skysight-inc/HackerNews huggingface dataset:
I work in the side of academia that feeds drug leads to pharma and have seen this process.

The big problem aside from time is cost and scale. You might start with either a million compound in silico 10000 compounds in a high throughout enzyme screening program. You might get 500 hits with reasonable affinity which you put those in cell cultures and get 50 compounds. Then you go a small scale mouse study and may get 5-10 decent hits that don't have very obvious tox issues. Then you do a large mouse study of those for efficacy. You will get 1-2 compounds that may be suitable to go into people and there is maybe a 10% chance you get through phase III and onto the market. Usually there is also a step in monkeys before it goes into people.

The main issue here is that at each of those steps the cost scales 10-100x so you really, really need cut cost as much as possible and eliminate non promising candidates. Realistically if a molecule doesn't work in mice sure it could work in humans, but you'd be better off just doing the mouse study so you only need to run one trial instead of 10 and use the savings to invest in other trials.

Human trials are insanely expensive. One of my colleagues works at a company that pays well over $100k for a single primate for preclinical testing. Doing it in people is even more expensive with the massive costs of just organizing and insuring a trial. Comparatively it is very easy and cheap to inject a couple dozen mice with a drug and watch them for 6 months.

Also mixing trial candidates is a really bad idea, CYP liver enzyme reactions are a real thing and are often very different for humans and animals. Doing it with one drug is dangerous enough, but mixing 25 where one may inhibit decomposition of another is a recipie for dead people. You'd also need a very very large number of people (likely thousands) to deconvolute the statistical noise.
It has the same name, but otherwise I don't believe it is a descendant of the code in the app that I run.
Bee Gees
I've worked as a web developer for my entire career, and spent a lot of time in the cryptocurrency space, since 2010. I've seen the entire space rise and fall, and expect a continued periodicity until the technology actually matures. I was always against short- and mid-term speculation of assets, and have been very outspoken against grifters.

But your comment entirely misses my point. There's nothing grifty about decentralized commerce, or crypto. When not involved in the space, you are mostly only exposed to the grifters. Only, the grift is surface-level... These people rush to market and make speculative promo videos aimed at investors, before even engineering a product.

They actively lie to their users and see them as unsophisticated investors, fools yet to be parted with their money. I've worked with people like this, and it's disgusting.

Yet so many amazing ideas and ecosystem have sprung forth, and people are still working tirelessly to achieve their vision, despite people like you lumping them in with grifters, whom they also despise. You're selling short all of these people in a moment of ignorance and perceived superiority.

I can say the same for the latest boom of generative technologies which many are calling AI. I've been doing ML since 2015 and again have witnessed this entire boom shape up from within. There is soooooo much to be excited about.

Look past the grifters. Focus on the technologies. Discard the ones built on false promises. We can have a discussion about what kind of action should be taken against grifters and people who take advantage of the clueless; please be discerning and do not lump myself nor anyone else working day and night to build cool and new things, and in some cases things whose importance is yet to be understood.

A lot of people thought the internet was a fad during the dotcom boom as well, and we see how that's turned out. Plenty companies went out of business or were dethroned due to making bets against the technology, or failing to learn and adapt around them. Try not to make the same mistake!
Barcelona is great! Lived there for 4.5 years, beautiful city, amazing food and wine, not as much culture as say Madrid, but you can get there in 2 hours by high speed train for cheap!

Also, great public transport, biking infrastructure, _very_ walkable, they've made incredible progress here by restricting cars with initiatives like the "super blocks", I lived near where they put the first ones and loved it (I'm quite anti-car in general though).

It does get too busy in the summer with tourists but just avoid the worst areas (like a New Yorker wouldn't spend time in Time Square for example, I almost never went to "Las Ramblas") or spend part of the summer somewhere else in Spain like most Spanish do, at the beach or escape the heat in "the green Spain" (Asturias, Coruña, etc).

