--- Log opened Wed Apr 19 00:00:36 2023
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02:13 < hprmbridge> jasonblick> just DM'd you
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04:13 < alethkit> Gutentag!
04:13 < alethkit> Out of curiosity, have any of you been in touch with Drexler lately?
04:14 < alethkit> He did mention some ways forwards at his latest Foresight Institute talk
04:39 < hprmbridge> Perry> He was never particularly communicative with me. Others have had more success.
04:44 < alethkit> https://foresight.org/summary/erik-drexler-cofounder-of-foresight-institute-msep-what-why-and-how/ has the main points
04:55 < hprmbridge> lachlan> The issue with what Eric Drexler (still) says, is that none of it involves actually going and building hardware
04:56 < hprmbridge> lachlan> The software side (molecular systems engineering platform, as he puts it) is obviously important, but it has almost zero value if there’s no way to actually manufacture stuff!
05:01 < hprmbridge> lachlan> They need to be build together as the capability of the manufacturing side increases
05:03 < hprmbridge> eleitl> Absolutely correct.
05:05 < hprmbridge> eleitl> https://news.ycombinator.com/item?id=35617100
05:16 < alethkit> From what I've gathered, the main pathways would be either biological or MEMS-adjacent?
05:16 < alethkit> (Software monkey here, so I couldn't really tell whether the details hold up)
05:20 < hprmbridge> kanzure> Direct atom placement would be best. Molecular biology is already a form of molecular nanotechnology, and should be used when appropriate, of course.
05:23 < hprmbridge> kanzure> On the protein side, take a look at recent work like rfdiffusion. It would be interesting to see (I mean mathematically model) if a protein mechanical computer would have competitive or at least interesting performance. Even so, we could build rods, shafts, gears, motors and other things out of protein, but protein assembly for computer-scale is less clear to me...
05:24 < hprmbridge> Perry> The phrase “direct atom placement“ is deceptive. There are a rare few times when you can directly place individual atoms. Mostly, atomically precise chemical reactions don’t involve moving one atom at a time.
05:25 < juri_> I can understand wanting to focus on the software side. that is still where our current 3d printing technology base is most lacking.
05:25 < juri_> it's easy to build machines that it's impossible to drive.
05:35 < alethkit> Personally, I would be a lot more comfortable with XNA, due to the intrinsic firewall
05:35 < alethkit> rfdiffusion seems like it would lead to accidental prions
05:35 < hprmbridge> kanzure> we are working on an XNA project too. a writeup will be posted soon.
05:35 < hprmbridge> kanzure> but slightly different initiative
05:36 < alethkit> Oh, good to know!
05:36 < hprmbridge> jasonblick> the anti academic sass in this drexler prez is so good
05:37 < hprmbridge> kanzure> the XNA project pertains more to improving DNA synthesis by several orders of magnitude.
05:37 < hprmbridge> jasonblick> his head is really in the right place on feasibility and implementation
05:38 < hprmbridge> kanzure> The cost of DNA sequencing has dropped by about 2,000,000x. Unfortunately DNA synthesis has been stuck for a long time.
05:38 < alethkit> I know Church's trying to speed it up with HGP-write
05:38 < alethkit> But I'm not sure that's going to be ready on time
05:38 < hprmbridge> kanzure> A few of the numbers of this chat actually got kicked out of HGP-write.
05:38 < alethkit> Wait, what?
05:38 < alethkit> Why?
05:39 < hprmbridge> kanzure> https://www.google.com/url?sa=t&source=web&rct=j&url=https://engineeringbiologycenter.org/wp-content/uploads/2019/03/Statement-of-Principle.pdf&ved=2ahUKEwiVrbqy-7X-AhU5lmoFHV7EBxsQFnoECBkQAQ&usg=AOvVaw2fGkXmPz_GFN6ZbvO3J62z
05:39 < hprmbridge> kanzure> er, https://engineeringbiologycenter.org/wp-content/uploads/2019/03/Statement-of-Principle.pdf
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05:41 < hprmbridge> kanzure> This was a result of the following article: https://www.technologyreview.com/2019/02/01/239624/the-transhumanist-diy-designer-baby-funded-with-bitcoin/amp/
05:43 < alethkit> Should have gone to India
05:44 < alethkit> https://nitter.unixfox.eu/pic/orig/media%2FFqQOV-yXwAEs6GX.jpg
05:54 < hprmbridge> eleitl> RFreitas has a pretty good bibliography on tooltip reactions among other things http://molecularassembler.com/Nanofactory/AnnBibDMS.htm
05:55 < alethkit> I'm confused as to how many experiments have actually been done
06:00 < hprmbridge> jasonblick> So nooby question here, but I recall a quote from Elon Musk on his post graduate research days where he says he "sought to leverage the billions of dollars spent toward R&D on semiconductor manufacture" to catalyze his formulation of an ultra capacitor based battery, and I was wondering where, in the context of the molecular assembler end goal, you guys think there are opportunities for us to
06:00 < hprmbridge> jasonblick> leverage existing ecosystems in a similar manner?
