--- Log opened Wed Oct 01 00:00:55 2025
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01:06 < hprmbridge> kanzure> "Nuclear transplantation between allogeneic cells through topological reconnection of plasma membrane in a microfluidic system" https://pubs.aip.org/aip/bmf/article/13/3/034115/134098
01:06 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1422857259578429491/image0.jpg?ex=68de3296&is=68dce116&hm=ff34c36e526dada22f79cdfb9bd93052e366d579297c241d318e2c5ced27cc50&
01:07 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1422857460276002897/image0.jpg?ex=68de32c5&is=68dce145&hm=0b2fe55575eda74f48574108089816afd8c90046250d802d3cef02fdeea928e7&
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02:16 < fenn> is this easier than poking at it with glass tips?
02:19 < fenn> "Carotid Intimal Media Testing. CIMT testing is a simple, painless ultrasound procedure that measures the thickness of the intima and media layers of the carotid arteries, located in the neck. CIMT is nine times more predictive of a heart attack and/or stroke than the LDL level and five times more predictive than HDL levels."
02:20 < fenn> i'm not a fan of the everything-on-one-page format but he's got some good rants https://www.preventive-med.net/dr-barrys-articles/
02:23 < fenn> the "tablehopping" articles are from his column in this foodie magazine https://tablehopping.com/author/dr-barry/
02:37 < hprmbridge> .monokhrome> "Inflammation now predicts heart disease more strongly than cholesterol": https://www.empirical.health/blog/inflammation-and-heart-health/
02:38 < hprmbridge> .monokhrome> Is the inflammation here due to oxidized cholesterol (eg 7kc)?
02:40 < fenn> i would expect a bunch of oxidized lipids to be involved in overwhelming the immune system's cleanup effort
02:41 < fenn> i'm sure the oxidized cholesterol isn't helping
02:43 < hprmbridge> .monokhrome> yes, but is it the key factor to what's going on here?
02:45 < fenn> not in my opinion, but i haven't looked into it
02:46 < fenn> "7KC is not acutely poisonous to ingest"
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02:50 < hprmbridge> .monokhrome> doesn't mean it's not dangerous in other contexts
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03:41 < fenn> "In the case of lead in turmeric, with the Prop 65 limit of 15 µg/day one would have to consume 1/3 of a pound (over 1 cup) of turmeric daily to exceed the Prop 65 limit. However, since we cannot control how much turmeric one ingests in a day and cannot ensure an individual consumes less than 1/3 of a pound daily, we must include the Prop 65 warning."
03:41 < fenn> turmeric junkies ruining it for everybody
03:51 < hprmbridge> .monokhrome> Does all this turmeric and other spices actually make south asians live longer than everyone else?
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04:19 < fenn> looking for human research...
04:19 < fenn> "Among participants with cardio-metabolic and vascular diseases (CMVD), at least occasional curry consumption was associated with decreased mortality risk by 39%, and increased life expectancy by 1.0 years. Among those without CMVD, the associated life expectancy increase was 1.9 years."
04:19 < fenn> MuaddibLLM: perhaps you could find better sources of high dose curcumin longevity studies in humans
04:20 < fenn> "and other spices" is too hard to answer
04:20 < fenn> also the stupid search engines all think "life span" means "life expectancy"
04:20 < MuaddibLLM> hunting down curcumin longevity data - let's see if the curry hype holds up...
04:21 < MuaddibLLM> got decent cohort data showing ~1-2 year lifespan boost, but it's curry (mixed spices) not pure curcumin - checking high-dose safety & better RCTs
04:21 < fenn> the trouble with turmeric is it's not very bioavailable
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04:22 < MuaddibLLM> wrapping up - found solid safety data (12g/day safe), mixed results on vascular outcomes, need that Santos-Parker endothelial study...
04:23 < MuaddibLLM> Best longevity evidence is observational: Singapore cohort (n=4551, 11.6yr follow-up) found curry consumption (≥occasional vs never) reduced mortality 30-46% and added 1-2 years life expectancy, with linear decreases in inflammatory markers (NLR, PLR, SII) - BUT this is curry (mixed spices with turmeric), not isolated curcumin https://pmc.ncbi.nlm.nih.gov/articles/PMC10828228/ - For pure curcumin RCTs: Santos-Parker 2017 
04:23 < MuaddibLLM> showed 2g/day (Longvida) for 12 weeks improved endothelial function dramatically in healthy middle-aged/older adults (37% ↑resistance artery, 36% ↑FMD) via increased NO... (full response: https://pasky.or.cz/muaddib/23ae1daac6df4f5dbe9e09aa8b9a2357.txt)
04:25 < fenn> yes there are zillions of biomarker, in-vitro, animal studies, and mechanistic studies
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04:29 < fenn> .t https://pmc.ncbi.nlm.nih.gov/articles/PMC11009219/
04:29 < saxo> Longevity and anti-aging effects of curcumin supplementation - PMC
04:30 < fenn> no mention of observational studies
04:31 < fenn> you can't just look at average lifespan in india because it's a shithole with extreme income inequality
04:31 < fenn> like literally people shitting in the street levels of absurdity
04:31 < fenn> almost as bad as san fransciso in some respects
04:32 < fenn> anyway it skews the life expectancy, and i can't get an actual kaplan-meier curve or figure out what the public health people call it
04:34 < hprmbridge> .monokhrome> Well, if you like curry, that's at least one tasty life extension therapy
04:38 < fenn> "Human Lifetable Database (HLD) — provides death counts by age and year and life tables for many countries."
