from Washington D.C., it's theCUBE, covering .NEXT Conference, brought to you by Nutanix. Welcome back to .NEXT everybody inside the district, kind of, this is Dave Vellante and Stu Miniman. We're with theCUBE, the leader in live tech coverage. This is day two of NextConf. Aditya Sood is here, he's the director of senior director of engineering and product at Nutanix and Benny Gill, who is the chief architect at the company. Gentlemen, welcome to see you. Welcome to theCUBE, good to see you again. So you guys had the great keynote. It was, I love how D. Raj interacts with you on the stage, asked you these Colombo questions, even though he's deep knowledge of what's going on. It's really quite good, but Benny, let me start with you. So first of all, what's the show like this year? You know, we've been, now this is our third year doing Next, we've seen quite an evolution. From your standpoint, from the hardcore product side, what are you seeing? I think it's exciting to be here. This year, we're seeing almost every year doubling of the attendance in the conference and also the excitement that we hear from our Nutanix technical champions and our customers is a lot more visceral in terms of how much we are doing, in terms of vision and mission. And as we are executing on our vision that has always been, you know, are you sure you can do it kind of thing? But as we deliver every year, there's more conviction that we are seeing from all these people here. So it's really exciting. But D. Raj, I wonder if you could talk about calm a little bit, I mean, it's your baby. And people say calm, I'm calm. Who's going to the joke going around today? What is calm? So calm is many things at once, but most of all it's a control plane at the application layer. How do you build this multi-cloud, hybrid cloud technology together and manage the entire life cycle, you know? Compliance, governance, provisioning, costing, visibility, all of these things together. And Aditya, there's many companies that have attacked this challenge. Why did you, when you help Co-Find and Found Calm, think that you could address this and bring us up to speed as to the acquisition last year. What has been, being part of Nutanix, what did that do to the product itself to lead us to today? I think, addressing the first part of your question, why we think this is different, right? Many people have tried to do these blueprints and these things over the many decades. Automation's been around. But I think this is fundamentally 10x to 100x better because of the logical approach we're taking, the data model we have built, which models applications, and tries to keep the logical layer separate from the physical layer or the virtual layer. The second part of the Nutanix integration was homecoming. This was, I mean practically nothing changed from our point of view, except that we got, became part of a much bigger family, a lot of warmth there, a lot of technical goodness, a lot of, I would say, systems level and platform goodness that got leveraged in. So it's been all pretty great. For the last, say what, nine months or so? All right, Vinny, want to get your viewpoint. Of course Nutanix has been growing its ecosystem. We've got a big expo hall with a lot of partners there. What were the goals that you wanted to make sure you hit by the time we came to this show with Calm to kind of meet your customers in this growing ecosystem? Yeah, I think what we're looking at is explaining how we're building an operating system. An operating system is a platform for running applications. And now the platform for running applications is in fact changing. Earlier it used to be Linux and Windows, now it's Clouds, Cloud is an OS. And when you talk about building OSes, it's about ecosystem, it's about the drivers, it's about the partners that build stuff for you. Calm is a way of inviting them to a marketplace. The repository for where you put your stuff. Calm is also your yum in an app get tool. You know, one click deployment of any application. The more simple you make it, more developers will be attracted to your operating system. So the message here is look, we are developing a marketplace, bringing Calm to the picture, giving you an operating system that can run on any hardware, hardware meaning any cloud, any hypervisor and so on. How much can I ask, how much, how much did that one click, if you think about the life cycle of what has to occur in that one click. And then by the way, everything else that you don't do, how much time do you think you're saving people? I mean, take database as a service. Yes, one click, but then you got to do regression testing, you got to do some recovery testing, but you're taking away a lot of the planning, presumably, do you have any sense as to, if it takes a hundred, how much you just shaved off with one click? Yeah, I mean, Aditya's the best person to answer that question. His team has been working on this for seven years. And this is something that again, touching back on what Calm does differently, that it understands that provisioning your application is only the beginning of your problems. You have an application, now you got to grow it, scale it, it's going to blow up, you need to upgrade it, test it, certify it and all that stuff. And that's where the application life cycle management part comes in. As a rough estimate, I would say, at least 70 to 80% of the complexity has gone away. There is still some complexity, because there is an essential complexity in every problem. Cannot reduce it beyond that. Right, say, off the ballpark, 70, 80? I like that number. So I've kind of baited you. The practitioner that we had on today said at least, at least, and he's being conservative because that's what IT guys do, he said at least 50%. So we can fairly say, let's say 50 to 70%, you've just taken off the table, so he can now focus on higher quality testing, recovery, and even in the fun stuff, as Stu likes to say. Absolutely, and Aditya, there was a joke in the keynote that this is not an app store. So what do you see, the one click obviously is a critical piece, but how is this different from, think of the Amazon