--- Log opened Thu Nov 09 00:00:20 2023
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00:30 < hprmbridge> alonzoc> https://arxiv.org/abs/2310.09217 just read this gem of a paper. Who doesn't wanna become a turn key tyrant
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00:40 < muurkha> everybody wants to rule the world?
00:40 < hprmbridge> alonzoc> I don't think of the paperwork
00:40 < muurkha> I don't think of it either
00:41 < muurkha> I just noticed that the prices of low-cost solar cells have fallen to 0.11 euros per peak watt, a record low and *half* the price at the end of last year: https://www.solarserver.de/photovoltaik-preis-pv-modul-preisindex/
00:41 < hprmbridge> alonzoc> I'll take a continent sized space habitat tho
00:41 < muurkha> I guess the price-fixing cartel they announced at Davos at the end of 02018 finally collapsed?
00:41 < muurkha> .t https://www.reuters.com/article/us-davos-meeting-solar-gcl-idUSKCN1PI2OQ
00:41 < muurkha> this is huge, given that people were already signing PPAs for 1.5-cent-per-kilowatt-hour power in 02020: https://pv-magazine-usa.com/2020/05/28/record-low-solar-ppas-in-the-southwest-means-carbon-capture-is-not-going-to-save-coal-plants/
00:41 < EmmyNoether> Party is over for dirt-cheap solar panels, says China executive | Reuters
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00:41 < muurkha> .t
00:42 < EmmyNoether> Record low solar PPAs in the Southwest mean ‘carbon capture is not going to save coal plants’ – pv magazine USA
00:42 < hprmbridge> alonzoc> Huh cool
00:42 < muurkha> based on the much higher module prices then prevalent
00:42 < muurkha> but energy is a much bigger part of the world economy than DRAM was
00:42 < hprmbridge> alonzoc> Solar power becoming more viable is always good especially now that we're gonna need to run off grid AI bunkers lol
00:43 < muurkha> (when the DRAM cartel collapsed in 01996 and memory fell from US$40 a meg to US$10)
00:43 < muurkha> you won't be laughing when the Computer Enforcement Agency drones you for operating an unlicensed computing device, boy
00:45 < hprmbridge> alonzoc> CEA drone strikes are a real worry
00:45 < muurkha> sorry, I was joking
00:45 < hprmbridge> alonzoc> Nah I found it funny hence the response
00:45 < muurkha> oh good
00:45 < muurkha> I hadn't been watching PV pricing this year because it had been so boring for the last four years
00:46 < hprmbridge> alonzoc> Written english is bad at nuance, gotta all start using ithkuil
00:46 < muurkha> so I'm astounded to see that it's become dramatic again
00:46 < hprmbridge> alonzoc> Look at the memory market now lol, Samsung made wayyyy to much
00:47 < hprmbridge> alonzoc> If only processors were as cheap as memory
00:48 < hprmbridge> alonzoc> Also kicking myself I didn't pickup all the second hand eth mining GPUs, issue was a lot of groups kept going after the merge in denial so timing was hard
00:51 < muurkha> yeah!
00:52 < muurkha> a thing I don't understand is how retail solar panels are still like a dollar a watt
00:52 < hprmbridge> alonzoc> Margins
00:53 < muurkha> okay but why doesn't anyone undercut those margins?
00:53 < muurkha> 75% is a large margin, 89% a ridiculous one
00:55 < hprmbridge> alonzoc> There might also be another layer of cartelness
00:55 < muurkha> hmm actually it looks like it's down to like 50 cents a watt now here in Argentina
00:55 < hprmbridge> alonzoc> Also just inertia
00:56 < hprmbridge> alonzoc> Markets take a while to react
00:56 < muurkha> like https://articulo.mercadolibre.com.ar/MLA-1375824901-panel-pantalla-solar-monocristalino-410w-eging-108-celdas-_JM is $184564 for supposedly 410 watts
00:57 < muurkha> according to https://preciodolarblue.com.ar/ the dollar is at $865 today
00:57 < muurkha> so that's US$213
00:58 < muurkha> are they cheaper or more expensive where you are?
