Yes, exactly this. I'm using a 10 year old elitebook folio g1. It's about 2 pounds and does what I need it to do. Available with a 4k screen if that's your thing. Does not feel sluggish. Given that I'm not gaming, video editing, or doing local LLMs (and I think there is a big chunk of the population in that camp), I feel like I am missing out on nearly zero.
(And I'm not trying to say anything is special about the laptop I'm using. I adore using trackpoint (so much that I brought my own trackpoint keyboard in to work to use there) so would gladly trade for an old thinkpad if what I had didn't already do what I need it to do).
I don't know much about this, but wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly viewed as unpleasant (inflamed, maybe nasal drainage, that type of thing) with the positive tradeoff that you get fewer actual infections?
Yep! But you are also a mouse who has limited venues in which to complain.
I wonder if the vaccine causes inflammatory and other unpleasant responses when administered. If so, I wonder if those responses go away after the last dose, when the three months of protection begin.
Here are the two paragraphs that I found interesting:
> The new vaccine, for now known as GLA-3M-052-LS+OVA, mimics the T cell signals that directly stimulate innate immune cells in the lungs. It also contains a harmless antigen, an egg protein called ovalbumin or OVA, which recruits T cells into the lungs to maintain the innate response for weeks to months.
> In the study, mice were given a drop of the vaccine in their noses. Some recieved multiple doses, given a week apart. Each mouse was then exposed to one type of respiratory virus. With three doses of the vaccine, mice were protected against SARS-CoV-2 and other coronaviruses for at least three months.
> It also contains a harmless antigen, an egg protein called ovalbumin or OVA
Here's hoping the final product doesn't have a side-effect of inducing an allergy to the main component of egg-whites.
Although even if that happened... Would it only apply to the raw materials, as opposed to cooked products where the ovalbumin was denatured by heat?
Edit: No, wait! What about "safe to eat" cookie-dough, which uses heat-treated flour and pasteurized eggs as ingredients!? The might still have intact ovalbumin, and obviously I can't give it up.
And what about people who eat actual raw egg? I routinely eat freshly-made cake batter (made with raw eggs; I just clean the bowl, I don't actually gobble tons of raw cake batter), for instance. It's perfectly safe because I live in a country where they actually check eggs for salmonella before selling them and people routinely eat raw eggs on top of things.
AFAIK people with egg white allergy also have to avoid cooked foods.
My understanding (not a chemist nor doctor) is that it's specific bits of the protein that trigger the allergic reaction, so eve if the whole protein breaks down parts of it will survive and will cause trouble.
I suppose this is similar to how we use broken down bits of virus to trigger immune reactions with vaccines.
A new area of research has opened up. This approach may be more useful for treatment than prevention. It's not really a vaccine; it's more like an induced vaccine response. Keeping the immune system in that state full time might be a problem. But after an infection, that's what's wanted.
I think that "vaccine" is really not the right word to use for this; they sound as different as bandages and blood transfusions. But if it works as advertised, it could be useful if used in the right situation.
I do wonder if the kind of people who got vaccinated 10 times against Covid-19 will end up trying to get a sniff of this every month? Kind of like how we overuse antibiotics in cleaners. It seems like it would be best if saved for an "oh shoot" kind of situation.
Me neither, but I got something similar from the abstract that I was about to ask, so adding it here: "Following infection, vaccinated mice mounted rapid pathogen-specific T cell and antibody responses and formed ectopic lymphoid structures in the lung."
That latter term (ectopic lymphoid structure) comes up in connection with persistent inflammation where the immune system sets up camp near the problem point. Is this good or bad? Do these go away once the infection clears up?
These are pretty common, physiologic structures associated with infections. They can be just a handful of cells on a slide or be quite large, and I don't know what they found in these infections. I didn't read the original paper. The ectopic lymphoid structures go away after the infection resolves. It seems that the immune system has ways to set up mini lymph node architecture right by the site of infections, which is very sensible. The same process is going on in a more organized way in the draining lymph node in parallel. Research into these was really hot in the 2010s, but people don't seem to be as into them anymore (but my research has also transitioned to innate immunity from adaptive, so it's likely that I'm no longer in that universe).
In general, it doesn't surprise me that when you prime the innate immune system, the adaptive immune system works well. The problem is that pathogens have an incredible suite of tools ready to evade these mechanisms. The doses of the pathogens are typically insanely high too, which I do not think model natural infections well. Anyways, this is intriguing, so I'll take a look at the original paper one of these days. Vaccine research generally is so boring. It's like, we vaccinated, and it worked, or didn't, no mechanism.
The tradeoff might not be something unpleasant. For example, it might be that the immune system uses a lot more energy in this state, which would be bad for survival in the wild with limited resources but probably harmless or even beneficial for modern humans with abundant food.
Yes, I've had exactly this ever since my first COVID experience. If I come across anyone with even a tiny level of COVID or flu, it sets of inflammation in my lungs within minutes. Haven't gotten sick in six years now but this inflammation has happened probably one hundred times and is indeed quite unpleasant.
