skysight-inc/HackerNews huggingface dataset:
I think this explanation is missing the real explanation of why CRISPR is useful.

I want to take a crack at it. Let's say we want to change in the genome the sequence (where each of the 'letters' represents a somewhat long stretch of base pairs):

ABCDE to ABC'DE

you would normally create the sequence

BC'D

in vitro and put it into the cells. The organisms contain mechanisms to match the B & D sections and thus 'swap out' the C section for the C' section.

Note that C could be "" which would make the process a straight insertion. C' could be "" which would make the process a straight deletion. C and C' could be a single base pair, which would mimic a point mutation, etc...

However, you don't have TOTAL control over this process, it's stochastic, and doesn't have 100% efficiency. So you have to do something clever to make sure you have what you want. Typically that involves inserting resistance to a chemical factor (e.g. antibiotic). So for insertions (if you don't mind a dirty insertion) it's fine, but for other transformations like mutations and deletions, you might have to be clever, and say, do C -> C' -> C'' where the C' includes the selection factor. And C'' is chosen either because it lacks a toxic factor that we put in alongside C' or by doing a reverse selection where we pick clones and test to see if they die (and keep some of the originals in case they pass the test).

This process generally works quite well in most microbes with small genomes (E. coli requires a tweak to the process). It is basically effortless with yeast.

With higher eukaryotes it's not quite so simple. A competing process is inserting the BC'D sequence elsewhere in the genome. It's not entirely clear why this is such a huge problem, but likely it's because of the increasing complexity and size of the genome. If C' contains a selectable marker, it becomes difficult to distinguish between what you want (ABC'DE) and just BC'D somewhere random in your genome. Both are resistant. And the process becomes bogged down by the need to isolate single cells, propagate them, and check to see if your strain has the substitution you want (relative easy, just a PCR reaction) and no other substitutions elsewhere in the genome (haaaaaaard).

The CRISPR advantage is that just before you add BC'D to your cell you create a scission somewhere in C so you're left with ABc//cDE - and what this does is triggers the cell repair system to search for B & D sequences to hook into. Naturally it will find BC'D. Well, if it doesnt, usually a fragmented chromosome will also result in death of the cell, so you're virtually guaranteed that the surviving cells have ABC'DE. With this, the rate of successful targetting so exceeds the rate of random insertion that the necessity to check is basically eliminated (or at least you don't have to search through so many clones to pull out a total success).

The net effect is that for many higher organisms genetic manipulation becomes much much much easier. YMM(still)V with some plants which have high level of repeats within the genome.
What is the technical blocker to installing OpenBSD without a FreeBSD shim, e.g. is there incompatible code in the OpenBSD installer?
When did this happen?

In my experiences, Youtube these days are pretty responsive to even the small guys in settling out problems of this nature.
What's even funnier is all the attacks aimed at Kirksville. What a funny little one-horse town that is.
This NYC Startup Is the Online Classified for Your Building or Neighborhood
> I am not aware of any statistics on this subject. How exactly this is related to my observation?

Its related to the validity of your "observation", in that, if teaching to code is not a female-dominated activity, your "observation" that she chose a female-dominated activity is false.

> All engineers I know who worth their salt acquired their skills mostly through self-education and lot of practice, and the process was gender-independent

Oh, well, if we are going to do dueling anecdotes, all programmers (even if including that population within engineers is proper, there are a lot of engineers outside of that group, and I'm not talking about them, since this is about teaching coding, not teaching engineering in some general sense) worth their salt I know started by being taught by someone -- usually in school or a similar environment, though sometimes tutoring by a family member with experience in the field played a similar role -- at a fairly young age, and then, after developing an interest there, proceeded to choose further education -- both guided and autodidactic -- and lots of practice.
The process for enabling the current (opt-in) two-factor verification is described here: https://support.apple.com/kb/PH14668?locale=en_US
That's a valid point! It could be. I wasn't offended, but it's an anecdote that supports the idea that women aren't seen as being programmers. Other examples: going to conferences and being asked if I was covering it for a blog. Also not a big deal, but it illustrates the stereotype.

