--- Log opened Sat Apr 08 00:00:20 2017
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03:22 < kanzure> nmz787_: nope don't know any.   i suggest you become friendly with the quake lab people.
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08:28 < kanzure> "Synthetic recording and in situ readout of lineage information in single cells" http://www.nature.com/nature/journal/v541/n7635/full/nature20777.html https://twitter.com/CRISPR_papers/status/850652714866360322
08:28 < kanzure> "Here we describe a synthetic system that enables cells to record lineage information and event histories in the genome in a format that can be subsequently read out of single cells in situ. This system, termed memory by engineered mutagenesis with optical in situ readout (MEMOIR), is based on a set of barcoded recording elements termed scratchpads. The state of a given scratchpad can be irrev...
08:28 < kanzure> ...ersibly altered by CRISPR/Cas9-based targeted mutagenesis, and later read out in single cells through multiplexed single-molecule RNA fluorescence hybridization (smFISH) [...] Finally, using simulations, we show how parallel MEMOIR systems operating in the same cell could enable recording and readout of dynamic cellular event histories."
08:43 < kanzure> and:
08:43 < kanzure> "Continuous genetic recording with self-targeting CRISPR-Cas in human cells" http://science.sciencemag.org/content/353/6304/aag0511.long https://twitter.com/CRISPR_papers/status/842695273784606721
08:44 < kanzure> "We present a self-contained analog memory device for longitudinal recording of molecular stimuli into DNA mutations in human cells. This device consists of a self-targeting guide RNA (stgRNA) that repeatedly directs Streptococcus pyogenes Cas9 nuclease activity toward the DNA that encodes the stgRNA, enabling localized, continuous DNA mutagenesis as a function of stgRNA expression. We demonst...
08:44 < kanzure> ...rate programmable and multiplexed memory storage in human cells triggered by exogenous inducers or inflammation, both in vitro and in vivo. This tool, Mammalian Synthetic Cellular Recorder Integrating Biological Events (mSCRIBE), provides a distinct strategy for investigating cell biology in vivo and enables continuous evolution of targeted DNA sequences."
08:47 < kanzure> ".. We hypothesized that if a PAM sequence were introduced in the DNA locus encoding the sgRNA, the transcribed sgRNA would direct Cas9 to cleave its own encoding DNA, thus acting as a stgRNA. After error-prone repair, the mutagenized stgRNA locus should continue to be transcribed and enact additional rounds of continuous, self-targeted mutagenesis. Thus, the stgRNA locus should acquire mutati...
08:47 < kanzure> ...ons corresponding to the level of activity of the Cas9-stgRNA complex. We hypothesized that by linking the expression of stgRNA or Cas9 to biological events of interest, one could then record the duration and/or intensity of such events in the form of accumulated mutations at the stgRNA locus. The recorded information could be read by sequencing the stgRNA locus or by other related strategies."
08:52 < kanzure> http://www.biotechniques.com/BiotechniquesJournal/2016/November/CRISPR-MODIFYING-THE-LIFE-SCIENCE-LANDSCAPE/biotechniques-365248.html?service=print
08:52 < kanzure> ""We have been working on creating individual memory units for cells," Lu explains. Imagine if it were possible to directly record when a certain protein becomes active or when a single neuron fires--without the need for imaging, multiple measurements of cell samples, or any experiments, in fact. This is what Lu and his lab have been working toward in recent years: creating a system where...
08:52 < kanzure> ... the cell actually records its own actions by making changes to its DNA."
08:52 < kanzure> "The general concept is not new. Previously, researchers tried to engineer such cellular memories using recombinase proteins as effectors that could produce the needed changes to the cell's DNA following a specific event. While that approach worked, Lu came to realize there was a limitation in using recombinases. "There are only a small number of recombinases, and this makes looking at man...
08:52 < kanzure> ...y different events in parallel or over time quite challenging," he says. His solution to the multiplexing problem came in the form of the CRISPR/Cas9 methodology--more specifically, the variability possible within the CRISPR guide sequences. These sequences can be used to engineer changes all around the genome, thereby enabling multiplexed records of cellular activity."
