CRISPR eliminates HIV-1 infection in live animals - <AUTHOR> http://www.sciencedirect.com/science/article/pii/S1525001617301107 <comment><USER2> Back in 2011, there was an announcement from MIT about a new approach to a broad-spectrum antiviral that appeared to work.[1] This goes way beyond an AIDS-specific cure. But it was at MIT Lincoln Labs, which doesn't usually do bio. So the researcher moved to Draper Labs, but didn't get much funding. Then that funding ran out. Now the guy behind this is trying to get funding on Indiegogo.[3] The problem seems to be that it's too far along for small-scale YC-sized funding, but not far enough along to sell to Big Pharma. The guy behind it clearly doesn't know how to get funded. He has a web site [4] and keeps trying for crowd funding.

Some VC needs to talk to this guy. This might or might not work, but the upside is good and the costs aren't that high.

[1] [https://www.ll.mit.edu/news/DRACO.html](https://www.ll.mit.edu/news/DRACO.html) [2] [http://www.businessinsider.com/todd-rider-draco- crowdfunding...](http://www.businessinsider.com/todd-rider-draco-crowdfunding- broad-spectrum-antiviral-2015-12) [3] [https://www.indiegogo.com/projects/dracos-may-be- effective-a...](https://www.indiegogo.com/projects/dracos-may-be-effective- against-all-viruses#/) [4] [https://riderinstitute.org/](https://riderinstitute.org/)

<comment><USER3> Given billionaires running their own space programs it makes me wonder why there aren't more billionaires running biologic research companies. Between life extension and immunity to (or protection from) really pathological conditions it seems like their interests would be aligned with folks like this.

<comment><USER4> I almost wonder if running your own space program is cheaper. As in the amount of regulatory BS you have to go through due to the monopolistic behavior of the large pharmaceutical companies...

<comment><USER3> And yet, if you're not really planning on selling the techniques you find on the open market could you save yourself a lot of time by ignoring the FDA?

<comment><USER5> You can spend hundreds of millions of dollars before you even get to the point where you can ask the FDA if you can start human trials. Even having spent all that time and money, you still won't have any guarantee that your drug will prove to be safe, effective, or better than any existing drugs.

<comment><USER6> > You can spend hundreds of millions of dollars before you even get to the > point where you can ask the FDA if you can start human trials.

What's a rough breakdown of costs? Salaries certainly don't seem to be the dominant factor. Is it lab equipment & facilities?

<comment><USER5> I'm not a chemist, but here's how I understand it to work.

It's all trial and error. You start with some model about how your target disease works. Perhaps, for the sake of argument, your model is that disease Q is caused by a deficit of protein N. Protein N is broken down by enzyme F, so obviously if you found a drug that suppressed enzyme F, you could cure disease Q. Now all you have to do is try every chemical you know how to make to see if it reacts with enzyme F.

Of course, you have to be a little more picky than that. Elemental Flourine would probably react with the enzyme, but might react with other important parts of the patient's anatomy as well; probably there would be side effects. So you screen millions of compounds against your enzyme, and against thousands of other molecules commonly found in the human body that you _don't_ want it to interact with, looking for the one that interacts with as few of them as possible. These days this part is somewhat automated. Machines can squirt thousands of chemicals into thousands of test cells every second, and automatically check them for chemical reactions. There are apparently whole companies that do nothing but this, on a contract basis. They maintain a library of compounds to test against, you ship them a big bottle of your enzyme F in solution, and they run all the tests for you. That takes a big logistical problem off your plate, which is nice. Since this is all they do, they can really specialize and increase their efficiency.

Now you've spent a couple of years on the project and identified a few dozen likely candidates. The next step is to optimize them to improve their effect. You're basically trying to guess what part of the molecule is most important (hopefully backing that guess up with some data), then changing the less important looking parts of the molecule to see what happens. Think of all the different combinations of side groups you could add to it, or remove from it, or swap out with other groups, etc, and try them all. Lots of synthesizing small batches of chemicals nobody else has ever synthesized before, determining their structures to make sure you synthesized what you set out to synthesize, lots of assays to see what kind of reactions they get up to, lots of failures.

After a few years of that and you might have something you can start testing in a real biological system. For this step you use cell cultures, rather than going immediately to the full complexity of an animal model. Your drug isn't much good if the liver immediately thinks it's a poison and dismantles it, or if it kills the cultured liver cells, etc.

If none of that goes wrong, then maybe you do tests in an animal model (provided you can find some animals that are susceptible to disease Q, or something close enough), and then later do human testing. Hopefully your disease model was correct; not all of them are. Look at all the alzheimers drugs that have failed, for instance. It seems that none of our hypotheses for how alzheimers works are correct.

Also, don't forget that at some point you also have to work out how to synthesize your drug efficiently, safely, inexpensively, and in large batches.

Labs are presumably a big part of the costs, but a lot of the cost of a lab is the people, not just the equipment.

I think changing the way the FDA works is a hopeless cause, because the real costs are at the beginning of the process. Fund basic research instead, so that we can find new types of chemicals to build, new ways of building them, new natural products, etc. Maybe someone will even crack the simulation problem (the problem is that accurate chemical simulations take months and years to run, and simulations that are faster than physical tests are inaccurate).

<comment><USER6> Thanks, that's great.

</comment></comment></comment></comment></comment></comment></comment></comment><comment><USER7> For anyone unfamiliar with CRISPR, I strongly recommend this quick introduction video from Kurzgesagt on YouTube:

[https://www.youtube.com/watch?v=jAhjPd4uNFY](https://www.youtube.com/watch?v=jAhjPd4uNFY)

<comment><USER8> There is a great radiolab podcast on it as well. [http://www.radiolab.org/story/update- crispr/](http://www.radiolab.org/story/update-crispr/)

<comment><USER9> I wanted to post the same thing. That episode of radiolab was great.

</comment></comment></comment><comment><USER3> Wow, I had not connected the idea of using CRISPR genome editing with targeting virus dna segments. If I understand the technique correctly (and I am not a biologist for sure!) they used an adeno virus modified with a specific Cas9 setup to elide HIV DNA from cells it infected (normally I associate viruses with _adding_ DNA rather than removing it :-)

Is that even close to a correct interpretation? It sounds like the technique could be used for pretty much any virus dna you wanted to target.

<comment><USER10> Correct. You can also use CRISPR to edit a person's own cells in a lab for injection back into the person's body to combat a slew of diseases, including cancer.

China is already experimenting on live humans: [http://gizmodo.com/china-is- racing-ahead-of-the-us-in-the-qu...](http://gizmodo.com/china-is-racing-ahead- of-the-us-in-the-quest-to-cure-ca-1794749183)

<comment><USER11> AIDs, cancer, etc., is great, but what about male pattern baldness?

<comment><USER12> In all seriousness, what could happen for trans individuals? What would be the actual effect of replacing all cells' XY's with XX's?

<comment><USER13> Female patient transitions to male, then gets male pattern baldness. /s

</comment></comment></comment></comment></comment><comment><USER14> It is worth noting that the real challenge in gene therapy at this time is not editing the genes, but in getting sufficient coverage of edited cells (and especially progenitors and stem cells) in an adult individual to achieve the therapeutic goal and make it last.

(Most studies of genetic alterations in the broader sense have bypassed this challenge by working with animal lineages, or animals in which the editing happens in the earliest stages of development, when there are very few cells needing to be changed. The alteration then propagates during embryonic and later development).

There have been a number of very promising studies in the past year or two with regard to gene therapies to apply to adults, such as animal studies that demonstrated a cure for an inherited muscular dystrophy, but in the bigger picture, comprehensive coverage of tissues and cells is still something that the research community is in the midst of getting to grips with.

<comment><USER15> This might be the biggest issue with CRISPR right now. The other issue is that we are not close to knowing what effect manipulating a single gene has on other areas. Especially if this gene is a switch for multiple genes.

<comment><USER16> Scientists are constantly performing RNA-seq analyses to determine where any given gene is active.

</comment></comment></comment><comment><USER17> If (like me) you don't have a good working understanding of CRISPR, check out this fantastic episode of Radiolab: [http://www.radiolab.org/story/antibodies- part-1-crispr/](http://www.radiolab.org/story/antibodies-part-1-crispr/)

<comment><USER18> There's also an updated version of the episode that they aired this year.

[http://www.radiolab.org/story/update- crispr/](http://www.radiolab.org/story/update-crispr/)

<comment><USER8> Just to add some info: The update recaps the original, and talks about advances over the year or two since the first one.

It's a great podcast episode.

<comment><USER9> And if you like the original episode, I also strongly suggest you listen to this: [http://www.radiolab.org/story/shrink/](http://www.radiolab.org/story/shrink/)

It is not CRISPR-related, but part of the same interview. It was really inspiring.

</comment></comment></comment></comment><comment><USER19> Full article is available here (it will show some loading page but the PDF should download immediately): [https://www.researchgate.net/profile/Won_Bin_Young/publicati...](https://www.researchgate.net/profile/Won_Bin_Young/publication/315775073_In_Vivo_Excision_of_HIV-1_Provirus_by_saCas9_and_Multiplex_Single- Guide_RNAs_in_Animal_Models/links/58e644dfaca2727858cc2d67/In-Vivo-Excision- of-HIV-1-Provirus-by-saCas9-and-Multiplex-Single-Guide-RNAs-in-Animal- Models.pdf)

<comment><USER20> Everything is on sci-hub anyway.

</comment></comment><comment><USER21> Gene therapy (and CRISPR) is ultimately going to eliminate most if not every ailment/issue/genetic problem that we have, including aging and eye problems. Very thankful we are reaching the point where we can go into our cells and fix ourselves.

<comment><USER22> I do agree, but that is just the good news. In other news although we can harbor optimistic thoughts for scientists, medical professionals, lawmakers and maybe even politicians all around the globe to do the "right" thing to preserve human life in a currently recognizable form, but there is not a force on heaven or earth that is going to stop parents from trying to give their children every advantage.

<comment><USER23> > to do the "right" thing

"right" according to whom? nature itself doesn't believe that

<comment><USER24> Despite academic/political/military/banking/corporate alignment against fundamental morals, "right" appears to be in agreement with nature/natural selection. The States had a more "right" society founded om constitutional and civil rights that was a big part of its climb from an English colony to the world power in less than 150 years after the constitution was written.

