| --- Log opened Mon Jan 23 00:00:28 2012 | ||
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| kanzure | god i'm tired of everyone and their mom saying "I SHOULD CREATE A PHPBB FOR TRANSHUMANISMS!!" | 08:31 |
|---|---|---|
| kanzure | No, you shouldn't, and you should get back to work on projects | 08:32 |
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| archels | But what if your project is creating a phpBB instance for transhumanisms? | 08:41 |
| kanzure | what the heck does that do? hooray yet another place to talk about transhumanism? | 08:43 |
| archels | 'Transhumanism' is just so general a topic. | 08:44 |
| kanzure | it'll probably be a bunch of ethics debates | 08:45 |
| archels | yeah, stop mentally masturbating about the subject and go invent the next generation of <insert technology here> already. | 08:47 |
| kanzure | doesn't have to be next-gen | 08:48 |
| kanzure | that would be nice and cool and all | 08:48 |
| strages_work | out of curiosity, what technologies are you working on? | 08:49 |
| kanzure | mostly software-related projects at the moment | 08:49 |
| kanzure | then all this stuff http://diyhpl.us/cgit/ | 08:49 |
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| strages_work | oooh :D | 08:51 |
| strages_work | nice list | 08:51 |
| kanzure | strages_work: feel free to do things here http://diyhpl.us/~bryan/papers2/diytranshuman_projects.v4.html | 08:52 |
| * archels computational neuroscience thesis | 08:53 | |
| kanzure | slacker... | 08:53 |
| kanzure | :) | 08:53 |
| strages_work | I'll run the list by some of the hackerspace folks I know, should speed stuff up should anyone bite | 08:54 |
| strages_work | I'm working on a mesh network setup for emergency use cases using off the shelf equipment. | 08:55 |
| strages_work | then buidling a quick communication infrastructure on top of that | 08:56 |
| strages_work | dns, captive portal, wiki, message board, chat, and crude voip | 08:57 |
| eudoxia | what about an h+ wiki? | 08:57 |
| kanzure | eudoxia: git clone git://diyhpl.us/srv/git/diyhpluswiki.git | 08:57 |
| kanzure | this controls http://diyhpl.us/wiki/ | 08:57 |
| kanzure | syntax is markdown | 08:58 |
| eudoxia | how do I use that | 08:58 |
| eudoxia | there's no search box ;_; | 08:58 |
| kanzure | do you know how to use git | 08:58 |
| eudoxia | never needed version control so no | 08:58 |
| kanzure | what do you think a wiki is? o.o | 08:58 |
| eudoxia | fine | 08:59 |
| eudoxia | never used it directly | 08:59 |
| kanzure | well, first, it's not a search box, but rather a way to keep a copy and edit it | 08:59 |
| kanzure | then you can push back changes | 08:59 |
| kanzure | would you like an account? | 08:59 |
| eudoxia | how do I get an index of the pages? | 09:00 |
| eudoxia | or does it work, uh, not like that | 09:00 |
| kanzure | i don't think there's currently an index module installed | 09:00 |
| kanzure | jrayhawk: right? | 09:00 |
| kanzure | eudoxia: the quickest way would be to look at the repository contents under cgit | 09:00 |
| kanzure | http://diyhpl.us/cgit/diyhpluswiki/ | 09:00 |
| eudoxia | If I git clone it do I get a bunch of folders and files with the contents? | 09:01 |
| kanzure | yes | 09:01 |
| eudoxia | great | 09:01 |
| kanzure | with their revision history | 09:01 |
| kanzure | what's your email? | 09:02 |
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| eudoxia | kanzure: eudoxiahp@gmail.com | 09:02 |
| kanzure | ah, hell | 09:02 |
| kanzure | well whatever | 09:02 |
| kanzure | see pm | 09:02 |
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| kanzure | ok that's all. | 09:04 |
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| kanzure | hi Z_ | 09:04 |
| Z_ | Hi all. First time here. | 09:05 |
| kanzure | eudoxia: can you play with our guest :3 | 09:05 |
| kanzure | i'll bbl | 09:05 |
| eudoxia | oh I feel honored | 09:06 |
| eudoxia | hey Z, how did you come across this channel= | 09:06 |
| eudoxia | ?* | 09:06 |
| Z_ | Sorry, was AFK for a min. Transhumanists I know via FB is the answer to your question. | 09:08 |
| Omega | I don't know how I found this place | 09:10 |
| eudoxia | and how long have you been interested un transhumanism? | 09:11 |
| Z_ | My turn - gonna ask a few things here. Approximate number of people who use this channel (total and at a given time), level of involvement and activity (average) of members, topics discussed, ultimate purpose of this channel? | 09:12 |
| kanzure | Z_: are you zeid | 09:13 |
| eudoxia | Doesn't fluctuate much from this number, either sporadic activity or long interesting discussions (Log size is proportional to this), the topic + lots of programming and biology, don't know | 09:13 |
| eudoxia | kanzure, what is the ultimate purpose of this channel? | 09:15 |
| Z_ | Yes. | 09:15 |
| kanzure | eudoxia: transhumanist tech development | 09:15 |
| Z_ | In order for that to be achieved, a focused collective of some sort (not necessarily geographically proximal) has to be formed. Kanzure, have you spoken to davidad? | 09:17 |
| kanzure | yes i know davidad | 09:17 |
| kanzure | why is everyone always telling me about forums, collectives, social media, marketing, promotion | 09:18 |
| kanzure | look, we have that covered- everyone and their dog knows about it | 09:18 |
| kanzure | hiveminds and memes | 09:19 |
| kanzure | knowing about these concepts isn't rare | 09:19 |
| Z_ | How do you envision significant tech development to occurr in the absence of unity of purpose? | 09:19 |
| kanzure | why are you assuming absence of unity of purpose | 09:20 |
| kanzure | that's somewhat insulting heh | 09:20 |
| Z_ | I have seen no evidence to the contrary; you yourself indicated your frustration with the 'talk'. | 09:22 |
| kanzure | yeah, i'm just not interested in forums of transhumanist philosophers, ethicists, riskists, etc. | 09:22 |
| Z_ | And I wasn't talking about hive minds and social media at Ll. | 09:22 |
| kanzure | they've been around forever writing position papers | 09:22 |
| Z_ | All* | 09:22 |
| kanzure | Z_: true, i was grouping yuo together with a stereotype that we see in here | 09:23 |
| Z_ | Stereotyping is illogical. Don't assume anything about me. | 09:23 |
| kanzure | i could say the same about your assumptions of tech development? | 09:24 |
| kanzure | oh well | 09:24 |
| kanzure | i should just write a faq | 09:24 |
| Z_ | I'm not interested in ivory tower debate either. I am, however, interested in practical , real, change. | 09:24 |
| kanzure | change? | 09:24 |
| kanzure | ok how about you pick a particular project | 09:25 |
| kanzure | like "I want to build a computer" | 09:25 |
| Z_ | Look, we can argue and bicker, or try to find common ground. The choice is yours. | 09:26 |
| kanzure | um, we're not arguing | 09:27 |
| kanzure | second, it sounds like you really really disagree with me about tech development | 09:27 |
| kanzure | but maybe you're not interested in that | 09:27 |
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| kanzure | maybe your interests are something else | 09:27 |
| Z_ | I mean significant tech develop,ent. That does not happen with DIY projects that anyone with a brain can do. Serious tech requires serious resources, and that requires a dedicated community. And that requires building such a comunity | 09:28 |
| jrayhawk | oh yeh, i should add search | 09:29 |
| kanzure | jrayhawk: or index | 09:29 |
| eudoxia | thanks jrayhawk | 09:29 |
| kanzure | eudoxia: jrayhawk is the sysadmin that picks up my slack | 09:29 |
| Z_ | Pardon the typos, iPads and Orc don't mix well. | 09:29 |
| Z_ | Irc | 09:29 |
| kanzure | you're on an ipad? | 09:29 |
| kanzure | Z_: so, even "serious tech" is done by individuals | 09:30 |
| kanzure | it might not be marketed as diy | 09:30 |
| kanzure | but it's still people behind it | 09:30 |
| kanzure | regardless of community | 09:30 |
| jrayhawk | ugh, my auth model does not do well with search. i should redo that. | 09:31 |
| kanzure | i don't know; you're welcome into this community, as you know | 09:31 |
| Z_ | Sure, you can have tech created by a random group of people. My point is, if you want specific tech, especially the kind that runs contrary to popular interests, you need a group of people who share some sets of goals in common. | 09:32 |
| kanzure | yes, you've found us | 09:32 |
| kanzure | do you want to work on a specific project with us? there's lots going on | 09:33 |