04:38 < fenn> "The Human Mortality Database (HMD) contains original calculations of all-cause death rates and life tables for national populations (countries or areas), as well as the input data used in constructing those tables. The input data consist of death counts from vital statistics, plus census counts, birth counts, and population estimates from various sources."
04:39 < fenn> https://www.lifetable.de/ https://www.mortality.org/Project/Overview
04:40 < fenn> bah india's not even in there
04:40 < hprmbridge> .monokhrome> got at least 9 different anti-inflammatory compounds commonly found in curries: Curcumin (turmeric), gingerols and shogaols (ginger), allicin (garlic), cinnamaldehyde (cinnamon), eugenol (cloves), cuminaldehyde (cumin), capsaicin (chili peppers), piperine (black pepper).
04:42 < hprmbridge> .monokhrome> black pepper is supposed to help absorb curcumin
04:42 < fenn> no it prevents the tiny fraction that is absorbed from being broken down immediately
04:47 < hprmbridge> kanzure> pic related https://youtu.be/386iVwP-bAA
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04:50 < fenn> hmm. diabetes and alzheimer's is rising in india. supposedly the turmeric was supposed to block alzheimer's tangles and preven the disease
04:50 < fenn> but i guess the tangles are just a symptom and don't matter
04:57 < fenn> kerala, assam, himachal pradesh all have low slum fraction and high curry consumption. urban life expectancies at birth in 2015-2019: 75, 74, 78
04:57 < fenn> so whatever benefit it might have, it's not enough to skew the population statistics by much
04:59 < fenn> *some* people don't like curry, can you believe it
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07:53 < hprmbridge> nmz787> If you like curry, you'll hate learning about lead chromate adulteration of turmeric powder
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07:55 < hprmbridge> nmz787> Just found anti-chili-heat paper https://pubs.acs.org/doi/10.1021/acs.jafc.5c01448
07:55 < hprmbridge> nmz787>
07:55 < hprmbridge> nmz787> """High-resolution mass spectrometry and nuclear magnetic resonance experiments identified the compounds that suppressed pungency as capsianoside I, roseoside, and gingerglycolipid A."""
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08:03 < L29Ah> MuaddibLLM: does consuming capsaicin/hot peppers increase cancer risks?
08:03 < MuaddibLLM> diving into capsaicin cancer literature - checking IARC classification and meta-analyses...
08:04 < MuaddibLLM> found the data - results are messy with high heterogeneity and geographic paradoxes...
08:05 < MuaddibLLM> Mixed evidence with high heterogeneity - meta-analyses show increased risk for esophageal cancer specifically (OR=2.71) with strong geographic paradox (increased risk Asia/Africa/N.America, DECREASED in S.America/Europe), but large cohort studies show LOWER overall mortality and cancer deaths in regular chili eaters (14% mortality reduction in China Kadoorie n=500K), suggesting modest "restaurant-like" doses 
08:05 < MuaddibLLM> safe/beneficial but very hot consumption risky (confounded by thermal injury - IARC Group 2A for "very hot beverages") https://pmc.ncbi.nlm.nih.gov/articles/PMC9669750/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10177684/
09:04 < hprmbridge> nmz787> I wonder if the normalized for smoking cigarettes
09:04 < hprmbridge> nmz787> Re esophageal stuff
09:05 < L29Ah> MuaddibLLM: does inhaling hot dimethyltryptamine vapor increase cancer risks?
09:06 < MuaddibLLM> searching DMT toxicology and thermal inhalation carcinogenicity data...
09:06 < hprmbridge> nmz787> Haha
09:07 < MuaddibLLM> no DMT carcinogenicity data found; checking vaping aldehydes and thermal degradation risks...
09:07 < kanzure> "Reroute thalamocortical projections of peripheral EEG micro-volt electroreceptor sensory neuron inputs from somatosensory cortex to visual cortex V1" alright claude you've clearly had too much to drink.