Likewise, if a man goes to a nursing conference, or a conference for elementary school teachers, he will likely face the same sorts of misunderstandings.
How to Jump into the Deep End of Change
Afaik FB actually tells Page owners that they prefer native content.
There is a bugtracker. It's just a very lowtech one, in the form of a) a form on the website, b) a mailing list.
Yup. Neato!
Interesting! But wait a second... how does this work with prepaid cards? Do companies need to preload funds onto the cards before employees can spend them?

E.g for an employee to spend up to $5,000 on a trip, would the company have to preload $5K onto the card? Or alternatively would employees have to get approval for each expense in advance of spending it?
Most companies will make plans to deal with associated problems, though, particularly when the company dictates the timing. I would expect problems if an employee suddenly quit without notice or became somehow incapacitated, but reddit seems to have made no effort to cover her job. It's as if they didn't realize what she was doing.
Because here, in the post-industrial world, it's very hard to make a living from one-off works of craftsmanship. That didn't used to be the case, when that was the only way to get things made. It happens today, but the economics make it an unusual situation. The labor involved forces the per-unit prices to be stratospheric, vastly limiting the market.

But we have an alternative: leverage digital technology's nigh-zero marginal costs and charge very reasonable prices to large numbers of people.

The idea that because the marginal cost is zero that the cost should be zero is a horribly greedy devaluation of creative labor.

So I'm all for new economic structures, but AFAICT no one's stepped up with a better way that's actually proven to allow creative folks to continue to make a living. (Or that even has a snowball's chance once tried outside of armchair philosophizing.)

One last thought, since it's universally sizable corporations who control those digital distribution channels... do we REALLY want to cede even more power over content to these entities? If we just drop IP laws, that further enriches these corps at the cost of individual and/or small creators. That makes no sense to me whatsoever.
I suppose you're forgetting that one of the most popular Windows releases didn't support Internet connectivity out of the box.
Highly offensive? I haven't heard that before. It seems like a pretty good term for what it describes.

Is this a case of people not liking a term that is used to call them out for poor behavior? Such as saying bigoted things and then objecting to being called racist?

I haven't run across someone calling it 'highly offensive' in the time since I learned it.
Here's a recent Ask HN thread that might be relevant:

https://news.ycombinator.com/item?id=9836508
I really wonder if it's just a matter of time before you get clans of technology in bio. Akin to the PHP vs Ruby vs Node vs Go evolution.

At the end of the day, they are just tools, and tools however technically shiny, don't by themselves deliver better end products.
Network effect. Google blocks non-GMail email, eventually you are forced to use them as your service provider. Can either be deliberate or happy unexpected outcome for Google.
5.8 is still currently in development/snapshot - not for amateur users.

5.7 is the latest official release. 5.8 is due on Nov 1.
Its use in this case demonstrates why it's highly offensive. It's being used to label someone's opinion as negative and discount it for no good reason.

Attaching words with negative connotation to a specific gender is highly offensive.
A reproach to internet
Playing+Startup
Load of bollocks.
First, it's about triggers. You are not allowed to carry guns on an airplane. "But I didn't shoot anybody." You didn't, but the people who do, carry guns. It's a negative trigger.

Second, when a technology becomes extremely mainstream, it begins to generate federation and structure around it. It's called evolution. This is higher in services where stakes are higher, and where giving an individual excess power can screw up other individual's lives. It is the same reason you cannot install your own cell tower. You can start a tiny in-house telephony service, but you cannot complain if AT&T declines to integrate with it.

Third, the openness is a wild, wild west concept. If openness allows him to install mail server, it also allows Google to block it.

Fourth, you underestimate the amount of turtles the spam cave has. A lot of very smart people, leave mail servers on for years sending only a few emails before using it as a spam weapon. These servers can be rented for high price on the black market. If you were a measly C++ program, it is impossible for you to distinguish his good motives from a bad person. From what Google knows from 99% cases, this server will start sending spam any moment now.

