| --- Log opened Mon Nov 16 00:00:26 2015 | ||
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| fenn | "embryo selection" was written by carl shulman + nick bostrom, not anders sandberg | 01:56 |
|---|---|---|
| fenn | personally, i care about others trying to hack my brain using airborne chemicals in a supposedly peaceful civilian environment | 01:57 |
| fenn | i don't want to live in a world where everyone must wear a gas mask everywhere | 01:58 |
| TMA | it is already happening -- the imunocompatible others smell nice wich makes us succeptible to their advances :| | 02:09 |
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| fenn | fuzzy booleans should have been the default in opencascade, this is ten years too late: http://dev.opencascade.org/index.php?q=node/1056 | 03:16 |
| fenn | fixes errors with boolean operations on shapes with touching boundaries | 03:17 |
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| chris_99 | http://motherboard.vice.com/read/biohackers-are-implanting-led-lights-under-their-skin - not quite sure of the idea behind that | 04:46 |
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| kanzure | fenn: sure you should monitor for those events but your ethics is not going to be able to convince them to not exist | 05:37 |
| kanzure | drethelin: irc channels don't need sponsors, but the channel's /topic was "sponsored by george church" for a few years | 05:38 |
| kanzure | chris_99: lookup "grindhouse wetware" in the logs | 05:38 |
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| archels | chris_99: this is closer to bodymod than anything else. the EEs in this community are obviously stuck at Arduino level | 05:44 |
| chris_99 | heh yeah, i wouldn't say adding some leds has much to do with biology | 05:46 |
| archels | well, implanting LEDs is all well and good, I have no gripes with that | 05:48 |
| chris_99 | sure, but it's not really biohacking | 05:48 |
| archels | just the way in which these guys are carrying it out, with a battery that runs out before long—and mostly the stupidly large sizes of the objects they're sticking under their skin | 05:48 |
| archels | sure, but it could conceivably work in symbiosis with it in the near future, e.g. when it comes to optogenetics | 05:49 |
| kanzure | it's obnoxious | 05:52 |
| kanzure | transobnoxious | 05:52 |
| chris_99 | heh | 05:52 |
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| FourFire | It looked stupid and useless, like a reprap | 05:55 |
| chris_99 | they could have at least used RGB leds | 05:55 |
| FourFire | most of the value being in "look I did a thing, and it's morally revolting/interesting somehow, look how hackerculture I am" | 05:55 |
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| kanzure | the only "revolting" thing about it is their impressive ability to ignore our advice... | 05:58 |
| FourFire | oh, I misused the word there, I meant something along the lines of boddy horror/selfmutilation aspects | 05:59 |
| kanzure | well, i guess the attitude is also obnoxious and revolting. hm. | 05:59 |
| FourFire | what advice was that? | 05:59 |
| kanzure | wireless power transmission | 05:59 |
| FourFire | yeah, I was surprised they did not have that. | 06:00 |
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| archels | I had a dream last week where one of these grinder people took one of those LED doohickeys that harvest cell phone radiated energy to flash in random patterns, and implanted it behind their ear | 06:00 |
| archels | shoot, maybe I shouldn't be giving them any ideas | 06:01 |
| FourFire | archels, seen black mirror? | 06:01 |
| archels | some | 06:02 |
| FourFire | there's one where society has normalized using a small object behind the ear acts as a lifelogging device, social dumbness ensues | 06:03 |
| FourFire | implanted* | 06:03 |
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| chris_99 | nmz787_i, i had more of a look through that patent it seems they actually are using microlenses, which maybe is novel | 08:40 |
| chris_99 | actually i guess some image sensors have those anyway (such as Canons), maybe it just helps reduce noise | 08:44 |
| nmz787_i | i saw that they said 'lenses' but then their comment about no dispersive elements made me think twice | 08:58 |
| nmz787_i | but yeah microlenses are nothing new | 08:58 |
| chris_99 | mmm | 08:59 |
| chris_99 | i still don't understand the figures, theres something which looks like a big lens | 09:01 |
| nmz787_i | the Lytro is a commercial camera with microlenses | 09:02 |
| chris_99 | yeah Canon cameras use them | 09:02 |
| chris_99 | too | 09:02 |
| chris_99 | not for plenoptic stuff | 09:03 |
| chris_99 | but for capturing more light afaik | 09:03 |
| nmz787_i | yeah | 09:03 |
| nmz787_i | I think that is pretty common for DSLRs | 09:03 |
| chris_99 | which might be what theyre using them here for? | 09:03 |
| nmz787_i | but that is on the CCD, not further away | 09:03 |
| nmz787_i | if that is what they're doing, idk | 09:03 |
| chris_99 | mmm | 09:03 |
| nmz787_i | even in the Toshiba CCD datasheet I think they recommend an on-chip microlens | 09:04 |
| nmz787_i | maybe they don't call it 'micro' | 09:04 |
| chris_99 | ah didn't notice that | 09:04 |
| nmz787_i | I think they showed a half-cylinder lens though, or maybe that image is from a spectrometer building guide | 09:04 |
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| andares | Hey, I haven't been able to find much info on ways of assembling arbitrary DNA fragments in cells using something like light to control from the outside | 12:16 |
| andares | (So that you don't need to synthesize oligomers inorganically) | 12:17 |
| andares | Are there approachrs | 12:17 |
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| kanzure | andares: https://groups.google.com/group/enzymaticsynthesis | 12:19 |
| kanzure | chemical oligonucleotide synthesis is always organic chemistry | 12:19 |
| kanzure | also, dna fragment assembly is usually a separate technique from oligomer synthesis | 12:20 |
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| kanzure | e.g. see gibson assembly, cycling ligase reaction, extension pcr, etc. | 12:20 |
| kanzure | http://diyhpl.us/wiki/dna/synthesis/notes/ | 12:21 |
| haskel | guys, how can we push h+ as fast and as hard as we can? | 12:21 |
| haskel | I don't want to be sitting around, as the clock ticks away | 12:21 |
| kanzure | haskel: http://diyhpl.us/wiki/transhumanism has an overview, but other than that i would say cheap simplified dna synthesis, more open-source software and more open-source hardware. | 12:22 |
