Hacker News: hirenj

New comment by hirenj in "The Unreasonable Redundancy of Nature's Protein Folds"

hirenj — Wed, 03 Jun 2026 07:10:15 +0000

Yes, that is exactly what I meant! Here’s an experiment to try: Frances Arnold got a nobel prize for work related to directed evolution. However, we know evolution is limited by the tools available to it as you mention. If we add random chaperones and co-factors to bacteria that we know other organisms use, can we push evolution outside of the known fold space? Is the limited fold space an absolute limit or the “accessible” limit?

New comment by hirenj in "The Unreasonable Redundancy of Nature's Protein Folds"

hirenj — Wed, 03 Jun 2026 06:59:12 +0000

I think there was a Twitter/Bluesky thread on the results from adding all the predicted folds from metagenomics too, and not ending up with many new clusters. If this continues to hold true as we keep looking at stuff, I will be relieved that at least natural protein folds and domains has a limited (tractable) solution space. All we need to do now is annotate the variation of these couple of thousands of fold variants. Challenging, but at least a bounded problem.

New comment by hirenj in "The Unreasonable Redundancy of Nature's Protein Folds"

hirenj — Wed, 03 Jun 2026 05:01:40 +0000

This approach is pretty much like the TED approach from a few years back. As far as I remember there wasn’t a ridiculous amount of fold diversity there either. It turns out evolution isn’t averse to a bit of liberal protein plagiarism.

https://www.science.org/doi/10.1126/science.adq4946

New comment by hirenj in "HopTab – Open source macOS app switcher and tiler that replaces Cmd+Tab"

hirenj — Sun, 22 Mar 2026 09:53:57 +0000

This looks very cool. Does the window picker for multi-window apps work with the pinning? So if I have a safari windows I want to have associated with a profile, and the option-tab will ignore all the other windows?

It is a constant pain when I cmd-tab in a space with safari, and it throws me out of the space to another one because the window that gets focus isn’t the “closest” one on the current space.

New comment by hirenj in "The EU moves to kill infinite scrolling"

hirenj — Sat, 14 Feb 2026 09:55:06 +0000

Even better, don’t ban it, but require companies to do age verification (above a certain age?) before displaying advertising. You get two wins in one: make the child market less attractive for algorithmic feeds, and you also can get a better product (no algorithmic feeds) without ads if you don’t age verify. Win-win situation!

New comment by hirenj in "Scientific production in the era of large language models [pdf]"

hirenj — Tue, 06 Jan 2026 07:22:21 +0000

Can you say what field that is? I hear this sometimes, but my feed there is significantly low signal to noise, and I have had to pollute my “connections” to the point where I accept everything, as I have been trying to advertise job openings using it too (which frankly has been pretty poor too).

New comment by hirenj in "Scientific production in the era of large language models [pdf]"

hirenj — Tue, 06 Jan 2026 05:29:46 +0000

It is a huge worry for me that unless we decouple the publishing “system” from the career pathways (i.e., rewards), we are going to lose access to both the careers (to robot-weilding bullshitters) and even worse, the shared space where scientific communication took place.

Does anyone know of any writing on the network effects of the publishing system? What would happen if the actual value of the journals (of the little they provide!) were to go away?

The death of scientific twitter, and the failure to establish any replacement makes me worry that we won’t be able to coalesce around a replacement system. Obviously preprints play a role, but we really need our scientific communities to engage with them in a more serious way.

New comment by hirenj in "How SQLite is tested"

hirenj — Wed, 17 Dec 2025 22:33:19 +0000

For prosterity, the original report on the pilot program with the checklist including introducing names of participants (doi 10.1056/NEJMsa0810119).

Possibly popularised by Atul Gawande “The Checklist Manifesto”.

Meta-comment: LLMs continue to impress me in the capabilities with unearthing information from imprecise inputs/queries.

New comment by hirenj in "How SQLite is tested"

hirenj — Wed, 17 Dec 2025 22:10:44 +0000

That is really insightful regarding the ritual improving outcomes through better communication - something I see reflected in many meetings I turn up to now which involve an introduction round between participants, and anecdotally improves participation in the meeting.

It would be amazing if someone had a link to a page with the MSF story, as that is a great reference to have! My google-fu hasn’t helped me in this case.

New comment by hirenj in "Paper2video: Automatic video generation from scientific papers"

hirenj — Sun, 12 Oct 2025 09:07:12 +0000

This is great - now I can get the authentic conference experience of a disengaged speaker reading out the slides in a monotone, without all the hassle of international travel and scheduling.

In all seriousness, there could be more utility in this if it helped explain the figures. I jumped ahead to one of the figures in the example video, and no real attention was given to it. In my experience, this is really where presentations live and die, in the clear presentation of datapoints, adding sufficient detail that you bring people along.

