MurphyA/hacker-news huggingface dataset:
by GistNoesis | 2025-09-26 22:32:25+00:00
Intellectually, I don't like this approach.

Predicting the end-result from the sequence of protein directly is prone to miss any new phenomenon and would just regurgitate/interpolate the training datasets.

I would much prefer an approach based on first principles.

In theory folding is easy, it's just running a simulation of your protein surrounded by some water molecules for the same number of nano-seconds nature do.

The problem is that usually this take a long time because evolving a system needs to compute the energy of the system as a position of the atoms which is a complex problem involving Quantum Mechanics. It's mostly due to the behavior of the electrons, but because they are much lighter they operate on a faster timescale. You typically don't care about them, only the effect they have on your atoms.

In the past, you would use various Lennard-Jones potentials for pairs of atoms when the pair of atoms are unbounded, and other potentials when they are bonded and it would get very complex very quickly. But now there are deep-learning based approach to compute the energy of the system by using a neural network. (See (Gromacs) Neural Network Potentials https://rowansci.com/publications/introduction-to-nnps ). So you train these networks so that they learn the local interactions between atoms based on trajectories generated from ab-initio theories. This allows you to have a faster simulator which approximate the more complex physics. It's in a sort just tabulating using a neural network the effect of the electrons would have in a specific atom arrangements according to the theory you have chosen.

At any time if you have some doubt, you can always run the slower simulator in the small local neighborhood to check that the effective field neural network approximation holds.

Only then once you have your simulator which is able to fold, you can generate some dataset of pairs "sequence of protein" to "end of trajectory", to learn the shortcut like Alpha/Simple/Fold do. And when in doubt you can go back to the slower more precise method.

If you had enough data and can train perfectly a model with sufficient representation power, you could theoretically infer the correct physics just from the correspondence initial to final arrangements. But if you don't have enough data it will just learn some shortcut and accept that it will be wrong some times.
by schoen | 2025-09-26 22:32:44+00:00
I see it as a great sign of maturity and civilization that we can make a firm distinction between words and violence. To me, the judge's "job" you mention is part of that.

This distinction could be something that has to be actively learned (like, maybe most people in human history would have instinctively resorted to physical violence over an insult). But if so, actively learning it is a great thing.
by didibus | 2025-09-26 22:32:45+00:00
Readers should make sure to contextualize this. We're talking about people researching AGI. Current LLM models are amazing, and will have business and societal impact. Previous ML models also had business and societal impact. None of that is contested here. The question is, what path leads to AGI, do LLM scale to AGI? That is the question being asked here, and some researchers think that it won't, it will scale superbly to many things, but something else might be needed for full AGI.
by lomase | 2025-09-26 22:33:34+00:00
Some years ago when everybody here gave their anecdotal evidence about how Bitcoin and Blockchain were the future and they used it every day. You were a fool if you did not jump on the bandwagon.

If the personal opinions on this site were true, half of the code in the world would be functional, lisp would be one of the languages most used and Microsoft would have not bougth DropBox.

I really think HN hive minds opinions means nothing. Too much money here to be real.
by philip1209 | 2025-09-26 22:33:36+00:00
I was trying to make a modern version of mailing lists with Booklet [1] - it just never got traction. I intend to open-source it soon. [2]

Async communications are underrated.

[1]: https://booklet.group

[2]: I did open-source my other project recently, though - so it's not an entirely hollow intention!
by avar | 2025-09-26 22:34:16+00:00
I'm aware of your and the GP's claim, I'm saying it doesn't survive contact with reality.

If you look at e.g. the per-dose price of insulin it's as low or lower in countries with single-payer universal systems, where someone requiring insulin is never going to have any idea what it even costs, because it's just something that's provided for them should they need it.

In that case it's usually some centralized state purchaser that has an incentive to bring prices down, or a government that has an overall incentive to keep the inflation of its budgetary items down, which ultimately comes down to public elections etc.

In any case, a much more indirect mechanism than someone who'd be directly affected paying the costs associated with the product, which directly contradicts this particular argument.
by benjiro | 2025-09-26 22:34:21+00:00
> And let's be honest who has those gigantic tables with more than 5M rows? Not too many I'd assume.

