--- Log opened Wed May 17 00:00:56 2017 00:39 < cevi_> .title https://arxiv.org/pdf/1704.01914.pdf 00:39 < yoleaux> cevi_: Sorry, that doesn't appear to be an HTML page. 00:39 < cevi_> .title https://arxiv.org/abs/1704.01914 00:39 < yoleaux> [1704.01914] The Proof of CSP Dichotomy Conjecture 00:40 < cevi_> the second serious proof has hit the arxiv 00:43 < cevi_> up to page 9, everything looks good, hopefully the rest checks out 00:46 < cevi_> it has the annoying feature that while the algorithm is polynomial time for each tractable type of puzzle, the exponent of the polynomial depends heavily on the specific tractable type of puzzle 00:46 < cevi_> i.e. solving systems of linear equations takes longer than arc consistency, problems that require you to combine these take even longer, and so on 00:48 < cevi_> hopefully later work will make this stuff more practical 01:12 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has quit [Read error: Connection reset by peer] 01:12 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has joined ##hplusroadmap 01:14 -!- maaku [~mark@173.234.25.100] has quit [Remote host closed the connection] 01:15 -!- maaku [~mark@173.234.25.100] has joined ##hplusroadmap 01:26 -!- Proteus [~Proteus@unaffiliated/proteus] has quit [Read error: Connection reset by peer] 01:27 -!- jaboja [~jaboja@vps.jaboja.pl] has joined ##hplusroadmap 01:37 -!- jaboja [~jaboja@vps.jaboja.pl] has quit [Ping timeout: 260 seconds] 01:44 -!- jtimon [~quassel@117.29.134.37.dynamic.jazztel.es] has quit [Ping timeout: 246 seconds] 01:52 -!- SuperJen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 01:55 -!- Jen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Ping timeout: 255 seconds] 02:02 -!- Jen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 02:04 -!- emeraldgreen [~user@pppoe.95-55-182-243.dynamic.avangarddsl.ru] has joined ##hplusroadmap 02:04 -!- emeraldgreen [~user@pppoe.95-55-182-243.dynamic.avangarddsl.ru] has quit [Client Quit] 02:06 -!- SuperJen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Ping timeout: 260 seconds] 02:13 < TMA> cevi_: finding a graph clique of size k is O(kn^k) -- i.e. polynomial for every k ; it still does not help in P ?= NP 02:13 < TMA> cevi_: if that's what you mean by 'practical' 02:21 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 02:24 -!- Gurkenglas [~Gurkengla@dslb-188-103-222-233.188.103.pools.vodafone-ip.de] has joined ##hplusroadmap 02:25 -!- Jen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Ping timeout: 258 seconds] 03:19 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has quit [Quit: Leaving.] 03:22 -!- Gurkenglas [~Gurkengla@dslb-188-103-222-233.188.103.pools.vodafone-ip.de] has quit [Ping timeout: 240 seconds] 03:22 -!- augur [~augur@noisebridge130.static.monkeybrains.net] has quit [Remote host closed the connection] 03:23 -!- augur [~augur@noisebridge130.static.monkeybrains.net] has joined ##hplusroadmap 03:27 -!- augur [~augur@noisebridge130.static.monkeybrains.net] has quit [Ping timeout: 246 seconds] 03:37 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has joined ##hplusroadmap 03:38 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has left ##hplusroadmap [] 03:40 -!- darsie [~darsie@84-113-55-42.cable.dynamic.surfer.at] has joined ##hplusroadmap 04:04 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has joined ##hplusroadmap 04:46 -!- Reventlov [~reventlov@unaffiliated/reventlov] has quit [Quit: WeeChat 1.7.1] 04:48 -!- Reventlov [~reventlov@unaffiliated/reventlov] has joined ##hplusroadmap 04:49 -!- Jen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 04:51 -!- chris_99 [~chris_99@unaffiliated/chris-99/x-3062929] has joined ##hplusroadmap 04:52 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Ping timeout: 240 seconds] 05:15 < kanzure> https://www.boringcompany.com/faq 06:06 -!