--- Log opened Tue Apr 18 00:00:29 2017
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05:15 < kanzure> "30x means youll get 0x coverage of 20% of genome"
05:26 < kanzure> whois avi roy <avijitguharoy@gmail.com>
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06:53 < kanzure> "Structure of the Legionella Dot/Icm type IV secretion system in situ by electron cryotomography" http://biorxiv.org/content/early/2016/11/07/085977 (2016)
06:57 < kanzure> .tw https://twitter.com/APDobbs/status/854253873602732033
06:57 < yoleaux> PhD starting in Sept17 available in my group. synthetic organic electrochem and photochem. Advert out shortly. Message me if interested (@APDobbs)
06:58 < kanzure> "The evolution of combinatorial gene regulation in fungi" http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060038 (2008)
07:03 < kanzure> .tw https://twitter.com/eboyden3/status/853994385855447040
07:03 < yoleaux> "Iterative expansion microscopy," just out in Nature Methods, expands samples twice, achieving ~25 nm resolution. http://rdcu.be/rk6X (@eboyden3)
07:04 < kanzure> "Iterative expansion microscopy" http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.4261.html
07:05 < kanzure> "Pyramidal neurons are not generalizable building blocks of cortical networks" http://journal.frontiersin.org/article/10.3389/fnana.2017.00011/full
07:05 < kanzure> from https://twitter.com/MargolisLab/status/844233325481000965
07:06 < kanzure> "A general method to fine-tune fluorophores for live-cell and in vivo imaging" http://biorxiv.org/content/early/2017/04/14/127613 https://twitter.com/biorxivpreprint/status/853125781706473473
07:06 < kanzure> scihub links chrome browser extension https://chrome.google.com/webstore/detail/sci-hub-links/olcgjijbclchlliaffaghajlbfppkbkl?hl=en
07:08 < kanzure> "Associative content-addressable networks with exponentially many robust stable states" https://arxiv.org/abs/1704.02019 https://twitter.com/wbialek/status/851898787316584448
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09:40 < kanzure> https://github.com/kanzure/pdfparanoia/issues/50
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10:28 < satori_> wassat
10:28 < satori_> ?
10:28 < satori_> oic
10:28 < satori_> nice
10:30 < kanzure> who are you
10:30 < satori_> <- satori
10:31 < satori_> hi
10:31 < kanzure> why are you here?
10:32 < satori_> someone interested in the topics
10:32  * satori_ points to the topic
10:32 < satori_> there a problem or somethin' ?
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10:38 < nmz787_i> ?
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11:00 < kanzure> https://www.illumina.com/products/by-type/sequencing-kits/library-prep-kits/truseq-dna-pcr-free.html
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12:14 < nmz787_i> kanzure: so no ideas/recommendations for where to try hiring for small CAD modelling jobs?
12:30 < kanzure> here is the transcript from the bioviva call http://diyhpl.us/~bryan/2017-04-18-bioviva.txt
12:38 < nmz787_i> well, that conversation went pretty much as I expected
12:38 < nmz787_i> sounds like you might have anti-life extensioned yourself by ~30 mins
12:38 < nmz787_i> though I guess networking can be anomalous enough to be hard to say
12:38 < kanzure> basically they said "we are only interested in sick people"
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12:56 < juri_> nmz787_i: if you're interested, i might have some students willing to undertake such a challenge.
13:00 < nmz787_i> juri_: that'd be great, my email is nmz787 at gmail . com
13:01 < juri_> nmz787_i: got some "this is about what i'm looking for" documents?
13:01 < nmz787_i> umm, yeah... not sure I can find it while here at work
13:02 < nmz787_i> this one is something I was reading recently: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwiDr-uF5q7TAhUL7WMKHeecAFIQFggyMAA&url=http%3A%2F%2Fwww.mdpi.com%2F2072-666X%2F2%2F2%2F179%2Fpdf&usg=AFQjCNFe15WNAirr4MGPzc1lCv5ek09p4Q&sig2=0Is3wS0LqUKJfIWhAjV6yA&cad=rja
13:02 < nmz787_i> err
13:02 < nmz787_i> sorry
13:02 < nmz787_i> www.mdpi.com/2072-666X/2/2/179/pdf
13:03 < nmz787_i> I'd like a model of each of the classes/types/examples shown in that paper
13:03 < nmz787_i> modelled using my python-brlcad-tcl framework/library
13:03 < nmz787_i> since that is what my fabrication software stack is relying on
13:03 < juri_> ah. i'm teaching ImplicitCAD here. :)
13:04 < nmz787_i> if that was reliable, I'd use it... but I don't think it was the last time I checked
13:04 < juri_> it's gotten better. use causes fixes. :)
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13:04 < nmz787_i> I thought kanzure would recommend some indian or vietnamese freelancer website
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13:08 < kanzure> oh, uh
13:08 < nmz787_i> I guess I can try asking in #brlcad too
13:08 < kanzure> actually, brlcad has a lot of indian students that show up regularly
13:08 < kanzure> for gsoc
13:08 < kanzure> go talk to their rejected students and offer them some money
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13:34 < nmz787_i> juri_: does that mean the test case I made, that you were using as a unit-test (I think) is working now?
