Dentin

Karma: 2,157

Dentin May 6, 2021, 11:57 AM
2 points
0
on: Fractal Conversations vs Holistic Response
For bulk exchange of information and state, holistic is really good. I strongly prefer the holistic approach, but I’ve found that it only works for entirely friendly conversations. If it’s adversarial, I find that branches get aggressively pruned to just the things that the opposing side can most easily attack.
And if you think about holistic being optimized for “exchange of information and state”, this makes perfect sense: adversarial conversations are rarely if ever about information exchange; they’re about “winning”.
It’s also perhaps worth mentioning that aggressively holistic comms can require more mental horsepower than some people have readily available or are willing to invest, so it’s best to tune the level of threading based on audience and discussion type.

Dentin May 6, 2021, 11:54 AM
3 points
0
on: Let’s Go Back To Normal
Given the current vaccination rates in the US, and the fact that supply is already beginning to exceed demand, I’d recommend full open in approximately a month. That gives most of the remaining unvaccinated people time to go get at least their first shot, and should allow us to get below exponential growth nationwide, even though we’re likely to have it in sub-populations. IMO the target should be ‘not overloading hospitals’.
After that, let it burn.
From the interviews and things I’ve seen so far, literally the only way to change a vaccine denier’s mind is for them to either 1) get sick, or 2) have a close contact get sick. At this point, I’m kinda ok with that, if that’s what it takes to get people’s attention back to ground truth, instead of socially constructed fake reality.
I’m personally trying to push everyone I care about in the vaccine direction, and I would be terribly sad to lose one of my family members when I’m unsuccessful. However, I also don’t want to live in a future world where it’s ok to be intentionally ignorant on decisions that affect your life. If that’s what it takes for my family to get a reminder that conspiracy theories are Not OK, that’s what it takes.

Dentin May 6, 2021, 11:43 AM
8 points
0
in reply to: Zac Hatfield-Dodds’s comment on: Let’s Go Back To Normal
I’d just like to point out that while “facing these tradeoffs is stupid and avoidable” (which I agree with), it’s much, much more accurate to say instead “facing these tradeoffs is effectively impossible to avoid even though it’s stupid and avoidable”. We might not like reality, but it’s not going to go away no matter how much we call it stupid and avoidable.

Dentin May 6, 2021, 11:40 AM
2 points
0
on: Alzheimer’s, Huntington’s and Mitochondria Part 3: Predictions and Retrospective
Having an overarching model (or several competing models) of which different parts can be tested independently seems like a structure which is very amenable towards different scientists, so I am disappointed none of the biological/medical community has started doing something like this.
This is actually done, quite a lot in fact, it’s just really hard and the search space is huge. Kudos to you for your analysis; it’s unlikely to be a major step forward, but given that idea search space is effectively exponential, it’s also entirely possible that it’s a unique insight. Please do attempt to publish it.
For an ‘off the top of my head’ example of this sort of modeling in the wild, this is a really interesting paper:
https://europepmc.org/article/pmc/pmc6520007
Basically, the model was “we’ve got a class of cancer cells with mitochondrial weirdness, what happens if we shut off both mitochondrial ribosomes at the same time?” And it turned out there were commonly available low dose drugs which do this.