08:53 < kanzure> "While at first glance, it looked as if the CRISPR/ Cas9 system could provide Lu the solution to his multiplexing problem, he did not stop there. He wanted a memory system also capable of recording the intensity of a cellular event and even how often that event occurred. This presented a unique technical challenge for Lu's team since recording intensity and frequency would require their syst...
08:53 < kanzure> ...em to generate multiple mutations at the same location in a cell's genome, a difficult task as CRISPR normally does not do this. So Lu and his colleagues needed to figure out a way for CRISPR to record multiple mutations at the same locus as a function of the signal to be stored in DNA memory."
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08:59 < kanzure> i wonder if that "optical in situ readout" method ("multiplexed single-molecule RNA fluorescence hybridization (smFISH)") is destructive
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11:04 < chris_99> saw http://kottke.org/17/04/incredible-low-light-camera-turns-night-into-day on HN, looks pretty awesome when it pans up to the stars
11:05 < heath> "Octopuses and squids can rewrite their RNA" https://news.ycombinator.com/item?id=14055552 http://www.cell.com/cell/fulltext/S0092-8674(17)30344-6
11:06 < heath> fenn: Former Google VP Starts a Company Promising Clean and Safe Nuclear Energy https://news.ycombinator.com/item?id=14056897
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11:33 < kanzure> "Decrypted content of eqgrp-auction-file.tar.xz" https://github.com/x0rz/EQGRP
11:48 < streety> The name for that camera is amazing - "X27 Reconnaissance Day/Night high Fidelity true real time low light/low  lux color night vision Imaging Security / Multi Purpose camera system"
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12:19 < nmz787_> imagine animals that can/could see as well as that camera
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12:31 < kanzure> i dunno how to do that.
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12:49 < nmz787_> pretty easy for me, once I watched the video :/
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12:51 < nmz787_> someone seems to think, on some forum, that owls have a camera ISO in the range of 25000 to 50000
12:51 < nmz787_> while that video was shot at 5,000,000
12:55 < cevi_> at some point you'd run into information overload, I'd think
12:56 < kanzure> information overload is a myth perpetuated by lazy people
12:58 < cevi_> taking things to the extreme, though, if the information is coming in at terabytes/second I don't think there is any hope of doing anything interesting with it
13:02 < TMA> the discrete nature of a series of mutually similar still images ceases to be observable to humans when the frequency of transitioning from one member of the series to the next is higher than about 20 Hz -- that's information overload's observable effect
13:07 < cevi_> oh, I'm just poorly informed - ISO measures sensitivity/speed, not pixels or whatever
13:08 < chris_99> yeah its how sensitive the sensels are to light
13:09 < chris_99> i guess the magic is, how it's not ridiculously noisey
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13:18 < cevi_> I'm finally watching the video - it's a bit mindblowing to see what looks like stars in the daytime - but it does seem fairly noisy to me
13:19 < chris_99> it's not in daytime though
13:21 < chris_99> oh sorry you just meant it looks like that
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13:38 < cevi_> wait, why are they listing DNA sequencing as a possible application of their camera?
13:45 < yashgaroth> pacbio's sequencer uses phosphorescent nucleotides that emit light when they're attached to a strand, so they have very sensitive cameras to pick up each addition
13:51 < kanzure> fluorescence stuff, etc
13:51 < kanzure> fluorophores
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14:39 < kanzure> .title https://www.youtube.com/watch?v=ef7w3pEXwic
14:39 < yoleaux> Fluorescent in situ sequencing - YouTube
14:52 < kanzure> .title https://www.youtube.com/watch?v=cMN1B8f-AbA
14:52 < yoleaux> in situ sequencing of mouse brain section - Mats Nilsson Lab - YouTube
14:54 < kanzure> "Best practices for applying deep learning to novel areas" https://arxiv.org/pdf/1704.01568
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15:14 < kanzure> .title https://github.com/bitcoin/bitcoin/pull/9871
15:14 < yoleaux> Add a tree sha512 hash to merge commits by sipa ? Pull Request #9871 ? bitcoin/bitcoin ? GitHub
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16:11 < opiate> Sup
16:14 < kanzure> greetings
16:14 < opiate> what are you up to kanzure?
