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| kanzure | what happened to the hemispherectomy idea. if you keep cutting the brain in futher halves and selecting for zero behavioral change, then you should eventually get something simpler to analyze, right? | 05:53 |
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| bjonnh | http://www.technologyreview.com/news/544376/this-ai-algorithm-learns-simple-tasks-as-fast-as-we-do/ | 07:55 |
| bjonnh | .title | 07:55 |
| yoleaux | Machine Learning Inspired by Human Learning | MIT Technology Review | 07:55 |
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| Diablo-D3 | http://www.sciencedirect.com/science/article/pii/S1756464615005034 | 08:40 |
| Diablo-D3 | .title | 08:40 |
| yoleaux | Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduced body adiposity and Lp-PLA2 activity in overweight subjects | 08:40 |
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| kanzure | lost some sleeptypes data, apparently i don't save in my sleep. | 09:23 |
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| kanzure | sorta sucky. i had a bunch of brain uploading things typed in that file before i went to bed. | 09:26 |
| kanzure | (when i woke up, i copied the file from a server, and then closed the file since i figured i had already copied it. oops.) | 09:29 |
| kanzure | i know that a few neural network models have implemented plasticity and long-term potentiation, but what about all the other methylation and gene regulatory network stuff? | 09:34 |
| fenn | http://www.smithsonianmag.com/science-nature/why--captured-MRI-mother-child-180957207/?no-ist | 09:36 |
| kanzure | on a slightly related note, the artists that bother to gather actually useful scans, are the ones that partly redeem all the other noise from the arts communities | 09:38 |
| fenn | i'm just amazed at how big the baby's brain is already, compared to the mother's | 09:40 |
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| docl | Has everyone seen this? http://www.sciencedirect.com/science/article/pii/S001122401500245X | 09:54 |
| docl | It's from this list: http://aurellem.org/thoughts/html/good-ideas.html | 09:55 |
| kanzure | .title | 09:55 |
| yoleaux | Big List O' Ideas | 09:55 |
| kanzure | "Aldehyde-stabilized cryopreservation" | 09:55 |
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| docl | kanzure: aurellem (Robert Mcintyre) is also is famous for hacking Pokemon Yellow: http://gnusha.org/logs/2012-12-08.log | 10:18 |
| kanzure | indeed, i contributed some changes to his vba-clojure and then forked it into https://github.com/kanzure/vba-linux | 10:23 |
| kanzure | oh, none of my changes appear in his vba-clojure.git, so perhaps i should not claim i have contributed | 10:23 |
| kanzure | anyway i was using vba-linux over here for this stuff: https://github.com/pret/pokemon-reverse-engineering-tools/blob/vba-automation/pokemontools/vba/vba.py | 10:24 |
| kanzure | that is, er, re: https://github.com/kanzure/pokecrystal .. but didn't know about his big list of ideas. if anything i attribute this to lack of sufficient stalking. | 10:25 |
| kanzure | "Perhaps there would be a way to rapidly evolve a symbiotic bacterial organism that could protect human tissues from freezing damage." haha he gets close | 10:26 |
| kanzure | ok emailed/fixed | 10:30 |
| kanzure | yeah i had emailed him in 2013 to ask questions about vba-clojure. entire email thread seems to be exclusively pokemon. ugh. | 10:31 |
| kanzure | thank you. | 10:31 |
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| kanzure | i rank this one a little higher than accidentally ignoring adam marblestone | 10:47 |
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| docl | kanzure: ASC is one of the top contenders for the brain preservation prize: http://www.brainpreservation.org/21cm-aldehyde-stabilized-cryopreservation-eval-page/ | 11:56 |
| docl | I see they have a recent article about Adam Marblestone as well http://www.brainpreservation.org/adam-marblestone-on-rosetta-brains-and-markers-of-synapse-function/ | 11:57 |
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| kanzure | we don't really need brain uploading as much as we need brain modeling. i wouldn't mind foregoing personal memories and training and education as an initial approach. but brain scanning is not the same thing as brain modeling. | 12:00 |
