skysight-inc/HackerNews huggingface dataset:
Can someone versed in immunology explain to me why both this and the Pfizer vaccines are both borderline-experimental mRNA vaccines (versus attenuated or recombinant)?

I understand that bog-standard protein vaccines don't protect much beyond 3-6 months, but why didn't we pump out tons of S1/S2, N, and E protein vaccines the second this virus was sequenced? At least it would have been better than nothing, and the safety issues are very well known.

I'm not anti-vax, by any means. Just trying to understand why we chose this path rather than tried-and-true. I'm sure plenty of people would be a lot less conspiracy-minded if the vaccine was just a run of the mill recombinant protein particle one, even if we needed boosters 2-3x a year.
And of course:

1. You have to have a control group, so half of test subjects would be exposed to the virus without having received the vaccine.

2. The highest-priority recipients for a vaccine are members of high-risk groups; it'd be pointless to run a challenge trial full of low-risk individuals.

So a challenge trial wouldn't just mean giving the virus to a few thousand vaccinated macho 20-year-olds. It'd mean giving the virus to unvaccinated 80-year-old care home residents.
So there’s solutions to this. They could show a notice asking the user what they would like to do. Something like “there’s a problem connecting to the internet: cancel | try without vpn”
Why government money can't fix poverty (2015, video)
> Also interesting to note: so we can develop and approve vaccines for new diseases within months?

It's a new type of vaccine that's never been approved before, apparently simpler to develop: https://www.theverge.com/2020/11/16/21569345/moderna-covid-1...

> Moderna was the first vaccine to enter clinical trials back in March. Only 63 days after the genetic sequence of the virus was posted online, the company injected the first volunteer with their candidate. They were able to move so quickly because they used a gene-based technology to create their vaccine. Those types of vaccines are relatively simple to create once researchers know the viral gene they’re trying to target.

> Pfizer and BioNTech’s vaccine was built using the same method. The two are made from tiny pieces of mRNA, which gives the human body instructions to produce copies of the coronavirus spike protein. Then, the immune system learns to defend against that protein. Gene-based vaccines are the long-promised future of vaccine development, but they’ve never been approved for use in people by the Food and Drug Administration. The early successes of the Moderna and Pfizer vaccines are a promising sign for the method.

And of course, being in the middle of a pandemic 'helps', in terms of funding, clearing red tape, and also seeing results in testing (with so many people being infected, you can start to see differences between placebo and not-placebo groups much more quickly).
Zoom, WhatsApp and other companies have recently been criticized for lacking proper end-to-end encryption as well. I don’t know much about that technology but it appears to be tough to do at scale, or at least, this is a more general flaw in the industry than specifically Apple’s problem.
The new AZERTY keyboard might allow to type "lǚ". I'll have to check.

EDIT : yep, looks the same at least… : ǚ

http://norme-azerty.fr/
Played and followed the AoE scene many times: 2002-2004, 2013-2014, and now playing again on AOE 2: DE. The new training scenarios in DE are quite helpful and I'd recommend them to new or returning players.

DE has led to a massive resurgence of interest and a 3rd generation of players. First gen was AoE2 (CD), 2nd gen was the forgotten empires continuing things, 3rd is DE. Some players have spanned all 3. My current favorite streamers are Viper and Hera.
While you're being downvoted, I agree with you. The artificially low interest rates are a huge burden to society, so while I'm optimistic about the vaccine, I believe that getting back to a society based on savings instead of debt will be extremely painful.
Paracetamol would almost certainly never be approved today; the lethal dose is much closer to the effective dose than almost any other medication. Many countries have more deaths from paracetamol than, say, ecstasy. So much so that it's commonly used for suicide attempts; do not try this because the likely outcome is survival with severe liver damage.
I think you should take another look at Sweden's data. Sweden (and a lot of countries) were doing fine, likely because the weather is nice and people were spending their time meeting outdoors, where infection risk is way lower. Now that it is getting cold, their case counts are on the way back up as are their deaths. It is worth noting that most of my Swedish friends say that many people were staying home anyways, just because they did not have a government mandated lockdown doesn't mean many people did not decide to avoid the risk themselves.