06:03 < hprmbridge> eleitl> Molecular biology in general, engineered enzymes and engineered proteins (e.g. structural scaffolding) specifically.
06:03 < hprmbridge> kanzure> well, molecular biology is 4 billion year old nanotech
06:03 < hprmbridge> kanzure> DNA is the most successful technology of all time. maybe even more successful than stellar fusion.
06:04 < hprmbridge> eleitl> More recently, you could see whether you can achieve a particular space filling a la virus capsid, with GA-engineered small, fast folders with ML folding forecast.
06:04 < hprmbridge> eleitl> All of this bases on existing, very large scale research.
06:06 < hprmbridge> jasonblick> Would you recommend NAMD/VMD, GROMACS, or other for Molecular Dynamics Simulation?
06:07 < hprmbridge> kanzure> have you used samson-connect?
06:07 < hprmbridge> jasonblick> Have not, should I? why?
06:15 < hprmbridge> eleitl> VMD/NAMD is very easy to use and supports the right force fields and water models to model very large wet biological systems. It can also handle machine-phase structures, though I'm not sure how accurate in vacuum it would be.
06:17 < hprmbridge> eleitl> I haven't tested it with ROCm, but it has very good CUDA support https://www.nvidia.com/en-sg/data-center/gpu-accelerated-applications/namd/
06:20 < hprmbridge> eleitl> ROCm support might be working already https://community.amd.com/t5/rocm/namd-3-0-delivers-scalable-molecular-dynamics-for-gpus/ba-p/531809
06:23 < hprmbridge> eleitl> https://www.amd.com/en/technologies/infinity-hub/namd or https://www.amd.com/en/technologies/infinity-hub/namd3 -- not sure what's the difference. Anyone having AMD Instinct hardware at your fingertips?
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06:25 < hprmbridge> eleitl> Not talking about cloud here, since the instance hours are so expensive that own hardware ROIs very quickly.
06:44 < alethkit> jasonblick: Have you looked into Atomic Semi?
06:46 < hprmbridge> eleitl> Here's an overview of several packages, especially if you're interested in the license https://en.wikipedia.org/wiki/Comparison_of_software_for_molecular_mechanics_modeling
06:47 < hprmbridge> Perry> I would recommend that you not think about simulating anything at this point. Unless you already have a very strong chemistry background, and already understand nanotechnology well, it’s premature.
06:49 < hprmbridge> Perry> there is also no particularly great need for software at this time. There is a tendency by computer scientists who get interested in nanotechnology to think “wow, I could really help accelerating this by writing some software!” But generally speaking, what’s needed at this point is people actually doing the work in the lab.
06:50 < kanzure> has zeloof published what exactly he wants to do with atomic semi? is he just doing a contract fabrication facility? will he be developing a custom PDK..?
06:53 < kanzure> maybe one thing a software monkey could do is make a better tool to monitor across the different equipment liquidation sites- i think that would be interesting across a range of projects
06:54 < hprmbridge> Perry> On behalf of whom?
06:54 < kanzure> these channel members, at least.
06:54 < kanzure> sometimes you get a good deal; that focused ion beam i bought was pretty cheap comparatively.
06:55 < hprmbridge> Perry> People who are really interested in this stuff should fill in their background, read Nanosystems, and contemplate actually building things.
06:55 < hprmbridge> Perry> The lab work is the hard part and is what we've been blocked on for 30+ years.
06:55 < hprmbridge> Perry> I filled in my own background in chemistry and physics. It was laborious but quite doable.
06:56 < hprmbridge> Perry> Now, with open courseware of various sorts online, one can do it even more easily.
07:14 < alethkit> There are equipment liquidation sites?
