--- Log opened Wed Nov 19 00:00:42 2025
00:58 -!- gl00ten [~gl00ten@2001:8a0:4aa7:ec00:1cbb:8ada:6e92:35b2] has joined #hplusroadmap
01:51 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has joined #hplusroadmap
01:51 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has quit [Remote host closed the connection]
01:52 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has joined #hplusroadmap
02:07 -!- gl00ten [~gl00ten@2001:8a0:4aa7:ec00:1cbb:8ada:6e92:35b2] has quit [Ping timeout: 265 seconds]
02:29 < hprmbridge> kanzure> "Dario Amodei from Anthropic believes AI can cure most forms of cancer, prevent Alzheimer’s, and double the human lifespan. / Anyone who understands biomedical and clinical research knows that AI won't magically compress a century of medical progress into 5–10 years. / It’s very odd to me that Amodei says this. Anthropic has very strict censorship on science questions b/c of Yudkowsky or Liron
02:29 < hprmbridge> kanzure> Super Ebola dystopian nightmare. You can’t even ask college level science questions, so how could it contribute anything towards “curing all diseases”? If that happens, (it won’t, you / Insilico are the farthest ahead in the world) Anthropic will not be playing a role." https://x.com/MelindaBChu1/status/1991060657886593307
03:13 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1440661267374411816/image0.jpg?ex=691ef7dc&is=691da65c&hm=a23dbcd6b81c57b6442882d79a909e41e6c4b1f767b618f6377f4a692aa096b9&
04:03 -!- Croran [~Croran@user/Croran] has quit [Ping timeout: 264 seconds]
04:16 < hprmbridge> kanzure> his ego has grown to unimaginable proportions https://x.com/Jiankui_He/status/1990800263960203397
06:42 < kanzure> female infertility from advanced age can be solved by human cloning.
06:44 < kanzure> someone should do a backup of jetpress.org
06:45 < kanzure> "The amorality of preference: A response to the enemies of human enhancement" https://jetpress.org/v19/jackson.htm (2008) because i was thinking about this section of jonathan anomaly's book that talks about beauty and i think jojack wrote about this in this paper.
06:46 < kanzure> "Vasculoid: A personal nanomedical appliance to replace human blood" https://www.jetpress.org/volume11/vasculoid.html (2002) by freitas.
06:46 < kanzure> "The vasculoid is a single, complex, multisegmented nanotechnological medical robotic system capable of duplicating all essential thermal and biochemical transport functions of the blood, including circulation of respiratory gases, glucose, hormones, cytokines, waste products, and cellular components.  This nanorobotic system, a very aggressive and physiologically intrusive macroscale ...
06:46 < kanzure> ...nanomedical device comprised of ~500 trillion stored or active individual nanorobots, weighs ~2 kg and consumes from 30-200 watts of power in the basic human model, depending on activity level.  The vasculoid system conforms to the shape of existing blood vessels and serves as a complete replacement for natural blood.  This paper presents a preliminary theoretical scaling analysis including ...
06:47 < kanzure> ...transport capacity, thermal conduction, control and biocompatibility considerations, along with a hypothetical installation scenario and a description of some useful optional equipment."
06:48 < kanzure> oh there's not that many publications
06:53 < kanzure> well that wasn't so hard.
07:12 < kanzure> freitas wants "neuronal microrobots" (endoneurobot, gliabot, synaptobot)  that fit inside of neurons and use atomic force microscopy to map out the membrane and features at nanometer resolution for the purpoess of brain uploading or brain scanning. https://jetpress.org/v26.1/martins.htm
07:12 < kanzure> "Extracellular space is extremely tight, with the average width of the free brain extracellular space (ECS) lying between 38-64 nm (Thorne and Nicholson 2006). ECS width around the cell bodies of oligodendrocytes typically measures 0.3-10 nm; the ECS around the cell bodies of astrocytes oscillates from 4-154 nm. By comparison, a synaptobot is 500 nm in its smallest dimension."
07:12 < kanzure> "The extracellular space (ECS) is thoroughly infiltrated by the extracellular matrix, a structure composed of negatively charged glycosaminoglycans and proteoglycans (Syková 2008) which play a major role in orchestrating the development of the CNS, are involved in remodeling the adult CNS after injury, and are involved in events that may underlie some aspects of memory (Syková 2008)."