The reason people probably have strong convictions about right or wrong is most likely _because_ of nature, not despite it. Groups that had this genetic trait built tribes, societies that had greater success in the long term.

In the short term, individuals, or even groups of individuals, can be successful by acting amorally, but this comes as a cost to their group's long term success--the cancer analogy.

Right now there is limited competition between groups in the world. Most of what we should be competing against is the coming extinction event when something else out there gets a whiff of all the artificial elctromagnetic radiation. Probably the reason we hear so little in the cosmos is because it is not a very competitive strategy.

<comment><USER25> > academic/political/military/banking/corporate alignment against fundamental > morals

"fundamental morals"? What are those and where the hell do you get them from?

> The reason people probably have strong convictions about right or wrong is > most likely because of nature, not despite it. Groups that had this genetic > trait built tribes, societies that had greater success in the long term.

Actually, couldn't agree more. But people do have _different_ convictions about right or wrong.

<comment><USER24> Re fundamental morals:

I would wager >95% of people agree on these. I've never met someone who didn't have an understanding of fundamental morals, except for a few people whom I consider to be a psychopaths.

I really would bet that most of us dont need an education to know that killing children for pleasure is wrong and disgusting. However, we might be split on whether spanking your children as punoshment is wrong. I think people understand the difference.

<comment><USER25> > I really would bet that most of us dont need an education to know that > killing children for pleasure is wrong and disgusting.

Can I remind you that abortion is legal and funded by the state in most of the first world?

It's not that I have a personal opinion on the matter (I find it too complex to develop a definite opinion), but it does come pretty close to what you're describing.

<comment><USER24> It's not. An egg moments After fertilization experiencing suffering requires quite a bit of inagination, while we all can agree a child can suffer. Where we draw the line between that is obviously somewhat up for debate (and no one in their right mind is saying we should kill born babies for pleasure).

<comment><USER25> You seem to be using subjective experiences and the ability to experience them as base for your moral system. Is it the case? Why?

<comment><USER24> I dont believe for a second that let's say you did something you knew to be evil, such as kill a child for convenience, and were hypothetically asked about this in an after life: "why did you do it, you knew it was evil," that you'd be able to say honestly that you didn't actually know that.

As far as I am aware anything is possible, but suffering and happiness seem to be real.

</comment></comment></comment></comment></comment></comment></comment></comment></comment></comment><comment><USER26> Just a reminder that MPEG LA has a CRISPR patent pool[1] and is willing to enforce it. It almost feels like satire.

[1] [http://www.mpegla.com/main/pid/CRISPR/default.aspx](http://www.mpegla.com/main/pid/CRISPR/default.aspx)

</comment><comment><USER27> Last time I read about CRISPR used to remove HIV from infected cells, the virus mutated to defeat the CRISPR attack - could this happen here?

<comment><USER28> Isn't the only way to mutate to avoid CRISPR to change your genes enough that CRISPR can't identify you? If so, doesn't that mean we just find the new genetic signature and generate a variation that targets it?

I see CRISPR as grepping through memory for running instruction code. Sure, the code can change, but if you see the behavior, then it's a matter of finding the new code signature manually and generating a new CRISPR variant target it. If that's accurate, the similarities to anti-malware are pretty cool. Just keep updating your virus DB.

<comment><USER29> Well, as CRISPR was originally found as a kind of immune system, there do exist a number of anti-anti-Cas9 systems against that evolved alongside it. There are a number of small inhibitors of Cas9 [1] (which themselves could be used to tune Cas9 in therapeutics). However up-taking such a defense is admittedly an unlike route for a virus like HIV to take to evolve resistance to a CRISPR-based therapy.

More practically, HIV has such a high mutation rate, that it's likely very difficult to target every HIV sequence with a sequence-specific Cas9 therapy. If the Cas9 guide sequence is too generic it'll take out stuff besides HIV (stuff you need). And if the guide sequence is too specific it won't get all the viral inserts because many are degenerate. As with all things though, 95% success with viral excision via CRISPR, in conjunction with 95% success via immunotherapy [2], and 95% from standard anti-retrovirals [3], get's you pretty good 99.9999% coverage.

That's the power of convergent technologies. It's an interesting slice through a number of modern therapeutic technologies all applied to one of the most challenging of tailored foes. You see convergence of small molecule biochemistry along with immunotherapy, along gene therapy, along with cutting edge synthetic biology - all approaching the problem from different angles.

[1] www.cell.com/cell/fulltext/S0092-8674(16)31683-X

[2] [https://serotiny.bio/notes/proteins/ecd4ig/](https://serotiny.bio/notes/proteins/ecd4ig/)

[3] [https://en.wikipedia.org/wiki/Category:Antiretroviral_drugs](https://en.wikipedia.org/wiki/Category:Antiretroviral_drugs)

<comment><USER30> "More practically, HIV has such a high mutation rate, that it's likely very difficult to target every HIV sequence with a sequence-specific Cas9 therapy. If the Cas9 guide sequence is too generic it'll take out stuff besides HIV (stuff you need). "

Unless I'm grossly misunderstanding how CRISPR works, there's no conceptual reason why you couldn't target multiple sequences _at the same time_ , with a cocktail method. That is, rather than trying a single overly broad match, you could go for (say) ten highly-specific targets at the same time. A particular HIV virion would then have to differ in _all ten_ regions to avoid getting chopped up.

Just spitballing here:

Google tells me that HIV has a mutation rate of about 4E-3 per base.

Let's say you choose target sequences ten bases long (I don't know what the maximum practical length for the technology is, nor the minimum length you'd need to reliably tell HIV from human, and Google isn't any immediate help there).

The probability that there will be a mutation in that sequence is then about 0.04. However, if you target ten sequences simultaneously, the probability that all ten would be mutated is (0.04)^10 ~= 1e-14.

That's likely more than good enough to assure that there weren't any resistant mutants around (if by some chance there are...lather, rinse, repeat).

This is hand-waving, to be sure. If you have better numbers, plug them in.

Edit: fixed fat-fingering the calculator.

<comment><USER31> I think ∼3E−5 per base per replication. Might be a more useful number [1].

If you use 10mers, that only gives you 1048576. I'd be almost certain that >90% of those sequences also exist in the human genome. So your target isn't specific enough (take out stuff you need as the parent suggested).

So you need to use a longer sequence, perhaps 25bp. Maybe there's a stable region or set of regions you can target (in which case the high overall mutation rate doesn't matter). Or a cocktail of sequences, specific to the global HIV population (I doubt this, HIV mutates more in a single individual than Flu does in the global population).

But if not, then you first need to figure out what the viral population in this individual looks like. So you sequence a subset of population, and come up with a 25mer or set of 25mers that target this population.

That might be a lot of sequences (significant problem). Which you then need to get synthesized (will take weeks).

Now. It's taken days to run your sequencing experiment, and weeks to get your CRISPR stuff synthesized. In this time the viral population has been generating 10E11 new virions per day. You're population has moved on, and almost certainly contains members which don't have your previous cocktail of 25mers in them and will survive the treatment.

Because HIV mutates so much, there was some interesting work I saw a while back on guiding the evolution of the population. You'd use drugs which don't wipe out the infection, but push the population toward specific genotypes. Specifically those which you have good treatments for, in the hope that you can wipe out most of the population at once.

[1] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530041/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530041/)

<comment><USER30> "Maybe there's a stable region or set of regions you can target (in which case the high overall mutation rate doesn't matter). Or a cocktail of sequences, specific to the global HIV population (I doubt this, HIV mutates more in a single individual than Flu does in the global population)."

Hmm... I would bet that there _is_ a cocktail of sequences such that if they are not conserved, the virus effectively becomes no longer HIV (no longer infectious, no longer capable of producing symptoms...).

HIV is obviously not a human being, right? Find every sequence where it differs, target them all. :-)

<comment><USER31> I did a quick literature search, but couldn't find anything. It should be easy to answer that question.

There appears to be at least one conserved protein. However there's a lot of scope for different underlying sequences due to synonymous codons.

Depending on how long a fragment you need to target, that could end up being a lot of sequences, and unpractical.

<comment><USER31> It's also possible that HIV could stick introns into the sequence too to avoid CRISPR...

</comment></comment></comment></comment></comment></comment></comment></comment><comment><USER32> From the abstract:

        Intravenously injected quadruplex sgRNAs/saCas9 AAV-DJ/8
        excised HIV-1 proviral DNA and significantly reduced
        viral RNA expression in several organs/tissues of Tg26
        mice. In EcoHIV acutely infected mice, intravenously
        injected quadruplex sgRNAs/saCas9 AAV-DJ/8 reduced
        systemic EcoHIV infection, as determined by live
        bioluminescence imaging.

Can a mod change the title to reflect the findings? The original title is "In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models" and should be kept. That way maybe some people wouldn't just reflex-upvote and actually at least read the abstract...

<comment><USER33> That abstract looks completely consistent with the submitted title. I don't see any reason to change it.

<comment><USER34> "Eliminates" is a very loaded term in viral therapy. This paper doesn't show elimination of virus, it shows that the integrated viral genome can be excised in -some- cells by administration of adeno-associated virus harboring the CRISPR system.

</comment></comment></comment><comment><USER35> In 2013 a very highly-placed Goldman Sachs exec, a friend of a friend, told me his AMFAR contacts predicted a 'genetics-based cure' in a 3-4 years instead of the 10 years they publicly projected. The rationale was donations would stop if people knew how close they were to a cure.

<comment><USER36> Even if AIDS is defeated, there's always other medical maladies that affect people. MRSA, for one.

<comment><USER37> That's not really the attitude towards curing disease.

<comment><USER38> It's not towards anything in life.

</comment></comment></comment></comment><comment><USER39> This, coupled with immunotherapy which boosts efficacy of our own defense mechanisms - for example, NK cell doping via LY49D/DAP12 - is quite exciting.

As someone else noted, THIS is what CRISPR was evolved to do. It was a DNA- based immune system used by bacteria to explicitly identify an invading virus via DNA, and to store a record of previously unknown virus for future reference. And, it was intended to function continually, in a living organism.

</comment><comment><USER40> Craig Venter, the first genome sequenced and first promoter of shotgun sequencing, disses CRISPR. He claims its not reliable enough. Nor can you prevent from altering unexpected parts of the genome. I dont know how much is not-invented-here and how accurate he is.