/Looks around all innocent ... does 57 billion count? Hate to tell ya but plenty of use cases when you deal with large datasets and normal table design will get out of hand. And row overhead will bite!

We ended up writing a specialized encoder / decoder to store the information in bytea fields to reduce it to a measly 3 billion (row packing is the better term) but we also lost some of the advantages of having the database btree index on some of the date fields.

Thing is, the moment you deal with big data, things starts to collaps fast if you want to deal with brute force, vs storage vs index handeling.

I can think of a lot more projects that can expand to crazy numbers, if you follow basic database normalization.
by jacquesm | 2025-09-26 22:34:24+00:00
Your best predictor of cell failure is brand + where you sourced it. Good brand cells sourced through a reliable channel are pretty much impossible to get a failure out of without gross abuse of the cells.

But far more dangerous than single cell failure is pack failure and there the quality of the welding and the balance wires is probably a much bigger factor than bad quality cells. You can easily create a nice looking bomb from grade A cells, and even manufacturers with good name recognition will mess this up from time to time.

So buy packs made with quality cells and ensure that whoever makes the pack has proper welding gear and QA in place to avoid surprises. Never ever use cells without a BMS unless they are in a 1S configuration.
by mattmanser | 2025-09-26 22:34:29+00:00
Never have FOMO when it comes to AI. When it's good enough to be a competitive advantage, everyone will catch up with you in weeks, if not days. All you are doing is learning to deal with the very flaws that have to be fixed for it to be worth anything.

Embrace that you aren't learning anything useful. Everything you are learning will be redundant in a year's time. Advice on how to make AI effective from 1 year ago is gibberish today. Today you've got special keyword like ultrathink or advice on when to compact context that will be gibberish in a year.

Use it, enjoy experimenting and seeing the potential! But no FOMO! There's a point when you need to realize it's not good enough yet, use the few useful bits, put the rest down, and get on with real work again.
by abhishaike | 2025-09-26 22:35:05+00:00
I think it has very limited therapeutic applications with what we know about RNA structure today! But there's a great deal of completely unknown RNA biology (some of which I touch on in the essay) that may greatly benefit from RNA structure. The bit I mention about Arrakis Therapeutics preclinical work in drugging the (structured) RNA version of the MYC protein points to that being a very real possibility. All interesting biotech startups are built on bets on where the future is going, and I'm very happy that someone (AtomicAI and others) is betting on this, because clearly the answer of 'is RNA structure useful' isn't super open-and-shut
by observationist | 2025-09-26 22:35:21+00:00
The difference between Gary Marcus and you is the capacity to tell right from wrong.

He has no problems pimping his credentials and shitting on other people's work and lying through his teeth to enrich himself. He's obviously intelligent enough to know better, but he's a singularly intellectually dishonest figure.

He's a one man version of The Enquirer or Zergnet for AI, and thrives entirely on dishonest takes and divisive commentary, subsiding on pure clickbait. There is absolutely no reason to regard anything he says with any level of seriousness or credulity, he's an unprincipled jackass cashing out unearned regard by grifting and shilling, loudly.

If you must, here's an archived link, don't reward him with clicks.

https://archive.is/L09dP

He really shouldn't end up on the top ten of HN, let alone the front page. It's like an SEO hack boosting some guy proudly documenting pictures of his bowel movements.
by fabian2k | 2025-09-26 22:35:41+00:00
RNA structures are really more of a basic research thing. Having better tools there would be useful to understand these parts better. That's not irrelevant, but it doesn't lead directly to therapeutic applications.

RNAs so far have been very bad drug targets. That is to a large part inherent in their properties, they have fewer different components (4 bases compared to 20 amino acids) and the RNA backbone is strongly charged and interactions with something like that are generally unspecific. Odds are that RNA will remain a bad drug target for almost all cases.
by nadis | 2025-09-26 22:35:52+00:00
If I recall correctly, last year's DORA report was the first to include AI-specific sections. I don't mind it being about AI but it potentially is a bit of a shift for DORA to be more explicit in that focus vs. it being a section of a broader state of development report.