07:18 < kanzure> the LLM slop machine proposes a non-drexlerian approach for a synapse nanorobot based on a microbe instead: "A synaptozyme is a genetically engineered, ultraminiaturized microbial organism designed to localize to neuronal axons, dendrites, and synaptic terminals and to perform high-temporal-resolution monitoring of synaptic structure and function via embedded biochemical reporter circuits, ...
07:18 < kanzure> ...membrane-targeting adhesion modules, and molecular recorders with nanoscale spatial specificity."
07:58 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=3e10b5cb Bryan Bishop: telencephalin is another knockout target for memory enhancement >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
07:58 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=ee816800 Bryan Bishop: extract a better table for mouse enhanced cognition, include references >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
08:00 < hprmbridge> kanzure> hey that worked out pretty well: https://cdn.discordapp.com/attachments/1064664282450628710/1440733355405742140/image.png?ex=691f3aff&is=691de97f&hm=340779e172e42fbb42866705f99c2e109a6cc8645dc590cbf0459f879dd09a1a&
08:01 -!- gl00ten [~gl00ten@186.255.114.89.rev.vodafone.pt] has joined #hplusroadmap
08:12 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=8e56c43a Bryan Bishop: fix table of contents for mouse memory and cognitive enhancement >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
09:10 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has quit [Quit: Avoid fossil fuels and animal products. Have no/fewer children. Protest, elect sane politicians. Invest ecologically.]
09:34 -!- gl00ten [~gl00ten@186.255.114.89.rev.vodafone.pt] has quit [Ping timeout: 264 seconds]
10:39 < hprmbridge> Eli> the Mice Against Ticks project uses embryonic gene editing
10:39 < hprmbridge> Eli> https://www.cbsnews.com/news/crispr-modify-mice-target-lyme-disease-60-minutes/
10:43 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has quit [Read error: Connection reset by peer]
10:44 < hprmbridge> Eli> We need to do this for malaria, the deadliest human pathogen in all of human history.
10:47 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has joined #hplusroadmap
10:50 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has joined #hplusroadmap
11:41 < kanzure> human malaria resistance is already on https://diyhpl.us/wiki/genetic-modifications/#Malaria_resistance but alternative approaches are welcomed.
11:43 < L29Ah> ddt carpet bombing
11:44 < kanzure> so have the genome encode lyme-neutralizing antibodies targeting borrelia burgdorferi and enable the expression of the antibodies. "The engineered antibody binds to outer surface proteins on Borrelia burgdorferi, especially OspA (Outer surface protein A) which is expressed in the tick midgut and is a long-standing target of Lyme vaccines and neutralizing antibodies. Some versions also target ...
11:44 < kanzure> ...OspC."
11:44 < kanzure> so you need a B-cell promoter basically.
11:45 < kanzure> 2-cell embryo microinjection is silly, why not just do the right technique instead of relying on microinjection? i guess it's simple and braindead so you might as well do it if you don't want to think about alternatives.
11:50 < kanzure> oops blocked by chatgpt
11:51 < L29Ah> MuaddibLLM: how much DDT does it take to obliterate malaria mosquitoes?
11:51 < MuaddibLLM> WHO recommends 1-2 g/m² for indoor residual spraying every 6 months, but during the 1955-1970 Global Malaria Eradication Program they used ~40,000 tons annually - that's some serious carpet bombing. Source: https://www.ncbi.nlm.nih.gov/books/NBK1724/
11:54 < hprmbridge> Eli> My recollection is that they were able to eliminate malaria from some places like the island of sardinia with DDT. But, they don't really do it a lot anymore.
11:54 < hprmbridge> Eli>
11:54 < hprmbridge> Eli> They've done a lot of stuff to the environment to get rid of malaria. One of the reasons we had a lot of African slaves in the south is because malaria was whiping out towns full of white people. Even back then, they realized that the Africans were surviving malaria somehow.
11:56 < hprmbridge> Eli> Seems like they are working on gene editing mosquitos to not carry malaria. That might be a better solution than trying to kill them all. Mosquitos have so many progeny, I'm not sure you could wipe them all out.
12:00 < hprmbridge> fodagut> This is a bit of a longshot, but someone here might be interested - we could use some help recovering a NIST database of surface structures, which they no longer maintain or distribute. The only version of this left out there is an old, unmaintained Windows program: https://www.fhi.mpg.de/1017073/oSSD
12:01 < hprmbridge> fodagut> We could use some help figuring out how to extract the NIST data from this program
12:01 < MuaddibLLM> [gpt-5.1] I'd start by running the .exe under Wine/VM and watching what files it opens (Procmon/strace) to locate the actual data, then use Ghidra/IDA on the binary to find the file parsing routines and reconstruct the on-disk format so you can dump it to e.g. CSV/SQLite - and since it's NIST, the data should be public domain so there’s no legal barrier to a clean-room extractor.