Fifth, you underestimate the effect spam has. This guy suddenly starts sending out phishy Apple looking emails, asking people to change password. Next thing you know, Jennifer's pics (or your wife's, or your daughter's) are online.

We, as hackers, drink way too much Kool-Aid.
Not to mention, their hawking their own service. Makes it hard to really trust the article itself.
Ousted Reddit Employee Victoria Taylor Finally Breaks Her Silence
Microsoft waves the white flag in battle with iPhone and Android
And with this, I hope we'll see a race for GC pauses improvements.
I have been through this, and the end result is a contact form that no one responds to. I filled it out a few months ago and again this week.

DMARC is enabled (and in one of the screenshots, Google shows it passing). I get reports from them, but it provides no insight into their decisions.
Inhaled Ribavirin Appropriate Use
Ask HN: Our Project Partner Is Resigning – Future Liability Question
I have been working on a SaaS product / website for 13 months in my spare time (evenings and weekends) with a friend, we have finished the product and are now ready to launch but due to health issues and fundamental differences about the future of the product my partner wants to resign from the project and hand over all equity / have nothing to do with the project anymore.

The domain name is the only real asset that he controls & before transferring it over to me and relinquishing future claims over IP / ownership, he wants me to sign a legal document which releases him from all liability which he could be exposed to from launching the website, the document states that if he ever got sued that I would need to cover all of his legal costs, without a limit, which seems odd.

We have only operated through an informal partnership (we both signed a letter which defined our roles & equity ownership %'s).

I wanted to ask others who have done this before, is this normal? Is there anything else that I should do in this situation?

Thank you in advance!
> Anyway, I'm hoping that the new static typing proposals can help make Ruby's tooling better.

Probably not. Keeping the language in place and focusing on tooling would make the tooling better; as others have pointed out, there are dynamic languages with better tooling.

And, its not like people who want the costs and benefits of static typing are ill-served by the current marketplace of computer languages.
Charles Manson's ex using him for his body
Many of the terms we associate with "the end of the world" have meanings which amount to "revealed truth": revelation, apocalypse, enlightenment, catastrophe.

The upshot of each is that your previous understanding of the world is overthrown. It's not so much that it's the world which has ended as your worldview.

Mental models are difficult and expensive to construct. It takes an entire childhood and adolescence for humans, arguably a fair bit of adulthood as well.

Leaving those comfortable confines, even where they're wrong, is pretty distressing. We'll often work hard to re-shoebox reality into models to which it fits at best poorly instead.
Why on earth wouldn't your mail server add that for you?
I think it's offensive. Imagine if we had a phrase called "womansplaning" to describe someone who sounds uneducated about the subject they're explaining, Would that be ok?
Ok, so what term would you suggest for discussion when a man talks down to a woman to explain something they already know (possibly better than the man) while trying to be 'helpful'?
That's already happened with NG DNA assembly. PIPES cloning vs. Gibson Assembly vs. ColdFusion, etc.

In the case of restriction enzymes, though, they've been around in continuous use since something like the 70s, they're very well characterized, NEB has had a continuous research program where they've been optimized out the wazoo.

Technically speaking they are fundamentally simpler than CRISPR (one component, vs. 2). They also are more generally useful when your genetic manipulation is done outside the cell. So there's a clear tooling difference in CRISPR/RE. Most people who use CRISPR, will use REs in the process of make the DNA piece they're putting in alongside the CRISPR. You'd be a fool to use CRISPR in E. Coli or Yeast.

So 'clan'ing ain't gonna really happen here.
> The author jumps to an unfounded conclusion which is pretty irritating and probably will make everybody who could help him not want to help him.

Apologies if you took it as a conclusion, it was only hand waving speculation, but google does have an incentive to make it difficult for the little guy...

> Gmail either rejects spam at SMTP DATA time, or delivers it to spam folders.