</comment><comment><USER41> how did they refine crispr? Around this time last year we had

HIV overcomes CRISPR gene-editing attack [https://news.ycombinator.com/item?id=11453737](https://news.ycombinator.com/item?id=11453737)

</comment><comment><USER42> Genomic responses in animal models do not mimic themselves in humans.

Great example is thalidiomide.

[https://www.quora.com/What-are-examples-of-drugs-that- showed...](https://www.quora.com/What-are-examples-of-drugs-that-showed- promising-results-in-clinical-lab-animal-trials-and-failed-miserably-in-human- trials)

[https://walkerma.wordpress.com/2007/04/27/animal- models/](https://walkerma.wordpress.com/2007/04/27/animal-models/)

I advise extreme caution and context on hyping this. Derek Lowe wrote a great post on this a few years ago that I still reference whenever I see HIV animal claims.

[http://blogs.sciencemag.org/pipeline/archives/2010/02/03/a_m...](http://blogs.sciencemag.org/pipeline/archives/2010/02/03/a_modest_literature_proposal)

<comment><USER43> You post the classic cautionary comment but reviewing your sources, none of them at all seem relevant:

"Genomic responses in animal models do not mimic themselves in humans" \- source? Thalidomide is just a random example of a traditional non-genetic treatment. Specifically the CRISPR mechanism clearly has no precedent of failure, as the Chinese only recently began human trials. There's no precedent of success, but there seems to be no reason to believe it won't work, since it works fine in vivo in other mammals.

And the Lowe link you provided is complaining about in vitro testing; this was in vivo. As far as I can tell, it's exactly what he suggests needs to be done before there's any hype.

If your point is simply that many things have been tried and failed in the past, sure, that's common knowledge. But CRISPR is not a similar approach, there is very little precedent, so IMO optimism is just as warranted as "extreme caution".

</comment></comment><comment><USER44> "animal models" is obviously a term of art but what does it mean in plain English?

<comment><USER45> It's any animal (mice, in this case) with a set of characteristics you keep constant between trials. It could be mice of the same age or weight or that have a specific gene or have the same diet.

<comment><USER46> There are specific 'model animals' that the scientific community uses however [https://en.wikipedia.org/wiki/List_of_model_organisms](https://en.wikipedia.org/wiki/List_of_model_organisms)

</comment></comment></comment><comment><USER47> Wow!

If this could be used to fight bacteria resistant to antibiotics then it is the start of something fantastic.

If it can be used to fight also diseases in animals (e.g.: foot & mouth disease in cattle) or plants (e.g.: citrus cancer) then it is even bigger.

</comment><comment><USER48> That title is false : the article states viral load was reduced.

</comment><comment><USER49> Is there any aggregated stream of information giving you information of vaccines and cures as they come in?

</comment><comment><USER50> CRISPR sounds extremely powerful. Like turning all blue eyes brown powerful.

</comment><comment><USER51> As exciting as this is, we already know how people have used the decreased danger of HIV infection to become careless about other types of STIs. Given that our antibiotics are losing their ability to treat many common STIs, an HIV cure without some advancement in antibiotics will be swapping one epidemic for a series of others.

Edit: I wanted to add a couple sources for my claims above. Once people stopped believing raw sex was an existential threat they started going nuts, falsely believing that everything else can just be cleared up with a pill. Let me also say that my SO worked on the front lines of public health for almost a decade so I might have a unique perspective on this issue because of what she experienced as part of her job.

[http://www.cnn.com/2017/03/01/health/syphilis-newborns- partn...](http://www.cnn.com/2017/03/01/health/syphilis-newborns-partner/)

[http://www.huffingtonpost.com/entry/std-rates-in-the-us- rise...](http://www.huffingtonpost.com/entry/std-rates-in-the-us- rise_us_5807bcf6e4b0b994d4c36002)

[http://www.ocregister.com/2017/01/26/syphilis- up-412-gonorrh...](http://www.ocregister.com/2017/01/26/syphilis- up-412-gonorrhea-204-why-are-orange-county-std-rates-through-the-roof/)

<comment><USER52> Only if we fail to educate people about the dangers of _other_ STIs.

<comment><USER53> Which is happening...

I would say the excessive mediatic exposure of HIV have definitely worked to supress awareness and care for other STIs.

For instance, I am HPV+ and didn't have a clue about the existance of such a thing before getting it.

<comment><USER54> I agree. By the numbers, most STIs aren't dramatic or fatal in the way HIV is, but rather "annoying little infections", though they can still affect the quality of the rest of one's life in a profoundly negative way. But they don't get much press.

</comment></comment></comment></comment><comment><USER55> Maybe Charlie Sheen would fund it?

</comment><comment><USER56> CRISPR mediated genome editing does, CRISPR itself is not a magic HIV drug. That should probably be in the editorialized title.

<comment><USER57> If one is familiar with the term 'CRISPR' in the first place, then the intended meaning is pretty clear.

</comment></comment><comment><USER58> It's awesome that this is possible. Right now HIV infections are basically a minor nuisance, provided you're taking the appropriate medication, but this bodes well for future treatment of viral infections.

<comment><USER59> > Right now HIV infections are basically a minor nuisance, provided you're > taking the appropriate medication

Even with your caveat, the fact that more than 1 million people died from HIV in 2015 is probably a good signal to not use the term "minor nuisance".

[https://www.cdc.gov/hiv/basics/statistics.html](https://www.cdc.gov/hiv/basics/statistics.html)

<comment><USER58> People who don't have access to truvada definitely aren't going to be getting cutting-edge gene therapy any time soon. And how many people died of type I diabetes in 2015?

<comment><USER59> That's another condition I'd probably not call a "minor nuicance".</comment></comment></comment></comment>


Doom's Creator Looks Back on 20 Years of Demonic Mayhem - <AUTHOR> http://www.wired.com/gamelife/2013/12/john-carmack-doom/ <comment><USER2> This was interesting:

 _" The worst aspect of the continuing pace of game development that we fell into was the longer and longer times between releases. If I could go back in time and change one thing along the trajectory of id Software, it would be, do more things more often. And that was id's mantra for so long: 'It'll be done when it's done.' And I recant from that. I no longer think that is the appropriate way to build games. I mean, time matters, and as years go by—if it's done when it's done and you're talking a month or two, fine. But if it's a year or two, you need to be making a different game."_

<comment><USER3> This is what ultimately did 3D Realms and Duke Nukem Forever in.

There was a lot of overlap between Apogee Software (later, 3D Realms) and id Software in the early days. The mantra of 3D Realms was, during Nuke Forever, that the game will be done _when it 's done_.

That mantra works great at a small scale. But when AAA titles go from Duke3d to Halo/CoD within the span of one development iteration, you're screwed. The cost of keeping up was, I suspect, just too great for a company the size of 3D Realms to keep up. Even id Software was diminishing, post-Quake 3.

Companies like Blizzard and EA have the resources to pump out WoW expansion #9, or Madden 2035 or whatever. For better or worse (my opinion, usually worse) the industry has become more like Hollywood blockbusters. The whole world hears about when GTA 5 comes out and makes billions of dollars the first week, or whatever. As a result, we're just going to get what Hollywood gives us in movies: sequel after sequel.

</comment></comment><comment><USER4> Perhaps I'm wrong but the opening sentence - "At the stroke of midnight on December 10, 1993, an executive at id Software uploaded a file to an FTP site on the University of Washington's network" \- seems inaccurate - the big ftp site back then was actually Washington University St. Louis - a different entity than U of W.

<comment><USER5> Yes-- wuarchive.wustl.edu and ftp.wustl.edu are what I was thinking of, too. I fondly remember pulling Aminet and Linux-related files off those servers back in the early-to-mid 90s.

<comment><USER6> Ahh.... me too. The Amiga community was great. _sigh_

</comment></comment></comment><comment><USER7> "And I have to say I was pleasantly heartened when the Call of Duty wave came over in more recent years and really took first-person back to the top of the heap in prominence."

CREATED DOOM AND QUAKE, THE EXEMPLARS OF ADRENALINE ACTION FPS

[Good Guy John Carmack]

HAS NOTHING BUT KIND WORDS FOR DILUTED ALSO-RANS LIKE COD

Seriously, I probably wouldn't be so soured on "modern warfare" shooters if I hadn't played so much Doom and Quake in my teens-to-early-twenties. They set the bar, a bar which has proven very difficult to meet.

<comment><USER8> You have to consider that Doom and Quake are on the same level that modern generic shooters. They were basically, find the keys( up to three ), find the doors and kill the monsters and nothing more. I think Doom and Quake were what CoD is today. And there is nothing wrong with that if you like twitch shooters, because that is what Doom is. ::hides::

<comment><USER7> What you're saying is that _Doom_ and _Quake_ had very basic mechanics. I won't argue with that. But the kind of gameplay they exhibited was very different from the CoD series. _Doom_ 's ridiculous weapon loadout, ridiculous number of monsters (especially on higher difficulty settings), the fact that your player character moved at highway speeds, etc. gave a sense of urgency and chaos to the game. CoD has nothing like the feeling of dread you get when you spot a bonus in a darkened room, naïvely cross the threshold, and hear the hissing of _multiple_ cacodemons emerging from hidden chambers directly behind you.

Another interesting mechanic in _Doom_ was the ability to either mow down monsters yourself, or save a bit of ammo by enticing them to kill _each other_ and mopping up the stragglers. This was widely copied in "Doom clones" of the day; the instruction manual for _Marathon_ even gave tips on "berserking".

CoD and its cousins in the "bloody screen, so real!" genre are quite different. They're fine for what they are, but some of us who have been playing FPSes for a while feel there's something missing. There's a series of parody videos on YouTube called "Call of Dooty" which are basically _Doom_ with CoD tropes: QTEs, tutorial levels, waypoints which walk you through the path you're supposed to follow (and penalize you for straying off the path), NPC dialogue that refers to the demons as "Russians", etc.

<comment><USER9> I played a _lot_ of Doom and Quake back in the day. I also enjoyed CoD:MW and MW2. All those games are very linear and scripted. The feeling of dread you describe works the first time you see it. The second time you get there you know what is going to happen - and that's perfectly fine!

Both Doom, Quake and the Modern Warfare games are essentially built on linear scripted sequences like that. I'd urge anyone to play "All Ghillied Up" (which may be one of the best levels of all modern shooters) and try to tell me they didn't feel at least some excitement.

By the way, if you're looking for something that carries the Doom/Quake torch of mowing down lots of enemies at crazy speeds, check out the Serious Sam series.

