Comments URL: https://news.ycombinator.com/item?id=49763660

Points: 15

# Comments: 2

Comments URL: https://news.ycombinator.com/item?id=49754158

Points: 2

# Comments: 0

China's entry into the WTO is really not a good evidentiary example for AI causing mass unemployment. Unemployment in the U.S. had already been increasing at the time, peaked soon after, decreased to well below the point it had been at China's entry, and only went up again during the Great Financial Crisis, which had nothing -- or at least very little -- to do with competition from China. That's not to say that jobs weren't lost, even en masse, but they were replaced, and U.S. unemployment has been near record lows in recent years. China's WTO entry is a supporting point, not a counterpoint, to the idea that jobs lost to AI will be replaced by new ones.

https://fred.stlouisfed.org/series/UNRATE

Beyond that, there's always tort law, which doesn't require intent.

Comments URL: https://news.ycombinator.com/item?id=49671432

Points: 3

# Comments: 1

Comments URL: https://news.ycombinator.com/item?id=49656389

Points: 2

# Comments: 1

Yes, and it would greatly aid alignment if the user could monitor the chain-of-thought! The open models, including very powerful ones like Kimi K3, are delivering this. The fact that OpenAI and Anthropic are not clearly indicates that a commercial consideration (avoiding distillation) takes precedence over alignment -- regardless of how much they bloviate about the latter.

I could just fish for perch, but what's the fun in that?

(I'm mostly kidding, I love fishing for perch too.)

Rivers seem to be better, with worm presence (or at least, obvious worm presence) being less common. Additionally, I've never seen worms in bottom-feeding fish like catfish and carp.

Some other inaccuracies I noticed in the post:

"DXO is more lipophilic, meaning it’s attracted to fats and lipids."

Dextrorphan is more polar, and therefore less, not more, lipophilic than dextromethorphan. It is still able to cross the blood-brain barrier because it is still a fairly lipophilic molecule.

"My first thought was replacing the methoxy group with 3-fluoromethoxy. On paper, this seemed like it could be an effective way to interfere with CYP2D6-mediated demethylation, but synthesizing a fluorinated DXM analogue would be difficult and costly."

There is no such thing as a "3-fluoromethoxy" group. What I think the author meant was "trifluoromethoxy" ("3-" and "tri" have very different meanings in chemical nomenclature). The trifluoromethoxylated derivative of dextrorphan has, in fact, been synthesized and patented (https://pubchem.ncbi.nlm.nih.gov/compound/24997117).

"The structure of DPO is (+)-3-(isopropoxy)-N-methylmorphinan, with the 3-methoxy group of DXM replaced by a 3-isopropoxy group."

The "+" indicates the direction that a chiral nonracemic compound rotates plane-polarized light in solution. While there are computational methods to predict it, it can't be assumed that the derivative of a "+" compound will also be "+". Better to use "R" and "S" (CIP nomenclature), since they are determined entirely by the 3D structure of the chiral compound and don't require a physical measurement to determine.

"The main problem is that DXO also contains an amine, and that amine can react during the process. So the first step would be to temporarily protect the amine so that it doesn’t interfere."

Anyone who's taken introductory org chem knows better than this. That's a tertiary amine, so you're not going to be protecting it. Not that the compound can't be made -- it probably has been already. I'd check on Reaxys but I don't really want a morphinan in my search history...