skysight-inc/HackerNews huggingface dataset:
Choosing another target is a good idea! But, as you can imagine, we've been trying a lot of targets and they don't seem to work as well. One issue is that CD19 is the only known target that is a) expressed throughout the entirety of the B-cell lifespan, b) fairly preserved under immunological pressure, and c) is not expressed on other cells. Other targets do not maintain those characteristics and as such either won't catch all the tumor cells or will catch too many other cells. (CD21, for example, is also expressed on T-cells.)

That being said, there are studies ongoing for some of these targets in like "last last resort" capacity, as well as certain dual-target CAR-Ts looking at CD19 + another (CD22 or CD123, for example), to try to widen the net while tolerating a degree of on-target but non-tumor effects.

One could also imagine a way to more rapidly alter a patient's CAR-Ts such that you could quickly switch targets, or update them if their malignant CD19 was mutating. Currently the manufacture and production of CAR-T cells is very slow and expensive process, but I do have some friends working on improving that. Some are also working on the idea of a sort of "blank slate" CAR-T cell line which could be used in anybody, rather than being harvested from the particular patient in question.

re: CRS. It is still a significant risk, but our understanding has definitely dramatically improved over the past 10 years. We're getting better and better at anticipating, appropriately triaging, and providing necessary diagnostics & supportive care. That being said, severe outcomes and death do still occur. I don't know the numbers, to be honest.

re: the wimpy response. I am less well-versed in the immunological complexities but there are just so many steps which could contribute. Part of the CAR-T cell success requires them to continue to clonally expand after infusion into the body, and sometimes after infusion they just... don't. Or only a tiny subpopulation of them does. Why? We're not sure. Sometimes they fail to recruit the body's immune response. Why? Also not sure. Maybe it has to do with the health of the T-cells when they were harvested? Maybe something went wrong with the CAR engineering? Maybe with the host immune system?

Here's a decent overview of some mechanisms of relapse after CAR-T which might be a good jumping off point: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863137/
I find on those that a liberal use of "[-]" and "next" make it possible to mine the slag for the good stuff.
I wonder if this has to do with how our brain associates the importance of us reading something on the smartphone vs. reading something on paper.

We spend much of our developing years reading from paper and taking tests, which may be telling our brains that things we've read on paper are likely to be of importance and worth remembering. Whereas smartphone use is mostly to browse / pass time so how brain takes things we've read via smartphone to not be as important.

Perhaps the study would show different results if there was a generation of children whose school textbooks were primarily digital and had little social media use.
It appears that this is a second home, not their primary residence.
The US makes extensive use of freight rail. Like look at the per Capita number at the end of https://en.m.wikipedia.org/wiki/List_of_countries_by_rail_us...

The modal share for rail is also relatively high.

A lot of it is bulk commodities of course.
reading this as a french, this is wild. AFAIK you can't even get more than 136A as an individual, you need to operate a company (if my calculation is correct - max. for individuals is 15kVa AFAIK). Huge majority is 6kVa / 230V => ~26A
It really blows my mind that the US makes it so hard to get in legally and stay. The US is turning away so many talented individuals that could vastly add to the nation in many different ways.
It’s perfect for stupid people, and there’s enough of them...
Hobo Hero – a game about being a hobo
> Developers are lazy. They don't want to write technical specifications. They can barely be bothered to write a README with the design or make an ADR. They can't even be bothered to write tests half the time.

I would be bothered if I was incentivized to write documentation instead of shipping features.
Geeze. You have to go all the way to the bottom to find the answer.

"Maximum length of a truck with a semi-trailer in Europe is 18.75 meters. Some countries have some exceptions, but generally that is the rule. In order to use the maximum of this length for the cargo the tractor unit has to be as short as possible. The best way to achieve that is to mount the cabin over the engine."

Cab-overs have no other advantages, and everything else the article talks about is a side-effect of the length limit.
> I met a UT campus police officer who refuses to live in or bring his family to ATX because of the risks and de facto lawlessness.

