--- Log opened Mon Apr 24 00:00:41 2023
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01:20 < alethkit> kanzure: Full CS (and mathematics), with a bit of electronics
01:21 < alethkit> I do happen to have a very strong Pauli field around me though
01:21 < alethkit> I can't even set up a 3D printer without unexpected tolerance issues screwing me over
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06:48 < superkuh> https://rootsofprogress.org/isambard-brunel-on-engineering-standards
06:50 < superkuh> "The Commission for Stopping Further Improvements"
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08:40 < docl> alethkit: I plugged your comment about having a strong pauli field into chatgpt with gpt3.5, describing it as a self depricating joke. first 2x it interpreted it as causing glitches in electronics, 3rd try it says you might not be the easiest person to get along with or might be a bit of a loner. I think you've come to in the right place. my background is similar, although only 2 year degree in CS, so 
08:40 < docl> I even have the autodidact knowledge gaps on that. am usually not hard to get along with but apparently I make people feel like I think they are ignorant when they aren't or something like that. navigating around the fact of other people being actual experts is tricky. well worth it though. probably the best thing about this channel is sme's you can actually talk to.
08:45 < docl> I kind of model it like there's a patience budget you have to be careful not to exceed too egregiously. but people learn by teaching so there's value an ignorant but attentive/willing to learn person can provide. helps if you can get in the prerequisites to a reasonably approachable level so they don't have to waste their time on the basic stuff though.
08:56 < alethkit> docl: Well, time to make my quips so esoteric that even ChatGPT can't understand them
08:57 < alethkit> But yes, that is indeed what happens
09:03 < docl> have you done deep dives on any cool bio, nano, etc. stuff so far? space stuff obviously :)
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09:53 < kanzure> http://sam.zeloof.xyz/second-ic/
10:10 < docl> OK I'm staring at the liu paper again https://europepmc.org/article/PMC/4277153
10:11 < docl> it looks like... the DNA can be any arbitrary pattern, random mutant base order. you then take a PNA that matches, connect it to your 8-mer or whatever by cleavable bonds, and use the pattern match to determine what position to put the short-mer in
10:12 < docl> can't you just do this with DNA?
10:13 < docl> figure 1-D
10:15 < hprmbridge> msnewgooty> I think the issue with using DEL for PNAs is that they will also bind the DNA?
10:17 < docl> ahh
10:20 < docl> maybe have the 8-mers for the strand to be synthesized be double stranded? already paired up with their bases
10:32 < muurkha> pretty often people who are doing cool but abstruse stuff are delighted to be able to talk about it to someone who is equipped to understand them
10:35 < docl> I may be slow / reinventing the wheel here, but I just recently cottoned on to the overall thought that 4^4 or 4^8 are small enough to work with as a character set, which means if you can reliably line those up and get them to connect you can avoid needing to deal with individual bases
10:40 < hprmbridge> jasoncrawford> comments from someone who went to the Starship launch: https://progressforum.org/posts/NskMryyCmndEx2wtY/reflections-from-seeing-the-starship-launch-firsthand
10:40 < hprmbridge> jasoncrawford> “Seeing Starship on the launch pad close up is a monumental yet somehow very personal experience… The experience of the launch didn't feel viscerally monumental in the same way as a solar eclipse. Instead it was more strange and subtle, like seeing the Aurora Borealis combined with a distant thunderstorm”
10:41 < hprmbridge> jasoncrawford> “The concept of a single, eventually reusable, vehicle that can put 150 tons in orbit is particularly compelling. … We might start to see second-order effects and feedback loops, where cheaper launches enable more space infrastructure, which enables a lower-cost higher-volume supply chain for space hardware, which enables cheaper launches.”
10:44  * L29Ah picks his nose
10:47 < muurkha> yeah, it would be a huge change
10:48 < muurkha> what are purple-capped property boundary posts?  when I lived in Texas nobody taught me this
10:50 < muurkha> for context, the ISS is 420 tonnes
10:52 < L29Ah> but is ton 1 tonne?
