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Yt-dlp: Upcoming new requirements for YouTube downloads

https://github.com/yt-dlp/yt-dlp/issues/14404
276•phewlink•2h ago•140 comments

US Airlines Push to Strip Away Travelers' Rights by Rolling Back Key Protections

https://www.travelandtourworld.com/news/article/american-joins-delta-southwest-united-and-other-u...
241•duxup•2h ago•217 comments

That Secret Service SIM farm story is bogus

https://cybersect.substack.com/p/that-secret-service-sim-farm-story
524•sixhobbits•6h ago•260 comments

Just Let Me Select Text

https://aartaka.me/select-text.html
29•ayoisaiah•39m ago•19 comments

Learning Persian with Anki, ChatGPT and YouTube

https://cjauvin.github.io/posts/learning-persian/
38•cjauvin•1h ago•12 comments

EU age verification app not planning desktop support

https://github.com/eu-digital-identity-wallet/av-doc-technical-specification/issues/22
160•sschueller•2h ago•99 comments

How to Lead in a Room Full of Experts

https://idiallo.com/blog/how-to-lead-in-a-room-full-of-experts
26•jnord•1h ago•2 comments

My Ed(1) Toolbox

https://aartaka.me/my-ed.html
30•mooreds•2h ago•10 comments

Rights groups urge UK PM Starmer to abandon plans for mandatory digital ID

https://bigbrotherwatch.org.uk/press-releases/rights-groups-urge-starmer-to-abandon-plans-for-man...
86•Improvement•2h ago•64 comments

S3 scales to petabytes a second on top of slow HDDs

https://bigdata.2minutestreaming.com/p/how-aws-s3-scales-with-tens-of-millions-of-hard-drives
86•todsacerdoti•4h ago•27 comments

Preparing for the .NET 10 GC

https://maoni0.medium.com/preparing-for-the-net-10-gc-88718b261ef2
33•benaadams•3h ago•27 comments

Huntington's disease treated for first time

https://www.bbc.com/news/articles/cevz13xkxpro
139•_zie•2h ago•43 comments

My game's server is blocked in Spain whenever there's a football match on

https://old.reddit.com/r/gamedev/comments/1np6kyn/my_games_server_is_blocked_in_spain_whenever/
236•greazy•4h ago•110 comments

I Spent Three Nights Solving Listen Labs Berghain Challenge (and Got #16)

https://kuber.studio/blog/Projects/How-I-Spent-Three-Nights-Solving-Listen-Labs-Berghain-Challenge
28•kuberwastaken•3d ago•8 comments

Exploring GrapheneOS secure allocator: Hardened Malloc

https://www.synacktiv.com/en/publications/exploring-grapheneos-secure-allocator-hardened-malloc
36•r4um•4h ago•0 comments

Everyone's trying vectors and graphs for AI memory. We went back to SQL

20•Arindam1729•2d ago•17 comments

Find SF parking cops

https://walzr.com/sf-parking/
776•alazsengul•20h ago•416 comments

Baldur's Gate 3 Steam Deck – Native Version

https://larian.com/support/faqs/steam-deck-native-version_121
541•_JamesA_•14h ago•378 comments

Deep researcher with test-time diffusion

https://research.google/blog/deep-researcher-with-test-time-diffusion/
62•simonpure•3d ago•10 comments

WiGLE: Wireless Network Mapping

https://wigle.net/index
15•dp-hackernews•2h ago•2 comments

Libghostty is coming

https://mitchellh.com/writing/libghostty-is-coming
764•kingori•1d ago•239 comments

Qwen3-VL

https://qwen.ai/blog?id=99f0335c4ad9ff6153e517418d48535ab6d8afef&from=research.latest-advancement...
396•natrys•17h ago•130 comments

How Neural Super Sampling Works: Architecture, Training, and Inference

https://semiengineering.com/how-neural-super-sampling-works-architecture-training-and-inference/
14•PaulHoule•3d ago•0 comments

Markov chains are the original language models

https://elijahpotter.dev/articles/markov_chains_are_the_original_language_models
423•chilipepperhott•4d ago•149 comments

Getting AI to work in complex codebases

https://github.com/humanlayer/advanced-context-engineering-for-coding-agents/blob/main/ace-fca.md
431•dhorthy•1d ago•360 comments

Top Programming Languages 2025

https://spectrum.ieee.org/top-programming-languages-2025
223•jnord•14h ago•345 comments

From Rust to reality: The hidden journey of fetch_max

https://questdb.com/blog/rust-fetch-max-compiler-journey/
236•bluestreak•17h ago•50 comments