| jrayhawk | the last commit to skdb.git is almost a year old! | 09:33 |
| Z_ | My primary interest is AGI. yours? | 09:33 |
| kanzure | jrayhawk: you should bug fenn | 09:34 |
| kanzure | Z_: human enhancement | 09:35 |
| Z_ | Biological/genetic or artificial/cybernetic? | 09:36 |
| kanzure | http://diyhpl.us/~bryan/papers2/ | 09:36 |
| kanzure | i focus on most aspects | 09:36 |
| kanzure | i don't really make much progress with agi, but i do have a partialness towards computational neuroscience and whole brain emulation | 09:37 |
| kanzure | or partial brain emulation as it were.. | 09:37 |
| Z_ | How's blue brain going? | 09:37 |
| kanzure | i think they are having funding issues? | 09:38 |
| kanzure | not sure | 09:38 |
| utopiah_ | Z_: they dont bother to say , http://bluebrain.epfl.ch had maximum 10 news since the project started and most were ads for IBM and how cool visualizations mattered :/ | 09:41 |
| Z_ | I love comp neuro and emulation. Too, but I don't think it will be achieved within my lifetime, hence my choice of AGI. Don't think huge progress will be made in your fields of interest due to silly cultural biases held by the masses. | 09:41 |
| kanzure | utopiah_: they are still publishing papers, however | 09:41 |
| kanzure | Z_: i'm not the masses; i think there has been tremendous progress in cheap diy open source lab equipment | 09:41 |
| kanzure | we've reduced the price of thermocyclers from $50,000 to $25 | 09:42 |
| kanzure | (ok i'm cheating a little) | 09:42 |
| Z_ | Fucking iPad, excuse any punctuation, grammar, etc errors. | 09:42 |
| Z_ | I'm not disputing g that. | 09:43 |
| Z_ | What I'm saying is that in order to understand the human brain in order to emulate it, you need ... Samp | 09:43 |
| Z_ | Es... | 09:43 |
| Z_ | Samples... | 09:43 |
| kanzure | sure | 09:44 |
| Z_ | At some point, living ones...destructive scanning processes ... Not going to happen. | 09:45 |
| kanzure | destructive scanning already works | 09:46 |
| Z_ | Non sequitur, but how cool is Eureka! | 09:47 |
| kanzure | the television show? pretty gimmicky? | 09:48 |
| Z_ | Not wha I meant. I meant - destructive scanning on living specimens? Ethical issues will prevent that from happening. | 09:48 |
| Z_ | No, the software program that automates research. | 09:49 |
| jrayhawk | we're not at the point of needing them; no sense caring about human brains at this point. | 09:49 |
| eudoxia | destructive scanning on dead specimens is more likely | 09:49 |
| eudoxia | ATLUM etc. | 09:49 |
| eudoxia | no ethical considerations on the dead, plus you might even bring them back! (lol) | 09:49 |
| kanzure | eudoxia: there's a few companies working on this, | 09:50 |
| kanzure | the diamond knife-edge microscope and all that.. like 3scan | 09:50 |
| Z_ | Agreed. AGI just seems more realis | 09:50 |
| kanzure | the 3scan guy (todd huffman) lives with fenn, iirc | 09:50 |
| Z_ | realistic and more likely to produce great things.* | 09:51 |
| jrayhawk | so long as you don't mind the obselesence of humanity | 09:51 |
| kanzure | i can't think of anyone who argues AGI development will be faster than whole brain emulation development | 09:51 |
| kanzure | *is faster | 09:51 |
| eudoxia | I want to know, how many people are working on AGI? | 09:51 |
| kanzure | considering the current progress in computational neuroscience | 09:51 |
| eudoxia | besides Ben Goertzel/Yudkowsky etc. | 09:51 |
| kanzure | eudoxia: well it depends on what you mean by AGI | 09:51 |
| Z_ | Exactly. | 09:52 |
| jrayhawk | faster for what purpose? | 09:52 |
| kanzure | jrayhawk: i don't know what purpose Z_ is arguing about | 09:52 |
| kanzure | but he's claiming AGI is more realistic than destructive scanning of brain tissue (something we've seen already) | 09:52 |
| kanzure | i think | 09:52 |
| Z_ | Noon, not at all... Sorry if I haven't been very clear, it's 4 am. | 09:53 |
| kanzure | do you have a keyboard for your ipad? | 09:53 |
| Z_ | Unfortunately not... | 09:53 |
| eudoxia | kanzure: AI that isn't bounded by a particular domain? that can learn general tasks? | 09:54 |
| eudoxia | I wouldn't know how to define it | 09:54 |
| jrayhawk | Real-time whole-brain emulation isn't viable with todays computational tools and probably be for another two or more decades | 09:55 |
| Z_ | Kan, thanks for introducing me to this channel btw. | 09:56 |
| jrayhawk | We don't really know the computational requirements for AGI, but, unless you're proposing that the human brain, borne of evolutionary happenstance, is a paragon of computational efficiency, it's presumably less. | 09:56 |
| Z_ | AGI is further away yet... But I think it holds a lot more promise. | 09:57 |
| kanzure | Z_: you're very welcome | 09:57 |
| jrayhawk | We don't *know* if it's further away, is the thing. | 09:57 |
| Z_ | I should clarify: iM talking about strong AGI. | 09:58 |
| jrayhawk | In many ways, whole brain emulation is the worse case scenario, since we can iterate real fast from a working brain model and get AGI one way or another. | 09:58 |
| jrayhawk | s/worse/worst/ | 09:58 |
| jrayhawk | wait, how did i get tricked into talking about strong AI in here | 09:58 |
| jrayhawk | i am just asking to get kicked | 09:59 |
| Z_ | M,m, but such an au would be very anthropomorphic.. | 09:59 |
| jrayhawk | It *might* be anthropomorphic. | 09:59 |
| kanzure | jrayhawk: you just need to be very careful when talking about "ai" | 09:59 |
| Z_ | Lol.... Strong AGI is frowned on here? | 09:59 |
| kanzure | saying things like, "i know what intelligence is" will get you kicked | 09:59 |
| kanzure | or using the word "intelligence", that too | 09:59 |
| Z_ | Baaahahaha | 09:59 |
| jrayhawk | We'll know it when we see it, guys, we swear | 10:00 |
| kanzure | i'm not even sure if i'm intelligent | 10:00 |
| Z_ | I I don't even know if intelligence is real... Getting a wee bit philoshical there though. | 10:00 |
| kanzure | exactly.. so how can you make something you don't know is real? | 10:00 |
| kanzure | wait, that's the wrong question | 10:01 |
| jrayhawk | Intelligence is the conceit that we are better than monkeys. | 10:01 |
| jrayhawk | So long as machines are conceit-free, we'll never have true AI | 10:01 |
| kanzure | isn't that supposed to be culture, not intelligence? | 10:01 |
| jrayhawk | CASE CLOSED | 10:01 |
| jrayhawk | damnit I SAID CASE CLOSED | 10:01 |
| Z_ | Ahahaha, a novel take. | 10:01 |
| Z_ | But in answer to the question how can we make something we don't even know to be real/possible... | 10:02 |
| Z_ | We're humans! | 10:03 |
| kanzure | we know human brains do something interesting; we don't know if "intelligence" is sufficient or relevant | 10:03 |
| strages_work | kanzure: are you involved with a hackerspace? | 10:04 |
| kanzure | *we don't know if <some vague, ill defined, emotion-evoking concept that "everyone knows"> explains exactly what human brains are doing that is interesting to transhumanists | 10:04 |
| strages_work | I don't remember | 10:04 |
| kanzure | strages_work: i was involved with the austin hackerspace for a while, but they moved away so i sorta stopped going | 10:04 |
| strages_work | moved away? | 10:04 |
| kanzure | they moved out of a hackerspace into their own hackerspace | 10:05 |
| kanzure | haha | 10:05 |
| kanzure | it's a long story | 10:05 |
| kanzure | but anyway, they are a few miles away now and i don't go in that direction often | 10:05 |
| kanzure | it used to be down the street from me, easy biking distance | 10:05 |
| strages_work | ah ok. one of the members from my local hackerspace recently visited them | 10:07 |
| kanzure | makelocal? | 10:07 |
| strages_work | correct | 10:07 |
| kanzure | make25something.. i forget which one you are | 10:07 |
| kanzure | ok | 10:07 |
| strages_work | makers local 256 | 10:07 |
| Z_ | In response kanzure: 'there are as many different visions of Transhumanism as there are Transhumanists to envision them' - I, for one, am fascinated by the phenomenon we term intelligence. | 10:07 |
| Z_ | Goddamn iPad, capitalizing my shit.. Lol. | 10:08 |
| kanzure | does ipad auto capitalize ipad? | 10:08 |
| strages_work | there's also a diybio exclusive hackerspace looking for space here in town. they're trying to foster a relationship with us as we're well established and have infrastructure tooling | 10:08 |
| kanzure | strages_work: genspace? biocurious? | 10:08 |