| haskel | kanzure, dna synthesis is just one step, how do you deliver that to all cells in the body? there needs to be cheap/robust/effective means of gene delivery | 12:23 |
| kanzure | why do you need to deliver to *all* cells in the body? what | 12:24 |
| haskel | kanzure, if you want a genetic upgrade, it seems reasonable you need for that to happen in most places of your body, unless you're targeting a specific organ or so | 12:24 |
| kanzure | if you need for some crazy reason (btw, i can't really think of a good reason) to deliver genomic changes to every single cell in the entire body, then the ideal method to use would be in-vitro fertilization and somatic cell nuclear transfer prior to the development of an embryo | 12:25 |
| haskel | kanzure, a bit late for us | 12:25 |
| haskel | kanzure, virus based gene delivery is as close as it gets | 12:25 |
| kanzure | well then stop making ridiculous demands like "every cell" | 12:25 |
| haskel | kanzure, dont set goals low | 12:25 |
| haskel | kanzure, it is theoritcally possible, not practically possible atm, but I think we can aim to get higher and higher coverage | 12:26 |
| kanzure | sounds like you don't actually want the "every cell" requirement? | 12:26 |
| haskel | kanzure, I think its a goal to work towards | 12:26 |
| haskel | kanzure, precision is key to modifying biology, let's rub a little cream here and there and that will do the trick won't get you anywhere | 12:27 |
| kanzure | which gene therapy technique uses a cream? i don't understand. | 12:27 |
| haskel | kanzure, not speaking about gene therapy in specific, but more generally, i.e. topical is not the solution | 12:28 |
| andares | Gibson assembly starts with small preexisting overlapping oligomers though right kanzure? | 12:30 |
| haskel | kanzure, my point is once you've synthesized a desired gene, what are you going to do next with it? | 12:30 |
| andares | Could those themselves be endogenously produced by bacteria and selected somehow? | 12:30 |
| kanzure | haskel: i don't think that gene therapy vectors are a useful contribution, unless you have a unique method. dna synthesis continues to be too expensive to generate anything in bulk. that's the bottleneck at the moment. | 12:31 |
| andares | Thanks for the link anyways | 12:31 |
| andares | Omg inkjet DNA synthesizer. Neat | 12:31 |
| haskel | kanzure, assume you take care of that, what then, now you have a ton of some desirable gene X, how do you get it to the cells that need that upgrade? | 12:31 |
| kanzure | haskel: "what are you going to do next" it doesn't matter. having the tool is extremely important to the debug/test/build lifecycle. turning on that lifecycle is way more important than giving everyone projects ahead of time. | 12:31 |
| fenn | i disagree, gene therapy vectors are very important even with "minor" changes to one or two nucleotides (very important if it's a disease-causing mutation) | 12:31 |
| kanzure | haskel: but if you insist, http://diyhpl.us/wiki/dna/projects/#igem-2013 | 12:32 |
| kanzure | haskel: i thought you were already aware of gene therapy... why are you asking me? | 12:32 |
| haskel | kanzure, I get your point, both are important, and from my understanding we can synthesize genes (perhaps not cheaply); so that bit is possible, but there is a delivery black hole that needs to be addressed | 12:33 |
| kanzure | fenn: gene therapy vectors are useful, but i don't see any suggestion here for how to make them cheaper or whethre their cost of synthesis is too high in the first place. so i'm not sure what you're trying to add to haskel's statements. | 12:33 |
| kanzure | gene therapy vectors are not a black hole | 12:33 |
| kanzure | http://diyhpl.us/~bryan/papers2/gene-therapy/ | 12:34 |
| fenn | i'm just saying the quantity of DNA is not the limiting factor with gene therapy | 12:34 |
| haskel | fenn, agree 100% | 12:34 |
| kanzure | why bring up quantity of dna? | 12:35 |
| haskel | kanzure, we need A and B for something to happen, A is possible (we can precisely construct DNA/RNA with precise codes) but not efficiently, B is still a bit elusive, so don't you think B deserves attention? | 12:35 |
| kanzure | i'm fairly happy with current gene therapy methods. | 12:35 |
| andares | I want to try some out | 12:36 |
| kanzure | why? | 12:36 |
| andares | RNAi seems rather accessible | 12:36 |
| andares | To make changes, of course! :) | 12:36 |
| andares | I am interested in knocking out DMRT1 | 12:36 |
| haskel | kanzure, so let's take the precise DNA/RNA codes we are pretty confident about, and deliver them? why not go for the full proof of concept? instead of focusing on the part thats done but maybe not as efficiently as you like | 12:36 |
| kanzure | i think you would have a neasier time finding someone to test gene therapy on you, than the difficulty you would face finding someone to give you gene therapy treatment for something specific that you choose. | 12:36 |
| haskel | kanzure, I don't believe that at all | 12:37 |
| kanzure | so i suggest if you really want to try gene therapy out for whatever reason, you focus on not picking the target type or treatment type. | 12:37 |
| kanzure | huh? there are already clinical trials for gene therapy, there just isn't "pick your own gene therapy target" out there at the moment, unless you do it yourself. but he said "i want to try some out", so i assumed he was talking about the thing i said (current stuff). | 12:37 |
| haskel | kanzure, I could get into dna synthesis right now if I wanted to, I have no idea how to start delivery | 12:37 |
| andares | Kanzure, I was thinking DIY (or rather, pipe-dreaming) | 12:38 |
| kanzure | er, what's wrong with the gene therapy literature i just linked you to? | 12:38 |
| kanzure | andares: i see. that makes more sense to me. | 12:38 |
| kanzure | andares: re: gibson assembly, see https://en.wikipedia.org/wiki/Gibson_assembly | 12:38 |
| andares | Basically, I'd need to get a 25bp DNA fragment synthesized. Then an RNA polymerase kit for producing dsRNA | 12:38 |
| andares | then produce SNALP vesicles using some lipids, that teflon machine and a micropore filter | 12:39 |
| andares | Then mix in the dsRNA with the SNALPs in solution, sonicate and inject | 12:40 |
| andares | (Hypothetically) | 12:40 |
| andares | Not really out of the realm of feasibility for DIY, just dangerous | 12:41 |
| haskel | kanzure, here's a target: telomerase gene therapy, we can precisely print he dna to create telomerase, so we're done right? since delivery is so easy and not an issue and easier than the former? | 12:41 |
