--- Log opened Fri May 13 00:00:21 2022
00:07 < juri_> https://www.statnews.com/2022/05/11/transfusion-of-young-cerebrospinal-fluid-is-memory-elevating-elixir/
00:08 < juri_> I can see the memory extension startup forming before my very eyes.
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06:17 < kanzure> lsneff: no i was looking for something on ribosome immobilization or as a tethered biosensor but haven't found anything
06:17 < kanzure> yashgaroth might know
06:18 < kanzure> "Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17" https://www.nature.com/articles/s41586-022-04722-0
06:19 < docl> .tw https://twitter.com/mechadense/status/1525057194147864579
06:19 < saxo> Molecular lego with selfassembly uses the wrong measures for progess IMO. / The most important measure is: / ▶degree of termination control and / — stiffness of assemblies https://twitter.com/mechadense/status/1525017332229316610 (@mechadense)
06:19 < docl> .tw https://twitter.com/mechadense/status/1525102213265227785
06:19 < saxo> A bit more on selfassembly: / There's are a few neat tricks I found that may not be well known. They require selfassemblies to be sufficiently stiff. / Trick one: https://twitter.com/mechadense/status/1525083979606634498 (@mechadense)
06:20 < docl> mechadense posting on selfassembly stuff
06:22 < yashgaroth> you can immobilize a ribosome or most other proteins pretty easily, strep tag or his tag or that spytag from the paper, there's a few others
06:23 < kanzure> ribosome seems to do tRNA matching by conformational changes to reject or accept the tRNA payload
06:23 < kanzure> maybe mechanical pressure against the 30nm structure of the ribosome can change conformation enough to change synthesis fidelity
06:24 < yashgaroth> changing fidelity is one thing, or at least reducing it...coding arbitrary protein synthesis is another
06:24 < kanzure> that paper is good, pretty sure it might all be marriman's idea
06:24 < kanzure> this one: https://www.pnas.org/doi/pdf/10.1073/pnas.2112812119
06:25 < kanzure> merriman's, rather
06:25 < yashgaroth> yeah sensing is far easier than writing
06:27 < docl> stepwise synthesis in a series of microscopic reaction vessels? using electric fields to push things around
06:28 < kanzure> if you had a sufficiently slow ribosome you could flow tRNA by it in short pulses, pretty sure this was nmz787's idea around enzymatic dna synthesis
06:28 < kanzure> https://groups.google.com/g/enzymaticsynthesis
06:30 < yashgaroth> ribosomes are already phenomenally slow by biology standards, eukaryotic ones do about 2aa/sec and like I say it's fairly easy to make a protein that just works shittier than the wild-type
06:30 < kanzure> oh it's only 2aa/sec??
06:30 < yashgaroth> ofc it works 10x slower than the prokaryotic ribosome because it has increased error-checking, but still
06:30 < yashgaroth> yeah it's hella slow, imagine how long titin takes to synthesize
06:30 < kanzure> that's actually pretty good for instrumentation of it
06:33 < yashgaroth> is the use case here just that it'd eventually outpace DNA synthesis being coupled to in vitro transcription and translation with a normal ribosome?
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06:33 < kanzure> just programmable protein synthesis
06:33 < kanzure> possibly for the manufacture of protein nanostructures
06:36 < kanzure> https://milan.cvitkovic.net/writing/neurotechnology_numbers_worth_knowing/
06:37 < yashgaroth> it's an understudied field, but mostly because traditional DNA->RNA->protein or chemical peptide synthesis cover the vast majority of use cases. You need to guarantee a higher fidelity than chemical synthesis (getting better than in vivo is out of the question), and both have very high throughputs economically
06:38 < yashgaroth> it's the same as with DNA synthesis, one missed or repeated insertion and you blow the protein. Not quite as bad as with DN
06:39 < yashgaroth> A, but proteins aren't super tolerant of indels either
06:39 < kanzure> polymerase is harder because it incorporates a few thousand nucleotides per second, so you have to flow faster or have shorter pulses of dense nucleotide fluid flowing over the polymerase
06:41 < muurkha> kbps
06:41 < yashgaroth> oh it's not really gonna be feasible for DNA synthesis in any reasonable timeframe. Just giving context to a 99% accuracy rate
06:44 < yashgaroth> the main use I can see for this would be in synthesizing a tiny quantity, like a few dozen molecules, of extremely different proteins. If you're looking to evolve a particular protein you'd do fuzzy synthesis coupled with ribosome display or something
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06:47 < yashgaroth> something like nanopore-based protein sequencing would be interesting to fill the gaps left by mass spec, weird that that's only been shown late last year https://ceesdekkerlab.nl/wp-content/uploads/2021/07/science.abl4381.pdf but at least it's happening
06:56 < kanzure> ribosome nanomanufacturing would be useful for nanofactory bootstrapping stuff... producing small protein tools that help you build other protein tools.