There are plenty of datasets that include date of death instead of reporting date and they show the count of deaths increasing again as well, on a lag, just like you would expect.

The low fatality rate we have enjoyed recently has been partially a result of the availability of improved medical care. Unfortunately that is a stepwise function where once you have surpassed the amount of available care, the improvements we have made in care revert to some extent. We don't know how much.

I see that you only really post about COVID stuff on hackernews, and I don't know why anyone would bother, but what truly blows my mind is the amount of hubris it takes to sit at home, read a few news stories, and say "I know better than the majority of people who have spent their lives studying disease because I know some statistics and read a few articles that disagreed with the mainstream."
> One of the issues I see with this is that the free market encourages companies to try to become a monopoly/oligopoly, because it's the only way to sustain profits in the normal idealized market models.

The idealized market models are models. It doesn't work like that in real life.

Example: McDonald's. They have all the competition in the world. Restaurants are one of the closest markets to idealized perfect competition there is. But McDonald's still makes plenty of money. Because as close as restaurants are to the ideal, the ideal doesn't actually happen in real life.

Coca Cola, Nike, Toyota, Starbucks. These are all multi-billion dollar companies with nothing even resembling a monopoly.
Is this also an mRNA vaccine like the Pfizer? No genetic vaccine has ever been widely deployed. As a young healthy person who could yet have more children, I’d rather get covid than take a genetic vaccine that might affect me or my offspring.

DNA vaccines have never been deployed because of serious concerns about the patient’s genes being modified by the vaccine. Scientists are saying they’re “sure” that mRNA vaccines can’t do that, but that seems overly sanguine. There is still so much we don’t know about genetics. How can you possibly have that certainty when observed epigenetic effects, for example, challenge many of our preconceived notions about the body’s genetic machinery but are so poorly understood. It seems that at least some processes currently thought to be “one-way” are actually not.
No, it is not possible to spread virus without being infected.

But...

It is certainly possible to spread virus without having any symptoms. Like children do with SARS-CoV2. All the time. Source: https://www.cell.com/med/pdf/S2666-6340(20)30020-9.pdf?_retu...

You can be infected, shed tons of virus and not have any symptoms.
Maybe, but at some point it is their own stupid fault.

The real question is the 5-10% that the vaccines don't work for - are they completely unprotected and we should wear a mask to protect them, or does enough protection exist such that they only get mildly sick vs die. There isn't enough evidence yet, but what we have suggests the former.
Which circles right back to the paradox. The moving persons reference frame has aliens still debating an invasion, and the stationary persons reference frame has the aliens already on their way. How can there be any room for free will in the deliberations of the alien government, if the timelines of both observers are equally valid? The article on relativity of simultaneity has much more detail on the subject https://en.wikipedia.org/wiki/Relativity_of_simultaneity
There are two different types of value, simultaneously existing. The content is valuable, certainly. But the actual physical artifact is also valuable, for different reasons.

I liken it to prototype/prerelease software - the data is certainly valuable, but at the same time a physical artifact with actual provenance can be worth a pretty penny too. It also irks me when people say "oh, it devalues the physical artifact if you preserve the data". No, because the physical artifact itself cannot be duplicated.
How EFI Fuel Pumps Work
Actually, speaking from experience, you can do this yourself (or mostly yourself with some guidance from professionals). Nolo press has a book ("Patent it Yourself") on the topic.
> The analysis was based on the first 95 to develop Covid-19 symptoms.

> Only five of the Covid cases were in people given the vaccine, 90 were in those given the dummy treatment. The company says the vaccine is protecting 94.5% of people.