| kanzure | haskel: because i don't see much value in "full proof of concept". i'm completely convinced that gene therapy works for certain definitions of work. telomerase gene therapy is completely unconvincing, though. | 12:41 |
| haskel | kanzure, because i don't see much value in "full proof of concept" are you serious? | 12:42 |
| kanzure | "full proof of concept" is fine if you have a good target-- but so far, nobody has a good target. | 12:42 |
| kanzure | yes, i'm completely serious. telemorase is not a good "proof-of-concept" target. | 12:42 |
| haskel | kanzure, so what's the point if we just want to toy around with and not do anything with it? | 12:42 |
| haskel | kanzure, why not full proof of concept? wtf | 12:42 |
| kanzure | yea if you don't fuck up your telomeres, you're just playing around | 12:42 |
| kanzure | wtf? | 12:42 |
| kanzure | http://diyhpl.us/wiki/genetic-modifications/ | 12:42 |
| haskel | kanzure, you just one to focus on one part of the bigger picture? which has been solved but not as efficiently as you like? | 12:43 |
| haskel | want* | 12:43 |
| kanzure | i think you're just making stuff up. | 12:43 |
| haskel | kanzure, please enlighten me | 12:43 |
| kanzure | evidence includes things like how you thought gene therapy was a black hole.... | 12:43 |
| kanzure | well i linked you to a bunch of papers on gene therapy | 12:43 |
| haskel | kanzure, it's far from solved buddy | 12:44 |
| haskel | kanzure, are you an expert in gene therapy? | 12:44 |
| fenn | "The DMRT1 gene is critical in the male sex determination and without this gene the default female characteristic takes over and male characteristic is slight or non-existent." i think i see where this is going... however, "When a DMRT1 gene is lost the most common disease is chromosome 9p deletion, which causes abnormal testicular formation and feminization." so you're too late, the damage has | 12:44 |
| fenn | been done, pick a different target | 12:44 |
| kanzure | haskel: fuck experts | 12:44 |
| haskel | kanzure, and there we go | 12:44 |
| andares | Kanzure, is the DNA inkjet printer being worked on actively? | 12:44 |
| kanzure | most experts can't even be bothered to read most of the literature- it's just authority bullshit | 12:44 |
| haskel | kanzure, for h+ to get anywhere things need to be approached scientifically, rigorously | 12:45 |
| kanzure | andares: uh depends on your definition of active! | 12:45 |
| kanzure | haskel: that has fucking NOTHING to do with "experts" you coward | 12:45 |
| andares | Fenn, you are mostly correct. But see http://www.nature.com/nature/journal/v476/n7358/full/nature10239.html | 12:45 |
| haskel | kanzure, so you've bothered to read most of the literature, and "experts" havent? | 12:45 |
| kanzure | haskel: but yes, i've read a lot about gene therapy. at the moment i wouldn't consider myself able to talk with gene therapy "experts" because my mind is full of fluff from dna synthesis and bitcoin, but i could brush up pretty quick i think. | 12:46 |
| andares | Here we show that sexual fate is also surprisingly labile in the testis: loss of the DMRT1 transcription factor3 in mouse Sertoli cells, even in adults, activates Foxl2 and reprograms Sertoli cells into granulosa cells. In this environment, theca cells form, oestrogen is produced and germ cells appear feminized. | 12:46 |
| kanzure | haskel: yeah, one of the things that aubrey de grey is quick to point out is that a lot of gerontology people don't actually read the literature. it's an important step to understand wtf is going on. | 12:46 |
| haskel | kanzure, why do you think gene therapy/delivery is done? | 12:46 |
| kanzure | haskel: anyway, it's 100% wrong to conclude that only "experts" can do science. correctness is something that exists independent of any institutionally-granted titles. | 12:46 |
| andares | Neat stuff, eh fenn? | 12:46 |
| kanzure | haskel: asking whether i am an "expert" is just.. stupid. who the shit cares whether i am an expert? what's important is my level of correctness. | 12:47 |
| haskel | kanzure, let's not get into semantics | 12:47 |
| haskel | kanzure, why do you think gene therapy/delivery is done? | 12:48 |
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| andares | Kanzure, are there people left around to talk about the design of the printer and give it a try completing it? ;) | 12:48 |
| kanzure | haskel: i am also completely unconvinced that i'm "focusing only on one part of a bigger picture". that's an absurd claim, and you need to give some serious evidence to back up that claim for me to accept it. | 12:48 |
| kanzure | andares: yes there are people around who have put in work towards that printer | 12:48 |
| kanzure | andares: at the moment the printer is on hold namely because we never found the right chemist to hire, and also because the assembly steps were not completely designed | 12:49 |
| kanzure | er, dna assembly, not machine assembly | 12:49 |
| haskel | kanzure, please enlighten me then, on what you think the bigger picture is, what you work on, and why that is moving things forward as fast as possible? | 12:49 |
| andares | Kanzure, ah for the annealing? | 12:49 |
| kanzure | haskel: you can't just wave your hand and get magical phenotype changes. that's not how biology works. nobody knows the exact mapping from genotype to phenotype for all possible changes. telomerase changes aren't going to produce easily observable effects for a long, long time. it's a bad "proof of concept". | 12:50 |
| andares | Plus isn't it pretty highly conserved? | 12:50 |
| kanzure | andares: dna annealing? no, not worried about hybridization. | 12:50 |
| andares | Oh! Neat then. What would you hire the chemist for? Design, or synthesis of the material? | 12:51 |
| kanzure | design, plus debugging of the chemistry | 12:51 |
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| kanzure | shit doesn't just work on first try. needs optimization and debugging. lots of stuff to go wrong. involvement during design stage also important. | 12:51 |
| andares | Ah, I see | 12:51 |
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| andares | Do grad students ever contribute to h+ projects like these off the clock? | 12:52 |
| kanzure | yes | 12:52 |
| fenn | there is no "off the clock" for grad students though... | 12:53 |
| andares | Haa, true | 12:53 |
| andares | Ah the lavish life of an industry programmer | 12:53 |
| haskel | kanzure, yet it's worked on mice, so what do you think is a better proof of concept; or do you think that doesn't matter, let's just focus on efficiently printing genes and not worry about anything else? | 12:54 |