16:19 < kanzure> immanentizing the eschaton
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16:19 < ballede> Sup
16:19 < kanzure> greetz
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16:19 < kanzure> immanentizing the eschaton, like i said
16:19 < ballede> what?
16:20 < kanzure> is that not how you spend your time?
16:20 < ballede> Oh yeah
16:20 < ballede> All the time
16:20 < kanzure> great. you're in the right place.
16:21 < ballede> what do you do for a living
16:21 < ballede> kanzure
16:21 < kanzure> so many questions
16:22 < ballede> just answer mofo
16:22 < kanzure> http://diyhpl.us/wiki/hplusroadmap
16:23 < ballede> Hmm I see
16:23 < ballede> but what are your skills kanzure?
16:24 < kanzure> programming, emails, science, i dunno what you're looking for. why the questions?
16:24 < ballede> because I'm trying to fit in here
16:24 < ballede> so I'd like to know the community better
16:25 < ballede> why wouldn't I question lol
16:25 < ballede> in what have you worked transhumanism related?
16:26 < ballede> kanzure
16:27 < kanzure> all your questions and more were answered in this recent radio interview https://soundcloud.com/heryptohow/andrew-poelstra-bryan-bishop-and-brian-deery starting about 24 minutes into it
16:28 < ballede> yes but jesus shit
16:28 < ballede> I'm here to discuss stuff
16:29 < cevi_> man, automated theorem provers seem a lot less usable than I expected them to be
16:29 < cevi_> also, incredibly poorly documented
16:29 < kanzure> doing coq stuff?
16:30 < cevi_> so far I've tried prover9, cvc3, and hol light
16:30 < kanzure> coq is usually the go-to option, why you avoiding it
16:30 < ballede> ELI5 automated theorem provers
16:30 < kanzure> all reddit users are banned, get out
16:30 < cevi_> the goacoq does automated theorem proving? I thought it was mainly for proof verification
16:31 < cevi_> oops, not sure where "the goa" came from
16:31 < kanzure> also there is a microsoft theorem prover called z something...
16:31 < cevi_> z3, I think
16:32 < ballede> one question
16:32 < cevi_> I was considering trying E, but the website says it doesn't come with any arithmetic built in
16:32 < ballede> are you true transhumanists
16:32 < cevi_> I'll give coq a shot now
16:32 < ballede> or do you implant magnets and your epidermis because it seems cool
16:32 < kanzure> finger magnets are also banned, get out
16:33 < ballede> nice then
16:33 < kanzure> ballede: shut up and read some papers http://diyhpl.us/~bryan/papers2/neuro/
16:33 < kanzure> http://diyhpl.us/~bryan/papers2/longevity/
16:33 < kanzure> http://diyhpl.us/~bryan/papers2/gene-therapy/
16:33 < kanzure> http://diyhpl.us/~bryan/papers2/bio/
16:34 < kanzure> http://diyhpl.us/~bryan/papers2/bitcoin/
16:34 < ballede> I already have to study this stuff for a living mate
16:35 < ballede> So I only improve if there is moneys to be made
16:36 < kanzure> cevi_: failing coq, i think haskell might have a relevant library for this
16:37 < cevi_> my goal here is to get my computer to solve math competition problems automatically
16:38 < kanzure> er, then maybe sage/sympy is more relevant in this case
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16:39 < cevi_> in this case, I want to find an automated theorem prover which is capable of finding all functions f: Z -> Z such that for all x,y we have f(x-f(y)) = f(f(x)) - f(y) - 1
16:40 < cevi_> (taken from a recent IMO shortlist)
16:40 < cevi_> this seems like the type of first order logic problem that saturation based provers should be perfect for
16:43 < cevi_> it'd make a great demo if I can get it to work
16:43 < kanzure> famous last words
16:44 < ballede> kek
16:48 < cevi_> ok, currently trying to figure out how to say "f is a function from integers to integers" in coq
16:49 < cevi_> for some reason the documentation refuses to just tell me
16:50 < cevi_> apparently I need ZArith?
16:51 < cevi_> "It is provided by requiring and opening the module ZArith and opening scope Z_scope."