Dentin May 6, 2021, 11:22 AM
11 points
0
in reply to: jefftk’s comment on: Why I Work on Ads
> its entire purpose is to alter people’s mental state without their permission
I think that’s the core of our disagreement?
Yes, and I think that would be a better path to attack my position. There’s two attack vectors in that quoted line—“alter peoples mental state without their permission”, and “permission”. I would recommend avoiding the first attack vector; that will be an exceedingly difficult sell to me.
Permission on the other hand is already a partially open attack vector, and you’re much, much more likely to change my mind by that route. Examples:
- I have very little objection to the ads on the Google web search interface. I don’t notice them, but I do sometimes click on them. The reason I have no objection is because “I was actively looking for something”, and the ads are almost always topical and don’t drown out real results. In other words, I gave implicit permission by searching for the thing that was being advertised to me.
- I have very little objection to the ads within the Amazon search interface. Again, it’s because I was explicitly looking for the thing in question, and typically the ads presented are factual results that answer my query.
In both those cases, permission isn’t some implicit, distant concept; I explicitly make the choice not just to navigate to the site in question, but to request specific results from the site, knowing that the ads would be there.
IMO, that’s quite different from pretty much all other advertising: I’m not giving ‘implicit permission’ to view dildo or BMW ads when I go to news sites, or when I click around at random places on the internet. I don’t click on an interesting link because I have an explicit, well defined target. When I’m browsing, it’s like I’m walking in a park seeing the sights, or walking around Burning Man looking at the art. My expectation is that people won’t bother me and that I won’t constantly have ads shoved in my face.
Instead, I have to keep up both adblock and a hostban list just so I won’t be bombarded with unrequested solicitations. I’m explicitly opting out, yet advertisers continue to try to find ways to bypass that, in spite of my explicitly stated preferences.
I think it would be possible to greatly clean up the ecosystem by effectively banning ‘push mode’ advertising, and strictly only allowing pull modes such as my two examples above. Sure, it would mean a hell of a lot less advertising, and a LOT of companies would have to find new ways to survive. But those companies (and people) will figure something out. Some of them might even succeed because they have excellent products that people actually want, instead of due to huge propaganda budgets.

Dentin May 6, 2021, 11:03 AM
4 points
0
in reply to: jefftk’s comment on: Why I Work on Ads
Here’s another version of your example: Some people aren’t watching nearly enough snuff and torture videos. There are people who would like to watch them, but don’t know it exists. If I place ads for torture and snuff videos and some people decide to click on them while other people don’t, is that a problem?
As I mentioned earlier, advertising is like weaponry. Your example also reads to me like a classic justification for ‘everyone having guns’: “but what if I’m attacked by a rabid dog? If I have my gun I can protect myself! See, guns are ok to have!” Just because it’s possible to point out a positive use case, doesn’t mean that the remainder of the field is also positive.
And to be clear, I consider your example to be about as likely as the rabid dog example. Sure, in a world with perfect targeting it could be done, but we’re not in that perfect world, and consumers have a vested interest in keeping it that way. The new privacy initiatives are a big part of that.

Dentin May 3, 2021, 10:36 PM
18 points
0
on: Why I Work on Ads
As someone who also works on Ads at Google, I have to take the opposite stance; I view advertising as a blight upon the face of humanity, something to destroy if we can at all figure out how to do so. I comfort myself knowing that Google Ads is arguably the best of what’s an awful ecosystem, and that I work in what’s arguably the ‘least bad part of advertising’, which is fraud and abuse protection. At least the systems I work on make things less terrible.
However, the ‘least bad part of advertising’ is still not ‘good’.
My favorite analogy for advertising right now is weaponry; specifically, guns. Advertising is like a handgun. Sure, it can be used for good, and sure, in the right hands it’s fine, safe even. However, the default for a handgun is that it is Unsafe, and you have to put forth effort to “use it for good” because it’s entire purpose is to kill living things. That’s advertising—its entire purpose is to alter people’s mental state without their permission. Sure, you can “use it for good”, and sure, you can make it ‘safe’. But it’s a lot easier to use it for abuse and clockwork orange scenarios.
I’ll be switching teams in the next few months to be out of Ads. Hopefully I can find something positive to work on.

Dentin Apr 25, 2021, 10:55 AM
2 points
0
in reply to: Teerth Aloke’s comment on: Best empirical evidence on better than SP500 investment returns?
I still have some remaining bitcoin, from the olden days when mortal man could mine it themselves. My advice to everyone I’ve ever talked to regarding bitcoin is to avoid it. I have been slowly divesting my holdings.
My rationale is that while both the dollar and bitcoin are fiat currencies, bitcoin is far, far less anchored to reality than most ‘normal’ currencies. The dollar and the euro at least have people trying to keep monetary levels somewhat tied to physical economic value. The value of bitcoin, meanwhile is largely driven by three things:
1. propaganda / marketing / bubble behaviour
2. money laundering
3. a belief that using bitcoin for transactions has the potential to be cheaper than transactions in the normal financial ecosystem
#1 is basically fad investing. It can yield huge returns, but is equally likely to yield losses and ultimately just moves money from people who are bad at predicting fads to those who are less bad at predicting fads.
Basing your holdings on #2 is going to be subject to diminishing returns over time, as governments get cranky about it and find ways to crack down.
Basing your holdings on #3 ignores how expensive bitcoin transactions have become, and how you have to either build what amounts to a miniature “normal financial system” on top of it in order to arbitrage the cost, or only do transactions that are sufficiently large that the costs aren’t important.