<comment><USER10> I wouldn't say that Doom is linear in the same way that many modern shooters seem to be linear. The labyrinth levels aspect is something that I miss.

</comment></comment></comment></comment></comment><comment><USER11> Cool; I just finished "Masters of Doom" by David Kushner.

It tells the story of ID Software, the groundbreaking games they developed up to the split of the two Johns and then some.

A real interesting read for anybody interested in the subject.

<comment><USER12> After reading this book, I realized I had WAAY underestimated Romero's impact on iD.

Point blank - without Romero, there is iD Software (it was his idea to form a new company). There is no Doom. There is no Quake. Romero was one of the primary creative forces behind iD.

Carmack was the tech genius who made their ideas come to life.

<comment><USER13> I've not read the book, but I've often wondered if things would have been that different without Romero.

Maybe in the beginning he was a driving force but I speculate something changed. Be it something with him, technology changes, or whatever but he later did not seem to have as big an impact.

I met Romero back during the beginning of the Ion Storm days and based on that short chat with him I was convinced that Ion Storm would succeed. Sadly it did not. Granted, Ion Storm did turn out some of the best games ever made but not the one that Romero made.

</comment></comment></comment><comment><USER14> As I've also recently finished reading _Masters of Doom_ (as a result of HN's discussion of Jeff Atwood's blog post about it [0]), I know that the Wired article has it wrong in the first sentence. Doom wasn't uploaded to a Univ of Washington server, rather Univ of Wisconsin.

The book was a really good and quick read. One point I'll make about its content was how it told of Carmack reading Steve Levey's _Hackers_ (1984) and thought that's where he belonged. I was happy to learn about his alignment with free software.

Wolfenstein 3d was my first non-console game. I enjoyed it tremendously, as with Doom and Hexen. I'm currently a COD addict.

The term "deathmatch" was an insight of Romero's upon experiencing the beginning of multiplayer. That was also nice to find out, that deathmatch came from Doom. It has totally stuck since, as team deathmatch is considered the default game type in COD.

[0][https://news.ycombinator.com/item?id=6570439](https://news.ycombinator.com/item?id=6570439)

</comment><comment><USER15> "WIRED: Doom is famous for having been ported to every possible platform, almost. Do you want to port Doom to Oculus?"

Carmack doesn't mention it, but you can get Doom on the Oculus here: [https://developer.oculusvr.com/forums/viewtopic.php?f=42&t=4...](https://developer.oculusvr.com/forums/viewtopic.php?f=42&t=4743)

</comment><comment><USER16> If you enjoyed reading this and want to learn more about Carmack, Doom and id software, Masters of Doom by David Kushner is a well researched and enjoyable read.

</comment><comment><USER17> _" (Carmack's responses have been edited for space and clarity.)"_

What atrocity! Only us the programmers can apreciate his _brain dump_ style of writting.

</comment><comment><USER18> I like the part where he writes the IOS version by going to an open source version of Doom, updating it for ios and re-commiting it.

</comment><comment><USER19> I was struck by this statement:

 _" There's something just intrinsically rewarding about turning around a corner and shooting at something."_

Do others feel this way? I've played shooter games when I was a kid, but I don't know that I feel intrinsically rewarded by shooting at stuff.

<comment><USER20> It's more of an immediate sense of action/consequence, like striking a billiard ball, rather than anything special about shooting.</comment></comment>


Dos and Don'ts for Winning Hackathons - <AUTHOR> https://ninefold.com/blog/2014/10/06/dos-and-donts-for-winning-hackathons/ <comment><USER2> It's a little annoying to see entrepreneurs and startup folks shoved into hackathons--I kind of prefer the notion of a pure technical hackathon where you're just playing with ideas, or finishing up side projects. Dealing with biz on the side, or decks or whatever, just kind of cheapens it for me.

</comment><comment><USER3> > _Do: Start with Rails_

> _A blog about all things Ruby & Rails by Ninefold and friends._

This post isn't very impartial.

<comment><USER4> That's like saying, anything published in the New Yorker can only be focussed on things that happen in New York

<comment><USER3> If the New Yorker said that New York City is the best city in the United States unironically, then yes, that would be bad.</comment></comment></comment>


A discussion on Fatwallet or Slickdeals? - <AUTHOR>

For those that are not familiar with the two sites, they are basically the two largest deal forums on the web. Pretty much any deal can be found there and posted pretty quickly.
I think the two sites are a mess. The frontpages are hard to navigate, and the forums don't seem like the main part of the sites' content.
I'm brainstorming a new deal site and would love some feedback from "hot deal shoppers."
Are you satisfies with one of the two sites overall? What would you do to improve them?
Some thoughts I had yo start the discussion: Posting a deal as a new user can be a hassle, I am tired of tedious forum registration.
Both sites are very cluttered and resemble web 1.0: classic forum software, directories as opposed to search.
The obvious service they are providing is the promotion of these deals around the web, is there another place "better" that one of these two sites? <comment><USER2> There are a few other sites that aggregate deals from various sources including those two and whats listed in the actual forums themselves. The real value in deals are in the forum discussions, not necessarily what hits the front page. This is true with most of the same type of deal sites. The forums are also a necessary function because its the community and the socialization that makes it happens, including those who submit deals.

I actually disagree with you that it's web 1.0 (in a sense), at least for SlickDeals. I don't go on there to hunt for deals as I have way in the early 2000s these days but I still go there to interact with the community. I can't comment on the FW side as I never got into it. But the customization of the forum software serves it's purpose in my honest opinion. And it may look like its just using standard forum software but there is a lot of heavy customization and backend work contrary to what you may believe. It just may not have that web 2.0 look to it.</comment>


Copy - <AUTHOR> https://copy.com

<comment><USER2> I took a look at your introductory video, which specifically calls out what I found to be a horrible weakness in dropbox, that everybody who shares a file, that file counts against their quota.

However, if that is your value prop/differentiator, why don't I see that on your homepage? Store, protect and share, makes you sound just like any other online storage. How about 'fairer sharing' or something like that.

Also, your video button is very small. Actually, gone at the moment because I closed the popup, and when I clicked on the link it took me to Youtube. Why? People coming to your site will watch the video if it is right in front of them. You've kinda hidden it, and then when I do find it, it takes me somewhere else.

</comment><comment><USER3> I don't think increasing Dropbox's space by 10x is going to make a dent.

When Gmail launched in 2004, Hotmail and Yahoo offered 2MB. Gmail offered 500x as much at 1GB. They made a splash with that.

Fast-forward and we're now in the same place, although space is multiplied by a thousand-fold. Dropbox is offering 2GB. So launch something that offers 1TB and you're set.</comment>


Ask HN: How does board recruiting work? - <AUTHOR> For startups and established companies, how do you recruit board directors?  Are you looking for established people to strengthen your company's focus, or those who can fill a weak point?  What is the vetting process and compensation model? <comment><USER2> Here's a good write-up on Boards > [https://techcrunch.com/2016/11/05/what- you-need-to-know-abou...](https://techcrunch.com/2016/11/05/what-you-need-to- know-about-startup-boards/)

Ultimately, the profile you're looking for is the Old Warhorse who's worked in and around the same industry/niche you're targeting. They want a piece of the action, willing to invest and provide advice. And importantly, trust you to run the day-to-day. Look for former senior operators/builders with deep personal networks.

<comment><AUTHOR> Thanks, that's a great article. I'm also looking at it from the perspective of building the attributes, skills, etc to become an independent board member in the future.

I currently sit on the board of my community association, and enjoy the advisory style of influence. I'd like to continue this experience with startups, non-profits, or for-profits.

I'm early in my career, and it sounds like a lot of the qualifications are time, experience, network, or money - but I'd like to take any active steps that I can at this time.</comment></comment>


The Tesla Valve: One Way Flow With No Moving Parts - <AUTHOR> http://blog.makezine.com/2012/01/05/the-tesla-valve-one-way-flow-with-no-moving-parts/ <comment><USER2> The whole field of fluidics is fascinating, including entire digital logic families that operate at kHz rates with no moving parts and no electricity, just air. I wrote a kragen-tol post about this in 2002 [http://lists.canonical.org/pipermail/kragen- tol/2002-April/0...](http://lists.canonical.org/pipermail/kragen- tol/2002-April/000706.html), when Air Logic still sold actual logic gates that ran on air, but since then Google Books has archived this June 1967 Popular Mechanics article, "How They've Taught a Stream of Air to Think": [http://books.google.com.ar/books?id=jSEDAAAAMBAJ&pg=PA11...](http://books.google.com.ar/books?id=jSEDAAAAMBAJ&pg=PA118&lpg=PA118&dq=taught+air+to+think+fluidics&source=bl&ots=Qt70QlAjgX&sig=axEWaqYpR8KHH76sJ4LOfIRTDoI&hl=es-419&sa=X&ei=evQtT861JomDtge7qoWNBg&ved=0CCYQ6AEwAA#v=onepage&q&f=false), and of course fluidics has become practically very important for on-chip microarrays. There's also a Wikipedia article now: <http://en.wikipedia.org/wiki/Fluidics>

<comment><USER3> See also: <http://catb.org/jargon/html/G/glitch.html#crunchly73-06-04> and follow the next-cartoon chain from there. I particularly like [http://catb.org/jargon/html/N/number- crunching.html#crunchly...](http://catb.org/jargon/html/N/number- crunching.html#crunchly74-12-25) .

</comment></comment><comment><USER4> I'm the one who made that 3D printed Tesla Valve shown in the pictures and video. I'm currently inventing a jet engine with no moving parts. If anyone wants to ask questions about the valve's workings or about Tesla, go right ahead.

<comment><USER5> Very cool, it would be interesting to build one (large) which would be wave pumped. You could cast it out of concrete I suspect. The idea being that waves would push into the end and then the flow back out would be self resisted, this would allow the wave energy to pump seawater up a bit. Then you provide a drain which runs through a micro-hydro station.

Would be fascinating to see what rate of wave action you would need to keep the flow going up hill.

On a pure art level building a pool on the beach that was filled with wave action like this would be kind of fun.

<comment><USER6> It's a cool idea, but you might want to just build it with a traditional valve. I think the Tesla valve relies on _moving_ fluid. If you just submerged it half way water would leak out in the wrong direction. So it won't work well for applications in the style of Maxwell's Demon.

<comment><USER7> Not moving water, but the potential for moving water, a pressure gradient.

