toufka

Also the fact that the president’s daughter, son in law, and his brother have a significant amount of their net worth invested in OpenAI via Thrive.

The administration is not known for taking into account second order effects.

The instantaneous instinct to strike an opponent when one can is not much more contemplated than that.

How much did Apple (via Google (via xAI (via SpaceX))) just crush their product?

Seems an awful lot like Apple will commoditize the models that power Siri, and just “sherlocked” a trillion dollar private company.

A large and rapidly growing number.

The largest commercial classes of multi-domain therapeutic proteins include the crispr (and similar) that drive gene therapies, and the chimeric antigen receptors (and similar) that drive cell therapies.

But lead optimization there look different than this page’s efforts.

I mean, the most cutting edge of iPhones, iPads and MacBook Pros _today_ are quite capable of running in realtime today’s high-end local LLMs.

If you project out that hardware just a couple of years, and the trained models out a couple of years, you end up in a place where it makes so much more sense to run them locally, for all sorts of latency, privacy, efficacy, and domain-specific reasons.

Not all that different from the old terminal & mainframe->pc shifts.

Finally - hardware has seemingly gotten out ahead of software that most folks use - watching YouTube, listening to music, playing a game or two. There was a time when playing an mp3 or watching a 4k video really taxed all but the nicest systems. Hardware fixed that problem, like it very well could this one.

1) Another OpenAI cofounder (Brockman) gave Trump’s superPAC the largest ever individual donation of $25m.

2) Trump’s son in law (Kushner) has most of his net worth wrapped up in OpenAI.

A representative idea: if you are the one to kill a deer to eat, you get a little bit of each cut - rib, loin, filet, heart, etc. When was the last time most people ate a filet mignon?

And if you gather food like berries and fruits - you (at least sometimes) get to eat foods ripened that day in the field. How many today get that luxury?

And if one of the things that provides joy to humans is to prepare their family’s food - many folks today would be disqualified.

What about the heterogeneity of the original cells?

Yep - cells would die. ...UNTIL they accrue enough dna damage to accidentally either:

- create a new way to generate thymidine

- fall into a proliferation strategy that no longer needs thymidine

Human cells did the same thing and created checkpoints to preclude malignant growth. There are a number of checkpoints already employed in your own bodies. But if you accrue enough DNA damage, you can get around each of those checkpoints (and get cancer):

- IF too much DNA damage, then die

- IF divided too many times, then die

- IF committed to die, actually die

But if a cell collects enough damage, it can get around ALL of the checkpoints. And evolution has shown us that there is no perfect watcher of the watchmen. Still pretty cool to create a new checkpoint this way.

And that’s why replies are helpful in these kind of explanations. My over-edits became wrong, and then an hour later, unfixable. bglazer is correct.

AAVs, unlike Lentiviruses, do NOT integrate.

If the DNA is in the cell's nucleus, the DNA will be utilized to produce whatever gene is encoded in the DNA. But if the DNA is just floating around on its own it will not survive a cell division event and the material would need to be periodically reinjected to keep working. However, if the injected DNA is part of a full chromosome, it will be replicated when the cell divides - and will be permanent as long as the cell or its progeny survive.

Some viruses will just inject the DNA into cells, but will not become part of the cell's genome ("transient" transduction). Other viruses (like lentiviruses and these adeno-associated viruses [AAVs]) inject their DNA not just into the cells, but also have machinery that splices their payload DNA directly into the cell's chromosomes ("integrated"). The location in the genome of the splicing event is relatively random. Random is not necessarily great as it could interrupt other genes already in the chromosome. CRISPR is a now-famous tool that helps "integrate" DNA into a specific spot in the genome by being guided to a specific location with a small piece of a specific sequence.

Once the DNA is integrated, any cell, and any of the cell's progeny, will produce or "express" the gene on the delivered DNA. In this case, they delivered the 5991 characters of DNA associated with the OROF gene [1].

[1] https://en.wikipedia.org/wiki/Otoferlin

Timestamp in the videos: 21:03-4:33 => 7.5hrs

There’s one law of physics difference here: (with a few exceptions) helium, because it’s lighter than air, will never replenish on our planet. There is currently most of what there ever will be. Unlike (almost?) every other object of commerce, there is an almost completely inelastic total supply. It is the ultimate non-renewable resource.

and youtube video of the 'reveal':

https://www.youtube.com/watch?v=n--zawliqvA

Indianapolis was too fast and hot that one year, one of the (two) tire manufactures disqualified their tires (and teams). So not even half the field ran the race. The Indy 500 course has a half-mile straightaway which allowed the F1 cars to build up unprecedented speed - all in hot midwestern summer heat.

Seems the diligence on local weather is not so good with these folks...

[*] "Michelin's tyre mistake sends US Formula One Grand Prix into farce" https://en.wikinews.org/wiki/Michelin%27s_tyre_mistake_sends...

Snowden also brought the goods (actual docs) so that the existing cases and inquiries could proceed without getting the Glomar response - “cannot answer the question of whether you have standing, as we can neither confirm nor deny the program either exists.”

And this was deliberate. Those in the know knew _of_ the program, but could do little actionable with that knowledge without Snowden’s public proof.

You (at least) have 3 systems that are optimized in concert in a (our) DNA/Protein world.

DNA base set, Amino acid set, Translation layer between DNA/Proteins.

