--- Log opened Fri Oct 09 00:00:52 2015
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00:05 <@nmz787> is there some world map (google-something?) that shows you maps of the world through-time/history?
00:06 <@nmz787> like with a slider bar for time
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05:29 < kanzure> "patents were a dumb idea" https://news.ycombinator.com/item?id=10358640 yay
05:30 < kanzure> "the milky way at different wavelengths" http://www.chromoscope.net/
05:30 < kanzure> commentary, https://news.ycombinator.com/item?id=10358660
05:32 < kanzure> "quantum effects in large-scale systems" http://nautil.us/issue/29/scaling/how-big-can-schr246dingers-kittens-get
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05:34 < kanzure> something about decapitating a mouse http://nautil.us/issue/29/scaling/why-the-russians-decapitated-major-tom
05:34 < kanzure> "As planned, Major Tom’s organs were dissected and split among specialists from six countries, resulting in 70 studies. His brain was subdivided in smaller parts—frontal cortex, visual cortex, hypothalamus, hippocampus, striatum, and substantia nigra—some of which were sent to Vladimir Naumenko, a senior researcher from the Russian Institute of Cytology and Genetics. In a study published in July 2014, Naumenko concluded that ...
05:34 < kanzure> ... “spaceflight decreased the expression of crucial genes involved in dopamine synthesis.”"
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05:41 < archels> but was it spaceflight per se?
05:41 < kanzure> 50-lane highway https://en.wikipedia.org/wiki/G4_Beijing%E2%80%93Hong_Kong%E2%80%93Macau_Expressway
05:42 < archels> that's 50 toll booth lanes though, right
05:42 < kanzure> http://i.huffpost.com/gen/3514284/thumbs/o-BEIJING-HONG-KONG-900.jpg?2
05:42 < kanzure> hm?
05:43 < archels> not actually any long stretch of 50 lane highway
05:44 < kanzure> oh :-/
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05:52 < archels> pretty steampunk  http://i.imgur.com/8Jr66RL.jpg
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06:29 < kanzure> archels: what did you think of that blue brain project paper from yesterday?
06:29 < kanzure> have you looked
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06:45 < streety> is the lm317 the way to go for that nmz787? How much power does the laser need? My first thought would be a switched mode power supply would be the way to go
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07:06 < archels> kanzure: "Reconstruction and Simulation of Neocortical Microcircuitry"?
07:06  * archels looks
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07:19 < archels> oh, they didn't do a full-volume reconstruction
07:20 < archels> they just rotated/perturbed a few stereotypes to fill the volume
07:23 < archels> they also classify neurons somewhat rigidly into this "Petilla terminology", while it's pretty much accepted now that it's a continuum
07:24 < kanzure> so they weren't doing their "statistically-informed generation of neural topology" technique?
07:24 < archels> it's a reasonable pragmatic choice at this point in time though, I wouldn't know how to sidestep that even for EM tech at present
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07:27 < kanzure> EM?
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07:29 < archels> In order to further increase morphological diversity, a cloning algorithm was implemented. This algorithm took
07:29 < archels> each morphology and injected noise into branch lengths and rotations, leaving the overall branching structure
07:29 < archels> unchanged, but resulting in completely unique space-filling for each clone.
07:29 < archels> and
07:29 < archels> At each bifurcation point, there were two
07:29 < archels> subtrees, each of which were rotated by a degree sampled from a Gaussian distribution of mean 0° and
07:30 < archels> standard deviation 10°.
07:30 < archels> that's their cloning process... so just some statistical perturbations
07:30 < archels> EM as in, electron microscopy
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07:34 < archels> I guess electrophysiological classification under an EM sectioning process is out
07:35 < archels> not sure how far they've come integrating RNA sequencing into that process
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07:37 < archels> (the videos of the BBP paper are kinda pretty, so long as you're not put off by the lack of detail)
07:38 < archels> but might be nice for highschool presentations
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07:59 < kanzure> modeldb mercurial repositories http://neuro.med.yale.edu/hg
08:00 < kanzure> recent random thing from that page, http://neuro.med.yale.edu/hg/181967/CutsuridisPoirazi2015/rev/4458d5a1a2c1
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08:01 < kanzure> "calcium accumulation into a volume of area*depth next to the membrane with a decay (time constant tau) to resting level given by the global calcium variable cai0_ca_ion"
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08:03 < kanzure> "slow Ca-dependent potassium current"
08:04 < kanzure> "cylindrical coordinate system  with constant annuli thickness to center of cell. Note however that the first annulus is half thickness so that the concentration is second order correct spatially at the membrane or exact edge of the cell."
