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kanzure | .wik ricci surgery | 04:14 |
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yoleaux | "In mathematics, the Poincaré conjecture (/pwɛn.kɑːˈreɪ/ pwen-kar-AY; French: [pwɛ̃kaʁe]) is a theorem about the characterization of the 3-sphere, which is the hypersphere that bounds the unit ball in four-dimensional space. The conjecture states:" — https://en.wikipedia.org/wiki/Poincar%C3%A9_conjecture | 04:14 |
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kanzure | "we’re calling for applications through our website, http://sf.indiebio.co/ for those interested in a $250k funding package per startup and we’ll be funding 15 more companies in this batc" | 04:34 |
kanzure | *batch | 04:34 |
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kanzure | "Self-cleavage of fusion protein in vivo using TEV protease to yield native protein" http://www.ncbi.nlm.nih.gov/pubmed/15741334 | 05:44 |
kanzure | "BASIC: A New Biopart Assembly Standard for Idempotent Cloning Provides Accurate, Single-Tier DNA Assembly for Synthetic Biology" http://pubs.acs.org/doi/abs/10.1021/sb500356d | 05:45 |
kanzure | "SELEX (Systematic Evolution of Ligands by EXponential Enrichment), as a powerful tool for deciphering the protein-DNA interaction space" http://www.ncbi.nlm.nih.gov/pubmed/21720957 | 05:46 |
kanzure | "DNA-based binding motives for a substrate of choice is to be found using SELEX. Around that one would engineer the scaffold to hold functional peptides via DNA-binding domains. Naturally, a covalent binding would be better, maybe somebody has an idea for this. The DNA part of the structure would be more durable than regular enzymes. Peptide parts could be replaced constantly." | 05:46 |
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kanzure | "Peptide nucleic acids are based on an amino backbone, they have higher binding affinity to DNA than DNA does, and you can conjugate peptides or proteins to them easily, albeit only in vitro." | 05:47 |
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kanzure | "Canonical genetic signatures of the adult human brain" http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4171.html | 05:48 |
kanzure | "The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability ... | 05:49 |
kanzure | ... are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated ... | 05:49 |
kanzure | ... compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry." | 05:49 |
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kanzure | "non-neuronal networks" what is the network then? | 05:50 |
JayDugger | Good morning. | 05:53 |
kanzure | "Unimolecular Submersible Nanomachines. Synthesis, Actuation, and Monitoring" http://pubs.acs.org/doi/abs/10.1021/acs.nanolett.5b03764 | 05:54 |
kanzure | "... found using single molecule fluorescence correlation spectroscopy that only the molecules with fast rotating speed (MHz range) show an enhancement in diffusion by 26% when the motor is fully activated by UV light. This suggests that the USN molecules give ∼9 nm steps upon each motor actuation. A non-unidirectional rotating motor also results in a smaller, 10%, increase in diffusion. This study gives new insight into the light ... | 05:54 |
kanzure | ... actuation of motorized molecules in solution" | 05:54 |
kanzure | not sure how to use that 244-atom construction though. i guess you can throw on some chemical cages for delivery, but then why did you need the motor if you are relying on mostly diffusion? | 05:54 |
kanzure | "Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons" http://www.cell.com/neuron/abstract/S0896-6273(15)00872-7 | 05:55 |
kanzure | "Reprogrammed cortical callosal neurons acquire identity traits of corticofugal neurons; Induced corticofugal neurons receive increased input from PV+ cortical interneurons; Projection neuron class-specific identity instructs afferent inhibitory connectivity; ... During development of the cerebral cortex, local GABAergic interneurons recognize and pair with excitatory projection neurons to ensure the fine excitatory-inhibitory balance ... | 05:55 |