Also, Spain has recently released a Digital Nomad Visa, so you could get a remote job in the US and move there.
>People know what to do. They just don't do it, and that's a different category of problem.

Most people dont understand weight loss isn't about Food or Nutrition. It is actually 99% mental model changes. Not to mention the possible depression etc you get while you are at it.

It is like people who want to do Gym and figuring out which Exercise is best for muscle growth etc. But actually getting into the gym is 99% of the job. Without it, you get nothing.
Fyi, it's actually easier for trains to be on time the longer the journey is - that's because sane travel times aren't calculated at max speeds. So if there is any delay, you can go at a higher speed than what was used in the calculation to catch up. On shorter journeys there are simply fewer opportunities to catch up.

Now, I wouldn't be exactly shocked if DB using too high speed assumptions in their stated travel times was part of their problem with delays.
No, I just went straight to the HN comments after seeing it requires camera permissions ;-)
> Like most drugs it's self corrective. Overdose is a good feedback loop.

WTF, bro!? It's an article about teenagers using steroids and overdose (the article even talks about Rhabdomyolysis) is considered a feedback loop?

Put down the keyboard and go outside.
find . -type f -exec sha256sum {} \; | sort

Gets you half way there.
It is true both countries were already industrious, but it was far from a given they could go back to their former self. They were both utterly destroyed, and things could have gone really badly, especially in Japan.

I can't find the reference right but I remember reading average adult calorie intake to drop to ~1200 kcals in 1947/1948 in "embracing defeat" by John Dower. That period has a huge influence on Japan to this day, including architecture of Tokyo through black market.

Both Japan and Germany had strong military govt culture, and became reliably democratic at the end of the allies occupation.
If there were more domestic producers would their chips still be worse?
I'd love to see Led Zeppelin perform again.
> Making smartphone SoCs is a huge profitable market that would have given Intel massive volumes to support R&D etc and slowed TSMC.

Not quite, and that's the core of the "innovator" dilemma. The reason why intel passed on making SOC, is the same why nvidia decided to pass on getting into xboxss and playstations. Those market have much lower margin than server side business.

AMD, and TSMC can operate in those space because they are much more efficient companies, intel is not.

Intel got addicted to fat server CPU margin, grew inefficient...
Ask HN: What's Your Favorite Game Dev Video Lecture?
I'm absolutely loving the video presentations from GDC: https://www.youtube.com/@Gdconf And wanted to find more non-GDC video lectures about making of video games, game design, board games, game mechanics, or generally gamificaiton.

My favorites so far have been: "How I got my Mom to play through Plants vs Zombies" , "Designing Marvel Snap", and "Balancing Mechanics for Your Card Game's Unique Power Curve"

What's your favorite?
Slowly, over a long period of time. Stackoverflow, javadoc of pattern, regexr
How A Gang Of Harmonica Geeks Saved The Soul Of The Blues Harp
A quick web search didn't find a formal definition, only information pages for specific parks with descriptions. I agree it's likely park rangers would use common sense in practice such that a vehicle with an extremely low first couple of gears, lockable differentials, appropriate clearance, and suitable tires wouldn't get cited as "not 4WD" because it doesn't have a selectable 2WD mode.

Incidentally, I once owned a Subaru from the 1980s which had a lockable center differential and separate high/low gearshift, which was synchronized and could be shifted in motion. It was not designed for serious off-road use, illustrating the folly of relying on criteria like these.
Forest Service orders Arrowhead bottled water to shut down California pipeline
I won't be following up further. I've shared all I have to share on this topic. On a personal level, I'm actually disappointed in how you take to critical feedback about your product and don't seem to be interested in understanding the problem domain you're developing for.

https://gist.github.com/protosam/35880f46ed3f3e80a4e2ec47e6b...
You'd intuitively think this is true, but empirically it has not been true anywhere ever.

Rising productivity yields rising inequality. The issue is that land rents rise to swallow all productivity gains (we end up calling this "cost of living," as if it emerges out of the ether).