07:05 < docl> true, but so would stepwise approaches (whether you use that to make DNA, RNA, or proteins directly). seems like a microfluidic factory on a chip could be quite versatile
07:07 < kanzure> i don't think anyone has demonstrated stepwise programming of polymerase or any other ticker tape enzymes
07:10 < docl> if you know the dna sequence you want, you can stepwise synthesize that. (I'm thinking in context of lots of home labs working in parallel without having to ship delicate molecules around, so they can experiment in parallel)
07:12 < docl> obviously polymerase (or any other naturally occurring protein) can be synthesized from dna/rna
07:13 < docl> maybe not so true for direct stepwise protein synthesis though
07:14 < yashgaroth> DNA is very stable for shipping, RNA the opposite. Proteins somewhere in the middle
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07:17 < docl> fair, but even with dna there's an advantage to being able to download the thing you want instead of wait for the postal service
07:20 < yashgaroth> oh definitely, though don't talk about useful home DNA synthesis too loudly or the three-letter agencies will visit
07:21 < docl> spiroligomer synthesis would also be an option for microfluidic labs
07:23 < kanzure> have useful things been made from spiroligomers?
07:26 < docl> https://www.researchgate.net/publication/232649704_A_Spiroligomer_a-Helix_Mimic_That_Binds_HDM2_Penetrates_Human_Cells_and_Stabilizes_HDM2_in_Cell_Culture
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07:33 < docl> wish I could find more details, but there are apparently atomically precise membranes you can make with them
07:33 < docl> https://www.osti.gov/biblio/1411063-atomically-precise-membranes-separation-hydrocarbons
07:35 < docl> https://www.longevity.technology/building-an-artificial-immune-system/
07:38 < docl> "We’ve made molecules that bind to protein, we’ve made molecules that accelerate chemical reactions, we’re making molecules that can assemble to make little triangular pores that we can crosslink into membranes that could then filter things through these pores selectively,” says Schafmeister. “Just like what proteins can do – except that we can control it with the ability to control the 
07:38 < docl> shape of the molecules. And if you control the shape, you control what they do.”
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07:46 < yashgaroth> there are plenty of applications for large rigid molecules with programmable moieties, but it's a bit of a stretch to argue they'll be better at catalyzing reactions than proteins
07:47 < yashgaroth> catalysis isn't usually just 'have the right atoms in the right places', there's a reason enzymes flex
07:49 < yashgaroth> plenty of room to beat antibodies in thermostability tho
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08:22 < kanzure> https://www.theonion.com/autistic-man-grateful-webpage-less-than-500-mb-t-1922605070
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09:36 < superkuh> Is every article link on https://www.brainstimjrnl.com/ broken for anyone else?
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09:41 < fenn> 403 Forbidden cloudflare
09:41 < fenn> but that's probably not what you meant
09:42 < superkuh> Correct. Every link like https://www.brainstimjrnl.com/article/S1935-861X(22)00083-3/fulltext goes to "This page does not exist"
09:42 < superkuh> "Mechanistic insights into ultrasonic neurostimulation of disconnected neurons using single short pulses"
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09:44 < fenn> both html and pdf links in the current volume work in chrome
09:47 < fenn> i may have had to turn off ublock to get it to work in chromium; it's very slow
09:48 < superkuh> I manged to assemble a pdf url manually from a sciencedirect mirror, https://www.sciencedirect.com/science/article/pii/S1935861X22000833/pdfft?isDTMRedir=true&download=true
09:51 < muurkha> cool
09:58 < nsh> \o/
09:58 < nsh> hyperlink assemblies for the hyperlink assemblinators!
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11:04 < kanzure> "Autistic reporter Michael Falk interviews new prison inmate, disgraced financier, Brian Wasserman, and becomes spellbound by the repetitive monotony of daily prison life."
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11:14 < fenn> public service announcement: git add -i
11:14 < fenn> "if you modify a number of files extensively, then decide that you want those changes to be partitioned into several focused commits rather than one big messy commit."
11:19 < fenn> i have to say though, this interface is weird
11:20 < kanzure> often i have to yank recent changes in a paste buffer because i only want to commit other changes to a file first
11:26 < fenn> http://git-scm.com/book/en/v2/Git-Tools-Interactive-Staging staging patches section explains how to do only a small part of a file
11:29 < fenn> jeez now google thinks i'm a robot
11:30 < fenn> i'm pretty sure that after the robot revolution happens, the robots won't think i'm a robot
11:32 < mrdata> how will they know?