I think you have evolution backwards. There only needs to not be a reason we need it to survive long enough to reproduce. Or more probabilistically, there needs to not be a significant reproductive benefit to it.
And bear in mind that most people don't have a problem surviving colds and the like long enough to reproduce even with no vaccines at all, and that was probably more true for much of our evolutionary history when we were living much more isolated lives, and not cohabiting with chickens and pigs.
At scale, yes. Because human males have significantly longer fertility periods than females, the specific adaptations of men who are healthier into later life can be passed onto offspring. The same applies to women who reach menopause while they're still healthy are able to continue caring for family without the risk of expanding the population, albeit for their offspring.
While human evolution is not predictive, it has selected for a wide variety of survival-associated adaptations beyond the mere individual.
>There only needs to not be a reason we need it to survive long enough to reproduce.
Humans had life expectancy even shorter than our fertility period until recently and they developed as social species hundreds of thousands years ago, for which living beyond fertility period is beneficial (grandparents were invented by evolution too).
> And bear in mind that most people don't have a problem surviving colds
That’s modern people with access to antibiotics etc.
> that was probably more true for much of our evolutionary history when we were living much more isolated lives, and not cohabiting with chickens and pigs
For much of our evolutionary history people were eating animals, getting viruses with them.
> That’s modern people with access to antibiotics etc.
Antibiotics don't help against viruses like colds. And we live a life that is has a higher degree of social connectivity than our ancestors, allowing for faster spreading of disease, so we're arguably worse off.
> Humans had life expectancy even shorter than our fertility period
That's largely due to infant/child mortality. Once you reached reproductive age, life expectancy was roughly 50, plenty of time to have plenty of kids.
Yes, and to get there we use immunity that is activated on demand. Clearly that was better from evolutionary perspective than preactivation or always-on.
> Yes, and to get there we use immunity that is activated on demand. Clearly that was better from evolutionary perspective than preactivation or always-on.
I don't think you understand evolution. Neither needs to be "better" for anything other than survival to reproduction. Evolution isn't min-maxing in a video game.
I don’t think you understand it, if you cannot connect the dots. And of course “survival for reproduction” is oversimplification of what’s actually happening. Chances for survival to reproduce of some individuals are greatly influenced by survival of their relatives in the same group. The traits that help whole group to survive will win in natural selection, including those that extend survival beyond what’s necessary to reproduce to what’s beneficial for the group.
> I don’t think you understand it, if you cannot connect the dots.
This doesn't mean anything.
> Chances for survival to reproduce of some individuals are greatly influenced by survival of their relatives in the same group. The traits that help whole group to survive will win in natural selection, including those that extend survival beyond what’s necessary to reproduce to what’s beneficial for the group.
Which, of course, has absolutely nothing to do with whether current traits are optimized for perfection, or simply sufficient for continued reproduction. Again, evolution isn't min-maxing your video game character. I'm not clear why you have such strident opinions on something you don't understand very well.
If you think that repeating the same sentence twice would make it a better argument, maybe you should think again. Saying “it’s not X”, when nobody claimed X is quite strange way to prove anything.
I suppose "repeatedly" complaining about how someone says you're wrong is easier than admitting you had no idea what you were talking about in the first place. Seems like a suboptimal life strategy, though.
Might be as simple as cost/effect in resource-constrained environment.
Inflamation uses up resources. When we were hunter-gatherers and had to survive ice ages - it wasn't a good idea to waste calories and vitamins just in case.
Better for 3 people out of 30 to die of flu than for all 30 to starve.
Nowadays the optimal trade-off might be completely different.
If something clearly helps survival and not an improbable thing to develop, the chances are high we would already have it. But we don’t and most species don’t. It is not the default, there likely exists a reason why.
> If something clearly helps survival and not an improbable thing to develop, the chances are high we would already have it.
Well sure, but "not an improbable thing to develop" is doing a lot of work there. Again, everything complex is "improbable to develop," in the sense that evolution takes a lot of time and is very path dependent.
We could have paper shredders, blenders, toasters, water taps, and so on that just ran all the time, but our utility bills would be ginormous. Same thing for our bodies.
So does getting infected over and over. Much worse damage. Evolution isn't some magic thing that gives you the most optimal creature for a given metric. The only metric is procreation. Not longevity. Not a pleasant life.
>wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly viewed as unpleasant (inflamed, maybe nasal drainage, that type of thing) with the positive tradeoff that you get fewer actual infections?
It might be worth it, at least during certain times of the year. For much of the winter, for instance, I already seem to have a lot of nasal drainage and other unpleasant symptoms for the whole time, along with the occasional actual infection which is much more unpleasant.
There's certain times when there's big flare-ups of infections such as flu, so maybe giving everyone an annoying vaccine during that time which gives them the sniffles would actually improve things overall.
People with severe allergies or at high risk would probably make the tradeoff even if side effects were a problem. If they're not a problem, I could see most people taking this regularly just to avoid the nuisance of respiratory infections.
Yes, this was the portal style and I still adore it and use it myself, where I can. As long as the page has a scannable information hierarchy, information dense sites are better when you just want to get stuff done (/look stuff up), which for me is most of the time. I don't care about the fluff and "hero images" and the rest.