16:51 < cevi_> very helpful
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17:25 < cevi_> so far I can't get coq to admit that f(0) probably isn't 0
17:28 < ballede> any papers on the repos about bipolarity disorders and effects on brain physiology?
17:29 < kanzure> not in my collection, no.
17:29 < ballede> aight, thanks kanzure
17:29 < kanzure> cevi_: i suggest looking up coq examples on github.
17:29 < ballede> what is the most interesting paper you've read lately?
17:30 < kanzure> ballede: the following,
17:30 < kanzure> "Synthetic recording and in situ readout of lineage information in single cells" http://diyhpl.us/~bryan/papers2/bio/Synthetic%20recording%20and%20in%20situ%20readout%20of%20lineage%20information%20in%20single%20cells%20-%20barcoding%20-%202016.pdf
17:30 < kanzure> "Continuous genetic recording with self-targeting CRISPR-Cas in human cells" http://diyhpl.us/~bryan/papers2/bio/Continuous%20genetic%20recording%20with%20self-targeting%20CRISPR-Cas%20in%20human%20cells%20-%202016.pdf
17:31 < kanzure> "Programmable genome editing tools and their regulation for efficient genome engineering" http://diyhpl.us/~bryan/papers2/gene-therapy/Programmable%20genome%20editing%20tools%20and%20their%20regulation%20for%20efficient%20genome%20engineering%20-%202017.pdf
17:31 < ballede> Oh, yeah
17:31 < ballede> the first one is interesting alright
17:31 < kanzure> "Delivery technologies for genome editing" http://diyhpl.us/~bryan/papers2/gene-therapy/Delivery%20technologies%20for%20genome%20editing%20-%202017.pdf
17:31 < kanzure> "Non-viral nucleic acid delivery strategies to the central nervous system" http://diyhpl.us/~bryan/papers2/gene-therapy/Non-viral%20nucleic%20acid%20delivery%20strategies%20to%20the%20central%20nervous%20system%20-%202016.pdf
17:33 < ballede> I'll take a look through all of them later ;)
17:33 < ballede> do you normally use this username in freenode ?
17:33 < kanzure> yes.
17:33 < ballede> okok
17:34 < ballede> I see that you are in ##re as well
17:34 < kanzure> i do reverse engineering things like https://github.com/kanzure/pokecrystal
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18:16 < cevi_> after playing around with it for a while, I've concluded that coq isn't powerful enough to (automatically) do anything interesting
18:18 < cevi_> even fairly trivial claims seem to be beyond its reach
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18:22 < opiate> .
18:24 < kanzure> not going to help your hacking expedition, dude.
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18:25 < kanzure> (from some DMs.)
18:28 < opiate> why not kanzure
18:31 < jrayhawk> emotiv epoc was also a cool RE project
18:36 < opiate> elaborate jrayhawk
18:37 < kanzure> we took apart the emotiv epoc device and reverse engineered it, https://github.com/openyou/emokit
18:38 < opiate> what exactly is it about
18:38 < kanzure> it pretends to be an eeg device
18:39 < jrayhawk> i suppose "cool" is maybe not that great a description. the hardware sucked, but a company overcharging for crippleware got slapped down, at least
18:39 < kanzure> it has proprietary software. so we wrote an interface that worked, instead.
18:39 < kanzure> oh yeah, they were overcharging for some shitty software or somethig too
18:39 < opiate> Oh, yeah
18:39 < opiate> I see
18:39 < opiate> I actually developed a version of my own on openBCI
18:40 < kanzure> also i recovered their proprietary header files through magic, but i don't think anyone has put this information to use yet in emokit.git
18:40 < opiate> so I'm assuming this would be a similiar on concept EEG
18:41 < opiate> Anyway
18:41 < jrayhawk> http://hplusmagazine.com/2010/09/13/emotiv-epoc-eeg-headset-hacked/ haha I never realized you were an author at H+
18:41 < opiate> Did the EEG device work?
18:41 < kanzure> eeg doesn't work, in general.