| jrayhawk | they make these things called "keyboards" i think you might like them | 10:08 |
| jrayhawk | i know i do! | 10:08 |
| kanzure | jrayhawk: keyboards are an amazing advancement in tech | 10:09 |
| strages_work | kanzure: very similar to both of those. I believe they've visited both of them. | 10:09 |
| kanzure | it's going to be the latest craze | 10:09 |
| kanzure | strages_work: where are you? | 10:09 |
| kanzure | alabama? | 10:09 |
| strages_work | Huntsville, AL | 10:09 |
| kanzure | yeah, i'm not aware of any diybio/alabama groups at the moment | 10:09 |
| kanzure | cool | 10:09 |
| strages_work | there are several genetics companies in town. Operon, Hudson Alpha, etc | 10:10 |
| Z_ | I have a 3 grand laptop with this magical keyboard you speak of 2metres away... But the iPad is a new toy :D | 10:10 |
| kanzure | Z_: ipad can use bluetooth keyboards | 10:10 |
| jrayhawk | okay, new plan: tape the ipad to your laptop | 10:11 |
| jrayhawk | or glue, i guess it doesn't matter | 10:11 |
| Z_ | I know lol ... But then it wouldn't be a proper tablet, to me anyway. | 10:11 |
| Z_ | Tell you what. | 10:11 |
| kanzure | jrayhawk: mom got herself this http://www.asus.com/Eee/Eee_Pad/Eee_Pad_Transformer_TF101/ | 10:11 |
| Z_ | On the way to ful emulation | 10:11 |
| kanzure | it lags like crazy when i try typnig | 10:12 |
| kanzure | *typing | 10:12 |
| Z_ | I'm sure you guys could fix me up with a DNI | 10:12 |
| kanzure | Z_: http://diyhpl.us/~bryan/papers2/neuro/implants/ | 10:12 |
| Z_ | then I'll just think to my iPad 25 | 10:12 |
| Z_ | And yes, it does citalise itself | 10:12 |
| Z_ | Capitalize | 10:13 |
| Z_ | Seems not to fucking spellcheck though | 10:13 |
| jrayhawk | ick, android | 10:13 |
| jrayhawk | ASUS used to be in the cool kids club with Intel and Nokia :( | 10:14 |
| Z_ | Gotta cruise for a bit... Take care. | 10:14 |
| jrayhawk | it kinda freaks me out that Linux of all things got worseisbettered by Android | 10:15 |
| jrayhawk | maybe that's a sign that linux is a "mature product" | 10:16 |
| kanzure | hey we need a responsive ui to take user input, | 10:19 |
| kanzure | let's use java! | 10:19 |
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| AlonzoTG | om | 11:22 |
| strangewarp | om nom nom | 11:22 |
| AlonzoTG | AGI is cool. | 11:30 |
| uniqanomaly | yep yep yep yep yep yep yep | 11:33 |
| jrayhawk | uh huh uh huh | 11:33 |
| kanzure | aweebawoo aweebawoo | 11:35 |
| Mariu | =) | 11:36 |
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| AlonzoTG | I am contemplating writing a post on cognitive engineering. | 12:08 |
| AlonzoTG | and try to explain, yet again, how the obsession of uploading has blinded to people to the hundreds of other variables and system organizations possible when the necessity of fitting around a human neural pattern is dropped. | 12:08 |
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| Stee| | bah, uploading | 12:24 |
| Stee| | thesus-shipping, aw yeah | 12:24 |
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| AlonzoTG | =) | 13:25 |
| Stee| | I view destructive uploading as personality death | 13:29 |
| kanzure | no, it's biological death | 13:31 |
| AlonzoTG | death is bad. | 13:32 |
| sylph_mako | +1 it being biological death. How could it be personality death if the personality persists? | 13:34 |
| kanzure | "it's biological death" is sorta indisputable by the concept "destructive uploading" i figure.. | 13:36 |
| sylph_mako | +1 disagreeing with the term personality death[whatever that will turn out to mean] then. | 13:38 |
| kanzure | it means it's time for our lunches | 13:41 |
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| strangewarp | To think you will not experience your uploaded state, after any kind of destructive upload, is to hold a belief that your present consciousness has soul-like properties, and/or that the uploaded consciousness would not. That is OK. Just don't beat around the bush. | 14:24 |
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| kanzure | strangewarp: or that "present consciousness" exists.. that's also a weird one | 14:24 |
| strangewarp | hmmm. | 14:25 |
| sylph_mako | I am not conscious, in fact, I'm a p-zombie. | 14:28 |
| sylph_mako | I just appear to be. | 14:28 |
| strangewarp | Incidentally, the changes in the brain, second-to-second, are already so drastic that it seems identity is based more on memory, than on any continuity of experience. | 14:30 |
| strangewarp | If this throws you into an existential crisis, since you know mentally and peceptually that you are actively experiencing your life, and that you possess your memories, well.. welcome to the club. | 14:37 |
| strangewarp | I've been poking at simulism to try to resolve the concern, but my ideas on the subject are all half-formed and unsatisfying so far. | 14:39 |
| sylph_mako | I don't feel second by second changes in my brain. Although the day by day ones are pretty jarring. | 14:55 |
| AlonzoTG | =\ | 15:04 |
| AlonzoTG | You have it backwards, strange. | 15:04 |
| AlonzoTG | I don't believe that there is some mystical, dualistic, "pattern" that is capable of endowing something else with my consciousness. | 15:06 |
| AlonzoTG | It might be sufficient to produce a consciousness that bares some resemblance to my consciousness. | 15:06 |
| AlonzoTG | But it's not mine, I will not have the privilege of experiencing what it experiences, and I will not be able to enjoy anything that is offered as a benefit of being an upload. | 15:07 |
| sylph_mako | You mean "who". "Who bares some resemblance". | 15:07 |
| AlonzoTG | Whatever. | 15:07 |
| sylph_mako | Hehehe | 15:07 |
| AlonzoTG | doesn't matter/totally unimportant/don't care. | 15:07 |
| AlonzoTG | As a strict monist, I see a living system that is indivisible. To suggest that it is, in fact, separable, is equivalent to claiming that that it has a dualistic nature. | 15:08 |
| AlonzoTG | and therefore anyone who claims that the human mind is separable from its body is a limp-wristed, fuzzy thinking, starry-eyed DUALIST!!! | 15:09 |
| sylph_mako | That's pretty interesting. | 15:09 |
| sylph_mako | related question, AlonzoTG, how much would you value a copy of yourself? If one existed? | 15:09 |
| AlonzoTG | 0.00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | 15:09 |
| sylph_mako | I'm almost prepared to call you out on that assumption and propose that you would love him. Almost. | 15:11 |
| sylph_mako | It would resemble the shoddy mode of self-perpetuation we've employed for our entire mammalian history- make a rough copy of yourself then die- but it would be so much more direct. So much more potent. | 15:15 |
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| strangewarp | [16:06] <AlonzoTG> I don't believe that there is some mystical, dualistic, "pattern" that is capable of endowing something else with my consciousness. | 15:17 |
| strangewarp | You misunderstand what I'm getting at. | 15:17 |
| strangewarp | If you have two identical consciousnesses, then they are literally the same thing. I am entirely unsure how the related experiential aspects would play out, or whether we should even care about them, as they may not be measurable. | 15:18 |
| strangewarp | This opens the door to thinking about resimulation in terms of both extreme futurism and simulism. No dualism required. | 15:20 |
| eudoxia | I'd be careful with the whole identical thing | 15:21 |
| eudoxia | functional equivalence holds to a point but they can only be one and the same if you have a perfect .pdb of the entire brain and a quantum chemistry simulation | 15:21 |
| eudoxia | higher-level simulations loose the detail of the real brain | 15:22 |
| strangewarp | Indeed, I was considering stating that, provisionally, there could be variance in states, but then that opens a can of worms about how flexible a person's identity can be.. | 15:22 |
| eudoxia | frankly I don't care whether or not it's the same | 15:22 |
| eudoxia | it opens the door to radical human enhancement | 15:22 |
| strangewarp | Indeed, agreed, I was just trying to simplify for my point about resimulation | 15:23 |
| kanzure | oh god philosophy | 15:23 |
| eudoxia | of course | 15:23 |
| kanzure | AlonzoTG: claiming consciousness (as you do) is to assert dualism | 15:24 |
| kanzure | a seperable system is not necessarily dualist | 15:25 |
| kanzure | i.e., if you separate energy from your body, you will die | 15:25 |