10:52  * L29Ah glares at usanians
10:53 < hprmbridge> msnewgooty> Maybe I missed it, but what’s the goal of the PNAs? I also wonder if you could just use their DNA binding capabilities naturally
10:53 < hprmbridge> msnewgooty> Like if you make a strand of DNA that will assemble the PNA k-mers, then you can fuse them
10:54 < hprmbridge> msnewgooty> Seems more dirext
10:55 < muurkha> L29Ah: prolly, but I'm not sure it's that important whether three hypothetical Starship payloads would be enough for a space station of 420 tonnes or just 408 tonnes
10:58 < hprmbridge> msnewgooty> https://pubs.acs.org/doi/10.1021/ja038058b
11:00 < hprmbridge> msnewgooty> also similar ish work from Jen when she was in David's lab
11:00 < hprmbridge> msnewgooty> https://pubs.acs.org/doi/10.1021/ja904712t
11:13 < alethkit> docl: I need to start looking into synbio
11:14 < docl> check out spiroligomers too https://www.youtube.com/watch?v=8X69_42Mj-g
11:15 < docl> lots of overlap since it's an organic chemistry approach
11:16 < docl> more recent talk: https://www.youtube.com/watch?v=yQ09nW8UhU4
11:18 < hprmbridge> lachlan> I wasn’t there, but I imagine this mirrors what I would’ve thought had I been
11:33 < docl> msnewgooty: this is exciting / a new idea to me. I'll reserve proper self skepticism, but I'm imagining systems. 8-mers lets you do a library you could fit on a sheet of paper, of every possible combination. say you have a 4Mbp randomized reference strand that has been read, and 4Mbp that you want to synthesize. 8-mers are too small for this since it's only 65536 combinations and there will be repeats 
11:33 < docl> to handle. but what you could do is figure out what 16-mers you will need in advance, then make those from the 8-mers. attach them in parallel (one for the lookup key, one for the written data) with cleavable bonds and double strand and protect the ends of the data group so only the key group can react to the reference strand. then it should self assemble as a sequence. deprotect and cleave, then 
11:33 < docl> amplify with taq polymerase...
11:35 < hprmbridge> msnewgooty> Wait are we still talking about PNAs or DNA here?
11:35 < docl> I'm talking DNA. unless there's a reason to talk PNA? taq can be agnostic so it produces DNA from PNA (my understanding)
11:36 < hprmbridge> msnewgooty> I don't know if you can template DNA from PNA
11:36 < hprmbridge> msnewgooty> oh apparently you can!
11:36 < hprmbridge> msnewgooty> https://pubmed.ncbi.nlm.nih.gov/34592573/
11:37 < docl> :)
11:41 < hprmbridge> msnewgooty> But just to understand--ultimate goal is DNA synthesis, and this currently goes from DNA->PNA->DNA. What's the role of the PNA intermiediary
11:42 < docl> this is kanzure and yashgaroth's scheme, not sure I'm supposed to talk about it yet...
11:44 < hprmbridge> msnewgooty> haha no worries! Just trying to be helpful
11:44 < hprmbridge> msnewgooty> As always, I just want to get cheap DNA
11:44 < hprmbridge> msnewgooty> think I probably burn 200k+/year on IDT/Twist these days
11:46 < docl> huge market potential :)
11:47 < hprmbridge> msnewgooty> though as I said earlier, Ansa etc are thinking about therapeutic development to justify the size of market
11:47 < hprmbridge> msnewgooty> like, internal development
11:48 < hprmbridge> docl> is that where you work? or own the place? I am ignorant as all get out
11:48 < docl> https://ansabio.com/
11:49 < hprmbridge> msnewgooty> Haha, no I am not involved. Just what I have heard
11:51 < kanzure> msnewgooty: see DM
11:59 < docl> ok so out of self skepticism I'm going to try to predict my scheme's problem. it looks like you'd have to conjugate all those 8-mers into 16-mers separately, at least for the write group. then pair them with the key group with cleavable bonds. that's a huge number of reactions to do separately. parallelizable though
14:20 < fenn> john gurdon proved cloning in xenopus frogs in 1962 (demonstrated in 1958) https://aws.labome.com/figure/te-151-2.png  was there any real reason it took until 1996 to do it in mammals? (dolly the sheep)
14:22 < fenn> that's a long delay
14:40 < fenn> "In 1984, Steen Willadsen at the British Agricultural Research Council's Institute of Animal Physiology, Cambridge, successfully used cells from early embryos to clone sheep by nuclear transfer. The procedure he developed was essentially the one used a decade later by Wilmut et al. to produce Dolly, the sheep, although in the latter case, nuclei from a mature sheep, i.e. not from sheep embryos,
14:40 < fenn> were used.