<comment><USER8> The kind you get in ocean currents, where such things a self-constructing Tesla valves are probably out there, somewhere, already ..

</comment></comment></comment></comment></comment><comment><USER9> My late-night reading currently consists of the book "Wizard: The Life and Times of Nikola Tesla; Biography of a Genius" by Marc J. Seifer. For anyone looking to learn more about the man, this seems to be the most comprehensive biography available. While only half through it so far, it's been an enjoyable and enlightening read.

The author's occasional dry humour is also quite welcome. Here's a sample: "Due to his meager funds and general inability to budget himself, Tesla had but one suit, which had withered from use. It was the time of a religious festival, and Szigeti inquired what Tesla would be wearing. Stuck for an answer, the youthful inventor came upon the clever idea of turning his suit inside out, planning thereby to show up with a seemingly new set of clothes. All night was spent tailoring and ironing. But when one starts with a wrong premise, no amount of patching can right the problem. The outfit looked ridiculous, and Tesla stayed home instead."

<comment><USER10> _My late-night reading currently consists of the book "Wizard: The Life and Times of Nikola Tesla_

I'd recommend "The Prestige" <http://www.imdb.com/title/tt0482571/>

which has a fascinating portrayal of Tesla as a kind of mad techno Wizard (played by David Bowie of all people).

<comment><USER11> The Prestige is complete fiction that merely uses his name because he is recognisable as a practical genius.

<comment><USER12> Yeah, but a good film none the less, and for those who know about Tesla, it was a very pleasant surprise to see him turn up.

Also, in some weird way, having Tesla as the inventor leant an air of credibility to an other wise ludicrous plot point.

<comment><USER10> Right, I thought the idea of Tesla, as a _wizard_ of science among mere squabbling magicians, a fun plot notion. That they dealt with him, almost alone and in his secret keep, surrounded by the mysteries of his work, a wonderful spin on the mythos surrounding Tesla.

It helps that Tesla's personality was bit off in real life, and he did things that even today we think of as a kind of magic.

Of course in the movie what he built _was_ impossible, but the notion that "any sufficiently advanced technology is indistinguishable from magic" kept creeping into my mind.

</comment></comment></comment></comment></comment><comment><USER13> How Telsa came up with most the things he did are beyond me. I have always thought he was the smartest man that has ever lived.

<comment><USER14> I have the feeling that, to an engineer/researcher who is well versed in fluid-dynamics, this sort of thing wont seem as ingenious - my guess is that it's at the analogous level of a waveguide.

No doubt that Tesla was a bright person though.

<comment><USER15> _"[...] my guess is that it's at the analogous level of a waveguide."_

In the field of fluid dynamics, it is referred to as a _check valve._ [1][2]

[1] <http://en.wikipedia.org/wiki/Check_valve>

[2] [http://www.spiraxsarco.com/resources/steam-engineering- tutor...](http://www.spiraxsarco.com/resources/steam-engineering- tutorials/pipeline-ancillaries/check-valves.asp)

<comment><USER16> Well the _function_ of restricting flow in one direction is well known.

But those sources you list describe several types of check valves, all of which have moving parts.

<comment><USER17> They also work. The Tesla valve allows a fair amount of bleed through, and unlike valves with moving parts you can't prevent that from stacking them. In other words it becomes less efficient as the presser differential decreases.

<comment><USER16> That bleed is also a function of viscosity.

There might be some interesting applications for a device that passes two things, say a fluid and a gas, in one direction and resists the fluid (but not the gas) in another.

</comment></comment></comment></comment></comment></comment><comment><USER18> That's pretty cool. The curved side channel actually pushes the main flow into the next side channel.

I wonder if a fractal version of this would work better. And what if there were side channels on the top and bottom too.

Of course, this will always pass some fluid. but if you need a complete shutoff valve, combining it with the tesla valve would allow you to use a smaller one and makes its failure less traumatic.

<comment><USER4> In regard to a fractal design being more efficient, you have to check out these topology optimized valves. They are really beautiful and peculiar, and have many branching channels to optimize their efficiency. [http://www.senlin41.org/topology-optimization-of-tesla- type-...](http://www.senlin41.org/topology-optimization-of-tesla-type- microvalve/)

<comment><USER18> nice. thanks!

</comment></comment></comment><comment><USER19> From the comments:

Reminds me of <http://en.wikipedia.org/wiki/Vortex_tube> Another simple yet fascinating device

<comment><USER4> I find that device fascinating too. That's why I designed the 3D printed Tesla Valve in the article. Things with no moving parts are amazing. Especially the esoteric ones that seem forgotten by time because other technologies progressed ahead of them.

</comment></comment><comment><USER20> Just imagine the day we get cheap 3D printers. We see this article on the internet on the Tesla Valve and want to try it out ourselves, so we download the blueprint and send it to our personal printer, which prints a copy of the Tesla Valve and then we play with it ourselves. I am guessing there are so many (expired) patents out there that, just like this one, can be converted to a blue print and everyone would get to experiment with it, instead of only large companies with enough cash to customise expensive equipment for it.

<comment><USER4> If you are still waiting for that day, you can get the valve 3D printed now from my shop: <http://www.shapeways.com/model/292339/tesla_valve.html>

And if you already have a 3D printer, you can get the files free here: <http://www.thingiverse.com/thing:16919>

</comment></comment><comment><USER21> That's very elegant. It's amazing (and a little terrifying) to think that he may very well have been able to mentally visualize the fluid dynamics to some extent. It's not like he was consciously solving navier-stokes, but it's still incredible what some human minds are capable of.

But then, he was thinking a lot about electron flow and built up a good intuition that had wider application. That doesn't make it any less amazing to me though. I'd like to be able to do that.

<comment><USER22> a patent is a record of the working device, not the process used to get to it.

thinking of anyone as a supernatural genius is nonsense. most of the time.

<comment><USER23> In the case of Da Vinci, Einstein, Tesla and a select number of others I think that thinking of them that way is well justified.

The general idea is that if the time is ripe for an idea then someone somewhere will have it, and if that someone would not exist someone else will have the idea a short while after.

But for the men mentioned above I highly doubt that would be the case, they were both way ahead of the curve at the time.

</comment></comment></comment><comment><USER24> From the video it looked like there was still some airflow in the reverse direction.

<comment><USER25> Yes, it seems better as a technique to introduce bias to flow than to restrict it altogether---valve-like, but not exactly a valve. Sufficient for a lot of valve applications, though, and the lack of moving parts is reeeeeally nice.

<comment><USER14> Looks like the shape tries to maximize turbulence in one direction, and minimize it in the other.

Probably it would be an effective mixing device too.

<comment><USER4> The Tesla Valve is a leaky valve, which is why we still use one way valves with moving parts. The amount of leakage depends on the design of the valve and how well it suits the incoming fluid. A faster fluid will result in a different looking valve compared to a slower fluid. The valves design would also change based on the viscosity of the fluid.

</comment></comment></comment></comment><comment><USER7> Is the unidirectional flow property dependent on the pressure gradient at both ends? It seems that at low pressure differences you could still get flow in the reverse direction. Yet, at high pressures I imagine you would see some leakage, too. Does it only work for medium pressures?

<comment><USER4> In will work in many regimes. In the microfluidic literature, the valve is judged by its diodicity. Different flow rates, sizes, and viscosity, results in different geometry for the tesla valve.

</comment></comment><comment><USER26> Does it work with incompressible fluids? Can someone test one with water?

<comment><USER4> Yes. It also works with incompressible flows. I have yet to give mine a test with water. I want to build an acrylic window for it first, and ink the incoming water.

</comment></comment><comment><USER27> Can someone post a link to the desktop version? Site is unreadable on iPad.

<comment><USER28> Scroll down and turn off The mobile version of the Wordpress theme.

</comment></comment><comment><USER29> If you haven't read Tesla's autobiography[1], I highly recommend it.

<http://www.tfcbooks.com/special/my_inventions_index.htm>

[1] I'm a bit confused as to whether it was genuinely an autobiography, or a compilation of articles. Either way, it was interesting to read, though very light on technical details.

<comment><USER30> It is a collection of articles for the "Electrical Experimenter" magazine: <http://en.wikipedia.org/wiki/Electrical_Experimenter> The articles were written by Tesla and they are autobiographical.

There are also some versions on the internet which include fake sentences inserted later by some religious zealot mentioning "God, Divine Being." Take care not to link to those.</comment></comment>


No More Virgins in New York - <AUTHOR> http://www.foxnews.com/story/0,2933,364422,00.html <comment><USER2> I can't say I've ever said this before, but why is this here AND receiving 8 upvotes (so far)?

<comment><USER3> Maybe because this is an indication of how disruptive the MP3 players alongside with digital downloads are becoming to the traditional music industry.

<comment><USER2> In 2008, how is that news?

Put it this way, when was the last time any of us purchased a music CD at a traditional music retailer?

For me, the answer is probably 1999, and not coincidentally, I recently found a paper gift certificate for $15 from 1999 for a Virgin Megastore.

<comment><USER4> I probably haven't bought a CD since maybe 2005.

</comment></comment></comment></comment><comment><USER5> I like the use of the ironic "not!" Maybe the writer was trying to take us back to a time when Mike Myers was on SNL and record stores were thriving.

</comment><comment><USER6> I can't believe they bulldozed the historic Luna Park bar in Union Square to make room for a restaurant when they could have instead put it in the old Virgin Mega-store. What a waste.

</comment><comment><USER7> Oh well. There was a day when poor (or rural) people would have to wait for the publication of a 4-handed piano arrangement of a Brahms' symphony in order to hear it.

<comment><USER8> Wow, was that more or less slow that 14.4 baud modems?

</comment></comment><comment><USER4> It's called a sunset industry. Why not switch industry instead of trying to stop the sun from setting?

</comment><comment><USER9> i c waht u did there</comment>


NeTV2 – An open video development board - <AUTHOR> https://boingboing.net/2018/05/11/free-as-in-to-air.html <comment><USER2> Bunnie is among a few people that I look up to a lot as not just being innovative as an inventor and engineer, but also a practical and fearless one at that. The "sue the US government" was a crazy and genius move.

I have hacked on his hardware -- the Chumby. I had a lot of fun working that was the inspiration for me to do many things that I do now.