I live in Downtown Austin, and this kind of picture simply does not fit with my day-to-day experience of Austin.
One of the more interesting aspects of this incident is that it's possible that they attacker discovered the attack via reading the bugfix:

https://twitter.com/kelvinfichter/status/1489050921938132996...

I love FOSS, but attackers being able to exploit bugs they read in fixes before they are deployed is certainly a downside - especially when the project manages billions of dollars.

What process can/should be implemented to address this attack vector?
Yeah, looking on Amazon now, the ones referenced that are $29.99 or lower all seem to require an additional subscription. Obviously, AirTags require an Apple device, but still function with phones as old as the 6s, which can be had for under $100. So even assuming you want an AirTag and need to acquire a phone, the AirTags come out considerably cheaper after just a few months.
Isn't that the point of playing the lotto?
It's not the original funds that were restored; one of the hedge funds behind Wormhole put in an extra $320 million to balance the books again. The hackers still have the original $320 million.
> ATX has the security measures of a third-world country

That's a pretty dramatic way to describe police not wanting to spend resources to get your $200 headphones back..
i struggle when reading pages that only have dark theme as it hurts my eyes which is really annoying, glad firefox has reader mode
Or rather, good engineers don't stay at amazon for more than 2 years
The US equivalent is the ELD [0], which basically does the same thing with minor technical differences. They've been mandated for years. I'm not a truck expert though.

[0] https://en.wikipedia.org/wiki/Electronic_logging_device
NASA's guidelines are not written in blood, but certainly in lost spacecraft. The most famous is the Mars Climate Orbiter that was lost due to ground system and orbiter using different units of measurement, but that's not the only example [1]

1: https://www.csoonline.com/article/3404528/8-famous-software-...
In Romance languages, the continent is known as the supercontinent "America", but in Germanic languages (like English) and other languages that borrow from it call them the "Americas" as two continents "North" and "South" America. So, for people to bring it over as 'America' can sometimes be seen as pedantry instead of insightfulness.
previous discussion: https://news.ycombinator.com/item?id=28940630
What do you mean by "these days"? My wife and I have done h1 porting 3 times in total during the pandemic (once during President Trump, others during President Biden), and the process was insanely fast (== 1.5 month total from starting email with lawyer to I797 in hand, including a week at DOL and about a week at USCIS for the I797). We used Premium Processing (never not used it, except during the time it was suspended a few years ago).

I was curious if it has ballooned back up since May 2021.
PipelineDP - Differentially private data aggregation
I ctrl-F for 'cost', then for '$', nothing. Close tab.
node.css - here we come.
I've always had this pointless desire to get a non-synchronous transmission truck driver's licence. I just think it'd be fun learning to drive an 18 speed crash box with double clutching and clutch brakes

I once had a commercial license paid for by a grant program as part of that job. I had to give it up when I moved states and no reason to redo it. I regret it a lot because it was useful in many ways. Probably different in Australia, but having a odd set of skills never hurt my life.
Berlin certainly too
Believe me, it's worth $15 per month to my wife! So happy.
Oh I still have (32 bit) Winamp on my desktop, and it works great when I need it so far... The problem is that as Windows creeps towards 64 bit compatibility only, I'll eventually have to retire the original .exe(s) I've used, and change to something that might be a terrible experience.... Even online reviews and advice about what software to use is corrupted by brigadeers and marketers, so it's a wild west of who you can trust. I appreciate your advice, but you could just as well be a developer trying to encourage me to use your app that may have required in-app purchases (no offence).

Another tactic that developers now use is to have a fully functional app in the first-downloaded instance, but then the application slowly degrades as updates occur to encourage an up-sell. As a dev myself, I've directly seen this happen with apps I cannot specifically shame online.

