--- Log opened Sun Apr 21 00:00:32 2024
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06:08 < hprmbridge> alonzoc> docl: I made mention of the "nitroplast" a few days ago. It's definitely very interesting, depending on the details it might be usable to engineer standard staple crops.
06:10 < hprmbridge> jason.crawford> Sarah Constantin did a writeup on the Minicircle follistatin thing. I only skimmed it but, she seems to be saying that it's plausible in theory, but that the data isn't there to prove anything. I know someone was calling bullshit on Minicircle and was planning to write up a debunking (won't name them in case they are not ready to go public with it). Has this been written up yet? cc @kanzure
06:10 < hprmbridge> jason.crawford> https://sarahconstantin.substack.com/p/minicircle-follistatin-gene-therapy
06:11 < hprmbridge> alonzoc> Most of the discussion I've seen on the nitroplast though is mostly investigating it's function and incorporating nitrogen fixation into the plants cells itself instead of working to improve the nitroplast and integrate the nitroplast itself
06:13 < hprmbridge> kanzure> @jason.crawford She is wrong. Check the comments.
06:14 < hprmbridge> kanzure> Separately I also replied to her on twitter
06:15 < hprmbridge> kanzure> she shouldn't be writing review articles if she doesn't actually know
06:15 < hprmbridge> kanzure> she even says in the blog post that she doesn't know
06:17 < hprmbridge> alonzoc> Even if everything minicircle says is correct, which it really isn't, you've gotta ask them "Why antibiotics for the off switch??". We're supposed to minimising antibiotic usage to reduce the risk of superbugs, this is the opposite of that
06:17 < hprmbridge> jason.crawford> yeah well she seems pretty open to input/criticism, I'm sure she will consider what you have to say
06:18 < hprmbridge> jason.crawford> I just saw other people discussing her post, and I knew you had thoughts, and I wanted to amplify any counterargument
06:19 < hprmbridge> alonzoc> Antibiotics don't even make much sense for this afaik as antibiotics main usage is for selecting for a transformation. If you've got your cool weird plasmids it'd be easier to code for some other signaling molecule that isn't an antibiotic
06:21 < hprmbridge> alonzoc> @kanzure just to highlight my potential ignorance, is there a reason for antibiotics as a stop method over anything else? Because I can't think of a good reason
06:25 < hprmbridge> yashgaroth> I did reply on her sustack (I'm Max btw) and yes I am still writing up the debunk. Sarah doesn't seem to have any context on how trash plasmids are. No one's arguing that follistatin increases muscle if you can get enough of it
06:26 < hprmbridge> yashgaroth> but I mean come on, fifty micrograms of plasmid to hit their claimed numbers? you could replace every monoclonal antibody therapy in existence if they're anywhere near their claimed numbers (considering the difference in half-life between follistatin and an antibody)
06:28 < hprmbridge> alonzoc> Defo a case of "If this worked you wouldn't need to start a dodgy clinic, you could just sell the technology to an established pharma company etc"
06:28 < hprmbridge> yashgaroth> antibiotic resistance isn't a concern tbh, it's not like they're put on it continuously and the dosage to activate Tet-Off is sub-therapeutic. It's just stupid to incorporate the "reversibility" when no one is gonna overdose on follistatin and the gene circuit for Tet-Off adds extra bulk to the plasmid and introduces a foreign protein
06:29 < hprmbridge> yashgaroth> yes if they made plasmids 1000x better, as they tacitly claim to do, it'd be multiple Nobels
06:32 < hprmbridge> jason.crawford> Yeah, makes sense, let me know when you have some longer writeup and I will help get eyes on it. (I don't have a particular side I'm pushing, but what you say makes sense, and I want to help get your objections out there)
06:34 < hprmbridge> yashgaroth> soon, I'll let you know
06:36 < hprmbridge> alonzoc> Also delivery of DNA with polyplexes isn't new so we'd already know if it worked so well
06:37 < hprmbridge> yashgaroth> yeah it's basically the worst method beyond just injecting naked DNA. But it is cheap and fairly safe, I'll give 'em that
06:39 < hprmbridge> alonzoc> Don't want your patients suing for giving them all cancer. Best to peddle snake oil
06:39 < hprmbridge> alonzoc> Also I'd be worried about mosaicism  as iirc plasmids and polyplexes don't like to travel that far
06:43 < hprmbridge> alonzoc> Tbh I'd love something nicer than viral vectors. But something that completely dodged the immune system and didn't require you take immunosuppressants is also basically the ingredient to a fairly bad bioweapon
06:49 < hprmbridge> yashgaroth> plasmids are fine for body-as-bioreactor therapies, where you just need some cells making a circulating antibody for you - Remicade or whatever. That's a $250B market on its own. And yes a sneaky viral vector is a great example of dual-use biotech
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08:59 < docl> would a semaglutide plasmid work? probably not, if the dose is milligram range
09:03 < hprmbridge> yashgaroth> semaglutide needs some weird chemical modifications to be effective, though you can probably overcome that by sheer quantity producing GLP-1 instead
09:06 < docl> would you want to make that in human cells directly, or could you use a gut microbe?
09:43 < hprmbridge> yashgaroth> native GLP-1 requires some post-translational modification that bacteria don't do. But the main problem is that unmodified GLP-1 doesn't cross the gut that effectively...even semaglutide has a terrible efficiency
10:00 < nsh> .m https://twitter.com/BrianRoemmele/status/1782047799514910720
10:00 < AugustaAda> ​“NASA Veteran’s Propellantless Propulsion Drive That Physics Says Shouldn’t Work Just Produced Enough Thrust to Overcome Earth’s Gravity” ␤  ␤ Article: <thedebrief.org/nasa-veterans-… https://t.co/XjP3M94a7J> ]
10:14 < docl> https://www.youtube.com/watch?v=DJjPi7uZ2OI&t=3696s // APEC 12/23: Asymmetrical Capacitance, Warp Drives & Torsion Physics
10:27 < L29Ah> 0 mentions of emdrive
10:28 < docl> seems like some kind of photon thruster?
