--- Log opened Mon Mar 23 00:00:30 2020
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01:35 < archels_> https://www.genengnews.com/virology/coronavirus/catching-up-to-coronavirus-top-60-treatments-in-development/
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04:15 < fenn> fltrz: it's not "trial and error" it's completely random shuffling during embryonic development. you get dealt a hand of a billion or so B-cells when you're born and that's it
04:15 < fenn> excluding bone marrow transplants etc
04:16 < fenn> .wik V(D)J_recombination
04:16 < saxo> "V(D)J recombination is the unique mechanism of genetic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation." - https://en.wikipedia.org/wiki/V(D)J_recombination
04:17 < fenn> when an antigen is present, ideally the antigen presenting cell stimulates the B-cell to start dividing
04:17 < fenn> immunology is horribly complicated and a rabbit hole
04:17 < fenn> not recommended
04:18 < fenn> there's no modification of RNA, it's a DNA-modifying process that is permanent
04:19 < fenn> immunity duration is because once the B-cell is no longer being stimulated, its population shrinks over time, in order to conserve energy and protein
04:24 < fltrz> fenn, thanks, any direct quote that that collection of B cells is fixed since birth, or couldn't the parent stem cells in bone marrow just keep producing B-Cells throughout life?
04:24 < fenn> uh i guess it's possible
04:24 < fltrz> also it displaces the question from time of infection to time of birth
04:25 < fltrz> how does the bone marrow or whatever parent cell make this high variation density in the genome code for antibodies without creating similar mutations in fixed function part of genome?
04:26 < fenn> read the VDJ recombination article
04:26 < fltrz> fenn, thanks for the link btw!
04:29 < fltrz> what, this somatic recombination also occurs in neurons?
04:29 < fenn> i would expect it's a one-shot process because the immune system is dormant during fetal development and during this period and only this period would you be able to switch off self-reacting immunoglobulins
04:30 < fenn> although some people on LSD claim their allergies magically went away after being exposed to the allergen while on LSD and in a particularly receptive state
04:30 < fenn> for what it's worth
04:30 < fenn> what about neurons?
04:30 < fltrz> I think we can safely discount that LSD thing
04:31 < fltrz> the WP article links to somatic recombination and states something similar happens in neurons APP
04:32 < fltrz> fenn, thanks for linking this, it's what I always tried to understand about adaptive immune system
04:32 < fenn> amyloid precursor protein is a sort of snot that is used to cover over bacteria in the brain, maybe it is similar to an antibody
04:34 < fltrz> it also mentions people with alzheimer have wider diversity of APP proteins,... so it looks like either immune system gone berzerk, or immune system failing against pathogen (although I suspect latter would be diagnosed as a brain infection)
04:34 < fenn> more likely immune system gone berserk
04:34 < fenn> chronic gum infections increase alzheimers risk
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04:36 < fltrz> fenn, the reason I suspect VDJ or other immune system variation occurs throughout the life of the organism, is because people can develop berserk immune systems over time, but I still agree there must be an early protected phase to make the immune system acquainted with self as long as the loss-of-protection signal is not received by immune system: perhaps getting born after spending 9months in uterus, or perhaps breaking out of an egg shell for
04:36 < fltrz> other animals
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04:37 < fltrz> before the Disney bubble is burst, ego gets acquainted with self
04:38 < fltrz> we don't show small children film noir, etc
04:38 < fenn> i think autoimmune reactions are caused by damaging agents; the damage causes localized immune signals to be sent, then the antigen presenting cells look around for antigens to present, and some of them are body proteins (or adducts or combinations of proteins) that were not switched off because they're normally not soluble
04:39 < fenn> like, myelin, or connective tissue
04:40 < fenn> leading to, respectively, MS and sjogren's
04:41 < fltrz> well, I guess simply living longer than expected can trigger the immune system in my theory too: if in a healthy young adult a self protein is invisible to the immune system, and only becomes visible by old age, or disease, then the immune system may interpret self as foreign
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04:42 < fltrz> I also think there must be a 2+ dimensional stress & appreciation signal, which gives feedback to the immune system
04:44 < fltrz> it can't just optimize for minimal stress, because then allowing attacked tissue to die would be interpreted as successful victory, which it isnt
04:44 < fltrz> it should strive for appreciation of the tissue cells that individually they report normal homeostasis
04:51 < fenn> "should" and "does" are not the same thing
04:52 < fenn> there are anti-inflammatory cytokines, prostaglandins, etc
04:52 < fenn> our terrible diet makes sure those never get release
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05:01 < fltrz> if a healthcare system will eventually run out of PPE, the dumbest thing seems to be to share PPE equally until the last limiting type of PPE. We shoulnd't just flatten the curve of the population, but also flatten the curve of hospital workers: if you want 90% of hospital workers active throughout epidemic, and convalescence takes on average say 2 weeks (just plugging numbers) you want to randomly select 10% of hospital workers to go naked before
05:01 < fltrz> only 10 x 2 weeks x 90% of wokers worth of limiting  PPE is left
05:02 < fltrz> this will be very unpopular among hospital workers though
05:03 < fltrz> until the *first limiting type of PPE sorry
05:04 < fltrz> and then the next 10% etc, so the first shift of naked hospital workers has healed while the second 10% shift is getting infected etc
05:06 < fltrz> of course the system should do its utter best to prevent running out of any PPE type
05:08 < fltrz> it will also be unpopular if it appears that the system may remedy the lack of PPE before all shifts have gone naked, so the first 10% should receive more compensation for taking the risk of going naked whereas the later shifts take the chance of receiving new PPE in time
05:15 < fenn> the whole reason this is a problem in the first place is hospital administrators are terrified of legal liability for exposing workers
05:16 < fenn> once they're out of masks, well, "there was nothing we could do!"
