alextheparrot

> Then I would add the dideoxynucleoside triphosphate mixtures, and another aliquot of polymerase

Ever thankful for heat stable polymerases.

Food macronutrients are labeled in grams, scales are in pounds. So this is the most natural way to purvey the information without needing conversions

[In the US]

If I recall the news release correctly it is:

a) If you currently make under 1$ million your rate will now be 15%

b) If you to over 1 million you will be charged progressively, so each additional dollar you now only get 70%

c) If you go over, the next year your starting rate will be 30% for every dollar

Couldn’t one take the view point that the formation of a transient ribosome could have created the conditions to solve replication?

This route would be much more of a dance than what you’ve implied. A transient ribosome makes a protein-based RNA replicase, replicase copies all local the RNAs including the RNA ribosomes. This process would eventually result in a large number of ribosome RNAs and replicase proteins without the need to have a “perfected process” prior to either step.

The whole process would be much messier than what we see today after millions of years of refinement, of course. The stability of an arbitrary RNA polymer is also increased by the presumed lack of RNases as well.

It has been a few years since I took a grad course covering the ribosome, so excuse my lack of currentness if new research has discounted this.

They even call it out in the paper, I hadn’t given it a thorough enough reading. Damn, they must’ve been a bit miffed.

I think the novelty they're pitching is the lower resources, but I wonder how much of a problem that is in practice.

If anyone is interested in DNA sequencing, I think the WENGAN paper [0] that came out the other day is pretty interesting too. They are using a hybrid input [1] in combination with their software package to reconstruct higher fidelity reference genomes.

The big impact from that paper is really summarized by this:

> WENGAN assembly of the haploid CHM13 sample achieved a contig NG50 of 80.64 Mb (NGA50: 59.59 Mb), which surpasses the contiguity of the current human reference genome (GRCh38 contig NG50: 57.88 Mb)

[0] https://www.nature.com/articles/s41587-020-00747-w

[1] Long and short reads, for example from Nanopore and Illumina, respectively

If it makes you feel any better, I burned my hand pretty bad when mowing the lawn as a kid when my dad’s exhaust pipe repair fell off.

No harm, no foul is what I mean to say, haha.

This is the practical usage, it is really language dependent, though.

C++/Wikipedia uses the definition of the original poster, while Java's @Deprecated annotation literally has a `forRemoval` boolean value attached. Personally, I am used to how it is used in semantic versioning where it is just a helpful hint for what the next release's breaking changes may be while introducing the migration behavior if possible in this release. This allows for clients to incrementally migrate instead of making it all or nothing.

Yeah, that's who the post was written by (Which I actually did read).

> I assume they may be selling something like that, but their "integration with my existing data stack" is pretty opaque.

The issue is that I have no clue what that actually looks like in practice and I'm not going to request a random demo to find out.

Anyone have a good data lineage story while still using mainstream data processing and ETL tools like Spark/Flink/etc.? I assume they may be selling something like that, but their "integration with my existing data stack" is pretty opaque.

To me, that's the core part (As the article also mentions) that allows data discovery. Otherwise you're just guessing with heuristics [0]. It also allows someone to go from map [Input Table(s) => This Table's Fields] which I think is half the battle in understanding a table.

[0] Not to say guessing is the worst, just that the information is already in the ETL code so why are we guessing?

I think jtanderson’s comment clarified the difference for me. Mustering intensity for me means being sincerely interested, so I actually wasn’t seeing the difference.

Thank you for the comment, learned something.

The idea was to try to cover some of his range, which isn't trivial given how many styles he can write in.

My favorite is the Secret Miracle, though. The idea of finishing your masterpiece in abstract of the fame, recognition, even impact is beautiful.

Here’s the ones we read and discussed:

Man on Pink Corner

The Secret Miracle

The lottery of Babylon

Three Versions of Judas

Deutsches Requiem

On Exactitude in Science

In Memoriam, JFK

The Zahir

From his collected fictions, the sampling was:

- The Secret Miracle

Personal favorite, I actually think it links well to this discussion of earnestness.

- Man on Pink Corner

A bar story, the characters are a bit rough on the edges. Action packed.

- The Lottery of Babylon

Mystical world where a lottery runs everything.

- Three Versions of Judas

This is a good example of Borges combining non-fictional and fictional elements, he is doing a critical analysis on a fictional author be made up regarding the “real” role of Judas.

- Deutsches Requiem

Part of his explorations on fascism and nazism, written contemporarily (1946) so it has a bit more rawness.