11:36 < fenn> heart rate variability by doppler radar
11:37 < fenn> a reverse voigt-kampff test
11:37 < fenn> my pattern of blinking will not conform to a simple fourier series autoregression
11:37 < fenn> etc
11:41 < mrdata> they will fix you with an implant, then
11:42 < fenn> the more implants the better
11:42 < fenn> sudo make me like tetsuo
11:45 < fenn> not THAT tetsuo
11:47 < fenn> tetsuo shima but without all the unresolved teen angst
11:48 < kanzure> nani?
11:49 < kanzure> voigt-kampff music https://www.youtube.com/watch?v=yMFUP2ny6dc
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12:49 < nmz787> I have the issue regularly (monthly?) where I work on a feature in a file, but don't fully complete it (and thus remain uncommitted), then find some unrelated bug and fix that... but then I have these changes that I want to commit separately... and yeah, saving the `git diff` and then selectively reverting stuff, committing, selectively adding in from my saved diff, and committing... is definitely a 
12:49 < nmz787> thing I do which I had a better means to accomplish
12:53 < nmz787> I just realized a tesseract is just a pixelated torus
13:22 < fenn> i don't think so. draw a connectivity graph/network
13:27 < fenn> googled for "tesseract connectivity graph", got CAPTCHA'd. "Why is this happening?" -> "Sometimes you may be asked to solve the CAPTCHA if you are using advanced terms that robots are known to use" uhhh i hope that's not the reason
13:30 < fenn> the real reason was "you weren't running javascript"
13:35 < fenn> in a 3d torus each node has 6 neighbors, but in a 4d cube each node has 3 neighbors
13:37 < fenn> .wik Torus fusion
13:37 < saxo> "Torus fusion (tofu) is a proprietary computer network topology for supercomputers developed by Fujitsu. It is a variant of the torus interconnect." - https://en.wikipedia.org/wiki/Torus_fusion
13:37 < fenn> i didn't realize there *could* be proprietary network topologies
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14:49 < nmz787> i mean if you look at the moving tesseract videos/gifs... it could just as easily be an inner-tube that is being rolled
14:49 < nmz787> (not rolled as in rolling a wheel along a road, orthogonal to that direction)
14:50 < nmz787> i.e. rolling the tube past the spokes of a wheel
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16:47 < kanzure> .wik armulator
16:47 < saxo> "ARM Instruction Set Simulator, also known as ARMulator, is one of the software development tools provided by  the development systems business unit of ARM Limited to all users of ARM-based chips." - https://en.wikipedia.org/wiki/Armulator
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17:21 < docl> planning to have a garage of my own this summer, so it's somewhat realistic to start planning out a hardware project. leaning towards trying an electrowetting approach to microfluidics for stepwise oligonucleotide synthesis
17:27 < L29Ah> sounds cool, i hope you'll have a blog with updates and pics
17:28 < fenn> i hope you'll accomplish something worthwhile, and then publish schematics and code sufficient to reproduce it
17:28 < docl> yeah, it's pointless if not well documented enough to reproduce
17:29 < docl> as a starting point I'm thinking of leveraging an existing e-paper display, like maybe the inkplate since it's open source
17:29 < docl> .title https://www.crowdsupply.com/soldered/inkplate-6
17:29 < saxo> Inkplate 6 | Crowd Supply
17:31 < docl> and I recently registered the domain moredoingstuff.com which is probably where I will host the blog
17:32 < kanzure> let us know if you need anything, specific equipment, random ebay stuff, etc
17:32 < docl> will do
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18:13 < nmz787> docl: have you seen the opendrop and gaudi labs knockoff (I think)
18:15 < docl> no, hadn't heard of them
18:15 < docl> looking at opendrop now
18:17 < docl> very cool!