10:32 < L29Ah> oh, "em drive"
10:36 < nsh> .g A system and method for generating forces using asymmetrical electrostatic pressure
10:36 < saxo> https://patents.google.com/patent/WO2020159603A2/en
10:50 < hprmbridge> alonzoc> Oh I saw that earlier and spent a while trying to figure out if it was another reactionless drive or just a badly written patent
10:51 < hprmbridge> alonzoc> Seriously it amazes me how many reactionless drive things is coming out of people affiliated with NASA
10:51 < docl> actually he's claiming it's an infinite energy machine. photon thruster is a possible explanation for what he's really seeing
10:52 < hprmbridge> alonzoc> Oh violating the universes space translational symmetry isn't enough? He's breaking time translation symmetry as well now?
10:53 < docl> ah, I wouldn't say that without scrutinizing his arguments (which I don't think I am quite qualified to do), he does mention those things
10:55 < hprmbridge> alonzoc> I'll give it a look when I have time, is he part of the quantised inertia people? All other reactionless drives I've recently justify themselves with QI
10:56 < docl> my dad invented one of these systems (claimed to have tested it before I was born with a tortion balance). it exploited permeability rather than permittivity to create the field asymmetry (2 fast switching magnets) but similar principle. I'm super skeptical but can't quite rule it out based on what I understand
10:57 < hprmbridge> alonzoc> docl: the symmetry thing is that conservation of momentum and energy is equivalent (assuming the universe is described by a Hamiltonian) to translation symmetry in space an time respectively. See Noether's theorem
11:00 < docl> hmm, so we just need to find a technicality where the equation is satisfied but you still get unintuitive effects like a continuously self-accelerating body that produces infinite energy :P
11:02 < hprmbridge> alonzoc> Hah. Well if you had negative mass that was negative *inertial* mass you could get a reactionless drive as the whole drive systems inertial mass would be zero so momentum would be conserved no matter what. Which is one reason why negative mass at macroscopic scales is suspect
11:03 < docl> an amusing bit in the video I linked, towards the end he suggests that we are accidentally making drives like this from space junk (asymmetric capacitors) and they keep accelerating until they make black holes -> why the aliens keep visiting us
11:05 < hprmbridge> alonzoc> Tbh if you want something that looked like a reactionless drive within known physics my main bet would be a neutrino rocket or if axions are real an axion rocket.
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12:03 < docl> well the effect in my dad's system would only depend on permeability constant + ability to switch two magnets fast enough that they keep breaking the acceleration symmetry. could perhaps map to something like axions but I don't know enough about those to say
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13:19 < docl> on closer examination, buhler's claimed mechanism seems to be static, not based on switching fields at all
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13:24 < docl> I wonder about the prospect of millimeter or smaller bioreactors for subdermal implantation. you could have a small colony of bacteria that are a reasonably low infection hazard if the container breaks, with pores to allow in feedstocks and allow drug molecules to exit
13:26 < docl> then you could maybe do natural selection on these, e.g. if their products worsen the skin condition around them, kill the bacteria and try again
14:24 < docl> (or yeast, etc)
14:41 < docl> https://joyfulmicrobe.com/winogradsky-column/
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16:05 < docl> .t https://www.nature.com/articles/s41467-023-39888-2
16:05 < saxo> Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes | Nature Communications
16:40 < docl> .wik In_vivo_bioreactor
16:40 < saxo> "The in vivo bioreactor is a tissue engineering paradigm that uses bioreactor methodology to grow neotissue in vivo that augments or replaces malfunctioning native tissue." - https://en.wikipedia.org/wiki/In_vivo_bioreactor
16:42 < docl> hmm, not seeing anyone insane enough to propose doing this with microbes
16:49 < fenn> bacterial LPS is super toxic to humans
16:51 < fenn> dialysis tubing would allow exchange of small molecules but you'd have to be very careful about it never having a slightly larger pore somewhere
16:52 < docl> maybe just pick a different microbe?
16:52 < fenn> the kind of bacteria that can survive the environment inside the human body are not the kind that you want inside the human body in large numbers ready to break loose and wreak havoc
16:54 < fenn> maybe cell free molecule systems would have the same benefits but without the disaster potential
16:55 < fenn> temporarily at least
16:56 < fenn> crimped dialysis tubing could be inserted under the skin with a large gauge needle
16:56 < fenn> i mean this is something you could have done regularly without any surgical complications
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21:08 < hprmbridge> nmz787> I burned my wrists today after welding for like an hour and a half with gloves that had cuffs which were too short. How much cancer am I getting?
21:10 < hprmbridge> nmz787> Also, bought this from AliExpress, bunch of parts were missing... I nearly cobbled it together but it doesn't run I think due to too many corners cut, trying to manage without all the parts https://www.nico71.fr/lego-vertical-pneumatic-engine/
21:11 < hprmbridge> nmz787> I guess that's what happens when you pay $23 to China for a thing that comes with a QR code to a not-pdf which has clear copyright marks to that dude's site :/
21:51 < jrayhawk> cancer's gonna depend on how well you take care of your immune system
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--- Log closed Mon Apr 22 00:00:33 2024