bhauth

Karma: 2,272

bhauth 17 May 2024 2:55 UTC
2 points
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in reply to: jmh’s comment on: introduction to cancer vaccines
That new Amgen drug targets a human protein that’s mostly only used during embryonic development. I think it’s expressed by most cancer cells in maybe around 0.2% of cancer cases. In many of those cases, some of the cancer cells will stop producing it.

Most potential targets have worse side effects and/or are less common.

bhauth 15 May 2024 6:12 UTC
4 points
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in reply to: Slapstick’s comment on: my note system
Obsidian is similar in that it uses folders of Markdown files. However...
- If you want version control, which I think you should, you’ll need to set up the same git + syncthing system on your Obsidian vault, which negates any advantages regarding easier syncing.
- I prefer the interface of some other Markdown editors.
- I don’t like how Obsidian discourages people from dealing with the filesystem directly.
- It’s not open source.
It’s not a bad piece of software, relatively speaking. Some people like it; if you don’t care about version control, then maybe you’d like it. It does have some fancy overview tools and it works on phones better.

bhauth 11 May 2024 3:21 UTC
2 points
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in reply to: jacquesthibs’s comment on: Quantum Computing, Photonics, and Energy Bottlenecks for AGI
OK. Why would you consider it a realistic enough prospect to study it or write this post? I know there were people doing analog multiplies with light absorption, but even 8-bit analog data transmission with light uses more energy than an 8-bit multiply with transistors. The physics of optical transistors don’t seem compatible with lower energy than electrons. What hope do you think there is?

bhauth 11 May 2024 2:28 UTC
2 points
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on: Quantum Computing, Photonics, and Energy Bottlenecks for AGI

Photonic devices can perform certain operations, such as matrix multiplications (obviously important for deep learning), more efficiently than electronic processors.

In practice, no, they can’t. Optical transistors are less efficient. Analog matrix multiplies using light are less efficient. There’s no recent lab-scale approach that’s more efficient than semiconductor transistors either.

bhauth 7 May 2024 2:42 UTC
2 points
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in reply to: Metacelsus’s comment on: introduction to cancer vaccines

Interestingly, many cancer “neoantigens” (for example, MAGEB1) are also expressed in meiotic cells in the testis. This is because they’re usually epigenetically suppressed in healthy tissues, but cancer cells have messed up epigenomes.

That’s very true.

I would disagree that synthesizing long polypeptides is easier than synthesizing long mRNAs

That’s not what I said: I said it’s not harder and seems better. I’m aware of the chemistry involved and stand by that. Contrary to your implication, oligonucleotide synthesis also requires protecting groups.

bhauth 7 May 2024 2:34 UTC
3 points
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in reply to: ChristianKl’s comment on: introduction to cancer vaccines

ctDNA can in theory be used to sequence the cancer.

I don’t think that’s a good idea. It’s not the same and would be hard to separate from other cfDNA.

Moderna has just put an individualized cancer vaccine into a phase III Do you think that trial is a bad idea?

What Moderna is doing is sequencing cancer cells and healthy cells, and using some algorithm to guess what mRNA vaccine would work. I think they’re not quite there yet: the hazard ratio with a checkpoint inhibitor isn’t much better than the checkpoint inhibitor alone, and I always discount the reported performance in small trials a bit. (And looking at the stock price, Wall Street seems to agree.) Note also that it’s specifically for certain types of melanoma, and comes after several failed cancer mRNA vaccine trials. That limitation to melanoma types indicates to me that their algorithm and its personalization are probably rather limited.

It’s not that I’m opposed to Moderna doing their trial per se, but I am a bit concerned that their patents could ultimately result in a net reduction in progress.

bhauth 6 May 2024 15:54 UTC
4 points
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in reply to: Yair Halberstadt’s comment on: introduction to cancer vaccines
There are a few issues with that.
1. The cost would probably be a significant fraction of the development of a new monoclonal antibody treatment, making this currently probably limited to billionaires.
2. Personalized drug development on that scale isn’t something that can simply be purchased, and if billionaires tried, governments would probably block them, because voters would consider that unfair, and because cancer researchers can’t simply be increased in proportion to budgets. There are only so many people with the relevant skills and inclinations.
3. Better methods for development wouldn’t just reduce costs, but would also reduce time taken. There would need to be a billionaire, diagnosed with cancer without a good treatment, who would clearly die from it, but not for a couple years.
4. Better methods and understanding wouldn’t just reduce costs and time, they’d also reduce risks. Targeting a receptor that’s actually important normally but wasn’t fully understood could kill someone before the cancer.

bhauth 6 May 2024 2:21 UTC
3 points
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in reply to: Ponder Stibbons’s comment on: introduction to cancer vaccines
That’s true; I misremembered that part when I wrote it. I’ll just remove that.

bhauth 25 Apr 2024 16:15 UTC
6 points
2
in reply to: gjm’s comment on: social lemon markets
You’re mistaken about lemon markets: the initial fraction of lemons does matter. The number of lemon cars is fixed, and it imposes a sort of tax on transactions, but if that tax is low enough, it’s still worth selling good cars. There’s a threshold effect, a point at which most of the good items are suddenly driven out.

bhauth 20 Apr 2024 23:18 UTC
2 points
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in reply to: ChristianKl’s comment on: hydrogen tube transport
Tubes for this would be more expensive but could be used for piping hydrogen. Pipes for moving hydrogen would be much smaller and at high pressure.