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| kanzure | "Deep molecular diversity of mammalian synapses: why it matters and how to measure it" http://redwood.berkeley.edu/vs265/smith-synaptic-diversity.pdf | 12:01 |
| kanzure | "This excellent paper by Stephen Smith and colleagues, [pdf here], suggests a few possibilities, including massively alternatively spliced adhesion molecules like neurexins, which could in principle generate a set of molecular rules underlying connectivity. As Smith puts it: “Two classes of synaptic adhesion proteins, the neurexins and protocadherins (PCDHs), have large numbers of isoforms and are present both during the initial ... | 12:01 |
| kanzure | ... formation of synaptic connections and in mature synapses. Vertebrates have three neurexin genes, each with two promoters that can drive transcription of a large α-neurexin and smaller β-neurexin95,96 (reviewed in REF. 83). Alternative splicing can generate over 1,000 neurexin isoforms, which are expressed in regionally distinct but overlapping brain regions97… With the potential for combinatorial expression of these large ... | 12:01 |
| kanzure | ... numbers of adhesion proteins, a vast number of unique codes would be available to provide molecular signatures for specific brain circuits in the mature brain.”" | 12:01 |
| kanzure | "Frequently asked questions about the atoms of neural computation" http://arxiv.org/pdf/1410.8826v1.pdf | 12:02 |
| kanzure | "Genes such as SAM68 (Iijima et al., 2011) can govern the activity-dependent alternative splicing of neurexin molecules (Treutlein, Gokce, Quake, & Südhof, 2014) that play important functions in the formation, maturation, and maintenance of synapses. The state of pre-synaptic neurexin splicing can even influence post-synaptic receptor trafficking (Aoto, Martinelli, Malenka, Tabuchi, & Südhof, 2013), potentially allowing for a ... | 12:02 |
| kanzure | ... configurational code that could integrate intrinsic and extrinsic cues; such neurexins are represented differentially across the brain, and across developmental stages (Iijima et al., 2011). Neurexins also interact with neuroexophilin ligands, which are differentially expressed in sub-populations of synapses (Born et al., 2014), to influence synaptic function." | 12:02 |
| kanzure | docl: in particular, check out his thesis (scalable neural recording and such) (molecular ticker tape for recording single-spike resolution data per neuron) | 12:17 |
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| kanzure | for the purpose of debugging what brain matter is doing, perhaps some method of expressing proteins that are able to shutdown neural activity in the presence of ultrasound stimulation. then use ultrasound phased array and deliver sub-mm^3 ultrasound stimulation to whatever regions and then determine whether this impacts behavior. then you can map brain-location-space to behavioral outcomes. | 13:00 |
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| kanzure | also would be nice to have localized positron emission tomography of very specific clusters of neurons in brains | 13:19 |
| kanzure | possibly using ultrasound + microbubbles to deliver | 13:19 |
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| kanzure | 13:59 < kanzure> andytoshi and i were actually thinking about writing a paper regarding the surprising difficulty of killing everybody | 14:07 |
| kanzure | 13:59 < kanzure> even if you blow up the planet there will still be a number of survivors due to existing infrastructure | 14:08 |
| kanzure | 13:59 < kanzure> cooking the atmosphere is also not enough, because of inventive assholes living inside fucking mountains and shit | 14:08 |
| kanzure | 13:59 < fenn> it's not surprising; it's every engineer's job to ensure the safety of people who use their system | 14:08 |
| kanzure | 14:00 < fenn> if you blow up the planet everyone will die | 14:08 |
| kanzure | 14:00 < kanzure> i'm not so sure | 14:08 |
| kanzure | 14:00 < kanzure> it really depends on what you mean by blow up | 14:08 |
| kanzure | 14:00 < fenn> yeah | 14:08 |
| kanzure | 14:00 < kanzure> moving the earth into the center of a star would definitely solve all of these problems | 14:08 |