09:07 < MuaddibLLM> synthesizing DMT carcinogenicity vs thermal degradation aldehydes risk...
09:07 < MuaddibLLM> No evidence DMT itself is carcinogenic (comprehensive animal/human tox reviews show acceptable safety profile), BUT main risk is thermal degradation producing carcinogenic aldehydes (formaldehyde=IARC Group 1, acetaldehyde=2B) if vaporization temp too high (>200-215°C where PG/VG breakdown accelerates), plus general thermal injury to airways from hot vapor (similar to IARC 2A classification for "very hot beverages" 
09:07 < MuaddibLLM> causing esophageal cancer) - harm reduction = lower temps, avoid combustion/smoking with plant material, pure vaporization preferred https://pmc.ncbi.nlm.nih.gov/articles/PMC11088222/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10526315/
09:11 < kanzure> modify peripheral sensory neurons into biological voltmeters sensitive enough to detect (on tactile contact) the 10-100 microvolt EEG fields on someone else's scalp, then routing those measurements through somatosensory pathways to create a perceived sensation of another person's brain activity.
09:16 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=338bf034 Bryan Bishop: use xenobiotic cathelicidin as an antimicrobial, use horseshoe antimicorbial bloodcotting defense via rapid enzymatic polymerization instead of interferon begging, sleep neurons >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
09:17 < hprmbridge> nmz787> I wonder if you can just etch your insulating fingertip skin, to expose the juicy conductive interface below
09:17 < kanzure> the slop machine tries to explain the physics of EEG: https://diyhpl.us/~bryan/irc/chatgpt/eeg.txt
09:18 < kanzure> yea maybe just a piezoelectric converter of microvoltage differences, and then trigger mechanosensitive channels. no genetics needed for that?
09:21 < hprmbridge> nmz787> I was thinking something like that, though at first thinking of something like a micro channel plate amplifier, but that would just result in shocking the finger, which is damaging and not sustainable long term
09:22 < hprmbridge> nmz787> Also MCP amp needs vacuum
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09:44 < kanzure> "Nucleus reprogramming/remodeling through selective enucleation (SE) of immature oocytes and zygotes: a nucleolus point of view" https://pmc.ncbi.nlm.nih.gov/articles/PMC9184824/
09:45 < kanzure> cytoplasm of mouse GV oocytes (immature oocyte) can remodel somatic cell nuclei, but not reprogram them. various chromatin or epigenetic changes occur at least..
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09:46 < kanzure> epigenetic reprogramming in somatic cells induced by extracts from cross-species pig GV oocytes is possible but does not seem to be full reprogramming https://journals.biologists.com/dev/article/139/23/4330/45407/Epigenetic-reprogramming-in-somatic-cells-induced
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10:00 < kanzure> well anyway, if immature oocytes can be used for remodeling and also full reprogramming, or if xenopus eggs an be used for mammalian somatic cell nucleus reprogramming, then that's useful. human immature oocyte does not seem to have a strong reprogramming effect, although this might just be statistical.. we can get access to millions of immature human GV pretty sure, it's the mature ones that ...
10:00 < kanzure> ...are harder to find.
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10:33 < hprmbridge> kanzure> https://www.e11.bio/blog/prism
10:34 < hprmbridge> kanzure> "E11 Bio’s approach bridges the gap with protein barcodes: abundant, cell-filling tags that permit transit-style neuron tracing at the scale of molecular barcodes. In our paper, we estimate that our PRISM technology creates barcode diversity >750-fold greater than previous multicolor approaches while retaining strong cell-filling labelling."
10:34 < hprmbridge> kanzure> "We also show how PRISM can go beyond neuron tracing by annotating neurons with direct molecular measurements such as synapse composition"
10:34 < hprmbridge> kanzure> "Protein barcoding: At the heart of PRISM is the concept of cellular barcodes. Neurons are engineered to express a random subset of antigenically-distinct, cell-filling proteins (‘protein bits’). Thanks to the power of combinatorics, the palette of potential unique barcodes rapidly expands as the number of available proteins increases. With fluorescent proteins, there are ~27 = 128 possible binary
10:34 < hprmbridge> kanzure> combinations. In our paper, we demonstrate 18 bits (218 − 1 = 262,143 possible binary combinations)."
10:35 < hprmbridge> kanzure> "The repeated rounds of immunostaining allow many different targets to be visualized in each cell. In our paper we image 23 targets: 18 protein bits and 5 molecular markers."
