--- Log opened Sat Aug 12 00:00:47 2017
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05:15 < kanzure> "Multi-scale approaches for high-speed imaging and analysis of large neural populations" http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005685 https://twitter.com/PLOSCompBiol/status/896209374850408448
05:16 < kanzure> seems to be: "use lots of imaging techniques" and "use calcium imaging y'all"
05:19 < kanzure> "... gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight ... might need a new business model." well maybe they should focus on reducing costs so that patients don't have to pay $100k/treatment. https://www.scientificamerican.com/article/gene-therapy-is-now-available-but-who-will-pay-for-it/
05:19 < kanzure> also: bioviva has much lower prices.
05:20 < kanzure> "Expoplanet transits as the foundation of interstellar communications network" https://arxiv.org/pdf/1707.03730.pdf
05:20 < kanzure> ... *Exoplanet
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05:44 < kanzure> hmm the xaar inkjet stuff looks sort of slow (only 6 khz and like 2 nozzles?)
05:57 < kanzure> added marblestone to hgp-write workgroup.
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07:33 < danfox> https://www.pubpub.org/pub/setting-the-scene-for-freedom-of-form-an-evolution-revolution---introduction
07:35 < danfox> Link contains an article outlining my work and plans going forward, to develop systems for genetic self-modification.
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07:54 < kanzure> danfox: i am having difficulty reading this document.
08:07 < kanzure> maybe it's just the grammar choices.
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09:15 < kanzure> .wik planetes
09:15 < yoleaux> "Planetes (プラネテス, Puranetesu, Ancient Greek: Πλανήτες Planētes, literally meaning, by Ancient Greek translation, "Planets", or "Wanderers") is a Japanese hard science fiction manga written and illustrated by Makoto Yukimura." — https://en.wikipedia.org/wiki/Planetes
09:24 < fenn> it's a good show, recommended
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10:02 < Storyteller> also very good
10:02 < Storyteller> https://www.youtube.com/watch?v=VTCeReX9qwQ
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10:11 < kanzure> .title
10:11 < yoleaux> Angel's Egg movie (English subbed) - YouTube
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10:56 < juri_> i also recommend planetes.
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11:15 < kanzure> who was the person listening to multiple text-to-speech audio streams of papers. was that enki--2something?
11:17 < kanzure> john something.
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11:17 < kanzure> john somethington.
11:17 < kanzure> hmm http://web.archive.org/web/*/http://lord-enki.net/
11:22 < kanzure> who the hell would make such a thing https://github.com/enkiv2/anxiety-generator
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11:29 < nmz787> looks fun
11:37 < kanzure> 09:44 < ENKI-][> kanzure: it's fairly frightening. opencog is prolog written in lisp with multivalue logic and a standard library of truisms. it's far too neat to be of use to AGI projects.
11:37 < kanzure> 09:45 < kanzure> iirc there's a nice hypergraph library in there
11:37 < kanzure> 09:45 < ENKI-][> not that it's fundamentally useless, but it won't give anybody an AGI in polynomial time by itself
11:37 < kanzure> 09:46 < ENKI-][> don't get me wrong. i like it. but it won't become a toddler in twelve years. it won't even become a cat in twelve years, whereas blue brain will become a cat in six
11:37 < kanzure> that was 2011-03-06. so....
11:38 < kanzure> 17:49 < ENKI-][> kanzure: i feed my bots both curated text and uncurated text. i also occasionally feed them arrangements based on carefully precalculated novelty curves. if there is something to be done with markov chain bots, chances are if someone in here thinks of it i've done it, planned to do it, half-implemented it, written about what i think would happen were it done, or done a ...
11:38 < kanzure> ...slightly less
11:38 < kanzure> 17:49 < ENKI-][> computationally intensive version of it and made pretty graphs
11:38 < kanzure> LORD OF MARKOV CHAINS
11:39 < kanzure> 2010-07-23.log:12:40 < ENKI-][> kanzure: i don't suppose i can convince you to translate all your documents into, say, plaintext and tarball them?
11:39 < kanzure> 2010-07-23.log:12:41 < ENKI-][> i have a hunger for gobs of plaintext
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11:42 < kanzure> 2014-11-27.log:19:10 < superkuh> I often listen to my computer reading papers.
11:42 < kanzure> huh maybe i had wrong person.
11:43 < superkuh> Multiple? As in, in parallel? Not me. Serial, very much so while I do other things. But usually I read the paper's normally first.