In the past job working for the IT department in a small state university right after graduating, I convinced the administration to buy a truck of overstock Best Buy-rebranded Chumbies. I converted those little boxs to an economical audio/visual/projector control system for our classrooms in 2012 (they are still used until today, I think!). If I recall correctly, that's even after the Chumby as a company dissolved. The software was largely abandoned at that point, yet it didn't stop great things like that to happen. I wrote quite a bit about hacking and putting weird software for the Chumby on my blog, but the highlight was that specific experience [1]. I hope the link I posted doesn't come out as self promotion, because the intention here is to celebrate the spirit that bunnie put into ordinary people like me. Honestly, I am pretty proud and every time I talk about that experience, it puts a smile on my face. All of that wouldn't have been possible without open hardware and free software.

I wish this world have more people like him, so we can all inspire people to make hardware and have fun with technology.

1: [http://www.tnhh.net/posts/crankshaft-chumby-do-you- believe-i...](http://www.tnhh.net/posts/crankshaft-chumby-do-you-believe-in- the-users.html)

</comment><comment><USER3> I bought the first NeTV back in ~2011, via Adafruit. I am not saying that any promises were breached, but I did feel that the platform was abandondoned pretty soon after the boards were made available for sale.

So, I guess what I'm saying is: don't buy this board for thinking they'll continue to develop the software after you buy it. If you buy it, make sure it is for what the software is today.

<comment><USER4> I'll add a little context from my own experience. I have two NeTVs, one I use on occasion for a particular project, and one in case that one breaks. I spent a lot of time figuring out working with the platform.

I got the impression, not that it was abandoned, but that bunnie and whomever else involved were hardware people, not software people. It had all the hallmarks of a hardware development kit without any serious software people on the core team. Software folks without experience working on underdocumented and undersupported hardware platforms had no place to go, no paths laid out, no real documentation for making the NeTV do things with just the built-in browser or kernel, like "what fonts are available out of the box" or "what is the equivalent WebKit/Chrome versions and how do I debug errors". The hardware folks expected the software folks to also be hardware folks, and they usually aren't.

<comment><USER3> There was however a relatively large software effort taking place before the launch. At least in terms of software velocity. Perhaps I was naive, but I expected that to continue. Instead it just stopped and Bunnie moved over to some other project iirc.

</comment></comment></comment><comment><USER5> I'm on board! I used the first NeTV to experiment with 10-foot UI design using web technologies. I would rather have a dumb panel television and roll my own interface but I very much remember running into the HDCP issue Bunnie is fighting against which prevented me from doing that.

I hope the new hardware will support HDMI 2.1.

</comment><comment><USER6> It would be interesting to connect something like this to different News outlets and conduct a sentiment analysis to determine objective bias.

<comment><USER7> It would, though it'd be a tricky research design to pull off well: too many moving parts (it turns out to be difficult even to partition video by speaker automatically, let alone everything else).

On a more conceptual note, sentiment analysis detects (linguistic markers of) sentiment, not bias. Pretty much every news source will have positive sentiment for heartwarming human interest stories, and negative sentiment about atrocities. That's as you'd expect; we don't produce or consume news in a vacuum.

<comment><USER6> I'm thinking you could compile a list of commonly used words in positive or negative articles and count their frequency as a starting point. Also, you could search for nouns of importance like Trump or Obama and hone your bias detection.</comment></comment></comment>


What Ötzi the Iceman's Tattoos Reveal About Copper Age Medical Practices - <AUTHOR> https://www.smithsonianmag.com/smart-news/what-otzi-icemans-tattoos-reveal-about-copper-age-medical-practices-180970244/?no-ist <comment><USER2> Photos here:

[http://blogs.discovermagazine.com/d-brief/2015/01/30/scienti...](http://blogs.discovermagazine.com/d-brief/2015/01/30/scientists- mapped-otzi-icemans-61-tattoos/#.W5xhfS2ZNTZ)

Not at all like modern tattoos. I wasn't expecting anchors and skulls, but these are very simple and don't appear to have any rounded edges.

<comment><USER3> What's striking to me is that they appear "precise", so it required training and technique. It wasn't some kind of amateur inking.

<comment><USER4> > the tattoos, which were created via small incisions traced with charcoal

That makes me assume that each of line was made with a single straight-line cut that was rubbed with charcoal.

</comment></comment></comment><comment><USER5> PBS (US) had a show covering this the other night. The tattoo locations corresponded to areas of arthritis. Also carried different fungi, one for fire starter, another for antisceptic.

Interesting that the tattoos, tools, and medicine pointed to a level of specialization that would have been supported by agricultural civilization, not by hunter gathers.

<comment><USER6> Interested in that statement (I know little about this area) but why do you say that specialisation would only occur in an agricultural civilisation?

<comment><USER7> The theory goes that hunter gatherers have to spend a lot more time just getting enough food to survive, and don't generate the surplus food to dedicate people to medicine or to manufacturing.

My understanding is that this is not very controversial within academic circles, but outside of academia, I personally know a lot of people who seem to think that living off the land is easy and would leave you with a lot of free time.

The other argument is one of density. For specialization, you need enough people nearby for the specialist to trade with. Hunter-gatherers need a lot more space per person than agricultural societies. In a hunter-gatherer society, you'd have to travel a lot further, potentially while carrying food and trade goods, to get to that doctor or that smith.

<comment><USER8> I doubt people would transition to agriculture if it was harder than living off the land.

<comment><USER7> > I doubt people would transition to agriculture if it was harder than living > off the land.

I'm mostly with you, so I'm not good at summarizing the other side's point. But I think there are several reasonable assumptions they talk about where they might be right:

1: these people usually assume that very low population densities are desirable (I mean, obviously, that's a prerequisite for hunter gatherer society) This is their strongest point, really, that no matter how fertile the area you live in, once you get more than a certain population density, you need to go agricultural or you need to starve.

2: before agriculture, perhaps people only lived in the areas where food was super plentiful naturally. It's totally possible, maybe even likely that there used to be more areas like that than there were after history started being recorded. - this argument is reasonable, but it's mostly a callback to 1. An active human eats a lot, and it doesn't take a whole lot of humans to deplete just about any eden.

I mean, the obvious counterpoint within this context is that density really helps encourage specialization, so even if the life of a low-density hunter- gatherer is easier, it's not going to involve a whole lot of specialization.

<comment><USER9> Regarding 2', many groups of humans found ways to live in the most remote and barren places on earth (the Arctic regions, the Australian desert...) for up to 18000 years.

</comment></comment></comment></comment></comment></comment><comment><USER10> What's with all the acupuncture?

<comment><USER4> My understanding is that acupuncture evolved from earlier bloodletting practices which were common throughout Eurasia.

</comment></comment><comment><USER11> This can't even qualify as pseudo-science.

<comment><USER10> Faux-science?

<comment><USER11> Whatever category reading tarot cards and tea leaves falls under...

<comment><USER12> If said tarot cards and tea leaves are 5000+ years old, then studying them could certainly be done scientifically.</comment></comment></comment></comment>


Ask HN: GMail blacklisting new domains? - <AUTHOR> Hopefully a Google employee or someone with insight into Gmail's spam algorithms/blacklists can help solve this puzzle.
I'm the founder of Goals.com, and we clearly inherited a very old domain name. Fifteen years old, to be exact. That means we've also inherited an unfortunate legacy of spam.
We've done everything right in handling this. We use SendGrid for our transactional emails, have set up white labeling to use DKIM, SPF, etc. And we've even made a point on user sign up of checking the spam folders/filters. We have close to 99% reputation, provide unsubscribe links or a link to email management, and try to make sure our emails don't read spammy.
Someone at SendGrid has been helping me out with this (Kyle – thanks, dude!), and his efforts have been great but futile. We finally buckled and registered a new domain, only to find that those emails, too, were being blacklisted. Kyle helped us out again, and again even the most basic, least spammy test emails were going straight to spam.
I was told that Google has no procedure for fixing this problem, that we are blacklisted with no option but to use '@sendgrid.com' for our emails. This could be fairly confusing to our users, so obviously I want to avoid this if at all possible.
Does anyone know how or why Google has been blacklisting domains (even new ones), or know how to fix such a problem? <comment><USER2> My company was in a similar boat with a decade plus old domain (though I don't think it ever had anything scummy associated with it before we bought it). When we first started testing our site in January '09, our "click here to verify your email address" emails were going to spam, and it was a major bummer. After a week of calling ~100 of our friends with @gmail accounts to sign up and mark the email as not spam, our messages finally started going through.

I have no idea if that's a normal sample size, nor any proof that that's what made the difference. Regardless, I strongly believe that having lots of people go to their spam folder and mark you as not spam has a huge effect; if I was designing a spam filter I'd definitely weight that feedback heavily. If you can somehow build that into your app (i.e. make people verify their email to continue), in the long term it should solve your problem. In the short term, your UX will be a little worse and you'll be constantly wondering how long it's going to take until google trusts you. Welcome to the nightmare that is email deliverability!

</comment><comment><USER3> I'm not a Google guy, but I've had some experience setting up new domains for email. You have nothing but my best wishes. Its a pain in the ass. Sounds like you've checked a lot, but in case you haven't, check to see if your IP(s) are on spamhaus and other blacklists.

<comment><AUTHOR> Yeah, I've checked that, unfortunately. We're not listed, and the new domain certainly wouldn't be.

</comment></comment><comment><USER4> Proabably not the domain but the IP? Have you checked the headers?

<comment><AUTHOR> The IP is SendGrid's, so that's not the issue. The variable that causes it go to spam is unfortunately the domain.

</comment></comment><comment><USER5> You need to add a DNS record authenticating sendgrid as a legitimate host to send mail for your domain.

Don't remember the exact details, since it differs depending on which spam- fighting protocol you're dealing with.

<comment><AUTHOR> I did that. They have you add an A record, three separate TXT records, and a CNAME.</comment></comment>


Web Page Performance Death by a Thousand Tiny Cuts - <AUTHOR> http://metroize.com/web-page-performance-death-by-a-thousand-tiny-cuts/ <comment><USER3> For those who haven't tried it, disabling JS completely makes pages load surprisingly quickly. You'll also realise how many sites inanely use tons of JS (the bulk in bloated libraries of which a tiny fraction is actually used by the site) just to serve static content. But a lot of sites also continue to work fine, despite what "common knowledge" says.

So before you dive into micro-optimising JS, consider whether you even need all that JS at all. Of course this is unavoidable for certain sites which must be app-like, but if plain HTML and CSS is sufficient, then you will have effectively optimised the JS to its ultimate end. (Don't serve CSS with thousands of rules which you don't use either.)