| haskel | don't get me wrong, efficently printing genes is important, but I think there is a lot more to it | 12:54 |
| fenn | haskel the point of making lots of DNA cheaply is to speed up research in general | 12:54 |
| haskel | fenn, what research are we speeding up? | 12:55 |
| fenn | oh little problems like "what is aging" | 12:55 |
| fenn | "how does the brain work" etc | 12:55 |
| haskel | fenn, that's a bit vauge, printing genes efficiently does not equate to automatic results for "what is aging" | 12:55 |
| fenn | of course not | 12:55 |
| fenn | but if you're involved in active research you need to print a lot of genes | 12:56 |
| kanzure | dna synthesis is required because you must have dna molecules to build proteins, molecular machines, reprogram other cells in bulk. you need to do this at large-scale because we currently don't know (or may never know) the actual rules of biochemistry and biophysics. instead, we can iterate over large possibility spaces to find the features and functions that we desire. | 12:56 |
| kanzure | research prospects are v. important to speed up, but there's a lot of low-hanging engineering fruit, telomerase doesn't seem to be one of them- mouse results are OK, but i don't care. show me a better demo, like restoring color/infrared vision. | 12:57 |
| haskel | fenn, kanzure, we are able to print genes, and the efficiency is getting there very quickly: http://www.npr.org/sections/health-shots/2015/05/07/404460240/dna-printing-a-big-boon-to-research-but-some-raise-concerns | 13:01 |
| haskel | kanzure, " telomerase doesn't seem to be one of them- mouse results are OK" can you be a bit more specific? | 13:01 |
| haskel | kanzure, I used the specific example of a mouse to give some evidence, can you give a specific example why telomerase gene therapy isn't worth exploring atm?. | 13:02 |
| kanzure | the mouse results for telomerase modification seem to be OK results, but i don't have 200 years to wait to see whether that works for humans | 13:02 |
| haskel | specific example/reason whatever | 13:02 |
| kanzure | old people are already way too damaged for those results to matter anyway; it's like trying to fix a 747 crashing into the ocean by flipping a light switch or something. | 13:03 |
| fenn | haskel: i'm quite aware of cambrian genomics, i used to live with the chief scientist. after austen's death the investors got skittish and pulled out, last i heard the lab was being auctioned off at near scrap prices :( | 13:03 |
| kanzure | biological cause of aging is highly likely to be multi-faceted, aubrey's WELT approach for replacing all bone marrow seems much more useful approach, i don'-- | 13:03 |
| kanzure | oh what was the final price? | 13:04 |
| haskel | kanzure, lol that's fundamentally flawed logic, for you to know if any anti-aging therapy will work over 200 years, you will have to wait that 200 years to know, no matter how accurate the computer models/etc. are | 13:04 |
| kanzure | did they get the $4M they wanted | 13:04 |
| fenn | ask t12 | 13:04 |
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| kanzure | i don't think t12 likes me :-) | 13:04 |
| fenn | hum who knows | 13:04 |
| kanzure | yeah i shouldn't claim that, i haven't asked him | 13:04 |
| haskel | kanzure, lol that's fundamentally flawed logic, for you to know if any anti-aging therapy will work over 200 years, you will have to wait that 200 years to know, no matter how accurate the computer models/etc. are | 13:04 |
| fenn | i doubt they got the rescue money or t12 would be doing stuff in the lab instead of puttering around his home shop | 13:05 |
| haskel | kanzure, move up the ladder from mouse to monkey | 13:05 |
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| kanzure | haskel: not really; you can perform a lot of rejuvenation work on super old people. but telomerase ain't going to be enough. it's not enough to show results in aging populations, in my opinion. unless you do large-scale statistical studies i guess... but i don't care about populations, i care about individuals. | 13:05 |
| fenn | haskel: anyway after seeing many corporations implement stuff i wanted to do and then ultimately fail or "pivot" or just not do the right thing, i realized it's important to be able do things that need to be done even if it seems like someone else is doing that | 13:06 |
| kanzure | yeah my lack of progress re: speculation on anti-aging therapies has lead me to believe that cryonics will probably be working long before anti-aging. | 13:06 |
| kanzure | however, my "young blood rejuvenation" ideas might be an interesting approach towards super-old rejuvenation; however, requires large-scale selective breeding, and i still think cryonics is a better use of that sort of facility, ahead of "young blood rejuvenation" breeding attempts. | 13:07 |
| haskel | kanzure, so you want dramatic results like a old person becoming "young" again, and the best approach to that is investigating printing dna (which is done, though not as efficient as you like, though companies are bridging that efficiency gap very very quickly) | 13:07 |
| kanzure | no, i don't want old->young, i think that's stupid | 13:07 |
| kanzure | dna synthesis is a requirement for working with biological systems. no exception. | 13:08 |
| haskel | kanzure, and dna synthesis is done | 13:08 |
| kanzure | that there are companies that sell you 1500 bp dna for $5000 is not interesting... that's useless. you can't do anything interesting with that unless you have like $200 billion. | 13:08 |
| haskel | kanzure, the efficiency bit will get there very soon with a lot of for-profit companies at it | 13:08 |
| kanzure | which companies do you have in mind? cambrian genomics? oops. twist biosciences? itdna? | 13:09 |
| haskel | kanzure, copying and synthesizing dna are two different things buddy, you pay for 1 synthesized bit, replicate it for much cheaper chemically | 13:09 |
| fenn | i still want a desktop dna synthesizer | 13:09 |
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| haskel | fenn, sure I do to, but then what? | 13:09 |
| kanzure | haskel: yes, i'm aware of the differences. i'm talking about de novo dna synthesis. | 13:09 |
| kanzure | haskel: we have already explained to you the "then what" part. what was wrong with the previous explanations? | 13:10 |
| haskel | kanzure, you did not explain, you said gene therapy is done, I asked you about that two times why you think it's done, care to elaborate? | 13:10 |
| kanzure | we seem to be having two wildly different conversations...... | 13:10 |