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07:53 < hprmbridge> yashgaroth> HGPauction is the big one, university surplus websites can be good but it varies, then eBay sellers and a few sites like LabX that mostly hunt underpriced equipment at auctions and flip for a markup
07:59 < superkuh> https://www.brainstimjrnl.com/article/S1935-861X(23)01745-X/fulltext?rss=yes "Sustained Modulation of Primate Deep Brain Circuits with Focused Ultrasonic Waves" "•
07:59 < superkuh> The stimulation is applied safely over the course of several months."
08:19 < docl> Spiroligomer chemistry is an APM pathway that's relatively mature (scalable synthesis has been demonstrated, you can make kilograms of anything you have the sequence for, 5kdalton molecules being the practical limit). It could probably benefit from tools that make it less expensive, much like anything else. Part of why I'm interested in cheap 3d printer kits for autopipetters. I'm also deep diving 
08:19 < docl> organic chemistry to see if I can spot a viable xna mechanism. The cool thing with spiroligomers is they don't avoid the low energy noncovalent effects that affect protein folding, so the folding can be predicted much more reliably/cheaply. The cando project is designed for this kind of molecular modeling. https://github.com/cando-developers/cando
08:27 < docl> er, do avoid
08:28 < juri_> does anyone have some favorite equipment liquidation sites here in europe? I got all into it in the states, but am a bit stymied here.
08:29 < hprmbridge> lachlan> docl: have you thought about working for schafmeister’s lab?
08:29 < docl> yeah have considered it
08:39 < kanzure> you would have to develop a healthy appreciation for lisp
08:40 < hprmbridge> lachlan> juri_: you were originally in the states?
08:40 < docl> I love the notion of lisp in the abstract. haven't *actually* gotten into it yet though. it would be an improvement over my current dayjob (java)
08:40 < kanzure> docl: maybe you could chemically polymerize a spiroligomer polymer from a non-spiroligomer template
08:41 < juri_> lachlan: yep.
08:41 < docl> kanzure: that's what I was thinking. maybe there's a polypeptide->spiroligomer route?
08:42 < hprmbridge> lachlan> in Germany now?
08:43 < kanzure> "Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids" https://europepmc.org/article/PMC/4277153
08:44 < docl> very cool, will read
08:44 < kanzure> david liu has a number of papers published on this kind of technique.
08:45 < docl> ahh, good to know
08:46 < juri_> lachlan: also yes. in berlin, now.
08:47 < juri_> I'm heavily interested in finding a SEM to repair, and tinker on / with.
08:47 < juri_> i miss my one from DC. :)
08:47 < kanzure> fix nmz787's electron microscope
08:48 < juri_> too far away. :)
08:48 < juri_> need one at my (yet to be purchased) getaway house, so my wife can get out of town and enjoy the outside, while i 'play' in my lab. :)
09:33 < hprmbridge> gourneau> https://www.forbes.com/sites/zinnialee/2023/04/19/billionaire-li-ka-shing-backs-biocomputing-startup-that-takes-on-ai-with-lab-grown-brain-cells
09:35 < hprmbridge> kanzure> ah that's great, I was just talking with cortical labs the other day
09:42 < hprmbridge> gourneau> Oh nice Stability.ai (the stable diffusion folks) just released their own open LLM named StableLM https://stability.ai/blog/stability-ai-launches-the-first-of-its-stablelm-suite-of-language-models
09:45 < alethkit> wonder if that's related to the "uh oh" tweet Emad posted 
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10:04 < hprmbridge> kanzure> "warming the surface of Mars by 50K using artificial aerosols" https://www.hou.usra.edu/meetings/ninthmars2019/pdf/6049.pdf
10:05 < hprmbridge> docl> good to see you here @gourneau
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12:30 < hprmbridge> nmz787> https://www.oregonlive.com/hillsboro/2011/08/worlds_largest_crane_--_the_lampson_ltl-2600_--_working_on_hillsboros_d1x_plant.html
12:30 < hprmbridge> nmz787> the crane, including it's 6.5 million lbs of auxiliary counterweights, weighs in over 10 million lbs
12:37 < hprmbridge> nmz787> https://developer.nvidia.com/blog/designing-arithmetic-circuits-with-deep-reinforcement-learning/
12:37 < hprmbridge> nmz787> https://ieeexplore.ieee.org/abstract/document/9586094
12:37 < hprmbridge> TTTA> Is that the same model they were using to stack/de-stack Starship before they finished stage 0?