I'm primarily referring to mobile apps. I have an SD card with my music library on it. The choice of apps there gets more complex... As phone makers remove SD card functionality, and headphone jacks, and limit out of the box music players, the ability to use my phone for music is also fading. I have had apps corrupt my locally saved music library as well in attempts to force me into buying streaming services perhaps, I no longer trust many services in app stores.
Last month flask has been downloaded 45 177 334 times, flask-wtf 3 466 675 times. That's 7%.
Doubly so if you're remote
"Incremental" is not the right word when you go from 700ms latency down to 30ms
Even in a single example such as your electric bill, this is absolutely impossible (or, maybe with a team of statisticians and accountants working on each customer's bill each month, and of course their associated costs).

The fact is, the utility does not know how much money you cost them in a given month and it's impossible to say. Some of your electricity is being generated from a plant planned and built 40+ years ago, long since paid for. Is that electricity sold at the cost of fuel and maintenance? Electricity generated from a new plant then has a corresponding capital cost component but how's it portioned out at the customer level? What if they had to go change your transformer 20 years ago but your neighbor's still on their old 50-year-old transformer next door?

Unworkable.
I wonder if we'll see higher civil asset forfeiture by police to make up for the funding loss.
The form is incredibly inefficient. It look a bit like design magazine, but the price you pay for that is incredible.
Look at the surface area of exterior walls and roofs compared to the inside volume!
A design like a four square would probably cost 1/3-1/2 of this for the same volume and be way easier to heat.
Homo sapiens lived alongside an estimated eight now-extinct species of humans. There were an unknown number of previous species before that.

They are all extinct.

To answer your question, the majority did not.
People can't get mortgages; I am skeptical that college dropouts could literally take out billions to create a shipping startup which is already a crowded space, without offering a significant value add, with no collateral or experience.
That totally resonates with me! I spent 6 years working as a data scientist and notebooks just make it a lot simpler to explore and interact with the data, so I totally understand my data science peers for sticking with notebooks.

Having said that, the challenge now is to hit a sweetspot between keeping the Jupyter interactive experience, and providing some features to help data scientists develop modular work. That's where most frameworks fail, so we want to keep our eyes open, and get feedback from both scientists and engineers to develop something that works for everyone.
Yeah, instead you won't shut up about it at work, on twitter, on hacker news, etc.
For sure. I meant to add that sort of sentiment but spaced. There is definitely a level of "poor Apple, lets break out the tiniest violin for them". It's hard to cry over the world's largest public corporation getting more scrutiny than some others.
> I wonder why they’re understaffed? Perhaps someone defunded them.

This meme keeps popping up without basis. No major city in the US actually decreased funding for the police overall in the last two years.

In this case, the APD budget for 2021-2022 was increased from $309.7 million (2020-2021) to $443 million, a whopping 43% increase.
I removed the speaker myself and hid one on my bike, I am super happy with it in Paris. Every minute its precise location is shared through Find My network and I get an alert when the bike is far from me when it is not at home.
As you get older, your corneas will begin to blur light into dark areas, at that point it is almost impossible to read black text on a white screen.

Dark mode makes it possible to see far smaller things than you can see otherwise. This is particularly important on phones with their tiny screens, or when doing things with lots of details, no matter how big the display.

The default used to be light text on a dark window, for decades before the Mac and Windows came along. There were many reasons for it besides avoiding screen burn.
..they did this a few days ago. You nailed the price point, too.

Notably, this is only about twice the cost of a high speed "business" internet connection from the cable companies in a high density area. Regular Starlink is priced at about twice a high speed "consumer" internet connection, so the premium seems reasonable for the available-in-austure-areas part.

I do hope they end up coming out with a version for RVers that has the lower throughput but allows arbitrary roaming.. but I do understand putting roaming on a premium plan first, since it plays such havoc with per-cell capacity planning.
That's actually.. totally fine. If I need to get good, I'll get good.
More than that.