Dentin Apr 17, 2021, 5:58 PM
4 points
0
on: On Sleep Procrastination: Going To Bed At A Reasonable Hour
I’ve found lighting, melatonin, and caffiene regulation to be wonderful additions to my sleep regime. I take melatonin pretty consistently at around 8:30 pm, and it seems like it helps make me sleepy ~45 minutes later. As per SSC though, melatonin isn’t particularly strong and the effect I’m noticing may very well be placebo. I always have caffiene, but rarely after 2 pm, and typically not more than two cups of coffee per day.
That said, I suspect my lighting and light policy is having a much, much bigger effect.
The primary light source in both the computer room and bedroom are a variant of these:
https://www.amazon.com/MINGER-Changing-Lighting-Flexible-Decoration/dp/B07JP5375R
I have a number of presets configured; every single one of them is orange, with no blue enabled, in both rooms. Even at full brightness, it’s rather dim compared to even a single overhead bulb, and I switch to progressively more dim presets later on at night. I only use the incredibly bright overhead lights if I’m searching for something, or working on a specific high-detail project.
My bedroom has blackout sheets on the windows.
I take all my showers/baths in the dark. I started doing this to better understand some of my visually impaired friends; I quickly discovered that I liked it more than having the lights on all the time.
All of my computer monitors are all set for the minimum brightness level that still allows reasonable contrast and visibility, as well as the lowest available color temperature.
And lastly, all apps/terminals that I use are set to a black background, except for the browser; my X session background is solid black. Websites in the browser are set to dark mode css if it’s available, and I have a ‘dark mode’ extension for sites without a dark mode css. All this said, I generally only flip on the extension in the evening.
I pretty consistently go to bed around 9:30 when I feel super sleepy, and can typically fall asleep in under five minutes. I’ve found that even a few minutes of using the overhead lights after 7:00 pm breaks this; I both don’t get as sleepy as normal, and find it harder to go to sleep if I go to bed anyway. Caffiene late in the day can also screw it up pretty badly, but that’s far more rare than needing the overhead lights for a few minutes for some task.

Dentin Mar 31, 2021, 12:21 PM
5 points
0
on: Goldfish Reading
Quick comment: I noticed that in all of your examples above, I chunk substantially bigger and fewer pieces. For example, in the “15 different bold bits” clip, I chunk it into about 8 pieces instead.
This is likely experience/background dependent; I happen to have a relatively strong background in ML and have read a stack of research papers recently, so I probably have both stronger noise filters and more complicated primitives available.
One possibly interesting side note: I never once, in any of your examples, considered metadata about the topic relevant. This includes things like the author names, “tested”, “study proposed”, etc. I suspect I’ve learned that 1) author names are almost never important, 2) test procedures are only worth thinking about if they’re very explicitly detailed (which was not the case above), and 3) even if the test procedures are ok, they’re typically only relevant as a cleanup/sanitization pass once the main concept is understood.

Dentin Feb 13, 2021, 4:47 PM
96 points
0
on: How Should We Respond to Cade Metz?
Let’s be blunt here: the NYT article is pure, unbridled outrage bait dressed up as journalism. It’s not trying to solve a problem, and it doesn’t have any agenda other than to pack as much outrage as possible into the publication form factor so as to maximize eyeballs. It simultaneously craps on EA, the tech industry, SSC, rationalists, MIRI, tech investors and a stack of others. (I’m surprised that they didn’t also include jordan peterson, because hey, why not?) That’s not the sign of someone being honest.
IMO the correct response here is to recommend that friends and family unsubscribe or avoid the NYT. As far as as creating/finding a rebuttal and explaining things to others, don’t. Instead, say the article was a hit piece designed to make everyone look bad, and shrug. Give it the kind of attention you give to crazy preachers on street corners. Let it fade into obscurity.
Remember that with outrage bait, you being outraged and complaining about the article to others is entirely the point. The only winning move is not to play.
What links here?
- ejacob's comment on How Should We Respond to Cade Metz? by DirectedEvolution (Feb 13, 2021, 6:07 PM; 17 points)