marketplace or other, we've talked about do we need an enterprise app store? How is this different? How do customers perceive this? What early feedback have you been getting? I think one of the problems that we are trying to solve and how we are looking at it is every platform, let's say every public cloud, every private cloud, they have some amount of tooling and automation already built in. But from a customer point of view, these are all just different independent silos. So if you go look at any, you look at the AWS marketplace, it's for AWS only. And what we are trying to do is, this is means to an end. I'm running five different kind of infrastructure stacks. I want a single app store for my consumers internally. My business user doesn't care where the application is provisioned as long as we can drive them the rise SLAs and cost ROI for their internal application. You know what's important about this? I wonder if we could sort of riff on it for a bit. So we weren't the first to say this, I think it was probably Benioff, that more non-tech companies will be SaaS companies than tech companies. So that says that they need a stack to build their SaaS. So that marketplace that you showed, you had Cassandra and Mongo, Mike Sequel and Redis and TensorFlow and all these tools that will allow a SaaS provider to build their own stack. So I wonder if we could talk about this a little bit in terms of the vision of the next generation company, not just tech company, and how you see yourselves fitting into that as an enabler, comments. I think as an analogy, I like to think how the electronics industry evolved. And back in the 70s and 80s, the semiconductor explosion happened. And any kind of functionality that I wanted, I looked up the catalog, I looked at the cost, the yield rates, the functionality that chip provided. I just went and bought those chips and I plugged them in and I built my bigger appliance out of it. And this is how I think that this is going to evolve. That we are going to just move the level of abstraction while in higher level, have these reusable fundament components, compose them together, and have a faster time to market. I mean, as an application developer, do I really need to understand how MongoDB scales and how it's provisioned and how it's backed up and everything. I want a single API or a one-click experience equivalent in my view to just plug it into my application and then go on from there. And then take this my application and deliver it as a unit to my user, which can then go ahead and just like Lego blocks, keep building higher and higher layers of functionality. Yeah, Aditya brought up a key point there with APIs, right? Anytime an OS is developed, after some point you have to talk about what is the standardization of APIs on top of this OS? Like POSIX was a standard of APIs in an operating system. This new cloud operating system is actually asking for a standardization of APIs so that the applications built on top of it can enjoy a guaranteed stable API that will be portable across various hardware and clouds. We are seeing the beginning of that kind of API with the work that Aditya's team is doing around App Blueprints, App Lifecycle, that's coming to the fore right now. All right, Aditya, one of the things I usually hear after a company gets acquired by a bigger company is just the amount of feedback they get from the customers. Nutanix is a little bit self-selecting, customers usually that are looking to try something different. What's been your experience with the Nutanix customer base? How has that impacted or shifted where you were looking to drive the product? It has certainly informed the product roadmap, but I wouldn't say it has fundamentally changed it because one of the key things and one of the great things about Nutanix is that we are building open systems which is why even in the keynote that you saw, when we are going and provisioning an application, we are not saying this is Nutanix only. We are treating each of the compute platform at an independent, equivalent level. And that was our vision right from the start, that bring the goodness at the top layer and then leverage some deep platform stuff. We can obviously will work best on Nutanix because we get underlying data from the storage systems, our virtualization systems and go run on that. But yeah, fundamentally it has not really changed anything. Ambitious. Yeah, Vinny, the question I have for you is if I look at the public clouds, they all want to own the applications in one way or another. Google's probably a little bit more open, but Microsoft, lots of business apps, Amazon, the next generation apps, how does Nutanix look at that app ownership? Obviously come from the infrastructure side, but how does your viewpoint differ from some other clouds? Our viewpoint is more like how players like Apple look at owning the app. I mean, you have an app store or a marketplace, but that is sort of democratic. I do have my own apps. I could have my mail app, my camera app, but I am neutral in the sense that I enable others to create a better app if they can because it only helps my platform. So we are in the business of creating the best in class operating system. We're calling it enterprise cloud operating system, and then enabling that cloud operating system to run on any form factor, any hypervisor, hardware, or going all the way to the edge, as you might have talked to others in this conference, our cloud operating system can run on a single node now, down from three nodes to two nodes to one node to an Intel node in a drone. That is where we're going, enable everybody, and now on these various form factors, different applications would run. I would say a small fraction of the applications that are key to most customers to get to 80% of their simple use cases might come from us, but a majority of the use cases would come from outside, and eventually we look at this as we primarily building the OS and the world building an app store or marketplace on top of us. All right, Gents, we have to leave it there. Thanks so much for coming on theCUBE. It was really a pleasure seeing you again. Thank you. Thank you. Thank you. Okay, keep it right there. Stu and I will be back with our next guest right after this short break. This is theCUBE, we're live from NextConf in DC. We'll be right back.