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20:50 < muurkha> .t https://www.imperial.ac.uk/news/236418/cells-block-nerve-cell-regeneration-with/
20:50 < saxo> T cells block nerve cell regeneration with age, but can be reversed – mice study | Imperial News | Imperial College London
20:50 < muurkha> with mabs
20:51 < muurkha> in mice
20:51 < lsneff> Good luck docl
20:52 < lsneff> let me know if there’s anything I can help with when you get started
20:53 < muurkha> I'm guessing T-cell involvement means that reversing this mechanism will cause cancer
20:56 < muurkha> if true, maybe there's epidemiological evidence for that in existing data, since there is existing population variability in aging-related cognitive decline
22:06 < lsneff> It’s difficult to figure out how to express nicely that it’s okay to be working on things that don’t matter, but don’t delude yourself that they do
22:31 < nmz787> docl: I guess purpledrop is the academic one
22:32 < nmz787> that team did some further work on integrating it into some automated workflows
22:32 < nmz787> I can't remember exactly right now what
22:32 < nmz787> sample prep or something
22:34 < nmz787> purpledrop repos have been committed to recently https://github.com/uwmisl
22:34 < nmz787> they used kicad, well that's cool
22:35 < nmz787> https://misl.cs.washington.edu/
22:35 < nmz787> Domains from molecular systems (like DNA storage!) to medical diagnostics rely on microfluidic devices for automation. This doesn’t just make things faster; it’s essential to minimizing human error and enabling new, more complex applications. The PurpleDrop hardware and Puddle software aim to make microfluidic automation cheaper, more reliable, and easier to use.The code is open source and 
22:35 < nmz787> developed on GitHub.
22:35 < nmz787> https://www.youtube.com/watch?v=uwiINEcYXLQ
22:35 < nmz787> .title
22:35 < saxo> ASPLOS '19 Lightning Talk - Puddle: A Full-Stack Microfluidics System - YouTube
22:38 < nmz787> that's a very nice 2 minute video
22:38 < nmz787> I want one
22:39 < nmz787> I'd want to be able to split up the drops to even smaller volumes, for transitioning to a silicon chip with nanofluidics on it
22:39 < nmz787> I wonder if electrowetting works on the nanofluidic level
22:39 < nmz787> .wik electrowetting
22:39 < saxo> "Electrowetting is the modification of the wetting properties of a surface (which is typically hydrophobic) with an applied electric field. /  The electrowetting of mercury and other liquids on variably charged surfaces was probably first explained by Gabriel Lippmann in 1875 [...]" - https://en.wikipedia.org/wiki/Electrowetting
22:40 < nmz787> .g electrowetting voltage
22:40 < saxo> https://pubs.rsc.org/en/content/articlelanding/2016/sm/c6sm01565d
22:40 < nmz787> .title
22:40 < saxo> Ultra-low voltage electrowetting using graphite surfaces - Soft Matter (RSC Publishing)
22:42 < nmz787> """Addition of a dielectric film to the surface of the substrate, which insulates the electrode from the liquid thereby suppressing electrolysis, has led to technological advances such as variable focal-length liquid lenses, electronic paper and the actuation of droplets in lab-on-a-chip devices. The presence of the dielectric, however, necessitates the use of large bias voltages (frequently in the 
22:42 < nmz787> 10–100 V range). Here we describe a simple, dielectric-free approach to electrowetting using the basal plane of graphite as the conducting substrate: unprecedented changes in contact angle for ultra-low voltages are seen below the electrolysis threshold (50° with 1 V for a droplet in air, and 100° with 1.5 V for a droplet immersed in hexadecane), which are shown to be reproducible, stable over 
22:42 < nmz787> 100 s of cycles and free of hysteresis. Our results dispel conventional wisdom that reversible, hysteresis-free electrowetting can only be achieved on solid substrates with the use of a dielectric. This work paves the way for the development of a new generation of efficient electrowetting devices using advanced materials such as graphene and monolayer MoS2."""
22:42 < nmz787> .g ewod dielectric thickness
22:42 < saxo> https://scholar.google.com/scholar?q=ewod+dielectric+thickness
22:48 < nmz787> https://aip.scitation.org/doi/10.1063/1.1504171
22:48 < nmz787> .title
22:48 < saxo> Just a moment...
22:48 < nmz787> Low voltage electrowetting-on-dielectric 
22:48 < nmz787>  Journal of Applied Physics 92, 4080 (2002); https://doi.org/10.1063/1.1504171 
22:50 < nmz787> """This dependence of applied voltage on dielectric thickness is confirmed through EWOD experiments for three different dielectric materials of varying thickness: Amorphous fluoropolymer (Teflon® AF, Dupont), silicon dioxide (SiO2) and parylene. The dependence on the dielectric constant is confirmed with two different dielectric materials of similar thickness: SiO2 and barium strontium titanate. In 
22:50 < nmz787> all cases, the surface is coated with a very thin (200 Å) layer of amorphous fluoropolymer to provide initial hydrophobicity. Limiting factors such as the dielectric breakdown and electrolysis are also discussed. By using very thin (700 Å) and high dielectric constant (∼180) materials, a significant contact angle change (120°→80°) has been achieved with voltages as low as 15 V. Based on these 
22:50 < nmz787> results, a microfluidic device has been fabricated and tested, demonstrating successful transporting (pumping) of a 460 nL water droplet with only 15 V."""
