That depends. Often vacuum tubes are used with DC (that is a rectifier) in some form though, in which case you can't do this since induction depends on AC. I'm not sure what purpose the article had for a triode though, depending on their application this might work.
If I may offer an anecdote, the output stage in my guitar amplifier is powered by a GEC tube that is now 55 years old. It sounds great. When I found the tube, it had been rolling around for a couple of decades at the bottom of a wooden box.
This could simply be survivorship bias, but it does appear that back in the day, they knew how to build these things to last.
Remember though that many other AIs had already run and found issues that were fixed. If you had a time machine and took Mythos back a year it probably would have found a lot more. (if anyone has access to mythos it wouldn't be hard to test - download a release from last year and check)
I care what works, not about debate. This seems to work and that trumps any debate about what the real means are.
Don't get me wrong, if you are in this area of research this debate is important. There may be other types of Alzheimer's that have a different means. This drug may actually target something else. There might be some other truth I haven't thought it - but to me as an outsider the important part is a treatment that works, not why it works.
You are wrong. This paper very clearly does not show that it "works". The debate exists for a good reason - the very thing this paper claims to show is the exact thing the person you replied to was questioning. And that is a central question in all of Alzheimer's research.
There are dozens of studies that show mice improving their memory/spatial reasoning as Alzheimer's models. None of them have led to a proven improvement in longevity or quality of life for human Alzheimer's patients. Some of them slightly slow the progression, but even then you're getting into a gray area - is it really "better" to be stuck in the Alzheimer's fog for longer? Are we actually improving quality of life? It's unclear.
So no, in order for us to say that this approach "works", we would need randomized controlled clinical trials in humans showing a strict improvement in quality of life and/or longevity. This is not even close to that level of evidence.
In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.
In general, sure, but in this specific instance (treating Alzheimer's by clearing amyloid-beta) it's been shown over and over again to not work in humans.
I’m kinda new to this - so what you’re saying is the mouse model induces beta-amyliods directly, rather than finding ways to give mice Alzheimer’s, whereas the human tests are for humans that have Alzheimer’s? Meaning we aren’t doing any tests of simply stimulating BA growth in humans?
I'm also not exactly on expert on this myself, take it with a grain of salt, but my understanding is that we don't really know what Alzheimer's is. To our knowledge there isn't a clear physical cause we can point to - a virus or bacteria or tumor or something. We have the symptoms, and we have the observation that Alzheimer's patients have amyloid plaques in their brain - among other differences!
Since mice don't ever get Alzheimer's naturally, and we don't actually know what Alzheimer's is, we don't know what it would even mean to give mice Alzheimer's. But for research we've genetically engineered mice that end up with lots of those plaques, and their behaviour does suggest an impairment similar to Alzheimer's, so that's what we've been working with. And in those models, various treatments that involve clearing the plaques does seem to help resolve that impairment - but they don't help humans with Alzheimer's, even if they do clear the plaques there too.
If I'm reading your question correctly, we can't stimulate amyloid plaque growth in humans for experimentation because that'd almost certainly be considered completely unethical. And also our methods for inducing the amyloid plaques involve mice that are genetically modified from birth rather than something we introduce in vivo, which would somehow be even more unethical than experimenting on live humans. It's possible we could make those genetic modifications in vivo now with recent developments in gene therapy, but...why?
Which is not the point of the research paper: the point of it is they've targeted a novel mechanism (waste clearing) and observed two effects impacting markers for Alzheimer's.
Amyloid beta might not be causative, but if you hit a mechanism then it stands to reason it might be indicative - in this case if Alzheimer's is partly or fully caused by a waste removal problem in the brain.
The word "benefit" does not apply here. The only "benefits" patients and families care about are: 1) does the patient live longer, and/or 2) does the quality of life improve in a meaningful way? Amyloid plaques are a surrogate marker, and (as already explained by many people in this thread) have not been established as a causal factor in disease. In fact, some work has even suggested a protective role for plaques. So we do not have enough evidence to say that a 42% reduction in amyloid-beta IN MICE relays any benefit at all to humans.