| kanzure | no, "then what" was not a question about gene therapy. you asked "then what" about desktop dna synthesis. | 13:11 |
| fenn | it's way past my bedtime and this conversation is way too confrontational and too fast to keep up with | 13:11 |
| kanzure | can't blame you, seeya | 13:11 |
| haskel | fenn, later, sorry if it is coming off as conforntational, just trying to understand | 13:11 |
| andares | Kanzure, re: DNA synthesis. I'm still not sure I understand if there are any approaches that don't involve externally synthesizing the DNA and then using a vector | 13:12 |
| kanzure | haskel: i think you would be wise to drop the accusational tone and look more closely at existing technology. also, you should not assume that telomerase is a magic silver bullet. results come from broad technology fundamentals building up over time and technical tools becoming better, not from riding a magic bullet into the singularity. | 13:12 |
| andares | I was thinking along the lines of toggling in a sequence via light pulses at a bacterial colony | 13:12 |
| andares | The Gibbs method seems like it could be a useful component of this | 13:13 |
| kanzure | andares: https://groups.google.com/group/enzymaticsynthesis discusses some theoretical ways to do in vivo dna synthesis as well as other ways to hijack proteins to synthesize both dna, rna and proteins; for example, electronically-controlled and light-controlled polymerase have been proposed, unfortunately nobody knows how to make that work yet. | 13:13 |
| andares | Ah, missed that link before. Thanks | 13:13 |
| haskel | kanzure, telomerase is one direction of many agreed, I mentioned that to give a specific example when you said there are no good gene therapy targets atm | 13:14 |
| * fenn puts in a good word for GDF11 | 13:14 | |
| kanzure | yes and i mentioned http://diyhpl.us/wiki/genetic-modifications/ but it looks like neither of you follow any god damn links :-/ | 13:14 |
| andares | https://groups.google.com/forum/m/#!topic/enzymaticsynthesis/DApMjXx8gS4 | 13:15 |
| andares | This seems exactly like what I was looking for | 13:15 |
| kanzure | andares: unfortunately that approach isn't exactly what i would call "promising" at the moment....... | 13:15 |
| andares | Ah | 13:15 |
| kanzure | oh, the tdt one | 13:15 |
| kanzure | ok | 13:15 |
| kanzure | that's not what i was thinking of | 13:15 |
| kanzure | because it's not in vivo | 13:16 |
| kanzure | haskel: you should read all of these http://diyhpl.us/~bryan/papers2/gene-therapy/ http://diyhpl.us/~bryan/papers2/longevity/ http://diyhpl.us/~bryan/papers2/bio/ http://diyhpl.us/~bryan/papers2/neuro/ | 13:17 |
| fenn | andares i think you'll have to either be very clever with multiple unusual DNA polymerases, or solve the protein folding problem and build a light-directed DNA synthase from scratch | 13:17 |
| kanzure | and http://diyhpl.us/~bryan/papers2/DNA/ http://diyhpl.us/~bryan/papers2/polymerase/ for good measure | 13:17 |
| kanzure | andares: this one also applies to you, http://diyhpl.us/~bryan/papers2/polymerase/ | 13:17 |
| andares | Yeah, and I just saw one thread about hijacking telomeraaw | 13:18 |
| haskel | kanzure, I understand there are technical challenges that need to be overcome to print dna, but creating copies is cheap, so with existing tech we can for relatively low cost print dna, then make as many copies as we want to play around with | 13:18 |
| kanzure | haskel: the problem is one of programming ("which changes?") | 13:19 |
| andares | Apparently it appends 6 nts, and through some magic you can make it an arbitrary 6 | 13:19 |
| haskel | kanzure, that's an informatics problem | 13:19 |
| kanzure | no... it's not an informatics problem. | 13:19 |
| haskel | kanzure, ...... | 13:19 |
| kanzure | bioinformatics is not going to tell you which changes you want that don't already exist | 13:19 |
| fenn | cue bad metaphor quote | 13:19 |
| kanzure | the jrayhawk quote? | 13:19 |
| haskel | kanzure, so what will tell us if not computational methods that can make sense of the huge web of gene/protein etc. interactions? | 13:20 |
| kanzure | large-scale dna synthesis of millions of competing different sequences. | 13:21 |
| andares | thanks again.for all these links, kanzure. You're the best! | 13:21 |
| haskel | kanzure, now is the 1st time you give me a direct statement on how large-scale dna synthesis can be used for practical gain | 13:21 |
| haskel | kanzure, so you're approach is to make dna printing cheaper, print out all sorts of de novo dna, and try them out? | 13:22 |
| kanzure | sort of? i mean, the other reason to have large-scale dna synthesis is for genome synthesis reasons. and then test variations of genomes in microbes and so on. these can be symbiotes of most kinds. | 13:23 |
| kanzure | but also many other uses of microbial genome synthesis | 13:23 |
| haskel | kanzure, I don't disagree with that, I think you would also need methods of automatically doing that, so you can try out millions of different things in millions of different cells, and then automatically keep track of results | 13:23 |
| kanzure | such as downloading genes from the interwebs (instead of begging for plasmids from gated communities) | 13:23 |
| kanzure | yes, it's true that you need to use automation, see http://diyhpl.us/~bryan/papers2/microfluidics/ | 13:24 |
| haskel | kanzure, thank you for clarifying your approach, that was what I was trying to get at with "what next", so the what next is: print all sorts of de novo dna and try them out, brute force an understanding of life | 13:24 |
| kanzure | i already mentioned large-scale dna synthesis as necessary for exploring possibility space, ctrl-f on http://gnusha.org/logs/2015-11-16.log | 13:25 |
| kanzure | for my own purposes i don't really care about understanding (although it's important), i care about engineering | 13:25 |
| kanzure | so e.g. large-scale dna synthesis can be used for the construction of molecular nanotechnology based on proteins | 13:25 |
| haskel | kanzure, sure bruteforce the code that gives you the desired result then? | 13:25 |
| kanzure | https://github.com/kanzure/nanoengineer | 13:25 |
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| fenn | "brute force" is not the goal, it's just being able to do an experiment without waiting around for days or months to see a result, and blowing your entire budget on a single experiment | 13:26 |
| andares | There's easyish ways of shotgun assembling completely random ~6nt DNA fragments right? | 13:26 |