Nuclear waste that stays radioactive for ten thousand years has an interesting design problem: how do you create a warning that people will understand after that much time has passed? A committee was created to study this problem, and one of the outcomes was formulating what message should be communicated. The above is that message.

The next step is figuring how to communicate that message in a language-agnostic and culture-agonistic medium.
They need one that keeps the user literally paralyzed, that would be a better ROI
As someone who grew up in the United Arab Emirates, being sweaty is your default state of being for most of the year.
>I think the problem was/is feature creep. I've been following the game since the original pitch, but never bought into it.

I feel that comes into the waterfall vs agile. Even with extreme levels of feature creep, it would have delivered already.

> The original pitch changed incredibly quickly due to how much money they got, and it seemed like that changing scope never really slowed down. Every time I would check in on it, it would seem like they were promising large new features every 6 months, or in some cases what seemed like entire games (their online multiplayer FPS).

When I consider Ludum Dare, people make working basic video games in a weekend. You can tack on features later, improve things here and there. You might have technical debt that needs repairing as you go but being 8 years past the deadline this can't explain it. It's too much time.

If I was alone and started building star citizen back in 2010. I would have delivered something...
Trying to imagine what you're insinuating here is ridiculous, and probably why you said the quiet part out loud (and left the loud part unsaid).
Yeah, and notice how a good chunk of the people asking to defund the police are from already very safe neighborhoods or very young and never had to live through lots of crime. I'm all for police reforms (eg; body-cam requirements, more training) but the whole defund the police movement is downright dangerous.
Well, even with a catalyst, my wood stove puts out a lot of emissions. But, I don't live in an area with an inversion layer.
That and parents who only kinda want to track their kids bags ... mostly ... I guess.
You'll note I specifically talked about main dishes. Yes, of course, every country will have some food that just happens to be vegan. But only a few countries and regions of the world have actual cuisines and main meals which are vegan.
But have you noticed how he got CFO attention with single replica? Such talent should be used in sales :-), or at least for the training of sales teams. "No Time To Retire" ...
I hear people say that, but is there research backing it up? I'm a bit dubious because inevitability is a common fall-back position in public affairs, similar to climate change deniers saying that climate change is inevitable so we just have to learn to adjust. They still get what they want, and try to create despair in their opponents.
Isn't Joe Rogan one of the most popular podcasts in the world and when Neil Young said "him or me", Spotify said him. Is that your definition of "shut down"?
True, most places would need to run A/C or heater much more often than California, but I doubt they need three times as powerful an A/C at any given moment.
Hey I was driving those in the Swiss Army, 2dm's they were called and a lot of fun once you got the coordination right, it's over 30 years ago... here in egypt I've seen preteens driving such trucks which brings a thought and suggestion, why not come to less "developed" countries to do such things on your bucket list... though I'm sure even your government doesn't have ubiquitous oversight in your "outback" so probably no need to leave your "island" :-)
And I thought free speech was dead. /s

I always plug them when someone whines about being moderated in someone elses house.
No, we didn't. The police were not actually defunded.
It is spending resources to catch a criminal. Very unlikely this loser is just stealing once and going back to being a decent citizen.
'Quantum friction' slows water flow through carbon nanotubes
>TV and podcasts are moving towards surveillance based advertising too.

Everything is moving this way. It's only a natural desire for those spending money on advertsing to want to know if the money is being spent effectively, or if they'd be just as well off lighting cigars with $100 bills.