You are correct that a series of clinical trials, which would take 7-10 years, would clear things up. But for now, we simply don't know.
I don’t think anyone is against a treatment that works, regardless of the mechanism.
The problem is that claimed success in these rat models has never transferred to humans. Either the problem is that rat Alzheimer’s is a poor model for human Alzheimer’s or the science being done is poor quality.
> Because reducing amyloid burden is clinically proven to improve functional outcomes, these preclinical results strongly support the rationale for testing this drug in early symptomatic Alzheimer’s disease
I believe this is the critical criticism of others. There’s now two camps. One side claims that the Amyloid movement is based on faulty science and outright fraud (true AFAIK) and the other side claims that there’s still evidence the amyloid hypothesis is accurate despite the flawed start to the hypothesis (possibly true). Generally I don’t trust a lot of effort being pushed behind a hypothesis that’s got such shady behavior from proponents and that rely on fast tracking drug approvals for drugs that reduce amyloids but clearly don’t benefit Alzheimer’s. Everyone gets to choose the priors they choose to evaluate the situation on.
If a beta-amyloid therapy eventually makes it to successful trials, there will still be people who believe the argument is already over and the therapy cannot work. The problem identified by Lowe and others is that some amyloid-oriented researchers were not only falsifying data but also acting as reviewers and editors of journals and tanking alternative explanations.
That has stopped, presumably, but alternative approaches haven't had much success yet either.
In all fairness the cabal was only busted up in recent years, and it was largely responsible for ensuring that alternate lines of research could never get meaningful funding by denying publishing. So where the amyloid plaque line of researxh has had decades the alternate lines of research are only really getting enough sunlight to begin growing now.
The amyloid plaque cabal has quite likely sentenced tens if not hundreds of millions of people to premature death through their actions by preventing appropriate and alternative lines of research.
Therapies targeting amyloid deposits has been tested extensively in actual humans, and it indeed removes amyloid deposits. The main problem is that none of the therapies in question usefully treat Alzheimer’s disease.
Sure, maybe an eventual useful Alzheimer’s therapy will remove amyloid deposits, and maybe it won’t, but it needs to actually treat or at least meaningfully slow the actual disease.
In the title "....in the APP/PS1 Mouse Model of Alzheimer’s Disease"
Given the decades of emphasis on clearing / preventing amyloids I would be fairly jaded. If someone (biotech) wants to spend $$$ chasing this down, good on them.
But a paper curing a mouse model of a human neurological disease does not move the needle for someone with or watching someone suffer from this disease.
> to me as an outsider the important part is a treatment that works, not why it works
Are you a mouse, perhaps? We have a plethora of treatments for mice suffering from human-induced Alzheimer's. None of those treatments have ever been shown to work for human patients, and this one is no different.
In America we generally ensure there are multiple people who can do the job. Somebody can go on vacation no nobody will know because the backup is just as good.
Every once in a while there is an exception. Then that guy says "If your sending me to Australia I'm going to use my vacation to scuba drive the Great Barrier Reef" - and his body is never found. True story, it took months for someone else to figure out everything that guy knew.
> In America we generally ensure there are multiple people who can do the job. Somebody can go on vacation no nobody will know because the backup is just as good.
So every single business, everywhere in American, has at least two full-time employees or at least one other backup that is available when you want to vacation and the stores/businesses never close? I'm guessing the ones that don't have that (if they exists), just never have vacation, or how does that work? Sounds like a fever-dream, but I guess if that's what your experience tells you.
Stores remain open because they ensure somebody isn't on vacation and thus able to work. They sometimes give extra pay if you work a holiday (this is rare though - generally there is somebody who wants the hours/pay more than this holiday off - they can take time off a different day).
For small business (think a plumber) it is common to arrange a competitor who will take care of your emergency customers needs.
