hirenj · HackerTrans

เดือนที่แล้วdiscuss

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?

hirenj

เดือนที่แล้วdiscuss

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.

hirenj

เดือนที่แล้วdiscuss

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

hirenj

4 เดือนที่ผ่านมาdiscuss

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.

hirenj

5 เดือนที่ผ่านมาdiscuss

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!

hirenj

6 เดือนที่ผ่านมาdiscuss

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).

hirenj

6 เดือนที่ผ่านมาdiscuss

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.

hirenj

7 เดือนที่ผ่านมาdiscuss

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.

hirenj

7 เดือนที่ผ่านมาdiscuss

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.

hirenj

9 เดือนที่ผ่านมาdiscuss

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.

hirenj

10 เดือนที่ผ่านมาdiscuss

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).

hirenj

10 เดือนที่ผ่านมาdiscuss

Arc institute probably.

hirenj

6 ปีที่แล้วdiscuss

Do we need one person to understand everything?

I don’t believe so, but there could be limits to the efficiency of collaborative understanding and action on complex systems, such that we have to have one person understanding multiple systems.

To play devils advocate, I see this in science all the time where the great insights come from people with deep knowledge in multiple areas.

hirenj

6 ปีที่แล้วdiscuss

Apart from the financial system complexity, I actually struggle to see how the systems mentioned are too complex to understand. They’re big, yes, and full of detail - but incomprehensible doesn’t sound right.

However, I’m sure that this is true in certain cases, and I would appreciate reading about specific examples of complexity that are well hidden, so the exact nature of the complexity can be described. What complexity do people systematically underestimate? What defies all understanding?

Throwing our hands up and saying it all is incomprehensible is akin to ceding control over everything to the few that have understood everything.

hirenj

14 ปีที่แล้วdiscuss

I'm afraid it isn't the most in-depth of a write-up!

I'm a postdoc computational biologist at the Copenhagen Center for Glycomics, so you could say this is somewhat up my alley ;)

Feel free to fire off an email (in the profile) if you've got any questions, and I can try to help out.

hirenj

14 ปีที่แล้วdiscuss

The common factors in this are having smart people looking at it, unfortunately. We're working on various ideas to become much more efficient at it, but it's a really hard slog.

hirenj

14 ปีที่แล้วdiscuss

Well, once you pinpoint a potential mutation on a gene - that gives you a starting point into the pathway that could be possibly producing this particular disease. From there, it's sort of like clicking outwards from a wikipedia page, except instead of wiki pages, its related genes. Every one you go to, you read and find out what people know about it. You then start to form a picture in your head as to what the mechanisms of action are for this particular gene - what it does and how it is regulated.

From there, you build your model for how the gene works, and do some knock-outs / knock-ins, test it in various cell lines, verify the kinetics, try to find out the 3D structure. Really, anything you can do to get a handle on how this actually works in the system. It's quite normal for people to spend their entire PhD studying the mechanism of action for a single gene!

hirenj

14 ปีที่แล้วdiscuss

First thoughts reading up on this pretty cool bit of detective work: Since this is a deficiency in production of Pngase F, I'm not sure a simple injection of Pngase F is going to work. I'd guess you'd need to target Pngase F into the ER to kick start the proper clean-up process, and the human form (http://www.uniprot.org/uniprot/Q96IV0) is different to the recombinant form that you can get synthesised (http://www.uniprot.org/uniprot/P21163). I'm not really sure how native Pngase-F is regulated!

That said - I'm about to start work on very similar work now (also in the area of glycobiology). With dirt cheap exome sequencing, we're going to get a whole bunch of really interesting leads from the data. This means that the follow-up research into the mechanism behind the action of the gene can be more likely to yield results.

Right now, I see the bottle neck in this whole process being the actual experimental analysis of these mutations. Once we solve how to scale up this hard work successfully, we can start looking at curing these incredibly rare diseases.