Hello and welcome to Harsh Critique. Every single time I do one of these I feel like I want to pull my own hair out and I'm sure today won't be any different. Today we're doing a Patreon requested critique of an SCP article so let's dive into it. All right we got the item number, we got the object class oh I'm not yeah not optimistic already just from look at all the addendums one two three four five six seven eight addendums I can't possibly be good it there's eight addendums but the description is what three sentences long oh god all right well let's dive into it I guess. is to be contained within a humanoid containment cell with a lead lined form fitting box that's not what a bot no nope what you're meaning is a lead line box probably with foam on the inside to fit it yeah that's what's what you mean and it's what you should say if that's what you mean access to SCP xxx for any reason comma yeah that's a weird sentence structure you've got going on there access to SCP xxx for any reason pause is restricted to those with level three clearance and above it's only to be moved from its containment when reality anchors are set in place and turned on is required to be moved containment cells once a week under the supervision of the project lead I don't mind you having the project lead for this because instead of a named person which is what a lot of people do but you capitalized the project lead as though it's a proper title not to mention just basic grammar is required to be moved containment cells once a week I think you mean is required to be moved is is required to be moved is required to be transferred between containment cells probably oh god if project lead is unavailable at the time when begins to show signs of unrest emergency powers are to be given to the senior researcher on site emergency powers to do what it doesn't explain it just goes right into failed transportation what you can't just say emergency powers and what do you mean oh man any failed transportation is to be documented in any personnel present at the time of failure are to be quarantined and contained as instances of SCP xxx-1 uh that wasn't a laugh that was a cough that was a laugh these instances of SCP xxx-1 are to be held at site 88 nice uh site 88 is the site that I write a lot of my articles into my restless nature of SCP xxx is noted during test log three what don't tell me that in the special containment procedures that has nothing to do with the containment procedures the restless nature also that's super off tone your tone's kind of iffy to begin with but it wasn't enough to be pointed out but the restless nature is super bad clinical tone jesus note as any special containment procedures what you don't need to differentiate if there's a separate set of special containment procedures covers everything it doesn't just I mean and you've already got it covering the SCP xxx-1 in things I guess what you're trying to say is like maybe the dash two instances is sort of a new thing but even if like I wouldn't make a differentiated like a bold big bold title for the second set of containment procedures but if you're gonna just be like new stuff is going on that kind of thing not what you have when further yeah because it's when further information is after this will be updated to reflect such events just say that at the beginning like you don't even need to you don't need to preface it with a bold note description oh man I read it had a little bit in my head here scp is an oval shaped container resembling an egg with markings and engravings of unknown origin scp xxx is currently unknown scp the scp is currently known to only be active when touched by human skin living or otherwise come on you can it's only active when it's touched by human skin what does active mean you can't just skip that part this draft come on currently undergoing testing and research due to the circumstances of its discovery of course that means you must immediately go into an addendum covering the discovery which you don't even need an addendum for you just put in the description proper after you finish describing your anomaly what's anomalous about this it's just a it's just an oval it's just an egg it's another fxxk an egg and here we abandoned clinical tone entirely great the scp was found visited on the desk a high ranking member of the o5 council when the council member walked into her office at the beginning of the day it was simply waiting for her simply she immediately called an anomaly containment team to remove it from her desk when the team arrived on site they attempted to move clad with standard anomaly clad with mother fxxker anomaly removal gear standard anomaly every anomaly is different this is the problem with the idea of thinking there are standard things you can do that's the whole point of the scp document as a as a concept right is that there is no standard you can have a few little things but like uh let's put on our anomaly removal gear oh like that's an actual thing of course it's an o5 member a high ranking member of the o5 council by the way not just any member because the o5 council is literally the highest ranking members of the foundation like o5 4 is the same as o5 7 it's oh my god and if you're going to say a high ranking member the o5 council just name them but don't even use o5 there's no reason why why the council member was instructed to move office switch offices any other way to phrase that that makes sense rather than move office move office you move office you i caveman you move office now while scp xxx was present i have an o5 council member encounters an anomaly calls an anomaly containment team but the team is the one that has to be like oh by the way you shouldn't be in here while we're doing this scp asa has caused great alarm in the facility again with the clinical tone not just not being there with no other options no other options you haven't described anything about this is this dangerous