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Ultimately to the end of allowing Pittsburgh and the surrounding area to be a place with agglomeration effects, growth, and opportunities enough to allow smart and ambitious young people to remain in the area as opposed to brain draining into the Acela corridor.

It’s sad when a city that could go either way chooses to rust and its most talented young people no longer have the option of staying in their home if they want dynamic careers.

you may mean exacerbate

BLM means Bureau of Land Management

Yes! Applications are open for YC Winter 2023!

Started out /s, but upon consideration I imagine YC really is the closest you could get to the spirit of HN in an in-person meetup.

That's true, but I have a thesis for why this might be good for the biotech ecosystem.

A lot of people will dismiss phage therapy on economic grounds, suggesting that you'd need to essentially design a new phage therapy for each individual infection you wanted to treat. But, with the advances we're seeing in microfluidics, diagnostics, gene sequencing, computational biology, laboratory automation, and the theory of precision medicine, that host specificity can turn from a disadvantage to an advantage. We know there are a lot of human-dwelling bacteria we wouldn't want to knock but can't save from a broad-spectrum treatment. With a personalized phage therapy, this isn't as much of a concern, and with the above advances, custom therapeutic design can scale economically.

But here's the most important implication of phage-host specificity for biotech business models. When a biotech company gets approved to roll out custom therapies for each individual patient, that opens the door to solving two important roadblocks to biotech innovation. First, firms could get around the problem where they're subject to regulatory scrutiny based on a naive interpretation of the difference between their manufacturing costs and their sale prices. Second, such a paradigm of treatment could permit biotechs to offer gradations of service and charge based on how finely-tuned your therapy is. This would enable them to much more closely fit the demand curve of patients. They could bring the latest technology to the masses cheaply and relatively quickly, while charging a premium for the cutting edge.

This site is actually doing something interesting through its curation, and I would be pretty impressed if that was how it was pitched to me.

But I have to agree, expecting a bookstore and then getting something totally other is too much of a clash. If you want a bookstore, nothing's going to beat a bookstore. If this site offers something different, it should be sold on its merits.

I think the concern is that you could still be getting pharmacodynamic effects at 1mg, so the control wouldn’t really be a control.

It’s entirely feasible that you could get good results and limited side effects at dose x, and poor results overwhelmed by side effects at dose 25x.

I remember exactly where I was, about a year ago today, when I realized Deep Thought was an existentialist. B2 Data Structures lab in a building called Fitz. I knew I couldn’t have been the first to realize this, but I couldn’t bear to look it up and see whether or not I’d been preempted.

And it was totally what he meant. The ASCII wildcard-existentialism theory is too consistent with the themes Adams explores through the series to have been an accident.

I fully agree with Musk when he said he regards the Hitchhiker’s Guide as a great work of philosophy, whether or not he was joking. It totally worked for me as I was trying to progress beyond nihilism.

Here’s how this gets broken: The more countries faithfully adhere to the global corporate minimum, the stronger the incentive becomes for a “cheating” country to lower its rate.

The tax haven could even get around an “enforcer” or governing board. For instance, such a country might change what it considers to be “profit” so that you’re paying $2 on $100 of revenue, whereas in the neighboring country you’d be paying $6. Same nominal tax rate, different effective tax rates. There are even more ways to play this: “Sure, we tax you at the required 20%, but you can then direct how those funds are used to reduce costs you’d otherwise have to pay directly.”

And this happens a ton— see the WTO and “effective” but not nominal tariffs.

Whether or not we see such a harmonized tax rate emerge and even if we could find a way to have some governing body try to “enforce” it, you’ll still see countries lowering their effective tax rates to lure firms or bolster growth. I bet there’s a maximum sustainable effective corporate tax rate, but I have no idea what it is (and for all I know it could be zero or negative).

Happy you found it helpful! The final section (imposters) of this [1] simplified exploration of “green beard altruism” might be of interest to you if you want to explore this further. If you’re interested in thinking about things like this generally, these are Nash equilibrium problems and the field is called game theory.