New comment by hirenj in "Open Social"

hirenj — Sat, 27 Sep 2025 07:05:22 +0000

I was ruminating about how Atproto would be great for re-thinking the peer review system for scientific journals.

Imagine a world where a preprint is “published” onto the social web, from which you could aggregate reviews/comments. I eventually ended up thinking about exactly what you raise - it would be great to have some degree of access control on this so both comments and published things can be selectively shared (with an option to make everything public later on, maintaining all the links).

New comment by hirenj in "SimpleFold: Folding proteins is simpler than you think"

hirenj — Fri, 26 Sep 2025 19:10:07 +0000

Arc institute probably.

New comment by hirenj in "Show HN: AI Peer Reviewer – Multiagent system for scientific manuscript analysis"

hirenj — Sat, 31 May 2025 14:45:42 +0000

It is a real shame that peer review reports were only first published relatively recently. These would have provided valuable training information as to what peer review performs. Unfortunately now, I fully expect the public peer review reports will be poorer in quality, and oftentimes superficial.

On this tool, I fully expect that it will not capture high level conceptual peer review, but could very much serve a role in identifying errors of omission from a manuscript as a checklist to improve quality (as long as this remains an author controlled process).

I will be interested to throw in some of my own published papers to see if it catches all the things I know I would have liked to improve in my papers.

New comment by hirenj in "Robin: A multi-agent system for automating scientific discovery"

hirenj — Tue, 20 May 2025 17:29:57 +0000

Not my subject area, but at least one other group looked at ABCA1, and judging from this abstract, it has been linked via GWAS already, and furthermore concludes it doesn’t play a role (I haven’t looked at the data though).

I don’t know, but if we were to reframe this as some software to take a hit from a GWAS, look up the small molecule inhibitor/activator for it, and then do some RNA-seq on it, I doubt it would gain any interest.

https://iovs.arvojournals.org/article.aspx?articleid=2788418

New comment by hirenj in "Mice grow bigger brains when given this stretch of human DNA"

hirenj — Sun, 18 May 2025 07:40:35 +0000

I guess that whatever recognises the enhancers must be conserved ish in mice for us to be able to drop this region into the mouse genome. That might be interesting alone apart from the functions of the frizzleds. Always a curious question about how much new “machinery” we have in humans, vs us being a specific configuration of common machinery (i.e., if we were to swap out introns/regulatory regions from a mouse with human, and assuming we don’t screw up any checkpoints, how far would it get with looking/acting like a human?).

New comment by hirenj in "Antiviral chewing gum to reduce influenza and herpes simplex virus transmission"

hirenj — Thu, 10 Apr 2025 11:33:34 +0000

My innate immune system is here for chewing gum and binding viral glycans, and I’m all out of specific lectins.

Looks like this works by apparently binding complex N-glycans on the viral envelope. I can’t imagine this is particularly specific, but the good news is that in the mucosa, you should see relatively few N-glycans, so I guess it will hit the right stuff?

New comment by hirenj in "Neonatal fungi: lifelong metabolic health via macrophage β cell development"

hirenj — Tue, 11 Mar 2025 09:14:46 +0000

This is pretty interesting, also that they get it down to the amount of mannan in the fungal cell walls being somehow related to the β cell amounts. There's probably a nice project in here to figure out what the receptors are on the macrophages that are modulating this process. Obviously candidates would be some of the lectins they carry (mannose receptor?).

New comment by hirenj in "Mucins keep the brain safe and could guard against ageing"

hirenj — Mon, 03 Mar 2025 07:31:07 +0000

Ancient medicine solves that problem

https://news.ycombinator.com/item?id=43196488

New comment by hirenj in "Mucins keep the brain safe and could guard against ageing"

hirenj — Sun, 02 Mar 2025 22:17:12 +0000

I think what you mean is the MUC1-20 (ish, numbering is a bit sloppy but hopefully we can clean it up in near future) genes encode for mucins, that are synthesised on a ribosome, threaded into ER, shuffled off into the Golgi and then enzymatically modified by the enzymes encoded by the genes GALNT2, 7 & 10 (at least).

There are a further 20-30 ish enzymes that can modify the mucins as they are traversing the Golgi, and depending on the cell type, it can get packaged into vesicles (alongside calcium) for secretion.

So, they meet a lot of enzymes along the way, but harbour no catalytic activity themselves (as far as we know!).

New comment by hirenj in "Mucins keep the brain safe and could guard against ageing"

hirenj — Sun, 02 Mar 2025 15:50:24 +0000

Mucins aren't enzymes (as far as we know!), and the gut mucins are a bit different from those found on the endothelium, largely because they have different functions. The gut (and generally mucous epithelial) mucus is there for (amongst other things) clearing and maintaining a microbiome. Endothelial glycocalyx probably has some other mucin proteins, but also likely lots of mucin-like proteins, and the set of functions of these are much less clear.