- jtimon [~quassel@117.29.134.37.dynamic.jazztel.es] has joined ##hplusroadmap 06:10 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has quit [Quit: Leaving.] 06:10 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 06:11 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has joined ##hplusroadmap 06:12 -!- Jen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Ping timeout: 240 seconds] 06:14 -!- esmerelda [~mabel@unaffiliated/jacco] has quit [Ping timeout: 240 seconds] 06:26 -!- esmerelda [~mabel@2601:602:9603:a3f8:65e5:be41:3c9c:c816] has joined ##hplusroadmap 06:33 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has quit [Quit: Leaving.] 06:34 -!- darsie [~darsie@84-113-55-42.cable.dynamic.surfer.at] has quit [Killed (herbert.freenode.net (Nickname regained by services))] 06:34 -!- Guest51930 [~darsie@84-113-55-42.cable.dynamic.surfer.at] has joined ##hplusroadmap 06:45 -!- jaboja [~jaboja@jaboja.pl] has joined ##hplusroadmap 06:50 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Read error: Connection reset by peer] 06:50 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 07:16 -!- SuperJen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 07:18 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Ping timeout: 240 seconds] 07:24 -!- eudoxia [~eudoxia@adsk-nat-ip2.autodesk.com] has joined ##hplusroadmap 07:41 -!- eudoxia [~eudoxia@adsk-nat-ip2.autodesk.com] has quit [Quit: Leaving] 07:42 -!- red-005 [red@gateway/shell/elitebnc/x-bfecicepamoiuzhj] has joined ##hplusroadmap 08:05 -!- Guest51930 is now known as darsie 08:19 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has joined ##hplusroadmap 08:20 -!- Gurkenglas [~Gurkengla@dslb-188-103-222-233.188.103.pools.vodafone-ip.de] has joined ##hplusroadmap 08:28 < kanzure> https://endpts.com/editas-loses-its-lead-in-the-biotech-race-to-launch-the-first-crisprcas9-human-study/ 08:30 < kanzure> "A thermostable Cas9 with increased lifetime in human plasma" http://biorxiv.org/content/early/2017/05/16/138867 https://twitter.com/biorxivpreprint/statuses/864676873015611393 08:30 < kanzure> "we show that the Cas9 protein from the thermophilic bacterium Geobacillus stearothermophilus (GeoCas9) catalyzes RNA-guided DNA cleavage over a wide temperature range and has an enhanced protein lifetime in human plasma. GeoCas9 is active at temperatures up to 70?C, compared to 45?C for Streptococcus pyogenes Cas9 (SpyCas9), which greatly expands the temperature range for CRISPR-Cas9 applic... 08:30 < kanzure> ...ations. By comparing features of two closely related Geobacillus homologs, we created a variant of GeoCas9 that doubles the DNA target sequences that can be recognized by this system. We also found that GeoCas9 is an effective tool for editing mammalian genomes when delivered as a ribonucleoprotein (RNP) complex. Together with an increased lifetime in human plasma, the thermostable GeoCas9 pro... 08:30 < kanzure> ...vides the foundation for improved RNP delivery in vivo and expands the temperature range of CRISPR-Cas9." 08:41 < kanzure> pretty wild that there's already cas9 companies out on nasdaq that anyone can dump money into 08:55 -!- strages [uid11297@gateway/web/irccloud.com/x-rvhizfwlvchqnvyd] has joined ##hplusroadmap 09:07 -!- CRM114 [~urchin@unaffiliated/urchin] has joined ##hplusroadmap 09:08 -!- red-005 is now known as red-002 09:14 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has quit [Ping timeout: 255 seconds] 09:22 -!- red-002 is now known as stallman 09:23 -!- stallman is now known as red-001 09:24 -!- SuperJen [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Read error: Connection reset by peer] 09:32 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has joined ##hplusroadmap 09:38 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 09:39 -!- poppingtonic [~brian@unaffiliated/poppingtonic] has quit [Quit: Leaving.] 09:47 -!