Chrisprattalpharaptr
Ave Imperaptor
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User ID: 1864
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
The development of big GWAS and tools like AlphaFold suggest to me that we’re nearing the point where useful empirical information overwhelms the capacities of human comprehension.
Exactly! I enjoyed this essay quite a bit. Maybe our fate was never to truly understand biology, but build an oracle that can.
A lot of the work of medicine has been outsourced to evolution, and we’ve cribbed from her notes on every antibiotic and biologic we’ve produced. But we’re getting close to the point where we can build magic bullets from first principles.
It's an interesting question. Perhaps the antibiotic discovery space has been completely saturated by Nature already, at least in terms of targets. In the late 2000s, we developed fully synthetic antibiotics never before seen in nature and bacteria developed resistance just the same. I wonder if the future will be more medicinal chemistry tricks or a pivot to something like bacteriophages...
In terms of biologics, are you referring to monoclonal antibodies? If I'm interpreting you correctly, one day having to raise the right antibody to your target will be trivial because you'll just feed the sequence into alphafold and you're done. I agree, the first person with a model capable of that is going to mint money for a while. There are still a host of other very difficult problems to be solved even at that point though; these kinds of models are only going to get us so far.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Or environmental factors (e.g. prevalent nutritional deficiencies)?
It's possible. People like to use height because, in the west at least, a very large fraction of the variation will be genetic. But who knows?
Incidentally, how do heritability estimates discriminate between genes that "causally" influence height (e.g. a gene that, when expressed, somehow biostructurally increases bone growth), and genes that dictate "unrelated" behavioral patterns which, in turn, affect the desired trait (e.g. craving/distaste for junk food)? Am I right in thinking that this is another major weakness of GWAS - even if you identify candidate genes, those genes might completely fail to transfer to, say, another population in which junk food doesn't exist?
You wouldn't, and that goes beyond GWAS. It's a fundamental problem with all the correlational genetic studies. Inferring mechanism is extremely difficult, and it's easy to be fooled by how you think about the trait rather than how biology thinks about the trait.
So if you run a GWAS identifying N promising genes for affecting height on US citizens, you couldn't use that to reliably increase the height of European babies?
I think it would probably work due to shared ancestry, particularly with their racial breakdown scheme. May not work as well in other races, although they do mention that the majority of their loci are shared.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
They mention that they analyzed the HapMap3 SNPs. Not clear to me whether they themselves reran the panels, if 23andme did, or if they just feed all the data into a model regardless of whether it has all the HM3 SNPs or not.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Thanks! I'll take a look. I do need to work on the stats side of things...
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I asked for formatting tips since the new site is different from reddit. ~ kept giving me strikethrough
edit: yeah the tilde is bugged
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Hilarious that foxnews.com is currently headlining an article about Desantis receiving a standing ovation, with the Trump announcement buried below Bankman-Fried, the LA mayoral race and the UVA football shooting.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
This isn't to say they aren't tasty in their own way, they just clearly aren't meat. The best ones I've had barely rise to the level of "gas station sausage patty" in terms of flavor and texture.
There's at least some niche segments of the market where this won't matter. Some people like meat but want to reduce how frequently they eat it for environmental and ethical concerns. Although given the manufacturing process, I wonder how the emissions for lab grown meat would actually stack up...
Economically though, the whole process is a nightmare because cell culture has been developed for the medical field where costs don't matter, not the consumer market where there's actual competition. I was looking into this awhile back because I had some startup ideas that ran into similar problems as lab grown meat. The generic stuff (amino acids, sugars, lipids, etc) isn't bad, but the big problem is 'growth factors,' or recombinant proteins. In your body, the division of most cell types (and particularly muscle) are strictly controlled to avoid cancerous growths. They're typically quiescent unless certain soluble proteins stimulate receptors on their surface. Growing and purifying a cocktail of these proteins has been horrendously expensive, so people typically use fetal bovine serum (FBS) instead which costs 1500-2000$ per liter, and you use it at a final concentration of 5-10% so...a 10L bioreactor would cost you 2k in FBS alone, and produce about 250g/L or 5lbs of meat.
Obviously things have gotten cheaper (one of those articles mentions a plant-based substitute for FBS which I hadn't heard about previously), and economies of scale, but that paper mentions a floor of ~20$ per pound of meat which is a big ask even for the most motivated millenial-pseudo-vegetarian. Essentially, these people are going to have to develop an entirely new array of techniques tailored towards economic food production rather than medical research. Or just grow yeast instead.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
You could run Twitter with 1500 people instead of 7000 (as I’ve argued many times, tech hiring sprees have bloated every big tech business), but you want those 1500 people to be the good ones, you want them to be able to take over for their fired coworkers, and you want them to be distributed so that at least some of the survivors are in all the critical teams you need with the accumulated knowledge to keep the ship moving.