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| kanzure | "researchers taking a stand against elsevier" http://thecostofknowledge.com/ | 18:12 |
| kanzure | not sure what this actually accomplishes | 18:12 |
| kanzure | why not just delete their servers | 18:13 |
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| delinquentme | so | 18:43 |
| delinquentme | If i want to start at the junction of ML and bioinformatics | 18:43 |
| kanzure | what sorta ml do you want to do? | 18:45 |
| delinquentme | well I'd like a biology related project | 18:46 |
| delinquentme | to begin wrapping my head around ml | 18:46 |
| kanzure | but i mean, you're asking for a random suggestion | 18:46 |
| kanzure | right? | 18:46 |
| eudoxia | a thing that identifies cancerous cells from optical micrographs | 18:47 |
| kanzure | a thing that analyzes the shapes of different polymerases | 18:47 |
| kanzure | for different polymerase properties | 18:47 |
| kanzure | shape classification, even | 18:48 |
| kanzure | feel-good homology phylogenetic tree stuff | 18:48 |
| delinquentme | eudoxia, what are optical micrographs? | 18:48 |
| eudoxia | I dunno, like electron micrographs but from an optical microscope | 18:49 |
| kanzure | doesn't matter, just think "image" | 18:49 |
| eudoxia | I was going to say electron micrograph but then I thought it was overkill so I swapped electron with optical and then I didn't know what to do | 18:49 |
| kanzure | delinquentme: what about edge detection in neural tissue imaging | 18:49 |
| kanzure | i.e. for neural reconstruction | 18:49 |
| kanzure | not quite the typical molecular-type bioinformatics project.. | 18:49 |
| kanzure | again, not sure what you're looking for | 18:49 |
| delinquentme | yeah | 18:50 |
| delinquentme | so complexity needs to be stepped down | 18:50 |
| kanzure | these are easy things, it just sounds complex | 18:50 |
| delinquentme | regardless | 18:50 |
| delinquentme | i want something thats doable in a few hours | 18:51 |
| kanzure | i consider "dna primer design" to be slightly harder ;) | 18:51 |
| kanzure | well, there's always boring work like "fix a bug in DNanonono" | 18:51 |
| kanzure | the dna/origami thing | 18:51 |
| kanzure | or "fix a ticket in bioperl/biopython/bioruby" | 18:51 |
| delinquentme | oh DUH | 18:53 |
| delinquentme | i spaced on the broad software thing | 18:53 |
| kanzure | ? | 18:53 |
| kanzure | you could do some bioinformatics pdf parser thing, that extracts charts/graphs :x | 18:54 |
| delinquentme | emailed ppl @ broad and sent along my stuff and basically asked " what can I contribute to ?" | 18:54 |
| kanzure | or an rss aggregator that sits on top of ncbi's data stream (you know, all the new proteins and shit that get submitted each day) | 18:54 |
| kanzure | what's broad? | 18:54 |
| delinquentme | the broad institute | 18:54 |
| delinquentme | lolol | 18:55 |
| kanzure | what are their suggestinos? | 18:55 |
| kanzure | *suggestions | 18:55 |
| delinquentme | i had to google to make sure that the spelling is the same as the derogatory female term | 18:55 |
| delinquentme | I have forwarded your information to the Gene Pattern group, which seems to best fit your interests. You can check them out here for more information: http://www.broadinstitute.org/cancer/software/genepattern/desc/expression. | 18:56 |
| delinquentme | Other open source projects that have come from the Broad are Haploview (http://www.broadinstitute.org/scientific-community/science/programs/medical-and-population-genetics/haploview/haploview) and CellProfiler (http://www.cellprofiler.org/). However, I am unsure of what projects are under development that meet your interests. It is my hope that the Gene Pattern group will have some input for you. | 18:56 |
| kanzure | how does cell imager distinguish cell/non-cell? shape can be anything, in certain situations | 18:57 |
| kanzure | pymol could use a new gui :/ | 18:58 |
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| kanzure | if there was just one single polymerase under direct human control, | 19:33 |
| kanzure | it would completely displace all of the current dna synthesis industry | 19:34 |
| kanzure | 10000 bp/second for every second of the day is 864M bp/day.. | 19:34 |
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| JayDugger | Good evening, everyone. | 19:41 |
| JayDugger | (Spent today reading Junji Ito manga while watching the contractor rebuild the bathroom. No nightmares, though.) | 19:41 |
| JayDugger | What's a good use for an Emotiv headset? | 19:43 |
| kanzure | the trashcan | 19:45 |
| eudoxia | haha | 19:45 |
| JayDugger | Not what I wanted to hear, and more valuable for it. | 19:45 |
| JayDugger | Anything else? :) | 19:45 |
| sylph_mako | Junji Ito's horror is what I would call deep horror. It's lovecraftian in its ways. To understand it is to enter madness. | 20:00 |
| JayDugger | Ah, hell...snobbery alert... | 20:00 |
| sylph_mako | It's the kind of stuff lovecraft writes /about/. | 20:00 |
| sylph_mako | Without actually successfully writing. | 20:01 |
| JayDugger | Junji Ito writes EC Horror style tales with way better art and an exotic settings. | 20:01 |
| JayDugger | Lovecraft writes about maltheism and nihilism. People still matter to Ito. | 20:01 |
| JayDugger | And $0.02 for the off-topic jar. | 20:01 |
| JayDugger | On the other hand, at least the reference gets noted here. :) | 20:02 |
| JayDugger | So don't pick up a cheap Emotiv unless I want to throw away money? | 20:02 |
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| delinquentme | kanzure, what are you talking about w the polymerase | 20:09 |
| delinquentme | you're saying you want control over what proteins are expressed within the body? kanzure ? | 20:10 |
| yashgaroth | he's saying that being able to reliably synthesize even a single molecule of DNA in a continuous strand, to order, would outcompete any/all current DNA synthesis processes | 20:14 |
| yashgaroth | probably any conceivable future processes too | 20:14 |
| yashgaroth | although technically pol doesn't generate de novo sequences, the idea is there | 20:16 |
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| kanzure | yashgaroth: there are some pol molecules that do template-free synthesis | 20:22 |
| kanzure | yashgaroth: http://diyhpl.us/~bryan/papers2/polymerase/ | 20:22 |
| kanzure | me strategizing last year http://diyhpl.us/~bryan/papers2/polymerase/notes2.txt | 20:22 |
| kanzure | tdt pol is interesting | 20:23 |
| kanzure | tth | 20:23 |
| yashgaroth | aside from telomerase? I'll take a look | 20:23 |
| kanzure | http://diyhpl.us/~bryan/papers2/polymerase/excellent%20-%20The%20conserved%20active%20site%20motif%20A%20of%20Escherichia%20coli%20DNA%20polymerase%20I%20is%20highly%20mutable.pdf | 20:23 |
| kanzure | who are you and why do you know what i'm talking about | 20:23 |
| kanzure | this is supposed to be incomprehensible jibberish | 20:24 |
| yashgaroth | I'm just some guy, and I seem to be one of the few here with some bio knowledge | 20:24 |
| kanzure | okie dokie | 20:24 |
| yashgaroth | let me scan that article real quick | 20:25 |
| kanzure | iorget if this motif is the one responsible for nucleotide discrimination | 20:26 |
| kanzure | *i forget | 20:26 |
| kanzure | this might have been the incorporation portino | 20:27 |
| kanzure | *portion | 20:27 |
| yashgaroth | it's more about mutating the pol itself while still retaining function, no? | 20:27 |
| kanzure | sort of, there are many strategies i can imagine | 20:28 |
| kanzure | like "try to get four different motifs in there, and use conformational changes to disable/enable certain nucleotide incorporation" | 20:28 |
| kanzure | and then do chromophores or some other light-based conformational change | 20:28 |
| delinquentme | yashgaroth, kanzure so someone mentioned measuring electrical fluctuation ... would this be applicable to monitor which bases are being sequenced? | 20:28 |
| kanzure | this is synthesis, not sequencing-by-synthesis | 20:28 |
| yashgaroth | the work in light-guided chain extension is promising | 20:29 |
| kanzure | i think i might have seen a polymerase on/off switch with light | 20:29 |
| kanzure | can't remember where.. but nothing specific | 20:29 |
| yashgaroth | probably, it'd be fairly easy these days | 20:29 |
| kanzure | state 1: polymerase normal | 20:30 |
| kanzure | state 2: fucked up polymerase | 20:30 |
| yashgaroth | pretty much | 20:30 |