- jaboja [~jaboja@jaboja.pl] has quit [Remote host closed the connection] 10:06 < kanzure> movement preparation stuff by removing neural inhibition of motor movements http://biorxiv.org/content/early/2017/05/17/138925 10:15 < kanzure> https://www.deskgen.com/landing/blog/machine-learning-crispr-guide-design 10:17 < kanzure> "Cell penetrating peptide-mediated nuclear delivery of Cas9 to enhance the utility of CRISPR/Cas genome editing" http://www.fasebj.org/content/31/1_Supplement/909.4.short 10:34 -!- emeraldgreen [~user@pppoe.95-55-182-243.dynamic.avangarddsl.ru] has joined ##hplusroadmap 10:36 -!- emeraldgreen [~user@pppoe.95-55-182-243.dynamic.avangarddsl.ru] has quit [Client Quit] 10:42 -!- jcluck [~cluckj@pool-108-52-166-30.phlapa.fios.verizon.net] has joined ##hplusroadmap 10:45 -!- cluckj [~cluckj@pool-108-52-166-30.phlapa.fios.verizon.net] has quit [Ping timeout: 240 seconds] 10:55 -!- augur [~augur@2601:640:8001:4222:9d73:d0a1:92d0:3599] has joined ##hplusroadmap 10:57 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Read error: Connection reset by peer] 11:00 -!- augur [~augur@2601:640:8001:4222:9d73:d0a1:92d0:3599] has quit [Ping timeout: 246 seconds] 11:20 -!- Gurkenglas [~Gurkengla@dslb-188-103-222-233.188.103.pools.vodafone-ip.de] has quit [Ping timeout: 240 seconds] 11:59 -!- transhumanism [5a68a698@gateway/web/freenode/ip.90.104.166.152] has joined ##hplusroadmap 11:59 < transhumanism> hi 12:00 < kanzure> hi. 12:00 < transhumanism> do you 12:00 < transhumanism> do singularity projects 12:00 < juri_> no. 12:00 < transhumanism> what's up here 12:00 < juri_> we bake pies. 12:00 < transhumanism> haha 12:01 -!- Gurkenglas [~Gurkengla@dslb-188-103-222-233.188.103.pools.vodafone-ip.de] has joined ##hplusroadmap 12:01 < kanzure> transhumanism: http://diyhpl.us/wiki/hplusroadmap 12:21 < archels_> .title https://www.wired.co.uk/article/improbable-quest-to-build-the-matrix 12:21 < yoleaux> Inside Improbable, the $1billion UK startup building the Matrix | WIRED UK 12:24 -!- transhumanism [5a68a698@gateway/web/freenode/ip.90.104.166.152] has quit [Ping timeout: 260 seconds] 12:24 -!- NikopolSohru [~NSohru@85.159.233.231] has joined ##hplusroadmap 12:29 -!- helleshin [~talinck@cpe-174-97-113-184.cinci.res.rr.com] has joined ##hplusroadmap 12:32 -!- hehelleshin [~talinck@cpe-174-97-113-184.cinci.res.rr.com] has quit [Ping timeout: 268 seconds] 12:47 -!- NikopolSohru [~NSohru@85.159.233.231] has quit [Ping timeout: 240 seconds] 12:50 -!- NikopolSohru [~NSohru@85.159.233.231] has joined ##hplusroadmap 13:00 -!- NikopolSohru [~NSohru@85.159.233.231] has quit [Ping timeout: 240 seconds] 13:09 -!- augur [~augur@74-95-6-5-SFBA.hfc.comcastbusiness.net] has joined ##hplusroadmap 13:09 -!- augur 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14:24 -!- preview [~preview@103.226.32.30] has joined ##hplusroadmap 14:31 -!- chris_99 [~chris_99@unaffiliated/chris-99/x-3062929] has quit [Remote host closed the connection] 15:39 -!- Malvolio [~Malvolio@unaffiliated/malvolio] has joined ##hplusroadmap 15:46 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has joined ##hplusroadmap 16:00 -!- CRM114 [~urchin@unaffiliated/urchin] has quit [Remote host closed the connection] 16:03 -!- augur [~augur@74-95-6-5-SFBA.hfc.comcastbusiness.net] has joined ##hplusroadmap 16:08 -!- augur [~augur@74-95-6-5-SFBA.hfc.comcastbusiness.net] has quit [Ping timeout: 268 seconds] 16:21 -!- adlai [~adlai@unaffiliated/adlai] has quit [Read error: Connection reset by peer] 16:36 -!- adlai [~adlai@unaffiliated/adlai] has joined ##hplusroadmap 16:41 -!- esmerelda [~mabel@2601:602:9603:a3f8:65e5:be41:3c9c:c816] has quit [Ping timeout: 260 seconds] 16:44 -!- Gurkenglas [~Gurkengla@dslb-188-103-222-233.188.103.pools.vodafone-ip.de] has quit [Ping timeout: 245 seconds] 17:00 -!- dustinm [~dustinm@68.ip-149-56-14.net] has quit [Quit: Leaving] 17:02 -!- dustinm [~dustinm@68.ip-149-56-14.net] has joined ##hplusroadmap 17:06 -!- esmerelda [~mabel@2601:602:9603:a3f8:65e5:be41:3c9c:c816] has joined ##hplusroadmap 17:09 -!