00:58 < hprmbridge> alonzoc> Prolly not I'm in the UK so it'll follow US and EU markets
00:59 < muurkha> surely it must be one or the other
01:00 < hprmbridge> alonzoc> It really depends, for a lot of things it varies and it's kinda unclear why
01:03 < hprmbridge> alonzoc> Usually it's whichever is more expensive /hj
01:07 < muurkha> I mean, surely it must be cheaper or more expensive than it is here
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01:10 < hprmbridge> alonzoc> Searching gives lots of variance but I can get a 330 watt panel for about £210
01:10 < hprmbridge> alonzoc> So $258
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01:33 < fenn> this is a bio-nano molecular assembly tool. i literally made it myself out of spaghetti and jello: https://fennetic.net/sd/tRNA_00023-1348851960.jpg
01:34 < fenn> the bit of jello on the end there is just barely stuck on
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01:40 < muurkha> hmm, that sounds more expensive per watt than here.  that's surprising!
01:40 < muurkha> fenn: this looks like a render
01:40 < fenn> it is logos made flesh
01:41 < fenn> (i typed a lot of words to get that image)
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01:56 < muurkha> logos made pixels
01:58 < hprmbridge> Katylase> Oh my, that tRNA is so cute🥰
02:01 < muurkha> yay Katylase is back!
02:06 < fenn> and here is how many iterations an intelligent designer uses bumbling around in the dark https://fennetic.net/irc/graphical_phylogeny1.png https://fennetic.net/irc/graphical_phylogeny2.png (1MB each)
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02:10 < fenn> missed some https://fennetic.net/irc/graphical_phylogeny3.png
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03:28 < hprmbridge> kanzure> what is the tRNA cargo here?
03:30 < hprmbridge> alonzoc> Never seen tRNA be referred to as cute before 😂
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06:23 < kanzure> welcome jkhales
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06:55 < docl> hmm. if you wanted to use longer codons (so they are cell specific), what would the technical barriers be? the amount of DNA needed would be higher unless you could compress it, but you might be able to use a denser polymer. main issue I'm seeing is you also need a new ribosome that can handle more than 3 basepairs per codon
06:57 < docl> if you could pull it off, you get cryptographic security and cell addressability. it could be a lot more virus-proof as well, since you can limit the tRNA to stuff no natural virus has a match for
06:58 < docl> plus if you shrink the size you can pack more functionality in the nucleus, like optical control systems. red/blue light patterns that match a cryptographic signature could completely rewrite a given cell on the fly
07:29 < hprmbridge> kanzure> I think there was a paper with an expanded genetic codon length up to 4
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07:47 < docl> hmm. bet that involves a funky evolved ribosome
07:51 < hprmbridge> boxious> has anyone used cell-free reactions to synthesize proteins from plasmids? id love to not deal with e.coli
07:54 < docl> a 20bp codon might be well outside what you can evolve from a ribosome, but I kinda think rational design could accomplish it with spirologomers or dna origami
07:55 < docl> @boxious sure seems possible in principle
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08:09 < docl> @boxius am looking at google results for that now -- takes some times to grok but I do see a lot of papers about cell-free synthesis
08:09 < hprmbridge> boxious> there are kits but was curious if anyone here has actually done it
08:09 < docl> https://www.nature.com/articles/s43586-021-00046-x
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08:25 < docl> "Perhaps the most important experimental evidence for a scenario in which triplet decoding is considered to be an evolutionary product of longer-than-triplet decoding is the fact that the modern translational apparatus supports such decoding. Quadruplet decoding was discovered as early as in the 1970s as a mechanism for a frameshift suppression [41]. It has been possible to isolate tRNA molecules with 
08:25 < docl> extended anticodon loops, whose incorporation into the ribosome results in quadruplet decoding that suppress +1 frameshift mutations (single nucleotide insertions in mRNA) [42]–[44]. The ability of certain mutant tRNA molecules to support quadruplet and even quintuplet decoding is now well documented [45]–[49]."