| yashgaroth | but afaik, generating a "new" DNA strand without a template is limited only to telomerase, and that technically has a template | 20:30 |
| kanzure | consider this: | 20:30 |
| kanzure | http://diyhpl.us/~bryan/papers2/polymerase/tth/ | 20:31 |
| kanzure | the other problem is that i've seen some mutated polymerases that are biased for purines and others against purines, | 20:32 |
| kanzure | but never discrimination within the groups | 20:32 |
| kanzure | hard to do directed evolution on this problem :/ | 20:32 |
| yashgaroth | sure, it's possible to get a protein that will generate a repeating DNA structure, or even a random one; the problem is specificity | 20:33 |
| delinquentme | TIL chromophores | 20:34 |
| kanzure | badass right? and that's an old technique | 20:35 |
| delinquentme | I dont quite understand the applicaion | 20:35 |
| delinquentme | application | 20:35 |
| delinquentme | kanz how much of these papers do you read | 20:35 |
| kanzure | all of them | 20:36 |
| kanzure | this isn't the dark ages | 20:36 |
| delinquentme | abstract and KW index it | 20:36 |
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| delinquentme | ? | 20:36 |
| kanzure | no | 20:36 |
| delinquentme | you read through the entire papers | 20:36 |
| kanzure | we call that memory | 20:36 |
| kanzure | yes... | 20:36 |
| delinquentme | weird | 20:36 |
| * delinquentme jelly | 20:36 | |
| kanzure | just start reading | 20:36 |
| kanzure | if you want, we can read together | 20:36 |
| kanzure | for motivation/peer pressure reasons | 20:36 |
| yashgaroth | competitive reading, 2044 olympics | 20:37 |
| delinquentme | lol | 20:37 |
| kanzure | yashgaroth: the main cateogries in my collection are more interesting, | 20:37 |
| delinquentme | i DID have a paper open which i have no idea where it disappeared to | 20:37 |
| kanzure | http://diyhpl.us/~bryan/papers2/longevity/ | 20:38 |
| kanzure | http://diyhpl.us/~bryan/papers2/neuro/ | 20:38 |
| kanzure | http://diyhpl.us/~bryan/papers2/neuro/implants | 20:38 |
| kanzure | http://diyhpl.us/~bryan/papers2/nanotech/ | 20:38 |
| kanzure | http://diyhpl.us/~bryan/papers2/DNA/ | 20:38 |
| kanzure | http://diyhpl.us/~bryan/papers2/bio/ | 20:38 |
| yashgaroth | I've browsed some; are you still keeping up with myostatin etc.? | 20:38 |
| kanzure | http://diyhpl.us/~bryan/papers2/neuro/ultrasound/ | 20:38 |
| kanzure | not recently, no | 20:38 |
| kanzure | i remember some of the "tegment issues" | 20:38 |
| kanzure | tendon issues, sorry | 20:38 |
| kanzure | didn't seem like a showstopper to me | 20:39 |
| yashgaroth | yeah, though that might be due to transgenic-from-birth conditions | 20:39 |
| kanzure | exactly | 20:39 |
| kanzure | i was going to add that caveat, but you've done my work for me | 20:39 |
| kanzure | hooray | 20:39 |
| yashgaroth | it's a pet project of mine | 20:39 |
| kanzure | so, i was thinking of expressing the myostatin inhibitor | 20:39 |
| kanzure | in a hairy root culture | 20:39 |
| yashgaroth | I was much more into plasmid delivery | 20:40 |
| yashgaroth | the "body-as-bioreactor" approach, as it were | 20:40 |
| kanzure | plasmid delivery via the eye perhaps? http://diyhpl.us/~bryan/papers2/neuro/Subretinal%20injection%20and%20electroporation%20into%20adult%20mouse%20eyes.pdf | 20:41 |
| kanzure | oh, there was also this | 20:41 |
| yashgaroth | eye? muscle is where it's at | 20:41 |
| kanzure | kidney-targeted naked dna injection | 20:41 |
| kanzure | http://diyhpl.us/~bryan/papers2/bio/Kidney-targeted%20naked%20DNA%20transfer%20by%20retrograde%20renal%20vein%20injection%20in%20rats.pdf | 20:41 |
| kanzure | ok. direct plasmid delivery to muscle sounds painful | 20:41 |
| yashgaroth | especially with electroporation, which would be the ideal way | 20:42 |
| yashgaroth | also, which inhibitor? because the monoclonal got dumped by wyeth for good reason | 20:42 |
| kanzure | i don't remember, where's my notes | 20:42 |
| kanzure | but also: why not just use anabolic steroids | 20:43 |
| yashgaroth | ironically it's probably easier for me to use gene therapy | 20:43 |
| yashgaroth | but true, steroids are very effective when well-controlled | 20:43 |
| kanzure | can't order roids online for some reason? | 20:43 |
| delinquentme | wth are you guys talking about ? | 20:44 |
| kanzure | transhumanist stuff | 20:44 |
| delinquentme | i see delivery of plasmids | 20:44 |
| yashgaroth | is there anywhere reliable for roids on the net? I imagine it'd be 90% BS | 20:44 |
| delinquentme | and then steroids | 20:44 |
| kanzure | yashgaroth: just hang out on bodybuilding.com and be careful | 20:44 |
| yashgaroth | true, true, but the theoretical upper limit for well-designed myostatin inhibitors is much higher | 20:45 |
| kanzure | i don't recall that at all | 20:45 |
| kanzure | but i also don't recall the contrary | 20:45 |
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| yashgaroth | conservatively +50%, anywhere up to +300% but that's mostly from-birth | 20:46 |
| yashgaroth | with systemic delivery and no suppression | 20:46 |
| kanzure | +50% by mass? | 20:46 |
| yashgaroth | probably, it's hard to get mice to benchpress, especially since most of the models already have a muscle disorder | 20:46 |
| kanzure | delinquentme: ask very specific questions if you want good answers.. :/ | 20:47 |
| yashgaroth | anyway, I think it's worth a shot regardless | 20:47 |
| yashgaroth | worst that happens, systemic immune response to muscle tissue | 20:47 |
| yashgaroth | :D | 20:48 |
| kanzure | meh who needs an immune system | 20:48 |
| kanzure | ... or myocytes | 20:48 |
| yashgaroth | I hate the immune system as much as the next guy | 20:48 |
| kanzure | so, i don't know how obvious it is, but synthesis is tremendously more important to me than sequencing | 20:49 |
| kanzure | sequencing is a done deal, there's a race to the bottom and i'm sure we'll get to $1/genome or some other nonsense | 20:49 |
| kanzure | but not any next-gen synthesis companies | 20:49 |
| kanzure | which is ridiculous, considering the huge synthetic biology buzz. the whole point of synthetic is synthesis... | 20:50 |
| yashgaroth | ehh, cutting and pasting will only get you so far, but it's still fairly far | 20:50 |
| kanzure | yeah, a new dna synthesis venture would have to start with oligo libraries | 20:50 |
| kanzure | maybe a microfluidic sythesis+sequencing (for verification) setup | 20:51 |
| delinquentme | kanzure, so you want a hella effective way to build the dna | 20:51 |
| kanzure | delinquentme: nothing on the market beats my polymerases in my body | 20:51 |
| delinquentme | hows it done now | 20:51 |
| kanzure | phosphoramidite chemistry | 20:51 |
| kanzure | and other ways | 20:51 |
| kanzure | like oligo library ligation | 20:52 |
| delinquentme | but like | 20:52 |
| kanzure | papers: http://diyhpl.us/~bryan/papers2/DNA/ | 20:52 |
| yashgaroth | I don't know if it's really a DIY thing, nice as it would be; feds would get mighty suspicious | 20:52 |
| delinquentme | arent polymerases performing synthesis by sequencing? | 20:52 |
| kanzure | heres the steps, delinquentme | 20:52 |
| kanzure | http://diyhpl.us/~bryan/papers2/DNA/synthesis.txt | 20:52 |
| kanzure | yashgaroth: i have a good relationship with my fbi agent | 20:52 |
| kanzure | yashgaroth: i would not worry about them | 20:53 |
| yashgaroth | even with the ability to synthesize the gene for botulinum toxin and all that shit? | 20:53 |
| kanzure | not sure :) | 20:53 |
| yashgaroth | haha, I avoided bringing it up with my FBI agent | 20:54 |
| yashgaroth | i.e. the one who started sitting in on DIYbio Seattle meetings | 20:54 |
| kanzure | ed? | 20:54 |
| kanzure | "agent you" | 20:54 |
| yashgaroth | possibly, he was asian | 20:54 |
| kanzure | yeah that was him | 20:54 |
| yashgaroth | seemed alright, but I'd moved to SD before I got a chance to really chat with him or anything | 20:55 |
| kanzure | http://web.archive.org/web/20080708235522/http://www.fbi.gov/hq/nsb/wmd/images/hrtppe.jpg | 20:55 |
| delinquentme | kanzure, this reminds me of a thing i just saw on tech review about using light / low electricity to valve around liquids @ micro levels | 20:55 |
| kanzure | yashgaroth: so you know elizabeth and um.. | 20:56 |
| delinquentme | so whats needed to make blood | 20:56 |
| yashgaroth | alec, and the rest | 20:56 |
| kanzure | alessandro.. hrm.. | 20:56 |
| kanzure | nile | 20:56 |