| kanzure | 14:01 < fenn> relativistic impactor of a few kilograms would be enough | 14:08 |
| fenn | more than a few kilograms it turns out | 14:09 |
| kanzure | how about one of those jupiter moons | 14:09 |
| fenn | more than enough | 14:10 |
| fenn | doesn't even need to be relativistic if it's that big | 14:10 |
| kanzure | is there really no defense for someone on the surface of the planet? | 14:11 |
| kanzure | surely there's a deep crust doom shelter that was designed to withstand this | 14:11 |
| fenn | well there are a couple problems, 1) surviving the initial blast, 2) rebuilding civilization without a functioning planetary ecology or sunlight | 14:12 |
| kanzure | well i would imagine you can set your sights a little lower than "rebuild civilization" | 14:12 |
| fenn | you need enough of an infrastructure to create food faster than you eat it | 14:13 |
| fenn | ideally enough food that you have time left over to do other things | 14:13 |
| kanzure | you're such a party pooper | 14:13 |
| fenn | i read "the knowledge" by lewis dartnell, it was kinda lame in that it didn't actually contain any actionable information that a catastrophe survivor might need | 14:14 |
| kanzure | also i'm not actually sure if deep crust doom shelters can actually withstand kinetic energy transfer from collision with large moon | 14:14 |
| fenn | it was more like speculation about what such a book might include, even though it's too much information to put in a book, and a lot of the information doesn't exist in any book at all | 14:14 |
| kanzure | i wonder if i could get pizza hut to sponsor a deep crust doom shelter as a marketing stunt or something | 14:15 |
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| andytoshi | does anyone here have a yubikey4? how do i make it touch-to-sign? | 14:40 |
| andytoshi | and how did they manage to get literally no documentation about this onto the internet? | 14:40 |
| kanzure | don't have one yet, but planning on it soon | 14:41 |
| andytoshi | it's pretty slick. but right now `gpg2 --sign` keeps working without even asking a pin number | 14:42 |
| andytoshi | and if you unplug the key you have to kill gpg-agent because it's a piece of shit | 14:42 |
| andytoshi | and gpg2 apparently requires it | 14:43 |
| andytoshi | found it! https://developers.yubico.com/PGP/Card_edit.html they link to a bash script to enable touch-required | 14:47 |
| andytoshi | impressive that you cannot find this through google and have to click through their website like a moron | 14:47 |
| andytoshi | hehehe! it works | 14:53 |
| kanzure | great now all you have to do is make sure all of your tor routing signatures are piped through your yubikey | 14:54 |
| kanzure | that's how this works, right? ..... guys? | 14:54 |
| andytoshi | the script you have to study is https://gist.github.com/a-dma/797e4fa2ac4b5c9024cc which tells you the raw commands u gotta send to the key through gpg-connect-agent | 14:54 |
| andytoshi | :) | 14:54 |
| kanzure | what are you going to do for your phone? | 14:55 |
| andytoshi | haven't decided yet. basically all my options are "it's not gonna work" | 14:55 |
| kanzure | maybe there is a usb port dongle | 14:55 |
| andytoshi | but i might put a burner ssh key on there so i can at least log into my server and have a single thing to disable | 14:56 |
| andytoshi | i won't be able to sign emails with it but that's ok cuz it's really hard to type emails anyway | 14:56 |
| kanzure | but... keyboard. you have one now. | 14:56 |
| andytoshi | oh, right, this is true | 14:56 |
| kanzure | better to say something like, "signing and sending can happen later, nothing is that urgent" | 14:57 |
| andytoshi | yeah | 14:57 |
| andytoshi | it'd be cool if there's a usb dongle or something but i bet the sw support is not there | 14:57 |
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| kanzure | instead of just ultrasound-receptive methods of shutting down neural activity, you could also use brain cysts in a clever distribution pattern. and possibly leak different neurotransmitters based on ultrasound stimulation. not sure how leaky microbial cysts tend to be in the brain though..... | 15:19 |
| kanzure | but that would allow fine-grained delivery of specific stimulation types | 15:20 |
| kanzure | then you would selectively probe how that modifies behavior based on different types of released stimulation in each region. | 15:21 |