| kanzure | fenn i am surprised your primarily research angling here... | 13:26 |
| kanzure | andares: er, i think you need at least 8-10 bp nt... | 13:27 |
| andares | Ah | 13:27 |
| andares | And then you sort with that microbead array + laser? | 13:27 |
| kanzure | well, that was cambrian genomics' approach... for the dna synthesizer discussed often in here, approach for dna assembly is still up in the air..... kinda open problem. | 13:28 |
| fenn | probably something like light-directed manipulation of droplets or beads though | 13:29 |
| fenn | just because of the huge numbers involved | 13:29 |
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| kanzure | i dunno, i'm still fond of my ping pong ball sorting machine concept | 13:29 |
| haskel | kanzure, fenn, but you need a system, you can't manually try out all sorts of de novo dna, unless you are using computational methods to engineer the de novo dna, so if you are not using computational methods, you need automation to try out the de novo dna, and if you do that in a large enough scale, then it is essentially brute force | 13:30 |
| kanzure | nobody disagreed about calling it bruteforce | 13:30 |
| kanzure | fenn's disagreement was with your claim that bruteforcing was the goal | 13:30 |
| fenn | i guess kanzure and i have a slightly different vision | 13:30 |
| kanzure | well, reducing research costs is important, but i want to actually use this stuff for my own insane engineering reasons | 13:31 |
| fenn | i would use computational methods to engineer the DNA | 13:31 |
| kanzure | i am v. selfish | 13:31 |
| fenn | however we also need to do experiments to develop the computational methods | 13:31 |
| andares | Kanzure, hehe me too. What do you think about self-experimentation BTW? | 13:31 |
| kanzure | self-experimentation is fine as long as your experiment isn't stupid | 13:31 |
| andares | My experiment probably would be | 13:32 |
| kanzure | experimental design is important | 13:32 |
| fenn | don't be a "grinder" and you're probably fine | 13:32 |
| andares | Unless I can degrade the RNAi somehow | 13:32 |
| kanzure | if you want to do stupid stuff, that's fine, but oyu should fully admit to said stupidity, and not smear the good name of science or other things | 13:32 |
| haskel | fenn, bingo I can agree with the computational/experiment feedback loop you propose which would benefit off of cheap de-novo synthesis | 13:32 |
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| andares | Kanzure , where do you learn about experimental clinical protocol for gene therapy? | 13:33 |
| haskel | fenn, this is what I was trying to get at, we dont build cars for the hell of it, we build cars to get from point A to point B | 13:33 |
| andares | Like E.g. I'd try it out on biopsy tissue first | 13:33 |
| kanzure | andares: you should start with a community college biology lab class | 13:33 |
| kanzure | haskel: speak for yourself, building cars for the hell of it is perfectly fine | 13:34 |
| andares | I was thinking of trying to volunteer at a UW lab | 13:34 |
| andares | And auditing some bio classes | 13:34 |
| haskel | kanzure, I can appreciate that sentiment as well, but I think h+ has very specific practical goals ;) | 13:34 |
| kanzure | biology classes can be done online, although lab classes often it's better in person | 13:34 |
| Aurelius_Work | kanzure : I was thinking of getting a supercar kit at some point | 13:34 |
| kanzure | Aurelius_Work: what the hell stopped you | 13:34 |
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| Aurelius_Work | kanzure : I have other things to do in my spare time like play fallout and learn scheme and ruby | 13:35 |
| Aurelius_Work | (and I don't have a garage) | 13:35 |
| Aurelius_Work | and I want it to be <5% of my assets | 13:35 |
| Aurelius_Work | lol | 13:35 |
| kanzure | can't you abuse a friend's garage? seems like american way. | 13:35 |
| fenn | andares i recommend taking a virology lab if you can, most other college classes are worthless | 13:35 |
| kanzure | virology why? | 13:35 |
| kanzure | why not uh, hm, molecular biology lab protocol class? | 13:36 |
| fenn | because you work with viruses and mammalian tissue culture, both of which are not used at all in any other class | 13:36 |
| Aurelius_Work | kanzure : I want me some garage power armor :P | 13:36 |
| andares | Well, I do want a strong theoretical background | 13:36 |
| kanzure | theory can be picked up outside of class... coursera, youtube, books, whatever. | 13:36 |
| kanzure | class does not teach you how to do good science theory or speculation | 13:36 |
| fenn | wikipedia | 13:36 |
| kanzure | wookiepedia too | 13:37 |
| andares | That's how I've been learning. | 13:37 |
| andares | Lol | 13:37 |
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| andares | Have y'all seen this? http://www.technologyreview.com/view/543491/now-you-can-genetically-engineer-living-cells-with-a-home-kit-should-you/ | 13:38 |
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| kanzure | andares: https://groups.google.com/group/diybio | 13:38 |
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| kanzure | fenn: tissue culture is good reason. i suppose i would also suggest synthetic/organic chemistry labs too, since those methods are highly relevant to sterility and synthesis.. | 13:40 |
| fenn | no, synthetic organic chemistry is something completely different than biology | 13:40 |
| fenn | it's just a weeding-out course for pre-med students | 13:40 |
| haskel | kanzure, and the channel's name is hplus**roadmap** which is essentially what I was trying to get at lol, thanks for answering my questions, fenn thank you as well, I think it is important to speed up the computational/experimental loop with cheap de novo synthesis, but I think we must also explore more immediate gains such as telomerase gene therapy etc. which involves getting the delivery part right, which I think is no where near done | 13:40 |
| kanzure | haskel: re: the channel, see http://diyhpl.us/wiki/hplusroadmap and http://diyhpl.us/wiki/transhumanism | 13:41 |
| kanzure | instead of telomerase i suggest looking at http://diyhpl.us/wiki/genetic-modifications/ and http://diyhpl.us/wiki/dna/projects/#igem-2013 etc | 13:41 |
| fenn | i am not convinced that telomerase is important, but gene therapy needs some work for sure | 13:42 |
| haskel | fenn, agreed, I definitely think telomerase is worth exploring, it's had an effect on mice, and it has a clear physical link to cell aging, and there is a clear method to restore telomeres | 13:43 |
| haskel | it sounds low hanging fruit to me in terms of things to be explored | 13:43 |