| kanzure | ron | 20:56 |
| delinquentme | if we're working the stemcell path its cytokines | 20:56 |
| yashgaroth | a surprising number of H+ people in that club | 20:56 |
| yashgaroth | I'm none of them, but you and I are friends on FB if you're up for a hunt | 20:57 |
| kanzure | yashgaroth: the h+ crowd is surprisingly underskille | 20:57 |
| kanzure | *underskilled | 20:57 |
| yashgaroth | especially in biotech, which is why I was very happy to make the discovery | 20:57 |
| kanzure | like, pathetically underskilled | 20:58 |
| kanzure | singularityu isn't helping either | 20:58 |
| yashgaroth | haha that fucking place | 20:58 |
| kanzure | i grabbed all of their student's emails once | 20:58 |
| kanzure | they don't know shit about security | 20:58 |
| yashgaroth | doesn't surprise | 20:59 |
| delinquentme | kanzure, any suggestions on DIYbioing broken ear lobes from gauged ears? | 20:59 |
| kanzure | are you kris ganjam? | 20:59 |
| yashgaroth | nope, oh screw it I'll just send you a message on there real quick | 20:59 |
| kanzure | wow impressive, you only show up twice in my "stalk everyone" database | 21:00 |
| yashgaroth | I try not to delve into FB too much | 21:01 |
| yashgaroth | I will say, alec nielsen is an awesome dude, I expect great things from him; otherwise, good DIYH+bio people are exceedingly hard to find | 21:02 |
| kanzure | so why'd you show up here only now? | 21:02 |
| kanzure | this is sort of the biohacker/transhumanist/hardware hacking nexus | 21:02 |
| yashgaroth | ehh, I'd perused logs occasionally, but you gotta admit this place is 90% coding | 21:03 |
| yashgaroth | 5% other shit, 5% bio | 21:03 |
| kanzure | what can i say, software is easy to talk about | 21:03 |
| kanzure | feel free to change the ratios.. | 21:04 |
| yashgaroth | I'd be making a lot more money if I'd gone into coding, but I already spend my free time at the computer | 21:04 |
| yashgaroth | I do hope to direct the discussion a little more toward bio when I can | 21:05 |
| kanzure | just be militant about it and it will happen | 21:05 |
| delinquentme | yashgaroth, i think thats the application we're after here | 21:05 |
| kanzure | yashgaroth: pm | 21:06 |
| yashgaroth | ! | 21:06 |
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| delinquentme | oke toodles! | 21:09 |
| kanzure | seeya? | 21:13 |
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| nmz787 | hi | 21:17 |
| kanzure | hi nmz787 | 21:17 |
| kanzure | yashgaroth: let's not do pm now :P | 21:17 |
| nmz787 | i am a biotechnology student 4 yrs into my B.S. | 21:17 |
| kanzure | nmz787 had some thoughts about dna synthesis | 21:17 |
| kanzure | um, nate i think your other stuff is much more telling than that | 21:18 |
| yashgaroth | oh? | 21:18 |
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| nmz787 | at best you would address the polymerase with 3 regulators | 21:18 |
| nmz787 | 2 for the active site could combine to 4 states | 21:19 |
| nmz787 | and 1 to control addition of a nucleotide... probably something that in the relaxed state, the active site was blocked/mis-aligned... and in the activated state (pulse of some chemical, light would be cool too, electrically induced ph change) it would add a nucleotide before dropping back to being inactive | 21:20 |
| yashgaroth | well, you'd be basically mimicking phosphoramidite synthesis, right? addition of a single base, blocking, unblocking, and repeat | 21:20 |
| nmz787 | no | 21:20 |
| nmz787 | polymerase uses the cleavage of pyrophosphate to push the polymerization reaction forward | 21:21 |
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| nmz787 | you could probably then move on to adding sulfurylase and luciferase to the mix, to get a reply signal that you had a nucleotide added | 21:21 |
| nmz787 | that might have licensing issues, not sure | 21:22 |
| kanzure | don't worry about licensing bs | 21:22 |
| yashgaroth | who cares about licensing | 21:22 |
| nmz787 | hah | 21:22 |
| nmz787 | yeah | 21:22 |
| nmz787 | just sayin | 21:23 |
| nmz787 | the binding pocket is sort of controlled by the DNA template strand | 21:23 |
| kanzure | so, i'm not sure anyone has ever mechanically stopped a polymerase in its tracts | 21:23 |
| kanzure | i've seen some "mechanical strain applied to polymerase changes its kinetics/rate" | 21:23 |
| kanzure | but nothing specific like "stop/start with one base pair resolution" | 21:23 |
| kanzure | an advisor of mine once suggested using a betaclamp in front of the polymerase | 21:23 |
| kanzure | DIAGRAM http://diyhpl.us/~bryan/papers2/polymerase/2008-06-06_beta_clamp.png | 21:24 |
| nmz787 | so maybe you eliminate the binding pocket, and the conformational change rotates an axle with a different nucleotide on 4 arms | 21:24 |
| nmz787 | yeah, well polymerase is a motor | 21:24 |
| nmz787 | so you'd probably have to break that | 21:25 |
| nmz787 | or modify it | 21:25 |
| kanzure | too many variables | 21:25 |
| yashgaroth | you guys talk about that like it'd be anywhere near trivial | 21:25 |
| kanzure | nmz787: so, dosn't pol move at 10kbp/sec | 21:26 |
| kanzure | you'd need a fast feedback cycle to control this | 21:26 |
| kanzure | i dunno what the conformational changes tend to be.. 10-200 ns i hope? | 21:26 |
| nmz787 | what I'm saying is that you'd break the motor activity | 21:26 |
| kanzure | how do you move the dna down "exactly one bp" ? | 21:27 |
| nmz787 | or interrupt it, regulate it... I don't know how it works/looks | 21:27 |
| yashgaroth | you're still relying on pol to do a completely novel activity | 21:27 |
| nmz787 | none of it is novel | 21:28 |
| nmz787 | i am explaining, wait a sec | 21:28 |
| nmz787 | it happens naturally, a nucleotide is attracted to the template strand via the complementary hydrogen bond pattern, when it arrives the pyrophosphate (two phosphate groups linked) is cleaved from the triphosphate... this releases a lot of free energy... and the molecule takes advantage of it by changing conformations which move it down the DNA template... and the cycle repeats | 21:29 |
| kanzure | no, there's a discriminatory motif in polymerase that selects a nucleotide to incorporate | 21:30 |
| kanzure | "selects" more like.. uh. discriminates. | 21:31 |
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| kanzure | it's true that complimentarity plays a part however | 21:31 |
| nmz787 | there likely is to some degree, but its probably not too much | 21:31 |
| nmz787 | the polymerase mostly sees the phosphate backbone | 21:31 |
| yashgaroth | if you can reliably trick the pol into adding the nucleotide you want, then sure it'd work | 21:33 |
| nmz787 | this video says that polymerase tests the nucleotide | 21:34 |
| nmz787 | http://www.youtube.com/watch?v=TC2mYWR8754 | 21:34 |
| yashgaroth | free bases float into the pocket until one binds well enough that pol accepts it and moves on | 21:34 |
| kanzure | this contradicts what i remember reading o.o | 21:35 |
| nmz787 | in that part of the video you can see the opposite side of the DNA template binding pocket | 21:35 |
| yashgaroth | same as protein translation, all the tRNAs bump into that pocket until the ribosome likes one well enough | 21:35 |
| yashgaroth | usually because it stays around long enough from complementary binding | 21:36 |
| nmz787 | you might be able to replace the binding pocket with 4 nucleotides that were separate, but moved into the active site in a regulated fashion | 21:36 |
| yashgaroth | also, that video says 500bp/sec, which is more in line with what I've heard, at least for bacteria | 21:37 |
| yashgaroth | I still say you'd be better off mimicking phosphoramidite synthesis, just using several different proteins combined in order | 21:38 |
| nmz787 | how do you react then separate the proteins for reuse though? | 21:39 |
| kanzure | this is useful for t7 dna pol http://diyhpl.us/~bryan/papers2/polymerase/The%20molecular%20basis%20of%20nucleotide%20recognition%20for%20T7%20DNA%20polymerase%20-%202008.pdf | 21:40 |
| yashgaroth | well, you have four that attach to a working strand and add one of the bases, which would probably need a 3' modification to prevent >1 base being added | 21:41 |
| yashgaroth | clear that out, another comes in the cleave the 3' blocker | 21:41 |
| yashgaroth | clear and repeat with the next base | 21:42 |
| nmz787 | but you said using multiple proteins in series | 21:43 |
| yashgaroth | indeed | 21:43 |
