--- Log opened Sun Nov 22 00:00:24 2020
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06:32 < Llamamoe> Hey kanzure, can I bother you for a moment? :o
06:37 < fenn> "don't ask to ask, just ask"
06:37 < Llamamoe> So be it then
06:39 < Llamamoe> I've been randomly googling around the internet for any leads and clues, hints and thoughts, towards DIY DNA synthesis, and kanzure's name keeps coming up in most of those things, but majority of links therein are dead, and most seem years old. I wanted to ask where I could get access to all that stuff and more.
06:40 < Llamamoe> I'm not planning on anything soon, for now I just want to know where to find the knowledge.
06:40 < fenn> http://diyhpl.us/~bryan/papers2/DNA/
06:42 < fenn> just read all those papers and you'll be on top of things :D
06:42 < Llamamoe> fenn: Are there any final conclusions on a hypothetical DIY-able protocol?
06:42 < Llamamoe> But yes
06:42 < fenn> depends what you consider DIY i guess
06:42 < Llamamoe> I like that link, I like it very much
06:42 < Llamamoe> :3
06:43 < fenn> phosphoramidite chemistry is not hard really
06:43 < fenn> especially if you just buy the precursors
06:43 < fenn> also depends what you consider synthesis
06:44 < fenn> pcr primers are only a dozen bases or so, and can tolerate loads of errors
06:44 < fenn> gene synthesis is thousands of bases and can tolerate roughly zero errors
06:45 < L29Ah> HOW TO ELIMINATE UNREACTED (N - 1) POLYNUCLEOTIDES
06:45 < L29Ah> ?
06:45 < Llamamoe> fenn: Good question about what I consider DIY, I'm not sure how to answer :o
06:46 < L29Ah> also polynucleotide-synthesis-as-a-service isn't terribly expensive, compared to the synthesizer you're going to build
06:47 < Llamamoe> I guess I'm curious about how I, as an individual citizen with limited monetary resources, could cobble together something workable for DNA synthesis. At least primers, ideally proper genes.
06:47 < Llamamoe> Specifically, I'm curious about how I might be able to synthesize DNA without living in a country that allows regular citizens to play with genetic engineering
06:48 < fenn> Llamamoe: "Error correction in gene synthesis technology" is a review article
06:48 < fenn> er, that was directed to L29Ah
06:49 < fenn> generally you let it sit for a while until it's almost fully reacted
06:49 < fenn> like 99.9999% reacted
06:49 < Llamamoe> I'll happily take a look at it myself, so np :P Still, isn't a paper from 2011 at least slightly outdated in a field as rapidly advancing as this?
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06:50 < fenn> you have some basic misunderstanding of how science papers work
06:50 < fenn> newer papers build on older papers, so you still have to read the older ones
06:50 < Llamamoe> Fair.
06:51 < Llamamoe> fenn: I've got pretty crippling chronic fatigue issues(that I'll probably be able to address soon, at last), so I just... skim stuff, novelty seeking and all. I just try to form an understanding of *what knowledge is out there*, rather than anything else.
06:52 < fenn> i'm currently reading a paper from 1963 because it's the only way to get a straight answer in plain english about basic stuff
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06:52 < Llamamoe> Out of curiosity, what paper is it? :o
06:52 < fenn> heat shield concepts and materials for reentry vehicles
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06:53 < Llamamoe> fenn: I guess I might be biased by the fact that machine learning was my first dive into reading science, and in ML, stuff from >2 years ago is overwhelmingly likely to be outdated and completely superseded already
06:54 < fenn> somehow i doubt it
06:54 < fenn> the performance is better with the latest mishmash of blind fumbling, but you still need to understand the concepts from 10 years ago
06:56 < Llamamoe> Hm. Fair enough.
06:57 < Llamamoe> I suppose when you look at it from a perspective of understanding the fundamentals rather than results of cobbling building blocks together, your perspective is far more valid than mine.
06:58 < Llamamoe> That said, stuff like transformers/reformers, and LSTM before that, certainly were revolutionary
06:58 < Llamamoe> And changed the landscape of what is possible drastically
06:58 < Llamamoe> At least in certain sub-domains
07:03 < Llamamoe> fenn: Regardless, I guess I'll just come back here when I can function better. Right now I'm just novelty seeking to offset the painful levels of chronic fatigue
07:03 < fenn> take magnesium
07:03 < Llamamoe> Thanks for humoring me even this much, anyway, I appreciate it :P
07:04 < Llamamoe> fenn: Yah I know about Mg. Mg, Zinc, B6, Creatine, melatonin for slight sleep correction. But right now I'm waiting for a PAP machine to treat my sleep disordered breathing, as ultimately that is the by far biggest thing holding me back
07:05 < Llamamoe> Lately, what I'm the most of specialties wise, is neurochem/neuropsych stuff
07:06 < Llamamoe> But that's on pause too since I don't presently have the energy for the deep dive going further from my current level of understanding requires
07:06 < fenn> sounds like you're already ahead of the pack
07:07 < Llamamoe> Maybe in some sense, but in so many others I'm so far behind. 9 years of brutal permanent fatigue and inability to invest myself into truly learning anything set me quite behind.