| fenn | you can say the same thing about choline | 13:43 |
| andares | I really really hate the way Amino calls genes "apps" | 13:43 |
| fenn | i really hate anything "design-centric" | 13:44 |
| andares | Everything about the style of this project is infuriating | 13:44 |
| kanzure | that's the only thing you hate about "amino"? | 13:44 |
| kanzure | yes, it's infuriating | 13:44 |
| andares | I haven't read what it actually contains yet | 13:44 |
| andares | Can't play audio | 13:44 |
| haskel | fenn, what is choline's physical link to cell aging? | 13:44 |
| kanzure | perhaps you shouldn't | 13:44 |
| kanzure | andares: only pain and hatred will you find that way | 13:44 |
| fenn | andares it contains "design" | 13:44 |
| kanzure | andares: you could read hplusroadmap logs to see our previous analysis of "amino" | 13:45 |
| andares | Where's File->Print? :p | 13:45 |
| andares | I'll go back and read for sure, on phone atm | 13:45 |
| kanzure | "menus? this is design, only buttons. in fact, only one button." | 13:45 |
| fenn | haskel: extends mouse lifespan 25%, increases insulin sensitivity and gene methylation, clear method to getting more choline into the metabolism | 13:46 |
| fenn | well DMAE but they're practically the same thing | 13:46 |
| andares | Oh, do you send away for your "app" to be synthesized? | 13:47 |
| haskel | fenn, but choline is involved in a lot of things, whereas literally the only purpose of telomerase is to restore telomeres which shorten each time the cell divides, that can't be good for your genes | 13:48 |
| fenn | uh that doesn't sound like the biology we all know and love | 13:49 |
| fenn | "the only purpose" is your simplified mental model | 13:49 |
| Aurelius_Work | 'literally the only purpose' makes me twitch and I don't even know/like biology | 13:50 |
| FourFire | ... | 13:50 |
| haskel | fenn, it's been a while for me, is there any other established role of telomerase ? | 13:50 |
| FourFire | haskel, the mammilian cell isn't even fully mapped, by anyone. | 13:50 |
| fenn | i have no idea what telomeres are for | 13:50 |
| fenn | (yes i know about the hayflick limit) | 13:50 |
| haskel | fenn, they are the buffer zone to your actual genes | 13:51 |
| haskel | fenn, each time the cell divides they get a bit shorter | 13:51 |
| FourFire | AFAIK the telomere is a correlation assumption: "oh the dna gets fucked up when these things run out, then that must be why blah blah" | 13:51 |
| haskel | FourFire, well dna gets shorter, so eventually that will eat into useful genes right? | 13:52 |
| haskel | FourFire, so a way to prevent that is to lengthen the telomeres, which I understand telomerase will do | 13:52 |
| FourFire | haskel, sure, but it's a massive assumption to believe that is the sole, or evne main purpose of a given molecule. | 13:52 |
| kanzure | haskel: what exactly was your objection to whole body stem cell replacement therapies? e.g. http://www.sens.org/research/research-blog/aged-stem-cells-and-niches-rejuvenated-systemic-factors-implications-wilt | 13:53 |
| kanzure | oh wait, bad link | 13:53 |
| kanzure | don't click oh god we're all gonna fucking die | 13:53 |
| haskel | kanzure, I have no objection as long as it is solid science, and practical | 13:54 |
| kanzure | .title https://www.youtube.com/watch?v=qcRDiPeNyas | 13:54 |
| yoleaux | WILT: taking cancer seriously enough to really cure it - YouTube | 13:54 |
| kanzure | uh apparently i don't have a WILT paper... wtf. | 13:54 |
| fenn | yeah linking to a video is surprising from you | 13:54 |
| kanzure | well, i literally can't find a thing about WILT | 13:55 |
| haskel | FourFire, is there any other established role of telomerase? (there may be some other role telomerase plays, but I think atm that is the only role we have established) | 13:55 |
| kanzure | and sens foundation is still around | 13:55 |
| kanzure | so lack of availability of WILT explanation is really surprising | 13:55 |
| fenn | 'telomeres may have a role in the prevention of cancer. This is because the telomeres act as a sort of time-delay "fuse"' | 13:55 |
| FourFire | haskel, I don't know, I think it's unknown in general, a great deal about Mammal cells is unknown in general | 13:56 |
| kanzure | world-class scientific modeling there, folks | 13:56 |
| haskel | fenn, but is that not through the same mechanism of action, keep telomeres long? | 13:56 |
| fenn | aubrey's solution is to kill telomerase because tumors use it to bypass the hayflick limit | 13:56 |
| kanzure | and also replace all yer stem cells once a decade because loldamage | 13:56 |
| haskel | fenn, aubrey is not god, and in fact he looks like the spitting image of a snake oil salesman to me | 13:57 |
| kanzure | nobody claimed he was god | 13:57 |
| kanzure | perhaps you are confusing him with father time? | 13:57 |
| fenn | well whatever, i'm just explaining what WILT is so you don't have to watch a video | 13:57 |
| haskel | fenn, sorry for coming off a bit harsh, thanks for the explanation | 13:58 |
| FourFire | I want to substantially change how DNA information is stored | 13:58 |
| kanzure | FourFire: have you considered using molecules? | 13:58 |
| haskel | FourFire, indeed, my point is simply that atm it is the only established role | 13:58 |
| haskel | FourFire, which is in contrast to many other chemicals/proteins which play multiple multiple roles | 13:59 |
| FourFire | I'd like to, if I can do it quickly enough, find a way to store the three bit encoding across a parity of multiple DNA molecules for each given sequence (so duplicate chromosomes) but I don't know exactly how that's going to work. | 13:59 |
| FourFire | haskel, sure. | 13:59 |
| FourFire | kanzure, of I'm not planning on removing anything, just adding functionality | 14:00 |
| fenn | forward error correction codes? | 14:00 |
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| fenn | ok sleep for real now | 14:04 |
| kanzure | fenn: yeah i know that anders didn't write that article, but i was talking about nick bostrom when i made that claim, not anders. | 14:09 |
| kanzure | ("what's so dumb about bostrom" was the prompt) | 14:09 |
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| kanzure | "The electrical implants aren’t turned on to provide chronic brain stimulation until two weeks after DBS surgery, which allows the brain to heal from the trauma of the surgery, which causes inflammation and brain shift of up to six millimeters." | 14:37 |
| kanzure | "DBS surgery... 8% risk of bleeding in the brain; 8% chance of stroke or permanent neurological deficits; 15% chance of infection; 5% risk of hemorrhage; 2% risk of seizure." | 14:38 |