| nmz787 | you need to recycle them, and make sure there isnt cross-contamination... otherwise you're spending a lot on proteins because you're dumping them to waste | 21:43 |
| yashgaroth | make each one responsive to a different wavelength/condition then | 21:44 |
| nmz787 | that's relying on complex infrastructure, protein sorters that are tuned to each protein's weight, etc | 21:45 |
| nmz787 | maybe | 21:45 |
| yashgaroth | they'd all exist in solution together | 21:45 |
| kanzure | ok that's right, | 21:45 |
| kanzure | i'm remembering something else | 21:45 |
| kanzure | called a "protein template" | 21:45 |
| kanzure | like in CCA-adding polymerases | 21:45 |
| kanzure | http://diyhpl.us/~bryan/papers2/polymerase/Structural%20basis%20for%20template-independent%20RNA%20polymerization%20-%20Tomita%20-%20Fukal%20-%20Ishitani%20-%20Ueda%20-%20Takeuchi%20-%20Vassylyev%20-%20Nureki.pdf | 21:45 |
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| yashgaroth | also proteins are fairly cheap if you make them yourself, and we'd be using nanograms; you only need a few good strands to amplify with PCR | 21:46 |
| kanzure | yeh there's tons of nanoliter PCR stuff out there | 21:47 |
| kanzure | look at the "protein template" thing | 21:48 |
| yashgaroth | the main problem is talking about designing completely novel proteins, or heavily modifying pol and several associated cofactors | 21:48 |
| kanzure | there's also antoher paper on a "protein template" here: | 21:48 |
| kanzure | http://diyhpl.us/~bryan/papers2/polymerase/Rev1%20employs%20a%20novel%20mechanism%20of%20DNA%20synthesis%20using%20a%20protein%20template%20-%20Nair%20-%20Johnson%20-%20Prakash%20-%20Aggarwal.pdf | 21:48 |
| kanzure | yeah, | 21:49 |
| yashgaroth | kk I'll take a look | 21:49 |
| kanzure | making a single modification to pol and checking it is a pain | 21:49 |
| kanzure | and then expecting multiple modifications to work is also a chore | 21:49 |
| kanzure | "the polymerase itself dictates the identity of the incoming nucleotide, as well as the identity of the templating base" | 21:50 |
| kanzure | gee, i'm glad i'm not crazy | 21:50 |
| yashgaroth | protein simulation has come a long way, but even folding them yourself on a supercomputer with some hyper-modded form of fold.it, it's still mind-boggling | 21:50 |
| yashgaroth | speaking of which that's always a good software project, fold.it modding | 21:51 |
| Stee| | ugh | 21:54 |
| Stee| | two DIY things I'd love to figure out | 21:54 |
| Stee| | is resin, and extrudable plastic | 21:54 |
| Stee| | I suspect the second is easier than the first, but would need to figure out a DIY cracker first | 21:54 |
| yashgaroth | don't suppose you're talking about chromatography resin? | 21:57 |
| Stee| | no | 21:58 |
| yashgaroth | damn | 21:58 |
| Stee| | sorry, talking about stereolithography | 21:58 |
| nmz787 | problem with phosphoramidite chemistry is that it sucks for long stuff | 21:58 |
| nmz787 | polymerase already has error-correction | 21:59 |
| nmz787 | if you could control the templating, you'd be pretty good to go I think | 21:59 |
| yashgaroth | totally, but it can't correct errors on something unless it's correcting from the strand being copied | 22:00 |
| nmz787 | right | 22:00 |
| yashgaroth | which you don't have since you're basically writing a single strand, no? | 22:01 |
| nmz787 | i was proposing the modified polymerase which could control what the template looked like at the active site only | 22:02 |
| nmz787 | i can draw a picture of it I think | 22:02 |
| yashgaroth | oh, well in that case it would work, yes | 22:03 |
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| nmz787 | well anyway | 22:04 |
| kanzure | diagrams are good | 22:04 |
| nmz787 | i was alternatively thinking of using something like sequential overlap extension PCR | 22:04 |
| nmz787 | where you'd have an oligo attached to a magnetic bead, held in place just before a silicon sieve that lets oligos through, but not the polymerase | 22:05 |
| nmz787 | because oligos are maybe 6-10 angstroms, but polymerase is easily 50 x 100 angstoms | 22:07 |
| nmz787 | there'd be a small resistive heater patterned on the silicon, and you'd basically do 1 cycle of PCR with the free-floating oligo as a template strand | 22:08 |
| nmz787 | melt, rinse, bring in next "template" oligo from a library of 5 or 6-mer oligos | 22:08 |
| nmz787 | magnet--restrictionSiteaa | 22:09 |
| nmz787 | ttac | 22:09 |
| nmz787 | blah | 22:09 |
| yashgaroth | that's basically what commercial synthesis does these days | 22:10 |
| nmz787 | ascii art won't work here | 22:10 |
| yashgaroth | and with hundreds of possible oligos | 22:10 |
| nmz787 | yeah, not too bad | 22:10 |
| yashgaroth | there's nothing super-terrible about current tech, I mean jcraig can generate a whole genome, it just takes a lot of resources | 22:11 |
| nmz787 | lots of $ | 22:11 |
| nmz787 | pretty terrible | 22:11 |
| yashgaroth | yes, but we won't be needing genome-sized fragments any time soon | 22:11 |
| kanzure | *cough* | 22:12 |
| nmz787 | yeah | 22:12 |
| kanzure | that's a lousy reason to suck | 22:12 |
| yashgaroth | fair enough | 22:12 |
| nmz787 | do you know what kind things kanzure compiles from source? | 22:12 |
| yashgaroth | less is more fellas | 22:13 |
| kanzure | that's what people who don't have more say | 22:13 |
| yashgaroth | sure, if you want codon-optimized genes you'd need to synthesize them and it would suck | 22:13 |
| nmz787 | cloning is kind of a PITA | 22:13 |
| nmz787 | it works, well | 22:13 |
| nmz787 | but its a lot of work | 22:14 |
| nmz787 | its a lot easier to sit in front of a computer for me, than it is to sit in a lab | 22:14 |
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| yashgaroth | cloning's still an art, sadly | 22:15 |
| nmz787 | synthesis is much more to-the-point | 22:15 |
| yashgaroth | but with that overlap extension in its traditional form, you can have basically any combination of existant sequences | 22:16 |
| nmz787 | right | 22:16 |
| yashgaroth | and very few long, new, and useful sequences have been found, though that's mostly because synthesis is expensive | 22:16 |
| nmz787 | but now the overlap stuff comes from long synthesized oligos | 22:17 |
| nmz787 | i'm saying use shorter pieces from a library, and don't synthesize | 22:17 |
| nmz787 | you could probably work out a system for brewing more library oligos using PCR or cell culture | 22:17 |
| yashgaroth | how you gonna separate each oligo from a library without having them synthesized separately? | 22:18 |
| nmz787 | have them synthesized separately the first time | 22:18 |
| kanzure | keep them separated | 22:18 |
| yashgaroth | then you're losing the advantage over traditional synthesis | 22:19 |
| nmz787 | how? | 22:19 |
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| nmz787 | i'd say losing a disadvantage | 22:19 |
| yashgaroth | you're still combining oligos, just shorter ones | 22:19 |
| nmz787 | yeah but using them as a template in PCR | 22:19 |
| kanzure | right now, oligo libraries are the more cost effective option | 22:19 |
| nmz787 | if they were 3' modified to be terminators, you could probably recycle them | 22:19 |
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| nmz787 | with the 3' terminator modification, the template library oligos wouldn't extend (they'd stay 6-mer) | 22:20 |
| kanzure | http://openwetware.org/wiki/Endy:Double_stranding_oligo_libraries | 22:20 |
| kanzure | hrmm where's my oligo library service provider | 22:21 |
| kanzure | this is alme | 22:21 |
| kanzure | *lame | 22:21 |
| nmz787 | or | 22:21 |
| yashgaroth | you'll still have a small error rate, and it'd be harder to correct, I'd think | 22:21 |
| yashgaroth | with overlapping 100mers you can pre-sort them to make sure they're the right length | 22:22 |
| nmz787 | at 6-mer library, that's 4^6==4096, 4096*6 nucleotides *$0.3/bp for primers | 22:22 |
| klafka | hey | 22:22 |
| nmz787 | ==$7372.8 | 22:22 |
| klafka | hmm are you guys talking about dna-write | 22:22 |
| nmz787 | last time i bought primers I paid $0.15/bp | 22:22 |
| nmz787 | so thats an overestimate | 22:22 |
| nmz787 | you only need to synthesize 1 strand, then you can PCR the entire thing to amplify it at the dn | 22:23 |
| nmz787 | end | 22:23 |
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| yashgaroth | once you have a single strand it's easy, sure | 22:23 |
