--- Log opened Mon Apr 20 00:00:57 2020
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04:27 < archels> hmm, we have so many open and interdependent open pull requests on GitHub, that it would be helpful to see a dependency graph
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06:26 < archels> haha, I just hit up sci-hub.tw/biorxiv.org because I spotted the "Preview PDF" button before "Download PDF"
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07:14 < fenn> you have to click "preview pdf" to get the "download pdf" to appear
07:14 < fenn> it's terrible
07:42 < fenn> "While the majority of the population has been infected with reovirus, infection is rarely associated with disease. However, reoviruses are considered to be oncolytic viruses meaning that they preferentially infect and lyse cancer cells. "
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08:09 < docl> reovirus based cancer cure?
08:13 < docl> .title https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918368/
08:13 < saxo> Reovirus in cancer therapy: an evidence-based review
08:14 < docl> "Reovirus, a double-stranded ribonucleic acid virus and benign human pathogen, preferentially infects and kills cancer cells in its unmodified form, and is one of the leading oncolytic viruses currently undergoing clinical trials internationally. With 32 clinical trials completed or ongoing thus far, reovirus has demonstrated clinical therapeutic applicability against a multitude of cancers"
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08:33 < docl> Immune system complicates everything. I kind of wonder if we'll replace the immune system with a synthetic one in the future.
08:38 < fenn> "Triscuit is baked by electricity, the only food on the market prepared by this 1903 process." (electricity biscuit, great band name)
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09:07 < docl> .wik https://en.wikipedia.org/wiki/Synthetic_immunology
09:07 < saxo> "Synthetic immunology is the rational design and construction of synthetic systems that perform complex immunological functions. Functions include using specific cell markers to target cells for destruction and or interfering with immune reactions." - https://en.wikipedia.org/wiki/Synthetic_immunology
09:08 < docl> Something recent: .title http://dx.doi.org/10.1021/jacs.9b11545
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09:12 < fenn> .title
09:12 < fenn> docl: welcome back to the land of the living
09:13 < docl> yeah I'm still alive :)
09:13 < docl> I'm doing science and I'm still alive
09:13 < docl> https://sci-hub.tw/10.1021/jacs.9b11545
09:13 < fenn> what could be better
09:13 < docl> .title
09:13 < saxo> Sci-Hub | A Multimachine Communication Network that Mimics the Adaptive Immune Response. Journal of the American Chemical Society | 10.1021/jacs.9b11545
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09:18 < docl> It occurs to me that a photonically controlled immune system could be possible
09:18 < fenn> go on
09:18 < docl> kind of like a photonically controlled polymerase for dna printing like kanzure was talking about
09:19 < fenn> ah yeah that was my first idea. but making the polymerase is the hard part
09:20 < fenn> how about a chip that does electricity induced dna synthesis? what was the keyword for that again?
09:22 < fenn> .title http://academic.oup.com/nar/article/33/14/e125/1021373
09:22 < saxo> Electrochemically directed synthesis of oligonucleotides for DNA microarray fabrication | Nucleic Acids Research | Oxford Academic
09:22 < fenn> low fidelity doesn't matter so much with high copy number
09:23 < fenn> the mutations may be beneficial, or they may cause an autoimmune reaction, but if there's no B-cell stimulation it shouldn't matter
09:24 < fenn> to be clear, this would be a complex and possibly dangerous implant
09:25 < fenn> it could even be used to deliver a virus directly into someone's bloodstream through the same data channel used to deliver immune system updates
09:27 < docl> If it can be done for DNA, it seems likely it could be done for glycoproteins/antibodies
09:28 < fenn> there are many more amino acids than DNA bases, (20 vs 4) so it would be much more complex
09:28 < docl> yeah it's basically hooking your genetic code up to the internet. you want really good security against malicious actors.
09:29 < fenn> also there are enzymes to amplify (duplicate) DNA, not so much for proteins
09:32 < docl> hmm. maybe it makes more sense to use DNA/RNA to produce the desired proteins rather than trying to make them directly on the chip
09:33 < docl> you could maybe have prefabbed proteins that are released from storage chambers where they are stored in dessicated form
09:35 < docl> produced by engineered bacteria externally
09:36 < docl> I wonder how much actual mass in protein we use up in a day for immune activity?
09:43 < fenn> a few grams
09:45 < fenn> you'd want to release transfection reagents to transform the body's own circulating immune cells
09:45 < fenn> or store some batch of cloned stem cells inside the chip
09:46 < fenn> human cells can't be dessicated and remain viable
09:46 < fenn> desiccated*
09:47 < fenn> .title http://www.nature.com/articles/nbt0200_168
09:47 < saxo> Trehalose expression confers desiccation tolerance on human cells | Nature Biotechnology
09:48 < fenn> probably relevant to cryonics etc
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09:50 < docl> yeah I've read that one :)
09:52 < docl> trehalose is a good cryoprotectant. major part of the tardigrade survival mechanism. desiccation is basically a form of high temperature vitrification.