08:25 < docl> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682656/ Codon Size Reduction as the Origin of the Triplet Genetic Code
08:26 < docl> so aparently at least some existing ribosomes do work for up to 5bp
08:28 < docl> https://www.sciencedirect.com/science/article/pii/S1074552102001072 Title: Custom Codons Come in Threes, Fours, and Fives
08:29 < docl> "The paper by Anderson et al. on pages 237–244 of this issue demonstrates that E. coli's ribosome can accommodate variably sized codon/anticodon interactions from the usual three up to five base pairs and that these may represent upper and lower bounds."
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08:52 < hprmbridge> kanzure> boxious: yes. if you have a specific question we can get it answered.
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08:53 < hprmbridge> kanzure> ok I was wrong, codon length up to 5
08:53 < hprmbridge> boxious> kanzure: ... any particular kit / mixture youv found to be most cost effective, any automation used?
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08:59 < hprmbridge> yashgaroth> cell-free is gonna be infinitely more expensive than e coli no matter what. NEB's kits work fine, I haven't tried others. There's not much automatable since you're just mixing a few reagents together
08:59 < hprmbridge> yashgaroth> is there a reason you don't like e coli
09:01 < hprmbridge> boxious> im sticking with e.coli for now, but thought maybe there could be more control with a cell-free mixture, especially if made in house.
09:04 < hprmbridge> yashgaroth> depends what you mean by control. Unless you have a specific reason for cell-free, eg expressing toxic proteins or non-canonical amino acid incorporation, I guarantee it's not worth the hassle
09:05 < hprmbridge> boxious> well, if i could make a cell free mixture myself, that would allow for testing out modified transcription proteins right?
09:09 < hprmbridge> yashgaroth> unless you have a fairly well-equipped lab, reconstituting the entire translation apparatus isn't really possible. Ultracentrifuge, HPLC, FPLC, etc. Can you provide details on what the modified transcription proteins are and what you need them for
09:13 < docl> kanzure: actually thinking it over we don't need long codons to assign 1 distinct encoding per cell because there are over a quadrillion ways to do it and under 100 trillion cells. the problem of some genes broken by being recoded is still an issue though. also you'd have to engineer a polymerase and tRNA synthase that update in sync if you want it to recode itself every time the cell divides
09:15 < docl> but like, in principle you could have an embryo that has every cell contain a unique encoding
09:15 < docl> not just "the individual has their own encoding" but "every cell"
09:37 < docl> I wonder if self-recoding e. coli would be useful
10:00 < docl> if that were easy to evolve, something would have developed it as a viral resistance mechanism, you'd think
10:06 < docl> ah, come to think of it polymerase mechanism just doesn't work in a way compatible with the change being to that, it replicates DNA by splitting it lengthwise and matching each side. replacing that with something that produces entirely different sets isn't trivial. basically you need to put one of the single strands through a modification routine first
10:33 < docl> @yashgaroth @kanzure have you considered feeding ssDNA through your DNA-write technique? producing recoded DNA that way seems like it would be easy, since the ribosome doesn't discriminate. might need to zip 3 strands to make it work though
10:36 < docl> and might need a slightly nonstandard ribosome
10:41 < hprmbridge> kanzure> https://patents.google.com/patent/US11339423B2/en
11:02 < hprmbridge> yashgaroth> are you talking about for codon recoding? that doesn't really make sense
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11:17 < docl> @yashgaroth yes, for recoding. substituting each triplet in sequence for the whole strand
11:23 < docl> forget hacking mitosis, that's a bit ambitious, but could be useful to have stem cells you can kill off easily with a virus without infecting healthy tissue. version control :)
11:41 < docl> this should actually be simpler since the tRNA (tDNA?) is selected by watson-crick pairing, you wouldn't be using promiscuous nucleic acid and it would be a single solution reaction
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11:55 < hprmbridge> Katylase> @fennfoot would you mind if I turned it into a sticker? To put into my notebook?