07:07 < Llamamoe> But I'm inclined to do my best to overcome that setback
07:07 < Llamamoe> And now at long last I have a *TRUE* solution, that targets the source of it
07:08 < fenn> the Final Solution
07:08 < fenn> hopefully not
07:09 < fenn> have you been measuring sleep quality?
07:10 < fenn> i'd suggest you start immediately recording data about how tired you feel, what you are eating, how long you sleep, etc
07:10 < fenn> this will give you a baseline to compare against any interventions
07:12 < Llamamoe> fenn: I've a set of plausible conclusions from recent reading, which is: 1) Sleep Disordered Breathing is /very/ underdiagnosed, esp. mild forms like UARS and NREM instability 2) it's undertreated because CPAPs are shit, 3) a substantial portion of ADHD cases are connected to SDB 4) subclinical ADHD is a thing and probably common, 5) ADHD and chronic fatigue both have energy metabolism at their core 6) 9/10 people
07:12 < Llamamoe> l dystrophy, many might have mild SDB and subclinical ADHD
07:13 < fenn> cut off after 6)
07:13 < Llamamoe> And about my sleep quality, I don't even need to track it to be sure, fenn, I've confirmed with every thing I can do without a sleep study that my airways are narrow, that sleep position affects my wellbeing. I have most symptoms of UARS, I have multiple craniofacial risk factors of SDB.
07:13 < Llamamoe> Ah crap
07:13 < Llamamoe> I thought the length limit is 500 sorry
07:13 < Llamamoe> 6) 9/10 people have craniofacial dystrophy, many might have mild SDB and subclinical ADHD
07:14 < Llamamoe> In fact, I would also posit 7) a substantial quantity of treatment-resistant mental health problems could be the fault of SDB
07:14 < Llamamoe> Because even very mild sleep quality reduction have pronounced, cumulative effects on the brain's ability to handle stress on a neurobiological level
07:15 < fenn> sounds plausible
07:16 < Llamamoe> It's overwhelmingly likely that arousals from sleep as defined by AASM criteria have extremely low sensitivity, and that's on top of them almost never being used in diagnosis, only full-out apneas/hypopneas, which are the most severe form of SDB
07:18 < Llamamoe> fenn: Also a funny thing I've come across, hormones influence conversion of airway abnormalities to SDB presentation, with men being overwhelmingly likely to have apnea than women, but for some reason UARS cases are acknowledged as 2:1 male:female... without mention of the fact that the phase of the menstrual cycle has very significant effect on airway resistance and thus SDB presentation.
07:18 < Llamamoe> And like a part of me thinks
07:18 < Llamamoe> "what if it's not 2:1, but rather women get tested at a random point in the menstrual cycle, with half of them having better results than their worst"
07:20 < Llamamoe> Statistically, studies report women with the same AHI/RERA indices having lower quality of life - what if it's just a consequence of women not being tested at the peak of their SDB, while still having QoL impaired by the chronic average?
07:20 < Llamamoe> Anyway uh, sorry for the random ramble
07:21 < fenn> i don't know what you've read about craniofacial dystrophy but i found the pictures on westonaprice.org from the early 1900s very interesting
07:22 < fenn> basically, we don't chew enough, and probably something about pasteurized milk
07:22 < Llamamoe> fenn: I'm just skimming stuff and cobbling thoughts together after preliminary confirmations that I'm not heavily misguided. I'm aware of the lack of rigor in my thought process, but I just do not have the energy to do better
07:22 < Llamamoe> And sec, lemme link
07:23 < Llamamoe> fenn: This guy has videos on this: https://www.reddit.com/r/UARS/comments/jrx8ve/critical_info_from_the_breathe_institute_course/
07:23 < Llamamoe> The 1st and 3rd talk about causes, presentation, and identification of craniofacial dystrophy
07:24 < Llamamoe> And their relevance to SDB
07:26 < Llamamoe> But I'll invest myself into this more once I have energy. For now I have Mg, Zn, B6, vitD and DIY nasal stents. Soon I'll have creatine, after that I'll have a PAP machine which should provide full or close to full resolution, after which I'm going the neurochem route for accelerating and augmenting my recovery
07:29 < Llamamoe> After that I'll be delving into SDB deeper to try and see what I can do about spreading awareness and helping people, then I'm learning biochem, neuropsych, working through some of my "substances of interest" backlog. Then we'll see, I'd like to try my hand at designing affordable and easy to build PAP devices. I know a basic time-cycle BPAP is trivially possible without knowledge of electronics, but w/ them more 
07:29 < Llamamoe> be very viable.
