I don't think Infinite Jest is itself depressing, but you'll want to avoid some of the books that came after. After reading Oblivion I didn't feel surprised that he killed himself.

From the wiki:

In general, Marshall Boswell claimed that this was Wallace's "bleakest" work of fiction. In Oblivion, he "uncharacteristically" provides "no way out" of solipsism and loneliness. Boswell further suggested that the collection "repeatedly undermines many of the techniques for alleviation" from loneliness, like communicating through language, that Wallace presented in Infinite Jest. "Oblivion," he writes, "remains unique in Wallace's oeuvre in its unrelenting pessimism."[26]

Fuck if even Brooks is seeing the light, maybe there is hope?

Chances are I'll still be in town doing the same old thing next April too. Keep us posted!

Do they freeze alright? Their parent cells are so finicky that somehow I doubt mine would be happy with a drop of DMSO in solution.

And making microglia:

Thu / Sun both work for me, keep us posted

I'll be around, I'm down for a pubski in meatspace.

"Nucleofector – Amaxa" and "Human Stem Cell Nucleofector Kit 1 – Lonza", I may need to play around with it though, as the protocol appears to have not worked very well (it was ~6M across 4 cuvettes, which may not be the optimal cell:cuvette ratio?...)

Wasn't this what Russians ridiculed Obama for as ineffective when he did it to them?

But maybe you are the person to innovate a "rifle scope" for CRISPR? Who knows?

Doubtful, I'm just using it to make separate cell lines, I have zero plans to optimize anything if I can get my 10 cells that look alright by the end of the year. But thanks, it's nice to hear encouragement.

There were some meetings between Trump officials and some Russians, but so far no more than you’d expect from a campaign that was publicly and proudly pro-Putin. And so far nothing we know of these meetings proves or even indicates collusion.

Is this guy actually retarded?

FWIW, from 23andme's privacy statement

We will not sell, lease, or rent your individual-level information (i.e., information about a single individual's genotypes, diseases or other traits/characteristics) to any third-party or to a third-party for research purposes without your explicit consent.

Definitely something to keep an eye on in the future (though companies can already get your genetic info through the incentive of healthcare discounts iirc.

I honestly prefer this aspect, of a formal regulation agency approving tests that have decent support for them. You can already download your SNP data from 23andme and run it through the genetic gauntlet with other services, but this adds convenience and separates the well-supported from the less-well-supported associations out there.

On the lists of politicians that you may surprisingly agree with: Bernie Sanders

Did you know that 2.5 millilon employees work in healthcare insurance and that a single payer option would probably reduce that in a huge way, creating a massive group of unemployed people? There are dozens of major insurance companies who, in the course of daily business operations, duplicate the work that is being done at competing companies. Obviously, Blue Cross' accounting department isn't going to do the accounting for Cigna, and so you get two accountants doind the same parallel work multiplied across all the companies. But if the US Gov't is going to do all the work in a single payer system, you'll have a massive cut in employment. No way around it. I don't think people realize that the sudden disappearance of probably 1.5 million jobs will be a reality in that case. Esepcially not Trump who has advocated for single payer and ran on a major employment focus.

FWIW, even countries with fully socialized medicine have their own private healthcare insurance industries (ex: UK). But even so, this strikes me as a backwards argument: health insurance is too expensive, so we should preserve the inefficiencies and bloat already present in the system.

So far, the clearest summary of the ACA's shortcomings has been that it addressed health insurance coverage without doing enough to address costs. So now you have fewer uninsured people waiting until the last minute to get treatment instead of preventative care, and fewer insured people being denied the coverage the payed for due to undisclosed domestic violence. But the drugs, the scans, and the doctor salaries are still roughly the same. And medicare still can't negotiate drug prices.

So the delta flow of money is still heavy in the direction of providers.

For me? Not to this date, no

Org is great! I've been using it for several years now:

Sadly, it a massive pita to interface with other platforms. I have like 4 intermediate steps to get scheduled items to show up on my phone, and even then it drops birthdays events with non-standard time ranges =/

Directory tree of .org files, version controlled with automatic commits every hour. by cron. .ical snapshots are created every hour using (org-icalendar-combine-agenda-files) and exported to a location accessible by private URL. Then google / windows live consume that URL to create calendars that show notifications on my phone / windows lock screen.

It's a mess tbh.

For sure, I've just seen a couple talks / papers now that describe some (non-cytokine) receptor as being the thing that polarizes cells in one direction or the other and I find it somewhat garbage science, at least in the Alzheimer's field. Especially since there does't seem to be any real consensus on how they're defined.

The microglia you're talking about in this context are with regards to young blood treatments?

Yep yep, realized that after replying and ninja edited.

I was referring to the microglia activation, but you def answered my question and more.

Microglial "activation" is sort of a misnomer in my opinion. But basically they show a state switch. Whether this is a response to less inflammatory factors secreted by neurons, improved blood flow to the area, magic electrical effects, decrease plaque production, etc is not well understood. They characterize in the paper that there is a state change (morphological, RNA expression), but not how / why.

There's some thought that microglia have 2+ states, a "pro-inflammatory" / "M1" state and an "neuroregenerative" / "M2" state, but in my opinion that's probably a baloney pigeonhole of what's actually going on.

Wild shit, and hopefully there is some clinical relevance to it.