- On Exactitude in Science

The title well describes this short piece.

- In Memoriam, JFK

Also short and incredibly well-written.

- The Zahir

The Zahir creates obsession, to the point of driving the obsessed insane.

Can you expand on the boringness? That conflicts with what I think because I believe that engaging hobbies are that vitality which manifests as “playful” and “fun”. Are you willing to try something new, and if you do, are you willing to learn to do it well enough to enjoy it.

Engaging with a hobby tends to involve making it part of me - the hobbies I haven’t committed to actually liking and just performed have always been the ones that get lost in the shuffle of things. Even more so, being so committed to a hobby pushes me to do more heavy lifting when it comes to doing it socially.

(Edit) After a bit more thought I decided an example would be good:

I love Jorge Luis Borges, so when my book club finally decided to read him I took the time to rate many of the stories, trying to collect an essence of his magical, gaucho, and mystical stories to help focus our discussion. That is what I mean —- to love something so much that effort becomes effortless because you’re bursting at the seems hoping to share. In this way we didn’t just read “Library of Babel”, but some of the little mysteries that show a different touch of his craft.

I personally use a password manager except in a few physical cases where I use the function approach or have just directly memorized the PIN (iPhone, YubiKey pre-fingerprint).

The function approach is a normal password, just that it scales O(1) with your memory for O(N) passwords. The expectation is that if you have a complex enough function it will be non-trivial to back-fit it, this doesn’t necessarily hold for any arbitrary function, of course.

There’s a key word that, I think, further validates what you said above and that I missed considering in my post. “Random” assumes one has equal security for everything, when there are things like email or cloud storage in general that should be protected above and beyond.

> This allows them to be more supportive and close when they need socialization because they aren't exhausted.

This part picks out an important detail, which is that if you’re capable of being alone social connection isn’t always load-bearing for your happiness and fulfillment. I don’t think this conflicts with the drive you mentioned, just that being okay without allows you to be more picky of how you are with.

It is similar to the difference between cooking whatever when you’re starving and finding richness and depth in being able to develop your craft for higher-order fulfillment. This premise, of course, relies on there being the availability of or willingness to build a larder containing the necessary materials.

This is a hard balance, though. Using unique, randomly generated passwords for the 30 or so sites I routinely use is safer against breaches, but starts to almost require a password manager, which presumably can be broken if someone is already exfiltrating secrets from your phone.

In my opinion, the only route to actually make this work and still be good against breaches is to memorize a function that generates a unique password given the website name. If you type it enough you’ll eventually memorize it, otherwise you can just use that function to figure it out more slowly.

Not to mention that if you have access to my texts a lot of sites will just let you reset my password.

I’m unsure why the original idea seems silly, when it simply states a possible reason for this problem today. Giving a developer observability is the first step, that’s what they are pointing out —- some ways developers interface with features don’t include information that could deliver a higher value feature. A company can choose whether to deliver that higher quality or not with that information, ignorance removes that choice.

If a company has that information and doesn’t care, that’s one thing. There’s more than a handful of companies that just don’t have the information to even know if they should care.

I think most people would agree that we should use tooling to make it so that developers are aware of their blind spots, such as supporting systems with lower resources or a more inconsistent network. The Netflix blog had a nice post that included a tool they used to observe the UX under certain failure cases, which is a nice example of this [0].

[0] https://netflixtechblog.com/keeping-netflix-reliable-using-p...

People still buy them for cleaning their ears, so at least a subset of their sales are not research dependent. One cynical hypothesis would be that they tried to prove they were beneficial, failed, and that’s why we have an absence of research to that point.

It also could be just as the original poster mentioned, maybe no one has really felt like the investment to ask the question would be worth it.

I think that’s a use-case for Nanopore in general, but they explicitly call out that the app here is only useable against small genomes (Virus/Bacteria). I actually really prefer the movement away from optical reads and using smarter materials, some of the PacBio stuff is still optical but is focused on single cell work mediated by nano-materials as well which is interesting.

The part I was really interested in was why portability matters, instead of just having a bench-top Nanopore. I think the idea is that it will be more hobbyist friendly, would be fun to sequence random stuff while hiking. My concern is that the market for these devices isn’t actually that large, as any place doing meaningful analytics is probably going to want a bench top unit.

Looking at the prices, now, though I think $1,000 for the minION is about what I’d be willing to pay for that vs a $50,000 benchtop unit. The fact that it does RNA too is huge, as that has a lot of benefits to doing it as close to site of harvest.