Is it me or it's incredibly light to shout victory yet and to announce any number? Unless you literally expose people to the virus in a laboratory setting you can't guarantee that both groups had equal exposure to the virus.
>There is a HUGE difference between passive secure defaults, which a normal user will never change, and active blocks / overrides that can not be removed.

Yes. That's why I think while this change is OK as a default, it's problematic to not be overridable -- and even if it was just a default it should be communicated clearly as a change, so those affected (e.g. people relying on VPN under some regime) know about them.

Those people are not the typical user case, but it's an important consideration still.

>An example of this is iphone vs android store policy, by default on Android you can not install untrusted APK's or other stores, however inside the phone there is a simply way to disable this block. This is an example of a passive secure default. Where on iPhone it is simply impossible to disable this block

One problem with this duality is that people will disable the block, and then complain plus have their info/data and those of others compromised etc, when they install malware at the first BS prompt that tells them to do so (to get some cool new game or some pirated stuff).

That is, it's not just those "knowing what they do" that will bypass those kind of defaults....

Apple chose to go with the "Most people don't know what they're doing, and if we allow it they will do it anyway", which is a defensible position. You use their OS knowing that they do that.

But this change now, was not the same kind or communicated as well.

>it is clear that apple intends to bring this type of Active Ownership control to the Mac ARM platform, this is just the first step, a warning shot if you will, of what is to come

If "what is to come" is a machine that "just works", has no malware, but has to get its software from the App Store and/or notarized by Apple, I'm fine with it. And hundreds of millions will probably also be.

Apple was never about tinkerers and customizations, they were always about cohesive, all-in-one, curated -- and that's ever since the Apple II.

It's not their fault that people who don't like this model feel like they have to still stay with Apple.

It's not 1999 anymore. Those days if they broke into your computer or if you got a virus you would lose some useless files and a few hours/day to reinstall your Windows. Nowadays you can lose a lot, and with working from home etc becoming more the norm, even more so...
I'm using a code generation approach both for 6502 and Z80, not as extreme and elegant as demonstrated here though.

Instead of a pure data description I have python scripts which generate C source code. The 6502 is perfect for code generation because instructions are very uniform, and the "interesting" part of instructions are the addressing modes which always run the same sequence of operations in front of the actual instruction-specific "payload". The Z80 instruction set has many more special cases, but it can be decoded "algorithmically" as well, see here:

http://www.z80.info/decoding.htm

My Z80 emulator basically implements this "recipe" in python, and generates a huge "unrolled" switch-case statement with one case-branch per instruction (ok not quite, the CB prefix instruction range is still decoded algorithmically to reduce the resulting binary code size a bit).

Complex instruction logic like DAA are still essentially hand-written C functions though, the code generation mainly helps with the "mundane" parts of an instruction, like opcode fetch, and regular memory load/store machine cycles.

One nice side effect of using code generation is that it is very easy to create variations of the emulator. For instance I created a cycle-stepped version of my 6502 emulator (versus the previous instruction-stepped version) with surprisingly few changes to the code-generation script.

PS: the whole stuff is here:

https://github.com/floooh/chips

PPS: an interesting approach (which I haven't tried) for 6502 emulation would be to use the 6502's decode ROM (aka PLA) as the "base-data" for code generation.
Linters: A Full Guide for 2020
https://www.nature.com/articles/d41586-020-03218-z

Tentative good news at least that the mutations hopefully won’t derail things!
We do know that this vaccine is highly experimental and never been tried on humans before. We know they have tried this on animals and we know that in several studies they are reporting severe long-term side effects.
“I disagree.” Can I downvote you now?

That’s what not requiring comments prevents: useless comments that are just posted so people can downvote. So now your comment section is flooded by “I disagree” comments and you can’t downvote those without leaving a comment as well. It’s a self-serving cycle.
Any half modern language has a syntax construct for it. Unfortunately Javascript is on it's way but not there yet.