That's why in ultra-high productivity locales like Palo Alto, $200k/yr is a welfare wage. The land is ludicrously expensive because those prices rise in lockstep with productivity -- which they don't have to. Land costs nothing to exist. It is there ready to be used no matter what the price is.

But everything on the land, which is everything, must then pay rent to the landowners, giving rise to "cost of living."

You can disprove this by showing me a location with high productive power and low land prices, or a location with low productive power and very high land costs (that's not abandoned or a vacation spot for highly productive people).
That's why we run all of our ML workloads in a distributed GPU cluster located in every employee's house
Yournextstore: Modern commerce with Next.js and Stripe as the back end
If you won't enjoy writing a book you won't write a book and you'll never taste the enjoyment of having written a book
No they do not. 64megabit
The optimal balance between natural preservation and human expansion is the one that maximizes the sum of human economic benefit from the expansion and the human phycological benefit from natural preservation.
The WTO is a creation of governments and ultimately under their control. If the US wanted to change how medical patents work it could absolutely do so. These are government failings and blaming them mostly or exclusively on private companies is ridiculous.
Creating less work for park rangers. If people drive unsuitable vehicles and get stuck, they will call emergency. That's independent of whether they abandon their cars.
Landowners get extremely hostile to the type of housing required to alleviate this problem and usually dies on the vine in any city council
The point was about vendor lock, which you asserted is not a good reason to make a move, such as this. The "tangent" about a SaaS product was to make it clear what happens when you build your system in such a way as-to become entirely dependent on that vendor. Just because Auth0 is not part of one of the big "cloud" providers, doesn't make it any less vendor-locky. Almost all of the vendor services offered on the big clouds are extremely vendor-locked and non-portable.

Where you buy compute from is just as big of a deal as where you buy your other SaaS' from. In all of the cases, if you cannot move even if you had to (ie. it'll take 1 year+ to move), then you are not in a good position.

Addressing your #1 point - if you use a regular database that happens to be offered by a cloud provider (ie. Postgres, MySQL, MongoDB, etc) then you can pick up and move. If you use something proprietary like CosmoDB, then you are stuck or face significant efforts to migrate.

With k8s, moving to another cloud can be as simple as creating an account and updating your configs to point at the new cluster. You can run every service you need inside your cluster if you wanted. You have freedom of choice and mobility.

> Most people looking into (and using) k8s that are being told the "you most avoid vendor lock in!" selling point are nowhere near the size where it matters.

This is just simply wrong, as highlighted by the SaaS example I provided. If you think you are too small so it doesn't matter, and decide to embrace all of the cloud vendor's proprietary services... what happens to you when that cloud provider decides to change their billing model, or dramatically increases price? You are screwed and have no options but cough up more money.

There's more decisions to make and consider regarding choosing a cloud platform and services than just whatever is easiest to use today - for any size of business.

I have found that, in general, people are afraid of using k8s because it isn't trivial to understand for most developers. People often mistakenly believe k8s is only useful when you're "google scale". It solves a lot of problems, including reduced vendor-lock.
Careers at Apple: Senior Software Engineer (Elixir)
If the random Deepak Chopra generator included some trigonometry, we'd have Bucky Fuller.

http://www.wisdomofchopra.com

Without context, that can be inspiring. But that doesn't make it meaningful.
> ”My local $2 shop didn't have a CR1225 cell, but they did have a CR1220 cell which is the same thickness and voltage.”

A CR1220 cell is by definition not the same thickness as a 1225.

CR = Lithium cell, round
12 = 12mm diameter
25 = 2.5mm height/thickness

With only 0.5mm difference, a 1220 and 1225 will be interchangeable in many applications. But not always!
> If the mind was purely matter, these fundamental building blocks for knowledge itself would be inaccessible.

The potential implications of this take on consciousness are fascinating.

This implies that a perfect computer simulation of a conscious brain would not be conscious, but only appear/pretend to be?