22:51 < nmz787> so 70nm + 20nm == 90nm.... 90nm/15V == 6nm/1V
22:52 < nmz787> or 1V / 6nm
22:52 < nmz787> electric field strength
22:53 < nmz787> 60 Angstroms for the 1V that a common CPU transistor might roughly see
22:53 < nmz787> doable with ALD for sure
22:56 < muurkha> ALD to deposit a single-atom-thick or single-molecule-thick layer of something hydrophobic?
23:05 < nmz787> it depends on the checmistry
23:05 < nmz787> chemistry
23:05 < nmz787> it could be 0.25 Angstrom per cycle, or 5
23:06 < nmz787> there's molecular layer deposition too
23:06 < nmz787> where it's molecules instead of atoms as the gas reactants
23:06 < nmz787> I saw a paper once with an amino acid I think
23:07 < nmz787> https://pubs.rsc.org/en/content/articlehtml/2017/ra/c7ra01918a
23:07 < nmz787> .title
23:07 < saxo> Bioactive titaminates from molecular layer deposition   - RSC Advances (RSC Publishing) DOI:10.1039/C7RA01918A
23:08 < nmz787> """MLD is a special case of the atomic layer deposition (ALD) technique, where the embedded building units are larger molecules, such as amino acids. The precursors are introduced onto a substrate in a sequential manner separated by purging steps to remove unreacted precursors. By doing this, gas phase reactions are avoided and uniform coverage even on complex three-dimensional substrates can be 
23:08 < nmz787> achieved. The cyclic nature of the process also enables monolayer control of the deposited films and provides the possibility to vary the type of building units as the film grows, ensuring control on the molecular level.4–8 Like ALD, MLD requires precursors with sufficient vapor pressure, reactivity and stability against decomposition at sublimation and deposition temperatures.3 This can be 
23:08 < nmz787> challenging when amino acids are applied as precursors, however, still possible, as will be shown in this paper."""
23:08 < nmz787> """ALD was primarily designed for deposition of inorganic compounds in the late 1970s.9 Since then, the range of applicable precursors by this technique has expanded continuously. Recently, the advancement of the MLD technique enabled formation of hybrid materials by using different types of organic and inorganic precursors.10–12 The major motivation for deposition of hybrid materials by MLD has so 
23:09 < nmz787> far been as gas permeation barriers and for its presumed flexibility.13,14 Moreover, it enables modification of optical and electrical properties of deposited films in a gradual manner.15"""
23:10 < nmz787> and of course, this nice database of ALD recipes: https://www.atomiclimits.com/alddatabase/
23:10 < nmz787> .title
23:10 < saxo> Database of ALD processes
23:11 < nmz787> they also seem to now have ALE recipes (atomic layer etch)
23:17 < muurkha> I meant to ask, what specifically are you saying is doable with ALD?  Depositing something hydrophobic for electrowetting, or something else?
23:21 < nmz787> yeah
23:21 < nmz787> at CMOS process level voltages
23:21 < nmz787> i.e. so you don't need to screw with high-voltage conversion
23:24 < muurkha> right, which is simple in theory but can be a huge pain in practice
23:27 < nmz787> just having 100V around, which might have AC-like behavior at times... is a danger I'd rather not have
23:29 < nmz787> plus it's sure to reduce the signal bandwidth, though I don't know how much of an effect relative to the capacitance at the end would be, where it meets the liquid
23:31 < nmz787> also I'm thinking about things like feeding DNA right through a transistor or something, at this point
23:31 < nmz787> .g ssdna diameter
23:31 < saxo> https://www.sciencedirect.com/science/article/pii/S0006349506722986
23:31 < nmz787> .g ssdna width
23:32 < saxo> https://www.sciencedirect.com/science/article/pii/S001457930601101X
23:32 < nmz787> I just want the number
23:32 < nmz787> wikipedia has it I think
23:33 < nmz787> "Both chains are coiled around the same axis, and have the same pitch of 34 ångströms (3.4 nm). The pair of chains have a radius of 10 Å (1.0 nm).[9] According to another study, when measured in a different solution, the DNA chain measured 22–26 Å (2.2–2.6 nm) wide, and one nucleotide unit measured 3.3 Å (0.33 nm) long."
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--- Log closed Sat May 14 00:00:15 2022