--- Log opened Fri Nov 25 00:00:20 2016
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04:25 < kanzure> hmph
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04:34 < JayDugger> Still no vowels?
04:35 < JayDugger> Nonetheless, thank you for transcribing andytoshi's mimblewimble talk.
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04:59 < kanzure> there were no answers at all. everyone dies now.
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05:51 < kanzure> "Directed evolution of cytochrome c for carbon-silicon bond formation: Bringing silicon to life" http://science.sciencemag.org/content/354/6315/1048
05:51 < kanzure> "Enzymes that catalyze carbon-silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological condi...
05:51 < kanzure> ...tions via carbene insertion into silicon-hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon-...
05:51 < kanzure> ...silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules."
05:52 < kanzure> "Yet, no known biological molecule contains a carbon-silicon (C-Si) bond, and no biological processes to form C-Si bonds have been identified" http://science.sciencemag.org/content/354/6315/970
05:53 < kanzure> hm the articles seem to be lacking speculation around useful silicon-incorporated biomolecules
06:30 < JayDugger> Perhaps 15-fold turnover than SOTA synthetic catalysts doesn't happen all that fast?
06:33 < kanzure> hehe someone has been trying to replace usage of the phrase 'human genetic engineering' with instead 'germinal choice technology'
06:33 < JayDugger> Seems the latter covers contraception.
06:34 < JayDugger> Why have one controversy when for three different words you can get a second one for free?
06:34 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=1711c1a1 Bryan Bishop: some more human genetic editing stuff >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
06:36 < cluckj> lol
06:36 < cluckj> that's a pretty nice obfuscation in the word change
06:38 < kanzure> "fetal rescue"
06:42 < cluckj> "embryonic preservation"
06:43 < kanzure> "little people rescue"
06:44 < kanzure> "abortional abort"
06:47 < cluckj> hah
06:50 < JayDugger> I think "embryonic preservation" got taken back when IVF started freezing extra embyros, but why not?
07:07 < JayDugger> "My friends at Stanford are convinced this exists and they just need to search the literature. Maybe this is also not actually opened. My heart is open, though." from mimblewimble presentation. Nice phrase.
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07:17 < kanzure> JayDugger: i think i got that line wrong, my transcripts aren't particularly accurate
07:18 < JayDugger> No worries, kanzure. I appreciate reading them. (Not enough to actually correct some of their typos, but certainly enough to feel guilty about not overcoming that laziness.)
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07:20 < kanzure> truly a triumph of the human spirit
07:21 < JayDugger> Yup. Man is something to overcome, etc.
07:21 < kanzure> pass the steak sauce
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12:35 < kanzure> yashgaroth: any thoughts on "things that were found in the past few years that are also missing from this page"? http://diyhpl.us/wiki/genetic-modifications/
12:38 < yashgaroth> rs17822931, not really super enhancement but it'd be nice
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12:41 < kanzure> yashgaroth: for optimizing random human enzymes, the trouble is the regulatory network disruption, right? e.g. the rest of metabolism doesn't expect one of its components to be working at 100x normal rates.
12:43 < yashgaroth> depends what you're optimizing for, if it's still operating within the cell then it's possible; if it's a multi-enzyme pathway and the modified enzyme isn't the bottleneck then yeah you could just build up a metabolic intermediate
12:43 < yashgaroth> some fraction of enzymes are regulated at some level by the presence of the metabolite, either upsteam or downstream
12:44 < kanzure> so "indsicriminate human enzyme optimization rampage" is probably not a completely safe thing to do, without lots of controls and feedback loop fixes
12:45 < yashgaroth> I mean if you can get the pathway into a cell and screen a billion permutations maybe, as long as you have a good way of monitoring the reaction
12:45 < kanzure> and i bet we don't know all the feedback mechaninsms fo reverything :\
12:46 < yashgaroth> not nearly, no, especially for membrane proteins since they're a huge pain to model
12:46 < yashgaroth> theoretically you can map small molecules onto non-membrane proteins and have an idea of the interaction in silico, for membrane proteins you pretty much need in vitro assays
12:51 < yashgaroth> there's plenty of enzymes for a given reaction in lower lifeforms that are waaay better at catalysis than what we have, since they have a generation time of under 1 day, and that builds up exponentially vs. like a 20 year generation time
12:59 < kanzure> ah right. if you're going to be dead, then metabolite build-up is pretty okay.
