--- Log opened Thu Jul 17 00:00:43 2025
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04:06 < hprmbridge> kanzure> bug catching is patented by none other than nintendo https://patents.google.com/patent/JP7493117B2/en
04:21 < jrayhawk> Maybe they let Bugsnax live due to having a Switch release.
04:29 < jrayhawk> more realistically it'd a public relations and jury question of "can we convince the average person that the game and its producers deserve punishment", for which it's relatively easy to sell Palworld and Pocketpair as bad guys regardless of the specific legal constructs used.
04:29 < jrayhawk> er, it'd be a
04:30 < jrayhawk> they painted quite the target on their backs
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07:22 < hprmbridge> kanzure> "That's reasonable, but I don't think you have good evidence for it, just low priors and limited imagination."
07:31 < hprmbridge> kanzure> how about ancephalic pet cloning for pet longevity + whole body transplantation. the benefit here is that it's not human and therefore you might not be imprisoned immediately for trying to do a thing.
07:51 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1395417563462107166/GZyLRsPaYAA3gB8.jpg?ex=687a5f60&is=68790de0&hm=dbb4fac540af12b67786e9ff91c524015f121b0a58c0c13e823bf22681f7c08e&
07:54 < hprmbridge> kanzure> parakeet > whisper https://huggingface.co/spaces/hf-audio/open_asr_leaderboard
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16:41 < hprmbridge> nmz787> well, first couple tries with this tapXR wristband and I'm not impressed
16:41 < hprmbridge> nmz787> i had to install some android app just to update the firmware
16:41 < hprmbridge> nmz787> and the taps just aren't recognizing
16:41 < hprmbridge> nmz787> I suppose I can try turning on a light
16:42 < hprmbridge> nmz787> but, *le sigh*
16:42 < hprmbridge> kanzure> "Third thing: [I find it implausible that a far future in our galaxy will be a situation where] total [economic] value divided by total atoms is greater than all [economic] value generated on Earth right now" https://x.com/AndyMasley/status/1945924108257997230
16:43 < hprmbridge> kanzure> @nmz787 Thank you for your sacrifice.
16:57 < hprmbridge> nmz787> maybe my messy desk is confusing it
16:57 < hprmbridge> nmz787> they probably didn't think such a disorganized person would buy their product :.
16:57 < hprmbridge> nmz787> :/
17:03 < hprmbridge> nmz787> room light doesn't fix it
17:03 < hprmbridge> nmz787> their app has some autocorrect setting, turning it on got me a few keypresses but then nothing
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17:32 < hprmbridge> nmz787> Oook return slip printed 😦
17:41 < hprmbridge> nmz787> Hrmm maybe I was wearing it wrong... I shall try once more
17:42 < hprmbridge> nmz787> Their one how it works webpage says it uses a neural processor, ugg
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18:04 < hprmbridge> nmz787> can you read me?
18:04  * L29Ah reads nmz787
18:04 < hprmbridge> nmz787> this
18:05 < hprmbridge> nmz787> ok, well I guess I was wearing it wrong... but it's really slow
18:05 < hprmbridge> nmz787> (back at kb now)
18:05 < L29Ah> slow as in "big delay" or "low throughput"?
18:09 < hprmbridge> kanzure> The “polygenic-only” thesis insists that, because most complex traits are controlled by thousands of loci, phenotypes can be altered only by editing a comparable number of sites; yet classic work from the 1970s-1990s shows that single-gene or few-gene manipulations routinely produce dramatic, heritable change. Cohen and Boyer’s 1973 plasmid swap gave E. coli tetracycline resistance with one
18:09 < hprmbridge> kanzure> operon; Genentech’s 1978 insulin cassette made bacteria crank out a human hormone; pronuclear injection of a single rat growth-hormone transgene doubled mouse size in 1982; Ti-plasmid delivery of one herbicide-resistance gene created the first transgenic plants in 1983; precise knock-out of individual loci in yeast and mice (Capecchi, Evans, Smithies, 1980s) linked single genes to immunity, coat
18:09 < hprmbridge> kanzure> color, and more; and two added carotenoid-biosynthesis genes turned white rice golden by 2000. These successes hinge on regulatory leverage—a master regulator or pathway enzyme can cascade through thousands of downstream genes—plus selectable markers that amplify rare edits and metabolic “patching” where a mini-pathway (often just 1-3 genes) yields a wholly new output. Together they debunk the
18:09 < hprmbridge> kanzure> notion that thousands of edits are prerequisite: targeted changes at one or a handful of loci, chosen for their outsized regulatory or biochemical impact, are sufficient to rewire cell or organismal traits.
18:18 < hprmbridge> nmz787> low throughput. it will take some learning... both the patterns and fingering movements that the camera can see
18:18 < hprmbridge> kanzure> who is the world champion fastest wpm using this device?
