--- Log opened Mon Apr 03 00:00:16 2017
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04:53 < kanzure> hmph
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04:57 < kanzure> openworm roadmap https://waffle.io/openworm/openworm?milestone=Produce%20a%20multi-panel%20figure%20representing%20the%20training%20and%20simulated%20data%20produced%20by%20the%20model
04:58 < kanzure> openworm propaganda http://payload252.cargocollective.com/1/14/457826/7358959/openworm_tesla_color.jpg
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07:17 < kanzure> https://blockstream.com/2017/04/03/blockstream-releases-elements-confidential-assets.html
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08:44 < kanzure> .title https://www.reddit.com/r/AskReddit/comments/632l67/if_you_could_go_into_a_shop_and_ask_to_get/
08:44 < yoleaux> If you could go into a shop and ask to get genetically modified. what modification would you ask for? : AskReddit
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10:56 < nmz787_i> http://southeasternmicroscopy.org/2017-2/
10:56 < nmz787_i> .title
10:56 < yoleaux> 2017 Meeting | SEMS
10:56 < nmz787_i> "Half-day Workshops on Wednesday will include:    RMC and an Array ultramicrotome (at Holiday Inn);    FEI and FE-SEM STEM and analysis (at GEM on UGA campus);    Negative staining with Sara Miller and Mary Ard (at GEM on UGA campus);    Protochips with wet/dry TEM sample holder. (at GEM on UGA campus);    Possible Confocal workshop with Zeiss (at the BioImaging Center at UGA)"
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12:27 < kanzure> fusion protein stuff https://news.ycombinator.com/item?id=13828894
12:28 < kanzure> "More times than not protein fusions work just fine for the desired definition of 'work'. If you are trying to tune the very last efficiency out of an enzyme, or push one organism's survival efficiency past another's, then yeah smashing domains together is not the way you arrive at an evolutionarily polished machine. However if you need to test or create new functionality it seems to work just...
12:28 < kanzure> ... fine. Biology is extraordinarily robust. A common technique is to combine these to approaches - build out a rationally designed functional protein by fusion, then run it through a few rounds of directed evolution to have the organisms themselves iron out the kinks. This strategy has been very successful."
12:28 < kanzure> "Just smashing GFP onto every protein in the yeast proteome resulted in ~80% successfully turning green without noticeably affecting the yeast growth.[1] Check out eCD4-IG - it's four components fused to become an extraordinarily effective anti-HIV drug. It is of a different kind and a different order of effectiveness then the small molecule drugs of the 20th century.[2]"
12:28 < kanzure> .title http://www.nature.com/nature/journal/v425/n6959/full/nature02046.html
12:28 < yoleaux> Access : Global analysis of protein expression in yeast : Nature
12:29 < kanzure> https://serotiny.bio/notes/proteins/ecd4ig/
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12:35 < nmz787_i> cool
12:41 < ebowden> kanzure, are there others of those fusion proteins made for HIVs that attack other receptors?
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12:59 < kanzure> dunno?
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16:40 < kanzure> everything gets to be a fusion protein, let's just fuse everything together at the same time
16:41 < kanzure> we can call it a utility monster
16:47 < nmz787_i> isn't that called 'fixing' tissue?
16:48 < nmz787_i> let's all huff/inhale meat glue! hooray!
16:48 < fenn> it's the preferred form of cryostasis (irreversible of course)
16:51 < fenn> they could deliver eCD4Ig with an HIV derived vector instead of AAV
16:51 < fenn> if the body mounts an immune response against the vector it will also be attacking the disease-causing HIV
16:54 < nmz787_i> oh man, now I am reading this (http://www.molecularrecipes.com/hydrocolloid-guide/transglutaminase-meat-glue/) and want to make meat noodles
16:56 < fenn> sliced pig ear, bleh
16:58 < nmz787_i> fenn: do you only ear ear nuggets?
16:58 < nmz787_i> eat*
16:58 < fenn> i don't eat ears
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17:04 < nsh> 'Researchers at the University of East Anglia (UEA) have shown that when photons - the fundamental particles of light - are created in pairs, they can emerge from different, rather than the same, location.' - https://www.eurekalert.org/pub_releases/2017-03/uoea-nri032817.php
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17:29 < kanzure> irreversibility is how you know it's safe-- if it can't be changed, then where does the information go?