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12:34 < hprmbridge> kanzure> https://www.theatlantic.com/politics/archive/2023/11/peter-thiel-2024-election-politics-investing-life-views/675946/
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12:57 < fenn> @katylase stickers are fine
13:00 < fenn> @katylase there's this goop you can get to 3d-ify small stickers with surface tension, google "domed resin stickers" i guess there's epoxy and silicone flavors
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13:06 < fenn> polyurethane, not silicone
13:06 < oxphi> im really excited for nanotech, when we gettin this party started
13:09 < hprmbridge> Katylase> You like stickers too?😄
13:11 < fenn> i saw it at the japanese dollar store where i get airtight plastic containers and ziploc bags
13:11 < oxphi> btw Im working on protein design - can follow my progress here: https://twitter.com/0xCF88
13:11 < oxphi> Haven't said much so far but I plan to be posting more.
13:20 < hprmbridge> Katylase> My mom bought me a sticker printer so I can make custom ones
13:20 < hprmbridge> Katylase> This lil guy:
13:20 < hprmbridge> Katylase> (I have the turquoise striped one) https://cdn.discordapp.com/attachments/1064664282450628710/1172284481110032485/IMG_2470.webp?ex=655fc200&is=654d4d00&hm=2b509daa6ec9d2463b342e8d5a9d656257d25ca4cd57c77baf6077d7077a63e1&
13:20 < fenn> oxphi: "Western Blot: This method can confirm the size of the protein, which can indirectly suggest proper folding if the size matches the expected one."
13:21 < fenn> oxphi: "Immunoprecipitation: This technique can be used to check protein-protein interactions, which can indirectly suggest proper folding if the protein interacts as expected"
13:21 < fenn> oxphi: "Immunofluorescence: This can be used to check the localization of the protein in cells, which can also suggest proper folding if the protein is localized as expected."
13:21 < fenn> fuckin amazing machine mind
13:22 < hprmbridge> Katylase> About protein folding, do you know the game FoldIt?
13:23 < oxphi> fenn: thanks, somewhat familiar with those. Also it seems NMR is good too
13:24 < oxphi> would absolutely love to do CryoEM but seems expensive AF
13:25 < fenn> @katylase be advised that thermal paper contains a lot of BPA which can get on your hands and be absorbed through the skin
13:25 < fenn> now you can justify doming stickers as a safety precaution :)
13:28 < fenn> oxphi: the bit about localization within the cell got me thinking, you could add a fluorescent tag on a long linker, to avoid needing a custom antibody
13:29 < fenn> you could bury protease cleavage sites inside the protein; if they're exposed they get cut much more easily
13:31 < hprmbridge> Katylase> (European Union banned BPA in things in 2011, so the stickers prolly got checked somewhere in their lifetime🤭)
13:34 < fenn> lol yeah right
13:34 < fenn> because BPS is toadally different~
13:35 < hprmbridge> yashgaroth> fenn was that from gpt because those aren't good methods for checking folding
13:35 < fenn> yes this is me asking GPT-4
13:35 < hprmbridge> yashgaroth> good, my job is secure for now
13:35 < fenn> what's wrong with western blot?
13:36 < hprmbridge> yashgaroth> western blot requires sds-page which denatures the protein, hence no confirmation of proper folding
13:36 < oxphi> lol busted
13:36 < fenn> k
13:37 < fenn> the next idea i had was aptamers; if you can predict the aptamer structure from sequence and it matches the protein structure...