kanzure | ... essential for proper circuit function. Whether the class-specific identity of projection neurons has a role in the establishment of afferent inhibitory synapses is debated. Here, we report that direct in vivo lineage reprogramming of layer 2/3 (L2/3) callosal projection neurons (CPNs) into induced corticofugal projection neurons (iCFuPNs) increases inhibitory input onto the converted neurons to levels similar to that of endogenous ... | 05:55 |
kanzure | ... CFuPNs normally found in layer 5 (L5). iCFuPNs recruit increased numbers of inhibitory perisomatic synapses from parvalbumin (PV)-positive interneurons, with single-cell precision and despite their ectopic location in L2/3. The data show that individual reprogrammed excitatory projection neurons extrinsically modulate afferent input by local PV+ interneurons, suggesting that projection neuron class-specific identity can actively ... | 05:56 |
kanzure | ... control the wiring of the cortical microcircuit." | 05:56 |
kanzure | blocking PARP1 and upregulating/activating ATM kinase results in telomere lengthening ("ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells") http://www.cell.com/cms/attachment/2040375994/2053862741/mmc1.pdf http://www.cell.com/cell-reports/abstract/S2211-1247(15)01205-X?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112471501205X%3Fshowall%3Dtrue | 05:58 |
kanzure | "Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model" http://stm.sciencemag.org/content/7/278/278ra33 | 06:00 |
kanzure | "Three-dimensional bioprinting of embryonic stem cells directs highly uniform embryoid body formation" http://iopscience.iop.org/article/10.1088/1758-5090/7/4/044101/meta | 06:01 |
kanzure | "Engineering intracellular biomineralization and biosensing by a magnetic protein" http://www.nature.com/ncomms/2015/151102/ncomms9721/full/ncomms9721.html | 06:01 |
kanzure | "The Architecture of a Eukaryotic Replisome" http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3113.html | 06:02 |
kanzure | "At the eukaryotic DNA replication fork, it is widely believed that the Cdc45–Mcm2–7–GINS (CMG) helicase is positioned in front to unwind DNA and that DNA polymerases trail behind the helicase. Here we used single-particle EM to directly image a Saccharomyces cerevisiae replisome. Contrary to expectations, the leading strand Pol ε is positioned ahead of CMG helicase, whereas Ctf4 and the lagging-strand polymerase (Pol) ... | 06:02 |
kanzure | ... α–primase are behind the helicase. This unexpected architecture indicates that the leading-strand DNA travels a long distance before reaching Pol ε, first threading through the Mcm2–7 ring and then making a U-turn at the bottom and reaching Pol ε at the top of CMG. Our work reveals an unexpected configuration of the eukaryotic replisome, suggests possible reasons for this architecture and provides a basis for further ... | 06:02 |
kanzure | ... structural and biochemical replisome studies." | 06:03 |
kanzure | "Cooperative insertion of CO2 in diamine-appended metal-organic frameworks" http://science.energy.gov/bes/highlights/2015/bes-2015-07-b/ http://www.nature.com/nature/journal/v519/n7543/full/nature14327.html | 06:05 |
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kanzure | "Think of a random walk on an infinitely large chessboard; regardless of the fact that you cannot walk the entire board in finite time, the proportion of times you step on a white or black square depends only on the fraction of squares that are white and black. Similarly, if the total number of folds is small and regularly distributed it is not difficult to imagine independent, convergent discovery of two domains in the same fold by two ... | 06:19 |
kanzure | ... very distantly related sequences." | 06:19 |
kanzure | "The total number of possible folds is much more difficult to estimate than the total number of sequences. Survey of the existing protein universe reveals a total of ~800 folds (3), but as this represents only the existing sample of solved structures it is difficult to extrapolate from this number to the actual size of the entire fold universe. Attempts aimed at estimating the number of folds that have evolved on earth vary from 1000 to ... | 06:19 |
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kanzure | ... 10,000 total folds, a discrepancy that highlights the difficulties inherent in these kinds of estimations (6, 19-24)." | 06:20 |
