Dentin

Comments

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.

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.

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?

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.

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.

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.

Making Vaccine

Ugh.  Thanks for the link.

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.

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."
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'.

Load More