Gas pipelines have lower losses at high pressure, which is why natural gas pipelines are typically >40 bar.

bhauth 20 Apr 2024 20:31 UTC
2 points
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in reply to: quiet_NaN’s comment on: hydrogen tube transport
Those Mach numbers are for the relevant speed in air. I would have written that differently, but that’s how the cited paper worded things.

Mostly-sealing against part of the tube before cutting it is less problematic than dealing with a large pressure difference.

Aerodynamic support and propulsion in hydrogen is less expensive than magnetic propulsion and support in a vacuum-filled tube. Building an unpressurized tube is cheaper than a tube that doesn’t buckle under compressive forces. And so on.

bhauth 20 Apr 2024 16:08 UTC
2 points
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in reply to: Dave5’s comment on: Upcoming unambiguously good tech possibilities? (Like eg indoor plumbing)
Downside is it doesn’t work. There are several reasons it doesn’t work, but one is: What happens to the vaporized rock? Were you thinking it just goes up a 20km deep hole without condensing on the walls?

bhauth 20 Apr 2024 0:26 UTC
4 points
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in reply to: Carl Feynman’s comment on: hydrogen tube transport
Using sliding electrical contacts for power is fine for current high-speed trains, but it doesn’t work as well above 200 m/s.

bhauth 19 Apr 2024 9:08 UTC
3 points
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in reply to: gilch’s comment on: hydrogen tube transport
It can’t use “air” around it for engines because what’s around it isn’t “air”.

Oxygen is much heavier than the fuel it’s used with, and you’d either need liquid oxygen (which increases costs) or pressurized tanks (which would perhaps double that mass). That’s still lighter than batteries, yes, but engines are also needed. Piston engines are inefficient and/or heavy, and gas turbines are somewhat expensive.

It’s not that difficult to separate water and hydrogen, that’s true, but processing that much gas is still rather impractical when batteries have enough specific energy. Simply condensing it in the tube is...possible, but would increase drag, especially considering density variation issues, and you’d have to deal with getting it out of a long sealed tube without leaking hydrogen.

Also, if batteries are good enough, the cost of replacing the hydrogen alone probably makes batteries better than burning the hydrogen.

bhauth 11 Apr 2024 23:43 UTC
1 point
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on: on the dollar-yen exchange rate
For a recent example of embezzlement, in Vietnam, 1 person embezzled about 3% of the country’s annual GDP.

bhauth 11 Apr 2024 23:40 UTC
2 points
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in reply to: Jiro’s comment on: on the dollar-yen exchange rate
How about burgers at restaurants, then? They’re more expensive in America too.

bhauth 10 Apr 2024 0:34 UTC
4 points
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in reply to: Ben’s comment on: on the dollar-yen exchange rate

In 2019, the average Japanese employee worked 1,644 hours, lower than workers in Spain, Canada, and Italy. By comparison, the average American worker worked 1,779 hours in 2019.

The real overtime cultures are China, India, Mexico, and South Korea.

bhauth 8 Apr 2024 7:16 UTC
2 points
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in reply to: Thomas Kwa’s comment on: on the dollar-yen exchange rate
It’s not like they were the only major investor in WeWork. There was Insight Partners, for example. But I could find some other examples if you want...

bhauth 7 Apr 2024 23:30 UTC
4 points
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in reply to: df fd’s comment on: on the dollar-yen exchange rate
To be clear, I was talking about the period up to 2019 and COVID. The cultural attitudes about investing in stocks vs money in bank accounts came from Nikkei performance before the last few years.

Since 2019, it’s up 2x, but the yen went down vs the dollar and there’s been some inflation. In terms of what a unit of the Nikkei can buy in America, the valuation is flat since 2019. Which might actually be a hint about what’s driving the relative valuation...?

bhauth 7 Apr 2024 23:23 UTC
9 points
3
in reply to: DanB’s comment on: on the dollar-yen exchange rate
I could easily write a similar list about American companies. Let’s see...
- Investors keep funding dumb money-losing ventures like WeWork and Juicero!
- Employees aren’t kept long enough to justify training them!
- Switching jobs frequently and smooth talk is valued much more than a solid track record!
- Developers keep switching to the latest JS framework for no good reason!
Maybe one culture is better economically than the other, but I can’t see it explaining a 2x wage difference. But if you posit that Japanese management culture is universally really bad, then you have to explain things like:
- lack of foreign firms coming in and outcompeting
- Japanese companies succeeding making cars in America