The problem is that in the rocket and electric car businesses, you can 'exploit' highly motivated talent because some huge proportion of aerospace engineers was raised on a steady diet of science fiction and October Sky. People are willing to do the crushing work weeks if they believe that their work is lifting humanity to the stars and enabling the first interplanetary colony in ways that they just won't to make sure MAGA/progressives can snipe at each other with meaningless, puerile gotchas. People at twitter are there for the paycheck, people at SpaceX are there for the dream.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Perhaps I should have specified that the current workforce is there for the paycheck, not the dream. Good luck if you end up there.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
'Meaningful' in this context is subjective. There are plenty of occupations and causes that are critical to humanity that still don't inspire enough fervor in their adherents to make them work 60 work weeks for below-market wages (i.e. graduate school, or at least it was once upon a time), regardless of how many websites are created due to fears of free speech limitations.
I'd be willing to bet that the current workforce isn't willing to work 60 hour weeks in the name of free speech. Whether there's enough people out there that care who will fill the gap after they leave remains to be seen, in addition to whether those people can keep the faith when their ideals collide with the reality of running a social media platform.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Violent nutjobs have gone after whoever they hated most - not infrequently, gays among others - since long before groomer discourse was a thing. You trying to hang this on anyone who ever complained about Drag Queen Story Hour is honestly kind of repulsive. As is trying to spin something out of "His grandfather is a Republican."
And you're not engaging with anything near a steelman of the argument he made. Painting relatively benign opponents as fascist white supremacists is not particularly productive, nor is it particularly controversial in these spaces that this kind of speech is dangerous. People don't like Arthur Chu talking about putting bullets in tumorous nazi Republican flesh or whatever that quote was. Seems fair to me that PM doesn't appreciate being called a groomer pedophile out to rape your kids, no?
Let's assume Aldrich was persuaded by LibsOfTikTok that we must stop the gays from grooming our children by any means necessary. It's still very unlikely that this otherwise stable and non-violent individual was just going to live a peaceful life until Twitter and grandpa told him about the "groomers."
Bad things happen. Bad people do bad things. We will always have bad people doing bad things. Therefore, why bother?
I hear this logic hasn't worked so well with defunding the police, and that actually, there are people who respond to incentives and the environment they live in. Seems pretty reasonable to me that there people out there who may not have been stable, peaceful individuals that nevertheless wouldn't have become mass shooters if it weren't for the toxic political waters we swim in.
I expect to see "If you say (fairly mainstream thing) you are Literally Killing People" on Twitter, but you offering it unironically here is crap argumentation.
It probably wasn't framed in an ideal way, nor does putting it in the context of his previous posts paint a very flattering picture, but...I think his point about not calling your fellow citizens pedophile groomers is valid? If you don't want to engage with it, you don't need to try and reduce it to puerile twitter one-liners.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
You're not wrong, but there's still a valid argument there to consider.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
So to make my point clear: I have concluded that the Democrats, on most levels, are completely against the norms, traditions, and legal boundaries that were supposed to define the nation they aspire to govern, and more relevant, are completely willing to discard said norms, traditions, and boundaries whenever they're an actual impediment to their own party's interests.
I often see very similar rhetoric in left-leaning spaces levelled against Republicans. Are you confident that Republicans hew to tradition, norms and legal boundaries?
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Ah, glad to see you've adopted some healthier epistemic practices comrade!
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
He's butthurt about this one. I specifically said it'd be pretty unreasonable to get that kind of data:
I assume we're never going to get (4) short of some really impressive investigative journalism, so I think it'd be an interesting conversation what kinds of evidence could stand in for it. If you want to convince me that some significant fraction of people involved in the trans debate are fetishists, I need some kind of evidence that a bunch of them are fetishists. Maybe really widespread reports of children who say they are not trans who were being pressured into it? Some kind of internal slack channels being leaked? The FBI busting some kind of pedophile ring implicating a bunch of these people? Maybe something like your post implicating just a few people, but it happens again and again for months on end?
But he's clearly still upset about it. /shrug
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
just maybe! – @KulakRevolt would be fuming about the global kraken of perfidious Albion exploiting American vulnerability under the false guise of allyship, rather than the other way around.