In answer: if we do discard the assumptions of game theory and we imagine nobody would ever think to “cheat,” it could work. But in reality it wouldn’t be just that some countries have huge advantages in some industries— they would have huge advantages in every industry. People and companies looking to maximize their opportunities would flee to the country with the lowest effective (nominal doesn’t matter) tax rate which could also guarantee their safety.

This is actually part of how the US ended up burying the Soviet Union/eastern Bloc with economic productivity— we kept poaching all their best engineers, scientists, mathematicians, and entrepreneurs.

[1] https://m.youtube.com/watch?v=goePYJ74Ydg

The point is that effective tax rates can be really subtle.

For instance, you could have a country change what it considers to be “profit” so that you’re paying $2 on $100 of revenue, whereas in the neighboring country you’d be paying $6. Same nominal tax rate, different effective tax rates.

There are even more ways to play this: “Sure, we tax you at the required 20%, but you can then direct how those funds are used to reduce costs you’d otherwise have to pay directly.”

And this happens a ton— see the WTO and “effective” but not nominal tariffs.

Whether or not we see such a harmonized tax rate emerge and even if we could find a way to have some governing body “enforce” it, you’d still see countries lowering their effective tax rates to lure firms or bolster growth. I bet there’s a maximum sustainable effective corporate tax rate, but I have no idea what it is (and for all I know it could be zero or negative).

Careful, there are a lot of people who wish IQ tests didn’t have anything useful to say about intelligence. Implying that IQ tests can be useful tools and that their results might bear some relation to intelligence usually brings them out of the woodwork.

People have definitely gotten smarter. Here’s a small case which might help illustrate how this happens in general: We know infection with hookworms and other soil-transmitted helminths will do nasty things to the intelligence of the patient, especially for children. Since humanity got rich enough to build sewer systems and shoes and anti-parasitic drug companies, soil transmitted helminths have become a lot less of a problem (and the same goes for their cognitive effects).

This just sounds like a really clever mechanism for solving the cold-start problem for the protocol. You generate a bit of initial demand to pull in some initial supply, which in turn generates its own demand, which pulls in more profit-chasing supply (of storage), which drives down the real price of storage, which is part of the value prop to the non-speculative demand, which is how the crypto asset might maintain its value long-term. Boom, now you’ve got a functional network, a valuable token, and a more efficient market for a raw material of the internet economy.

The word bootstrap comes to mind.

At the beginning of the pandemic the world health organization was saying that there was no evidence of human to human transmission, when there was. The surgeon general of the United States was saying that masks don’t work. Right now a lot of the establishment dismisses the possibility of a lab leak out of hand. If contradicting any of these narratives were illegal, we’d be in a worse country and I’d be trying to find the America of the 2020s, just as the Soviet mathematicians and scientists and entrepreneurs and engineers did before me. And that last point is why we shouldn’t ban free speech beyond that which poses a clear and present danger: because the damage to the country of losing people who value free speech in particular and freedom in general is much greater, over the long term, than the danger that comes from dealing with an informationally enfranchised public.

Here’s the thing to understand: the “economists” you’re watching on TV are not representative of the field, and TV economics is hardly a better source of information on economics than Facebook is on immunology. Confusing the cargo-cult for the real thing is the actual mistake here.

I think it’s easy to claim all the economists at Harvard, Stanford, MIT, and UChicago have no clue what they’re doing, and you could design a market better than Vickrey himself by throwing darts at a wall.

But the reality is that while they do disagree about a great deal, this disagreement isn’t different from the disagreement you see on the cutting edge of cancer biology or physics.

And sure, you’ll be able to find “Marxist Economists” for every Nobel Prize winner with a PhD in mathematics, but if you stick with the respectable academics (and especially with those focusing on microeconomics and game theory) they tend to agree about much more than you’d expect.

Watching a tech company break free of legacy media and seize control of its narrative and position in the culture is awe-inspiring. Stripe is all the more impressive because their business wasn’t media-adjacent like Netflix’s.

I’m seeing a company that nails things so consistently and effortlessly that I am convinced that in a decade it’ll be Amazon but for finance. Potential competitors will be terrified of Stripe the same way they are of Amazon. They just execute too well to be comfortable around.