or even weird it showed up in her office what someone could have left that this could be the word this could be a prank someone just like left an egg on her desk has great alarm in the facility with no other options they set up a makeshift testing chamber by lining the walls with lead and covering the windows they then why they then had d class go into the chamber and attempt to move it with different tools and items once d class one d classes are to pick up with their bare hands by doing so it was picked up with great ease anytime anytime in a clinical document that you feel a need to put quotes around something pick something else you don't have to quote the person involved your job is to rephrase it in a way that is going to be clearly understandable to the audience and in this but in in universe it's clearly understandable to anyone reading it that's the point of clinical tone if you give up on that and just go well joe said it was easy to pick up like there's no point in doing that sva also revealed some of its anomalous properties by lighting up I know what you mean now sort of like it's it's an egg that lit up which again still is an anomalous but when you say it revealed some of its anomalous properties by lighting up I'm just imagining an egg smoking something something advertiser friendly by the way when put in a containment box to be transported became immovable immobile I think maybe is the word you're looking for here and the boss was unable to be lifted confused they had the d-class who had put oh my god oh yeah you just completely abandon your clinical tone for this like you're not even trying anymore into the box to attempt to lift it once more he did so was then escorted to a containment cell where it would be hell all right all right let's keep going let's just subject the object procedure to d-class personnel send into the room d-class one is instructed to dawn the latex gloves placed on the plastic table next to the wooden table oh my god you don't need to go into this much detail come on this is just words for words sake this is just in look I know look I know when you were in school or you were in college and people were like write a 20 page essay on subject and you just had to fill things up with uh filler words and all this other stuff don't do that for this is instructed to don the latex gloves the latex gloves which we've already been introduced to latex gloves they've been a character they went to my brother's wedding the latex gloves placed on the plastic table next to the wooden table let's be very specific here this is just work like it's just words for words sake is given instructions to pick it up with an instructor to throw you could during the uh what is wrong with these people during the time it took d-class one to dawn the latex gloves it seemed to glow a red hue as if to indicate distaste you cannot be attributing emotional factors to an egg especially when up to this point nothing and I do mean nothing that you've described would indicate to me that this is an emotional egg the red hue then subsided and gave off a distinct blue and yellow glow the red hue gave off a blue and yellow glow kind of synastructure is that when d-class two through capitalize your t for no reason to d-class one wait that's just the whole sentence usually when you say when something did something there's like an after like a consequence in the same sentence so it'd be like when d-class two through s e p x x x to d-class one the whole world exploded you you have to have something that happens after that or else it doesn't make any sense when d-class one attempted to catch he was thrown to the floor from the weight uh to help was told to stop why after 36 is struggling and began to complain of a temperature 30 seconds of a temperature based discomfort in his hands that were under rhythm can glow red again after four minutes had reached an extreme brightness bathing the entire and no one's like oh let's just see what happens screams and cries of pain all at once the light receded cooling down to a blue and yellow glow as seen when being held by open hands was then instructed to put it back in the containment like i mean like all at once anytime anyone uses something like all at once i'm always reminded of that poem the end of the world by archmal mcleish like quite unexpectedly the top blew off yeah the problem with it is that it's not clinical obviously but at the same time not only is it non-clinical it's not descriptive enough it doesn't tell me what the f**k is going on all at once but it's just you don't even need the beginning of that sentence it could just be the light receded but what is cooling down to a blue and yellow you can't describe a light cooling down i know what you mean because a blue color is cooler than i want to say cooler i mean like literally in the sense of red being hot and blue being cold colors but of course when it comes to actual temperature blue is way hotter than red so just like yellow is very is hotter than red it's not way hotter but in actual temperatures like if you heat something up and it's red it's hot if it's yellow it's very hot if it's blue it is incredibly hot so when you say something cools down from red to blue i'm like what the f**k are you talking about you're using the wrong words for everything the conclusion come to by researchers again your tone everything that says is as follows sb is activated by touch but big caps around but could you imagine getting an official report with big caps around a butt like that we'll just start italicizing things like but can only be safely held by bare skin i mean come on after some other similar tests why would you like the idea that something like okay all right all right all right this was a really interesting test lots of interesting things happen let's do the exact same thing over and over again after some other similar tests the researchers have which you don't show and you've got a test log too right beneath this i can see it but you don't do anything about it after some other similar tests the researchers have concluded the researchers no one specific have concluded that it was