13:34 < nmz787_i> juri_: the tobacco mesophyll protoplast fusion device?
13:39 < juri_> it requires more ram than i have, to render at a useful resolution. i use it as my 'torture test'.
13:48 < nmz787_i> disk caching doesn't work?
14:28 < nmz787_i> some kind of Journal publisher looking for AI/ML laborers: http://stackoverflow.com/jobs/136814/machine-learning-scientist-freelance-research-square
14:29 < nmz787_i> oh, nevermind, it is some kind of editing service
14:52 < juri_> it works, but it'll take a month. i use the torture test to shave minutes off of that at a time. ;)
14:53 < nmz787_i> hmm, BRLCAD works almost instantly for my tests... though I think I didn't finish porting that specific case. Guess I should look into finishing that
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18:44 < kanzure> .tw https://twitter.com/andpru/status/854423019913084928
18:44 < yoleaux> Our first @OpenEphys rig, streaming data within 5 minutes of opening the box. Hardest part was finding spare USB on my Mac. https://pbs.twimg.com/media/C9uFMf9W0AYuuJs.jpg (@andpru)
21:05 < fenn> maybe i'm missing something but how can gene therapies be expensive? can't you mass duplicate them for essentially the cost of growth medium?
21:05 < yashgaroth> mammalian growth media's expensive as fuck
21:06 < fenn> it's not $750k expensive
21:07 < nmz787_i> quality control?
21:09 < yashgaroth> it's not the whole cost, but it adds up to hundreds of dollars per liter since 1) you have to expand the cells and they divide once a day 2) you gotta supplement the media to get good yields 3) you need to culture cells to produce the inoculating virus too
21:09 < yashgaroth> then there's purification where you're either using ultrafuges or resin that costs $100 per mL and you need liters of it
21:10 < yashgaroth> plus capital equipment, utilities, buffers, QC, labor
21:10 < yashgaroth> it's not $750k expensive, shit like glybera is there because they gotta make profitz and because no one's buying it
21:11 < yashgaroth> if a million people want a gene therapy the unit cost goes way down
21:12 < yashgaroth> purification is usually more expensive than cells anyway, especially when it's for injectables...ok I'm done
21:12 < fenn> ok thank you for confirming my understanding of basic economics
21:13 < yashgaroth> just saying, with it being so niche right now, capital expenditures are a big chunk
21:13 < fenn> i can't believe capital is more than $100k
21:14 < yashgaroth> a large mammalian bioreactor costs more than that
21:14 < fenn> doesn't need to be large
21:15 < yashgaroth> ehh the yield's pretty shit for most viral therapies, and you'll lose quite a bit to get it pure enough to inject
21:15 < yashgaroth> kind of ironic since people'll be on heavy immunosuppressants so a little host cell protein is nbd, but that's the FDA for you
21:16 < yashgaroth> but true you can basically make your own wave bioreactor for very little
21:17 < yashgaroth> I told bioviva if they'd spent the money they'd wasted on one human-sized dose, they could've built a lab to produce those doses for under 20k a pop
21:17 < yashgaroth> but it was already spent
21:18 < fenn> they can get more money
21:18 < yashgaroth> they did, and then they paid it back to their initial funders, and I gave up trying to help
21:28 < fenn> lol glybera "they expected a clinical trial of 342 patients. Executives wryly noted that there were only 250 people with the disease"
21:28 < yashgaroth> I remember reading that no one has actually bought glybera, that might have changed
21:28 < fenn> there was one purchase in germany
21:29 < yashgaroth> ah maybe it was just one yeah
21:29 < fenn> $1 million per patient (?) is apparently difficult to justify
21:30 < yashgaroth> europe is much more prudent about drug pricing, I don't blame them
21:30 < fenn> it seems the only sensible way to do this is to build pipelines for custom therapies rather than just doing the therapies with what already exists
21:31 < yashgaroth> you mean new genes, or new vectors?
21:31 < fenn> at the end of the day you're just making a virus with a custom genetic payload
21:31 < fenn> no need to build a new lab for that every time
21:32 < fenn> i'm guessing it's a regulatory problem rather than a technical one
21:33 < yashgaroth> you can definitely do it all in one lab, but through official legal GMP channels a majority of the cost is trials and documentation
21:34 < fenn> why is there no experimental treatment loophole that lets you do this without doing trials?