Although if the adoption of AI is as high among developers as the DORA report found, then perhaps those are effectively the same thing nowadays.
by Marsymars | 2025-09-26 22:35:55+00:00
I had the parent comment, not the one you're directly replying to... but that actually seems a bit odd to me.

Clearly if you're not an advertiser, you can call out brands by name for having junky products (e.g. "The Worst Air Purifier We’ve Ever Tested" by Wirecutter on the Molekule air purifier). Similarly clearly, if you're an advertiser, you'll fall afoul of laws around false advertising if you tell non-truths in ads.

I expect that the reason Honeywell or Coway aren't punching down on Molekule in their ads isn't that they're afraid of lawsuits more than the Wirecutter, it's simply that their ads are meant to build their own brand awareness so they don't want to name any other brands.
by matthewmacleod | 2025-09-26 22:36:07+00:00
Isn't a larger issue the number of immigrants who are NOT contributing to the economy, living at taxpayers' expense, with many immigrants engaging in crime?

No, this is not supported by any real evidence.

They could create a polite British form of ICE

I can think of few things the UK should do less than ape American attitudes to immigration currently.
by lordofgibbons | 2025-09-26 22:36:18+00:00
Why do people even listen to Gary Marcus?

His stance on LLMs can be modeled by a simple finite state machine:

State 1) LLM performance stalls for a couple of months: - "See I told you, LLMS are a dead end and won't work!"

State 2) New LLM release makes rapid and impressive improvements - "AI is moving too fast! This is dangerous and we need the government to limit the labs to slow them down!"

Repeat
by jacquesm | 2025-09-26 22:36:22+00:00
Yes, especially wearables and toys. Those are a real problem. One of my kids was gifted a toy that had an embedded Lithium Ion pouch battery of spectacularly bad quality, the pouch had already inflated to the point that it was unsafe to dispose of when he got it. I ended up hand delivering the whole thing to the local disposal site where they have the proper gear to deal with these.
by aabhay | 2025-09-26 22:36:24+00:00
People can laugh at Gary Marcus all they want, but there’s one aspect that people don’t understand.

If you have a high conviction belief that is countervailing to the mainstream, you suffer a great deal. Even the most average conversation with a “mainstream believer” can turn into a judgment fest. Sometimes people stop talking to you mid-conversation. Investors quietly remove you from their lead lists. Candidates watch your talks and go dark on you. People with no technical expertise lecture at you.

Yet, inevitably, a fraction of such people carry forward. They don’t shut up. And they are the spoon that stirs the pot of science.

It’s totally normal and inevitable that people start to take victory laps at even the smallest indication in such situations. It doesn’t mean they’re right. It is just not something worth criticizing.
by josephg | 2025-09-26 22:37:34+00:00
Yeah. I wish there was a way to turn off full indexing of content. Content search always shows me pages and pages of junk. "Oh, looking for your todo list? That word showed up in this 1gb video file! And all these C header files. And ..."

The last good file search I've ever used was in windows 98. There was no indexing. When you did a search, it looked through all the subdirectories for a filename which matched the search term. It was glorious.
by jffry | 2025-09-26 22:38:10+00:00
Apparently from a F@H blog post [1] they say it's still useful to know the dynamics of how it folded, in addition to the final folded shape. And that having ML-folded proteins is a rich target for simulation to validate and to understand how the protein works

[1] https://foldingathome.org/2024/05/02/alphafold-opens-new-opp...
by gwern | 2025-09-26 22:38:14+00:00
Demonstrating that Rich Sutton was never really on the 'LLM bus' in the first place. Note the remarkable absence from the essay of language models & large language models from that essay despite BERT and GPT-2 and 'unreasonable effectiveness of data' etc. He only briefly mentions speech recognition. (Note also Sutton's general absence from LLM research, the Edmund Plan or switch from DeepMind to Keen Technologies as DeepMind was forced into LLM-centric research, and his published research since 2019's emphasis on small models and trying to fix their pathologies like catastrophic forgetting.)