I could explain it, but it's already described here better than I could: https://gist.github.com/MaiaVictor/bc0c02b6d1fbc7e3dbae838fb...
(scroll to "do-notation")
Will bots replace your job?
> Also interesting to note: so we can develop and approve vaccines for new diseases within months? It doesn't have to take 10 years if we really want to eradicate a disease? My conclusion: we're under-funding research in microbiology. "We" as in: the entire world.

Perhaps, perhaps not. This is far outside my field of expertise, but here is an analogy: the fact I released 9 games in 9 months a decade ago does not imply that all games can be coded, foley-ed, and art-ed, in one month by a junior developer with Eclipse, Photoshop Elements, Bryce, and Audacity.

I assume there are many diseases where the treatment is the equivalent of an indie platformer while others are the equivalent of a AAA-headliner and yet more are the equivalent of currently fictional games like The Oasis.
We are definitely not safe
Dartmouth Launches Computation and Just Communities Center
It may not be a risk to the young people, but they need to understand that their actions have consequences for the people around them (which is exactly why people are encouraged to wear masks). A lockdown may not be the best solution, but it surely makes it so young people have a harder time infecting those who are immuno-compromised.
Ask HN: How to prevent account suspension on SendGrid?
We've been a happy SendGrid customer for a couple of years. About 200k emails per month, all transactional emails to/from users of our software. We have 2FA configured and follow all their best practices. Last month their compliance team suspended our account for 6 hours on a Friday with no warning.

I've been talking to their support team for a couple of weeks, and they can't explain why we were suspended. They say that they only suspend accounts for suspicious behavior, but can't tell us why our account looked suspicious or how to prevent the problem from recurring.

Are there any best practices for preventing the "compliance team" from suspending our account? Or strategies for recovering faster? If not, are there any companies like SendGrid with better/faster customer support?
I came to the comments wondering about this. I have always wanted to learn chess, beyond the basic rules, but never dedicated to it. I think I had some version of Chessmaster, but didn't really do much with it. I just don't know if it makes sense to really spend time on. I have, spent so much time on video games such as Starcraft 2, and other RTS games even. They sucked me in way more than chess.

But, with a new daughter, I wonder if it makes sense as maybe something I can teach her in the future. As a way of teaching those concepts. Especially slowing down, and being on a screen less (something I am already a horrible influence on). I would like to teach her 'right' vs just some random horrible ideas I have (but also not crush her and discourage her)

Do you have any thoughts on that?
Thats why you have a lot of people in the trial, and why its a double blind
Big Sur style icons for popular macOS apps
Did any of you replying actual read my comment or did you just auto-reply "buy a supported Linux laptop"? I said ". With Windows I can buy pretty much any laptop and expect it to work with", and you are saying "Just research if the laptop you want to buy works with Linux", you are completely missing the point. I do not want to have to bother researching if a specific laptop will run Linux and research if all the hardware in that particular laptop will work. I want to buy the laptop I like and I want Linux to support that laptop, since it is commodity hardware. Same as I expect of Windows and Windows delivers in this aspect.
You seem to be implying that it was "mocked" because the protection rate was "only" 92%. That was never the reason that it was mocked, and I'm curious where you got that impression.
This is what makes parenting so exhausting and so rewarding. Action/inaction, advice or advice withheld, you are constantly setting the environment that will shape your child’s entire life.

That said...I can remember phrases that my parents said in passing that for whatever reason stuck deep in me that I carry to this day, while doubtless advice they gave countless times I have no recollection of.

So, the stakes are extremely high, but the variance is also so high that it’s important not to let it paralyze you.
> we're under-funding research in microbiology. "We" as in: the entire world. In general.

Yes, definitely?

Someone I know in immunology reported that only 5% of grant proposals received funding. There are absolutely huge areas that would benefit from more funding.
My company has always stated back to the office was the goal. Working from home is useful, but talking to real humans in person is also useful
"I'm sure plenty of people would be a lot less conspiracy-minded"

I think that is a ridiculous statement. The conspiracy-minded folks will be that way regardless of objective reality.
My risk of dying from COVID is higher than that. Sign me up.
I've come across WebP images a few times in the past whenever I've needed to download images for marketing material, etc.