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08:18 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=93922489 Bryan Bishop: short summary of dna synthesizer for maaku >> http://diyhpl.us/diyhpluswiki/dna/synthesis/notes/
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08:26 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=
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08:43 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=98445094 Bryan Bishop: better explanation of hplusroadmap >> http://diyhpl.us/diyhpluswiki/index/
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08:50 < kanzure> maaku: summary has been written, i'd be happy to extend the text to include whatever you identify as missing when you look http://diyhpl.us/wiki/dna/synthesis/notes/#summary
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10:19 < maaku> kanzure: hey thanks!
10:20 < kanzure> maaku: anything missing from it? plz spew generic questions
10:22 < maaku> kanzure: is the inkjet able to get accomplish precise manufacturing?
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10:24 < kanzure> maaku: inkjet printheads are amazing and you're missing out
10:24 < maaku> reading the summary sounds like you're doing spray-and-pray of A, C, T, and G
10:24 < kanzure> each droplet is a separate reaction chamber
10:24 < maaku> i see...
10:24 < kanzure> surface tension prevents the droplets from merging (and also the great distance between individual droplets)
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10:25 < maaku> ok so seach deposited droplet is a reaction chamber, that's something I was missing from the description
10:26 < kanzure> were you thinking "nanometer-precision deposition and stacking"?
10:26 < maaku> kanzure: yes, which is why I thought it was crazy
10:26 < maaku> what's the two-sentence summary of how you get long strands of dna from that?
10:26 < kanzure> reaction yield prevents superlong dna strands because even with 99.99% yield at each step you are going to get at least one error by the time you hit 100 bp length
10:27 < kanzure> sooo instead you have to conjugate separate dna molecules from different reaction chambers. the mechanism of introducing them into physical proximity in a programmed, control way is still undecided.
10:27 < kanzure> s/conjugate/ligate (combine)
10:30 < maaku> ok so let's see if I understand: using traditional techniques you make a <100bp (<10bp?) dna strand, and using an inkjet you place droplets containing these and the necessary joining catalysts on a surface
10:30 < kanzure> popular proposals for this have included: use pipettes to move the samples around and conduct reactions; come up with single-pot reaction biochemistry with enzymes to ligate the dna molecules together; use lasers to push microbeads (from inside the droplet reaction chambers) around; use liquid crystal matrix displays and photoconduction to move droplets of water; etc.
10:30 < maaku> then as the droplets join the pieces join together?
10:30 < kanzure> traditional technique is giant column that you pump the reaction reagents through, dna strands are "grown" on the material packed into the column
10:31 < kanzure> as the droplets join, there is a mixing of the reagents from the original reaction outputs, but then another reaction has to occur to get the molecules to join together
10:32 < maaku> right, but you've positionally placed the necessary reagents and catalysts close together
10:32 < kanzure> the technique for synthesizing a strand of dna in a droplet is much more well understood than "what the heck are we going to do to conjugate the dna molecules together?" -- can't really have a pipetting robot that focuses on 1 micron diameter droplets. very hard to do.
10:32 < kanzure> yes basically
10:33 < kanzure> ((and even if you do have a 1 micron droplet pipetting robot, you have 100 million droplets on the surface anyway, so certainly can't be some linear robot that pipettes each droplet individually; would take forever and never get done))
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10:34 < kanzure> to be even more specific, there has been a previous inkjet dna synthesizer project where the team was able to print dna on a surface with i think it was 10,000 drops or whatever, but they were just leaving the dna there (for a technique called dna hybridization arrays). so they didn't even bother to try to conjugate the dna molecules together.
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10:38 < maaku> kanzure: at what point does the DNA start folding?
10:38 < maaku> I assume that would be the upper limit on utility of this technique
10:39 < kanzure> some of the conjugation techniques (wait, all of them?) require enzymes and basically the reaction conditions for polymerase chain reaction, which involves cycles of heating and then cooling. the enzymes are good at grabbing on to the dna molecule and finding the ends.