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13:03 < yashgaroth> well there's that too, but if you want an enzyme that metabolizes e.g. a sugar super efficiently, with a high reaction rate and maybe even a small protein size and auto-regulation through binding of the downstream metabolite, a bacterium that's had 2^30 generations to optimize it will probably have a better solution than a mammal that's only had [whatever the equivalent # of generations would b
13:03 < yashgaroth> e] generations
13:04 < yashgaroth> meiotic recombination helps but not that much
13:06 < yashgaroth> oh that'd be some other stuff to add to the site yeah, enzymes that break down our accumulated side-products...what was that cholesterol metabolite that builds up in atherosclerotic plaques? aubrey was looking into that
13:07 < yashgaroth> ah 7-Ketocholesterol, like yeah we just die with a bunch of it after X years, not much selection for some mutant that can break it down, at least not on timescales that matter
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13:24 < ybit> this was just shared with me: https://m.reddit.com/r/dataisbeautiful/comments/5eowv6/neural_network_structure_msr_resnet50_large/
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15:02 < kanzure> .title https://news.ycombinator.com/item?id=13037063
15:02 < yoleaux> Speech-to-Text-WaveNet: End-to-end sentence level English speech recognition | Hacker News
15:03 < kanzure> https://github.com/buriburisuri/speech-to-text-wavenet
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15:14 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=c447d8cd Bryan Bishop: rs17822931 >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
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15:45 < kanzure> greets justanotheruser
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16:11 < kanzure> "The transcriptional repressor DEC2 regulates sleep length in mammals" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884988/ (hDEC2-P385R)
16:17 < kanzure> "A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans" https://go.aastweb.org/Resources/journalclub/journalcluboctober2014.pdf
16:18 < kanzure> (more DEC2 and BHLHE41 (basic helix-loop-helix family member e41) mutations)
16:18 < archels_> what's the magnitude of those effects?
16:20 < kanzure> total of 4-5 hours sleep/night
16:20 < kanzure> and resistance to negative effects of sleep deprivation
16:21 < kanzure> in a single protein/enzyme mutation O_o
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16:28 < kanzure> "The M1, M5, and M35 mutants lost its repression activity on CLOCK/BMAL1 transactivation. Interestingly, one of these constructs, M33, harbored an Ala to Ser amino acid change at position 380 (close to the 384 candidate area). Analysis of the 1000 Genome Project data and National Center for Biotechnology Information shows that this allele (p.Ala380Ser) (rs1057206) occurs naturally in the CEPH ...
16:28 < kanzure> ...population (European from Centre d'Etude du Polymorphisme Humain), although it is rare and sleep data are not available. This in silico mutation has a similar effect on CLOCK/BMAL1 transactivation as BHLHE41-p.Tyr362His and BHLHE41- p.Pro384Arg variants found in our subjects. Overall, these results indicate that variants in the region between p.Tyr362His and p.Pro384Arg result in altered rep...
16:28 < kanzure> ...ression activity of BHLHE41 on CLOCK/BMAL1 activation and likely will affect sleep duration and response to sleep deprivation."
16:32 < kanzure> i wonder if delivering mutant DEC2 to the brain would be sufficient
16:35 < kanzure> "Resisting sleep deprivation by breaking the link between sleep and circadian rhythms" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173912/
16:39 < kanzure> "This finding suggests that behaviorally resistant subjects were able to respond to extended wakefulness by significantly dampening oscillating expression patterns. Subjects that were behaviorally sensitive appear to suffer a transcriptional resistance to the changed internal milieu; they failed to make the necessary molecular adaptations, and continued to express genes in a daily fashion as t...
16:39 < kanzure> ...hough they were still on a normal sleep/wake cycle. A recent elegant study showed that desynchrony between sleep and circadian phase (i.e., mistimed sleep) also dampens the amplitude of rhythmic changes in blood gene expression.14 While circadian regulation of the transcriptome allows for specialized cellular functions to optimally match time of day and sleep/wake state, this specialization li...
16:39 < kanzure> ...kely impairs vigilance quality and cognitive functioning when it orchestrates specific cellular, molecular and metabolic processes to occur during sleep. Turning down this specialization (i.e., dampening the circadian regulation to better maintain the "waking molecular signature") may be advantageous in unanticipated sleep/ wake states and individuals resistant to sleep deprivation may be ...
16:39 < kanzure> ...able to do this more efficiently than sensitive individuals."
16:58 < kanzure> "Cholinergic augmentation modulates visual task performance in sleep-deprived young adults" http://www.jneurosci.org/content/28/44/11369.short
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17:24 < pasky> ooh do want
17:25 < kanzure> easy to get that funded too.   at minimum there's the education craze in asian markets that would put a lot of pressure on funding that..
17:26 < kanzure> also military i suppose. but paperwork, so yeah..
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18:03 < kanzure> "Practical blood flow restriction training increases acute determinants of hypertrophy without increasing indices of muscle damage" http://journals.lww.com/nsca-jscr/Abstract/2013/11000/Practical_Blood_Flow_Restriction_Training.20.aspx
18:07 < kanzure> hmm https://scholar.google.com/scholar?cites=10529410175940918875&as_sdt=5,44&sciodt=0,44&hl=en
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20:54 < kanzure> http://diyhpl.us/~bryan/papers2/neuro/sleep/
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21:56 < kanzure> yep..
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--- Log closed Sat Nov 26 00:00:21 2016