trentmkelly/LessWrong-43k huggingface dataset:
Alzheimer's, Huntington's and Mitochondria Part 1: Turnover Rates
by J Bostock — 2021-05-03T14:46:41.591Z

Epistemic status: Big if true, I don't have much time now but I might try and write part of this up into a more formal scientific letter to a journal or something later. I am reasonably confident that my models here are significant in some way but I do not have much experience in the field and I've written this up over the past weekend instead of revising for my exams.

Introduction

It is sometimes said (often here, rarely in the places where it ought to be) that the turnover rate of amyloid-causing proteins in the brain is too high for them to be the primary causative agent of Alzheimer's disease (AD). While this is an important piece of evidence, I do not think it is as definitive as many suggest, due to biochemical reasons I will go into later. In order to investigate further I decided to compare AD to a better understood disease: Huntington's disease, and found an unexpected link in mechanism between the two. I have decided to write my findings up here.

This series of three posts will be rather scattered. This post aims to explain the motivations for my initial investigation, and also goes into some of the mathematics of amyloid formation. The next post will be a quick review of several pieces of evidence I have found and the assembly of this evidence into a (reasonably) cohesive model of AD progression. The third will be some predictions of mine based on this model, and a retrospective on the process of building this model.

Why turnover rates might not matter

The motivation for this investigation was to cement whether or not the high turnover rate of amyloid-causing proteins is strong evidence against them being causally involved in AD. The two amyloid-causing proteins are Tau and Amyloid Beta (Aβ). Tau forms aggregates inside neurons and turns over with a half-life of around 23 days in the central nervous system.(1) Aβ forms aggregates outside neurons and turns over even faster, with a half-life on the order of a few hours.(2)

There are some reasons why I thought that (counter-intuitively) that may not be the case. Cells in the body are generally under many layers of regulation, especially towards the concentration of different proteins, so rapid synthesis and degradation of proteins is not necessarily evidence that they can only cause diseases on long timescales. To see how this is relevant imagine the following model of an amyloid fibril:

Proteins are joined...
The Schelling Game (a.k.a. the Coordination Game)
by jchan — 2021-05-03T14:31:38.267Z

Summary

The Schelling Game (or Coordination Game) is a simple but fun party game that seems to have been independently invented several times. (One might even say it represents a Schelling point in game-space...) I have played it both with LessWrong meetups and with other groups; good times were had by all. This article describes the rules of the game as I've seen it.

The purpose of the game is to discern Schelling points among the group. You should have at least 4 players; there may be an upper limit at which the game becomes unwieldy, but I've never seen it get that large. (The most I've seen was about 15 players, and that seemed to work fine.) No materials are required, although paper-and-pencil are helpful.

On each turn, play proceeds as follows:

Someone (the "prompter") names a category (e.g. "Living people").
Everyone (including the prompter) precommits to some answer in response.
Everyone reveals their answer, and each player gets as many points as there are other players giving the same answer.

A round is completed when every player has given one prompt. The number of rounds should be set in advance, usually such that there are 10–20 prompts in total. (The game tends to get boring if it goes on much longer.) At the end, whoever has the most points wins.

Rule variants

The unanimous answer rule

If all players give the same answer for a prompt, then under the basic rules everyone would get the same number of points, so the turn is effectively a wash. To discourage this, and encourage more interesting prompts, you can say: If everyone gives the same answer, then everyone gets 0 points, except for the prompter, who loses 1 point.

Sudden-death tiebreaker

If, at the end of the pre-set number of rounds, multiple players are tied for first place, you can enter a "sudden-death round" to determine the winner. Take turns giving prompts in the same order as before, but skip any player involved in the tie. All players should answer the prompt, but only the first-place contenders are eligible to earn points. The game ends as soon as the tie is broken, regardless of whether the turn order has completed.

Talking during turns

Under the most strict rules, all players must be silent after the prompt is given and before the answers are revealed (since anything said aloud might create a new Schelling point). You may find that this makes the game less fun, so you can relax this restrict...
Maps of Maps, and Empty Expectations
by Nora_Ammann — 2021-05-03T09:59:04.110Z

[cross-posted here]

This post is a recap of some

naturalism studies

I did a few months back. At the outset, I didn’t know where the studies would take me. Now, I believe they taught me about how to do the “real” version of the thing you’re trying to do, where “real” tries to point at things like “the territory” and “what actually matters”.

To communicate my idea, I will rely on two central examples and offer two frames of interpretation. I want to offer people several, slightly different footholds, such that, if one example or one frame clicks for you while the others don’t, you can run with the one that did. I end the post with some thoughts on how to respond to the problem I’m outlining.

Outline

Examples

“Ideal solutions”
“Being helpful”

Interpretative Frames

Maps of maps
Empty expectations

What to do in response?