They do if you have DMARC enabled, and a REJECT policy, although they still seem to ignore it sometimes and I have no clue my mail is sitting in a spam box.
Out of curiosity, what is wrong with Qt's open-source version?
In my experience introducing loaded terms generally kills any useful dialogue pretty quickly. Instead, why not acknowledge that you understand the parent poster's points / story, and then explain why you disagree with what they have to say.
"As previously explained, however, in-order updates (i.e., better crash behavior) are not practical in multitasking environments with multiple applications."

They say this is the obstacle to the best approach using the same interface. I say look at our best results in DB, concurrency, and distributed computing research to see if there's a solution that might work given a certain number of cores or applications. There's also the possibility of processor enhancements that put this sort of thing in the I/O architecture.
Thanks, I just assumed their whole block would be blacklisted. I'll try some more.
"There’s even a term for the useless software that people make: vaporware. The idea is that it’s created, and then it evaporates because nobody works on the project after the hackathon (despite everyone’s best intentions)."

Has anyone ever heard this definition of vaporware before?
£7.20 is a sick joke. Perhaps the punchline should be that MPs be paid this "living wage" with no expense allowances (because few of us get chauffeured around for free).

They might set it to something sensible then.
Anecdotal information:

I run my own mail server and manage a number of small business clients who have mail servers. Email trust is getting more and more tedious.

Recently I was resolving a domain registrar issue with Network Solutions. They required forms filled out and signed, a copy of a utility bill from my client, a copy of my ID...

I bundled up everything and emailed them the scans. I contacted them 5 business days later, they claim to never have received it.

I sent it again while I had a rep on the phone, it went into their spam hole, probably due to size of attachment.

They helpfully suggested I get a GMail account to send the same message.

They are my registrar, they host my DNS, including my MX record. I have an spf record...

I thought it was pretty farcical, and a sad statement of digital trust/authenticity.

Some of my clients are giving up and just going with the flow, I have had several conversions to Google/Microsoft cloud-hosted solutions for email...
Have you thought about Heroku free tier?
Interesting.

BTW, there is a glitch in the animation. One city -- Lincoln, Nebraska, I think -- does not expand smoothly.
Nothing. Since that's a fabricated situation being used to justify the existence of the word.

Two people have a conversation. Sometimes one knows more than the other, sometimes the person that knows less is unaware of that.

I don't think that needs its own term and if it did have a term it absolutely doesn't need to be a gender based insult.
Seems like the reaction will need to be (in order to combat/penalize this): Any app which does this sort of thing will automatically get a Play Store/App Store 1-2 star review. Even if it's otherwise a great app.

Engage in dark patterns/socially abusive behavior? Deal with the repercussions.
Application for Open Source Project Subscription
- http://resources.xamarin.com/open-source-contributor.html
Postgres for your website, SQLite for the mobile.
You guys should check out our high performance GPU graph processing library, Gunrock: http://gunrock.github.io/gunrock/ We are working on multi-GPU distributed version now.
For that example, there's no question it was licensed. Russell Brand writes for the Guardian. http://www.theguardian.com/profile/russellbrand
I remember the very day that PG, Khaled, and James sat down in 2012 and defined the future of Tilt. Amazingly exciting to see how it's grown since. I love that the nicest founders in our batch are doing the best :)
> Ok, so what term would you suggest for discussion when a man talks down to a woman to explain something they already know (possibly better than the man) while trying to be 'helpful'?

I think its unwarranted, and arguably sexist, to put that characterization, regardless of the word used, on the question offered upthread along with an anecdote that provided context.
BaseKB Gold Ultimate – Replacement for the Freebase API Shut Down by Google
Except automatically deciding what buildpack to use, what does it offer more to have official buildpack ?

I mean, when you know about Heroku's buildpacks you have access to all of Heroku raw power.
Sort of off topic, but I saw an ad for prgrmr.com on a Safeway checkout conveyer belt divider in Mountain View, CA On Shoreline road near Google. I was wondering how effective this advertising has been.
Neat, he's even got the pinched hysteresis loop going on.