05:16 < fenn> they should be reusing and disinfecting masks right now, and at least it seems like they finally figured that out
05:17 < fenn> there's no "curve" for health workers anyway so the metaphor doesn't quite work
05:17 < fenn> there are other infectious agents besides the virus to worry about, e.g. antibiotic resistant Clostridium dificile
05:18 < fenn> there won't be enough new PPE to meet demand
05:20 < fenn> many hospitals have less than a week of masks remaining, at the current rate
05:21 < fenn> seeing how this is just getting started, i'm really wondering what they're thinking
05:22 < nmz787> how is it that they don't use masks all the time?
05:22 < nmz787> like, aren't enough infectious diseases capable of airborne transmission?
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05:24 < fenn> we've mostly eliminated things like tuberculosis
05:25 < fenn> airborne infectious diseases get public health priority, for obvious reasons
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05:34 < nmz787> but like, isn't every flu virus an airborne thing?
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05:36 < fltrz> nmz787, I think hospital workers all get flu shots?
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05:37 < fltrz> fenn, so there will be a lot of hospital workers getting CV simultaneously :/
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05:38 < fltrz> so not only governments didn't stock up proper pile of PPE for population, also hospitals didn't stock up PPE for their own workers for this type of event?
05:39 < fltrz> perhaps we deserve this shit
05:40 < fenn> no, trump voters deserve this shit
05:40 < fenn> the rest of us are innocent casualties
05:40 < fenn> also, you're belgian?
05:41 < fenn> i've only been talking about US hospitals, no idea what the situation is like in EU
05:41 < fenn> i saw a photo of a UK nurse wearing a trash bag and pleated mask
05:43 < fenn> i'm wondering what the hold up is with hydroxychloroquine. it seems to me there's more than enough data, and it's safe enough to just start giving it to literally everybody
05:44 < fltrz> fenn, double nationality, but yeah, born and raised and living in belgium
05:44 < fenn> in the mean time, while the government gets its shit together, if that ever happens, we can take certain supplements, which i'm supposed to be researching right now
05:47 < fltrz> fenn according to http://www.microbe.tv/twiv/twiv-593/ the choloroquine trials indicate that it is effective in reducing viral load, ... while increasing severity and mortality. also treatment and control arms were not blind "who wants to be guinea pig?"
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05:48 < fenn> 2 hours
05:48 < fenn> who the fuck has time for that
05:48 < fenn> podcasts
05:48 < fltrz> it's in the first half hour
05:48 < fltrz> IIRC
05:50 < fltrz> he said it was even in the papers of the preliminary trials; the head nurse / doctor in the podcast complained that the title of the trial paper said it was effective, but reading the paper itself its clear that it seems to work to decrease viral load, but complications are worse for some reason
05:51 < fenn> shouldn't it still be effective for prophylaxis?
05:55 < fltrz> fenn, like give to the general populace?
05:55 < fenn> yes
05:55 < fltrz> I don't think it's that cheap
05:55 < fenn> it's cheap enough
05:55 < fenn> $5 a person
05:56 < fenn> they're talking about a trillion dollar bailout
05:56 < fenn> or more
05:56 < fltrz> our government proudly announced they had secured enough (kg's) to treat patients
05:57 < fenn> each person needs a few grams
05:57 < fltrz> fenn, bailouts are mostly for fils-de-papa's and propping up health of our economy, soviet style
05:57 < fltrz> and making sure there will be enough bars when the crisis is over, so we can keep those flip-flops in the drunkard consumer state
05:58 < fenn> oh yeah, the bars and restaurants, great way to waste your altruism dollars
05:59 < fenn> usually they just give it straight to the bankers
06:06 < fenn> re: hydroxychloroquine paper, the treatment arm was mostly composed of elderly with severe cases, and the control arm was younger people
06:07 < fenn> this makes it "bad science" i guess, but i still think it's useful data
06:11 < fenn> this guy is full of shit
06:13 < fenn> right now we still have the luxury of ventilators, we can buff our nails and scoff at the lack of double blind randomized trials, but before long people will just be keeling over left and right
06:13 < fenn> in that situation throwing whatever at the wall and see what sticks makes a lot more sense, but since we *know* this is going to happen, we are already in that ethical context
06:14 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=9602a806 Michael Folkson: Add Miniscript workshop transcript >> http://diyhpl.us/diyhpluswiki/transcripts/advancing-bitcoin/2020/2020-02-07-andrew-poelstra-miniscript/
06:14 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=0da2051c Bryan Bishop: Merge pull request #82 from michaelfolkson/add-miniscript-workshop >> http://diyhpl.us/diyhpluswiki/
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06:32 < fltrz> fenn, thats a good point, I am trying to locate the paper he was discussing but have trouble finding it, do you have the paper for the french trial?