18:41 < kanzure> it is a bad idea
18:42 < jrayhawk> do you shudder in horror at having your name associated with h+mag
18:42 < kanzure> i was humanity+ director of R&D, there are worse stains on my soul here
18:42 < opiate> why would he jrayhawk
18:42 < kanzure> because they are boring and ineffective
18:42 < opiate> hmm
18:42 < opiate> I see
18:43 < opiate> when I asked before about transhumanism magnets and wetware and shit
18:43 < opiate> I can see you guys don't like that stuff at all
18:43 < opiate> Is that right?
18:43 < kanzure> is that what they are calling them now, "transhumanism magnets"?
18:43 < opiate> Ok, good
18:43 < opiate> Because I've tried ENDLESSLY to search for a good forum on biohacking and similar concepts
18:44 < kanzure> this place stays good because i kickban all the idiots
18:44 < jrayhawk> anything i have to perform invasive surgery to use is transhumanist
18:44 < opiate> And everything I found was basically about delusional dudes blasting their dermis to insert leds underneath their skin
18:44 < jrayhawk> phlebotomy? transhumanist tubes. Earring? transhuman hoop.
18:44 < opiate> oh shut up jrayhawk
18:45 < jrayhawk> Oh, sorry, continue on about your transhuman LEDs.
18:45 < opiate> anyway why do you think humanity+ is boring kanzure
18:45 < opiate> (I was jk jrayhawk <3 )
18:45 < kanzure> they are more focused on media than doing anything, they have spent 30+ years bullshitting around instead of developing important skills or talents
18:46 < opiate> what about DARPA
18:46 < opiate> what do you make of it
18:46 < kanzure> humanity+ is not associated with DARPA.
18:47 < opiate> I know x)
18:47 < kanzure> DARPA might be funding one of our projects soon, or i guess it's an hplusroadmap spin-off project i guess, sort of unclear about nomenclature here.
18:47 < opiate> But I would like to know your thoughts on DARPA alone
18:47 < opiate> By the BTO?
18:48 < kanzure> i don't have those details at the moment. maybe in may.
18:48 < opiate> I see
18:48 < opiate> can I get more details on that project, or info to read?
18:48 < kanzure> it's an engineered polymerase enzyme, http://diyhpl.us/~bryan/papers2/polymerase/
18:49 < kanzure> we have a draft paper in progress but it's not ready yet.
18:49 < opiate> I see
18:49 < opiate> most of this papers are old
18:49 < kanzure> essentially the idea is to use optical and electronic control of a tethered polymerase enzyme for DNA synthesis
18:49 < opiate> with papers I mean docs
18:50 < opiate> Which polymerase enzyme in question?
18:50 < kanzure> a bunch of 'em, no preference.
18:50 < kanzure> see page 18-25 http://diyhpl.us/~bryan/irc/2017-02-03-beacon.pdf#page=18
18:53 < kanzure> also page 15 has unrelated cool things
18:56 < opiate> Right, I'm listing it all out to study later
18:56 < kanzure> page 2 of the slides answers your question about what i do
18:57 < kanzure> for a living.
18:58 < fenn> is darpa involved in hgp-write?
18:58 < kanzure> no it's about the polymerase stuff
18:58 < kanzure> something andrew arranged
18:58 < kanzure> i mean, andrew is involved in hgp-write i guess.
18:58 < kanzure> i'm not sure why he didn't go to hgp-write with the project.. but whatevs.
18:58 < fenn> it certainly seems relevant
18:59 < kanzure> shit i forgot to write a proposal
18:59 < kanzure> i was going to submit something about homologous recombination, but tethered polymerase antics would have been a good one to mention
19:00 < fenn> sorry i haven't been more active
19:00 < kanzure> their conference is really packed http://engineeringbiologycenter.org/2017-agenda/
19:00 < kanzure> not sure i can switch that quickly between typing for sessions
19:00 < fenn> lots of ethics and politics bullshit
19:00 < kanzure> might have to do some prep to setup the files
19:02 < kanzure> i expect a bunch of interest from journos... so, lock everything down.