07:36 < fenn> ok apparently all the photos of smiling native children are no longer on the website, but they are in his book, "Nutrition and Physical Degeneration"
07:38 < Llamamoe> Yeah I'm familiar with the differences, it's pretty stark
07:39 < Llamamoe> And just starts to feel brutally outrageous when you reaize it might be connected to a large swath of contemporary health problems that are on the rise
08:55 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=188a871a Michael Folkson: Add additional MuSig blog posts >> http://diyhpl.us/diyhpluswiki/transcripts/stephan-livera-podcast/2020-10-27-jonas-nick-tim-ruffing-musig2/
08:55 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=56eaaf5c Michael Folkson: Merge pull request #179 from michaelfolkson/musig2-edit >> http://diyhpl.us/diyhpluswiki/
08:55 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=505a1068 Michael Folkson: Add Christian on SLP >> http://diyhpl.us/diyhpluswiki/transcripts/stephan-livera-podcast/2020-08-13-christian-decker-lightning-topics/
08:55 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=75995225 Michael Folkson: Merge pull request #180 from michaelfolkson/christian-slp >> http://diyhpl.us/diyhpluswiki/
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09:31 < kanzure> Llamamoe: https://diyhpl.us/wiki/dna/synthesis/notes/
09:37 < fenn> https://diyhpl.us/wiki/dna/dna-synthesis.html
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10:37 < kanzure> "A survey of ECDSA threshold signing" https://eprint.iacr.org/2020/1390.pdf
11:01 < archels> .title https://www.doublerobotics.com/
11:01 < saxo> Double Robotics - Telepresence Robot for Telecommuters
11:01 < archels> $4k telepresence bot
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11:02  * archels would like to DIY something like this at some point
11:05 < kanzure> .title https://news.ycombinator.com/item?id=25177045
11:05 < saxo> Booting from a vinyl record | Hacker News
11:06 < kanzure> "When I was a CS major in the 90's, one of my professors told me a story of his own college days, with punch-card computers. His university bought a tape reader (like, punched paper tape, not magnetic tape) to do the boot code of the computer, on the theory that tape was a little easier to manage than punch-cards for the boot (you can't lose one of the cards, or get them out of order, etc ...
11:06 < kanzure> ...with tape). So my prof and some of his friends start playing with the tape reader, and they realize that what controls the IO speed of the tape is actually the tensile strength of the tape -- if the feeder tries to put too much force on it, it will tear the paper tape. The actual computer can read the instructions much faster than the tape can physically handle. So they got some plastic tape ...
11:06 < kanzure> ...instead, and punched the boot code in the (much stronger) plastic tape. Then, to boot the computer, they'd feed the plastic tape through the part of the reader that actually read, bypassing the mechanical part that pulled and wound the tape, and then manually grab the other end and yank on it as hard as they could, basically starting the computer like it was one of those old lawnmowers that ...
11:06 < kanzure> ...you pulled the cord to turn over the engine."
11:08 < fenn> archels: i love the image of it in the machine shop, with the sad machinist on the display looking useless
11:09 < L29Ah> :D
11:10 < kanzure> this is just the instructions? https://rebrickable.com/mocs/MOC-46228/KingsKnight/space-shuttle-1110-scale/#details
11:11 < fenn> of course
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11:12 < fenn> the "buy parts" tab is pretty interesting - looks like it's doing database queries to lots of different used brick suppliers
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11:14 < fenn> looks like the parts are over $200, although i can't get the "multi-buy optimization" thing to work
11:15 < lsneff> The range of this channel is quite impressive; dna synthesis one minute, legos the next.
11:15 < fenn> they're not that different
11:15 < kanzure> well you can buy the batman space shuttle https://rebrickable.com/sets/70923-1/the-bat-space-shuttle/#parts
11:16 < fenn> that's an official set
11:16 < lsneff> Yeah, I guess they're not
11:16 < kanzure> i think https://www.ldraw.org/ is still a thing
11:16 < lsneff> I've got the the atlas V lego set
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15:14 < kanzure> ligandal is pitching "Peptide antidotes to SARS-CoV-2 (COVID-19)" https://www.biorxiv.org/content/10.1101/2020.08.06.238915v2
15:14 < kanzure> cc yashgaroth ^
15:19 < yashgaroth> whole lot of weird just in the abstract, so his peptide also binds to anti-covid neutralizing antibodies? "single-micromolar binding affinities" would be absolute trash for an antibody where nanomolar is the norm,
15:20 < yashgaroth> "soluble ACE2 abrogates binding of RBD to neutralizing antibodies, which we posit is an essential immune-evasive mechanism of the virus" uhh what, of course something that binds to RBD would be inhibited if the RBD is stuck to something else, that's not covid being sneaky
15:21 < yashgaroth> idk, if lilly and regeneron's antibody cocktails don't seem to do shit, I doubt this will either
15:22 < e7illice> wtf
15:23 < yashgaroth> both those antibody cocktails worked super good in the dish (like he tests here, with ACE2-expressing cells), but utterly fail to prevent deaths in actual patients despite costing probably six figures per patient
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17:30 < lsneff> Been working most of the day on getting a softcore (picorv32) to work on my fpga
17:30 < lsneff> Got it working, and then a few minutes later it doesn't, so ¯\_(ツ)_/¯
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18:29 < kanzure> that's numberwang
18:47 < lsneff> numberwang?
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19:36 < kanzure> lsneff: https://louh.github.io/2048-numberwang/
19:59 < lsneff> Ha! A 2048 variant! 2048 was all the range when I was in middle school
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--- Log closed Mon Nov 23 00:00:24 2020