12:13 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=10f25dd2 Bryan Bishop: better overview of oligonucleotide synthesis chemistries >> http://diyhpl.us/diyhpluswiki/dna/synthesis/notes/
12:14 < kanzure> is there a good ikiwiki option for rendering chemical structures? and hopefully also caching the renderings so that they don't get re-generated each time the wiki updates.
12:15 < MuaddibLLM> [gpt-5.1] I don't know of an off-the-shelf ikiwiki chem plugin, but the normal trick is a tiny IkiWiki::Plugin::filter that recognizes SMILES/InChI blocks, shells out to Open Babel/RDKit (or a CLI like obabel/rdkit2png) to spit out SVG/PNG into the underlay, and then lets ikiwiki’s dependency tracking cache those images so they only get regenerated when the source page changes.
12:15 < kanzure> "DeepSeek-OCR: Contexts optical compression" https://arxiv.org/abs/2510.18234v1 this is good at chemical structure OCR.
12:27 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1440800675322663084/image.png?ex=691f79b1&is=691e2831&hm=6781b7ce257f7e9b549ef229ff4339ede7dec63afdf08a952213fb3b5b4b8120&
12:27 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1440800745644626121/image.png?ex=691f79c2&is=691e2842&hm=569eeecaabb376b29313bf3a2134a080b73d15fbb1eea52c3643f8ef0687dd3a&
12:28 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1440800864183914616/image.png?ex=691f79de&is=691e285e&hm=37bcc1de1727a90dc65cc2c1376b0ea423d6b171fb817422e18e49386b9d7dc1&
13:35 -!- gl00ten [~gl00ten@186.255.114.89.rev.vodafone.pt] has joined #hplusroadmap
13:48 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=8f7c3311 Bryan Bishop: more oligonucleotide synthesis chemistry >> http://diyhpl.us/diyhpluswiki/dna/synthesis/notes/
14:02 -!- Gooberpatrol66 [~Gooberpat@user/gooberpatrol66] has quit [Quit: Konversation terminated!]
14:03 -!- TMM [hp@amanda.tmm.cx] has quit [Quit: https://quassel-irc.org - Chat comfortably. Anywhere.]
14:03 -!- TMM [hp@amanda.tmm.cx] has joined #hplusroadmap
14:07 -!- Gooberpatrol66 [~Gooberpat@user/gooberpatrol66] has joined #hplusroadmap
14:42 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=75198be1 Bryan Bishop: improve chemistry page >> http://diyhpl.us/diyhpluswiki/dna/synthesis/notes/
14:42 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=abebbd58 Bryan Bishop: even more oligonucleotide synthesis chemistry >> http://diyhpl.us/diyhpluswiki/dna/synthesis/oligonucleotide_synthesis.mediawiki
14:47 < kanzure> Is there anything else that should be included on that page? I think that some of these topics will be more heavily censored from large language models in the future. So it would be good to get a wishlist going now ahead of time.
14:47 < kanzure> diagrams, images etc would be helpful
14:48 < MuaddibLLM> [gpt-5.1] Wishlist: step-by-step mechanism diagrams for each cycle step (detritylation, coupling, capping, oxidation), tables comparing protecting groups and coupling reagents (pros/cons, typical yields, sequence-length limits), graphics of solid supports and pore sizes, flow schematics of a synthesizer (valves, reagent lines, timing), plots of yield vs length and error types, panels of common failure modes with 
14:48 < MuaddibLLM> troubleshooting, side-reaction schemes (depurination, branching, oxidation artifacts), and a small gallery of annotated chromatograms/mass spectra of clean vs bad synth runs.