10:39 < kanzure> and the temperature also changes the behavior of the dna molecule
10:39 < kanzure> and the enzymes
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10:44 < fenn> "100s of millions of drops per second" is not correct
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10:47 < fenn> maaku the inkjet only holds single bases, not strands
10:47 < fenn> the strands are formed on the surface
10:47 < fenn> for DNA origami, it only folds when you add the complementary sequence
10:48 < maaku> fenn: I'm thinking more regular old chromosome folding
10:48 < kanzure> the $5k printhead seemed to do ~200 million drops/sec
10:48 < fenn> well, that's the goal. supposedly DNA origami is a bitch because the sequences like to fold spontaneously
10:48 < kanzure> dna also twists and contorts into weird shapes, isn't just folding
10:48 < maaku> "because the sequences like to fold spontaneously" <-- yeah that's my worry
10:49 < maaku> it's just something you got to try and see though
10:49 < kanzure> enzymes are good at handling long dna molecules
10:50 < kanzure> if you created a dna molecule so long that it had physical twisting and other behavior that enzymes can't completely deal with yet, you could do directed evolution of enzymes to handle progressively longer dna molecules.
10:50 < kanzure> but there are species with superlong genomes and the enzymes for handling those genomes are mostly the same as any other
10:50 < fenn> you expect way too much from evolution
10:50 < fenn> you can't just dump a truck full of pigs from an airplane and expect to get a superpig
10:50 < kanzure> nah that was based on informed expectations from known-mutations we've already seen
10:50 < kanzure> right, you look at the damage to the pigs, find the least damaged pigs, and then breed those together
10:51 < maaku> kanzure: right. so I was asking because I'm trying to figure out how this is used to create a whole chromosome (e.g. 1G base pairs)
10:51 < maaku> so you build up to large (1k? 1M?) segments, and then do more traditional biochemistry to stitch together the pieces
10:51 < kanzure> once you have superlong dna molecule, conversion into an actual chromosome is less problematic
10:52 < kanzure> segments will probably start at 20 bp to 100 bp in size, unlikely to be less than 20 bp
10:52 < fenn> you can use ligase and gibson assembly up to ~10k and then homologous recombination in yeast for larger fragments up to 1M?
10:52 < kanzure> sounds right to me
10:52 < fenn> a chromosome is less than 1G
10:52 < kanzure> oh yeah, right, divide by 46
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10:55 < kanzure> fenn: that's like saying that the foxes just finally decided to give up after a few generations, instead of any selective pressure for tameness by not breeding very-not-tame foxes.
10:56 < fenn> https://en.wikipedia.org/wiki/Mycoplasma_laboratorium#Bacterial_chromosome_synthesis
10:56 < kanzure> i doubt you can find a good argument against directed evolution and iteration itself, however you could have a reasonable argument about "what the actual genetic landscape happens to be"- e.g., the amount of mutation and combinations to test to get a pig that doesn't die from 20 km drop might require more combinations of mutations than we have time left for in lifetime of universe, or something. that would be a valid rebuttal.
10:57 < kanzure> but v. difficult to guestimate about shape and structure and nature of genetic landscape
10:58 < kanzure> also makes things hard to decide when to give up on an attempt at evolutionary search over genetic landscape
10:58 < kanzure> because for all you know the necessary mutations might be very close in mutation-choice-space....
10:59 < kanzure> i suppose if you know the actual set of problems that cause termination of 20 km dropped pig, then you could figure out whether you feel it's reasonable that simple mutations could effect those results
10:59 < fenn> yeah the pig might have really large ears
10:59 < fenn> very strong hoofs
10:59 < kanzure> for example, bone breaks might cause the death of the pig (among other things!), so better bone density, or shock-absorption bones or something, bone density is easy to imagine a series of simple mutations contributing to, shock-absorption not as easy to imagine....
11:00 < kanzure> bone density easier to imagine because i think we've actually seen dense bone mutations somewhere, not sure where
11:01 < kanzure> i think it was aubrey de grey that was arguing that if you run a steamroller over some pigs and breed the results, you'll just get a bunch of pigs that survive steamrollers. and i was like "yeah? that sounds great to me."