11:43 < superkuh> papers.
11:43 < superkuh> Also, that thalamocortical twitter bot link was nice, as was the cortical layers paper. Thanks.
11:45 < kanzure> hrmmm there was at least one person who was doing multiple audio streams
11:47 < kanzure> wait was it me?
11:52 < kanzure> http://superkuh.com/tktts.html
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14:38 < kanzure> yashgaroth: any ideas for the workgroup charter? i tried to highlight a few missing things (like whether there would be a requirement for open access publication).
14:38 < kanzure> for hgp-write.
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14:45 < yashgaroth> OA is a big one, otherwise it's a question of how much money they get, like if there's a $1m grant do that pay twist to make a bunch of Y chromosome fragments, or do they plow it into R&D? how about $10m+
14:46 < kanzure> "production goals" document is forthecoming according to yesterday's email
14:46 < kanzure> they do seem to be planning R&D that is separate from any such "production goals"
14:47 < yashgaroth> plus, synthesis tech versus figuring out what stuff can be deleted or modified in the genome
14:47 < yashgaroth> no point just copying a chromosome, even if we could today
14:47 < kanzure> well, PCR.
14:48 < yashgaroth> ok resynthesizing, and not with that stupid cre/lox shit they sprinkled in the yeast genome
14:50 < yashgaroth> like I don't know if "testing the phenotype of cells harboring synthetic/edited DNA" implies testing modifications to see what we can delete, but I doubt that's what they mean
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14:51 < yashgaroth> minimizing ALU repeats and other junk DNA is a big cost/time savings if we can figure that out
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14:55 < kanzure> well.. that goes back to my claim that biologists will figure out how to use this DNA if it happens at all. but it's OK for those goals to be included i guess, i don't care.
14:58 < kanzure> yashgaroth: also they want both a roadmap and a whitepaper (see your inbox)
14:58 < yashgaroth> I feel like they're not focusing enough on *why* we'd synthesize a genome, aside from bragging rights and scaring conspiracists...practically speaking, copying DNA is always cheaper, but the more changes you make, eventually it becomes easier to synthesize the thing versus doing some large number of mutations
15:00 < kanzure> in what way do you see that as important though. like you're saying that we should be writing large sections of text to explain the motivations?
15:00 < yashgaroth> just that if we get money, some of it should be dedicated to streamlining the genome, or otherwise making improvements to it
15:01 < yashgaroth> otherwise it's not gp-write, it's just write-abunchofDNA
15:01 < kanzure> add a line (in suggest mode) to the charter, something like "maintain a document of recommended genome optimizations or design changes" ?
15:02 < kanzure> s/recommended/interesting
15:02 < yashgaroth> not just maintain a document, but actively fund research into what can be changed
15:02 < yashgaroth> but yes I'm typing something
15:02 < kanzure> well, the group might not have any spending authority
15:03 < kanzure> that's sort of uclear to me at the moment.
15:03 < yashgaroth> you and everyone else
15:03 < kanzure> "make recommendations" would make more sense if there was a budget that the group was responsible for spending and allocating.
15:16 < kanzure> yashgaroth: also check the "methods" document; he plans to turn the comments on that document into the roadmap v1 and the whitepaper.
15:16 < yashgaroth> kk
15:19 < yashgaroth> ugh "Discussion here will be limited to CRISPR, the most efficient"
15:20 < kanzure> that was for the grant application that he submitted.
15:21 < yashgaroth> sounds like the kind of title you'd give to a bureaucrat-king "Harold, The Most Efficient, long may he rule"
15:23 < yashgaroth> I'll try to phrase a comment for that document too
15:28 < kanzure> i was going to add a comment about 'accuracy'.  e.g. about my error-prone DNA synthesis ideas. unfortunately last time i circled around to that, my conclusion was just "fix the errors with DNA editing enzymes". which isn't very helpful.
15:29 < kanzure> given a 20% error rate,  the proteins are just going to fail and suck and die.
15:29 < yashgaroth> still an open field, be it enzymes, laserbeads, what have you
15:30 < kanzure> you would need to make proteins that can tolerate many errors, up to 20% either in a long stretch or over individual pieces. and that seems like an unreasonable ask. you'd have to iteratively test the proteins against biochemistry assays or whatever, until the protein continues to function the same even when you introduce random errors.
15:30 < kanzure> so each protein would need to be re-designed to tolerate errors. and then you need a new type of promoter... so that transcription will start, even in the presence of 20% errors for the promoters... ugh.