19:04 < fenn> hmm there is less ethics crap on the schedule than i remember, maybe it changed
19:04 < kanzure> why can't it be good ethics, like i'd even settle for nick bostrom nonsense
19:04 < fenn> it's mostly defensive
19:05 < kanzure> nobody ever gets anywhere by giving into broken ethical frameworks
19:06 < fenn> i'd sure like to hear more than 10 minutes on dnascript.co (thomas ybert)
19:06 < kanzure> opiate: last year, http://diyhpl.us/wiki/transcripts/hgp-write/2016-05-10/
19:06 < kanzure> ah maybe i'll ask andrew about ybert/dnascript
19:06 < fenn> also when the hell did we get a .co tld?
19:06 < fenn> that's maximally confusing
19:07 < opiate> Hm?
19:07 < opiate> Are you also taking part in HGP kanzure?
19:08 < cluckj> well they got art caplan so they can't be totally bad...
19:08 < kanzure> fenn: yea it's almost as bad as 1-bit flip from .com
19:17 < fenn> is there like a summary of art caplan's position on various issues? wikipedia is like 6 pages of "he is a bioethicist" but with more words
19:19 < cluckj> he's not a position-on-stuff bioethicist, he does more of a "these are the issues to consider" type
19:21 < fenn> "he was the chair of the Advisory Committee to the United Nations on Human Cloning and served on the special advisory committee to the International Olympic Committee on genetics and gene therapy"
19:21 < fenn> this doesn't tell me much except that he probably conformed to the expectations of those organizations
19:21 < fenn> like "gene doping is bad mmkay" "cloning, the next menace"
19:22 < cluckj> yes
19:22 < fenn> i mean it's rare for entrenched organizations to call for anything radical
19:22 < fenn> so why is radical HGP-write associating themselves with art caplan?
19:22 < kanzure> blackmail?
19:24 < opiate> what are the views of caplan on hgp write?
19:24 < cluckj> cause he's an expert on bioethics issues?
19:25 < cluckj> because andy hessel wants to have lunch with him? idk...
19:25 < kanzure> becaue you have to pay the bioethicists off otherwise they start whistleblowing
19:25 < cluckj> that is also probable
19:41 < kanzure> hmph
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20:17  * kanzure stalks https://twitter.com/CRISPR_papers/followers
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20:34 < kanzure> hm one of the followers claims to be a time traveler
20:36 < fenn> anti-aging propaganda http://cqjournal.com/content/email/cq46/cq46-winners-notification/CQ44_Cover_grande.jpg
20:59 < kanzure> "Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting" http://www.nature.com/articles/ncomms14958 https://twitter.com/GaetanBurgio/status/850289823495540736
20:59 < kanzure> "cas9 nickases"
20:59 < kanzure> "catalytically dead Cas9-FokI fusion nucleases"
21:05 < kanzure> "A marker-free co-selection strategy for high efficiency human genome engineering" http://biorxiv.org/content/early/2017/03/15/116251 https://twitter.com/doyonlab/status/842152428829069313
21:07 < kanzure> https://transparent-human-embryo.com/
21:10 < kanzure> "Transdimensional visualization and analysis of early human development" http://www.cell.com/cell/fulltext/S0092-8674(17)30287-8
21:10 < kanzure> er.. *tridimensional
21:18 < kanzure> .title https://www.youtube.com/watch?v=RRfH4ixgJwg
21:18 < yoleaux> Transport inside the brain: The basic mechanisms of neuronal trafficking - YouTube
21:18 < kanzure> from https://twitter.com/PeetVanBergeijk/status/588768471464419328
21:26 < kanzure> .title https://innovativegenomics.org/multimedia-library/george-church-lecture/
21:26 < yoleaux> George Church Lecture on "Future, Human, Nature : Reading, Writing, Revolution" - Innovative Genomics Institute (IGI)
21:27 < kanzure> .title https://vimeo.com/209623759
21:27 < yoleaux> Future, Human, Nature : Reading, Writing, Revolution -- An Evening with Dr. George Church on Vimeo
21:39 < kanzure> new twitter game: how long can you click around on random twitter profiles until you run into new george church content? so far it seems to be at most one hour for me.
21:39  * kanzure sleeps
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--- Log closed Sun Apr 09 00:00:21 2017