Podman Desktop celebrates 3M downloads

https://podman-desktop.io/blog/3-million
206•twelvenmonkeys•17h ago•60 comments

A webshell and a normal file that have the same MD5

https://github.com/phith0n/collision-webshell
81•shlomo_z•3d ago•39 comments

New study shows plants and animals emit a visible light that expires at death

https://pubs.acs.org/doi/10.1021/acs.jpclett.4c03546
150•ivewonyoung•11h ago•122 comments
Open in hackernews

Huntington's disease treated for first time

https://www.bbc.com/news/articles/cevz13xkxpro
139•_zie•2h ago

Comments

petesergeant•2h ago
More information on the approach: https://www.uniqure.com/programs-pipeline/huntingtons-diseas...

> AMT-130 consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene, leveraging our proprietary miQURE™ silencing technology. The therapeutic goal is to inhibit the production of the mutant protein (mHTT)

and the actual announcement: https://uniqure.gcs-web.com/news-releases/news-release-detai...

> 75% slowing of disease progression as measured by Unified Huntington’s Disease Rating Scale (p=0.003)

> 60% slowing of disease progression as measured by Total Functional Capacity (p=0.033)

> 88% slowing of disease progression as measured by Symbol Digit Modalities Test (p=0.057)

> 113% slowing of disease progression as measured by Stroop Word Reading Test (p=0.0021)

> 59% slowing of disease progression as measured by Total Motor Score (p=0.1741)

basisword•2h ago
What do those progression numbers mean in terms of outlook? For example, if someone is treated before showing symptoms (as they know they inherit it) is the progression slowing enough to give them a normal life expectancy and quality of life?
CookiesOnMyDesk•2h ago
It’s covered in the article

>It means the decline you would normally expect in one year would take four years after treatment, giving patients decades of "good quality life", Prof Sarah Tabrizi told BBC News.

>The first symptoms of Huntington's disease tend to appear in your 30s or 40s and is normally fatal within two decades – opening the possibility that earlier treatment could prevent symptoms from ever emerging.

didgeoridoo•1h ago
I don’t think this quite answers the curiosity of whether starting treatment e.g. at birth would virtually eliminate morbidity, or whether it only slows the decline once it has started.

Consider that the disease typically manifests in your 30s — does this mean it would begin 4x later (and thus basically never manifest), or that your 15 year progressive decline from ~35-50 would take 4x longer (giving you a normal lifespan, albeit perhaps with some limitations in your later years)?

sleight42•5m ago
To me, as an HD widower, it would have meant that my dead wife would had lived until 2043 and had a decade more of a mostly normal life.
bjornsing•2h ago
Why does it have to be delivered through brain surgery?
JoshTriplett•2h ago
Guessing: bypassing the blood-brain barrier.
adcoleman6•2h ago
I’m assuming the viral vector can’t pass the blood-brain barrier.
bjornsing•1h ago
But it doesn’t take 10+ hours to surgically get a virus across the blood-brain barrier, right?
devilbunny•44m ago
The video specifies that the drug is infused over 8-10 hours. Probe placement - again, as depicted in the video, because I don’t see a real methods section - should take about 1-2 hours. The video isn’t clear if this is interactive MRI or just a preop scan that is then loaded into a stereotactic navigation system in a regular operating room, but the former would add another hour at least. MRI is not fast.
Sebalf•1h ago
The major hurdle of current gene therapies is delivery to the tissue where the defective gene product is causing damage. For instance lipid nanoparticles are only being used to deliver gene therapies to the liver, because if you inject them they just end up there and not much anywhere else. In this case they are using an virus called "adeno asociated virus 5" (AAV5), which does not naturally infect the brain AFAIK. The blood brain barrier (basically just extra impermeable blood vessels), as well as other immunological features in brain tissue, evolved specifically to keep the brain as unaffected as possible from anything bad going on in the body, seeing as any infection/poisoning of the brain is varying degrees of catastrophic and would easily kill you in the ancestral environment.

I don't know the details of why AAV5 in particular is their vector of choice in this case, but for whatever reason thats what they've gone with. AFAIK there are no viral or other vectors that consistently infect all brain tissue when injected/ingested, so maybe that's just the best option available. Anyways, it seems that in order to get it to the actual brain tissue that is damaged by the huntington protein (all of it? One particular area?), the best way is to inject it where it needs to go. If you could just pump it into the CSF that would perhaps make things a little bit more tolerable, seeing as you could then just do a spinal tap and inject it that way, but apparently that doesn't work. Or maybe a generalized AAV5 infection has more side effect then targeted injections. Just speculating here.

bjornsing•56m ago
I guess it needs to get across the blood-brain barrier. But that shouldn’t take 10+ hours of surgery, I don’t think.
mattkrause•3m ago
Surgery can be slow, and brain surgery doubly so.