| kanzure | somehow this seems even more ugh than "try to learn about all the ion channel types and all the receptor types and messaging molecule types". | 15:21 |
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| bjonnh | reminds me of time reversal ultrasounds | 15:44 |
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| andytoshi | fucking ssh | 16:34 |
| andytoshi | debug1: Offering RSA public key: cardno:000604038384 | 16:34 |
| andytoshi | debug1: Server accepts key: pkalg ssh-rsa blen 279 | 16:34 |
| andytoshi | debug1: Trying private key: /home/apoelstra/.ssh/id_rsa | 16:35 |
| andytoshi | it offers a key from my smartcard, the server says OK, then it looks for the private half on my harddrive | 16:35 |
| andytoshi | what does it think a smartcard key is ??? | 16:35 |
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| kanzure | "Sure -- I'd love to talk! You've actually picked the best possible time to get in contact with me; let me bring you up to speed on what I've been doing: I left MIT and started working at 21st Century Medicine, where I developed Aldehyde-Stabilized Cryopreservation (ASC), a method for preserving the connectome of an entire brain. This research was published in the journal Cryobiology: http://dx.doi.org/10.1016/j.cryobiol.2015.09.003 I ... | 17:58 |
| kanzure | ... entered 3 rabbit brains and 2 pig brains, all preserved using ASC, to | 17:59 |
| kanzure | Ken Hayworth's Brain Preservation Prize ( http://www.brainpreservation.org/21cm-aldehyde-stabilized-cryopreservation-eval-page/ ). | 17:59 |
| kanzure | "Now I've quit 21st Century Medicine to start my own company, Nectome, with my long time friend and business partner from MIT, Michael McCanna. I moved to the Bay Area around 2 weeks ago to do this. My plans for Nectome are nothing less than a full-service industrial-scale mind uploading operation. I have a clear vision on how to get there, and though uploading is many decades away at least, I believe that a fully verified brain ... | 17:59 |
| kanzure | ... preservation procedure can be created and offered to humans within the next 10 years." | 17:59 |
| kanzure | "Our mid range goal (5-10 years) is to develop a proof-of-principle mind-uploading pipeline, supported by the neuroscience community and further supported by direct simulation of selected human neural circuits. Our long term goal is to develop industrial-scale mind uploading technology." | 17:59 |
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| andares | Augh so cool | 18:09 |
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| aurellem | (this is me, Robert McIntyre) | 18:45 |
| aurellem | they guy who is starting Nectome | 18:45 |
| aurellem | are there any questions I might be able to answer? | 18:46 |
| kanzure | hi! sorry about having to run. i'll be available in a handful of minutes again (had to discuss a certain catastrophe with boss). | 18:46 |
| Diablo-D3 | kanzure: yeah, unfortunetly, I doubt either of them know how to do that | 18:52 |
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| kanzure | aurellem: this was the 90s group http://diyhpl.us/~bryan/papers2/neuro//nematodeuploadproject/murg.html | 19:07 |
| kanzure | other files available here http://diyhpl.us/~bryan/papers2/neuro//nematodeuploadproject/ | 19:07 |
| kanzure | http://diyhpl.us/~bryan/papers2/neuro//nematodeuploadproject/references.html | 19:08 |
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| aurellem | what happened to them? | 19:10 |
| Diablo-D3 | kanzure: do you have an aggregator setup somewhere so I can follow all the links you post in here? | 19:11 |
| kanzure | randal koene joined halcyon molecular (with the andregg brothers) and that went belly up when they bought a bunch of electron microscopes and then had to liquidate because ?? | 19:12 |
| kanzure | they were doing transmission electron microscopy dna sequencing as an initial product | 19:12 |
| aurellem | yeah, it's too bad that it didn't work out for them | 19:12 |
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| aurellem | it looks like they were working on C.elegans? | 19:13 |
| aurellem | something like openworm | 19:13 |
| kanzure | davidad (dalrymple) was working on nemaload for a while... http://web.archive.org/web/20150703194527/http://nemaload.davidad.org/ | 19:14 |
