I loveee the concept of drawing rooms with a mouse to enable spontaneous conversations. the site is incredibly wordy and doesn't drive a CTA, but that is really nice. when can I use it?
No everything on the internet needs to be about pixel trackers, A/B testing, micromanipulating users, conversion rates, ARPU, analytics and all that boohoo. Can we just pause for a second and be honest with our users? May be respect them? Try to make insanely great products that people have no other option than to fall in love with them?
In fact, I want to go to sites that don't lie to me and backstab me, treat me like some kinda of a ephemeral datapoint consuming their giant wad of VC cash.
In many cases A/B testing, conversion rates, analytics are used to actually improve user experience and create a better product. I don't think the problem is the analytics themselves, but what you do with the data. For example, you can see based on analytics that users spend more if feature A is implemented but they have a better experience and rate product higher if feature B is added instead. The stats allow you to have this insight, but then it's up to the company if they want to go for profits only or to actually create a better product.
Perhaps understanding the problem deeply, thoroughly and putting yourself in the shoes of the customer insteading throwing a bunch of semi-random iterations over the fence and squeezing every last bit of data from the customer's private behavior?
Imagine if I buy tomatoes from the grocery store, but they run an A/B testing on me to see what the customer wants - may be I prefer the 85% ripe ones over 95% ripe ones, the farmers watch the reaction of their users as they cook and taste tomatoes in a live video stream from their customer's home. WTF, get out of my house (browser). It is my private property. I just want a goddamn tomato (send an email or post a photo or read news).
What happened to user's privacy? That last mile optimization is bothering me as a user.
Server farms are weird concept to me. I feel the infrastructure the internet is build upon is a bit archaic and could use a more rewrite. not sure how though
I'm at the limit of my understanding myself, but here's what I think is being said:
CRISPR refers to the kind of DNA site that can be targeted for cleavage, while CAS9 is a protein that, paired with an RNA matching that site, can cleave wherever it encounters a matching sequence.
I think these guys are pairing a variation of the CRISPR approach with a laser. They pre-bond with the DNA, but the actual cleavage occurs when they shine a laser at the right frequency at the site. That lets them decide when and where on the DNA strand cleavage happens.
If anyone understands this better than me, I'd appreciate any corrections to my explanation ;P
The RNA guide (sgRNA) is chemically caged here, so it has some molecular decorations that are removed with light. The sgRNA can't fully match the underlying DNA it's recognizing until those decorations have been removed with the laser, at which point Cas9 then cleaves the DNA strand.
Think of the sgRNA like a regex pattern. Cas9 is like the regex engine here (but instead of capturing a group, it cuts the sequence), and DNA is the search space. In this system, we essentially have a full match, and Cas9 is in position (having found the match) but it can't cleave yet, because the decorations are blocking the way. As soon as the decorations are removed by light, the sgRNA can move down into a full match, and Cas9 then cleaves.
Ah, thank you. So is the benefit of this system that the Cas9 sticks around for a while, and at any point one can cleave all the sites at once instead of cleaving each as the Cas9 bumps into it?
Even in standard CRISPR/Cas9 systems, Cas9 sticks around for quite a while - which is one of the issues in using it for actual medical treatments. You don't really want a programmable DNA cleavage engine roaming around in your nucleus...
The primary benefit here is that you can temporally synchronize Cas9. In standard systems, you introduce Cas9 into the cell, and you have no control over when it performs cleavage, since it's essentially a greedy cleavage mechanism - as soon as it finds a match, it cleaves.
This system basically introduces a semaphore, so that you introduce Cas9, allow it find a match and pause. You can then signal for cleavage to begin. As stated in the abstract, this is useful for e.g. studying the kinetics of DNA repair, since you can control when DNA damage (Cas9 cleavage) is happening.
I am fortunate to have had a colleague explain it to me but this is my understanding as well. Normally the cleavage would take time with possible undesired effects as a result of the process.
The Cas9 protein (from the CRISPR system) has 2 functions:
1) It binds to DNA based on where a template RNA strand matches DNA in a genome. That RNA strand has 2 pieces - a piece that attaches to the Cas9, and a piece that matches whatever sequence of DNA you want to bind.
2) It cuts the DNA it has bound to.
(The first property is very special to Cas9. The second property is actually pretty common. The common intention in using Cas9 is to cut DNA at a place that needs editing and hope the cell's own repair machinery fix it properly.)
Important to understand about biology/chemistry, things rarely happen "IFF and only IF", but more often, happen at a rate (i.e. 1 event per microsecond).
So better more true functions of Cas9 are actually:
1) Cas9 spends a larger fraction of time near its target sequence than it does around random sequences.
2) Cas9 cuts DNA ever 1/N timeperiods, and that might be sped up when it is attached to DNA.
So Cas9 should hang out around its target sequence, most of the time, and that the cutting event happens relatively randomly. So _in general_ Cas9 will cut at its site of interest, however, it will also cut elsewhere, purely statistically speaking. And if you want to be guaranteed a cut at your spot of interest, you're likely to get cuts elsewhere ("off-target" cuts to DNA. These are undesired as you really don't want random changes to your DNA that you're not asking for...).
----- now comes the paper -----
If you make it so Cas9 cannot cut because the homing device is kinda kinked or boxy or otherwise not quite right (but it is still able to home in on particular sequences of DNA), you can make it so Cas9 runs around and finds where its supposed to be, but just hangs out there; Function 1 still works, but function 2 is turned off. These scientists made a special version of RNA that only permits the Cas9 to work when light is shined. So the RNA absorbs the light from a laser, breaks a seal, and the Cas9 snips right then and only then (in a matter of seconds). And any Cas9 molecules that did not get light cannot cut - they just continue to hang out and don't do any damage that they otherwise might do, statistically.
If you're trying to cut a specific sequence and only a specific sequence, this increases the statistical chance you are correct by shortening the time period (and spatial localization) when Cas9 can actually take its second, cutting action.
CRISPR systems are molecular "scissors" you can use to cut a particular piece of DNA right where you want to, which is useful when doing gene editing. Usually, you put the scissors inside the cell, and it just sort of goes and cuts on its own timeline, you can't really control it. Here, they've designed a pair of scissors that will go right to where you want to cut, but then just hang out there not doing anything until you give the signal. When you give the signal (activation by light), the scissors make the cut "on demand."
So before, if you want to study/control the processes that go on after that cut, you'd be a bit out of luck since you didn't know when the cut would happen to start experimenting, it would be a hard messy problem. Now, you can just trigger the cut to happen right when you're ready for it.
Hi, We have posted on a couple of sites looking for feedback. We intend to analyze the source of our visitors and their feedbacks. We can filter the sites where we get valuable feedback and ignore the rest in the future.
it is a digitalized version of a college lecture is a terrible format in the first place. instead of taking the liberty of the internet and of the online world, it just brings the old methods that don't even work offline into the online world.
we need classes that helps us learn through collaboration, memorization, and practice. and I feel the internet can give us that. but Moocs and online classes do not.