The only constant in every timeline is a man named kulakrevolt fuming about something.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I have a deep, abiding love for the cyberpunk aesthetic. I've worshipped at the altar of Sterling, Gibson and Stephenson. And unfortunately I'm going to have to hard disagree and express puzzlement with:
No one expected anything from Edgerunners, even fans of the franchise had forgotten it was coming out… but the series was incredible. It might outstrip studio trigger’s earlier Kill La Kill. Aside from a, somehow simultaneously, slow and rushed pilot-episode complete with poor dubbing (outside of ep1 the dub is amazing) the show is an exceptional and damn near flawless story harkening back to not just western Cyberpunk stories, but old-school kickass Cyberpunk Anime like Akira or at points even Cowboy Bebop.
Unless you are just constitutionally incapable of watching any anime…100% watch Cyberpunk: Edgerunners on Netflix… Its a 10/10 masterpiece.
The first episode is much weaker than the rest, but every episode doubles in quality til you hit episode 6 and it might just be one of the 10 best episodes of television ever made.
As a disclaimer, I haven't played Cyberpunk:2077 so I likely missed some minor tie-ins. But Edgerunners was a good series with an amazing aesthetic that profoundly failed to live up to it's promise. Here are the problems:
**** MAJOR SPOILERS BELOW *****
-
Gratuitous character deaths. Pilar dying in episode 4 was shocking, and let you know we're playing for keeps. By the time Rebecca and David explode into puddles of gore, it's impossible to give a fuck anymore because the entire team died in stupid ways that don't further the plot. Just watching violence for the sake of violence isn't particularly attractive.
-
Utterly pointless climax. The culmination of the series is just a reheated 'Do it for her' meme. Love interest is abducted. Main character acquires
macguffin(okay, giant mecha suit) to rescue love interest, dying in the process. All other main characters die pointlessly, with one possible exception (Maine dying of cyberpsychosis. But also...what's Maine's backstory? Why is he randomly running in the desert? Why should I care that he's dying?). -
Complete lack of meaningful character progression. Nobody has a relevant backstory. The closest thing we get is David's mom dying early in the series, which changes virtually nothing because David already had a pile of reasons to hate the corpos. Now he hates them more. Profound. Meanwhile, what do we know about Pilar? Maine? Dorio? Kiwi? Rebecca? All these characters die and it's just impossible to care because they're sad cardboard cutouts without motivations or actual stories.
**** Spoilers done ****
And because I'd be remiss if I didn't mention the good:
Incredible worldbuilding and aesthetics. The combat sequences with the Sandevistan and cybernetics more generally are fun as hell. David and Lucy's song is a major earworm.
We are almost certainly going to get more stories out of the Cyberpunk franchise, sequels, new series, new games (an expansion is already about to release for CP 2077) and between this and other Scifi properties that have come out recently, its very likely we’re going to see a widespread revival in Cyberpunk the genre… And I’m really looking forward to it.
Color me deeply skeptical. Cyberpunk and fantasy are fairly played out and at this point there isn't a whole lot of new ground to tread, just the occasional talented author who can write an excellent interpretation of the old formula. We'll keep seeing the occasional hit or new franchise, but there's not going to be a renaissance of talented authors bravely taking cyberpunk to new places.
By the way, does this site support spoiler text? The old >! !< doesn't seem to work.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
To some extent, De gustibus non est disputandum and all that. I grant that you can have different tastes that are valid, or that you can relate to characters that I find disinteresting. That being said:
I feel like you expected the story to be "And that's how we decided to do "Big important heroic thing" and advance "the good" and this is the story of our noble sacrifice..." no the point of edgerunners is they're just trying to achieve their personal ambitions, make it out alive, not be crushed by the world around them... and everything escalates because the intense friction and pressure they're under just achieving that.
Writing a quality story is orthogonal to whether the story is uplifting or has a happy ending. You can have a story whose message is ultimately nihilist or tragic, even one where every main character dies, and do it poorly or do it very well. In your mind, what differentiates Edgerunners from a lower quality tragedy or film/novel with similar themes? Or what changes could have been made to the plot that would make it better or worse?
For example, since you highlight it: David's relationship with his mother is never really examined. She knew he was talented, had big dreams for his future and made significant sacrifices to give him those opportunities. He completely rejects everything she wanted and turns to a life of a crime. That's fine, maybe he was even forced into it, but...doesn't he have any feelings whatsoever about betraying his mother's dreams and throwing away her sacrifices? Shouldn't he at least grapple with this a little bit? The closest we get is him laughing about being on top of Arasaka tower like his mom always wanted in the last episode.