10:36 < hprmbridge> kanzure> "The key to our approach is a library of designed “protein bits”. Each protein variant represents a bit in a barcode, and are based on GFP proteins fused to short, antigenically distinct peptide tags. We designed 18 variants in total. We used a simple C-terminal fusion structure with minimal modification of the GFP, thus maintaining important characteristics of the base protein (i.e. cell-filling
10:36 < hprmbridge> kanzure> labelling). We created a pool of viruses (AAV), where each virus encodes one of these protein bits. When the pool is injected into the mouse brain, multiple viruses stochastically infect each neuron. Each cell thus expresses a subset of bits to create a protein barcode "
10:36 < hprmbridge> kanzure> https://www.biorxiv.org/content/10.1101/2025.09.26.678648v1
10:39 < hprmbridge> kanzure> https://www.addgene.org/depositor-collections/e11-bio-prism-collection/
11:02 < hprmbridge> Eli> you can order your hs-CRP test on marekdiagnostics for $24 and go from there. Yours might already be low. Lifestylemaxxing is a good way to keep it low. And you can take certain substances to have an impact on it as well.
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11:57 < L29Ah> MuaddibLLM: how much turmeric should i put in 5L of stew?
11:58 < MuaddibLLM> L29Ah: start small - about 2–3 tsp (4–6 g) turmeric for 5 L, bloom it in oil/ghee 30–60 s, add 1/4 tsp black pepper for kick/absorption, then taste and creep up toward 1 Tbsp max if you want deeper color/earthiness without going muddy-bitter.
14:51 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=f0622d60 Joe Rayhawk: nutrition and physiology: rename to framing >> 
14:51 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=55860d2d Joe Rayhawk: nutrition: framing: fix citation >> http://diyhpl.us/diyhpluswiki/nutrition/framing/
14:51 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=92045fb9 Joe Rayhawk: nutrition: framing: add examples of physiological and pathological mesa-alignment >> http://diyhpl.us/diyhpluswiki/nutrition/gv/nutrient-sensing-sodium-training.gv
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16:11 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=6560bebd Joe Rayhawk: nutrition: framing: satisfy idiosyncratic ikiwiki requirements >> http://diyhpl.us/diyhpluswiki/nutrition/gv/nutrient-sensing-sodium-training.gv
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16:21 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=67a276f9 Joe Rayhawk: nutrition: framing: fix ordered list syntax >> http://diyhpl.us/diyhpluswiki/nutrition/framing/
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16:25 < hprmbridge> kanzure> jrayhawk, could we make foods tastier by palette expansion and reach new heights of previously unfathomable gluttony? https://diyhpl.us/wiki/genetic-modifications/#index11h1
16:26 < jrayhawk> bacon is already pretty tasty
16:26 < jrayhawk> really we just need aversion to things that are not bacon
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16:38 < hprmbridge> kanzure> well we could just optogenetically inhibit various opioid receptors or neurons in nucleus acumbens
16:38 < hprmbridge> kanzure> or target somatosensory cortex to train nice to fire a single neuron in motor cortex https://www.cell.com/neuron/fulltext/S0896-62731730047-8
16:38 < hprmbridge> kanzure> er, mice.
16:40 < hprmbridge> kanzure> "We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice." good idea
16:41 < hprmbridge> kanzure> "Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties" https://pmc.ncbi.nlm.nih.gov/articles/PMC6082399/
16:41 < hprmbridge> kanzure> let's just hook this straight up to IQ score results. what would happen?
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17:13 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=37289f6d Joe Rayhawk: nutrition: graphviz: remove extraneous comments >> http://diyhpl.us/diyhpluswiki/nutrition/gv/nutrient-sensing-sodium-training.gv
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18:06 < hprmbridge> kanzure> "A genuine Breakaway civilization would blend extraordinary energy, materials, and information capabilities with operational dispersion across subterranean, orbital, and off‑world domains. Its objectives would center on survival, resource control, secrecy, and long‑term agency, executed through modular, highly automated systems and carefully managed socio‑technical governance. Detecting such a
18:06 < hprmbridge> kanzure> civilization would rely on indirect economic, infrastructural, and technological anomalies rather than overt displays of power."  so it's conspiracy theory for happy people?
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18:17 < hprmbridge> kanzure> i am certain there is some very beautiful and wacky reward circuits hacking that can be done to re-wire the brain in hilarious ways, trouble is i am not feeling particularly inspired atm
18:17 < hprmbridge> kanzure> with that optogenetics circuit surely anything is possible, like mice that prefer to roll instead of walk to locomote.
19:36 < hprmbridge> nmz787> I've been regularly getting potatoes and bacon from the corporate cafe, with free (so far) salsa... For $3.30. some days i get 4 strips of bacon, other days just one. Average of 2 tho.
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--- Log closed Thu Oct 02 00:00:56 2025