kanzure | from http://arxiv.org/pdf/q-bio/0603028.pdf | 06:21 |
fenn | "Transient opening of the blood-brain barrier results in activation of microglial cells, which then start engulfing amyloid plaques" | 06:29 |
fenn | i was wondering how ultrasound could affect amyloid plaque | 06:29 |
kanzure | "activation" | 06:29 |
thundara | fenn: http://stm.sciencemag.org/content/7/278/278ra33 ? | 06:35 |
fenn | well i don't see any images or article text or even an abstract | 06:35 |
kanzure | i wonder if there are any proteins that are "self-cleaving" once the amino acids exit the ribosome pore and fold for a bit. something like voluntarily removing a chunk of matter. | 06:37 |
thundara | feen: Paywall-removed http://jean.markov.codes/pub/278ra33.full.pdf | 06:37 |
fenn | oh, thank you | 06:37 |
thundara | No idea if it'd work in something the size of human brains, but given the complete lack of progress in AD, it's worth a try (And guessing the authors are going forward with it) | 06:38 |
kanzure | i was thinking there might be a way to use multiple ribosomes extruding amino acid sequences that combine in a way to more carefully control shape, instead of only a single amino acid sequence strand that folds on itself. however, the ribosomes would have to be positionally constrained to be in extremely close proximity and both would have to be working at roughly the same time. | 06:38 |
kanzure | (and the strands would have to partially fold at least to create functionality to seek out the nearby neighbor amino acid sequence strand and then cause the two strands to be positioned together in some useful way to influence some output shape) (but not sure whether this is more easily controlled than trying to control single-amino-acid-sequence folding) | 06:40 |
fenn | ribosomes are really big | 06:41 |
kanzure | specifically, i don't mean fusion proteins | 06:41 |
kanzure | or proteins with subdomains that combine with other proteins (this usually happens only after folding) | 06:41 |
fenn | you would have to have some kind of chaperone "tube" to convey the unfolded sequence to the center of your assemblage of ribosomes | 06:42 |
kanzure | maybe; but some proteins seem to be good at seeking out targeted small molecules, without the presence of a tube. | 06:42 |
fenn | i'm just saying the protein sequence usually folds immediately after it exits the ribosome, while the rest of the sequence is still being put together | 06:43 |
kanzure | i don't see any advantage of this multi-ribosome technique over "make proteins connect in known ways" | 06:43 |
thundara | fenn: Herp, broken file, fixed now | 06:43 |
kanzure | thundara: if you are asking whether you can transmit ultrasound into human brains through the skull, the answer is yes... | 06:44 |
thundara | kanzure: Well, there's two parts to that, the first is if it's as efficient (If you said yes or no, I'd believe it, I have no background here), the second is if there's actual therapeutic benefit | 06:46 |
kanzure | thundara: http://diyhpl.us/~bryan/papers2/neuro/ultrasound/ | 06:46 |
fenn | one advantage of multiple protein sequences being assembled into one structure is for extruding very large/long macrostructures that are covalently bonded, like for making a very long beta sheet without having to zig-zag? | 06:47 |
thundara | kanzure: Any favorites in there to start with? | 06:48 |
kanzure | that sounds like something that would work with protein-protein binding of separate substructures that combine into megastructure | 06:48 |
kanzure | i think protein-protein stuff sometimes uses covalent bonds | 06:48 |
kanzure | i was thinking of multi-ribosome because of inherent difficulty of imagining how to fold a piece of string to get an exact 3d shape, various problems like "oops you already visited that part of the graph" or "now you can't go back" in same way as plotting a path through a maze. but a second sequence strand can be whatever you want and can revisit certain regions based on molecular affinity push/pull over existing surface versus new amino ... | 06:50 |
kanzure | ... acid sequence "surface" you are extruding from the second ribosome. | 06:50 |
kanzure | "surface versus new" uh.. i mean "surface via new" | 06:51 |