14:55 < L29Ah> 404
14:55 < kanzure> caruthers lecture on oligonucleotide synthesis https://www.youtube.com/watch?v=YpC9HLqOLv4
14:56 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=e6f91db9 Bryan Bishop: add videos >> http://diyhpl.us/diyhpluswiki/dna/synthesis/notes/
14:57 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=010f563c Bryan Bishop: link >> http://diyhpl.us/diyhpluswiki/
15:12 -!- gl00ten [~gl00ten@186.255.114.89.rev.vodafone.pt] has quit [Ping timeout: 244 seconds]
15:34 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has quit [Read error: Connection reset by peer]
15:54 < hprmbridge> kanzure> another robot https://www.sunday.ai/beta-program
16:07 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has joined #hplusroadmap
16:33 < hprmbridge> kanzure> new embedding models https://x.com/OpenRouterAI/status/1991158802482340218
16:49 -!- stipa_ [~stipa@user/stipa] has joined #hplusroadmap
16:52 -!- stipa [~stipa@user/stipa] has quit [Ping timeout: 250 seconds]
16:52 -!- stipa_ is now known as stipa
16:53 < hprmbridge> kanzure> "Okay so in the SPOS process I’d say what would be the best thing I wish I had a reference on is the combinatorial options available for therapeutic RNA amidites (this means 2’-OMe, 2’-MOE and 2’-F, and besides standard Bz, Ac, iBu protection what is alternatives and how they get used) and then like basically a guide for BOM based on synthesizer types, scale, and in particular what kind of options
16:53 < hprmbridge> kanzure> (I.e. benefits and drawbacks) across different types of auxiliary reagents  (different blocks DCI, different activators ETT vs BTT, different oxidizers and thiolating reagents, XH and then other PS reagents DDTT etc., other capping reagents). Last is repository of all amidites ever characterized/publicly disclosed. (XNA Alphabet). One criticism for the page is saying capping step in the cycle is
16:53 < hprmbridge> kanzure> optional, that’s somewhat misleading. I mean maybe for small scale DNA for micro-array screening but like therapeutic oligo synthesis you cannot really skip this because you’ll form odd impurities. From CMC perspective you can’t skip that."
16:58 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has quit [Read error: Connection reset by peer]
17:12 < hprmbridge> kanzure> gpt-5.1-codex-max-extra-high
17:17 < hprmbridge> kanzure> "Vitrification (the egg freezing that works) was declared non experimental by ASRM in 2012, so 13 yrs ago. And ethical for elective reasons in 2016."
17:17 -!- L29Ah [~L29Ah@wikipedia/L29Ah] has joined #hplusroadmap
17:35 < superkuh> gemini-3 got me past a brick wall with substance P tacr1 blood brain barrier permeable small molecules with it's ability to do long free search. There are no such small molecule agonists known for tacr1, only antagonists. Asked it to look up transcriptional genomics papers for the tacr1 expressing neurons and look for specific receptors which co-expressed with tacr1. And it found one, the cell membrane estrogen receptor (not the nuclear one) and t
17:35 < superkuh> here are plenty of bbb passing small molecule agonists for it.
17:38 < kanzure> what data set was it searching?
17:39 < kanzure> oh i guess "papers" in general. ok.
17:40 < kanzure> it might be faster to use the FDA API to find already-approved drugs and then just read the full list of approved drugs. there can only be a few thousand, right.
17:40 < kanzure> that's what i was thinking when i learned about CCR5 antagonists the other day.
17:44 < superkuh> Yeah, just general. It was nice coincidence that both the gper1 and tacr1 had the same cAMP -> calcium second messenger and timescales of activity.
18:02 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=d50b1e03 Bryan Bishop: transcript: caurthers on oligonucleotide synthesis >> http://diyhpl.us/diyhpluswiki/transcripts/caruthers-2018/
18:22 -!- darsie [~darsie@84-113-82-174.cable.dynamic.surfer.at] has quit [Ping timeout: 240 seconds]
19:54 -!- justanotheruser [~justanoth@gateway/tor-sasl/justanotheruser] has joined #hplusroadmap
20:37 -!- Croran [~Croran@user/Croran] has joined #hplusroadmap
22:12 < hprmbridge> kanzure> https://www.renaissancephilanthropy.org/news-and-insights/why-we-wont-fund-research-towards-the-creation-of-mirror-organisms
22:13 < hprmbridge> kanzure> that's very odd, it's not like everyone publishes a list of what they won't invest in.... I wonder if someone has been shopping around a cool project?
22:50 -!- Guest36 [~Guest36@2601:640:8002:4f30:2dbc:e03d:5f63:1d85] has joined #hplusroadmap
23:24 -!- Guest36 [~Guest36@2601:640:8002:4f30:2dbc:e03d:5f63:1d85] has quit [Ping timeout: 250 seconds]
--- Log closed Thu Nov 20 00:00:43 2025