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13:38 < hprmbridge> yashgaroth> if you're doing e coli expression, if you can purify the protein it's probably folded; else it'd end up in an inclusion body and/or degraded
13:38 < fenn> uh, context is: @0xCF88 "I need cheap methods for detecting successful protein structure / function"
13:38 < fenn> it might fold differently than expected
13:39 < hprmbridge> yashgaroth> mhm you're basically limited to functional assays at that point
13:40 < hprmbridge> yashgaroth> for binders, tag it with 6xHis or something and do an ELISA with your target immobilized and an anti-6xHis antibody
13:40 < hprmbridge> yashgaroth> for enzymes, ehhh can't really hallucinate those with alphafold but best of luck
13:41 < fenn> personally i am more interested in, uh, "bio-nano-mechanical engineering"
13:41 < hprmbridge> kanzure> @Katylase one of the users here was ranked top 20 for FoldIt
13:41 < hprmbridge> yashgaroth> excuse me I was top 10
13:42 < hprmbridge> boxious> the only reason I'm interested in protein design despite being primarily interested in broader molecular nanotechnology is:
13:42 < hprmbridge> boxious> 1) the biotechnology nanosystem is already fully functional, and thus synthesizing proteins from dna sequences is straightforward and cheap
13:42 < hprmbridge> boxious> 2) our bodies are already in this format
13:42 < hprmbridge> boxious> 3) "diamondoid" nanotechnology development and manufacturing is going to significantly lag biotechnology for reason #1, despite its theoretical superiority in performance to biotech formats
13:42 < hprmbridge> boxious> I find there are a lot of people who are completely disinterested in biotech in favor of more diamondoid like nanotech, overlooking the fact that biology is engineerable *now*
13:43 < fenn> even drexler said we should forget about diamondoid for now and focus on protein engineering
13:46 < alethkit> exactly how cheap is protein engineering supposed to be?
13:47 < alethkit> It still seems that it's in the cent range for a BP
13:47 < fenn> https://web.archive.org/web/20160319050356/http://metamodern.com:80/tag/protein-engineering/
13:49 < fenn> alethkit you only have to print the DNA sequence once
13:49 < fenn> one cent per BP is ridiculously cheap for R&D
13:50 < docl> it's mainly a cost difference wrt competing approaches like spiroligomers. dna self replication makes it cheap.
13:51 < fenn> and all the other stuff to scale up
13:51 < fenn> how much to build a house out of spiroligomers
13:53 < docl> it's just chon, so not much if you solve self rep first
13:54 < fenn> i must be missing a few hundred steps
13:54 < fenn> how do you get bulk spiroligomers from self replication?
13:54 < alethkit> oh, right
13:54 < alethkit> I still need to learn how this stuff works
13:55 < alethkit> fenn: any book recommendations?
13:55 < fenn> sorry, i haven't read a book in years
13:56 < oxphi> alethkit: how dna/protein synthesis work?
13:57 < hprmbridge> kanzure> we have a DNA synthesis method that we have not published yet. work in progress.
13:57 < hprmbridge> kanzure> but other methods are on the wiki for the channel
13:58 < oxphi> kanzure: what is the end-goal with that, will it be open source / enzyme sequences available?
13:59 < fenn> if the DNA is left handed, it's probably not a good source of info: https://i.ytimg.com/vi/3IlqO4qsqUQ/maxresdefault.jpg
14:00 < alethkit> yes
14:00 < alethkit> fenn: so you just read papers?
14:00 < fenn> i don't know man
14:01 < docl> the basic feedstock is trans-4-Hydroxy-L-proline. so you could design a process leveraging spiroligomers to synthesize that directly or to let you grow a microbe that makes it. then use spiroligomers to produce the building spiroligomer block molecules. then you would need to assemble them in the desired structures, which could be done with spiroligomer based machinery. then transport them in the shape 
14:01 < docl> of a house, which you'd use different spiroligomer structures to do.