The brain is slightly elastic, so you'd want to advance a needle glacially slowly (microns/second) into it so it ends up at the right position. The injection itself is also done slowly (microliters/minute) so you don't cause pressure damage.

They might also do some intraoperative imaging (some ORs have MRI or CT machines), which slows things down, and of course there's tons of cleaning and repair work afterward.

jmcgough•1h ago
The brain-blood barrier typically only allows small, non-polar molecules to pass through into the brain, which complicates a lot of neuro/psych treatments.
saretup•1h ago
What does 113% slowing mean? I thought if the speed is x then 80% slowing means the speed is now 0.2x
nicoburns•1h ago
Perhaps it means the effects of the disease are actually reversed?
tkfoss•1h ago
"The data also shows the treatment is saving brain cells. Levels of neurofilaments in spinal fluid – a clear sign of brain cells dying – should have increased by a third if the disease continued to progress, but was actually lower than at the start of the trial."
sleight42•7m ago
It always seemed that an mRNA treatment was going to be the way forward for treating HD, speaking as an HD widower.

And here my government is actively working to suppress mRNA therapies because of fucking politics. Fuck them.

OskarS•2h ago
This is incredible, what a miraculous thing for sufferers and their families. Feels rare to see such a such an unquestionably good news story these days.
tomrod•2h ago
Quick skimmed, is there a peer reviewed paper?
mbreese•1h ago
I don't see one yet -- but the main people mentioned in the article have a long publication record on Huntington's. This trial has been going on for a while and this is an interim media report. I don't think they've reached an endpoint yet.

I believe this is the clinical trial they are reporting on: https://clinicaltrials.gov/study/NCT04120493

This trial also appears be open at UCSF...

goatherders•2h ago
Wow. Just an incredible medical development
karmelapple•1h ago
What part of this discovery was made thanks to NIH and/or NSF funding from the USA, or the NIHR in the UK?

I don't ask to strictly bring up politics, but instead to try and address the broad lack of understanding of how medical breakthroughs like this are made.

It's not done just by drug companies. The article says:

> UniQure says it will apply for a licence in the US in the first quarter of 2026 with the aim of launching the drug later that year.

That's true, but that doesn't talk about the tens to hundreds of research papers that have been published over likely decades to make this discovery a reality. And it doesn't talk about how much public money went into this discovery.

Many people reading this article probably have a vague idea that more than just this company was involved, but I feel it is not at all clear to the vast majority of people, since the vast majority of people are not involved in biomedical research.

I wish there was an easy way to figure out how many dollars, how many grants, how many researchers, went into achieving this breakthrough. And that the media would put that into news articles like this. Trace all the citations back a few orders, and I bet you'll find a massive number of NIH and NIHR grants.

There is unfortunately not more massive, bipartisan public outcry in the US over defunding the essential basic research the NIH does... and it's not new to the current administration, since it was attempted to be done back in 2017, too [1].

Scientists need better messaging or else we're going to stop having breakthroughs like this... and the breakthroughs are already going to slow down thanks to things like the $783 million in cuts to NIH grants that the US SCOTUS authorized in August [2].

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC5468112/

2. https://www.scotusblog.com/2025/08/supreme-court-allows-trum...

amelius•1h ago
It's standing on the shoulders of giants, and the one on top gets to reap all the benefits.
mattkrause•12m ago
Even that quote is a bit of a disservice to modern science: it's a massive pyramid made of thousands and thousands of individual contributions, including many bits of deep background and outright "failures".

Biology is tough in that you can't just "reason" your way to success; it often really does require trying something to see if an approach works.

jmcgough•1h ago
> Scientists need better messaging or else we're going to stop having breakthroughs like this

Sure, but it's really sad that scientists need to justify their funding to the public - they already spend so much time justifying it to the NIH and others for funding.

So many people have had their careers jeopardized by finding pulled mid-project. I am really concerned about our research pipeline, because my post-doc friends are all applying to jobs outside the US now.

mattkrause•9m ago
This is where the funders really ought to step up.

A spokesperson from (say) NINDS really ought to be shouting to anyone who will listen about how excited they are to see their <many year>, <many dollar> investment in Huntington's pay off.

I'd love it if they highlighted some of the especially "weird" studies that went into this to demonstrate how important fundamental research is and how it goes in unexpected directions.

drstewart•2m ago
>Sure, but it's really sad that scientists need to justify their funding to the public

No, it's not sad that you need to justify the use of public money.