<comment><USER4> I have JS disabled by default except some sites. I just want to notice that usually it is not only JS fault. Javascript in general is not slow - <USER2> problem is usually with third-party scripts (analytics, advertisement, social network buttons) that add huge load on a browser. They load large JS frameworks, create many iframes (and every iframe is like a new tab in a browser - it has own DOM, own stylesheets, its own JS VM), track events like mouse movement. For example Google AdSence can add several additional iframes per banner.

For example, reddit frontpage (which doesn't have much ad) has 6 additional iframes. It makes 76 requests (775 Kb) while loading of which only 15 (taking 335 Kb) belong to reddit domains, other are third-party. So by just disabling third-party services (you can do it on the browser side) they can make the page two times smaller.

Techcrunch has 19 additional iframes. It makes 273 requests (of which approximately 190 are third-party) and loads 2.1 Mb of data (of which approximately 1.1 Mb account for third-party domains). Opening single techcrunch page is like opening 20 new tabs in your browser.

And as a site owner you cannot optimize your ad provider scripts. Yet you can "optimize" them out at a browser side as a user.

Instead of blaming everything on javascript or jquery people should look at network tab in developer tools.

<comment><USER5> You can sort-of optimize your ad javascript. Some of the ad networks are starting to require that you ads come essentially pre-packaged and be under a certain size.

They still might have dumb code and overly fancy animations of course.

</comment></comment></comment><comment><USER6> Dedicating your development time to a laundry list of "best practices" doesn't pay off that well. Measure where your web page is spending its time and fix that. Take image sprites for example. Setting them up takes extra steps and complexity in your build process and requires you to track which images you are using. With HTTP2 becoming common the cost of individual image requests isn't that bad.

<comment><USER4> Usually most time is spent loading third party trackers, advertisement and social network widgets. You can "optimize" that only on client side by blocking them.

<comment><USER7> We iFramed them on one of the major websites I worked on. Didn't affect the revenue. And they render completely separately, don't block anything / cause layout thrashing.

</comment></comment></comment><comment><USER8> Plug for my (open source) project, mod_pagespeed: it can automate all of these.

> not using image sprites

sprite_images filter: [https://developers.google.com/speed/pagespeed/module/filter-...](https://developers.google.com/speed/pagespeed/module/filter- image-sprite)

> not using a cookieless domain for images and other static content

MapRewriteDomain directive: [https://developers.google.com/speed/pagespeed/module/domains...](https://developers.google.com/speed/pagespeed/module/domains#mapping_rewrite)

> not using a CDN

Once you have a (pull) CDN set up, mod_pagespeed can rewrite your resources onto it with the same MapRewriteDomain directive.

> blocking javascript - worse if it's in the head

defer_javascript filter: [https://developers.google.com/speed/pagespeed/module/filter-...](https://developers.google.com/speed/pagespeed/module/filter- js-defer)

> not minifying your javascript and CSS

rewrite_javascript: [https://developers.google.com/speed/pagespeed/module/filter-...](https://developers.google.com/speed/pagespeed/module/filter- js-minify)

rewrite_css: [https://developers.google.com/speed/pagespeed/module/filter-...](https://developers.google.com/speed/pagespeed/module/filter- css-rewrite)

> not optimizing caching policies

mod_pagespeed automatically longcaches everything: [https://developers.google.com/speed/pagespeed/module/filter-...](https://developers.google.com/speed/pagespeed/module/filter- cache-extend)

> not gzipping your content - most if not all popular web servers support some > type of compression

mod_pagespeed automatically enables gzip compression

About half of these are enabled by default (minifying css and js, optimizing caching, turning on gzip) and the rest need to be configured.

(If I were making the list I would also have included resource combining for css and js, which mod_pagespeed does by default.)

<comment><USER9> Very cool project (and in C++)!

HN is not bad with 91/100: [https://developers.google.com/speed/pagespeed/insights/?url=...](https://developers.google.com/speed/pagespeed/insights/?url=https%3A%2F%2Fnews.ycombinator.com%2Fnews)

Compared to PageSpeed home (unfair) 64/100: [https://developers.google.com/speed/pagespeed/insights/?url=...](https://developers.google.com/speed/pagespeed/insights/?url=https%3A%2F%2Fdevelopers.google.com%2Fspeed%2Fpagespeed%2F)

;-)

PS: The FAQ source code link points Google Code (instead of GitHub: [https://github.com/pagespeed/mod_pagespeed](https://github.com/pagespeed/mod_pagespeed))

</comment></comment><comment><USER10> If you're doing green field development I strongly recommend you turn on network throttling and set it to 3G (I'm assuming you're builing a web app that could be used on a phone). That ways performance doesn't become an expensive after thought, and you avoid optimizing things prematurely.

</comment><comment><USER11> "Bottom line. Try not to overdo it (on company time). At the end of the day you need to ship it."

What kind of abusive management structure has this guy thinking he has to work for performance issues on his own time? I shudder to think what company he's working for or what manager has instilled such a sense in him and I truly feel sorry for him that he thinks this way.

<comment><USER12> I think that's a bit unfair. He's not saying you are required to commit your own time in order to meet performance requirements; he's just saying that the business needs to take a balanced view on priorities in order to ship. So if you care enough about a deprioritised issue that you can't sleep, and the company is unable or unwilling to change its priorities, feel free to fix it on your own time. Or don't. Your call.

Now if the company demanded certain perf issues be resolved ahead of shipping and didn't provide company time for it, that would be a different matter and I'd agree with you.

</comment></comment><comment><USER13> The article links to a bunch of jsperf.com benchmarks, but I believe[1][2] these microbenchmarks are not very useful, since they don't reflect real-time performance differences.

1\. [http://mrale.ph/blog/2014/02/23/the-black-cat-of- microbenchm...](http://mrale.ph/blog/2014/02/23/the-black-cat-of- microbenchmarks.html) 2\. [http://mrale.ph/blog/2014/12/24/array-length- caching.html](http://mrale.ph/blog/2014/12/24/array-length-caching.html)

</comment><comment><USER14> A lot of the advice is useless (or harmful) for modern HHTP/2 or SPDY serving (image sprites, CDN, etc).

And minifying doesn't make sense if you gzip your content -- you just add an extra processing step for little to no benefit at all.

<comment><USER15> Anyone have a credible resource for when HTTP/2 might be more common? Akamai has it, but it's in "beta". The apache module is marked as "experimental". Cloudflare says about 25% of current browser traffic is from browsers capable of using it.

</comment></comment><comment><USER16> Performance isn't something you argue over, performance is something you measure, optimally with a highly detailed profiler.

<comment><USER15> I agree with that at a high level, but it's not necessarily practical to do that definitively and cover

      - all the various browsers
      - all the various network speeds (3G, 4G, DSL, Fiber, etc)
      - all the different devices

There is value in having some set of high level guidelines or best practices, which of course, can be argued over.

</comment></comment><comment><USER15> The bullet point list misses the culprit that I find most often...just too many page assets. Usually driven by either:

\- Not combining javascript or css files where it makes sense

\- Not using lazy loading for pages with lots of images

<comment><USER17> Or simply not caring about the end user.

</comment></comment><comment><USER18> > blocking javascript - worse if it's in the head

> not minifying your javascript [...]

If you designed properly with progressive enhancement, the page will at least _work_ while the javascript is still loading. For most situations it's fine if the fancier features are not immediately available as long as the page itself is readable immediately.

> third party javascript partners

Aka shady ad/tracking networks. This isn't a technical problem.

</comment><comment><USER19> My steps for better performance:

      1. apache gzip rules
      2. apache expires headers
      3. smaller images with ImageAlpha/ImageOptim
      4. javascript to bottom of the page

Simple things to make your webpage load faster.

<comment><USER20> Agreed, although I'm not sure how much #4 matters for a "CRUD" app written in Angular - there's nothing worth seeing until JS runs :-)

... other than a div that says "Loading..." for half a second to a second. Yeah, not great, but it's an app (HUGE government form), not a marketing flyer.

<comment><USER21> Is there any advantage to moving JavaScript to the bottom of the page when most browsers support <script async> and <script defer>?

</comment></comment></comment><comment><USER22> The very first step in web performance is to just load less: it's truly amazing how much unnecessary crap is put on pages these days to just convey some simple information.

The modern web is perfectly fine and fast, it's just abused to hell by all the extra "design", images, ads, videos, analytics, etc. Just keeping it simple would solve more problems than anything else.

<comment><USER23> That's easy to say. Tons of websites can actually function financially due to those ads and analytics.

<comment><USER22> I know, I work in the ad industry.

However a good 75% of it is unnecessary and because of bad business management rather than technical reasons. There are better ad networks and analytics services, combined with better site architecture and code, that can make a big impact if the publishers cared to do it.

</comment></comment></comment><comment><USER24> Everyone recommends to use CDN then lots of sites appear hidden beneath Cloudflare hoping they will load faster on cellphone.

<comment><USER25> Could you expand? I'm going through this right now and it would probably be useful.

<comment><USER26> I think he's noting a cdn won't help with low bandwidth on the client end, i.e. assumably cellphone users, which make up a large proportion of the Internet. Only reducing the size of the site would help.

<comment><USER27> Yeah. I think we've all seen sites that use an image CDN to serve up a 4 MB PNG, which ends-up scaled down to 1/3rd size on the page anyway.

The CDN might help the ping time of that request, but on a low-bandwidth device, 4 MB is still 4 MB no matter what server it's coming from.

<comment><USER28> Yeah, though CF does have content optimization features, including one that auto-resizes images to the type of device.

<comment><USER25> That's awesome. Do you have link to docs?

<comment><USER28> It's more a marketing page than documentation: [https://www.cloudflare.com/mirage/](https://www.cloudflare.com/mirage/)

They have a bunch of similar features: [https://www.cloudflare.com/features- optimizer/](https://www.cloudflare.com/features-optimizer/)

</comment></comment></comment></comment></comment></comment></comment><comment><USER29>
       "What about other areas and under-the-covers code that just
       needs rework? Just do what I do, and work on it on your own
       time."

Yeah because doing unpaid work for your company is the way to go.

Get a life and learn to leave work at work.

It's not the developer's fault if the manager is not dedicating enough man- hours to finish something, only to find out later on that messy code eats up many more man-hours than having it written cleanly the first time with much lower maintenance costs later on.