Indeed, though what'll probably not be mentioned in the press releases is "Extended Data Figure 5: A 40 Hz light flicker does not affect Aβ levels in hippocampus or barrel cortex." ... There is still a lot of work to be done.

OPTOGENETICS. APP/PSEN1 MODEL EXTRAPOLATION. IMMUNE SYSTEM ACTIVATION. A SIMPLE TREATMENT THAT WILL TOTALLY BE ON SHELVES IN WALGREENS WITHIN A YEAR.

Yes, high potential for either breakthrough or years of pseudoscience to come out of this. Much excitement. Wow! They're looking at others models now, but I'm probably not supposed to share that until it's at least being presented publicly.

Is the paper out? that is kind of a wild result. What was the optogenetics targeting? I'm assuming the neurons responsible for the gamma rhythm, and the microglia activation was unintentional, and that's why the decided to attempt the effect with an external light source?

Yep. Optogenetics targetted parvalbumin interneuron and did not show an effect in excitatory neurons (PV-Cre vs. αCamKII-Cre in fig 1) or at non-40 Hz pulses. Why the microglia get activated is anyone's guess / for follow-up work to determine.

The light source was used after the optogenetics experiments showed an effect because, as one prof put it: "We're more than a decade away from optogenetic therapies in humans". Note they switch the explanation from "hippocampus" to "visual cortex" when they explain that in the video though. In theory, any signal that gets a stimulus at 40 Hz to the hippocampus should be effective, but not all circuits from the eyes / ears / mouth / fingers / nose are as direct.

Had no one seen that before? Optogenetics and EEG stuff was never on my plate, so I have only a cursory understanding.

The closest is deep brain stimulation for Parkinson's, which sort of works okay but isn't very well understood. This is the first (mouse) therapy of the sort, and the first that I know of that links dysregulated signaling to stimulation to targeted activation of certain cells in a certain region to actual non-invasive therapy.

Bamn

Yep, but only on certain actions (i.e. opening up the app drawer). I'm not sure how much a fan I'd be of my phone feeling like a vibrator on the day to day though. I've found I prefer just not using it as much when I can spare the self control.

Never tried an ergonomic + mechanical keyboard so your mileage may vary. I will say that I feel the same thing on styluses pressing on hard screens, made ~10x worse with fingers on hard screens, fingers on touchpads, and fingers on low depth keyboards (a la mac keyboards). Something about the backpressure just makes the tendons inflamed lightning fast. Vertical mice did wonders for me though.

Let me know if you find a better solution, keyboards and mice are mostly a solved problem for me, but hard glass screens and stiff buttons are still my Achilles heel so to speak.

He also started the DEA. But I'm willing to accept that a president can have pros and cons despite being universally hated by liberals in the present.

Haven't tried Tai Chi, but Yoga's been on and off for the past three months. But while upward dog feels amazing (and is basically the stretch I've been assigned to do 4x10 times a day), forward fold will make things hurt in under 10 seconds. And that's been in spite of hamstring stretches twice a day for the past two weeks.

It would be a herculean labor to convince me that any "startup" has access to or has put the effort into training a car to drive in such a way that won't lead to tragedy.

I include Tesla in that grouping.

Ditto, though it seems like Google has at least taken that approach. I'm a little surprised that Tesla skipped the line on the regulation. Maybe something to do with the legalese of how the feature is offered?

That's an admission that neural networks are unknowable, but an assertion that they are better because, you know, neural networks.

I'd imagined that that statement was based on some collection of training and test data run through various simulation algorithms. It's hard to imagine where comma one would have gotten such a data set, but the problem he's commenting on is one universal to all of machine learning. What algorithm do you use to identify pedestrians from a point cloud? What is the estimated velocity of neighboring vehicles? Is that debris on the ground roadkill or nails?

At the end of the day you're mapping some noisy inputs to an abstracted output, and you can try fitting a bipedal model to a person, but that may error on statues near a roadway. Or you can plug the whole thing into a shiny set of general algorithms that integrate over space and time, let them work their magic, and pick the one with the highest false positive or false negative.

Not saying it's a right or wrong approach, and obviously any tests should include an appropriately large data set, along with added perturbations for all manner of lighting, noise, angles, added vehicles, etc. But it's a common question: do you trust the most accurate model or the one you understand the most? Ideally the former is the latter, but that can sometimes only come after years of analysis. I think the hip-young computer scientist answer to this would be make all data and analysis pipelines open, but something tells me comma wants the quick and easy solution.

Sounds about right, though there's a sweet spot in the early days of joining a lab when it definitely pays off to optimize a workflow. I may have missed that as I move into my third year and pass into my second and third large sets of samples.

I will automate the shit out of my analysis though. It definitely gets under my skin when I hear about errors in conclusions due to a hidden bug in an excel formula.

Lambda is just an instance of MegaHAL, trained on the conversations that occur in the channel.

There's some scripts lying around my src directory to run something similar by scraping hubski comments and using them as the brain MegaHAL (same markov bot as lambda). I killed all instances a while ago, but if anyone is interested, they can talk to thundarabot on #zombski @ irc.hubski.com:

11:38:41 <@thundara> thundarabot: When her best friend died, she rebuilt him using artificial intelligence

11:38:42 < thundarabot> thundara: It's not the most artificial of artificial inflations! They're not too substantially as i've had wrist, ankle, and i have a friend right now.