11:01 < kanzure> you might accidentally get pigs that metamorphize into having a second-stage of life where they are just a blob of meat with broken bones and puncture wounds. but that's technically still survival.
11:03 < kanzure> various troubling questions about opportunity cost and when to give up on an evolutionary search attempt for some problem
11:03 < kanzure> "well just limit the search length to some cost less than the saved cost of not having to clean up 20 km dropped pig carcass from street surfaces"
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11:08 < kanzure> trying to find that old evolutionary search site about TANSTAAFL
11:09 < kanzure> instead found some thesis about "evolvable virtual machines" https://ourarchive.otago.ac.nz/bitstream/handle/10523/1910/NowostawskiMariusz2008phd.pdf?sequence=3
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11:17 < kanzure> http://no-free-lunch.org/
11:20 < kanzure> site is operated by martin sewell <martin@martinsewell.com>
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12:19 < maaku> kanzure: interesting find (EVM)
12:24 < kanzure> natasha vita-more has been posting some emails to extropy-chat upset about the criticism over her cryonics and celegans memory work here https://news.ycombinator.com/item?id=9594201
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12:55 < nmz787_w> http://hackaday.com/2015/10/09/optical-rectenna-converts-light-to-dc/
12:55 < nmz787_w> pretty sweet
12:55 < nmz787_w> we should find their protocol
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12:58 < Aurelius> Sorry for nickspam
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13:05 < nmz787_w> streety: power-wise the lm317 should be fine... the laser itself is probably 100mW or 500mW... who knows, it came from ebay and originally China. From a lithography standpoint, with the laser being focused, it is already much too powerful. As is, and I haven't tried maxing out the feedrate settings on the XY gantry, but it is etching and cutting paper easily... so I'm sure that is about 10 or 100X (or maybe 1000X) too bright f
13:05 < nmz787_w> you need something like a few mW per sq centimeter I think
13:06 < kanzure> you have cutoff at "(or maybe 1000X) too bright f"
13:06 < nmz787_w> so focusing a 100mW beam at even 100 microns sq (circular? elliptical? eh figure a square)
13:06 < archels> nmz787_w: that's output power though, right? what's the input power?
13:06 < nmz787_w> (or maybe 100x) too bright for photoresist
13:06 < nmz787_w> 1000X *
13:07 < nmz787_w> sorry, I am on webchat
13:07 < nmz787_w> surprising it doesn't auto take care of long lines
13:07 < nmz787_w> I mean on webchat.freenode.net
13:07 < nmz787_w> archels: oh, hmm, idk how cheap chinese lasers are marketed
13:07 < nmz787_w> I've usually only heard they're severely under-labelled, so they can get through customs
13:08 < nmz787_w> I can hookup a current meter though this weekend
13:08 < nmz787_w> but in general, I feel like burning/cutting paper is still 10-1000 times too bright for photoresist
13:08 < nmz787_w> you only want the molecules to recajigger, not discombobulate
13:09 < nmz787_w> :P
13:09 < CaptHindsight> sounds like post-doc stuff to me
13:10 < nmz787_w> the jargon?
13:10 < nmz787_w> no, I think that's appalachian
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13:24 < fenn> the c. elegans vitrification paper looks fine
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13:28 < fenn> i don't see what being published in a big name journal has to do with the quality of the science
13:28 < fenn> you'd think people would know that, but i guess there are idiots everywhere you look
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13:30 < Betawolf> big-name journals have a bigger readership and so articles come under more scrutiny (after publication). Smaller journals less so.
13:31 < Betawolf> This doesn't mean a paper in a smaller publication will be bad science, it means that if it was bad science it'd be more sensible to submit it to a smaller journal.
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13:48 < fenn> you need a montage: http://youtu.be/qJckchby55E
13:48 < fenn> .title
13:48 < yoleaux> Push It to The Limit Petman, Atlas Boston Dynamics - YouTube
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14:24 < kanzure> openworm videocast-only brain emulation journal club https://plus.google.com/u/0/b/117948341754627144949/events/cv9l18020h2cc0doj62h29errn0?n=1
14:25 < kanzure> ugh so many videos, so few transcripts (none). how inconsiderate.