| kanzure | nemaload was an off-shoot of openworm stuff. the murg people were doing celegans before openworm existed but yeah. | 19:14 |
| kanzure | well, i guess it's unfair to describe nemaload as related to openworm | 19:14 |
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| aurellem | I see, and then openworm eventually absorbed nemaload | 19:15 |
| aurellem | that's pretty cool | 19:15 |
| kanzure | here's russell hanson talking about nanoCT and gold nanoparticles for synapse-resolution scanning http://gnusha.org/logs/2014-11-28.log | 19:16 |
| AdrianG | kanzure: hows your cryonic mice thing going | 19:30 |
| kanzure | AdrianG: ran out of cheese | 19:34 |
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| docl | aurellem: Nectome sounds ambitious! How do you plan to verify the procedure? Will it be limited to the clinically deceased like cryonics currently is? | 20:21 |
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| aurellem | the idea is multi stage | 20:35 |
| aurellem | first up was dealing with structural preservation | 20:36 |
| aurellem | now that's on a much surer footing than it was a year ago | 20:36 |
| aurellem | next up is verifying that the brain preservation technology is compatabale with the leading theories of memories | 20:36 |
| kanzure | what are those, anyway? recently i have seen a lot of http://diyhpl.us/~bryan/papers2/neuro/DNA%20methylation%20in%20memory%20formation%20-%20emerging%20insights%20-%202015.pdf | 20:37 |
| aurellem | this can be done by demonstrating that not only is structure being preserved, but that important chemicals necessary for memory are also being retained | 20:37 |
| aurellem | I'm still working out what qualifies as "important" | 20:38 |
| aurellem | This will be determined with leading neuroscientists | 20:38 |
| aurellem | but right now I'm worried about CaMKII proteins | 20:38 |
| aurellem | neurotransmitters in general, ion channels | 20:39 |
| aurellem | preservation of DNA | 20:39 |
| kanzure | .wik CaMKII | 20:39 |
| yoleaux | "Ca2+/calmodulin-dependent protein kinase II (CaM kinase II or CaMKII) is a serine/threonine-specific protein kinase that is regulated by the Ca2+/calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory." — https://en.wikipedia.org/wiki/CaMKII | 20:39 |
| aurellem | and then to a lesser extent, good preservation of myelin | 20:39 |
| aurellem | again, this is still being worked out, but the idea is to confirm preservtion of all necessary molecules as determined by say the top three leading theories of memory | 20:40 |
| aurellem | then neuroscience has to be *very* wrong for us to not be preserving memories | 20:40 |
| aurellem | then the next stage is demonstration of functional preservation | 20:41 |
| aurellem | because you can't be sure that you have it all until you try to build it | 20:41 |
| aurellem | so we'll do FIB-SEM on preserved/embedded brain tissue | 20:41 |
| aurellem | and demonstrate a simulation of selected neural circuits | 20:42 |
| aurellem | so that's an empirical "spot checking" of the preservation procedure | 20:42 |
| aurellem | I feel like anything less than that is probably going to be missing something important | 20:42 |
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| kanzure | yeah i like hte idea of pointing a microscope at synapses to count vesicles as a method of not having to record every single receptor type | 20:43 |
| aurellem | but with analogies to reading a human genome, you're proven that you can read an entire human genome in principle once you've read one gene | 20:43 |
| aurellem | yeah see here: | 20:43 |
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| aurellem | http://www.sciencedirect.com/science/article/pii/S0166223603001620 | 20:44 |
| aurellem | so that's a paper where they're able to infer synaptic strength from electron microscopy | 20:45 |
| aurellem | once you have a detailed understanding of how each neuron type works in vivo | 20:45 |
| aurellem | it gives you a tremendous inferencial power to determine the dynamics of a particular arrangement of neurons, just from electron micrographs | 20:46 |
| aurellem | like, you can tell exactly what neurotransmitter must be in the vesicles you see in the electron micrographs if you know the morphology of the cell | 20:47 |