14:42 < fenn> in 1952 robert briggs and thomas king cloned a frog by nuclear transfer of embryonic cells
14:55 < fenn> in 1975 derek bromhall transferred the nucleus from a rabbit embryo cell into an enucleated rabbit egg cell, which formed an embryo, but he never transferred the embryo to a rabbit womb (reason unknown)
14:57 < fenn> it's interesting that the author continued to deny that the book was a hoax: https://en.wikipedia.org/wiki/David_Rorvik#In_his_Image
15:06 < kanzure> yes we could have been doing a lot of this a long time ago, we simply did not
15:07 < fenn> https://ia800108.us.archive.org/1/items/OMNI197908/OMNI_1980_10.pdf (search for "predestinations" to get to the article by rorvik)
15:08 < fenn> i remember dolly being presented as a big deal and an accomplishment that took a lot of effort
15:09 < fenn> why is human cloning illegal again?
15:09 < fenn> is it simply tyrrany of the religious majority?
15:10 < fenn> tyranny*
15:10 < L29Ah> not many people wish to feel the impact of it into the traditional social order of things
15:10 < hprmbridge> jasoncrawford> How much of that is just the “valley of death” for ideas in between academia and industry? Academia proves a concept --> now it's not “new” so you can't get academic cred for it, but it still doesn't really *work* in an engineering sense, so it's not ready for VC either… hard to get funding for the engineering/invention work needed at this stage
15:13 < L29Ah> e.g. there're many misconceptions about cloning, as if it were a factory that produces adult copies of some human
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15:34 < fenn> hm the middle of the article by rorvik is missing from that scan
15:34 < fenn> oh well
15:39 < hprmbridge> kanzure> maybe we ask him for it
15:51 < fenn> .t https://www.ebay.com/itm/364122651591
15:51 < EmmyNoether> Search eBay
15:51 < fenn> Omni Magazine October 1980
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16:51 < fenn> .title https://www.youtube.com/watch?v=AUTWgpxSKIY
16:51 < EmmyNoether> Yuri Deigin | Epigenetic Rejuvenation by In Vivo Partial Reprogramming: Past, Present, and Future - YouTube
16:52 < fenn> another recent foresight institute tele-talk
16:53 < fenn> yamanaka factors (OSKM factors) reverse epigenetic aging and also many other hallmarks of aging, but can cause teratomas. if you only turn them on for a few days, you don't get teratomas
16:58 < fenn> one of the figures shows rejuvenation at a rate of 3.8 years per day of OSKM induction and its safe (in mice) for even 10 months
16:58 < fenn> now i'm wondering how long it took to develop teratomas - 10 months is a long time for a mouse
17:01 < fenn> i wish e-conferences would just record a local video directly from the presenter's laptop to upload to youtube
17:35 < fenn> greg fahy is trying to regenerate thymus tissue with growth hormone https://foresight.org/summary/greg-fahy-intervene-immune-thymus-rejuvenation-progress-update/
17:37 < hprmbridge> kanzure> there's also the lymph node organoid implant company. lysozoidal inc? I forget.
17:41 < fenn> yuri deigin makes a good point that stopping aging also stops the risk of dying from increasing exponentially; if you stopped aging at age 60 you'd expect to live another 100 years before dying of disease
17:41 < fenn> on average
17:43 < hprmbridge> msnewgooty> Also Bryan Johnson is getting on hgh
17:54 < fenn> re transplants, fahy says "the thymus has two jobs, manufactures cells to destroy enemies, and manufactures cells that do not destroy self (thymus). The second aspect is really interesting, because if you have a decent amount of thymus, you could re-engineer thymus to accept any graft and accept it."