kanzure | no results for "amino acid braiding" | 06:55 |
kanzure | .wik fusion protein | 06:56 |
yoleaux | "Fusion proteins or chimeric proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this fusion gene results in a single or multiple polypeptides with functional properties derived from each of the original proteins." — https://en.wikipedia.org/wiki/Fusion_protein | 06:56 |
fenn | that's a joining of the DNA or RNA sequence | 06:57 |
kanzure | gah naming | 06:58 |
fenn | i don't think braiding is necessary because van der walls forces are large enough already between relatively straight overlapping segments | 06:58 |
kanzure | oh, agreed, i was just trying to think of names that someone else might have already used | 06:59 |
kanzure | .wik protein subunit | 07:00 |
yoleaux | "In structural biology, a protein subunit is a single protein molecule that assembles (or "coassembles") with other protein molecules to form a protein complex." — https://en.wikipedia.org/wiki/Protein_subunit | 07:00 |
kanzure | not helpful that ribosome itself has multiple subunits, makes for difficult searching | 07:01 |
fenn | this is kinda cool https://en.wikipedia.org/wiki/Collagen#Molecular_structure | 07:01 |
kanzure | "Three polypeptides coil to form tropocollagen. Many tropocollagens then bind together to form a fibril, and many of these then form a fibre." | 07:02 |
kanzure | oh right, biology people don't say braid they say helix -_- | 07:03 |
fenn | they're different things | 07:03 |
fenn | a braid is topologically halfway to being a knot | 07:04 |
kanzure | "Computational Design of Self-Assembling Protein Nanomaterials with Atomic Level Accuracy" http://www.sciencemag.org/content/336/6085/1171.short | 07:05 |
kanzure | "Structure of a designed protein cage that self-assembles into a highly porous cube" http://www.nature.com/nchem/journal/v6/n12/full/nchem.2107.html | 07:06 |
kanzure | "De novo protein design: how do we expand into the universe of possible protein structures?" http://www.sciencedirect.com/science/article/pii/S0959440X1500069X | 07:11 |
kanzure | see the figure under "Parametric protein designs achieved so far" | 07:11 |
kanzure | not very encouraging | 07:14 |
kanzure | here is a strange one, "Controlled Self-Assembly of Proteins into Discrete Nanoarchitectures Templated by Gold Nanoparticles via Monovalent Interfacial Engineering" http://pubs.acs.org/doi/abs/10.1021/acsami.5b02823 | 07:16 |
kanzure | "Placing molecules with Bohr radius resolution using DNA origami" http://www.nature.com/nnano/journal/vaop/ncurrent/full/nnano.2015.240.html | 07:20 |
kanzure | yep not encouraging | 07:25 |
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c0rw1n | i spose everyone's read it already but topical xkcd is topical https://xkcd.com/ | 09:12 |
kanzure | i think you mean http://xkcd.com/1605/ | 09:15 |
c0rw1n | yeah, the last one | 09:18 |
archels | mhm the final panel kindof takes the sting out of the argument by saying (and I paraphrase) "1000 times worse" | 09:20 |
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archels | it's not 1000 times worse, it's a whole different playing field | 09:20 |
kanzure | machine code is wonderful, by comparison | 09:20 |
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nmz787_i | kanzure: am I correct to think git rebase dev would be different than git rebase origin/dev ? I'd guess the former means your latest local dev commit, while the latter means the latest local dev commit as origin sees it | 10:17 |
nmz787_i | so if I was already in dev, made some commits, then pull and merge some other peoples' commits, and wanted to rebase the merge away, I would be able to use the git rebase origin/dev to do this | 10:18 |
nmz787_i | otherwise, I won't commit to local dev, I'll git checkout -b someTempBranch then go back to dev, pull, go back to someTempBranch and rebase to dev, then merge someTempBranch into dev | 10:18 |
kanzure | "latest local dev commit as origin sees it" nope... it's "the latest local dev commit that your git repository knows about for the name origin/dev" | 10:19 |
kanzure | you have to run "git fetch origin" to update your local git repository's copy of whatever the remote "origin/dev" state actually is | 10:20 |
kanzure | yes, you should always be working with temporary branches to avoid debilitating blunders | 10:20 |