- preview [~preview@103.226.32.30] has quit [Ping timeout: 268 seconds] 17:18 -!- preview [~preview@103.226.32.30] has joined ##hplusroadmap 17:48 -!- justanotheruser [~justanoth@unaffiliated/justanotheruser] has quit [Ping timeout: 240 seconds] 17:49 -!- emeraldgreen [~user@pppoe.95-55-182-243.dynamic.avangarddsl.ru] has joined ##hplusroadmap 17:51 -!- justanotheruser [~justanoth@unaffiliated/justanotheruser] has joined ##hplusroadmap 18:00 < kanzure> "Enzymatic elimination of errors from extremely low-cost, very large chemical DNA synthesis using error correction codes" https://groups.google.com/d/msg/enzymaticsynthesis/WvDidIldm7c/q7aQTnmkAAAJ 18:09 -!- strages [uid11297@gateway/web/irccloud.com/x-rvhizfwlvchqnvyd] has quit [Quit: Connection closed for inactivity] 18:09 < cluckj> sebastian cocioba and josiah are livestreaming talking about various things 18:10 < cluckj> https://youtu.be/IPEvttUe9UI 18:14 < cevi_> you know, one of the very simplest error correcting codes is triple repetition 18:16 < cevi_> so, how about making three high-error-rate attempts at producing the same DNA 18:16 < cevi_> and then... doing a majority vote 18:17 < nmz787_> just opened it 18:17 < nmz787_> cevi_: how do you enzymatically-majority-vote though 18:17 < cevi_> wish I knew 18:41 -!- JenElizabeth [~Jen3@cpc76808-brmb10-2-0-cust571.1-3.cable.virginm.net] has quit [Ping timeout: 240 seconds] 18:42 -!- Darius [~quassel@66-215-89-229.dhcp.psdn.ca.charter.com] has joined ##hplusroadmap 19:14 < nmz787_> also, cevi_ having more molecules means slower reaction rate... since you depend on them all finding each other... so having the three molecules in-line, localizes things a bit better, maybe 19:50 -!- augur [~augur@noisebridge130.static.monkeybrains.net] has joined ##hplusroadmap 19:59 -!- juul1 is now known as juul 20:01 -!- yashgaroth [~yashgarot@2606:6000:cd4d:3300:f5e0:f867:a11d:8d52] has joined ##hplusroadmap 20:05 < nmz787_> sup yashgaroth 20:05 < nmz787_> how was the trip back? 20:05 < yashgaroth> yo 20:05 < yashgaroth> delayed but otherwise uneventful 20:05 < nmz787_> I had a decent window seat 20:05 < nmz787_> and daylight the whole way 20:05 < yashgaroth> luckyyy 20:06 < nmz787_> yeah not too shabby, took the train back to the airport, twice as long but 5x cheaper 20:06 < yashgaroth> yeah it took 45 minutes just to get to the tunnel for me 20:06 < yashgaroth> nature reporter's not gonna write anything up for the meeting, but that's fair since without funding it was just a regular academic conference 20:07 < nmz787_> some decently dressed dude at the airport bus stop was collecting transit tickets, apparently he takes them to some office and cashes them in 20:07 < nmz787_> huh, oh well 20:07 < nmz787_> he'll have material for when you make it big ;) 20:08 < yashgaroth> he was like 'let me know if diybio does anything interesting' and I was like, wait, they've never done anything interesting 20:08 < nmz787_> haha 20:08 < cluckj> :\ 20:09 < nmz787_> I got a CO2 laser cutter up and running in my garage recently, thinking I will cut some acrylic and make myself a gel box 20:10 < yashgaroth> oh yeah I was gonna ask you about spider silk extrusion; seems like we can make the monomer protein with high yield but extruding a large amount is a pain 20:10 < nmz787_> but I also have to go pickup this FIB that I've come into ownership of... which is 3300 lbs for just one unit... so I've got my hands full with thinking about that and reorganizing the garage to accept 20:10 < yashgaroth> ah congrats 20:11 < nmz787_> well FIB can make pores/apertures... so I think that could be useful for some electrospinning apparatus 20:11 < nmz787_> but I don't know why that stuff never took off 20:11 < nmz787_> whether it was the production or the spinning 20:11 < yashgaroth> yeah, just the holes gotta be like 2 microns in diameter, that's the main problem 20:11 < nmz787_> oh, that should be pretty easy 20:12 < nmz787_> main problem is if the starting material is too thick, you waste FIB time 20:12 < yashgaroth> I figure we can extrude a sheet like a centimeter wide but 2 microns thick and use that, but idk what the tolerances are like for nanofabrication 20:12 < nmz787_> hmm, wide and thick here are confusing me 20:12 < yashgaroth> it's gotta shoot out into this dehydrating solution, but if it's more than a few microns thick the interior doesn't assemble and the strength sucks 20:12 < nmz787_> you don't mean 1 cm long? 20:12 < yashgaroth> length is gonna be meters 20:13 < nmz787_> what is the 1 cm then? 20:13 < nmz787_> oh, sheet 20:13 < yashgaroth> like an aperture 2 microns x 1 cm 20:13 < nmz787_> not thread 20:13 < yashgaroth> yeah thread will take forever unless you can connect a hundred pores to one feed 20:13 < nmz787_> hmm, that might be more challenging then, but still seems possible 20:13 < nmz787_> many pores adjacent seems better for strength reasons 20:14 < nmz787_> and would be similar in fab challenge 20:14 < nmz787_> two razor blades carefully aligned wouldn't do it, huh? 20:14 < yashgaroth> yeah but collecting them all seems like a pain, and you may have to do fancy stuff, like the spider gland gets gradually narrower to impart shear forces etc 20:14 < yashgaroth> if the tolerances is less than 500nm maybe 20:14 < nmz787_> hmm 20:15 < nmz787_> might be able to polish them with a FIB to get around that 20:16 < yashgaroth> the main thing I feel is getting the thickness low enough that it can all assemble, but downstream processing would be far easier with sheets 20:16 < kanzure> you could do a consensus polymerase by binding to three strands of dna, moving on each one at the same time, and nucleating/cutting the molecules, i think over time you end up with only molecules that match or something. 20:17 < kanzure> yashgaroth: https://groups.google.com/d/msg/enzymaticsynthesis/WvDidIldm7c/q7aQTnmkAAAJ 20:18 < yashgaroth> one problem is maintaining a triple helix, so 4 strands would be easier to start with; 3 is the optimal minimum 20:19 < kanzure> doesn't need to be helix, could be 3 separate ssDNA attached to three separate DNA binding pockets 20:19 < yashgaroth> I just mean for when it's sitting around as a genome 20:20 < yashgaroth> idk about longer codons since you need at least one base to be constant, unless you've got some sort of checksum for the codon which I can't imagine 20:21 < kanzure> constant? 20:21 < kanzure> longer codons + fuzzy match codons 20:21 < nmz787_> recoding tRNA to transfer a nucleotide is interesting 20:22 < yashgaroth> current codons have some 'wobble' bases but the first nucleotide can't be changed 20:22 < yashgaroth> if it's long enough you could make them all wobble but they'd have to be rather long to retain enough stringency 20:22 < kanzure> with ~63 codons and only 3 letters, not much room for error. but 8 bp codons would allow fuzzy match and a few errors or something. 20:23 < yashgaroth> yeah that might be doable, but we're just assuming DNA synthesis will stay shitty forever and designing an elaborate workaround 20:24 < yashgaroth> tbf it probably will stay shitty since everyone seems to have agreed that pamidite is eternal 20:24 < nmz787_> 4life, yo 20:25 < kanzure> yeah i mean after hgp-write it seems like nobody has good ideas for next generation dna synthesis 20:25 < yashgaroth> cough 20:25 < kanzure> you might have got the pitty vote for citizen whatever :( 20:26 < kanzure> we should probably ask them to not say that in the future 20:26 < yashgaroth> yeah it was a little embarassing 20:26 < nmz787_> if I can find yashgaroth a job up here, he can move in and we can be some sort of dynamic duo 20:26 < kanzure> "and here is a bear on a unicycle" 20:26 < nmz787_> lol 20:27 < yashgaroth> oh yeah nmz it was http://ab-sci.com/ up in vancouver 20:27 < nmz787_> the logo and name seems familiar 20:27 < yashgaroth> their patent is on some bullshit dual promoter but I thought about applying since antibodies from e.coli would be neat 20:28 < nmz787_> I guess they were a sponsor at the Oregon Scicene Startup Forum I went to recently 20:28 < kanzure> someone made a zinc finger recombinase 20:29 < kanzure> but it does both zinc finger dna search+match and also the recombinase core site search+match ( 20:29 < kanzure> :( 20:30 -!