18:44 < hprmbridge> nmz787> Probably the employees
19:01 < hprmbridge> kanzure> https://help.openai.com/en/articles/11487532-chatgpt-record
19:07 < hprmbridge> kanzure> 'avoid mitochrondria disease by moving genome of fertilized egg into a donor egg'
19:08 < L29Ah> so which mom gets the legal motherhood?
20:24 < fenn> that's almost exactly the same as "mitochondrial replacement therapy" except the egg is fertilized afterwards https://www.researchgate.net/figure/Mitochondrial-replacement-therapy-three-parent-baby-Eggs-are-harvested-1-from-the_fig15_329379756
20:30 < fenn> not to be confused with mitochondrial transplantation which is for larger animals
20:34 < fenn> infants with anencephaly "do not survive longer than a few hours or days after birth" so how's that gonna work for your whole body donor clones
20:38 < fenn> presumably there are dozens of different mechanisms for slightly different phenotypes, all called anencephaly, and a few of them have better survival odds?
20:39 < fenn> "In the United Kingdom, a child born with anencephaly was reported as the country's youngest organ donor. Teddy Houlston was diagnosed as anencephalic at 12 weeks of gestation. His parents, Jess Evans and Mike Houlston, decided against abortion and instead proposed organ donation. Teddy was born on 22 April 2014, in Cardiff, Wales, and lived for 100 minutes, after which his heart and kidneys were
20:39 < fenn> removed. His kidneys were later transplanted into an adult"
20:40 < fenn> so there's legal precedent even
21:18 < fenn> https://undark.org/2016/12/23/three-parent-babies-battle-mitochondria/
21:18 < fenn> you wouldn't want the "superhero" mitochondria because it could never be displaced in the future
21:19 < fenn> also it sounds like cancer, but what do i know
21:40 < jrayhawk> cancer is the absence of homeostatically mitochondria-regulated BCAA/glucose transporter expression, mitochondria-regulated apoptosis, and mitochondria-provided oxidative phosphorylation
21:42 < fenn> andy masley, director of EA DC, says he became "panopticon-pilled" because women are oppressed, or something like that. nevermind what they're actually using the panopticon for
21:45 < jrayhawk> which is self-reinforcing in the sense that mitochondria are more sensitive to oxidative stress than other organelles, so once a cell has switched over to unregulated glucose fermentation, it's very hard to re-create an environment where mitochondria can be re-introduced
21:46 < jrayhawk> Somehow stem cells do it, though. I don't know how that works.
21:48 < fenn> are there cancer drugs to inhibit that whole metabolic pathway? i mean, you don't really need it right?
21:49 < fenn> .wik Lonidamine
21:49 < saxo> "Lonidamine is a derivative of indazole-3-carboxylic acid, which for a long time, has been known to inhibit aerobic glycolysis in cancer cells." - https://en.wikipedia.org/wiki/Lonidamine
21:50 < fenn> "inhibits both respiration and glycolysis" :|
21:50 < jrayhawk> Yes, though, in practice, you also have to suppress glutamine energy metabolism.
21:50 < jrayhawk> https://scholar.google.com/scholar?q=cancer+glutamine+press-pulse
21:53 < hprmbridge> Eli> I think that's sort of why people are doing keto for some types of cancer, no?
21:54 < jrayhawk> Ayup.
21:56 < fenn> can i just chug keto and not eat anything else and "go keto" that way?
21:56 < fenn> ketones*
21:57 < fenn> i have a small bottle of ketones which claim to be edible
21:57 < fenn> i'm not sure how it's intended to be used
21:58 < jrayhawk> uh... well, time-scales of application get complicated
22:00 < jrayhawk> acutely, you'd still want electron transport chain co-factors and some means of managing the oxidative stress involved in handling ketone bodies
22:00 < fenn> it's this but different marketing copy (no mention of IQ or energy or caffeine) https://ketone.com/products/ketone
22:01 < jrayhawk> but also acutely, cancer cells can survive off of stored BCAAs and autophagy for a while
22:01 < fenn> er, actually it's "ketone esters" not the new diol product
22:02 < fenn> oh i guess this company got bought out. it was called hvmn
22:03 < fenn> anyway
22:03 < fenn> jrayhawk: isn't the goal to blast cancer cells with oxidative stress tho?
22:04 < jrayhawk> that's the traditional model. if you're targeting energy pathways directly, it makes more sense to just kill them by cutting off energy supply.
22:05 < jrayhawk> I don't know if you've seen someone go through traditional cancer therapy, but it, uh, leaves something to be desired.
22:06 < fenn> there are less cytotoxic ways to create oxidative stress than existing chemo drugs, like low dose radiation or cold oxygen plasma
22:07 < fenn> transdermal ozone
22:08 < jrayhawk> which, hilariously, have the side effect of trashing mitochondria, which was the initial problem.