15:31 < yashgaroth> even if you solve the protein folding problem I doubt that'd be possible, especially when many errors will just introduce a stop codon
15:31 < kanzure> ya stop codons would have to be modified to be larger or soething
15:32 < kanzure> *something.
15:32 < kanzure> bleh. okay. fine.
15:33 < kanzure> my comment was going to be: "Agreed that accuracy is a problem. However, inaccurate DNA synthesis will always be cheaper especially at large-scale. It would be interesting if inaccurate DNA could be made to be biologically useful. There's a way to do this for arbitrary data storage (in DNA) using error correction codes -- which is an information encoding technique that, basically, adds ...
15:33 < kanzure> ...redundancy to the information to make it retrievable even after errors made during writing. Instead of spending $ on accurate synthesis tech, it may be more cost effective to spend $ on tech to make cells tolerate more errors in its genome, like up to a 20% error rate. But this doesn't work for biological DNA: if there are errors, then proteins will just fail at some stage (gene ...
15:33 < kanzure> ...transcription, protein folding or it folds and the protein just fails to do its job) and the cell dies. Whoops."
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15:37 < kanzure> what about: do really large-scale genome synthesis, every cell in the culture has a synthesized genome, the synthesis technique has an error rate of like 20%,   and then just make a quadrillion versions with different errors. it would be an interesting experiment to confirm that all of the cells die.
15:37 < kanzure> and each cell would have a uniquely-wrong genome
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15:38 < kanzure> ah you would be left with the cells that didn't get the new DNA.
15:38 < kanzure> you would be selecting for their rejection of the DNA material :-)
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15:47 < justanotheruser> http://bioengineering.illinois.edu/news/article/23435
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15:47 < justanotheruser> .title
15:47 < yoleaux> Handheld spectral analyzer turns smartphone into diagnostic tool | Bioengineering | U of I
15:48 < yashgaroth> assume a quadrillion cells; I think a lot of the centromere crap could be done with super high error rates since it's bulk filler, the size and overall structure is important but not specific sequence
15:51 < kanzure> all you need is for at least one of the cells to survive.   and then sequence it, make a quadrillion very wrong genomes again (based on the one that survived), and repeat a few thousand times until you have a genome that has survived many different kinds of errors.
15:53 < kanzure> ok that wont work.   it will just always end up being the ones where the 20% errors were clumping around non-critical regions of the genome. :(
15:54 < yashgaroth> maybe given a septillion cells and as many years, you could wait until the laws of physics change enough for it to be feasible
15:54 < kanzure> (whereas the reality is that you need it to survive errors to critical regions, not just survive by pure luck of the error-prone synthesis tech)
15:54 < kanzure> if you increase the number of cells then you are reducing the number of required years, though
15:54 < yashgaroth> I factored that in
15:54 < kanzure> heh
15:55 < kanzure> what about error-prone polymerases, haven't those been tested in cell culture?
15:57 < yashgaroth> I think you mostly get low cell viability
15:58 < kanzure> probably the error rate is only 1/500 or something....
15:59 < yashgaroth> it's really just the protein coding parts that are hypersensitive; not just the active sites, but if you swap a phenylalanine for a lysine the whole protein's gonna flip inside out
15:59 < kanzure> well there's also random transcription factor stuff outside of protein genes
16:00 < yashgaroth> yeah, but it's slightly more tolerant since you'd just get % lower binding of the transcription factor, in most cases
16:00 < kanzure> interesting point.
16:00 < yashgaroth> even if you had proteins that were so tolerant, they'd have such low catalytic rates that doubling times would be years+
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16:01 < kanzure> yes, the first proteins that can survive that much damage are most likely to be horribly inefficient. annnd they are likely to be locked into that part of the evolutionary landscape anyway.
16:02 < kanzure> what about viruses?
16:02 < kanzure> i guess you still need a payload that does the right thing in the target..
16:02 < kanzure> but a virus itself will only have a few proteins that need to be able to survive the errors of error-prone dna synthesis
16:03 < yashgaroth> they tend to operate with just enough errors that some tiny fraction are minimally altered between generations
16:03 < kanzure> the virus workflow would be: keep infecting your cells with random crap until something seems to do the thing you wanted.
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16:05 < yashgaroth> you also tend to get a large number of defective particles even in wild-type viruses, plus often a mutant genome will still get packaged/processed correctly since many different copies are being generated per infected cell
16:06 < yashgaroth> but yes viruses will naturally mutate very quickly given enough targets
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16:18 < kanzure> this is hard.
