A question: Is 'Immersion Learning' a term that you have coined? If not, does this have anything to do with Luis Von Ahn's immersion concept on duolingo?

I have always tried to "Build Small Skills in the Right Order", but I think it has been detrimental or even crippling to my learning process in some cases.

I'm pretty good at math, but I haven't studied advanced math and would like to begin a program of self-study. I have started a few times, usually reading the first couple of chapters of a high-level calculus book (Apostol or Spivak), or something at a similar level.

I already know calculus well, having used it as a physics major in college and taught it as a private tutor for high school students, but I am not completely familiar with all the subtleties, such as why Taylor series converge and under what conditions. Reviewing calculus before diving into an advanced book on real analysis seems like a good idea because I know I can understand the calculus book, and reading it will prepare me to study more challenging material.

Nonetheless, what usually happens is that I get impatient at the slow progress, bored with the material, and want to jump straight to the more difficult book. If I do, I feel like I am "doing it wrong" by ignoring the small skills, but if I don't, I wind up abandoning the program of study. I think I would have learned much more than I have by now if instead of a schedule of small skills, I'd simply opened advanced books to whatever section interested me and started plugging away, going back to review as necessary.

Similarly, early when I was a competitive distance runner, I read scores of books and internet forums for advice on training, then designed detailed training programs with careful "periodization" which would gradually build up my total amount and speed of running to the right quantities at the right time of the year. I also had many different gym exercises to do to build all requisite fitness before I could undergo the hardest training.

The result was that I was overly worried about whether my training was "correct", frequently got worn down or injured, and didn't perform well. Later, when I stopped worrying about all the small skills involved and simply ran every day for an amount that felt right to me, I improved a lot.

These examples aren't intended to contradict the advice to build small skills, but to point out that even if a skill is both small and helpful to your larger goals, it is not necessarily the right skill to work on. In one case, the skills I chose were actually too small; in the other they were distracting.

I don't normally like to blather on about myself, but I feel that a bit of self-exposition might help some people with their apparent ... Fundamental Attribution Error, perhaps?

I have an extremely malleable identity in certain types of social situations, to the point that I literally come to believe whatever I need to believe in order to facilitate rapport with whomever I'm talking with.

For example, I normally have a pretty strong aversion to infidelity in relationships, but on a few occasions I've deeply connected through prolonged conversation with friends who were engaged in relationship infidelity. It is sort of a running joke among my closest friends that I can get almost anybody to open up to me and share their deepest darkest secrets, and the way I do it is that I am genuinely nonjudgemental, and the method by which I am genuinely nonjudgemental is that I have a "core" module that has my actual beliefs and then I have my surface chameleon module which is actually talking which just says whatever it needs to say to establish the connection.

All of this babbling is to convey that if you were to interrupt me in the middle of doing this and say, "moridinamael, was that a lie?" I would answer "No." Because although I might be saying something that isn't in line with that "I" (whatever that is) don't really "believe" (whatever that means) it doesn't in that moment feel like a lie, it actually feels really good and pure and warm because I'm connecting with somebody over their pain.

Now, there are some people in this discussion thread who I feel like would think I am some kind of monster. And I think my brain probably works very, very differently than theirs, or at least the social circuitry is wired differently. But just bear in mind that people like me exist and we can't really help the way we are ... or if I could help it, I should say, it would basically cripple me.

The lab next door to mine uses this system out the wazoo in mammalian tissue culture and someone in my lab is thinking of using a modified version of it in yeast.

Step #1 - hold your horses. Generally good advice in most biological circumstances.

This system when unmodified and vanilla is a great way to make a few germline modifications more efficiently than the usual methods. It is made from elements appropriated from a bacterial antiviral defense system. It consists of two segments, the Cas9 protein and guide RNAs. Cas9 is a nuclease, a DNA cutting enzyme, that requires a GGG triplet to exist directly next to its cut site (nobody's modded that that I've seen so far, I don't know enough about its structure to know if thats possible). The rest of its targeting is mediated by the guide RNA - a small 100ish base pair RNA that consists of a constant hairpin structure that latches into Cas9 and a 20 base-pair segment that you can modify to contain any sequence. With that 20 base pair sequence adjacent to the GGG cut-site, you can target the nuclease activity to anywhere in a large genome with pretty good specificity, about one in trillions of random base pairs (ignoring things like repetitive sequence which is all over the place in actual genomes).

The point for heritable genetic modification being that when you create a DNA lesion like this, the DNA repair mechanisms kick in and try to repair the chromosome off of any similar DNA in the cell (usually the other copy of the chromosome) via homologous recombination. A paper on zebrafish genetic modification I've seen with this system microinjects into eggs RNA coding for the CAS9 protein, guide RNAs, and DNA containing the transgene and chunks of homologous sequence bracketing it so that the genomic DNA just keeps getting cut until it repairs off the introduced DNA. They got mutagenesis efficiency between 75% and 99% with this method, a good deal higher than usual for zebrafish microinjections. I know it's been done in mice but I don't know how efficiently, although these days the main way you transform mouse germline DNA has been doing low-efficiency transformation and selection of embryonic stem cells in culture followed by 2 generations of mucking around making chimeric embryos from those stem cells and breeding the resulting animals so this definitely saves time if it works well. People are also using it along with the usual methods of getting nucleic acids into cultured cells to produce stable changes to such cultured cells at high efficiency and specificity - most introduction of DNA into tissue culture is either temporary with the DNA never making it into chromosomes and going away before too long, or done via retroviruses and thus is kind of random in terms of where and how frequently it inserts.