06:35 < fltrz> surely it shouldn't be hard to find a small fraction of elderly who understand controlled trials and who understand a trial is a guess either way, and are prepared to take a randdomized placebo/drug?
06:37 < fltrz> if all the dead elderly could look back and realize their non-participation was a missed chance to save lives of others, ... they are collectively doing it to themselves
06:40 < fenn> this is a draft
06:40 < fenn> .title https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view
06:40 < saxo> Hydroxychloroquine and azithromycin as a treatment of COVID-19.pdf - Google Drive
06:42 < fenn> there are plenty of different healthcare systems in the world. if the USA gives hydroxychloroquine to everyone and EU does not, that will give us plenty of data
06:42 < fenn> you don't need to say, ok, half of the people at this hospital get to die, the other half get to live, for science!
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07:00 < kanzure> ecdsa threshold signature scheme https://github.com/binance-chain/tss-lib
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07:39 < archels_> https://i.imgur.com/aIv1cde.jpeg
07:42 < fltrz> fenn, according to ecks and yuriwho the V(D)J recombination occurs constantly through life
07:43 < fltrz> archels_, lol
07:53 < fltrz> archels_, yeah really jealous about a bunch of significant other alternative histories
07:54 < fltrz> especially 1998
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08:04 < kanzure> "Verifiable secret redistribution for threshold sharing schemes" http://www.cs.cmu.edu/~wing/publications/Wong-Wing02b.pdf
08:07 < fltrz> kanzure, are you aware of any offline cryptocurrency proposal closer to cash?
08:13 < kanzure> chaumian banks?
08:13 < kanzure> not really offline...
08:14 < kanzure> perth mint has goldpass certificates that could presumably be stored offline
08:15 < kanzure> the problem with offline is the double spending problem: you have to be online to check for double spends.
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08:46 < abetusk> Anyone have opinions on this 'open source' qPCR machine? https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179133#sec014
08:46 < abetusk> The main component looks to be https://www.digikey.com/products/en?keywords=oda-6wb-500m-nd
08:50 < fltrz> kanzure, in UBI schemes, double spending is not too bad, because you can deduce the double / triple / ... spends from the offenders income
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08:51 < fltrz> so there is no need to immediately detect double spends, just eventually detect them
08:52 < fltrz> well suicidal people can do a final spending binge...
08:52 < fltrz> which will then force them to "make it count"
08:54 < kanzure> you do need to immediately detect it because otherwise whole sectors of the economy can be based on double spends
08:54 < kanzure> and by the time you detect it, it's too late- you'd be destroying large portions of the economy
09:19 < kanzure> .title https://eprint.iacr.org/2019/017
09:20 < saxo> Cryptology ePrint Archive: Report 2019/017 - CHURP: Dynamic-Committee Proactive Secret Sharing
09:35 < kanzure> .tw https://twitter.com/gottapatchemall/status/1242126431825489924
09:35 < saxo> RecV recombinase system for in vivo targeted optogenomic modifications of single cells or cell populations / https://www.nature.com/articles/s41592-020-0774-3 (@gottapatchemall)
09:36 < kanzure> https://gitlab.com/lightning-signer/docs/-/blob/master/README.md
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09:49 < kanzure> prehaps it's fate that today is the 4th of july, and you will once again be fighting for our lives, not from tyranny, oppression, or persecution, but from annihilation
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09:51 < fenn> is that from "independence day"?
09:52 < kanzure> yep
09:57 < fenn> http://nypost.com/2020/03/20/majority-of-nycs-coronavirus-cases-are-men-between-18-and-49-years-old/
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11:12 < fltrz> kanzure, individuals trading with other individuals don't need immediate verification, only the high value transactions, the individuals will simply no longer receive UBI until their UBI has payed off the debt
11:13 < fltrz> this can also come with a borrowing surcharge
11:15 < fltrz> basically it just needs a way to reach concensus on the date a stranger will be allowed to spend again, like a blacklist of expiration dates
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11:58 < kanzure> hmph
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--- Log closed Tue Mar 24 00:00:31 2020