Recent Discussion

As johnswentworth recounts in Core Pathways of Aging, as an organism ages active transposons within it's stem cells duplicate and that mechanism might lead to increased average transposons count in stem cells. Those transposons then produce DNA damage which in turn leads to cell senescence.

If that hypothesis is true, there's evolutionary pressure to keep the count of active transposons low. That evolutionary pressure is greater in organism that reproduce at a later age then for organisms that reproduce at an earlier age.

As Bret Weinstein describes, breeding protocols for lab mice have lab mice reproducing at an earlier age then mice that live in the wild because it's economical to make the mice reproduce at a young age. Weinstein made the hypothesis that this leads to laboratory mice...

2dkirmani43mMy model is that transposons duplicate in all somatic (non-reproductive) cells, not just stem cells. The evolutionary basis of aging (and negligible senescence, like in hydras and naked mole rats) is still a total mystery to me. The arguments for why aging is adaptive [https://atlasofscience.org/aging-is-adaptive/] all rely on group-selection, which I am wary of. The argument is basically that you grow old and die to benefit the tribe, just as your cells commit suicide when it is useful for you. I'm relatively unconvinced by this argument, as I believe that intra-tribal competition is a much more powerful selective force than inter-tribal competion, giving rise to (machiavellian) intelligence as well as extremely metabolically costly dominance competitions. Getting old doesn't make sense if you're the only one doing it. Those who oppose the adaptive aging hypothesis [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803632/] generally fail to take into account the fact that naked mole rats exist, leaving us without an explanation as to why we have senescence and they don't. My model here is: Longer teleomeres -> Higher Hayflick limit [https://en.wikipedia.org/wiki/Hayflick_limit] (number of times cell can divide before dying) -> Higher cancer risk, as tumor cells can divide more (decreases chance of being alive in late-life), as well as higher capacity for tissue damage repair, as existing cells can divide more to replace missing ones (greater chance of being alive in early-life) This is consistent with longer telomeres being a reallocation from late-life health to early-life heath, and that tradeoff starts making sense when you reproduce at an earlier age. With respect to transposons, though, I don't understand what the trade-off is. With longer telomeres, you get an increased tissue regen rate at the expense of increased cancer risk. With transposons, you get senescence, but for what?

My model is that transposons duplicate in all somatic (non-reproductive) cells, not just stem cells.

They also duplicate in other somatic cells but in cells that have a low half life it doens't matter as much. 

With transposons, you get senescence, but for what?

You don't get anything in return just like you don't get anything in return for getting infected with COVID-19. 

You need evolutionary pressure to prevent transposons from constantly doublicating and accumulating in the DNA of your lineage.

Getting completely rid of transposons would be all up... (read more)

I'm finally beginning to feel that I have a clear idea of the true nature of counterfactuals. In this post I'll argue that counterfactuals are just intrinsicly a part of how we make sense of the world. However, it would be inaccurate to present them as purely a human invention as we were shaped by evolution in such a way as to ground these conceptions in reality.

Unless you're David Lewis, you're probably going to be rather dubious of the claim that all possibilities exist (ie. that counterfactuals are ontologically real). Instead, you'll probably be willing to concede that they're something we construct; that they're in the map rather than in the territory.

Things in the map are tools, they are constructed because they are useful. In other words,...

The underlying thought behind both this and the previous post seems to be the notion that counterfactuals are somehow mysterious or hard to grasp. This looks like a good chance to plug our upcoming ICML paper, w

hich reduces counterfactuals to a programming language feature. It gives a new meaning to "programming Omega." http://www.zenna.org/publications/causal.pdf