17:30 < kanzure> nsh: perhaps location isn't an entirely coherent concept
17:30  * nsh nods
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18:19 < kanzure> kolle: hi.
18:19 < kolle> hi kanzure
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18:20 < kolle> what's the buzz here?
18:22 < kanzure> oh, the low murmur? don't mind that, it's just the wall of computronium rushing to gobble up the planet..
18:23 < kolle> my surf-mother-board is ready to go into space
18:24 < kanzure> "DND1 maintains germline stem cells via recruitment of the CCR4-NOT complex to target mRNAs" http://www.nature.com/nature/journal/v543/n7646/full/nature21690.html https://twitter.com/NatRevMCB/status/849050979299450880
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18:27 < kanzure> "Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids" http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.4237.html
18:28 < kanzure> "Systematic identification of phosphorylation-mediated protein interaction switches" http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005462
18:29 < kanzure> some historical papers about antibodies and stuff http://www.nature.com/milestones/mileantibodies/timeline/index.html
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18:31 < kolle> http://www.nature.com/milestones/mileantibodies/images/slide1-image.png hillarious!
18:32 < kanzure> it's fake, look at the pixels.
18:34 < kolle> all is illusion
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18:36 < kanzure> "Mesenchymal stem cell-derived exosomes for cell-free therapy" http://onlinelibrary.wiley.com/doi/10.1002/stem.2575/full https://twitter.com/StemCellsJournl/status/848982617105944576
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18:40 < kanzure> "Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering" http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174789
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18:43 < kanzure> "Temporally precise labeling and control of neuromodulatory circuits in the mammalian brain" http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.4234.html https://twitter.com/naturemethods/status/848971187522867202
18:44 < kanzure> "We present iTango, a light- and ligand-gated gene expression system based on a light-inducible split tobacco etch virus protease. Cells expressing the iTango system exhibit increased expression of a marker gene in the presence of dopamine and blue-light exposure, both in vitro and in vivo. We demonstrated the iTango system in a behaviorally relevant context, by inducing expression of optogene...
18:44 < kanzure> ...tic tools in neurons under dopaminergic control during a behavior of interest. We thereby gained optogenetic control of these behaviorally relevant neurons. We applied the iTango system to decipher the roles of two classes of dopaminergic neurons in the mouse nucleus accumbens in a sensitized locomotor response to cocaine. Thus, the iTango platform allows for control of neuromodulatory circuit...
18:44 < kanzure> ...s in a genetically and functionally defined manner with spatial and temporal precision."
18:44 < kanzure> er, so it's just the usual approach of optogenetics?
18:45 < kanzure> "Live birth derived from oocyte spindle transfer to prevent mitochondrial disease" http://www.rbmojournal.com/article/S1472-6483(17)30041-X/abstract from http://www.nature.com/news/genetic-details-of-controversial-three-parent-baby-revealed-1.21761
18:47 < fenn> i wonder if "artificial thymic organoids" would be effective enough to substitute for a shrunken thymus as a result of natural aging
18:49 < kanzure> "CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome" http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3853.html https://twitter.com/NatureBiotech/status/848952272059060224
18:49 < kanzure> "Large genome-mapping consortia and thousands of genome-wide association studies have identified non-protein-coding elements in the genome as having a central role in various biological processes. However, decoding the functions of the millions of putative regulatory elements discovered in these studies remains challenging. CRISPR-Cas9-based epigenome editing technologies have enabled precis...
18:49 < kanzure> ...e perturbation of the activity of specific regulatory elements. Here we describe CRISPR-Cas9-based epigenomic regulatory element screening (CERES) for improved high-throughput screening of regulatory element activity in the native genomic context. Using dCas9KRAB repressor and dCas9p300 activator constructs and lentiviral single guide RNA libraries to target DNase I hypersensitive sites surr...
18:49 < kanzure> ...ounding a gene of interest, we carried out both loss- and gain-of-function screens to identify regulatory elements for the ?-globin and HER2 loci in human cells. CERES readily identified known and previously unidentified regulatory elements, some of which were dependent on cell type or direction of perturbation. This technology allows the high-throughput functional annotation of putative regu...
18:49 < kanzure> ...latory elements in their native chromosomal context."
18:49 < kanzure> fenn, well they probably wont work for transplantation, maybe just hook it up to the blood supply in a plastic case or something and hope for the best?