If developers don't man up and let the managers crash and fail for it, they will be supporting greed and exploitation in the workplace and probably make it worse.

<comment><USER30> Not if you love your work and you are lucky enough to work for a good company that you really want to contribute to.

I think its a bit rude for you to suggest someone who brings some work home has no life. Many developers are passionate about their job, they love learning and most importantly they love a good challenge. You don't stop thinking about a challenge at work as soon as the clock hits 5.

<comment><USER31> Perhaps this is a great contrast between individuals that pushed themselves into programming for a job and people who fell in love with it and got a job out of it.

Its also a shane that the former is what most people find themselves in. A means to an end in a world that isnt very kind to everyone.

<comment><USER15> That's not the only two groups in question here.

There are those that spend off-time programming, just not for their employer's tasks.

The quid-pro-quo of employee-employer loyalty is largely gone these days, so it's not unreasonable to only work the hours you're compensated for.

<comment><USER32> Why would loyalty have any impact on gifting your employer free work? You can be loyal without giving away things for free.

<comment><USER15> Perhaps we're using the term in two different contexts.

I'm using the term loyalty for lack of a better term. There was a time when employees would often go above and beyond for their employers, because the reverse was also often true. Roughly, the shift away from the "lifetime employment" model.

Things like:

\- Somewhere in the 1980's, when layoffs started to happen even in relatively financially healthy companies

\- The move from pensions to 401k's

\- The shift of a higher percentage of healthcare costs to the employee's portion

\- More focus on hiring outsiders into higher level positions, versus training/placing internal candidates

Specifically, I might be incented to occasionally "work for free" if I thought the company would, for example, not lay me off during a particularly rough financial period.

<comment><USER32> Ah, I see. Personally, I think it's a bit healthier regardless to see your employment as a fair exchange of time for money, and not read anything else into it. There's no confusion about who owes what -- it's all spelled out for you.

</comment></comment></comment></comment></comment></comment></comment><comment><USER33> Beware of poor web page performance: You will LITERALLY die from 1,000 cuts.

<comment><USER34> Lol</comment></comment>


Volcanoes on Venus are still active - <AUTHOR> https://phys.org/news/2020-07-scientists-volcanoes-venus.html <comment><USER2> > These results may help identify target areas where geologic instruments > should be placed on future missions to Venus, such as Europe's EnVision that > is scheduled to launch in 2032.

Russia has also been talking about renewing their famous Venera program for some time, which was the first human-made probe to land on another planet:

[https://en.wikipedia.org/wiki/Venera](https://en.wikipedia.org/wiki/Venera)

>> Venera-D is a proposed mission to Venus that would include a highly capable orbiter and a lander. From the standpoint of total mass delivered to Venus, the best launch opportunities occur in 2026 and 2031 Venera-D could incorporate some NASA components, including balloons, a subsatellite for plasma measurements, or a long-lived (24 hours) surface station on the lander.

<comment><USER3> the year is 2289. Russia fully occupies Venus. USA controls most parts of Mars. China has an estimated ownership of 80% of all astroids in our planetary system. Europe is still not aligned on budgeting and long term planning.

<comment><USER4> You're very optimistic if you believe today's political structures will have anything to do with what we'll have in 250 years.

<comment> maze-le > the year is 2289. Gazprom fully occupies Venus. Walmart controls most parts > of Mars. Cosco has an estimated ownership of 80% of all astroids in our > planetary system. Volkswagen is still not aligned on budgeting and long term > planning.

<comment><USER5> > spaceship software runs on Electron

<comment><USER6> It kinda does already. The displays in SpaceX capsule are chrome based...

<comment><USER7> Oh dear.

</comment></comment></comment></comment></comment></comment></comment><comment><USER8> I saw a fascinating documentary that said the entire surface of Venus is only about 500 million years old. Which implies that the entire surface was molten at the same time and has only recently cooled. 500 million years being "recent".

</comment><comment><USER9> I see great potential in manufacturing a probe that can actually continuously function in Cytherean environment. Gallium nitride seems promising!</comment>


Chesapeake Energy CEO Dies in Fiery Car Crash - <AUTHOR> http://www.syracuse.com/us-news/index.ssf/2016/03/pioneering_chesapeake_energy_ceo_aubrey_mcclendon_dies_in_fiery_car_crash.html <comment><AUTHOR> He was driving on a deserted road completely sober and ran into a wall....</comment>


The Birth Of A Really Bad Idea: Peter Thiel And Knowing Less As A Life Strategy - <AUTHOR> http://www.forbes.com/sites/billfischer/2011/06/28/the-birth-of-a-really-bad-idea-peter-thiel-knowing-less-as-a-life-strategy/

<comment><USER2> [Disclosure: I am a 20-under-20 mentor.]

I think this guy has it exactly backwards. These kids _are_ going to Greenland, which is to say, the real world, and hanging out with the Eskimos (who, by the way, do not actually call themselves Eskimos, which is one of the many things this guy would have known had he actually gone and hung out with them). It's the kids going to college who are browsing the Burberry catalogs. They come out with their shiny diplomas and their sparkling academic records, which make them look very presentable at interviews, but render them largely useless on the ice.

<comment><USER3> The author of this article seems to be under the impression that the _only_ way to learn "more about the world" or to tap into the years of accumulated knowledge, is to attend a traditional university. Talk about arrogance!

Learning is good, education is good, knowledge is good. I don't think Peter Thiel would argue against any of those statements. And none of them are incompatible with his program.

There are many paths to gaining knowledge, and not all of them include 4 years at a traditional university, immediately after high-school.

</comment></comment><comment><USER4> The 20-under-20 isn't about "no formal education". It is about formless education, which is different to no education. Formless education is a style of seeking knowledge, not just from formal educators, but Ali from practitioners who are not normally engaged as a teacher.

Bruce Lee had explained that having "no form" means having access to all the forms. But this is distinct from having no form at all, which is just undisciplined fighting.</comment>


Well Hello - <AUTHOR> https://www.os2museum.com/wp/well-hello/ <comment><AUTHOR> I submitted the HTTPS variant of the link but at least in some browsers (Firefox for me) the images don't work. So you might want to just use that HTTP variant if you are only there to consume information and not provide any: [http://www.os2museum.com/wp/well-hello/](http://www.os2museum.com/wp/well- hello/)

<comment><USER2> It's true, the images didn't show for me either. This is because the image elements all use a URL with HTTP. I believe this can be solved if you change the site URL in the admin/backend to start with HTTPS.</comment></comment>


Uber set to raise $200M at a $3.5B valuation - <AUTHOR> http://techcrunch.com/2013/07/25/uber-tpg-3-5b/

<comment><USER2> That disclosure is pretty close to a lie with its alternate-history of Crunchfund. Arrington started Crunchfund in AOL's employ with AOL's money, and then they cut a check to Uber, and then some time later an AOL employee wrote this story about a company AOL is almost directly invested in.

[http://www.nytimes.com/2011/09/02/technology/michael- arringt...](http://www.nytimes.com/2011/09/02/technology/michael-arrington- techcrunch-blogger-to-invest-in-start-ups.html?_r=2&)

</comment><comment><USER3> Isn't the valuation of $3.5 Billion a little too much?</comment>


Even Wikipedia Celebrates the April Fools' Day - <AUTHOR> https://en.wikipedia.org/wiki/Main_Page

<comment><AUTHOR> I really like the Osama Bin Laden and extraterrestrial spiders one.</comment>


A Queer Taste for Macaroni - <AUTHOR> https://publicdomainreview.org/2017/02/22/a-queer-taste-for-macaroni/ <comment><USER2> A different take on macaroni: The Macaroni in 'Yankee Doodle' Is Not What You Think [https://news.ycombinator.com/item?id=12356070](https://news.ycombinator.com/item?id=12356070)</comment>


At Facebook, Creating Empathy Among Cyberbullying - <AUTHOR> http://www.nytimes.com/2014/10/23/fashion/Facebook-Arturo-Bejar-Creating-Empathy-Among-Cyberbullying.html <comment><USER2> I find it difficult to believe the number of people who claim to be "just making a joke" were honestly doing just that, and had no offensive motives.

Isn't that the _classic_ response to offense? "I was just kidding!"

I'm guessing these folks were in CYA mode when they responded to these surveys. "Oh shit, Facebook is going to discipline me if I tell them I was being mean on purpose!"

<comment><USER3> In general, people experience an emotion first, take action based on the emotion, and then their brain covers up self-harmful reflections on the action by building a rationale for their action being appropriate. We can do this astonishingly quickly, enough so that other people will also believe that it was a reasoned action and not just an emotion.

</comment></comment><comment><USER4> I can't believe there is a team of 80 people at facebook to help people act nicer.

<comment><USER5> I believe i read once that facebook has highly correlated people's engagement when interactions are more or less positive. So it might make sense to have a team work on creating mechanisms that improve the interactions so they trend more positively. Though i'm sure its sold as facebook "just trying to make a difference"

<comment><USER6> Also: why there is no "dislike" button

<comment><USER7> Related: No down voting (for 90%+?) on HN.

</comment></comment></comment></comment><comment><USER8> _Interestingly, more often than not, the posts were not meant to hurt, but were jokes lost in digital translation. When Facebook asked people why they shared a post that hurt someone else, around 90 percent of respondents said they thought their friends would like the post or would think it was funny._

Even my dog knows the limits of that particular excuse. It's nice that Facebook is throwing some resources at this problem, but giving people stickers, really? Why not call in a linguistics expert like Deborah Tannen, or do some epidemiology-type modeling of meme transmission to see whether differently-freighted transmissions take different vectors around the network?</comment>


Bitcoin Auction to Find Most Valuable YouTube Video - <AUTHOR> https://www.mostvaluablevideo.com

<comment><USER2> This has been posted 3 times, all with suspicious voting patterns: [https://hn.algolia.com/?q=mostvaluablevideo.com#!/story/fore...](https://hn.algolia.com/?q=mostvaluablevideo.com#!/story/forever/0/mostvaluablevideo.com)

</comment><comment><USER3> ...why...exactly would I bid for a video?

This smells an awful lot like someone just trying to get people to give them money.</comment>


Microsoft Offers Price Reductions on Select Azure Services - <AUTHOR> http://azure.microsoft.com/blog/2014/09/25/microsoft-offers-price-reductions-on-select-azure-services

<comment><USER2> Looks like we took down the web server :)</comment>