Unless you think it's sad that the military needs to justify their funding to the public to get more. The military could have a $2 trillion dollar budget but people would ask "why!" when it clearly doesn't need to be justified. Agree?

Here's another thing you'll no doubt agree on: we should fund science with no justifications - I say that we need a $100b invested into more research into the link between vaccines and autism. No justification needed, of course.

oulipo2•49m ago
I'm pretty sure some of it is direct funding by governmental agencies, but even if that wasn't the case, all the basis of the theory, and the groundwork was laid by researchers and universities using those grants. You need public money for a healthy society
sleight42•12m ago
There's little money to be made with HD. It's a 1 in 30,000 disease. There's been little reason for anyone other than state sponsors to support its treatment. Add this to the reason's to be disgusted by capitalism. Spoken as a widower of an HD wife.
melagonster•9m ago
We even do not need to calculate NIH grants; I am pretty sure that all databases that were used here are from NCBI. If there were no NIH, all research would be impossible in modern biology.
siva7•1h ago
Medical progress has been insane in the last few years through technological breakthroughs. It's not out of reach to think that most types of cancers will be curable 20 years from now on.
oulipo2•48m ago
Yet JFK and Donold "Diapers full of shit" Trump think that Tylenol causes autism lol
kstrauser•36m ago
This isn’t the place for that.

Yes, the autism+Tylenol thing is infuriating, but there are nobler ways to express that opinion.

calewis•37m ago
I think its like WW2, loads of amazing tech came from war. Covid was a bit like that for bioTech.
ksajadi•1h ago
This is off topic, slightly but I think a good place to say this:

I wish the media outlets would mention the fact that at least one of the scientists in this post is an immigrant in the UK. (in this case I’m not sure 1st or 2nd gen)

In the current climate of anti-immigrantion rhetoric around the world, simple things like that might help a little with the perception of immigrants as freeloaders.

Just a thought.

mjburgess•35m ago
This seems helpful, but I think the misattribution of a general "anti-immigrant" sentiment to immigration detractors is part of the problem.

Very few detractors in the west have any issues with highly qualified immigrants occupying scientific or research roles. Being opportunistic with which kind of immigrants one offers as Good is partly what's aggravating the issue. It's a radical kind of dismissiveness and denialism which is provoking people and ignoring their issues.

The broad western detraction against immigration at the moment is targeted at specific waves of mass immigration with specific compositions that have specific effects on the places those immigrants have landed.

People are primarily concerned about the ability of state, social and corporate institutions to absorb immigrants at this pace and scale without significant zero-sum effects. And, in addition, the significant amount of state support segments of those populations (eg., esp. asylum seekers) have to receive at a time when gov. are under inflationary pressures, debt pressures, etc. and cannot service their own welfare obligations.

Going, "oh but we get good cancer research from immigration!" is so dismissive to these concerns, that the backfire against this messaging is one of the major contributors to people's disaffection.

The idea that people need to be told that there are people who want to immigrate that are in our national interest to absorb, is just plainly absurd. This is uncontroversial and obvious.

Hasz•32m ago
I strongly disagree with this. While I am generally pro-immigration, injecting a political view into an article ostensibly about a new scientific discovery is how science loses credibility and objectivity. See the "trust the science" phrase weaponized during COVID in the US.

Let people draw all the inferences they want about the origins of the scientists involved, but a hamfisted paragraph about a.b scientist being an immigrant from y country does not have a place here.

whatsupdog•21m ago
Also it sends a message that only scientists are welcome as immigrants. There's millions of immigrants who contribute positively to the society, who aren't scientists.
jmclnx•53m ago
This needs to be said, with Trump's cutting of College Basic Research Funds, many of these great breakthroughs will occur in other Countries. The US is/was the lead in biotech, it is now giving up its lead. That means one of the US largest industries, employing many with high pay, will shrink, due to US policies. In a few years it may not exist unless funding is restored soon. I personally know people who's grants have been cancelled due to these cuts.

But, glad to see other Countries funding their research. I wonder in face of one of the largest blunders made by the US, are they increasing funds ?

sleight42•3m ago
Even more: mRNA. Trump is trying to kill mRNA research because he sees it as tied to the politics of COVID.

Good science is not political. Politicians making it so are idiots at best and evil at worst. See also "Hanlon's Razor"

sleight42•14m ago
Tearing up at this.

I lost my first wife to HD in 2013. She was one of the lucky few whose optimism and love of humanity stayed with her through to the end.

If there is a God, I'll never accept it as "loving" as HD is as cruel a slow torture as it comes.