Currently, we've got: 4 DNA bases, 3 bases/AA, 20 AAs; 4^3 => 20

If you change one of those numbers, you'll need to rejigger the rest, and you'd need to reoptimize. And there are competing goals which at least include: - maximize access to biophysical/chemical diversity - minimize energy expenditure to produce each component, chemically - minimize energy expenditure to both copy instructions & produce products - maximize information fidelity - minimize or at least degrade gracefully in the context of errors

In the context of a 3-base system, you very well could throw off those optimizations given the consequences for the other 2 parameters (#AA & nt/AA). 3^3 = 27, which is very close to the maximum of 20 amino acids. Which means you'd probably need a 4nt->AA translation layer to keep the same number of AAs, and that alone would add 30% more energy expenditure. If you kept the 3nt->AA system you'd BOTH need to reduce the number of accessible amino acids AND you'd lose some of the error correction mechanisms of having degenerate codons code for the same amino acid.

BUT, if you look at the codon table, precisely because it's base-4 and not base-3, many base flips are silent when coded.

By using base-4, there's enough space to permit lossiness of the coding itself - given the number of amino acids and the 3-NT encoding.

So you really aren't optimizing JUST for nucleotide encoding, but you're also optimizing in concert with 3-nt/AA, and 20AA codes.

So if you have to optimize for information density and fidelity, given X-nucleotides, Y nucleotides/AA, and Z AAs, and sample as much chemical and physical diversity in those AAs life has settled upon: X=4, Y=3, Z=20.

If we went with X=3, you might need Y=4 to get the same kind of fidelity, but that cranks up your energy costs by 30% (from 3 to 4 NT per AA).

Which is why an enormous number of people will be fired, furloughed or reduced to minimum wage on Monday if this isn’t resolved.

And in this case, tech savy individuals are willing to send $XXM in 6 clicks, 3min after getting a slack message. That's a pretty quick kind of run relative to old-school 'stand in line for your personal life savings' kind of run.

The quotes seem to be OCR’d with 500 being 5oo, and punctuation in weird spots too.

It seems “simple” from a chemistry perspective. But as pointed out, the special part is that this is simple chemistry, _that also works in standard biological conditions_ without harming biology: bio-orthogonal. So it allows complex chemistries to be brought into biological contexts easily and completely. So the discoveries made with this novel chemistry will be biological in nature. That makes for an awkward audience when one is siloed either on the chemistry side or the biology side and can’t quite see how much of a door is opened when you combine the disciplines.

Deere bought the startup Blue River for $300M. Drones to identify and specifically spray just them. Not quite mechanical removal, but closer than spraying the whole field:

https://medium.com/@dcvc/john-deere-acquires-blue-river-tech...

This is an unhelpful article because it straw-mans every argument, and mischaracterizes the primary material.

More recently, Bostrom has said that "unrestricted altruism is not so common that we can afford to fritter it away on a plethora of feel-good projects of suboptimal efficacy," such as helping the poor, solving world hunger, promoting LGBTQ rights and women's equality, fighting racism, eliminating factory farming and so on.

If you actually link to the article, the quoted sentence does exist, but the following implications very clearly are absent. There is no such suggestion that "fighting racism" is a "project of suboptimal efficacy". This is very clearly a disingenuous argument.

As are many of the other of the article's points. There's plenty of room for honest and productive critique - this is not that.

“Don't it always seem to go That you don't know what you've got Till it's gone They paved paradise And put up a parking lot”

There are opposite versions of that story where the drug is a specialized 1-off custom living biological product (often a patient's own engineered immune cells). An entire company's years of effort and existence are tightly coupled to a patient's survival, and sometimes they're hundreds of miles apart.

Those plane tickets, with coolers of ice in hand, are crazy to me.

And yeah, there are those cases where batch 1 was sent 'on time' with Courier 1 who didn't realize what they had, and let it thaw. And so backup batch 2 was sent 'super-express' with Courier 2 with minutes notice.

And the numbers themselves that can be entered manually.

5 payment modalities with a thin piece of plastic.

Uh, gold _is_ backed by chemistry. If gold were to change nearly any of its chemical properties, it would instantly lose its value. It is stable, generally non-reactive, non-toxic, lustrous, and of generally low abundance - all properties derived directly from its chemistry.

That is actually one of the strongest arguments, to my mind, for why some variant of a cryptocurrency will survive as a store of value. Gold kind of "organically" found its way into value almost precisely because it is backed by the physical laws of nature. Cryptocurrencies went up a level to be backed by the laws of mathematics.

It's also much more complicated to define "silent" in the context of a virus. In a larger-genomed organism there is a relatively clear (though still not completely clear) function of a coding region, where the change of a nucleic acid will have no effect on the protein made - but still might (subtly) effect regulation in some way.

In a virus, most nucleic acids have multiple, layered, and unknown functions - it's much much harder to assign any given nucleic acid as "silent", and be confident that that is the case from an evolutionary perspective.

As another posted, it's a good hypothesis that's straightforward to test statistically against all of the other variants. But on its own, it's not necessarily convincing here that the S/NS ratio is particularly concerning (and as above, doesn't speak to how directed evolution works either).

I think their point is that the leak has a plausible route - and whatever protections we would institute were that to have been true - we still should implement - precisely because they could have been true.

In many safety contexts, the strong possibility of an accident is often considered as the failure - not just the accident itself.