MontyCarloHall

5 ms·

1.
European commission adds exemptions to portable battery removability rules(environment.ec.europa.eu)
2 points by MontyCarloHall 3mo ago|0 comments
2.
by MontyCarloHall 3mo ago
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 time remaining: ZZZ seconds” Instead, the whole system jus
3.
by MontyCarloHall 3mo ago
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 last year or so. [0] https://github.com/reso
4.
by MontyCarloHall 3mo ago
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 direct reflection of the quality of the underlyin
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by MontyCarloHall 4mo ago
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, and each guide is on the order of 100 bases.
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by MontyCarloHall 4mo ago
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 given therapy, e.g. [0]. Just like if you performed th
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by MontyCarloHall 4mo ago
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 would be infinitesimal.
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by MontyCarloHall 4mo ago
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 repair the mutant allele, whereas CRISPR/Cas12a2 will a
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by MontyCarloHall 4mo ago
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 mechanisms (a formulation-diverse cocktail of LNPs + eVLPs [0]?
10.
by MontyCarloHall 4mo ago
>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, which is still a very tough problem. It would also not solv
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by MontyCarloHall 4mo ago
>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 killing its neighboring ce
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by MontyCarloHall 4mo ago
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 that would then be promptly selected for.
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by MontyCarloHall 4mo ago
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.nlm.nih.gov/articles/PMC2538882/
14.
by MontyCarloHall 4mo ago
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 Cas9, which just damages the DNA at the target sit
15.
by MontyCarloHall 4mo ago
>[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 factor, though very aggressive financial incentives for p
16.
by MontyCarloHall 4mo ago
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 my part. My general point is that all the activities I listed
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by MontyCarloHall 4mo ago
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 the other replies was a mistake on my part. >But having chi
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by MontyCarloHall 4mo ago
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 example of things that lead to individual happiness that are anti
19.
by MontyCarloHall 4mo ago
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 good sleep/health habits, keep a flexible schedule un
20.
by MontyCarloHall 4mo ago
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) does very little to reverse this trend [1, 2]. My hypothesis
21.
by MontyCarloHall 4mo ago
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 simple partitioning of a line. [0] https://woodg
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by MontyCarloHall 4mo ago
>[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 company they work for. Downsizing the office footprint of
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by MontyCarloHall 4mo ago
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 to dramatically reduce their lease burden via WFH. Why would
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by MontyCarloHall 4mo ago
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 UNIX shells had a preference! (Dillinger is also shown ru
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by MontyCarloHall 4mo ago
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 the wake of AI companies' free (as in freedom)
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by MontyCarloHall 5mo ago
Did You Say “Intellectual Property”? It's a Seductive Mirage. [0] [0] https://www.gnu.org/philosophy/not-ipr.html
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Did You Say "Intellectual Property"? It's a Seductive Mirage(gnu.org)
5 points by MontyCarloHall 5mo ago|0 comments
28.
by MontyCarloHall 6mo ago
>There’s always The One Factory In North Carolina That Produces The Essential Ingredient and it turns out that it’s just the price optimal one and there is enough capacity around the world to substitute. If you're referring to Spruc
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by MontyCarloHall 6mo ago
>Yes, because it's not an argument the letter is making. It literally is though. The full quote from the Buzzfeed piece is: Reich’s claim that we need to prepare for genetic evidence of racial differences in behavior or health i
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by MontyCarloHall 6mo ago
The crux of that letter is the "need to recognize that meaningful patterns of genetic and biological variation exist in our species that are not racial." This is true. However, this does not mean that there aren't also meanin

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