17:55 < fenn> so a possible path to transplants without needing immunosuppressants
17:55 < fenn> a lot more complicated than just injecting growth hormone of course
18:00 < kanzure> and then there's this.. implanting genetic circuits for hormone production cycles https://twitter.com/4LOVofScience/status/1650563006021918731
18:03 < fenn> but humans already have hormone production cycles
18:03 < fenn> why not just activate those
18:04 < fenn> presumably zayner means gene regulatory networks? the arpa-h site doesn't have any content
18:05 < fenn> a gene therapy that cycles HGH production could be useful for anti-aging stuff
18:30 < fenn> it's light controlled gene induction https://pbs.twimg.com/media/Ft7lWWSWIAQlV8C?format=jpg&name=medium
18:45 < docl> nifty! maybe it could be useful for diabetics too
18:46 < fenn> unfortunately there's this thing called the sun, which ruins most of my plans
18:46  * fenn hisses
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21:09 < hprmbridge> nmz787> Why would I mail order a plasmid or seeds of some exotic rare endangered plant, if it was already sequenced and available for download in a few minutes from NCBI, and if the synthesis was pennies or dollars and took days at most?
21:13 < hprmbridge> msnewgooty> Fair. Though if the genome was extracted once (to sequence it) you could just archive that. Or do a WGA to make enough material. But yeah, if the technical hurdle gets crossed then I see it
21:17 < hprmbridge> msnewgooty> Concept (high level)—you could circumvent this hypothetically with a circuit that responds to a ratio of wavelengths that’s more alien relative to the sun. Not that this is the dominant issue here
21:21 < hprmbridge> nmz787> Do you still order DVDs mail order from the one remaining Blockbuster Video?
21:22 < hprmbridge> nmz787> I migrated to Netflix when they were a DVD mailorder service, and haven't looked back since it all became available over the net
21:32 < hprmbridge> msnewgooty> True. Though in both cases there is a shipment
21:51 < hprmbridge> docl> Hmm. If you have two single strands of DNA with complementary base pairs, they tend to match up in a solution where they line up, since that's where the lowest energy set of hydrogen bonds is. So perhaps you could have specialized protecting groups on your k-mers which attach to short single strands of DNA at 90 degrees. Once they combine, still protected, it forms a T shape with the tail being
21:51 < hprmbridge> docl> the double strand with two protecting groups at the center. Immobilize, remove any remaining 90-degree molecules, cleave the protecting groups from the middle.
21:55 < hprmbridge> msnewgooty> You need the protecting groups in the middle?
21:56 < hprmbridge> msnewgooty> Oh this also reminded me of the huge unsolved problem: is there any good way to take a chemical ‘diff’ between two genomes
21:56 < hprmbridge> msnewgooty> That would be a huge one
21:57 < hprmbridge> msnewgooty> A fun trick that ppl don’t use much is CRISPR eater: turn any dna into guides
21:57 < hprmbridge> docl> Yeah it's the vertex of the 90 degree molecule you assemble the T shape from
22:00 < hprmbridge> docl> one arm of it is a k-mer you want to assemble, the other is one of two complementary strands
22:00 < hprmbridge> msnewgooty> https://benchling.com/pub/crispr-eating
22:01 < hprmbridge> docl> what would be sweet with this would be going from like 4 to 8 to 16 and so on. so with a small number of reactions you get a long molecule
22:06 < hprmbridge> docl> or maybe you could put orthogonal single strands on the protecting groups at both ends of the k-mer. then you could have the entire long molecule self assemble
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22:24 < fenn> netflix had a way better selection of DVDs than the movies they have now, due to IP licensing deals restricting what they can send on the net (a not irrelevant observation wrt DNA sequences, which can be patented if not found in nature)
22:26 < fenn> once genetically engineered sequences get out into the wild, they will be chopped up and mangled resulting in new and unintended functionality. who's the inventor then? there's no real answer but it will cause endless drama and court cases
22:30 < fenn> for a "chemical diff" you could use proteins that bind to mismatched DNA, chop everything up with restriction enzymes, then precipitate out the stuff with mismatch binding proteins on it
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22:31 < fenn> works for small mutations anyway
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--- Log closed Tue Apr 25 00:00:42 2023