> The bitter lesson is based on the historical observations that 1) AI researchers have often tried to build knowledge into their agents, 2) this always helps in the short term, and is personally satisfying to the researcher, but 3) in the long run it plateaus and even inhibits further progress, and 4) breakthrough progress eventually arrives by an opposing approach based on scaling computation by search and learning. The eventual success is tinged with bitterness, and often incompletely digested, because it is success over a favored, human-centric approach.

You could easily seem most LLM work as a dead end because it is about 'building knowledge into your agents' (eg. by paying data labelers billions of dollars total to supplement your scrapes), and not about 'search' (still a major open problem for LLMs - o1-style serial reasoning traces are obviously inadequate) or 'learning' (LLMs depend so heavily on the knowledge already encoded in so much data for them).
by skn3 | 2025-09-26 22:38:29+00:00
This is why you should program for fun instead of just for money. Sure its fun creating some interface for an API. Sure its interesting to figure out a problem some customer is having. Sure, it can be rewarding to create a new system as part of your companies product. But you know what is really fun? Creating something from scratch. Sculpting it. Refactoring it. Trying things. Cutting things. Learning things. Exploring new ideas. All of the stuff that typically doesn't fit well when money is involved.

If you really want to reconnect with the pure art of programming, just start a hobby project. Burn that candle at both ends. Grind through the self doubt. Grind through the challenge. Just keep perusing that 1 idea. If you finish it, you created your own little universe. If no-one sees it, who cares? Art is a form of expression and so is programming.
by ebolyen | 2025-09-26 22:38:40+00:00
It is the initial purpose of a microbiome to be at least commensal, in that it is usually prohibitively expensive to maintain a sterile environment so the odds of a true pathogen colonizing a system is greatly reduced if you simply have a crowded space of neutral participants.

Once that's true it does seem there's a lot of host and microbiome interactions we've only begun to explore, but it shouldn't be surprising that co-evolution of the microbiome and host begins to take over as soon as you have one. One great example is short-chain-fatty-acid (SCFA) producing bacteria in the human gut. [1] These seem to be essential, and if there was a general takeaway to improve health, it would be to eat your roughage so they can do their job.

This is also why high alpha-diversity (community richness in particular) is such a dead-ringer for healthy vs diseased states. And frustratingly, is often exactly where the story ends for a lot of observational studies.

Also, in case you are curious, artificially sterile mice (gnotobiotic mice) tend to act differently than other mice, which is pretty odd to be honest, and why the gut-brain axis is a plausible mechanism to research further. [2]

[1]: https://pmc.ncbi.nlm.nih.gov/articles/PMC10180739/ [2]: https://www.sciencedirect.com/science/article/pii/S088915912...
by TheOtherHobbes | 2025-09-26 22:39:12+00:00
This time everyone voted for Starmer and got friend-of-Epstein Mandelson via McSweeney as a cut-out.

PMs don't drive the agenda. The UK is one of the most corrupt developed countries in the world. The people driving the agenda are billionaire and multi-millionaire donors.

PM is a sales job, not a strategy job, and increasingly ridiculous PMs have been selected because the donors have had enough of liberal democracy as a concept. If it stops working - which it pretty much has - there's going to be less resistance to removing it altogether.

Which is why there's resistance to Digital ID. There's widespread distrust - with reason - of the political establishment right across the divide.
by danabramov | 2025-09-26 22:40:32+00:00
>The arrows do seem to imply that commenting on my posts goes into my repo, but I'm sure that's just an imprecision trying to express an idea. The whole thing seems very cool and decentralized.

The way I used arrows might’ve been a bit confusing because I use two types of them.

The solid ones pointing from @alice.com downwards indicate ownership. They’re the same thing as grouping by color. All blue stuff is Alice’s.

The dashed ones pointing between records are links. Those are equivalent of <a href>. Any record can link to any other record, no matter which repositories either is in.

When you comment on someone’s post, your comment goes into your repo, but it has a link to the parent post (which may be in any repo). That’s usually how you want to represent it in the data model so that anyone indexing both records can reconstruct the relationship.