I seem to recall browsing what appeared to be the complete source back in the day. I put in a bit of an effort to get it compiling, but it was only released as poorly scanned printouts of the source code and OCR wasn't so good then so the project was bigger than I hoped.
That would be the source code posted to that sonic.net site. It was a mix of raw dumps of FORTH blocks and printouts converted to PDFs. It wasn't the full source code, and there weren't any design documents in there.
I disagree with your disagreement, for example HN is readable but the linked site feels too small for my eyes on a 21.5" 1080p monitor. It also doesn't respect browser preferences, unless you enforce a minimum font size (which can break display elements on other sites):
There's no reason why you couldn't have smaller font while still respecting browser scaling. However, they might also want to just leave it at 1 rem and let the folks that prefer higher information density to customize their own browser settings, since those are what most well developed sites should respect and it might be more accessible by default on most devices (for my eyes, at the very least).
As for targeting specific screen sizes for non-standard font scaling, media queries also would help!
In regards to missing information dense pages, try changing your browser font settings, it might actually be quite pleasant for you to see many sites respecting that preference!
I agree that too many sites now will narrow the text area and pad too much. The issue here is a fixed pixel size that will look quite different depending on the specific monitor setup you have.
And honestly if this type of thing bothers you as much as it does me, unfortunately it means adding a bunch of stylus sheets everywhere...
That's also not a perfect recollection, but is what my recollection was until I was looking up this history in the past week and found this nugget and posted it elsewhere. Quoting myself:
>So we know these were originally called PCMCIA cards, then later PC Cards, right? Well, I think I might have found the first mention of PCMCIA in PC Magazine. It is in a Dec 1991 column by Dvorak where he "introduces" the "PCMCIA PC-Card". Here's a quote, "In fact, the card should be referred to as the PCMCIA PC-Card, or the PC-Card for short. PCMCIA is the Personal Computer Computer Memory Card International Association (Sunnyvale, Calif., 408-720-0107), and it's the governing body that has standardized the specifications for this card worldwide. JEIDA works with the PCMCIA; it's specifications are identical."
>So at least according this Dvorak column, these were ALWAYS properly called "PC-Cards" (he used a hyphen), but early on people definitely were calling them PCMCIA cards and I remember the shift to everyone later (much later than this 1991 column) calling them PC Cards.
Neat, definitely a part of history that I'm not familiar enough with myself since I was only ~6 or so around then when the article was published.
It definitely seems to reinforce the joke backronym of "People Can't Memorize Computer Industry Acronyms" for the whole thing given how badly it was all refered to. It's a lot like the whole Clippit/Clippy situation with the Microsoft Office assistants. Originally it was only named Clippit but Clippy got coined by everyone else and even Microsoft ended up giving in and using it in marketing materials not too long after the fact.
Does anyone remember the 1980s PBS show Newtons Apple? A segment on that show was called "Newtons Lemons" and would show an old newsreel from I'm guessing from the 1940s or 1950s. Each one would feature some sort of "futuristic" gadget, and invariably it would be something that never panned out and I had never heard of as a kid. I distinctly remember one of these featuring basically a scooter with a small gas motor and the narrator talking about great it would be for commuting to work when we can all own these. By my recollection, it looked very much like escooters of today, just gas.
When escooters became a thing, I looked for this newsreel for a while and never found it. Anyone else remember this?
I thing I learned only recently is that the write protect switch on the SD card is not an electrical switch connected to anything in the SD card itself: it just hits a lever in the SD socket that opens a contact closure and it's up to the system (hardware and software both) to bother to look at it. So on many systems the write protect switch doesn't even work.
>But it leads to ridiculous whoppers like this, and ends up in practice excusing what amounts to the most corrupt regime in this country in over a century, if not ever.
Amen. Preach it, brother!
>No, this is just bad, on its own, absent any discussion about what someone else did. There was no equivalent pardon of a perpetrator of an impactful crime in a previous administration I can think of. I'm genuinely curious what you think you're citing?
I don't know what the poster was referring to, but I AM mad at Biden for pardoning his family. It's a molehill of an issue compared to the current administration though.
I would be very mad at Biden pardoning his family if the next president was going to be Bush. With all of Trump's calls for retribution, and actions in that direction since the election, it is hard to blame Biden for trying to shield his son from unjust exercises of the law, while Trump was publicly touting him as one of his biggest enemies.
You called an "interrupt," which was basically a system call. That changed a bunch of timing registers within the video hardware. For a long time you basically could only do 40, 80 columns of text and 25, 43, or 50 lines. With some trickery you could get the video hardware to output 90 columns and with even more trickery you could get 60 rows.
If you made a custom font you could also have more diversity in the number of rows too but this was rarely done.
Eventually different text modes became available with higher resolution video cards and monitors. 132 columns of text were common but there were others.
(And I'm not trying to say anything is special about the laptop I'm using. I adore using trackpoint (so much that I brought my own trackpoint keyboard in to work to use there) so would gladly trade for an old thinkpad if what I had didn't already do what I need it to do).
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