2JBlack12hA "counterfactual" seems to be just any output of a model given by inputs that were not observed. That is, a counterfactual is conceptually almost identical to a prediction. Even in deterministic universes, being able to make predictions based on incomplete information is likely useful to agents, and ability to handle counterfactuals is basically free if you have anything resembling a predictive model of the world. If we have a model that Omega's behaviour requires that anyone choosing box B must receive 10 utility, then our counterfactuals (model outputs) should reflect that. We can of course entertain the idea that Omega doesn't behave according to such a model, because we have more general models that we can specialize. We must have, or we couldn't make any sense of text such as "let's suppose Omega is programmed in such a way...". That sentence in itself establishes a counterfactual (with a sub-model!), since I have no knowledge in reality of anyone named Omega nor of how they are programmed. We might also have (for some reason) near-certain knowledge that Amy can't choose box B, but that wasn't stated as part of the initial scenario. Finding out that Amy in fact chose box A doesn't utterly erase the ability to employ a model in which Amy chooses box B, and so asking "what would have happened if Amy chose box B" is still a question with a reasonable answer using our knowledge about Omega. A less satisfactory counterfactual question might be "what would happen if Amy chose box A and didn't receive 5 utility".
2Chris_Leong9h"And ability to handle counterfactuals is basically free if you have anything resembling a predictive model of the world" - ah, but a predictive model also requires counterfatuals.
1TAG7hNo, prediction and counterfactuals share a common mechanism that is neutral between them. Decision theory is about choosing possible courses of action according to their utility, which implies choosing them for, among other things, their probability. A future action is an event that has not happened yet. A past counterfactual is an event that didn't happen.There's a practical difference between the two, but they share a theoretical component.: "What would be the output given input Y". Note how that verbal formulation gives no information about whether a future or state or a counterfactuals is being considered. The black box making the calculation doesn't know whether the input its receiving represents something that will happen, or something that might have happened. I'm puzzled that you are puzzled. JBlack's analysis, which I completely agree with, shows how and why agents with limited information consider counterfactuals. What further problems are there? Even the issue of highly atypical agents with perfect knowledge doesn't create that much of a problem, because they can just pretend to have less knowledge --build a simplified model -- in order to expand the range of non contradictory possibilities.

In partisan contests of various forms, dishonesty, polarization, and groupthink are widespread. Political warfare creates societal collateral damage: it makes it harder for individuals to arrive at true beliefs on many subjects, because their social networks provide strong incentive to promote false beliefs. To escape this situation, improving social norms and technology may help, however if only one side of a conflict becomes more honest, the other side may exploit that as a weakness, just as conquerors could exploit countries were less violent. Coming up with rules analogous to rules of war, may help ratchet partisan contests toward higher levels of honesty and integrity over time, enabling more honest coalitions to become more competitive. What follows is a naïve shot at an ethos of what such rules...

I am not sure that is actually true. There are many escalatory situations, border clashes, and mini-conflicts that could easily lead to far larger scale war, but don't due to the rules and norms that military forces impose on themselves and that lead to de-escalation. Once there is broader conflict though between large organizations, then yes you often do often need a treaty to end it.

Treaties don't work on decentralized insurgencies though and hence forever wars: agreements can't be credibly enforced when each fighter has their own incentives and veto power. This is an area where norm spread can be helpful, and I do think online discourse is currently far more like waring groups of insurgents than waring armies.

1Gentzel1hWhy would multi-party conflict change the utility of the rules? It does change the ease of enforcement, but that's the reason to start small and scale until the advantages of cooperating exceed the advantages of defecting. That how lots of good things develop where cooperation is hard. The dominance of in-group competition seems like the sort of thing that is true until it isn't. Group selection is sometimes slow, but that doesn't mean it doesn't exist. Monopolies have internal competition problems, while companies on a competitive market do get forced to develop better internal norms for cooperation, or they risk going out of business against competitors that have achieve higher internal alignment via suppressing internal zero-sum competition (or re-aligned it in a positive-sum manner for the company).
1Gentzel1hI don't think you are fully getting what I am saying, though that's understandable because I haven't added any info on what makes a valid enemy. I agree there are rarely absolute enemies and allies. There are however allies and enemies with respect to particular mutually contradictory objectives. Not all war is absolute, wars have at times been deliberately bounded in space, and having rules of war in the first place is evidence of partial cooperation between enemies. You may have adversarial conflict of interest with close friends on some issues: if you can't align those interests it isn't the end of the world. The big problem is lies and sloppy reasoning that go beyond defending one's own interests into causing unnecessary collateral damage for large groups. The entire framework here is premised on the same distinction you seem to think I don't have in mind... which is fair because it was unstated. XD The big focus is a form of cooperation between enemies to reduce large scale indiscriminate collateral damage of dishonesty. It is easier to start this cooperation between actors that are relatively more aligned, before scaling to actors that are relatively less aligned with each other. Do you sense any floating disagreements remaining?
1Gentzel1hThat's totally fair for LessWrong, haha. I should probably try to reset things so my blog doesn't automatically post here except when I want it to.