| kanzure | man it's almost like they should listen to me when i tell them to use remote ultrasound | 14:39 |
| kanzure | "Given the problems with DBS research, and with growing evidence of bias in much clinical trial research conducted, it's perhaps no surprise that many of the doctors and specialists involved in these DBS trials were paid by device manufacturers and/or provided with research funding. For instance, among the investigators involved in the initial Canadian trial, Dr. Helen Mayberg holds patent and licensing rights for the treatment of ... | 14:41 |
| kanzure | ... depression through DBS of the Cg25. Neurosurgeon Dr. Andres Lozano is a consultant for Medtronic and holds intellectual property rights in DBS; in 2010, he founded of a DBS investigational company called Functional Neuromodulation, a partner company of Medtronic." | 14:41 |
| kanzure | eh, i don't think that's a big concern, unless you are looking at disease treatment outcomes. but it seems rather hard to lie about whether stimulation is occurring? | 14:41 |
| kanzure | from http://www.madinamerica.com/2015/09/adverse-effects-perils-deep-brain-stimulation-depression/ | 14:41 |
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| kanzure | oh they choose very strange entrypoint choices... http://www.madinamerica.com/wp-content/uploads/2015/09/image-of-insert-300x274.jpeg | 14:43 |
| kanzure | nah probably fine just jam it right through the frontal cortices, people don't need neural integrity there, right? | 14:44 |
| kanzure | cool "Regarding the IRB, the motion stated that “Stanford’s IRB is immune from liability under California’s Peer Review Statute Civil Code." | 14:47 |
| kanzure | "Burr hole cover for cranial surgery" http://www.google.com/patents/US5961519 | 14:49 |
| nmz787_i | /me electrolytes, it's what polymerase craves | 14:52 |
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| nsh | hey kanzure | 14:53 |
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| kanzure | nsh: sup | 14:53 |
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| nsh | idea: write a script on crontab that tracks the citation numbers for all the papers you have archived, be configurable to set alerts on any change in delta-cites over some nested periods above some threshold | 14:54 |
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| kanzure | inverse is also important | 14:54 |
| kanzure | things that people are /not/ citing | 14:54 |
| nsh | right | 14:54 |
| nsh | especially if displaced | 14:55 |
| kanzure | hm | 14:55 |
| nsh | so you can determine if things are just falling off, or being replaced with a better reference | 14:55 |
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| kanzure | sorta inbetween thing i do regularly is look up papers by researcher | 14:55 |
| nsh | former implies loss of currency/interest; latter implies better synopsis | 14:55 |
| kanzure | to see what they are up to | 14:55 |
| * nsh nods | 14:55 | |
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| kanzure | but by-researcher is bad approach because most people are one-hit wonders | 14:55 |
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| nsh | aye | 14:56 |
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| kanzure | http://www.prutchi.com/pdf/implantable/nuclear_pacemakers.pdf | 19:06 |
| kanzure | oh they actually implanted and used nuclear pacemakers | 19:08 |
| kanzure | huh.. | 19:08 |
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| kanzure | i wonder who those nuclear pacemaker recipients are | 19:11 |
| kanzure | "no make mine nuclear, please" | 19:11 |
| drethelin | heh | 19:12 |
| drethelin | I thought the nuclear ones came first actually | 19:12 |
| drethelin | because that was the only way to get a long-lasting battery for a while | 19:12 |
| drethelin | before induction charging maybe? | 19:12 |
| kanzure | looks like modern versions are just lithium-ion batteries :-/ | 19:13 |
| kanzure | no induction power transfer | 19:13 |
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| nmz787_i | sup | 19:14 |
| kanzure | just putting some plutonium dangerously close to hearts | 19:14 |
| nmz787_i | apparently the prodigy had a new album this year | 19:14 |
| nmz787_i | ah | 19:15 |
| nmz787_i | word | 19:15 |
| kanzure | i wonder if that sort of implant would make you subject to the export/commerce control rules | 19:16 |
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| c0rw1n | my grandma had a nuclear pacemaker ^_^ | 19:29 |
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| kanzure | why? | 21:17 |
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| kanzure | http://diyhpl.us/~bryan/papers2/cryonics/rana-sylvatica/ | 21:27 |
| kanzure | phil suggests we should sequence this frog because nobody has sequenced this frog yet | 21:28 |
| kanzure | i am willing to chip into cover those costs if someone would be willing to arrange the mundane details of actually catching a few of those | 21:28 |
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| kanzure | phil says he wrote a grant a few years ago to pay for this but had to justify it with various diabetes reasons... man this world sucks. | 21:32 |
| kanzure | "my point is there is a very complex mechanism that lets it survive 2 or 3 degrees colder temperature. so the question is how valuable this is for cryopreservation; maybe a lot, since it does allow circulation to stop." | 21:35 |
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| kanzure | jrayhawk: secure.diyhpl.us cert expired a few days ago, could you fix? | 22:18 |
| jrayhawk | ugh, okay | 22:22 |
| -!- drewbot__ [~cinch@ec2-174-129-78-214.compute-1.amazonaws.com] has quit [Remote host closed the connection] | 22:27 | |
| -!- drewbot [~cinch@ec2-54-147-166-114.compute-1.amazonaws.com] has joined ##hplusroadmap | 22:28 | |
| -!- poppingtonic [~Thunderbi@unaffiliated/poppingtonic] has joined ##hplusroadmap | 22:49 | |
| -!- haskel [~haskell@203.188.241.206] has left ##hplusroadmap ["Leaving"] | 23:00 | |
| -!- FourFire [~FourFire@185.7.192.138] has joined ##hplusroadmap | 23:09 | |
| -!- Act [uid89656@gateway/web/irccloud.com/x-hqdwskczjyrckcxc] has joined ##hplusroadmap | 23:16 | |
| -!- yash [~yashgarot@2602:306:35fa:d500:f5e0:f867:a11d:8d52] has quit [Quit: Leaving] | 23:26 | |
| -!- Darius [~quassel@cpe-158-222-160-123.nyc.res.rr.com] has quit [Remote host closed the connection] | 23:38 | |
| --- Log closed Tue Nov 17 00:00:27 2015 | ||
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