14:25 < kanzure> ( https://plus.google.com/u/0/+OpenWormOrg/posts )
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14:29 < maaku> kanzure fenn : thanks for explaining the DNA printing process. it makes a lot more sense now how it integrates with the broader transhumanist project
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14:36 < kanzure> maaku: now that cambrian genomics is dead in the water, i think it's up to hplusroadmap to continue their short-term mission of replacing 30-60% of all plant dna on the surface of the planet with synthetic alternatives
14:36 < kanzure> fenn: errors-of-omission are the worst. what's missing on the wiki?
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15:11 < kanzure> howdy neals
15:15 < neals> sup kanzure
15:15 < neals> another busy day in ##hplusroadmap
15:16 < kanzure> elliptic curve stuff is up
15:17 < neals> cool, what are you working on?
15:17 < kanzure> reading libsecp256k1
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15:36 < kanzure> re: "100s of millions of drops per second is not correct" should be, 5k nozzles at 20 khz is 100M/sec
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16:17 < kanzure> "genetic landscape" is not an actual term according to wikipedia... what's the one that means "the stuff that evolutionary search is finding out for you"?
16:43 < neals> https://en.wikipedia.org/wiki/Evolutionary_landscape ?
16:44 < streety> sounds like the input power for that laser isn't going to be too massive. If it can run on a lower voltage then the lm317 may work fine.
16:44 < streety> I have a book or two and some course notes on power electronics if it is proving trickier than anticipated
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16:46 < kanzure> "In either case, movement tends to be toward areas of higher fitness, though usually not the global optima."
16:46 < kanzure> what?? movements should be capable of going in any direction away from fitness or towards.
16:47 < kanzure> "What exactly constitutes an "evolutionary landscape" is confused in the literature. The term evolutionary landscape is often used interchangeably with adaptive landscape and fitness landscape, though other authors distinguish between them. As discussed below, different authors have different definitions of adaptive and fitness landscapes. Additionally, there is large disagreement whether it should be used as a visual metaphor ...
16:47 < kanzure> ... disconnected from the underlying math, a tool for evaluating models of evolution, or a model in and of itself used to generate hypotheses and predictions. Clearly, the field of biology, specifically evolutionary biology and population genetics, needs to come to a consensus of what an evolutionary landscape is and how it should be used."
16:47 < kanzure> rofl
16:48 < kanzure> let's see what tim schmidt's gang says about this, http://beacon-center.org/blog/2012/10/08/evolution-101-fitness-landscapes/
16:49 < kanzure> "In reality, fitness landscapes are highly dimensional and impossible to visualize"
16:50 < kanzure> js simulation of fitness landscape stuff http://www.cse.msu.edu/~zamanlui/processingJS/draw_fitness/
16:53 < kanzure> hmm this population doesn't seem to ever grow even if you connect different peaks for the population
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16:59 < kanzure> .title https://www.youtube.com/watch?t=2&v=FTBUIJwlVBg
16:59 < yoleaux> Visualizing coevolution in dynamic fitness landscapes - YouTube
17:00 < CaptHindsight> fenn: 2656 nozzles x 40Khz = 106,240,000 drops per second max for one printhead, crazy but some printers actually achieve >2 Billion drops per second using multiple heads
17:06 < fenn> i stand corrected
17:06 < kanzure> this is an okay one: http://beacon-center.org/blog/2014/04/07/beacon-researchers-at-work-holey-fitness-landscapes/
17:06 < kanzure> i have no idea why nobody has tested >1M drops/sec with a printhead for dna synthesis reasons
17:07 < CaptHindsight> http://www.memjet.com/products/labels  is between 100M and 600M drops per second depending on how you count or overlap drops
17:07 < fenn> 64k ought to be enough for anybody
17:08 < CaptHindsight> kanzure: the printhead manufacturers don't care, they don't share specs and they want you to spend $100K on your first batch of heads
17:08 < kanzure> if $100k gets me 1 trillion drops/sec then things start getting really interesting
17:09 < CaptHindsight> closer to 1 billion drops per second
17:09 < fenn> it seems like they are just parallelized so meh
17:09 < CaptHindsight> they wish they could be drug companies
17:09 < fenn> too many parallelized cooks in the kitchen
17:10 < CaptHindsight> yeah only 4-8 channels/colors/fluids per head
17:10 < kanzure> i think you mean too many parallel turtles all the way down
17:10 < CaptHindsight> most are 1-2 channels
17:11 < kanzure> are the >1B drops/sec printheads assuming a controlled atmosphere?