Let’s go!

Examples

“Ideal solutions”

Some time ago, I was working on an important work project. I cared about doing it well. Initially, things went well but soon I started to feel stuck and grew increasingly averse to working on the project. Whenever I would turn to thinking about the project, I had an experience of my mind “cramping” or “tensing up”, and a veil of fog settling over my mind, preventing me from thinking clearly and making progress. I’d start to feel increasingly frustrated, self-judgemental, and averse to working on the project.

A central part of the phenomenology of this experience is a sense of “trying really hard”, but failing to really get a grip on the problem. It’s a chain of

trigger-action patterns

where, when I notice I get stuck in this way (trigger), my mind reacts by “trying harder” (action), which in turn makes my mind tense up more. This creates more of the mind-fog preventing me from being able to think clearly, meaning I’m even less able to make progress (trigger), causing my mind to want to try even harder (action), etc. The resulting experience is one of “drifting away from” rather than “towards” a clear understanding of the task/problem.

When I first ran into this problem, I didn’t understand what was going on. So, I started studying this tensing-up experience, which eventually led me to an insight that was central to my making progress on this problem.

I realized that I was holding the subconscious belief that there existed, somewhere, an ideal, a perfect solution to my project. I didn’t have access to this “id...
Open and Welcome Thread - May 2021
by habryka — 2021-05-03T07:58:03.130Z

If it’s worth saying, but not worth its own post, here's a place to put it.

If you are new to LessWrong, here's the place to introduce yourself. Personal stories, anecdotes, or just general comments on how you found us and what you hope to get from the site and community are invited. This is also the place to discuss feature requests and other ideas you have for the site, if you don't want to write a full top-level post.

If you want to explore the community more, I recommend reading the Library, checking recent Curated posts, seeing if there are any meetups in your area, and checking out the Getting Started section of the LessWrong FAQ. If you want to orient to the content on the site, you can also check out the new Concepts section.

The Open Thread tag is here. The Open Thread sequence is here.
Small and Vulnerable
by sapphire — 2021-05-03T04:55:52.149Z

Anyone who is dedicating the majority of their time or money to Effective Altruism needs to ask themselves why. Why not focus on enjoying life and spending your time doing what you love most? Here is my answer:

I have a twin sister but neither of us had many other friends growing up. From second to fifth grade we had none. From sixth to eighth we had one friend. As you might guess I was bullied quite badly. Multiple teachers contributed to this. Despite having no friends my parents wanted us to be normal. They pressured me to play sports with the boys in the neighborhood. I was unable to play with an acceptable level of skill and was not invited to the games anyway. But we were still forced to go 'play outside' after school. We had to find ways to kill time. Often we literally rode our bicycles in a circle in a parking lot. We were forced to 'play outside' for hours most days and even longer on weekends. I was not even allowed to bring a book outside though sometimes I would hide them outside at night and find them the next day. Until high school, I had no access to the internet. After dinner, I could watch TV, read and play video games. These were the main sources of joy in my childhood.

Amazingly my mom made fun of her children for being weirdos. My sister used to face a wall and stim with her fingers when she was overwhelmed. For some reason, my mom interpreted this as 'OCD'. So she made up a song titled 'OCD! Do you mean me?' It had several verses! This is just one, especially insane, example.

My dad liked to 'slap me around. He usually did not hit me very hard but he would slap me in the face all the time. He also loved to call me 'boy' instead of my name. He claims he got this idea from Tarzan. It took me years to stop flinching when people raised their hands or put them anywhere near my face. I have struggled with gender since childhood. My parents did not tolerate even minor gender nonconformity like growing my hair out. I would get hit reasonably hard if I insisted on something as 'extreme' as crossing my legs 'like a girl in public. I recently started HRT and already feel much better. My family is a lot of the reason I delayed transitioning.

If you go by the checklist I have quite severe ADHD. 'Very often' seemed like an understatement for most of the questions. My ADHD was untreated until recently. I could not focus on school or homework so tryi...
Sexual Dimorphism in Yudkowsky's Sequences, in Relation to My Gender Problems
by Zack_M_Davis — 2021-05-03T04:31:23.547Z
Link: http://unremediatedgender.space/2021/May/sexual-dimorphism-in-the-sequences-in-relation-to-my-gender-problems/

(content warning sexism)

(content warning implied transphobia)

(content warning too much information about weird sexual fetishes)

(content warning WTF did I just read)

(May 2021, ~16,000 words)
There’s no such thing as a tree (phylogenetically)
by eukaryote — 2021-05-03T03:47:48.876Z
Link: https://eukaryotewritesblog.com/2021/05/02/theres-no-such-thing-as-a-tree/

[Crossposted from Eukaryote Writes Blog.]