Where does your consciousness come from then? Was it hanging around and jumped onboard your brain when it developed? Will there be enough consciousness units available if we reach 15 billion world population? Or maybe those can reproduce or come into existence from nothing? Hmmm, so they can be created but never destroyed? So are there actually trillions of consciousness units wandering somewhere, like a memory leak for minds? Or maybe it's all about reincarnation, but, what if the earth is vaporized by colliding with another planet? In what beings would all these consciousness units reincarnate into? And what part of you comes from your consciousness in the first place? Is it some vague perception/awareness of existing? Or is it your full mind, with memories, logic, langage and emotions? But then what is the brain doing if it's not the processing supporting these features of the mind? Is it some kind of antenna for beyond-physical communication with the actual non-physical mind? But then what makes the matter in our brain able to perform this communication, special? Could we figure this out and get beyond-physical communication in the lab?

Sorry for this wall of questions, it's just... much more fascinating than the usual boring explanation, where the brain, neurones, axiomes and impulses allow information to flow and be processed so that you can form thoughts and reason about the world and yourself, and where all that processing stops with death and that's it, what was emerging from it can't go on without it.

It is not only a boring description of what happens when you die, it is also very disappointing. I would love for some grand cosmic resolution to my life. But I have troubles believing that it's actually real, as nice as it sounds to me. Wishes of reality, reality of wishes.
Mujmap – Synchronize JMAP mail with notmuch
Figma were running on ECS before, so they weren't just running dedicated servers.

I'm a K8S believer, but it _is_ complicated. It solves hard problems. If you're multi-cloud, it's a no brainer. If you're doing complex infra that you want a 1:1 mapping of locally, it works great.

But if you're less than 100 developers and are deploying containers to just AWS, I think you'd be insane to use EKS over ECS + Fargate in 2024.
I'd give them the benefit of the doubt that they're not someone who'd be taken in by that kind of demagoguery.
USPS text scammers duped his wife, so he hacked their operation
I'm also surprised with the lack of mention of keycloak. It's been great to work with, and immediately curious how it would compare.
> This used to occur in the 90s.

Did it? Is there any documentary evidence? And, if it actually did occur, how often did it occur? I'm skeptical.

Let's say Microsoft employees did throw chairs at walls in the 90s. You can bet management would pull the employees doing that aside and read them the riot act. And get them to pay for any repairs to the walls.
I've done that kind of movement at least once as a CTO of similar-sized companies. There are risks involved. Over engineering this system would be my biggest concern.

Hit me up if you want to talk. Contact info in my profile.
I wish I could get it to respect advanced filters. I can understand how a problem I type in might be very similar to a simple one, but there needs to be a way to signal differentiation. I know they track me, and you're telling me that clicking on the first 5 links to only revisit the search in under a minute and try a new link is not a signal that I'm not getting what I want? Is visiting page 2 not further signaling?

I don't need a different variation of the same result, I need a different result. While the former can be certainly useful, it is absurd to think this is all there is.

If you ever search anything with any bit of nuance, you'll have experienced this. I'll give an example: try searching "out of distribution" and try to find a result that is not about ML based OOD detection. They do exist and you'll find some better queries, but that result still dominates (and frankly, they are poor results).

For our example query `statistics out of distribution -"machine learning"` has a top result of mathworks on neural networks and all results on the front page work. "statistics" is ignored before variations of "Machine learning." Top few results for `statistics out of distribution -"machine learning" -"deep learning" -"artificial intelligence" -"neural network"` returns to me an ICLR paper who's title that ends in "Deep Neural Networks" and many results are still ML based...

How do I tell Google (or any engine) that I want to exclude results!?