kanzure | you can also make a local branch that is a copy of origin/dev by a different name, like: git fetch origin && git checkout -b dev2 origin/dev; then you run git checkout <commit-id-of-stuff-you-wrote> and then type git rebase dev2 | 10:21 |
kanzure | in general i recommend never using "pull" | 10:21 |
nmz787_i | hmm, ok, I will play it safe for now... I am at least comfortable with the temp-branch for rebasing | 10:22 |
nmz787_i | and yeah, I want to avoid headache filled blundering | 10:23 |
justanotheruser | the future of sysadmin involves Doom https://www.cs.unm.edu/~dlchao/flake/doom/ | 10:37 |
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kanzure | .title https://news.ycombinator.com/item?id=10588341 | 12:53 |
yoleaux | When Software Eats Bio | Hacker News | 12:53 |
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archels | how the heck did I manage to introduce this Heisenbug in Python | 13:14 |
archels | if t > 0.0255: | 13:14 |
archels | import pdb;pdb.set_trace() | 13:14 |
archels | the whole thing works if those lines are there and I just keep hitting c | 13:14 |
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kuudes | memory leak error somewhere where otherwise something would write to a memory address over something else but importing and tracing causes word boundary alignment or similar and the thing gets just written to unallocated space or similar? | 13:20 |
kanzure | what's the error? | 13:21 |
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kanzure | what's the difference between http://ralphmirebs.livejournal.com/ and http://lana-sator.livejournal.com/ | 15:39 |
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kanzure | http://www.scientificamerican.com/article/china-s-bold-push-into-genetically-customized-animals/ | 19:17 |
kanzure | "scientists at Yunnan Key Laboratory of Primate Biomedical Research have used CRISPR to augment the neurological development of monkeys" | 19:19 |
kanzure | "If safety and efficacy issues can first be addressed, he is open to the future possibility of therapeutic uses, but not to eugenics. “In human beings CRISPR could be used to correct the mutation, which cause genetic human diseases, and it should not be used to generate any particular traits which some people may favor.”" | 19:21 |
kanzure | haha at people calling "favorable changes" the same thing as "eugenics" | 19:21 |
kanzure | people are awful | 19:22 |
JayDugger | I favor the trait of disease correction, | 19:24 |
andares | Popular figures aren't having mature conversations | 19:25 |
andares | It'll all be irrelevant when DIY becomes accessible, no? | 19:25 |
andares | Or will they make it some kind of felony? | 19:26 |
JayDugger | Yes to both? | 19:26 |
kanzure | "becomes accessible" what does that even mean? wtf | 19:26 |
kanzure | do you think the enzymes just evaporate when you touch them outside a lab? (well, they do, but you know what i mean) | 19:27 |
JayDugger | I assumed andares meant price points for equipment. | 19:30 |
kanzure | lotta people dump $20-$50k into random car hobbies and stuff, that's enough to cover most of the costs | 19:36 |
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andares | I meant mostly: < $100k, equipment is available to individuals and expertise required takes less than a couple years to master | 19:38 |
andares | Arbitrarily, basically | 19:38 |
andares | The point at which tens of thousands of people are doing it | 19:39 |
andares | Already aren't there some labs refusing to sell oligomers to private individuals? | 19:39 |
kanzure | equipment presently costs less than $100k as long as you either build it yourself or buy used equipment or buy equipment from something other than sigma aldrich or thermo fisheye | 19:40 |
kanzure | yes in general you should prefer to make your own dna | 19:40 |
andares | Can I get my hands on the equipment for that today? Or do I have to finish building the DNA printer? | 19:40 |
kanzure | you can buy used dna synthesizers on ebay for <$10k | 19:41 |
kanzure | but they probably wont work without some repair | 19:41 |
kanzure | which isn't so bad | 19:41 |
andares | Can I get things like RNA polymerase, tris etc. Delivered to my door? | 19:41 |