- preview [~preview@103.226.32.30] has quit [Ping timeout: 260 seconds] 20:30 < yashgaroth> well you don't want a promiscuous recombinase going nuts on a chromosome, but yeah that seems quite limited 20:30 < kanzure> in the email i describe a method of iterative enzymatic editing of dna to remove 'encoding' artifacts and convert them to decoded dna on the same molecule 20:30 < kanzure> yes we need a promiscuous recombinase, then attach that to a zinc finger nuclease 20:30 < kanzure> or rather, a zinc finger dna domain 20:31 < yashgaroth> if you can regulate it so that an exact sequence match causes a conformational change to activate the recombinase, then sure; otherwise it'll chew up everything 20:31 < kanzure> actually i think that promiscuous recombinases in general would be very helpful for progressive conversion of 'encoded' dna molecules into 'decoded' dna molecules 20:32 < yashgaroth> you have far too much faith in biology 20:32 < kanzure> needs to be promiscuous recombinase-- for a not-necessarily-palindromic target site-- and then only insert a specific ssDNA in that location 20:33 < kanzure> well primarily the problem with my "convert encoded dna into decoded dna" concept is that we have no proteins that can selectively replace long fuzzy match stretches of dna with smaller fragments of pre-specified dna.... but this doesn't seem as much as a stretch as other shit we talk about. 20:34 < yashgaroth> well we talk about some weird stuff, but you're right it's more doable than some 20:34 < kanzure> using oligo inkjet dna synthesis stuff, we can already synthesize absurdly large molecules at very low cost, albeit slowly (so do many in parallel). we just end up with a lot of errors. 20:35 < yashgaroth> I'd suggest synthesizing a new strand using the first one as a template, rather than doing a million insertions 20:35 < kanzure> so with an error correction genetic editing technique using enzymes, we would synthesize like 10x more dna for 'encoded' dna, but end up with significantly less decoded dna. 20:35 < kanzure> well that sounds more like ribosome's activity-- taking codons and converting them to a single amino acid. 20:35 < yashgaroth> exactly; they've also gotta be fuzzy wrt length since most pamidite errors are deletions 20:36 < yashgaroth> actually mostly that since the vast majority of pamidite errors are deletions 20:36 < kanzure> yes i was thinking each 'codon' would be surrounded by NOPs (no-operation) nucleotides... once too many nops are detected, the enzyme should fall off or whatever. 20:36 < kanzure> (and these could be unnatural nucleotides of some special type) 20:37 < yashgaroth> true, no one's really messing around with non-ACGT nucleotides for long synthesis 20:37 < yashgaroth> if there were a reaction chemistry that had far higher affinity you could convert from that, but I feel like 99% is pretty much the limit for chemistry as-is 20:37 < yashgaroth> err, efficiency rather than affinity 20:38 < kanzure> i am not sure how to make a polymerase do what you suggest. i think that's more difficult.. i guess you would look for polymerases that take input and have errors that look like the conversion function you want, and then over time select for the mutant polymerases that do more of those 'errors'. 