14:02 < fenn> i started in college but i find the computer graphics animations by drew berry better than most of the explanations in a textbook: https://www.youtube.com/playlist?list=PLD0444BD542B4D7D9
14:02 < fenn> skip the malaria lifecycle
14:03 < oxphi> im guna agree on that, those animations are high quality
14:04 < fenn> an important caveat is that there are zillions of molecules bouncing around everywhere and only a tiny fraction randomly follow the seemingly intention-directed paths shown
14:06 < fenn> also david goodsell https://pdb101.rcsb.org/sci-art/goodsell-gallery
14:12 < fenn> ah jeez of course they only have the high resolution versions as ~100MB TIFF files
14:14 < fenn> nothing a little URL hacking can't solve https://cdn.rcsb.org/pdb101/goodsell/png/bacteriophage-t4-infection.png
14:14 < fenn> (large png)
14:16 < fenn> "Illustrations are free for use under a CC-BY-4.0 license" cool
14:16 < fenn> i'm gonna use the crap out of these then :)
14:18 < hprmbridge> kanzure> https://diyhpl.us/wiki/dna/dna-synthesis.html
14:18 < hprmbridge> kanzure> https://diyhpl.us/wiki/polymerase/notes/
14:19 < fenn> he had so many sars-cov-2 illustrations in 2020 and i've never seen any of them in the wild
14:20 < docl> how large of synthetic peptides can fit in a ribosome?
14:25 < hprmbridge> kanzure> I don't understand the question.
14:25 < hprmbridge> kanzure> fenn did you try that visualization tool I linked to the other day
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14:28 < fenn> webgl and me don't get along. also it wanted to display 100 million atoms
14:28 < hprmbridge> kanzure> do you remember the name? having trouble here.
14:28 < docl> er, synthetic amino acids
14:29 < hprmbridge> kanzure> there are some review papers on unnatural amino acids that are compatible...
14:30 < fenn> mol-* https://molstar.org/dev/me/examples/
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14:30 < hprmbridge> kanzure> thank you
14:30 < fenn> can you actually run the visualization?
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15:04 < docl> kanzure: I'm specifically wondering if PNA triplets can fit, so you can produce a PNA molecule matching your strand exactly, just with a different set of basepairs per triplet. otherwise you would have to run the process 3x using different tRNA each time and combine the results somehow.
15:07 < hprmbridge> yashgaroth> no
15:30 < kanzure> n>5 length codons https://gnusha.org/logs/2017-05-12.log
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15:59 < hprmbridge> kanzure> peter thiel is very, very bored: https://cdn.discordapp.com/attachments/1064664282450628710/1172324685703299154/F-hX76AXUAAkkRe.png?ex=655fe771&is=654d7271&hm=f3bf44ea0fbc88168f0fbdab6ef6930820a3aaa7d820356bd2a405c6ba33ab27&
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17:29 < hprmbridge> kanzure> fenn: works for me? https://cdn.discordapp.com/attachments/1064664282450628710/1172347367605948426/image.png?ex=655ffc91&is=654d8791&hm=ce77caabbadd82ccded0235273bfd697e5c32fbe81ceb3a4e97a1bfdd6020010&
17:30 < hprmbridge> kanzure> and https://cdn.discordapp.com/attachments/1064664282450628710/1172347565333807115/image.png?ex=655ffcc0&is=654d87c0&hm=2657e14976d420c7524bada4930e48c1686fbd60a2f46c7d2277d7c362839335&
17:31 < kanzure> it's a little bit slow for me.
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19:17 < fenn> n>3 codons increases the risk of frame shift mutation per amino acid
19:17 < fenn> perhaps you could have a frame marker codon
19:18 < fenn> part of the fun is that everything speaks the same language though
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21:35 < docl> it occurs to me that DNA compression is doable. you could have long, long strands that predictably compress to a single base. given this, could you print it with an inkjet? it would need to come out laying in a specific direction, and I'm not sure that's doable. any ideas?
21:55 < hprmbridge> boxious> inkjet? what do you mean
21:57 < docl> I'm picturing a special ink that goes in something like a regular inkjet printer in place of colors. RGB+Black gives you chambers enough for 4 base pairs of information. but I suspect this approach can't work because of fluid dynamics and the need to limit degrees of freedom for the strands.
22:00 < docl> for a long strand like this ideally you'd immobilize most of it apart from the ends and carefully place them end to end. doing it by hand would be a bit tedious though
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22:28 < docl> maybe the strand can be anchored in a micron scale plastic plate that tends to lock in place with an adjoining plate, something like that.
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23:39 < fenn> spacex starship launches in a few days maybe
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--- Log closed Fri Nov 10 00:00:21 2023