18:50 < fenn> i was thinking subcutaneous injection
19:00 < fenn> .title http://www.nature.com/ncb/journal/v16/n9/full/ncb3023.html
19:00 < yoleaux> An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts : Nature Cell Biology : Nature Research
19:01 < fenn> how-to article for artificial thymic organoids
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19:16 < docl> https://www.reddit.com/r/rational/comments/637c2q/d_monday_general_rationality_thread/dfs3fs8/
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19:17 < docl> uploading to an in-vitro brain culture
19:24 < kanzure> his interest in consciousness is holding him back, he wants some sort of offloading to prostheses except our brain implant tech really sucks right now
19:25 < kanzure> pig abdomen storage of human brain matter is probably a more viable long-term project for storing human memory beyond normal death
19:25 < fenn> if given extra capacity i wouldn't expect existing structures to get copied over to the prosthesis
19:25 < fenn> existing neural structures*
19:26 < fenn> so when you die all that good stuff like knowing how to talk and walk goes with your dead brain
19:26 < fenn> and maybe the prosthesis will still be really really good at pokemon if you manage to interface to it
19:26 < kanzure> if we get really good at dna synthesis inside of neurons then maybe the barcoding stuff has a chance, you will have to excrete lots and lots of dna molecules with the neuronal barcodes (addresses) and also information about mRNA expression... this requires some handwaving about cellular machinery that we have not yet developed.
19:26 < kanzure> pig abdomen storage of living brain seems more viable to me, and also will not completely offend that user
19:27 < kanzure> you can also handwave some basic gene therapy to make the brain more compatible with pigs, and of course engineering of the pigs themselves to be better xenotransplantation hosts
19:27 < fenn> engineering the pigs seems easier
19:28 < kanzure> brain aging will probably still occur anyway.... and fixing aging was the problem he was trying to escape.
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19:29 < kanzure> vitrification seems like a good way to go, does he have aything against that?  esp. if we can start capturing protein expression levels everywhere with that multiplexing antibody-antibody-ssDNA-FISSEQ stuff.
19:32 < fenn> vitrification doesn't maintain continuity of memory
19:32 < kanzure> also, if your goal isn't uploading just making sure a roughly-approximate person continues to exist, you could train uploaded brains on your sensory input (cameras etc) and then just pick-and-choose based on what systems seem similar to what you would do.  unfortunately this approach assumes that we have good agi or whatever.
19:32 < kanzure> what is "continuity of memory"
19:33 < fenn> having an unbroken episodic memory of your life happening from one moment to the next
19:33 < kanzure> prove to me that i have this
19:33 < fenn> well you probably don't
19:33 < fenn> but some people value having it in principle
19:33 < fenn> i'm not doing a good job at arguing for this point of view
19:34 < kanzure> maybe because they are buttheads and you don't believe them
19:34 < fenn> usually these ship of theseus schemes are trying to maintain some kind of continuity
19:34 < fenn> otherwise you'd just slice and scan
19:35 < fenn> and in that case why not do the much easier formaldehyde fixation?
19:35 < kanzure> i don't want to be the ship of theseus, i want to be the fleet. or something.
19:36  * kanzure inquires with the the atlas replicants until they stop mumbling
19:36 < fenn> i thought they were just engineered clones
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19:42 < kanzure> slice and scan isn't enough yet, is it
19:42 < kanzure> i guess we do roughly know a good set of proteins we should be labeling and scanning
19:43 < kanzure> recostruction from slices doesn't really work yet.... so..
19:43 < kanzure> (especially for following dendrites/axons across long distances.)
19:44 < kanzure> also re: pigs, maybe even with brain aging, maybe it's not so bad, we don't really know if brain aging causes actual memory loss or if things are just turned off and inaccessible.
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19:50 < kanzure> yashgaroth are you here for the pig party
19:50 < yashgaroth> hell yee
19:50 < fenn> sliced humanized pig ear coming right up
19:50 < fenn> it's the closest thing to legalized cannibalism
19:59 < kanzure> https://github.com/tothemoon-org/extension-blocks/blob/master/spec.md
20:00 < kanzure> https://medium.com/purse-essays/ready-for-liftoff-a5533f4de0b6
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20:42 < kanzure> "Some people have commented that the amount of noise generated by a change is inversely proportional to the complexity of the change."
21:02 < kanzure> re: bikeshed.com
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