17:11 < kanzure> any special pressure/temperature requirements beyond range of consumer inkjets?
17:12 < CaptHindsight>  >1B drops/sec printer or printhead array, a single head is ~100M drops per second
17:13 < CaptHindsight> just out of the wind is all
17:13 < CaptHindsight> and temp is controlled for consistent jetting since the viscosity of the fluid will change over temp
17:14 < kanzure> inkjet controls temp, or is that the responsibility of your junk around it?
17:14 < CaptHindsight> industrial heads will have built in heaters
17:14 < kanzure> cool
17:15 < CaptHindsight> some even have microprocessors that adjust the waveform based on head temp
17:15 < CaptHindsight> built into the head
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17:16 < CaptHindsight> but they don't even share the programming spec for those even under NDA, you might have leave them your liver
17:16 < kanzure> i never wanted a liver anyway, they can have it
17:17 < CaptHindsight> they change you ~$50K to program those heads for you
17:17 < kanzure> "2 High dimensionality means a large number of genes (loci) or number of nucleotides."
17:18 < kanzure> this seems like the wrong definition; i thought dimensionality was supposed to be based on selection criteria.
17:18 < CaptHindsight> I mean develop a ~2k bit file for you for the internal eeprom
17:18 < kanzure> hmm they have annual report http://beacon-center.org/wp-content/uploads/2014/10/BEACON2014AnnualReport_Public.pdf
17:19 < kanzure> hm page 6 claims they have insight into the evolution from single cell to multicellular life
17:20 < kanzure> seems to be based on concept of metabolism and metabolic byproduct mutations being poisonous to other processes
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17:25 < kanzure> on page 25 i'm not sure why they think a markov model is an evolutionary search algorithm (they are using a markov model for protein folding predictions)
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17:30 < kanzure> page 43 mentions some work about dna secretion systems
17:33 < kanzure> there was a 2013 igem team funded by beacon
17:34 < kanzure> calling themselves "darwin's bulldogs", evidently
17:36 < kanzure> hod lipson is an adivsor for beacon, and ellington shows up in this doc. hrm.
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17:59 < kanzure> tim schmidt introduced me to someone at beacon back in january (titus brown) but it turns out that titus was someone i met on slashdot in 2007
17:59 < kanzure> but only now realizing this. oops.
18:07 < kanzure> i wonder if there's an equivalent to shocking a heart that works for dying/dead livers, such as those that die before transplanting 'em
18:08 < kanzure> heart and lungs survive 4-6 hours, kidneys up to 36 hours, livers up to 12 hours. damn.
18:08 < kanzure> http://www.transweb.org/faq/q24.shtml
18:08 < kanzure> relevant chart http://www.transweb.org/images/content/faq_q24.gif
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18:36 < kanzure> Jawmare: welcome back
18:36 < Jawmare> hi
18:41 < kanzure> 21:54 < kanzure> david dalrymple got into that marblestone thesis
18:41 < kanzure> 21:54 < kanzure> very sinister
18:41 < kanzure> was checking my email, turns out dalrymple introduced me to marblestone in 2012... oops. dropped the ball on that one.
18:44 < kanzure> world is much smaller than i originally anticipated
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18:58 < kanzure> "Dalrymple & Co. LLC is closed for business due to the upcoming holiday on Monday, October 12th. We will resume business at some point and will reply to your request shortly thereafter. [This is an automated message. This is a no-reply address. Please direct further inquiries to support@dalrymple.co.]"
18:58 < kanzure> friendship is weird
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19:34 < mgin> does anybody here want to live forever?
19:48 < drethelin> marblestone?
19:48 < drethelin> mgin: how do you know I'm not already living forever
19:50 < mgin> hey
19:50 < mgin> can you unban me from lesswrong
19:50 < mgin> lol
19:50 < mgin> it's been like a year
19:51 < drethelin> do you mean slatestarcodex?
19:51 < mgin> hm?
19:52 < mgin> wait wut?
20:02 < kanzure> no, i'm the one you banned from slatestarcodex
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--- Log closed Sat Oct 10 00:00:52 2015