Dentin Feb 11, 2021, 10:15 PM
4 points
0
on: Speedrunning my Morning Makes the Coffee Taste Weird
I do a low-grade speedrun in the morning, every day. If you make it a habit, it becomes less of a stressful “speedrun”, and more of “how you do things”.
Example:
- Roll out of bed, grab phones
- While walking through hallway flip on heat
- Wander to office, put phones on desk where they’ll sit all day long
- Put on clothes and socks that were put on my chair the night before
- Bathroom
- Stumble to kitchen
- Fill teapot, put on stove
- Fill water purifier back up
- Put coffee grounds in mug
- Do a set of pushups
- Go to office, power up monitors, start catching up
- Go to kitchen after a few minutes, shut off stove, pour coffee
You know, from the outside, that looks pretty ridiculous. It is fast and efficient though. Thank you, Covid lockdown?

Dentin Feb 10, 2021, 12:33 PM
25 points
0
on: We got what’s needed for COVID-19 vaccination completely wrong
I think this might be (very slightly) unfair to mRNA vaccines, as the comparison between them and peptide vaccines is pretty situation dependent:
- We have reason to believe that peptide vaccines will work particularly well here, because we’re targeting a respiratory infection, and the peptide vaccine delivery mechanism targets respiratory tissue instead of blood.
- That said, mRNA vaccines are expected to elicit much stronger immune responses than peptide vaccines would.
- I suspect that the low efficacy of mRNA vaccines (only 95% - low is relative) is likely because they’re only targeting the spike protein, which apparently has ‘high mutant escape potential’. We have a LOT more information about the virus now than we did when the mRNA designs were finalized. If companies had been allowed to make mRNA vaccine updates without resetting all the clinical trials, I believe we’d have a substantially better/stronger vaccine than just 95%, with a single shot instead of two.
- mRNA vaccines are really just a technology demo at this point; sure, you can make vaccines with the tech, but that’s not the real superpower here. The superpower is that we have a platform we can use to generate arbitrary proteins in live cells, including proteins we know about but for which we have no reasonable delivery mechanism. Not all proteins/peptides are water soluble, and fewer are able to get through cell walls.
- As a technology demo (and not a simple one at that), it’s surprising that companies have as much production capability as they do. I would expect that capacity to be ramped up substantially in the next few years as we start aggressively making use of mRNA treatments to address a host of issues.
To sum up, my view is that mRNA technology is pretty great and I’m really, really glad someone was able to make use of the disaster that was 2021 to ram through safety and clinical trials. My issue is less with the technology and it’s large promise, and more with how vaccine testing and rollout has been botched or unnecessarily slowed down at every level.
Peptide vaccines are easy and fast to both design and construct, while being safe unless you really screw up, and effective as long as designed correctly. However, they do have rather substantial limitations, and it’s just happenstance that they’re particularly well suited for the situation. I could see mRNA vaccines having a much wider berth.

Dentin Feb 10, 2021, 12:18 AM
8 points
0
in reply to: koroviev’s comment on: Making Vaccine
In my case, I’d estimate that I’ve spent around two hundred hours over the last several months coming sufficiently up to speed on the topics that I can reason about them. I started with about your level of biology (or possibly less), but probably a slightly stronger chemistry background.
For the basics, I started with cell biochemistry, DNA/RNA, mRNA and protein construction. From the vaccine side of things, I just started looking up things I found in the whitepaper which I didn’t understand, and once I understood all the terms I started looking for and reading research papers. When I found something I wasn’t sure about, I researched it and learned about it.
As examples, in early January, I spent about ten days reading up on VED (vaccine enhanced disease). Shortly after, I spent a few days digging into chitosan, and trying to understand how sensitive nanoparticle creation is to changes in the mixing process (hint: not very.) Everything I searched for I was able to find, and pretty much everything reinforced the same internally consistent view of the world.
When you find something that doesn’t make sense and you’re stuck, write it down, file it away and come back to it later. Eventually you’ll be able to make sense of it.
When you’re able to read through most or all of the whitepaper and understand both what’s being discussed and why specific things were selected, you’ll be in pretty good shape.
It’s not particularly difficult, it just takes time and effort.