Course, any time you cut the DNA like this you have a reasonable subset of cells not actually repair off a template but just nonspecifically stitch any recently-cut DNA (not necessarily from the artificial cut site, DNA is breaking and repairing everywhere all the time) together via non-homologous end joining. I don't know how frequently this happens with this protocol and how frequently when it does happen it leads to something problematic. I would imagine that this would become more of an issue any time you are cutting at multiple sites at once with multiple guide RNAs (which you can do with this system) and care about getting the same number of outputs you got out as inputs you put in without lots of selection of successes from the failures. There's also apparently detectable levels of off-target effects, where a few base pairs difference between the guide RNA sequence and the DNA sequence still allows cutting at similar but not identical sites.

In short people are excited because of its sequence specificity and ability to target DNA changes via DNA repair in a single generation as opposed to multiple, it's cool, and works pretty efficiently as opposed to methods that need lots of selection. It's an incremental improvement, even if it is a pretty nice and big increment.

I have a hard time understanding how you could use this for somatic gene therapy with much more success than has already been done with retroviruses. No matter how you slice it, if you want to do gene therapy in a multicellular creature you STILL need to get a package of nucleic acids into a cell which is not easy at all in a living organism as opposed to a monolayer of cells in a controlled environment, or a population of microbes that you can just select the successes from and discard the more numerous failures. Perhaps it's a way to make the cells you do manage to modify less likely to turn all cancerous, but it doesn't solve the problem of actually getting the nucleic acids INTO them.

To me, work going on in which people are mutating Cas9 to kill its DNA-cutting activity and modifying it to use as a scaffold for programmable transcription factors/repressors for artificial regulatory systems is rather more interesting. Using these systems you can potentially arbitrarily target any gene and mess with its expression once you get the required bits into the genome. A major boon for research and artificial genetic systems. Cutting DNA in vivo can be a messy proposition compared to regulating it sometimes even if the artificial not-tuned-by-evolution regulation is at times low-precision.

I get the impression that Crispr would be possibly faster for that than the gamete selection option, but slower than the 'find modal genome digitally, print it out to DNA' option. I imagine its primary usefulness is eliminating known genetic diseases / introducing known good genes.

Personally I fail to see how encoding something in physical matter makes the pattern any more real.

That is equivalent to saying you can't understand how mathematics could be a construct; or how mathematical anti-realism could possibly be true. I find that odd.

If it turns out to be 'discovery' then there is no foul in ending a mind emulation, because each consecutive state can be seen as a theorem in some formal system, and thus all states (the entire future time line of the mind) already exists, even if undiscovered.

No further foul. If Platonism or Tegmarkism are true and if mind states are fuilly captured by mathematical structures, then there's zillions of yous in states of agony bliss and everything inbetween. Scary enough for ya?

The first time I took supplemental potassium (50% US RDA in a lot of water), it was like a brain fog lifted that I never knew I had, and I felt profoundly energized in a way that made me feel exercise was reasonable and prudent, which resulted in me and the roommate that had just supplemented potassium going for an hour long walk at 2AM.

Experiences since then have not been quite so profound (which probably was so stark for me as I was likely fixing an acute deficiency), but I can still count on a moderately large amount of potassium to give me a solid, nearly side effect free performance boost for a few hours.

Your claim seems important if true. My personal tendency is to preserve data where I don't understand what's going on, and my impression is that lots of data is stored in the biochemistry itself... precisely which receptors exist, how deeply they're embedded in membranes, what kinds of fatty acids a membrane is made of, and so on. Dendrites and axons engage in chemotaxis where they follow genetically programmed ion and/or protein gradients. If you wipe out the chemical gradient information then how do you know what sorts of ways that the dendrites should regrow in the weeks and months post-resuscitation?

A divergence of opinions here could be due to different assumptions about what kind of knowledge will be available in the context of resuscitation. If your resuscitators have vast and deeply tested knowledge of the operation of many kinds of brains, then they might be able to mock up plausible values for all the chemistry and produce someone "similar enough" (and its certainly better than nothing but a bunch of letters and photos and Madeleines). If they're doing this for the first time in a sort of "1950's plucky engineer mode", then I would naively suspect that plastination pushes someone closer to information theoretic death than even membrane-damaging no-vitrification cryonics of the sort that was standard operating procedure in the mid-1970s.

There's a reason we can't reliably provision a generation ship, and it's that we have never yet tried to completely and permanently sever ourselves from Earth's ecology and biosphere. We may think we've got it all covered, but if there's a leak in the cycles somewhere, or something missing we never knew was important, our intrepid astronauts are going to be in for a hard time, either immediately or generations later.

So redo Biosphere 2, for longer. Even the first time it was done, it worked remarkably well! They did make some mistakes but recovered, and came out healthier than they went in. That suggests a multi-generation-capable version is not as far off as one might pessmistically conclude. The most valuable information is always the first information - if a problem doesn't appear quickly, then it probably isn't that important...