kanzure | probably, but i recommend purifying your own | 19:42 |
andares | Hrm, how do I do that? | 19:42 |
kanzure | http://diyhpl.us/wiki/diybio/faq | 19:43 |
kanzure | hmm reagent suppliers aren't listed- this would be a good thing for you to add | 19:43 |
kanzure | (it's a wiki) | 19:43 |
andares | Or perhaps a more practical question: has anyone here successfully done a transfection using all their own equipment at home yet? | 19:43 |
andares | I'm assuming too that once it becomes a big deal, the government will watch bio equipment like they watch chem equipment for the drug war | 19:44 |
andares | So eBay will be out of the picture | 19:44 |
kanzure | yes a few people in here have done transfection projects | 19:44 |
kanzure | ebay is always going to list biotech equipment from liquidation auctions etc | 19:44 |
kanzure | the government (specifically the fbi) has already been in contact with us | 19:44 |
kanzure | in particular this channel was assigned to their division of weapons of mass destruction | 19:45 |
kanzure | i took notes-- http://diyhpl.us/wiki/transcripts/fbi-diybio-2012/ | 19:45 |
kanzure | they are okay with diybio stuff existing as long as we report the freaks to them, e.g. the people planning genocides and such | 19:46 |
andares | That's awesome! (Re: successful transfection) | 19:47 |
* andares waves at the nice federal agents | 19:51 | |
andares | If only they could all be like Agent Cooper | 19:51 |
kanzure | they are armed, so don't touch your belt under any circumstances | 19:51 |
* andares stops resisting | 19:51 | |
kanzure | he said the word resist, get him | 19:52 |
kanzure | if you want to find particularly-friendly suppliers then i recommend searching the hplusroadmap logs for http://store.p212121.com/ or the same on https://groups.google.com/group/diybio | 19:59 |
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kanzure | 20:14 <jcorgan> i am the "wumpus" of gnuradio | 20:18 |
kanzure | 20:16 <jcorgan> i recognize "superkuh" and feel like i should know him but i can't place him | 20:18 |
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superkuh | rtlsdr stuff probably. Plus I talk/idle in #gnuradio and every other amateur radio channel. | 20:23 |
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docl | How powerful is crispr? From what I've been reading in the news lately, it can do darn near anything (in terms of editing the genome), super cheap. Is this hype? | 20:43 |
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justanotheruser | http://www.scientificamerican.com/article/china-s-bold-push-into-genetically-customized-animals/ | 20:52 |
justanotheruser | .title | 20:52 |
yoleaux | China's Bold Push into Genetically Customized Animals - Scientific American | 20:52 |
justanotheruser | docl: funny, is that why you mentioned it? | 20:52 |
docl | Not just that article, there's been a lot of them lately. | 20:53 |
justanotheruser | or is this just baader meinhof phenomenon | 20:53 |
docl | http://www.newyorker.com/magazine/2015/11/16/the-gene-hackers | 20:53 |
justanotheruser | never heard of it before | 20:54 |
justanotheruser | before I read the article then saw you mention it within 2 minutes | 20:54 |
docl | I think it's just a super hot topic lately? | 20:54 |
justanotheruser | appears so http://www.google.com/trends/explore#q=crispr | 20:55 |
docl | http://www.nytimes.com/2015/11/15/magazine/the-crispr-quandary.html?_r=0 | 20:55 |
docl | I've been wondering a lot about the idea of adapting mammals to cryogenic conditions. Normal mammals don't have a chance of surviving cryonics, but if we could introduce genes for cryoprotectant synthesis or import proteins into every cell, it might actually be possible. | 20:58 |
docl | If crispr is able to deliver precisely targeted genetic alterations to every cell of the body, you might even see a cryonics tolerance gene therapy for humans at some point. | 20:59 |
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kanzure | oof | 22:05 |
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nmz787_i | sloof | 22:58 |
nmz787_i | andares: the-odin for supplies | 22:59 |
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andares | The odin? | 23:47 |
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