21:34 < fenn> i mean 250 people is not enough to do a trial anyway
21:35 < fenn> someone has to take the first dose no matter what
21:35 < yashgaroth> often with rare diseases the trial is the treatment
21:35 < yashgaroth> at least for the group that gets the drug
21:35 < yashgaroth> and with gene therapy supposedly being permanent
21:36 < yashgaroth> there's been plenty of trials, just most don't show efficacy...there's a limited pool of disorders that are common enough to justify the investment, and that're actually treatable with gene therapy
21:38 < yashgaroth> now, for enhancement, there's plenty of targets, but regulatory bodies don't approve bleeding-edge gene therapies for healthy people to double their muscle mass or w/e
21:38 < fenn> there ought to be lots of targets for gene therapy that are currently being treated with drugs
21:40 < fenn> everyone's incentives are screwed up
21:40 < yashgaroth> enzyme replacement therapies are pretty rare, and if you develop a gene therapy replacement the drug mfg.er can always drop their price, which is fucked up but that's how it is
21:40 < fenn> jeez where is the soviet union when you need it
21:41 < yashgaroth> only in our fond memories, sadly
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21:42 < fenn> is enzyme replacement the only kind of gene therapy currently being attempted?
21:43 < yashgaroth> oh there's others, like follistatin for muscular dystrophy which I still follow up on, but that's like changing the oil on a car fire
21:44 < yashgaroth> some companies are looking into monoclonal antibody gene delivery, but it's not cost-competitive with drugs for now
21:44 < abetusk> https://www.kickstarter.com/projects/antonyevans/glowing-plants-natural-lighting-with-no-electricit/posts/1786250?ref=backer_project_update
21:44 < abetusk> .title
21:44 < yoleaux> Glowing Plants: Natural Lighting with no Electricity by Antony Evans -- Kickstarter
21:45 < fenn> that aids vaccine eCD4Ig looked interesting
21:47 < yashgaroth> mm, but who's gonna pay 5-6 figures per person for it; the first world has truvada and the third world can't afford it
21:47 < fenn> but what i'm saying is it doesn't need to be a lot per person
21:47 < fenn> once you can mass produce it
21:48 < yashgaroth> ten grand is still a fuckton of money when exposure rates are so small
21:49 < fenn> is the problem that you need a lot of viral yield?
21:50 < fenn> i mean if there were in-patient viral replication would that drop the cost by 4 orders of magnitude?
21:50 < fenn> replication of the vector
21:50 < fenn> say it only replicates when you're on immunosuppressants
21:51 < yashgaroth> then you have live virus going in, since it has all the genes for its own replication
21:51 < fenn> and what's the problem with that?
21:51 < yashgaroth> you get a live virus in an immunosuppressed host
21:51 < fenn> how long does it take to die from AAV when immunosuppressed?
21:52 < fenn> i mean does this scheme even make sense?
21:53 < yashgaroth> well it needs several genes from adenovirus to replicate, so you're coinjecting those, so either you have live adenovirus too, or your producer population is small since only cells with the adenovirus genes will produce virus
21:53 < yashgaroth> sure, with a decade of engineering work!
21:53 < yashgaroth> I mean that is the ideal, a megavirus that spreads to neighboring cells, and once their neighbors are infected, it shuts off and the cascade spreads through the entire body
21:55 < yashgaroth> but right now we're still at the artful vandalism stage of biotherapeutics
21:56 < cevi_> what about a "semi-live" virus that has the genes to create a virus which can't replicate at all?
21:58 < fenn> .wik helper virus
21:58 < yoleaux> "A helper virus is a virus used when producing copies of a helper dependent viral vector which does not have the ability to replicate on its own. The helper virus is used to co-infect cells alongside the viral vector and provides the necessary enzymes for replication of the genome of the viral vector." -- https://en.wikipedia.org/wiki/Helper_virus
21:59 < fenn> i had thought they were using live viruses for gene therapy in the first place
22:01 < yashgaroth> nah you strip out the genome and replace it; the producer cells have the virus genome integrated or in a plasmid that's inaccessible to the payload packaging machinery
22:02 < yashgaroth> but AAV for example is expelled when the host cell dies so you're limited there
22:04 < yashgaroth> some of them do bud, like lenti/retro, but it's still a lot of work to have the body as bioreactor safely; it could certainly be done though
22:05 < fenn> i'm imagining a two-part system where you first eestablish a beach-head of AAV producing cells and those  produce the vector in the body of the patient
22:05 < fenn> hmm connection issues bbl
22:12 < yashgaroth> yeah if you could get them to secrete it instead it'd work, not strictly impossible but difficult with non-enveloped viruses
22:13 < yashgaroth> also there's an advantage to a massive single bolus injection; everyone has anti-AAV antibodies which are still around even on immunosups, so if you're making a trickle of virus they'll inactivate it and degrade it, even w/o an immune system
22:14 < yashgaroth> whereas with a bolus it overwhelms whatever antibodies you may have
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--- Log closed Wed Apr 19 00:00:30 2017