You want to keep it grimdark and nihilist, but still have some emotional valence? Alright. His mom (who supposedly dies offscreen) was instead sold to human traffickers by the doctors to cover the unpaid medical bills. She ends up the pet of an Arasaka exec. David sees his mother one last time and her disappointment with what he's become just before being smashed by Mr. Smasher. Roll credits.
Or how about the fact that Pilar's death, while shocking, is utterly inconsequential to the story and other characters with deep connections to him? Rebecca is mad for that scene, they kill the nutjob, great...then nobody ever mentions him again beyond Maine suggesting that David take his cybernetic hands? The loss of her brother seems utterly inconsequential to Rebecca. If I'm remembering correctly, the next scene after Pilar dying is Lucy and David being intimate with neither of them seeming to care that their friend just died.
Contrast that to Ned Stark's imprisonment and death, which had huge consequences for the show and the characters. Rob has an emotional breakdown and needs to be comforted by his mother, highlighting the fact that he's a 16 year old boy in over his head. It marks the beginning of Arya's quest for revenge. Tywin and Tyrion bemoan Joffrey's excesses and realize the North will never sue for peace now. Jon nearly breaks his vows to ride south.
the rest we get to gleen so much of their personalities, their values, what little part of life they're holding onto, just from how they behave an interact.
no the point of edgerunners is they're just trying to achieve their personal ambitions
Really? How would you describe Kiwi's personality, besides mercenary, and why is she the way she is? How about Dorio? Why is Maine an edgerunner, what's his endgame, why is he addicted to cybernetics at the expense of his sanity? I don't even know the personal ambitions for...well, any of the characters besides Lucy wanting to go to the moon. David wanted to be an edgerunner, but he gets that in the first few episodes. What does anyone else want?
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I believe you misremember. He acquires macguffin because he's hired to do so, but she gets abducted in the meantime so he uses it to try to free her, no ?
Yes, you're correct.
For the other point, see my response to Kulak.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Very little. Even attempting to study this can be a career-ending choice. This is because causal models often translate into curative models.
Who/what are you thinking of when you say this?
A large scale GWAS was published in Science a few years ago which is about as far from career-ending as you can get. Another from 2017. Here's a brain imaging/PGS paper from 2021. Evo psychobabble about the hypothetical evolutionary fitness of homosexuality. Here's a paper investigating associations between same-sex attraction and 'psychological distress (anxiety and depressive symptoms), and risky sexual behavior.' A search for 'same-sex attraction psychology' yields a hundred forty odd results in the last five years and is by no means exhaustive. Here's a review from 2020 that discusses genetics, birth order, in utero hormones and environment, abuse as a child, sexual orientation of the parents, etc which covers most of the ideas I've come across (not that I'm particularly knowledgeable about this field).
@Pasha depending on what exactly you're looking for, you most likely won't find a satisfying answer to your question. Our current answer for virtually all of these complex traits is the same: genetic and environmental factors play a role, GWAS can identify a large number of low-impact, difficult to understand variants that explain ~5-40% of the heritability and correlation with a number of environmental factors. Maybe some brain-imaging studies showing a 5 +/- 2% increase in activity in some corner of the brain in same-sex attracted individuals. Grand psychological theories like refrigerator mothers have mostly gone out of style.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I'm unsure whether or not I'm parsing your post correctly, but 'academically inclined progressives who have drunk the kool-aid of ID-Pol' describes approximately 0% of the userbase here. I'd also be shocked if any significant fraction of holocaust deniers or JAQers were academically inclined progressives, so unless your definition of anti-semitism extends to people who express doubts about Israel's treatment of Palestine, I'm not sure I follow your point.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I still don't believe we're witnessing complete course reversal, but this could just be the first legitimate W for the right.
It's not, though, and the people crowing about it don't understand how the game is played. And I'm not saying that because I'm butthurt that some journo I've never heard of that's supposedly 'on my side' is the unlucky ox du jour.
When the left deplatforms someone, they genuinely believe (rightly or wrongly) that they're righteously fighting racism/inequality/injustice. They're saving lives from COVID. They're supporting the downtrodden in society and giving them a chance to improve their lives. Contrary to the conflict theorists, it's neither arbitrary nor intended to make 'disfavored groups' suffer.