I’ve previously outlined many of the best options for securing a second residency, and some reasons you may want to do so.

Panama had one of the most unique, accessible, and attractive programs for doing so. Unfortunately, this program’s rules will be changing on August 20th, becoming much more restrictive, to the extent that I likely would not have mentioned the program under the new rules.

I’m interested in putting together a trip for EAs and Rationalists interested in securing Panamanian permanent residency, and in 5 years potentially citizenship, under the existing rules. I believe that there are some significant benefits to securing second citizenship, and to doing so under the existing Panamanian rules, together.[1]

Currently, I’d like to assess interest for this trip before taking further action. I previously...

3Josh Jacobson2hFWIW, this, and similar practices that imply dual citizenship isn't allowed, anecdotally seem to be a very common (perhaps the standard) situation. For example, the US doesn't expressly allow dual citizenship, and there's language in multiple places about renouncing other citizenships, but I've seen estimates that ~5-10% of US citizens have another citizenship and multiple US Congressmen are public about having multiple citizenships as well. I haven't heard about any US enforcement against multiple citizenships. Having looked into many citizenships and residency programs, this situation is common amongst a high percentage of them, and outside of a few rare country exceptions (not present here) everyone seems to move forward being dual citizens without issue despite this. I do wish laws were clear and explicit about these sort of things, and that there was express permission for multiple citizenship, but it does seem that for a long time across many (most?) international jurisdictions multiple citizenships have been and are allowed in practice, even when commonly 'officially' disallowed. For example, I mentioned this in response to a comment about Netherlands citizenship on the original post: https://www.lesswrong.com/posts/jHnFBHrwiNb5xvLBM/?commentId=psZcBFaZfQnzJDXeq [https://www.lesswrong.com/posts/jHnFBHrwiNb5xvLBM/?commentId=psZcBFaZfQnzJDXeq] I do think, however, moving forward on this does require some willingness to accept that in-practice behavior differs from what may be implied by a country's official regulation, and that isn't a fit for everyone. For what it's worth, to me, after learning quite a bit about this issue moving forward doesn't feel messy at all, but I certainly understand others feeling differently.

That's good to know, thanks!

3Josh Jacobson2hI don't think it'd be very annoying at all. If, for example, you weren't doing significant economic activity in Panama on an ongoing basis, your US taxes would be unaffected and you wouldn't need to file any taxes in Panama (pretty confident). If you're aiming for citizenship like I would be, then the main work is: * The upfront time and monetary investment * Showing investment / interest in Panama and knowledge about it for the 5 year later evaluation (probably involves at least 2 more visits to Panama during that time) * Then renewing your passport every 5-10 years

Painscience.com and Hargrove's "A Guide To Better Movement" are pretty good for a model of predictive processing and the roll of the nervous system in chronic pain and movement. I still don't feel like I have a good model of bone and joint health in general, however. Eg, I'm currently nursing a flare up of patelo-femoral pain in my left knee. I've done a number of things over the past few months to deal with it, with some success, including buying and reading Painscience's book length patelo-femoral tutorial. Recently I've had a bit of pain in my foot, possibly in the tibiocalcaneal or tibionavicular tendons. I find that even though I now know a fair amount about PFS and the way the nervous system processes pain, these...