22:14 < fenn> the dose makes the poison
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22:27 < jrayhawk> a dangerous sentiment when the dose is introduced into a system where the distribution of cellular vulnerability is already empirically generating risk of unmanaged cancer initiation, and the dose can also either decrease immune capacity to manage the initiation, or amplify the differentiation of phagocytes to endocytose the oxidative stress bomb of the cancer cell, which can then itself migrate 
22:27 < jrayhawk> and permeate barrier membranes while proliferating controllably.
22:27 < jrayhawk> it's just not a great paradigm
22:27 < jrayhawk> er, proliferating uncontrollably
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22:33 < fenn> noted.
22:34 < jrayhawk> There are other awkward tradeoffs involved in the ketosis approach, of course. Reactive oxygen species are one of the main things the immune system looks for in doing cleanup tasks, so countering the unregulated insulin sensitivity of cancer cells by radically lowering insulin winds up making them less obvious to the immune system.
22:38 < jrayhawk> If there's some abnormal surface expression the adaptive immune system can use as an antigen, is it better to learn it in an environment with a clear signal-to-noise ratio?
22:39 < jrayhawk> People getting cancer do so through a combination of metabolic dysfunction and immune dysfunction, so there's also a question of what sort of lifestyle changes can be expected to modify tradeoffs
22:40 < fenn> not if later on that same antigen is expressed by all the healthy cells
22:40 < fenn> that's autoimmune dysfunction
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22:42 < jrayhawk> like if a person is never going to produce appropriate myeloid differentiation factors due to lifestyle decisions, that whole consideration of immunologically managing cancer goes out the window and you're stuck with every initiation becoming an exogenous management problem
22:43 < jrayhawk> in such circumstances, cancer initiation is a *lot* more costly a risk to take on
22:44 < jrayhawk> and, similarly, forcing slow growth and selecting for slow-growth mutations in the fast-evolving cancer mass might not have a real downside in that case
22:48 < fenn> i'm coming at all this from the idea that in the ancestral environment, humans had periods of feast and famine, and it was during the famine that fatty tissues were converted into ketones
22:49 < fenn> so i'm sort of unclear what you mean by "lifestyle decisions"
22:50 < fenn> it's not like you're going to be in permanent ketosis
22:51 < fenn> tom nufert was eating butter and velveeta, and still died of cancer
22:51 < fenn> his main concern was whether to supplement testosterone to maintain muscle mass, given that this would also stimulate his cancer cells
22:52 < fenn> i don't know what he decided
22:53 < jrayhawk> The combination of retinoids and vitamin-D, the combination of docosahexaenoic acid and arachidonic acid, the absence of tissue-permeating immunogenic proteins, biologically appropriate membrane and stored fatty acid ratios, etc. The usual stuff.
22:54 < jrayhawk> The ancestral environment had a lot going for it besides famine.
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23:15 < jrayhawk> the ancestral environment also had bioavailable minerals (non-phytate-bound, non-picolinate-bound, non-inorganic), low xenoestrogen load (avoiding a feedback cycle between estrogens and histamine), no folic acid (TH1/TH2 modulation equivalent to methotrexate), no dense carbohydrate loads without accompanying Nrf2 upregulating polyphenols...
23:16  * fenn mumbles about honey
23:17 < jrayhawk> honey is chock full of polyphenols
23:17 < jrayhawk> at least, raw honey
23:18 < fenn> i didn't know that
23:19 < fenn> 10mg/100g
23:21 < fenn> vs 200 for grape juice
23:23 < jrayhawk> as a signal rather than a nutrient, variety is also helpful
23:24 < fenn> yes honey has all the different flavonoids apparently
23:33 < jrayhawk> yeah, i find it a tragedy that reviews like this don't make any particular effort to classify study by pasteurization https://www.mdpi.com/2072-6643/15/13/3056
23:35 < jrayhawk> statistically less pathological than sucrose? okay, but you could probably statistically get there by filling your sucrose with wax esters, so i am not overly impressed by your study design
23:37 < jrayhawk> but that's industry-funded science for you. designed from the start to be free of risk of learning something new.
23:38 < fenn> tell an AI to write a review article
23:38 < jrayhawk> it'd be footwork of calling up researchers and finding out what products they were using, then calling the producers of those products to find out what sort of processing went into them
23:39 < fenn> "total phenolic content (TPC) from different honeys ranged between 0.65 ± 0.42 and 84.17 ± 30.40 mg/100 g" is quite a large range of values
23:40 < fenn> i'm sure it depends on what the bees were eating
23:40 < fenn> i vaguely recall some horror story about a leaking train tanker car full of HFCS with red dye, the only reason they tracked it down was it was giving the honey a crazy red color
23:43 < jrayhawk> you need better horror stories. i recommend The Great Boston Molasses Flood.
23:43 < fenn> the molassacre, i am aware
23:43 < jrayhawk> lol
23:59 < fenn> "interval hypoxia hyperoxia therapy" 1 hour sessions for training your mitochondria https://fit4life.ch/ihht/wissen/ 
--- Log closed Fri Jul 18 00:00:44 2025