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10:08 < docl> https://sci-hub.tw/10.1006/cryo.2001.2324
10:08 < docl> .title
10:08 < saxo> Sci-Hub | Desiccation Tolerance in Human Cells. Cryobiology, 42(3), 207–217 | 10.1006/cryo.2001.2324
10:10 < docl> They also managed to get human cells to withstand desiccation without the adenoviral vector induced trehalose. Unfortunately it sounds like they were limited to 5 days or so (speculated to be due to free radical damage from fluorescent lights)
10:13 < docl> .title https://sci-hub.tw/10.1021/acs.nanolett.9b04109
10:13 < saxo> Sci-Hub |  | 10.1021/acs.nanolett.9b04109
10:13 < docl> "A Cold-Responsive Nanoparticle Enables Intracellular Delivery and Rapid
10:14 < docl> Release of Trehalose for Organic Solvent-Free Cryopreservation"
10:14 < docl> "In this study, a cold-responsive polymer (poly Nisopropylacrylamide-co-butylacrylate) is utilized to synthesize nanoparticles for encapsulation and intracellular delivery of trehalose. The trehalose-laden nanoparticles can be efficiently taken up by mammalian cells. The nanoparticles quickly and irreversibly disassemble upon cold treatment, enabling controlled and rapid release of trehalose from the n
10:14 < docl> anoparticles inside cells. "
10:15 < docl> I always wondered if microencapsulation would be the ticket to better cryonics
10:16 < fenn> don't you need a crapton of trehalose? how do you get so many nanoparticles inside of cells?
10:16 < fenn> like single digit x% by weight
10:19 < docl> maybe they aren't achieving vitrification, just slow-freezing with viability (ice forms outside the cell and slowly draws out the water until the cytosol inside the cell vitrifies)
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10:27 < docl> hmm. they didn't actually go to low temperatures in that experiment, just 0 celsius
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10:39 < docl> .title https://sci-hub.tw/10.1016/j.cryobiol.2018.11.002
10:39 < saxo> Sci-Hub | Apatite nanoparticles mediate intracellular delivery of trehalose and increase survival of cryopreserved cells. Cryobiology | 10.1016/j.cryobiol.2018.11.002
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10:41 < docl> "A large amount of trehalose (up to 237 ± 8.5 mM) can be delivered to smooth muscle cells incubated in a medium containing trehalose and apatite nanomaterials at 37 °C for 6 hours. Our data showed that trehalose was efficiently delivered intracellularly with the aid of nanoparticles (NP), with a loading efficiency up to 137.3 ± 34.5%, thus allowing for cryopreservation of LMC with nontoxic sugar as
10:41 < docl> the sole cryoprotectant."
10:44 < docl> assuming they are talking milimolar in the sense of moles per liter, that's not really all that high of a concentration. I think vitrification was 6.0 molar or something
10:53 < fenn> 6M sounds too high
10:55 < fenn> from another paper on oocyte preservation,  "intracellular trehalose concentration was kept between 0.05 and 0.08 M"
10:58 < docl> 9.3 M according to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781097/
10:59 < docl> .title
10:59 < saxo> Physical and biological aspects of renal vitrification
10:59 < fenn> that's the extracellular concentration
10:59 < fenn> less than 9.3M anyway
10:59 < docl> Of course, they would have ramped up to that slowly starting with a lot less.
11:00 < fenn> also 9.3M of what, it doesn't say
11:01 < fenn> it's a type error
11:03 < fenn> "M22 is composed of 2.8 M Me2SO, 2.8 M formamide, 2.7 M ethylene glycol, 0.5 M N-methylformamide, 0.3 M 3-methoxy-1,2-propanediol, 2.8% (w/v) (less than 0.006 M) polyvinylpyrrolidone K12, 1% (w/v; less than 0.006 M) polyvinylalcohol-polyvinylacetate copolymer [61], and 2% (w/v; less than 0.03 M) polyglycerol [1]. We refer here to “% M22” (v/v) as the percent of that maximum working
11:03 < fenn> concentration (9.4 M) used."
11:03 < fenn> nevermind the unit errors, it doesn't contain trehalose
11:04 < fenn> the amount of stuff (and mass) for a given concentration is proportional to the molar mass
11:13 < docl> looks like they perfuse the full strength concentration after cooling to -22C (hence the name), lower concentrations at higher temperatures (8.4M already by the time they reach that step).