The lure of targeting, tracking (ad effectiveness, not people per se), etc is just too inticing for those non-techies that haven't pulled back the curtain to see that the all powerful wizard isn't wearing any clothes (to mix metaphors). Those of a certain age that depended on Nielsen ratings and what not buying TV/Radio ad time were always very interested in knowing how effective the ad buy really was. Then, the digital ads folks come along telling them they can hit exactly the demo they want to target and then show click through rates, etc. It's like a dream come true with a cherry on top under a rainbow with the leprechaun delivering a pot of gold riding on the unicorn's back. They all bit hard hook,line,and sinker.
People seem mostly mad about the IAP thing, so I don't understand why everyone keeps lumping third-party payments and third-party app stores together. They're completely orthogonal.
One downside (as a consumer) of this bill is that it requires app store owners to allow spamming users

"A Covered Company shall not impose restrictions on communications of developers with the users of the App through an App or direct outreach to a user concerning legitimate business offers, such as pricing terms and product or service offerings."

Yay, more spam (probably all starting with "Dear user, we have a legitimate business offer for you!")
> Some American politicians have hinted at the possibility of mass amnesty for illegal immigrants, but it is an issue that is widely unpopular

That's just not even remotely true. It's wildly popular.

https://www.pewresearch.org/fact-tank/2020/06/17/americans-b...

74% want to give legal status to all children. 75% want to give a path to legality for everyone. Even most of Republicans want to do so!

There aren't that many positions in the US that are so wildly popular.

Can you imagine anything more popular than giving people free money in their bank accounts? Well that's only supported by 78% of people. Legalizing illegal immigrants is as popular as giving everyone in the US free cash.

https://www.nytimes.com/2021/02/03/us/stimulus-check-polls.h...

Now, that's with actual humans. Politicians often care about businesses more than humans, and US businesses benefit tremendously from this underclass of workers that have no rights and often live in fear.
> Roughly 18 months ago folks were demanding that cities "defund the police", and that's what we got.

It's literally not. Every major city in the country increased total funding for policing. Minneapolis was the only city that voted to defund the police, but ultimately even that was reversed before it ever went into effect.
Over 800,000 people have died in the US alone, more than any other event in US history.
Yeah, I hate watching 15 minutes of something at low quality because one TCP packet was dropped. Paranoia leads to the most user satisfaction ("at least the show didn't freeze") but I would rather buffer the thing locally and watch in uninterrupted 4k @ 50Mbps or whatever. (Also, what's the point of gigabit internet if I can't watch a measly 50Mbps stream?)
That hope is based on a misunderstanding. There's no human consciousness deciding on such 'practices' - it's just a stochastic cloud, as are the complaints. Stochastic clouds don't listen to stochastic clouds.

Even if that weren't true, it would still be a bad trade for HN to put anything other than discussion quality at the top of the priority list. That would be a much faster track to the deterioration of the site.
This is exactly what happened on his last big space project (Freelancer) - way over time/budget, too much random micromanaging of meaningless things, etc. Microsoft had to swoop in at the end and save the project, removing him in the process.
I did play the game in october 2020, and from I remember there were no life support upgrades back then. And back then I don't think there were "hazardous systems": it was just that some systems were completely empty (no stations at all), while others were not, and the only way to know was to actually go there. So you might not realize you were without air until you're 3-4 systems away.
Can't you just sponsor your own investor visa?
> Starlink was publicly announced in January 2015, with bandwidth to carry up to 50% of all backhaul communications traffic, and up to 10% of local Internet traffic, in high-density cities. CEO Elon Musk said that there is significant unmet demand for low-cost global broadband capabilities.

Source - https://en.wikipedia.org/wiki/Starlink

It's typical Musk - announcing something that sounds super cool and impossible, because it's impossible. Ad later quietly scale it down to something still pretty cool, but nothing like it was presented initially. And ride the hype as much as you can in the process.
Maybe they want to supercharge 2 or 3 EVs at once.
1-99.99999999% of people on earth is 0.8 of a person. Forgive me if I don't buy into your thesis. Seeing as the vast majority of people don't even understand the implications and extent of always-on pervasive ubiquitous tracking and surveillance, an honest metric would be: what percentage of tech-literate people don't want to be forced to have wifi-tracking enabled to access a feature which doesn't need wifi-tracking. As you can see from this forum, that percentage is quite high.