Considering the current covid hysiteria and censorship on social media platforms I'm finding it hard to find reasoned discussion of Geert Vanden Bossche's ideas. They seem to be centered around vaccine immune escape and original antigenic sin. If you have anything to contribute please do. Thanks

Rationalism seems somewhat like a proto-religion to me. It has norms of behavior very different from society at large. It has apocalyptic prophecies which it's members strive to stave off. Still, what's missing? I think a few things:

  • Rituals
  • Symbols
  • A community
  • Institutions around which to build a rationalist life
  • The normalization of rationalism as a central identity rather than a peripheral one or a non-identity

Rituals

Rituals come in many shapes and sizes. Some rituals are recurring and universal. Passover, Petrov Day or Eid all happen once a year at the same time for all believers. Others are singular and specific to the individual. A Bar-mitzvah, Hindu marriage or Irish wake all happen at different times for different individuals and mark transitions from one part of life to another. Some are happy....

This is a linkpost for https://dynomight.net/alcohol/

Say you're an evil scientist. One day at work you discover a protein that crosses the blood-brain barrier and causes crippling migraine headaches if someone's attention drifts while driving. Despite being evil, you're a loving parent with a kid learning to drive. Like everyone else, your kid is completely addicted to their phone, and keep refreshing their feeds while driving. Your suggestions that the latest squirrel memes be enjoyed later at home are repeatedly rejected.

Then you realize: You could just sneak into your kid's room at night, anesthetize them, and bring them to your lair! One of your goons could then extract their bone marrow and use CRISPR to recode the stem-cells for an enzyme to make the migraine protein. Sure, the headache itself might distract them,...

Looking at alcohol consumption by country, however, East Asia seems pretty middle of the pack. The main trends seem to be Europe and majority European-settled countries are rather high, and the Middle East and North Africa are very low (religious prohibition). 

https://ourworldindata.org/alcohol-consumption

Since the west is high, the rest is low, or not so-high, with parts of East Asia overlapping parts of the west, it seems like these genetic predispositions aren't as strong in effect as someone might predict given the culture. I have heard Japanese a... (read more)

3alexlyzhov6hYep, the first google result http://xn--80akpciegnlg.xn--p1ai/preparaty-dlya-kodirovaniya/disulfiram-implant/ (in Russian) says that you use an implant with 1-2g of the substance for up to 5-24 months and that "the minimum blood level of disulfiram is 20 ng/ml; ". This paper https://www.ncbi.nlm.nih.gov/books/NBK64036/ [https://www.ncbi.nlm.nih.gov/books/NBK64036/] says "Mild effects may occur at blood alcohol concentrations of 5 to 10 mg/100 mL."
2Gunnar_Zarncke18hIf then it would work best early on or in combination with someone helping you, e.g. your spouse Or your parent. Could parents give it to their teenagers before they go to a party: "You can go but take this pill first."
1peterbarnett19hThere's a drug called Orlistat [https://en.wikipedia.org/wiki/Orlistat] for treating obesity which works by preventing you from absorbing fats when you eat them. I've heard (somewhat anecdotally) that one of the main effects is forcing you to eat a low fat diet, because otherwise there are quite unpleasant 'gastrointestinal side effects' if you eat a lot of fat.

I listened to an interview with Patrick Collison were he claimed that when coding one should always optimize for speed - even when speed is not an issue. (Presumably because it leads to good coding practices, clean code, less build up of unnecessary functionality etc.)

Assuming that is correct - and I think there is something to it - it makes me wonder: is there something similar that one could optimize for in life? Life is such a multivariate thing that it can at times be hard to know what to prioritize.

What parameter is a candidate for having most positive side effects on your life when optimized?

I think Patrick is giving bad advice.  Almost always optimize for readability and future updates, all other considerations are specific to need.  Idiomatic and efficient implementations are a a very good habit, but "optimize" implies making tradeoffs.  

Other aspects of life are similar - almost always optimize for the long-term, but the specifics of what that means is individual.

1davidgasquez4hI've heard that interview but I'm having some issues finding it back. Would you mind sharing a link to the Patrick Collison interview?
4Answer by G Gordon Worley III4hSlightly different than optionality, optimize for Pareto improvements. The more you can achieve efficiency across the entire frontier the better off you'll be and the less you'll be forced to make tradeoffs along that frontier because you keep expanding it.
5Answer by Dave Orr5h"Premature optimization is the root of all evil." - Tony Hoare by way of Donald Knuth. See also: https://m.xkcd.com/1691/ [https://m.xkcd.com/1691/]