It's usually impossible to: import those images anywhere, modify them, or basically do anything with them (even open them outside Chrome).

As a consequence I've had to install another browser to ensure the images were not WebP.

Was that the intended purpose?
That is almost as good as the 98% of Vitamin-D.
I wonder if they checked for that.
Well, this is great news for malware developers (including intelligence agencies)! Apple might as well just have said: "Here, malware developers, focus your efforts on these few apps. The payout when you find an exploitable vulnerability is fully unmonitored, unfettered access to the network (by default) to do as you please."

This is beyond irresponsible. Apple knows there's going to be bugs in their code. Doing it anyway is completely hypocritical to their own privacy-focused marketing.
> Similarly, Pfizer received $1.95 billion to make 100 million doses whether it was approved or not.

That statement is false. See the press release: https://www.pfizer.com/news/press-release/press-release-deta...

"The U.S. government will pay the companies $1.95 billion upon the receipt of the first 100 million doses, following FDA authorization or approval."

Approval is required to receive payment, and the product has to be delivered to receive payment as well.
Sure, but what about the other 10's to 100's of Corona vaccines that are currently undergoing phase 2 and 3 trials?

I'm not convinced by the argument that developing and approving a vaccine this fast is mainly possible because of technological advances that happen to be in sync with the pandemic.
I personally consider the approach very solid from an engineering perspective, however, it's definitely a hell of a work to implement: with more complex ISAs, e.g. Sharp LR25902 (the Gameboy Classic's), it becomes a very demanding work of balancing right level of abstraction; lowering the level too much will cause the generator to be intricate, raising it too much will make the generator too difficult to recycle for other architectures.

I did something very similar, going as far as automatically generating the test suites (note that this is a WIP):

- generator: https://github.com/saveriomiroddi/libemuls/tree/master/compo...

- example cpu: https://github.com/saveriomiroddi/libemuls/blob/example_code...

- example test suite: https://github.com/saveriomiroddi/libemuls/blob/example_code...

The metadata itself is generated from another generator (!), then the required code is manually added, along with the autogenerated one.

I think the 6502 is a very good target for this type of work, as (AFAIK) it's very common in commercial contexts, so that the documentation is more rigorous. Since the GBC CPU was used just for a now obsolete console, the information sources are more or less hacked together.
Excellent.

Looks like they've removed the tests for RIAA member videos as the only change, which I assume helped get this restored: https://github.com/ytdl-org/youtube-dl/commit/1fb034d029c8b7...
Here is the commit: https://github.com/ytdl-org/youtube-dl/commit/1fb034d029c8b7...

It seems that only removing the test was enough.
Good news.

What if someone were to write a separate script that generated the necessary tests for youtube-dl?

Then prior to releases they could privately generate the code and run the tests, but still ship it not referencing any copyrighted material.
OP here - Thank you very much.

Yes it was a simple debugging everything done with the browser and with some code review :)
thank you for this project. Great idea of how to "hack" around GH. Hope it can be used as inspirations for similar projects!
I'm almost never looking for all my devices to be going over VPN. Rather it's generally one one device at a time and even within that I'd often prefer it to be one app at a time. I have run a VM with the VPN only running in the VM but the overhead of the VM itself is not worth it.
It's a disturbing trend today to project your 21st century moral code on ancient writings and philosophers. The author clearly doesn't understand Mahabharata and its context. It's like with Aristotle studies https://studyfy.com/ banned for being sexist. What a joke!
I often wonder this and perhaps it would be less bad because people were less mobile (or it'd spread slower) - but worse because of the presumably worse treatment options.

Perhaps we today would be 20 years ahead in terms of medicine and tech given the real pressure for innovation that would have been needed ('war is the mother of invention' - or something), but for a higher cost in casualties back then.

So many variables! - It's an interesting thought experiment.