I get it, and I actually agree that the culture you describe isn't a good look.

What I'm going for is more the idea that if you consider the best alternative I can think of to the "holistic" approach, you get selecting applicants purely based on entrance exam scores. In such a world you'd be punishing a kid who plays with Arduino out of interest. Any energy devoted towards something other than test prep is energy wasted.

In the American system, as I'm coming to see it, the kid who plays with Arduino is punished less. The test won't take you all the way anyways, and you even get a little "refund" on attention sunk into some types of activity which qualify as extracurricular.

I used to think that the “holistic” criteria elite US colleges use to select students was a failure of meritocracy. My view was that the non-objective metrics were excuses for colleges to let in students who wouldn’t grind but wanted prestige and had rich parents.

But if you tie a person’s social status to performance on a single test, you suffocate all the useful things people could be doing if they didn’t have to solely dedicate themselves to prep. So maybe we’re doing okay as-is.

The idea is that you want a trusted third party because either of the two adversarial parties could screw the other over.

The company could say: we’re going to pay you 125 and you could sue us and spend 60k and two years or just settle for that, after he’s already done the work.

The guy could demand the payment directly to his account and then not deliver, and the firm would be in the same situation.

By depositing the funds in escrow, they’re making sure that the money is there and in the hands of people whose only incentive is to give it to the correct party upon fulfillment of the contract.

I don’t think it’s accurate to say Tesla is developing an AGI. I mean, the point of the project is to get a computer to drive a vehicle, not interpret French literature, which means the “AI” will be pretty “specialized,” which is kind of counter to the “general” in AGI.

So maybe they’re developing an “ASI.” But because there are already plenty of those and we call them “AI,” we might just say Elon’s trying for a harder, higher scale, and more commercialized version of a set of technologies that already exist. Kind of like all the other “impossible” things people mocked him for missing deadlines on in the past. And now, we’ve arrived at the point.

I mean he was promising to land rockets and put men in space and launch a mass market electric vehicle for quite a bit before he did any of those.

Loads of people called Elon a charlatan, but for them criticism came at virtually no cost, unless you account for the cost of not betting on him.

1: Agreed.

2: One of the problems a lot of people see barring the use of bacteriophage therapy for combating bacterial infection in the clinic is the really fine specificity of most phages to their hosts. The skeptics will suggest that you'd need to essentially design a new phage therapy for each individual infection.

With the advances we're seeing in microfluidics, diagnostics, gene sequencing, computational biology, laboratory automation, and the theory of precision medicine, that host specificity can turn from a disadvantage to an advantage. We know there are a lot of human-dwelling bacteria we wouldn't want to knock but can't save from a broad-spectrum treatment. With a personalized phage therapy, this isn't as much of a concern.

On top of that 1Password is quite pricey, albeit fully featured. I probably wouldn't use it if not for my family's plan.

I use 1Password for my mfa; I can access my one time passcodes from any device I’m signed in on, and my passwords and secondary authentication are conveniently managed together. If issues like water damage or losing your device are concerns for you, their service might be worth checking out.

Disclaimer: I’m very far from a cybersecurity expert.

I legitimately wanted to evaluate the argument here but there’s so much backstory and political contextualization I gave up reading this without ever having found out what the Viennese did.

I used HN to quit Reddit and I must say it’s been a change for the better.

I think it’s fine as long as people know what they’re getting themselves into. I’m sure I would’ve found whatever was happening on Parler abhorrent, but in the same way Merkel and Macron were concerned by the tech deplatforming that followed the capitol riots, so am I.

I don’t think filecoin will ever demolish a fantastic business like S3 based on stealing away customers. The interesting value proposition from the protocol is probably more about censorship resistance and adjacent issues.

I'm not sure, I'm not an expert in this and I've never been in the military.

However, I bet there's little to nothing uniquely good about OODA over the alternatives you mention. My guess is that having a standardized rapid decision making framework is valuable compared to the frantic scramble that might take place otherwise.