Viewing profile — MontyCarloHall

Right. If this were truly a pure scaling issue, I’d expect the interface would offer an archive.is-esque “Claude is at capacity; your prompt is #XXX/YYY in the queue; estimated tim…

Another data point: GitHub is extremely insistent its employees maximally use AI for internal development [0], and we’ve concomitantly seen its reliability fall off a cliff in the …

I don’t prompt Claude anymore. I have loops running that prompt Claude and figuring out what to do. My job is to write loops. — Boris Cherny, head of Claude Code Reliability is a d…

Including additional guides is negligible with respect to the overall LNP capacity, which can contain a few thousand nucleotides. The CRISPR/Cas mRNA is about 5 kilobases total, an…

Sure, but my point is that convergent selective pressure across different individuals' tumors is strong enough that they independently arrive on the same resistance mechanisms to a…

In practice, you’d use multiple guides targeting multiple mutations, so that the probability of having/acquiring multiple resistance mutations abrogating every guide from binding w…

Even with 100% delivery efficacy, editing efficacy is nowhere near 100%. CRISPR/Cas editors will reliably detect the target sequence but will not reliably edit it in order to repai…

Agreed. Assuming it's ultimately proven to work in vivo , I think the endgame of this therapy is multiple guides targeting multiple mutations along with multiple delivery mechanism…

>Depending on how the LNPs are designed, would resistance also potentially cripple the cancer cells? Yes, if the LNP could be engineered to target an essential surface receptor, wh…

>there's no "be a better/stronger cancer and spread more effectively to more hosts" No, but there is "be a better/stronger cancer cell and don't succumb to whatever therapy is kill…

This would shorten the timeframe for cells to mutate and acquire resistance mechanisms, but would not address the issue of cells with preexisting (epi)genetic resistance mechanisms…

Nonetheless, we see the exact same resistance mechanisms to the same therapies recur across individuals, e.g. [0]. Convergent evolution is a harsh mistress. [0] https://pmc.ncbi.nl…

The idea of using CRISPR/Cas to detect tumor-specific mutations that aren't necessarily oncogenic and then kill the cell is not a new one [0, 1, 2]. However, previous studies used …

>[B]y far the most common reason given is that the cost of living has risen to such an extent that they feel that rearing children has become unaffordable. That's certainly a facto…

As I wrote in another reply, I meant “hedonism” in its non-colloquial, neutral sense, i.e. the pursuit of individual pleasure and happiness above all else, which was a mistake on m…

Agreed with everything you wrote. I meant “hedonism” in its non-colloquial, neutral sense, i.e. the pursuit of individual pleasure and happiness above all else, which judging by th…

I never made any value judgment on whether it’s bad or good. “Hedonism” is simply the focus of individual pleasure and happiness above all else, and everything I listed is an examp…

I'd call it hedonism if a couple wants to be able to go out on a date on a whim, easily take a vacation, watch adult-appropriate movies on a big TV in the living room, maintain goo…

This has happened to every single society [*] as it industrializes [0], and offering extensive support and incentives to parents (e.g. as has been tried in Scandinavian countries) …

A modern take on Matthias Wandel's classic [0], which has you guess a variety of geometric attributes (e.g. angle bisection, centroid locating, shape regularization), not just simp…

>[T]he same individuals who are able to make leasing decisions for office space are co-invested in commercial real estate But those individuals are much bigger shareholders in the …

I never understood this argument. Most companies do not own their office buildings, but rather lease space from corporate landlords. It is in the best interest of these companies t…

One of my favorite details of this movie is that the semi-antagonistic ENCOM executive Dillinger uses emacs [0], while Flynn uses vi. Clearly, the VFX artist who made the film's UN…

Or that the notion of "Imaginary Property" was a seductive mirage to copyleft folks, many of whom have since realized that they do, in fact, value intellectual property rights in t…