So you’ve heard about how fish aren’t a monophyletic group? You’ve heard about carcinization, the process by which ocean arthropods convergently evolve into crabs? You say you get it now? Sit down. Sit down. Shut up. Listen. You don’t know nothing yet.

“Trees” are not a coherent phylogenetic category. On the evolutionary tree of plants, trees are regularly interspersed with things that are absolutely, 100% not trees. This means that, for instance, either:

The common ancestor of a maple and a mulberry tree was not a tree.
The common ancestor of a stinging nettle and a strawberry plant was a tree.
And this is true for most trees or non-trees that you can think of.

I thought I had a pretty good guess at this, but the situation is far worse than I could have imagined.

CLICK TO EXPAND. Partial phylogenetic tree of various plants. TL;DR: Tan is definitely, 100% trees. Yellow is tree-like. Green is 100% not a tree. Sourced mostly from Wikipedia.
I learned after making this chart that tree ferns exist (h/t seebs), which I think just emphasizes my point further. Also, h/t kithpendragon for suggestions on improving accessibility of the graph.

Why do trees keep happening?

First, what is a tree? It’s a big long-lived self-supporting plant with leaves and wood.

Also of interest to us are the non-tree “woody plants”, like lianas (thick woody vines) and shrubs. They’re not trees, but at least to me, it’s relatively apparent how a tree could evolve into a shrub, or vice-versa. The confusing part is a tree evolving into a dandelion. (Or vice-versa.)

Wood, as you may have guessed by now, is also not a clear phyletic category. But it’s a reasonable category – a lignin-dense structure, usually that grows from the exterior and that forms a pretty readily identifiable material when separated from the tree. (…Okay, not the most explainable, but you know wood? You know when you hold something in your hand, and it’s made of wood, and you can tell that? Yeah, that thing.)

All plants have lignin and cellulose as structural elements – wood is plant matter that is dense with both of these.

Botanists don’t seem to think it only could have gone one way – for instance, the common ancestor of flowering plants is theorized to have been woody. But we also have pretty clear evidence of recent evolution of woodiness – say, a new plant arrives on a relatively ba...
Thoughts on Re-reading Brave New World
by chemslug — 2021-05-03T03:28:27.914Z

I recently re-read Aldous Huxley's masterpiece of dystopian fiction Brave New World for the first time in at least a decade. Like any worthwhile piece in this genre, some predictions seem prescient (increase in sexual freedom and unproductive distractions), while others seem off the mark, even considering publication date (no significant automation of routine tasks). This isn't a formal book review, and I won't deliberately spoil the plot, but I will be discussing the implicit predictions and judgments about human nature, society, and technology, and I'll need to talk about the world-building to do that properly.

Synopsis of Huxley's World-Building

The story takes place in the Year of Our Ford 632 (which by my calculations should correspond to 2495 CE) in London and surroundings, with a brief sojourn to New Mexico. The world is under a unified government that prioritizes stability and tranquility. Families are no more; embryos are incubated in vitro, decanted en masse, and conditioned chemically and psychologically to fill just the niche they were created to occupy. Higher-caste individuals ("Alphas" and "Betas") are one-of-a-kind, but members of society's lower orders ("Gammas", "Deltas", and "Epsilon semi-morons") are created as masses of clones and shaped with growth hormones and poisons to have just the right size, temperament, and intellectual ability for their lives of drudgery. Further control is achieved through endless repetitions of mantras during sleep, as well as copious, promiscuous (heterosexual) sex and liberal doses of soma, a sort of combined antidepressant/hallucinogen/tranquilizer. Everyone is tremendously happy with the situation, because they've been conditioned to be so. Well, almost everyone. We couldn't have much of a plot without some sort of conflict now, could we?

Predictions About Technology

Brave New World was published in 1932, and we need to take that into account when reading it in 2021. For example, lots of progress had recently been made in automation of the big-machines-in-factories type (hence all the references to Henry Ford), but computers, to the extent they existed at all, were big, clunky, and not at all in the public consciousness. Certainly, they wouldn't have appeared to Aldous Huxley, a man educated in the humanities, likely to be of importance. Hence, ...
The Neuralink Monkey Demo
by XelaP — 2021-05-03T02:29:05.288Z

The Neuralink YouTube channel (which is apparently a thing that exists) released a demo of their technology using Pager, a nine year old Macaque monkey.

WHO'S A GOOD MONKEY! YES YOU ARE!

Video Overview

In the video, Pager plays two games using a joystick. For the first, he moves a cursor to an orange square in a grey grid, then moves it to the next square to pop up. For the second, he plays his favorite game, Pong.

While he plays, the Neuralink team have been analyzing the neural activity in his brain using a Neuralink implanted in his brain. They are able to receive data in realtime, and figure out which patterns of activity correspond to each hand movement.