I still think the Nanopore people just have a tough product to fit into the market. This technology had much higher error rates than traditional sequencing (~15%) and the use cases where I want to analyze something out in the field so badly are not numerous. Collecting samples and sending them to your centralized sequencing facility is going to remain the most cost vs quality effective option. Additionally, sequencing is a huge overkill for a diagnostic test, especially when with the cost and complexity of analysis being so high.

Anyone have an idea of a market or research project where this thing is a first-choice tool?

Edit: I stand corrected, seems some people are trying to use it in front-line clinical tests with post-analysis accuracy roughly on par with Illumina machines.

[0] https://www.nature.com/articles/s41587-019-0156-5

[1] https://www.nature.com/articles/s41591-020-1105-z

The fragment amplification stage is definitely oversampling. I feel the original poster might have been referring to how the input DNA could’ve been heterogenous as it is from multiple cells. Could’ve also been confounding GWAS with sequencing, too, I suppose.

Given the technical limitations of single cell techniques it seems you both could be technically correct regarding the sampling.

I always love some of the “Letters to my lord” regarding willow bark (aspirin).

> There is a bark of an English tree, which I have found by experience to be a powerful astringent, and very efficacious in curing aguish and intermitting disorders. About six years ago, I accidentally tasted it, and was surprised at its extraordinary bitterness

One letter, which I couldn’t readily find, eventually reduced to “My lord, I had a tooth ache and was chewing on random things in the forest. Willow bark made me feel better”

[0] https://royalsocietypublishing.org/doi/10.1098/rstl.1763.003...

Exactly, a tech job would fire me after realizing how inconsistent and slow the internet is at the house I grew up at in rural Wisconsin.

Even my cell phone hardly works if it rains or snows. I can’t even port my number to Verizon because they apparently won’t service 715 prefixed numbers.

> If you can brew your own beer or grow your own cannabis, you probably have learnt a thing or two about caution

The idea that selling drugs is something special misses and should remain illegal seems to only partially consider the implications of what that means.

One side of safety concerns is consumption safety. An at home production facility is of lower quality, exemplified by many more cases of methanol poisoning during the US Prohibition era [0]. Another is production safety, cooking methamphetamines is real chemistry —- I would much prefer to have a factory doing that rather than my residential neighbours. Finally, we have access, growing plants indoors is non-trivial and processing them into something resembling a finished product also so. Given this, I’m convinced that limiting illegality to trafficking doesn’t stop the war on drugs, because it has always been about trafficking — the hard part is moving the product and selling it to people. If the “do as you want” resolves to making trafficking legal, then it seems the drugs are simply legal.

[0] https://gardenandgun.com/articles/will-drinking-moonshine-ma... (The actual source is apparently a book the writer references)

Epic has been trying to move on for years, or so a recruiter told me half a decade ago. Their job posting now describes “Using leading-edge technologies and languages like JS, TS, and C#”, though I wouldn’t put a bait and switch past them.

> A military in a democratic, sovereign nation should have oversight from civilian authority

Would it not be fair to say that in a representative government those elected representatives are the civilian authority? The US Congress approved using military force in Iraq, by quite large majorities in both bodies.

That is not to say the war was good or the reasons true, just that the second paragraph of your critique seems unfounded as there was oversight by the republic’s civilian authority.

This may be a conservative view point, but showing that it would increase the translatability of mice trials to humans seems like a prerequisite for the criticism to change anything, though. No one is saying that our current animal trials are optimal, one of the professors in the news article I linked is quoted as saying the exact opposite "The animal models used to understand the safety and efficacy of drugs are flawed". It just is the case that retraining, to draw analogy to computational models, our model animal is not free because the evaluation of its performance after that change is much more complex and expensive than an ROC curve produced from labeled data.

I’m only vaguely familiar with Weinstein’s claims, but you might find the following news article about some research I remembered going to a talk to about 5 years ago [0]. There’s a lot of proposals in the stem cell community like this, though I lack the insight to vet whether that’s happening in practice.

> About 80 percent of experimental drugs fail in human clinical trials because they are unsafe or ineffective, with some 30 percent found to be toxic in people despite promising results in animal studies

Effectively, a huge percent of drugs are failing out in clinical trials — so a few false negatives where the phenotypes aren’t measured correctly or are on an incompatible time scale seems pretty expected.

I haven’t seen anyone showing that “fixing” lab mice would’ve resulted in different animal trial results — is Bret claiming this?

[0] https://madison.com/wsj/news/local/health_med_fit/tissue-chi...