When Elon (or some figure on the right) deplatforms someone, 1) best case, he's having to grapple with the realities that many people said he would (thus the smugness) or 2) worst case, he's being driven by petty personal or 'own the libs' revanchism. The small fraction of principled libertarians are slinking off, having lost again, while the conservatives pretending to be principled libertarians are cheering the fact that the libs are getting owned.
They miss the fact that really winning, and not just eking out a transitory term in the white house, requires articulating a vision for the future that wins the hearts and minds of the people. And it needs to be more inspiring than 'we're going to keep things the way they are/turn back the clock to the 1970s/1950s/1776!' People need to believe that tomorrow can be better than today. It needs to be more than 'I'm really angry after the last 5 years and after forfeiting all my morals I just want to hurt my outgroup,' which, I don't mean to pick on that commenter personally, but that's the vibe I get from most of the conservatives here.
And you know what? There's plenty of room to articulate a vision for the future that is better than what democrats have to offer. I wish someone would try, and we could see two visions of utopia competing for popular support rather than the depressing political morass we've been languishing in for the last decade. Something has to change; I'd welcome any thoughts people might have on what that might be.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
You're modeling the entire right here as a completely cynical enterprise with no goals beyond hurting their outgroup. I think perhaps you could make some sort of case for an individual, such as Elon himself, but to model the entire right that way is missing the point. And worse, it is inaccurate.
That's not it at all, although I can see how I communicated my point poorly. I don't think either side has any reasonable claim to moral superiority.
However, regardless of whether it's a better model of reality, the story the left tells itself for why it does what it does is much more compelling than what the right does. Particularly in these cases of 'tit for tat' where we're measuring winning or losing in who gets banned from a platform. Leftists wanted to deplatform people to avoid COVID misinformation to save lives. Elon wanted to stand for free speech until his ideals made contact with reality, and now he wants to deplatform people who fucked with his family. Maybe things will balance out, and it will turn into 'your rules but applied fairly' and all doxxers will get banned regardless of affiliation. But 'your rules applied fairly' is still not a particularly proactive or compelling vision for the future.
You could argue, with some merit I'm sure, that the greatest harm comes from the best intentions, and self-righteousness or believing too strongly in your cause is a great way for the left to coast down some slippery slopes towards making the world a worse place. But I'm not even convinced that the right cares about solving the same problems anymore. Is there a competing vision for dealing with homelessness, besides putting them on buses to San Francisco and New York? For drug use, besides being angry at PMCs/neoliberals/deep state traitors who sold out the country to China (maybe the law and order messaging? It's conspicuously absent in discussions about the opioid epidemic though). For social alienation, for assimilating immigrants, for spreading democracy in the world, for poverty? Please, if I'm ignorant fill me in, but to varying degrees I get the impression that these issues just aren't very salient to the right anymore. Nor can I discern any kind of cohesive messaging or worldview the way I can with Reagan or Obama.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
You know, I think you're usually more even-handed than most (or at least seem to make an effort)
Thanks.
but that is an utterly preposterous claim completely unsupported by evidence.
It's a claim about the story they tell themselves, not an actual evaluation of their character.
You're correct that there are people on the fringe who are irredeemably toxic people who just want Republicans to suffer. I think there's a much larger cohort in the middle who can be toxic at times, but justify it to themselves with the rationale I laid out above. And some smaller cohort of idealists who actually try and live up to their principles. I think this dynamic is probably also reflected on the right.
But what I also see is the near hegemony of 'woke thought' or left-leaning answers to social problems. The right would say this is due to censorship, biased media, the deep state, etc and there's certainly some grain of truth to that. But I think it goes deeper than that - I don't think the right currently has a cohesive ideological framework (at least that I can articulate or grasp) for dealing with society's ills in the same way that Reagan did (cut taxes/regulation, business does great and the lower strata of society will prosper along with everyone else) or that woke people do (patriarchal white supremacist ableist society needs to be checked for the lower strata to prosper).
Do you think that's fairer, or still off the mark?
We'd have to dig pretty deep into their data to get the true answer to this, but their study is sufficiently powered to detect extremely low effect sizes. For example, if they're detecting 12,000 significant associations and they've explained 45% of the heritability, they're sufficiently powered to detect variants that explain much less than 0.004% of the heritability.
Someone else with a better handle on the math could give you a more robust answer though.
As for saturation, they split their data into significant and non-significant SNPs and find that the former explain 'around 100%' of the SNP based heritability.
Again, someone else with better stats skills could better answer the question. It's something I should work on but it's not terribly relevant to my day job...
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