12:38 < hprmbridge> nmz787> no idea
12:38 < hprmbridge> nmz787> I'm just reviewing some highlights of local fab builds
12:53 < hprmbridge> docl> I wonder if there are ways to optically steer monomers to desired reaction sites in a solution. maybe forms of xna where you have 4 intercompatible backbone molecules (or weakly bonded side chains you can cleave off before or after polymerization occurs) that reflect light in a certain frequency range like a solar sail so you can push them into place. could maybe involve directional fluorescence
13:00 < hprmbridge> nmz787> solar sail works in vacuum tho, right?
13:00 < hprmbridge> docl> well it's not dependent on that. small amount of force per amount of light though
13:00 < hprmbridge> nmz787> at the least, there'd be less friction
13:00 < hprmbridge> nmz787> ( in vcauuo)
13:01 < hprmbridge> nmz787> vacuuo
13:01 < hprmbridge> docl> good point. maybe vacuum oligosynthesis is a better application for this approach
13:01 < hprmbridge> nmz787> I've considered gas phase oligo synthesis a bit
13:02 < hprmbridge> nmz787> there's demonstrated MLD (molecular layer deposition) with amino acids
13:02 < hprmbridge> nmz787> I believe that was just conformal coating tho, not site-selective
13:03 < hprmbridge> nmz787> (though one could extrapolate possibilities from there)
13:04 < hprmbridge> docl> hmm. the antenna molecule might double as a protecting group, which you need to avoid duplications
13:05 < hprmbridge> nmz787> https://pubs.rsc.org/en/content/articlehtml/2017/ra/c7ra01918a
13:06 < hprmbridge> nmz787> "The films were deposited in an F120-Sat reactor (ASM Microchemistry Ltd) using TTIP and glycine, L-arginine, L-aspartic acid and succinic acid as precursors. The different organic precursors are sketched in Fig. 1 together with their names as used in this paper. Nitrogen was used as carrier gas supplied at a total rate of 500 cm3 min−1 from a Schmidelin-Sirocco-5 N2 generator with a purity of
13:06 < hprmbridge> nmz787> 99.999% with respect to N2 and Ar content. The films were deposited on precleaned single crystal substrates cut from Si(100) wafers."
13:06 < hprmbridge> nmz787> I passed up an ebay opportunity to get a relatively-local to me F120 SAT reactor
13:06 < hprmbridge> nmz787> 😦
13:06 < hprmbridge> nmz787> "I'll just build my own" I said
13:07 < hprmbridge> docl> very cool. I was thinking in liquid solution though, might be cheaper (if doable)
13:07 < hprmbridge> nmz787> "maybe this will be a waste of $$ and will just rot in my garage" I said
13:09 < hprmbridge> docl> https://en.wikipedia.org/wiki/Photolabile_protecting_group
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13:13 < hprmbridge> nmz787> oh look https://www.ebay.com/itm/394555474214
13:13 < hprmbridge> docl> nice!
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15:51 < hprmbridge> Perry> consider the size of an amino acid versus a wavelength of blue light.
17:44 < hprmbridge> nmz787> This is some sort of template-driven click chemistry sort of thing? The monomers just bond when they're adjacent?
17:44 < hprmbridge> nmz787> This paper isn't written clearly enough for me to tell, and I've been staring at it for a few minutes
17:45 < hprmbridge> nmz787> Re: https://europepmc.org/article/PMC/4277153
17:47 < hprmbridge> nmz787> "a catalyst or reagent initiates coupling between building blocks, resulting in their oligomerization"
17:48 < hprmbridge> nmz787> "Since the 5’ end of the DNA template contains a group capable of coupling with the first building block, the synthetic polymer emerges from the translation process covalently linked to its encoding template."
17:49 < hprmbridge> nmz787> "We tested the efficiency and selectivity of both types of substrates using five candidate coupling chemistries: amine acylation, reductive amination, oxime and hydrazone formation, and Cu(I)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC or “click” chemistry)."
17:51 < hprmbridge> nmz787> "After oligomerization of the substrates, dithiolthreitol (DTT) was added to cleave the disulfide linkers and liberate the synthetic polymer products."
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--- Log closed Thu Apr 20 00:00:37 2023