20:40 < yashgaroth> the easier it is to do directed evolution the better, even if it requires developing a new method for directed evolution 20:41 < yashgaroth> just remember that we're still at the banging-rocks-together stage in biology, some people have made some cool rocks but that's about it 20:43 < yashgaroth> at best you find an enzyme that does almost what you want, then spend a few years to make it do something slightly different 20:43 < yashgaroth> getting a polymerase to spit out a conversion will take a long time, until we solve the protein folding problem, which will take an even longer time 20:44 < kanzure> i really thought you would suggest promiscuous gene editing enzymes, not polymerase. w/e. 20:45 < yashgaroth> oh I'm just referring to what I assume was a quote that you posted, but yeah it'll probably be sequence-recognition enzymes 20:45 < kanzure> what's this about codons and their first nucleotide? 20:46 < yashgaroth> there is codon degeneracy but the first nucleotide is always constant, so they're not fully degenerate 20:47 < yashgaroth> in fact there's a fun rule of thumb where purines and pyrimidines in the first position tend to code for...one was hydrophobic amino acids maybe? lemme check 20:47 < kanzure> now for some dumb questions. are there any dna replication related enzymes that do error checking on both strands from a double helix? 20:48 < yashgaroth> there are endonucleases that will excise non-matching base pairs, but it's random since they don't know which one is correct 20:48 < yashgaroth> the patent on nicking oligo synthesis had a whole section on error-correction using them 20:49 < kanzure> as a programmer i always thought the primary argument for a double strand was information integrity preservation-- but now that i look more closely, at best i can see some chemical stability arguments (which somewhat confers information preservation) but it's really not a mechanism to directly instruct enzymes 20:49 < kanzure> *to directly instruct enzymes on both strands at the same time 20:50 < yashgaroth> when a pol is synthesizing a new strand it defers to the parent strand, so if it puts in the wrong nucleotide it'll excise the one it just added 20:50 < kanzure> sure, but that's just the current strand it's checking, there's a whole 'nother strand available 20:51 < yashgaroth> and outside of incorrect replication bases don't just flip to another nucleotide, they usually get turned into something else so that's easy to correct 20:51 < kanzure> i'll take a look at the nicking oligo synthesis patent. 20:51 < kanzure> lotta patents getting written about non-biological information encoding with error correction codes-- but this is less interesting to me- it's trivial to encode non-biological information that you're not going to convert into biologically-executable dna. 20:52 < yashgaroth> e.g. "The method of claim 8, wherein the mismatch-specific endonuclease is a CEL endonuclease." 20:53 < yashgaroth> but that's just to degrade sequences with errors 20:58 < yashgaroth> any data from D. radiodurans would be useful since out of all organisms it would be likeliest to have some super error correction enzymes 20:59 < kanzure> lotta dna repair pathway stuff. 21:00 < yashgaroth> like it definitely relies on genome duplication, so if you wanted some multi-strand error correction complex it'd be there 21:03 < cevi_> weren't water bears supposed to do something weird with dna? 21:03 < yashgaroth> there's supposed to be some relation with desiccation resistance and DNA repair, so possibly 21:07 -!- preview [~preview@2407:7000:842d:4078:ab39:1b65:59a7:cd65] has joined ##hplusroadmap 21:08 < nmz787_> sorry, went to go put on some media 21:08 < nmz787_> on the stove 21:16 -!- drewbot [~cinch@54.158.127.181] has joined ##hplusroadmap 21:45 < nmz787_> do we know anyone in sacramento or thereabouts? 21:47 -!- emeraldgreen [~user@pppoe.95-55-182-243.dynamic.avangarddsl.ru] has quit [Ping timeout: 240 seconds] 21:58 -!- Darius [~quassel@66-215-89-229.dhcp.psdn.ca.charter.com] has quit [Ping 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