Dentin Feb 8, 2021, 11:51 AM
5 points
0
on: How do you optimize productivity with respect to your menstrual cycle?
I have two data points for dealing with this successfully, and both amount to “make it stop” instead of “improve things”:
- One of my sisters “doesn’t have time for this crap” and one day just stopped taking the placebo pills from her normal birth control and stayed on the active hormones continuously. This apparently suppressed her period. After doing this for about ten years, she stopped and successfully conceived at almost 40 years old. This is not medical advice, do your own research, etc blah blah.
- One of my female friends has had an IUD for ~15 years now, which over time reduced her period to occasional light spotting and dramatically reduced general symptoms and inconvenience. The startup period (first year) was rough though, as was the first six months after the first replacement five years in. The second replacement was basically not a problem.
It should be noted that I’m aware of multiple attempts to use IUDs within friends and family, but only have one data point that was long term successful. Apparently the first year of an IUD can be brutal and it’s not uncommon to give up after a few months.

Dentin Feb 6, 2021, 12:33 AM
2 points
0
in reply to: habryka’s comment on: Making Vaccine
Ugh. Thanks for the link.

Dentin Feb 6, 2021, 12:22 AM
6 points
0
in reply to: johnswentworth’s comment on: Making Vaccine
I believe that initial post is what got me going down the rabbit hole of peptides and proteins and dna and rna and transcription factors oh my! It’s been a long ride.

Dentin Feb 6, 2021, 12:20 AM
8 points
0
in reply to: ChristianKl’s comment on: Making Vaccine
Sarah Constantin is confused, and likely has not spent significant time reviewing the vaccine design. From page 32 of the whitepaper:
“Empirical evidence should dominate selection criteria. Here are some best types of evidence:
- Mapping of epitopes in blood and other samples collected from convalescent patients (ideally stratified by severity of illness). This can be accomplished by a few primary means:
  - 3D structural studies and modeling of neutralizing antibody binding to a viral antigen (e.g. Spike protein)
  - Mapping of linear B-cell epitopes by binding antibodies in convalescent sera to a library of peptides representing viral antigens. A strong signal in a linear epitope mapping study does not guarantee that the epitope peptide in the context of a vaccine will trigger the production of an antibody that binds to this epitope within the context of the virus. However, it is a good indicator that this is at least possible. Peptides can be constrained to approximate native conformation, making it more likely to bind the native epitope.
  - Mapping of T-cell epitopes by stimulating convalescent T-cells with epitope peptides, and measuring their response (e.g. cytokine secretion; ELISpot)
- Epitope peptides from a peptide vaccine that has shown protection against
  infection
- Successful use of epitope peptides in vaccines that elicit antibodies (or serum)
  effective in virus neutralization assays. B-cell epitopes that allow antibody binding
  to the virus but don’t block viral function might increase risk of
  antibody-dependent enhancement.
- Mapped epitopes that are effective in virus neutralization assays (e.g. peptides
  compete with viral sequences in cellular infection assays).
- Successful use of epitope peptides in vaccines that elicit T-cell responses, or
  peptides shown to stimulate T-cells or cytokine production in ELISpot or other
  T-cell assay in cells from convalescents.”

Dentin Feb 6, 2021, 12:15 AM
2 points
0
in reply to: Yoav Ravid’s comment on: Making Vaccine
Sorry about that; I believe I misread your comment as implying that if the moderator is ignorant, he won’t have enough information to form a reasonable prior. My disagreement was along that line, as it seems that misinformation, especially about medical things, is so prevalent that everyone’s default prior should be ‘fraud unless lots of evidence points the other way’.

Dentin Feb 5, 2021, 11:20 PM
22 points
0
on: [Link] Sarah Constantin on RaDVaC
A couple of minor quibbles:
1. The peptides did not “come from in silico studies”; they came from the antibody profiles of real patients, who really had covid, and really recovered from covid (ideally without having a Bad Time during recovery.) So there’s more than just computational reasons to believe they will be useful.
2. It’s questionable to complain that radvac did not have a single “research study using any of the peptides in the RADVAC white paper that found they inhibited SARS-CoV-2 infection in cells, let alone animals or humans”, when the pfizer vaccine (which we know works) was designed via the same process a year ago, when we had even less information about effectiveness.