The voiceover states that "After only a few minutes of calibration, we can use the output from the decoder to move the cursor instead of the joystick". The team then unplugs the joystick and has Pager play. Pager is then able to just think about moving his arm, and is able to play Pong using his mind.

Pager plays MindPong

Implications

First of all, Neuralink was launched 1 year ago, and we already have monkeys playing games with their mind. I predict with 70% confidence that, within a year, Neuralink will be placed in a human and will have basic functionality. If I'm wrong, I think it'll mainly be because of Neuralink not being legally allowed to conduct a human trial, or due to long term safety concerns as opposed to short term ones.
[Weekly Event] Alignment Researcher Coffee Time (in Walled Garden)
by adamShimi — 2021-05-02T12:59:20.514Z

I'm organizing a weekly one hour coffee time for alignment researchers to talk about their research and what they're interested about, every Monday starting tomorrow. The time (9pm CEST, see here for your timezone) was decided after I polled a number of people, to allow timezones from PT to IDT (sorry for people in Asia and Australia).

It will happen in the Walled Garden, in the central house which is directly up when you pop up in the Garden. The link of the event is public, although the event is by default reserved for AF members and people invited by them.

Here is the link.

Some basic infos:

The restriction to AF members and invitees is mostly so that we don't have to reexplain AI Risk 101 every time. This is not the point of this event. If you're genuinely interested in alignment, and if you've read some of the posts in the AF and are starting to form an image of the field, then by all means come discuss.
No obligation to come everytime. The goal is mostly that if you want to talk to a relatively broad range of people instead of having one-on-one calls, you can do so the next week instead of waiting for the next big event.
By default there is no talk planned, but if attendees feel like shaking the structure a bit, that's fine.
[Linkpost] Teaching Paradox, Europa Univeralis IV, Part I: State of Play
by adamShimi — 2021-05-02T09:02:19.191Z
Link: https://acoup.blog/2021/04/30/collections-teaching-paradox-europa-univeralis-iv-part-i-state-of-play/

I particularly wanted to discuss Paradox’s games, as compared to other historically rooted games, because I think Paradox’s oeuvre is a particularly rich vein to mine. I have already heard from multiple college-level instructors that they have students coming into their classes specifically to learn the history behind these games, which in turn means that these games are serving to shape those student’s understanding of history before they even enter the classroom. Moreover, and we’ll get deeper into this as we go along, the very presentation of Paradox’s games, which use their efforts at historical accuracy as a key selling point, encourages players to think about them as exercises in history rather than just games.

But more than that, more than most historically set games, Paradox games are interesting because they are built with what I think is a detectable theory of history. Unlike other games which blunder through historical eras thoughtlessly, Paradox games, intentionally or not (in the event, I think it is clear from speaking with a couple of their developers, there is quite a lot that is intentional) have something to say about history. As we’ll see, some of that I’ll agree with and some of it I will disagree with, but the great value of Paradox’s games is that there is an ample theory of history to agree or disagree with.

[...]

So we are going to approach this question from two related frames, first, what should the student of history be thinking about when playing Paradox’s games; what unspoken assumptions should they be aware of, or even forewarned about? And what of those assumptions are grounded in real arguments among historians (or, put another way, where does Paradox have its feet firmly in the scholarship in crafting its games)? And second, what ought teachers of history know about these games and take into account if they find themselves teaching students for whom Paradox is the historical ‘mother tongue’ and actual history only a second language?

A linkpost to the great blog A Collection of Unmitigated Pedantry is long overdue. The author, a historian, examines pop culture through the lens of history, as well as some more direct historical topics from time to time. It's great, fascinating, and quite different from the other blogs and websites I usually follow.

This specific link is to a series that started this week, looking at a franchise of h...
Car Seats Three Across
by jefftk — 2021-05-02T02:00:04.832Z

When I

posted about how we were thinking
of getting a car, and specifically that we were thinking of having
three kids in car seats across the back of a hatchback, several people
told me they wouldn't fit. This is a common enough view that there's
an econ paper about it:

Car
Seats as Contraception (which I

disagreed with). When we decided to

share a 2013 Honda Fit I was pretty
confident it would work since I knew how wide the seats were, how wide
the space was, and I had done something similar with a different
collection of car seats. But I hadn't actually tried our particular
seats in this particular car.

With the baby getting closer, about a month out, I put the seats in
for practice. I tried two different ways:

The version with the baby in the middle fits the easiest, with enough
room to use the wide booster. On the other hand, that requires getting
the baby plus carrier farther in, which could be awkward? The
version with the baby on the side does work, but you do need to use
quite a narrow booster seat in the middle.

These three car seats are ones we chose for being narrow, but there
are still many options at this size. This is a 17" infant seat, 17"
convertible, and either a 17" booster (baby in the middle) or 13"
booster (booster in the middle).