I wouldn't say "every single business", there's no universals. But there's a lot of American business owners who basically don't take vacations until they have enough staff to run things in their absence, and American culture in general treats vacations as much less sacrosanct. I usually check Slack every few days when I'm on vacation, in case something's come up I can quickly help with.
When those work well they're fine but be very careful. It's not uncommon of for smoke to go out what you think is the in intake and often those aren't correctly built as a chimney and so you can burn your house down.
Knowing how ours were built, I don't even know what you describe could happen. The intake vents are on the floor with a standard height raised hearth (12"???) while the exit vents are about 6' off the floor. Not really sure how smoke is any where near the intake. The smoke is contained within the chimney. I'm at a loss at how to design something so poorly that the smoke is near any vents. Then again, I've grown up around construction, so maybe that knowledge is preventing me from thinking dumb???
Maybe I misunderstand your description. I'm referring to the fresh air inlet for the fire, not additional HVAC pipes. It is common for attempts to put a fresh air inlet in a fireplace to instead have smoke go out that fresh air inlet.
My understanding is that the venting dylan604 is describing relate to airflow around the firebox / chimney, rather than in or out of the firebox.
An incorrectly-placed firebox intake, or even a poorly-drafting open-hearth fireplace, can indeed dump smoke (and carbon monoxide) into the living / heated space.
Until you get a log so tough, it just stalls up when you draw a splitter. Happened more than once. Usually the log is stuck so far in the wedge you can't get it off either.
Yikes. That sounds like the kind of lesson one tries to learn secondhand, or at most once. Like the time I stalled out a tow-behind wood chipper (the kind tree services use).
It was a smaller one, and the process for getting the log out involved taking the jack off the trailer tongue and hooking it up to the feed roller springs assembly to spread the rollers far enough to pull the log out.
When I was a kid Dutch Elm disease was killing all the elm trees around me so that is what everyone was heating with. An elm log that is just large enough you need to split it can stall out a wood splitter (not every time, but you will get several in a day of splitting). When splitting by hand it is common to have the handle of the maul sticking out of the log and you can't see it from the top where it went in, you just keep beating it hoping it eventually goes.
Then we got a large oak tree once, logs you couldn't even life split clean when you barely did more than blow on them.
> In other words, if I have the full formal spec of f(), isn't that the same thing as having f()?
In some cases, however quite often, the spec is much simpler. For instance, it's easy to say that after running sort on some list, that the result is sorted. However, it is very hard to come up with the algorithm to do that from the specification. Sometimes that is even a point. Bubble sort, quick sort, tim sort, we can go on and on. There's a huge number of different sorts that computer science have discovered over the years. They all should have the same result and so you should be able to prove they do the same thing. However, in the real world there are often reasons you would prefer one to another despite all meeting the same spec.
Another obvious example are cryptographic hash functions: if you have a function f(s) = h, you can trivially specify a function inverse_f(h) = s st f(s) = h, and if you can infer a non-brute-force algorithm for that, you’ve just inferred a cryptographical weakness!
How often will AI look at something that can't be proven because you change requirements and decide to change the code and your requirements to make the proof easier though? I haven't played with proofs at all, but I do know that occasionally when I say, this test failed after making a change, AI will just change the test instead of making the code pass both the old test and the new test which is most often my intent.
That's up to the harness. Right now, my harness doesn't have any tools that would allow the agent to change contracts. Also, agents working on a Rocq proof don't have write access to the C+ACSL code; they can review it, and propose structural changes to the coordinator, but all they can do is iterate on the Roqc proof or give up. The weakest part of the harness today is that the agents that do C+ACSL work can modify both C and ACSL, even though they're usually run with the explicit intent to not change the semantics of the C code (although it's totally within bounds, and often required, for them to change e.g. `foo & 3` to `foo % 4`) -- so there's weakness here, but it's bounded, and since the contracts live in header files that they can never write, it's worked so far. It's a starting point, at least; I certainly wouldn't say this is a mature, or even good, tool chain, but still learning.
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