And before someone says GPT/Claude or some other LLM, the problem persists. Yes, I've paid. Yes, for the most advanced models. Derailing these tools from the wrong track is difficult. Even harder the longer the conversation goes (i.e. if you don't recognize you're headed in the wrong direction). The nuance matters.
Omi – Open-source AI wearables
https://www.nps.gov/cany/learn/management/compendium.htm

> High Clearance Four-Wheel-Drive (4WD) Vehicles

> A Jeep, sport utility vehicle (SUV), or truck type with at least 15-inch tire rims and at least eight inches of clearance from the lowest point of the frame, body, suspension, or differential to the ground. Four wheel drive vehicles have a driveshaft that can directly power each wheel at the same time and a transfer case that can shift between powering two wheel or four wheels in low or high gear. All wheel drive (AWD) vehicles do not meet this definition.

I completely agree they'll use their discretion, but either way, that definition is specifically a part time 4WD system with low range.
You have 4. wrong. 4 is It isn't an emergency
Your fear is correctly placed.

I've seen plenty of companies rewriting complex software written by a third party considered ineffective.

Here's why they fail:

- Underestimate the work and assign a team of 4 juniors to replace the work done by an entire company

- Implement new features during the rewrite: never do that, focus on getting a 1:1 replica first

- Business people pressure the team in various stupid ways (artificial deadlines, scrum) because they've never done software and have no idea what's a software project or because they've read blog posts from influencer and they're bad at their jobs

At 200-300M you're at the size where you can do your own software.
I'd recommend to:

- Buy the third party you complain about, then improve it

- If that fails, pay people above average and good people will come. Try to find technical leaders with experience in product (think ex startuppers). Pay a bonus for good results. Give them operational freedom as long as they deliver results. It doesn't matter if they are employees or a software agency or contractors, they just need to be good and give you ownership of the code. Given you don't have talent in house, find a friend who is a good CTO or VP of eng and pay him/her to do some interviews.

Best of luck
Hybrid Mobile Development at Disney
If there was a nuclear war, you might have to do all your work from an underground bunker. Is that a reason to do all your work from an underground bunker now?
Usually you don't replace sugar 1:1 with sweeteners like Erythritol for these kinds of reasons. Sometimes you mix it with other sweeteners to bulk them up and other times you include other non-sweetening agents combined with recipe adjustments to compensate for the lack of certain effects. In general you usually include more erythritol than you would sugar, even with these other things accounted, to get the same level of sweetness (but not a ridiculous amount more, like 40% or so depending on what else you change). That said it's often impossible to get something people like more than real sugar no matter what you use/do ;).

E.g. a Cleveland Clinic article about it which headlines "Erythritol is a common artificial sweetener found in baked goods, beverages, gum and candy" https://newsroom.clevelandclinic.org/2024/08/08/cleveland-cl...
I once hitchhiked almost 2000 miles with a truck driver who had invented perpetual motion. "non-traditional science" flourishes everywhere there are people.
What makes you so sure the DOJ won't ask the court for divestment of chrome, android, etc? It's hard to imagine what else would be large enough to impact the finding of a de facto monopoly.
No, they don't abandon them: they call for help and require both government and commercial assistance to get their cars unstuck.
Russia sure excels at making friends /s
Heat death aside, with ‘infinite time’ and probably long before we arrive to affordable interplanetary travel of our squishy forms, we will have found a way to upload ourselves to silicon (or whatever substrate computes the best), where we can do whatever we want on our own little isolated wafers – if that’s what we wanted.
Typical keyboard is USB Low Speed device (which is why it has relatively thin flimsy captive cable). If you do not care about actually meeting the spec and are only concerned about the thing working reliably you can bit-bang that on essentially any “8bit RISC MCU” made in last 20 years.
It's important to note that Hispanic is an ethnicity and not a race. These two get conflated often. To be considered hispanic you just need Spanish roots, I think it's nonsense that people from Spain are not considered "White" but generally all other countries in Europe are. My point being that it's strange that other colonizing peoples descendants (Britain & France) are not tracked the same way descendants of Spanish people are.
> But if you gamify it, it can make it easier to endure and repeat

Gamifying it doesn't do much if you don't accept playing the game and continuing when you lose.
The best they can do without BLAS. Doesn't have to be as fast as numpy, just faster and more memory efficient than doing it in native Python, without the dependency.