| bjonnh | http://www.theatlantic.com/science/archive/2015/12/why-human-genetics-research-is-full-of-costly-mistakes/420693/ | 20:56 |
| docl | so cool! that's a huge point in favor of brain preservation (assuming good morphological preservation can be achieved). | 20:56 |
| bjonnh | .title | 20:57 |
| yoleaux | Why Human Genetics Research Is Full of Costly Mistakes - The Atlantic | 20:57 |
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| docl | and the pictures you present with the ASC results sure look like a heck of a lot of morphological detail is being preserved. | 20:58 |
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| docl | http://www.brain.riken.go.jp/labs/mns/nakahara/papers/Kasai03TINS.pdf | 21:15 |
| docl | I like a lot of the ideas at http://aurellem.org/thoughts/html/good-ideas.html | 21:23 |
| docl | kanzure: did you see the one about evolving microbes to protect human tissues from cryogenic temperatures? | 21:24 |
| kanzure | better to fix the human tissue itself | 21:27 |
| kanzure | human tissue is overrated anyway | 21:27 |
| kanzure | .title http://www.sciencedirect.com/science/article/pii/S0166223603001620 | 21:27 |
| yoleaux | Structure–stability–function relationships of dendritic spines | 21:27 |
| docl | aurellem: is the effect you mention under Paramagnetic CPA the same as the magnetocaloric effect? | 21:28 |
| docl | I think the MCE might involve a phase change? | 21:28 |
| docl | https://en.wikipedia.org/wiki/Magnetic_refrigeration | 21:29 |
| docl | The most popular suggested use is for refrigerant-free freezers. But for those you can use lots of cycles. In cryonics, you would want to cool everything in one shot (or perhaps two, one to get past the chilling injury zone and another to get past the ice formation temperature). | 21:32 |
| docl | kanzure: how do you evolve the tissue? by growing organs out of stem cells and implanting them to make sure they still work? | 21:42 |
| kanzure | genetic engineering, in vitro fertilization, gene therapy, pick your poison | 21:43 |
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| docl | evolution needs feedback. you could intelligently introduce the mutations, but you still have to validate them somehow. | 21:44 |
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| kanzure | yep that is why i suggest focusing on small animals first | 21:45 |
| docl | it just seems to me like the physiology of existing mammals isn't adaptable enough to the cold. maybe if you introduce genes from other species, you could make some headway. | 21:46 |
| docl | the main thing you need is vitrifiability. (and lack of chilling injury, but that's probably something we can work around.) vitrification requires either rapid temperature drop, ice blocking polymers, or very high concentrations of osmolytes (dissolved things). rapid temp drop isn't something you can evolve in mice and transplant to humans. | 21:49 |
| docl | not unless you evolve them to grow carbon nanotubes threaded throughout their tissues or something weird like that. | 21:49 |
| kanzure | darwin had this idea of using gas for rapid temperature drop | 21:50 |
| kanzure | high-pressure gas | 21:50 |
| docl | yeah that's been around. you could maybe evolve them to tolerate persufflation better. | 21:50 |
| docl | tougher endothelial cells? | 21:51 |
| docl | imo, adaptation to trehalose import (or trehalose synthesis) while knocking out trehalase would be a good start. it's a small sugar molecule that mammals don't have which helps protect against dehydration | 21:59 |
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| docl | improving tolerance to persufflation might be something that yields better to a nanotech approach than a genetic approach. you could perfuse nanoparticles designed to settle throughout the endothelium and act as a supporting system (also increasing thermal conductivity). | 22:08 |
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| Diablo-D3 | is this worth mentioning here? http://www.wsj.com/articles/does-matcha-beat-green-tea-in-health-benefits-1450111818 | 22:17 |
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| Diablo-D3 | jesus, is everyone from #bitcoin showing up here? ;) | 22:18 |
| Diablo-D3 | nanotube: :D | 22:18 |
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