| nmz787 | but for redundancy you could still plan to have 10,000 starting strands attached to magnetic beads, and still have tons of oligo library 6-mers for a long time | 22:24 |
| yashgaroth | the cost of the oligos won't be the majority of the expense on something like that though | 22:24 |
| yashgaroth | I mean, if you had development money I'm sure it would work fine, but that's a bit beyond DIY | 22:25 |
| kanzure | that's usually $0.30 or $0.15/bp from synthesis services, | 22:25 |
| kanzure | the actual cost per bp in material costs is like... zilch | 22:25 |
| yashgaroth | and you can always make the whole process smaller anyway | 22:26 |
| nmz787 | smallest order of primers is 0.025 micromoles | 22:26 |
| * AlonzoTG is now about 20 pgs into Accelerando. | 22:26 | |
| nmz787 | (6.023*10^23/1000000)*0.025 = 1.5*10^16 oligos per order | 22:26 |
| yashgaroth | but if we're talking about using current commercial gene synthesis, versus designing a whole new system like this, it won't become cheaper for some time | 22:27 |
| AlonzoTG | I don't like the way the book is headed already but I'll try to stick with it, at least until I come across something I just can't stomach. | 22:27 |
| nmz787 | if you need to flush in 100,000 oligos at a time, to attempt to hybridize 10,000 growing strands | 22:27 |
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| AlonzoTG | I don't have any genes to synthesize at the moment. =~( | 22:27 |
| nmz787 | you have 150 billion reaction steps | 22:28 |
| nmz787 | even if you only extended by 1 bp per PCR cycle, that's a lot of directed DNA synthesis | 22:29 |
| nmz787 | problem would be synthesizing repeats | 22:30 |
| nmz787 | so back to needing an addressable polymerase | 22:30 |
| nmz787 | i think its only a matter of time before that is reality | 22:30 |
| yashgaroth | yes, but it's a bit beyond our means at the moment | 22:31 |
| kanzure | i don't think universities are going to do it | 22:31 |
| yashgaroth | pfft, there's plenty of money to be made, big biotech is already doing plenty of research into it | 22:31 |
| klafka | kanzure you don't think universities don't want to revolutionize dna-write? | 22:31 |
| kanzure | it's not like "oh let's casually take control of dna polymerase" is fundamental/basic research | 22:32 |
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| nmz787 | it seems like a lot of companies are content with the level of production and cost | 22:32 |
| nmz787 | both in biotech reagents and medicinals | 22:32 |
| yashgaroth | it is fundamental-level research, compared to most of the field | 22:33 |
| yashgaroth | and yes if you've got 100mil to spend developing a drug, a few grand for gene synthesis is nothing | 22:33 |
| klafka | kanzure actually i'd say that is fundamental research | 22:33 |
| klafka | like absolutely | 22:33 |
| nmz787 | if it does come at the professional level, I bet it would still be significantly marked up in cost (though cheaper than current prices) | 22:33 |
| nmz787 | *suppliers are satisfied with the costs* | 22:34 |
| nmz787 | not buyers, they always want cheaper | 22:34 |
| yashgaroth | all the current oligo providers are just making the exact same process cheaper than each other, there's only so far it can go | 22:36 |
| klafka | yeah | 22:36 |
| yashgaroth | it's one of the few places in biotech without an obscene markup | 22:36 |
| klafka | there needs to be a fundamental advance in research | 22:36 |
| klafka | it's probably going to come from physics | 22:36 |
| klafka | or material science | 22:36 |
| klafka | and some guy is gonna be like 'wtf we can use this for synthing dna' | 22:36 |
| kanzure | yashgaroth: i'm not convinced they are making it cheaper than each other | 22:36 |
| Stee| | it's really lucky 95% of my research has been theory only | 22:36 |
| Stee| | and only 5% validation | 22:37 |
| Stee| | thank god | 22:37 |
| Stee| | otherwise I'd be stuck here even longer | 22:37 |
| klafka | hahahaha | 22:37 |
| klafka | yes | 22:37 |
| * klafka escaped academia | 22:37 | |
| Stee| | job interview wednesday | 22:37 |
| yashgaroth | costs for oligo synthesis are decreasing using the same old method, though there's likely some price-fixing there | 22:37 |
| Stee| | we'll see how that goes | 22:37 |
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| nmz787 | well i'm off, back to studying | 22:41 |
| nmz787 | bye | 22:41 |
| kanzure | seeya | 22:41 |
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| yashgaroth | I do agree with klafka that we're waiting for physics, to help solve the protein folding problem | 22:42 |
| yashgaroth | either for that modified polymerase or a protein version of phosphoramidite base-by-base extension | 22:42 |
| klafka | i mean these advances are _clearly_ going to either chem directly from physics or from materials/nanoscience | 22:42 |
| kanzure | the protein folding problem is irrelevant | 22:42 |
| yashgaroth | to rational protein design? | 22:42 |
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| kanzure | rational? we just need it to work :p | 22:43 |
| yashgaroth | ha | 22:44 |
| yashgaroth | there's only one human-designed enzyme, and that came from simulated folding | 22:44 |
| yashgaroth | ...and thousands of experiments, but mostly in silico folding | 22:45 |
| nmz787 | which enzyme? | 22:46 |
| nmz787 | refs? | 22:46 |
| yashgaroth | http://depts.washington.edu/bakerpg/drupal/system/files/jiang08A.pdf | 22:46 |
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| yashgaroth | sure, it's a useless reaction with a slow catalytic rate, but still awesome | 22:51 |
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| yashgaroth | oh wait they've done a couple other similar things with that backbone, but yes generally it's from computer-aided design | 22:54 |
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| kanzure | Omega-: can you die please | 22:56 |
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| nmz787 | yeah i remember reading that or a similar one | 22:56 |
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| yashgaroth | anyway, I should have started with a disclaimer that novel gene synthesis techniques aren't exactly my realm of expertise, though they're always interesting | 23:01 |
| nmz787 | not mine either, but i've been interested in it throughout school so far | 23:04 |
| AlonzoTG | I'm about a million miles away from making productive use of such a technology. =\ | 23:04 |
| yashgaroth | don't worry, we got it covered | 23:05 |
| @kanzure | actually i think we don't but should work on it | 23:05 |
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| yashgaroth | same thing really | 23:05 |
| nmz787 | cheap DNA synthesis @ home will be useful, very quickly | 23:08 |
| nmz787 | if someone can do that, it wouldn't be much to lay on top a microfluidic e. coli or yeast transformation system | 23:09 |
| nmz787 | so it literally would be an auxiliary DNA programmer for those organisms | 23:09 |
| @kanzure | or anything else really | 23:10 |
| nmz787 | using that you could even start to do genetic knockouts, so you can start to remodel your strains aside from auxiliary DNA (plasmids) | 23:11 |
| nmz787 | then we'd need to worry about downloading DNA and SOPA | 23:12 |
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| yashgaroth | SOPA's already in practice if not law | 23:13 |
| nmz787 | i thought it got dropped | 23:13 |
| yashgaroth | and the day after, the entire public filesharing architecture started to crumble, except torrents | 23:14 |
| yashgaroth | they can just stretch other laws to cover it | 23:14 |
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| yashgaroth | most of the restrictions related to DNA come from bioterror alarmism anyway | 23:15 |
| yashgaroth | patent infringement doesn't really become a concern until you try to commercialize | 23:17 |
| @kanzure | that's only if you commercialize in the u.s. | 23:17 |
| @kanzure | or a state that respects patent laws | 23:17 |
| yashgaroth | good luck selling it in a place like that before someone else does the exact same thing to you | 23:18 |
| @kanzure | alright | 23:18 |
| @kanzure | sounds good to me? | 23:18 |
| yashgaroth | ...yeah, me too | 23:19 |
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| yashgaroth | aight I'm out for the night, will check back in tomorrow | 23:33 |
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