The first talk I ever gave was on Memristors at a Rochester Bar Camp in '09 as a college freshman: https://docs.google.com/presentation/d/1GVqEeFUJyI7VmzqYPabQ...
Mia Freedman copped a bit of flack for saying somethingn similar: http://www.smh.com.au/entertainment/tv-and-radio/mia-freedma... and has published about this issue on her site http://www.mamamia.com.au/social/19-year-old-pedophile/
If someone said "I know! Women complain a lot, so we'll call it womplaining!", the Internet would be filled with rage.
Is there any such thing as part-time freelancing? I have weekends and 2-3 hours a day that I can give. In total, I believe I can give about 20 hours for sure but I am not sure if that's something people like. What are your views on this?
You can't assume the videos are owned by someone just because they uploaded them first - many videos are ripped from other sources and uploaded first by unlicensed parties.

They followed the same procedures as described in the DMCA (even if this probably wasn't an official takedown request): if someone claims they represent the copyright holder and the videos are infringing, the service provider must take them down expeditiously.
I would like to use prgmr.com because I appreciate the no-nonsense way they seem to do business but (especially with the now-worthless Australian Dollar) they're so much more expensive than DigitalOcean.
The point of the term (as I understand it) is the situation where someone one in the majority explains something to someone in a minority that that person already knows, possibly quite a bit better, ending up bro condescending while possibly trying to be helpful.

Since that seems to be a very frequent occurrence for men to do to women (relative to the reverse) it seems fair to me.

Let's take a different context. When southern white racists would explain to African Americans in the south how they were well treated and free after the civil war (say the 1930s) would a term like 'whitesplaining' not fit?

Seems like a clever portmanteau to me.
I've had the same problem myself.

My best guesses as to why my domain has been dinged:

1) It's on a VPS, that IP may be flagged already

2) I often use a VPN, and sometimes send emails out through my server using it. This probably raises the red flags.

3) It's a non-standard TLD, .co

4) I don't use any Google services with that email address/domain (I assume doing so adds some level of measurable trust)

5) I'm not in the address book of a lot of gmail users, because this is my private server, that I use only for job seeking, and personal communication.

This has really done damage in the past. I've applied for jobs, and heard back weeks after they hired someone, letting me know, woops, I ended up in their spam folder.

Trying to meet with a friend? I can't email them, I need to use Facebook or Gmail... welp.

This is super annoying. I kind of understand why it happens, but it's just a little sad that building your own fort, so to speak, is so impossible.

Things I tried to do to mitigate this:

1) Made my web domain https only (why not?)

2) set up DKIM and SPF (didn't seem to have any effect)

3) proper SMTP authentication, secure port only

4) Reached out to Google via the typical forms they offer, and heard nothing, obviously.
The LM80 will show a much higher number, but in reality, it's usually the drivers that fail much sooner.
I'm still surprised at the level of efficiency, but glad to hear that you can back it up. I wasn't doubting that an underdriven LED would last that long, rather I was surprised that the remote phosphors would last that long without decrease in output. But reading more elsewhere, I now see that the lifespan of the remote phosphors can be excellent: http://www.digikey.com/en/articles/techzone/2014/apr/develop...

For others who are interested, here's another interesting link on the remote phosphor approach:

http://www.ledsmagazine.com/articles/print/volume-9/issue-7/...

And a nice overview of the efficiencies of white LED's, and where the losses usually are:
http://www.sandia.gov/~jytsao/SSL_Trajectories_Proc_IEEE.pdf

The exact figure in the last are already somewhat out of date, but if you plug in the specs for the newer LED's, presumably the underlying physics hasn't changed.
Rare system of five stars discovered
Also see the new definition of shareware: an app going viral because so many people are sharing it.
Ask HN: Would love your feedback on my artificially intelligent resume
Maybe YouTube can make it easier for content owners to flag FB content. Or maybe YT can ask the content owner for transfer of ownership (i.e. buy it from them), so they can then turn around and sue FB for violation?