11:16 < fenn> .units 2.8+2.8+2.7+0.5+0.3+0.006+0.006+0.03
11:16 < saxo>  Definition: 9.142
11:16 < fenn> so i guess they're just adding up the individual concentrations
11:21 < docl> .title https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001869/
11:21 < saxo> Genetic Suppression of Cryoprotectant Toxicity
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12:38 < kanzure> our draft on electronic manipulation of DNA polymerase - http://diyhpl.us/~bryan/papers2/bio/Electronic%20manipulation%20of%20polymerase%20for%20DNA%20synthesis.2017-12-04.pdf
12:38 < kanzure> cc docl fenn
12:47 < docl> thanks kanzure
12:50 < fenn> i'm pretty sure i never read the whole thing the first time
12:52 < fenn> it's kinda crazy that cordycepin isn't even toxic in small amounts
12:54 < fenn> "Because cordycepin is similar to adenosine, some enzymes cannot discriminate between the two. It can therefore participate in certain biochemical reactions (for example, incorporation into an mRNA molecule, resulting in premature termination of protein synthesis)"
12:55 < fenn> i had read somewhere that it's a potential antiviral because viruses go through so much RNA, and partial viral genomes are not very replicatory
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13:01 < fenn> cute idea: "phage antibodies: filamentous phage displaying antibody variable domains"
13:01 < fenn> no rabbits needed
13:02 < fenn> that was 32 years ago. how have we not kicked every infectious disease off this planet yet
13:03 < yashgaroth> that became phage display technology
13:04 < yashgaroth> turns out phages are pretty immunogenic themselves
13:05 < fenn> you can cut the protein off the phage body first
13:05 < fenn> i think it's more useful as directed evolution for antibody optimization
13:06 < fenn> use bacterial hosts engineered to present e.g. SARS-2 spike protein on their surface, the phage mutates to more readily bind to that antigen
13:07 < yashgaroth> that first one just sounds like e coli-based protein production with extra steps, and yes the bulk of it is/was used for antibody optimization before better platforms came out
13:07 < fenn> (for an enveloped virus it'd make more sense to use something without a cell wall)
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13:07 < yashgaroth> ehh e coli still have an outer membrane
13:08 < fenn> it's all gnarly
13:08 < yashgaroth> phages seem to stick to it and endocytose okay, can't be that bad
13:08 < fenn> yeah but it's not like a virus coat
13:09 < yashgaroth> true, but from my experience with phage display it's close enough to not matter, if all you need is a strong binder
13:10 < fenn> i wonder why i never learned about this in school
13:10 < fenn> i thought it was much more recent because i only learned about it in 2011-ish
13:11 < yashgaroth> it's a niche technique, but it's been around for a while...the closest I learned to it in school was yeast two-hybrid
13:11 < yashgaroth> but nowadays for finding antibodies most labs will use something like humouse
13:15 < fenn> antibody therapeutics only became a thing post-2010 right? (humira, etc)
13:16 < fenn> 2015+
13:17 < fenn> hmm humira was approved in 2002
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13:21 < fenn> god these new drug names are impossible
13:22 < fenn> ok at least the US does the sensible thing of appending random letters to the drug name for biosimilars
13:29 < yashgaroth> yeah a lot of the still-current blockbusters are from ~2000, the low-hanging fruit days; earlier than that were mouse antibodies from hybridomas which had...problems
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13:52 < fenn> .title https://www.newsweek.com/tissue-surgeon-ear-mouse-human-organs-transplant-cell-phones-666082
13:52 < saxo> Exclusive: Whatever Happened to the Mouse with the Ear on Its Back?
13:54 < fenn> "It didn't actually live happily ever after, did it?
13:54 < fenn> Of course it did. The happy little mouse. That little mouse was very pleased that he could contribute in some way and make people's lives better."
13:55 < archels> thinking of buying this https://www.ebay.de/itm/Lenovo-ThinkPad-X1-Yoga-1st-Gen-i7-6600U-2x-2-6GHz-16GB-RAM-256GB-NVMe-SSD-Touch/352824820273
13:55 < archels> and upgrading to a 1 TB SSD
13:55 < fenn> don't encourage them
13:56 < fenn> there's really no reason to get a new "lenovo"
13:58 < archels> new used
14:00 < archels> they're making ThinkPads with AMD Ryzens now, if my budget was inf, I'd probably go for those
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16:08 < lsneff> .title https://phys.org/news/2020-04-scientists-uncover-principles-universal-self-assembly.html
16:08 < saxo> Scientists uncover principles of universal self-assembly
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