16:31 < kanzure> in computer science terms, what we have is a highly error-prone communication channel, reducing error rate is prohibitively expensive, there's a "decoder" on the other side of the channel but its rules are sort of unknown and message->decoded outcome is kinda unknowable without extreme cost,  and certain corrupted messages cause total system failure,   buuuut you have nearly unlimited ...
16:32 < kanzure> ...parallelism.
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17:11 < kanzure> yashgaroth: isn't there a mutagenesis technique where you can target any gene for mutagenesis? and the polymerase only mutates the crap out of that gene?
17:13 < kanzure> really it should be:  use error-prone dna synthesis to make many randomized errorful versions of only 1 protein.  then, remove the original gene from the organism, insert the new randomized genes (just one replacement per original inclusion-- or more, i don't care).   then you select for the survivors. you do this for each of the proteins in the genome, even if you don't know their function.  ...
17:13 < kanzure> ... in total, you will get viable mutant genes that confer survival in the presence of errors.
17:14 < yashgaroth> in vivo? maybe, sounds unreliable...you could if you swap the gene onto a plasmid, since you can use a unique polymerase to replicate the plasmid
17:14 < kanzure> oh. fine.
17:15 < kanzure> i am just not convinced about your septillion years claim.
17:17 < kanzure> well... even if it worked, you only end up with a genome that can survive errors. you will not be able to write new dna in the future without also selecting for error survival for every new construct. blah.
17:18 < yashgaroth> might as well just get a whole new biological system at that point
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17:18 < kanzure> we really, really need an enzyme that can decode information and re-encode it into a translated version. :(
17:19 < kanzure> AAAAABBBBBBCCCCCAAAAAA -> xyzAAAAA (intermediate snapshot)
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17:25 < kanzure> this seems unlikely to work because the enzyme might drop-off before it's done excising each A.
17:26 < kanzure> and then you have xA, which will be converted to xx on a future pass
17:30 < kanzure> that might be a fake problem.  maybe falling off can be prevented.
17:30 < kanzure> things fall off in nature because otherwise stuff will be permanently stuck, it turns into junk that accumulates and soon the molecule is unusable.
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18:06 < kanzure> https://www.nytimes.com/2017/08/10/health/gene-editing-pigs-organ-transplants.html
18:07 < kanzure> "Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9" http://science.sciencemag.org/content/early/2017/08/09/science.aan4187
18:10 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=0ad57402 Bryan Bishop: add links to retrovirus removal study >> http://diyhpl.us/diyhpluswiki/transcripts/hgp-write/2017-05-09/xenotransplantation/
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18:41 < kanzure> copenhagen suborbitals guy has been arrested, accused of murder.
18:41 < kanzure> https://arstechnica.com/gadgets/2017/08/biggest-amateur-built-sub-sinks-owner-is-suspected-of-killing-passenger/
18:41 < kanzure> https://news.ycombinator.com/item?id=14998270
18:42 < kanzure> "Actually, there are two amateur spacelaunch projects working out of Copenhagen - both of them because of Peter Madsen. Copenhagen Suborbitals was his original setup, from which he was ousted several years ago, reportedly after repeated clashes of opinion and personality (Madsen is known to have a temper which occasionally flares out of proportion). Copenhagen Suborbitals and Madsen's new ...
18:43 < kanzure> ...venture, Madsen Spacelab, were set to perform test launches in the Baltic later this month - both having been assigned the same area and different timeslots on the same day. The sub was planned to sail towards the site - based off the island of Bornholm - this weekend. It is now probably safe to assume that only the Suborbitals launch will be going forward."
18:43 < kanzure> "Also interesting is this submarine's home page. It used to be owned by an association of enthusiasts headed by Madsen, by earlier this year there was a prolonged conflict regarding ownership which led to everyone else surrendering their claims and transferring complete ownership to Madsen."
18:43 < kanzure> didn't know about madsen spacelab
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20:36 < kanzure> .tw https://twitter.com/malwareunicorn/status/896121106481856512
20:36 < yoleaux> RE102 is live now: An introduction to reversing Delphi RTL, shellcode extraction, encryption, unpacking, and evasion https://securedorg.github.io/RE102/ https://video.twimg.com/tweet_video/DG-pDpmU0AE3iog.mp4 (@malwareunicorn)
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--- Log closed Sun Aug 13 00:00:48 2017