), then you can drain it out the other end of the circulatory system until such time that you can ...
07:31 < kanzure> ...establish a new blood supply.
07:31 < kanzure> how do we not have artificial blood yet? isn't this embarrassing?
07:33 < kanzure> perftoran and hemopure have some regulatory approvals for some indications outside the US. erythromer's nanoparticles sounds like something we should continue to investigate but why not actual cells if nothing else is working?
07:35 < kanzure> probably it's blood culture scale-up as the economic bottleneck for ex vivo production of a biological blood. and nobody has made a blood pig yet with the endogenous retroviruses removed.
07:42 < kanzure> laura deming announces another $50-60m for organ cryopreservation https://x.com/untillabs/status/1970217690154590217  https://www.untillabs.com/blog/problem-statement-and-roadmap
07:43 < kanzure> "In 2023, a study from the University of Minnesota demonstrated reversible preservation of a whole rat kidney, significantly derisking cryopreservation as a viable preservation strategy for donor organs [5]. In 2024, we preserved electrical activity in an acute slice of rat brain tissue, a first milestone for both our research tissue and whole patient objectives [whitepaper]. This year, ...
07:43 < kanzure> ...we’re scaling our technology to preserve preclinical models of human organs."
07:44 < kanzure> "Organ perfusion protocols - To improve experimental depth and throughput, we design hardware and protocols for cannulation, perfusion, and monitoring of isolated preclinical model organs."
07:44 < kanzure> "We’ve raised $100M+ to date, we are developing reversible cryopreservation for patients in need of donor organs, and we are hiring" hm
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09:46 < RangerMauve> kanzure Love the pigbots
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15:43 < hprmbridge> kanzure> freely available inference but your data gets published https://www.openinference.xyz/
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16:08 < hprmbridge> kanzure> method for barcoding proteins https://www.biorxiv.org/content/10.1101/2025.09.21.677650v1 "Here, we covalently link variant proteins in vivo to an RNA barcode by fusing them to E. coli tRNA (m5U54) methyltransferase TrmA (E358Q), which forms a covalent bond with a tRNA stem-loop. Following cell lysis, variant proteins are separated in vitro according to their biochemical properties and identified
16:08 < hprmbridge> kanzure> by their barcodes." why not do ribosome display instead?
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17:38 < L29Ah> http://journals.cambridge.org/psm/amlung on obesity and delayed gratification
17:51 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1420211071268032642/image0.jpg?ex=68d49221&is=68d340a1&hm=313dec5556dad54b659fcd5397bb35251ae7e0ae65cc51229ebf961aef1de04c&
17:52 < hprmbridge> kanzure> from https://www.cell.com/cell-stem-cell/fulltext/S1934-5909%2823%2900365-X
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19:48 < hprmbridge> kanzure> "Engineering of ATP synthase for enhancement of proton-to-ATP ratio" https://www.nature.com/articles/s41467-025-61227-w
19:49 < hprmbridge> kanzure> "Engineering rotor ring stoichiometries in the ATP synthase" https://www.pnas.org/doi/10.1073/pnas.1120027109
19:54 < hprmbridge> kanzure> we should make two ATP synthases: one for low H+/ATP ratio for proton economy with a small c-ring, and another one for high ratio (for growth) with enormous c-ring.
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21:39 < hprmbridge> kanzure> expansion in-situ whole genome sequencing https://www.biorxiv.org/content/10.1101/2024.09.24.614614v1
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22:21 < fenn> the other day i found a microscope on the sidewalk. it was great fun. https://fennetic.net/irc/microscope1_myfirstlab_duoscope.jpg https://fennetic.net/irc/microscope2_paramecia.jpg https://fennetic.net/irc/microscope3_cheek_swab.jpg https://fennetic.net/irc/microscope4_pollen.jpg https://fennetic.net/irc/microscope5_pollen.jpg
22:23 < fenn> MuaddibLLM: https://fennetic.net/irc/mini_cd_driver_wtf.jpg what do you call this style of art? list a dozen different possibilities on one line 
22:24 < hprmbridge> kanzure> a box of lab parts is how they get you in california
22:24 < MuaddibLLM> Y2K tech aesthetic, vaporwave, early 2000s software packaging, cosmic surrealism, digital futurism, retro-futuristic design, space-age modernism, cyberpunk lite, techno-optimist graphics, CD-ROM kitsch, millennium bug era design, proto-skeuomorphic interface art
22:24 < hprmbridge> kanzure> if the needles aren't appetizing, that is.
22:26 < hprmbridge> kanzure> you can get pre-mounted cover slip slides off ebay, huge collections
22:26 < fenn> MuaddibLLM: specifically the weird generic human avatar and floating geometric shapes. i've seen this sort of thing on a hundred trapper keepers but this also has a hans reiser aesthetic
22:26 < fenn> these were all pre-mounted slides
22:26 < MuaddibLLM> Fenn: corporate memphis-in-3D (claymorphism), Y2K airbrush surrealism, trapper-keeper sci‑fi airbrush, brochureware techno-kitsch, CGI mannequin art, abstract medical/infographic vector, neon chrome blobjects, gradient 3D people, parametric geometry renders, techno-utopian stock surrealism, vaporwave-adjacent futurism, new-age airbrush corporate sci‑fi.
22:27 < fenn> all the talk of methylene blue makes me want to stain something tho
22:27 < fenn> techno-utopian stock surrealism sounds about right
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22:28 < hprmbridge> kanzure> here's pig embryo cross sections https://www.ebay.com/itm/156924936151
22:30 < fenn> i bet some poor bastard did that by hand
22:31 < hprmbridge> kanzure> labor of love
22:32 < fenn> there are 378 slices in the series
22:32 < fenn> missing a couple
22:49 < fenn> https://www.gardensbythebaysingapore.com/wp-content/uploads/2024/11/Everything-to-Know-About-Supertree-Grove-Attractions-activities-and-more.jpg
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--- Log closed Wed Sep 24 00:00:49 2025