In the example, Bob comments on Alice’s post. So Bob’s comment is in Bob’s repo and Alice’s post is in Alice’s repo.

To clarify your specific point, a person commenting on your post will create record in their repo. In fact one can never create records in somebody else’s repo. That’s the central premise.

Hope that makes sense.
by josephg | 2025-09-26 22:41:09+00:00
> So buy packs made with quality cells and ensure that whoever makes the pack has proper welding gear and QA in place to avoid surprises. Never ever use cells without a BMS unless they are in a 1S configuration.

How do you put that advice into action? When I'm in an electronics store, they don't typically let you look at the welds inside each battery bank. (And if they did, I have no idea what I'd be looking out for.)
by andy99 | 2025-09-26 22:41:26+00:00
No. There is a difference between being a contrarian who is making a bet and acting on their different viewpoint, and someone who is simply a debbie downer and wants to say something negative all the time with no skin in the game. Marcus is the latter.

It's easy to be a faux contrarian that just always says we're in a bubble or x is overhyped. Everyone knows that, it's the nature of markets and not an insight. The only value is having some actual insight into where and how things stop and where there is some upside. Otherwise you're just a jealous loser.
by didibus | 2025-09-26 22:41:31+00:00
For Yann LeCun, he says it here: https://www.weforum.org/meetings/world-economic-forum-annual...

He's personally moved on from LLM and exploring new architecture more built around world models.

Which he describes here: https://x.com/ylecun/status/1759933365241921817

Also I think the 2022 quoted refers to this Paper by Yann: https://openreview.net/pdf?id=BZ5a1r-kVsf
by paulbjensen | 2025-09-26 22:41:44+00:00
Blog post author here, and I’ll respond here.

I added the context of the British Empire and the Commonwealth to point at the fact that these historical activities have transformed the UK over a period of time.

These timing of British Empire runs on for a while, but around the time when it ended post-WW2, that is when citizens of the British commonwealth countries (an institution that exists as a result of the British Empire) were invited to come and help rebuild the UK.

A couple of generations later, and London becomes one of the most diverse cities in the world.

So that is the context in which I meant the phrase “because of all this”. It’s playing out over a long time as a casual link, not all things happening at the same time.

On the 2nd question of why it is impossible for England to say no to immigration now rather than the preceding 200 years. I would offer these points.

1 - Technically, we have always had immigration. It’s a question of how much did it matter to the people at the time?

I would argue that perhaps we aren’t as familiar with British history in the 1700s as we ought to be. For example, I had no idea until a few years ago that the first Black person to vote in the UK was a person named Ignatius Sancho: https://en.wikipedia.org/wiki/Ignatius_Sancho - https://www.boughtonhouse.co.uk/sancho/

A slavery abolitionist and a composer who lived in London. Who knew?

Secondly, the reason why I think immigration is such a hot topic in the UK’s public sphere is because:

1 - The tabloid press have dedicated so much time and attention to it - https://migrationobservatory.ox.ac.uk/press/migrants-in-the-...

2 - Multiple politicians have used it to position it as a problem that they are uniquely positioned to solve (Michael Howard under the Conservatives during the 2005 Election Campaign, Nigel Farage in the 2015 UKIP election campaign).

3 - It was promoted as a problematic issue during the EU Referendum - flyers were distributed suggesting that Turkey was about to join the EU, and that 80m Turkish citizens would have the right under freedom of movement to move to the UK. It wasn’t true but the flyers were distributed anyway: https://blogs.lse.ac.uk/politicsandpolicy/unfounded-claim-tu...

So over time, the UK’s public opinion has been shaped and steered in the direction of treating immigration in a negative context.
by Tycho | 2025-09-26 22:42:43+00:00
I don’t understand what is wrong with this system:

“Please employ me.”

“OK, fill out this form with your name, D.O.B. and national insurance number, and if it matches against the government database then you can have the job.”

What am I missing here? I suppose they could use someone else’s details, but then HMRC should be able to easily see that the NI account seems to have multiple taxpayers.