touched by bear if touched by human but through some means of thin protection will increase its external temperature to the melting point of that object in order to in an attempt okay you're again you're ascribing human motives to this thing it is it is trying to a touch your skin no it's not it is doing things that may lead to that but it doesn't have a motivation it's just an object at least so far you haven't given me that this is a human being like object you haven't given me that this is got a personality or emotions i mean you keep describing it in the narrative as though it has emotions like it got angry and turned red you know or in this case it's trying to touch people's skin but you haven't described the object in your three sentence description in a way that tells me that this is a sentient or sapient or any kind of intelligent object like whatever test log two okay here we go tendy class version now we're sending into its containment cell number of them work i get this because it's still a draft it's fine they were closed in a full body lead shield during previous says it's covered they gave off a very faint amount of radio wait hold on this is this literally is test two so you said there were similar tests done after test one so this isn't test two that they're internal consistency is not here during previous says it was discovered that it gave off a very faint amount of radiation while active it was thought to it was thought of to test a diverse group i'm not even gonna talk about the tonal problems anymore because like it's obvious it's pervasive we're just gonna we're just gonna move on it was thought of to detest a diverse group of personnel to see if oh no oh no to see if a specific racial group or gender caused it to give off more radiation we had the d-class pass the object from one to another in a circle oh dear the 3d class with the lead line suits are not to what are they there for then also apparently the number was three as the test took place it was passed between a Caucasian male and female an Asian male and female and an African male and female and a Caucasian male with red hair the results are as follows normal radiation why would anyone think of this as a test like what indication did this thing give that this was a possibility this is why you need another test in between if you're gonna do it this way like there needs to be some sort of lead up to this it just comes out of nowhere hey let's see if the angry red egg is racist Caucasian male normal radiation output Caucasian female in spite of abnormal but not unsafe levels Asian male normal same thing for Asian female is the Caucasian female African female a spike but very small hike you probably meant spike there i'm just gonna say compared unless you just compared to the even the Caucasian female spike red haired Caucasian male the radiation spikes need to match that of the African female okay what's wrong with these people all right and it's just pretty inconclusive i can't tell if it's racist or not let's do a lot more tests i want to see if this egg is racist oh this makes no fucking sense at all none what inclusion really reaches that it seems to output radiation at random so they've discovered it's not racist although they've decided to this the wider pool of satellites before they come to a conclusion like it's probably not racist but let's check again with more people also by the way nothing about the above indicates that it's random because every female had a radiation spike that's not random that's not how any of those words work during the exits from the containment cell the Caucasian female fell unconscious i'm not no no i got a racist egg is what we got here i'm forgoing all clinical tone because she is coming with what clinical tone the end of this top secret is not to be seen here without a level four clearance an incident noted at the end of tesla 2 following as an audio log taken from a terminal outside an elevator in wing h start of audio log i am forgoing all clinical tone because she is coming first of all this is the writer telling you that they're not going to use clinical tone in this because they don't want to have to use it because it's you know a normal person talking or whatever but second of all there never was any clinical tone in this article and don't do that you don't have to say it just give it the context alone should say it you're telling me a context when you're not showing me a context my name is dr. Emma twiss i am a researcher at site 64 many containers human owners she you're calling it she she doesn't seem to be interested in other anomalous human oids located down here she she just wants us an explosion can be heard in the background where are you mommy miss twinkle wants to have tea a grown woman can be heard saying this in a background a grown woman oh god save me we were running somebody after she woke up and mommy i don't know no one much closer now than i heard i'm making the voice of a child help me dr. twiss pleads into the panel for us in yes baby do you want me to play with miss riss twinkle the woman continues yes sweetie would you like to go pick your room to play no i want to play here a loud stomp is heard over the mic ding the sounds of an elevator of ding you actually wrote ding the sounds of an elevator doors opening can be heard every switch apps sounds of gun cocking who are you i didn't invite you did you invite them miss riss twinkle miss riss twinkle didn't invite you either after this the sound of wind gushing when gushing and then gunshots fills the microphone the sound of three bodies hitting the floor can be heard afterwards that was a close one sarge a male voice is heard wrong dr. twiss can be heard you dispatched an instance of scp xx xx xx one with the mental faculties of a child which turned out to be which turns out to be very dangerous you are constantly introducing random elements that have no narrative through thread like there's nothing that connects this to the thing that came before there's nothing that connects the thing that came before the thing that came before none of this makes any sense you just throw a bunch of random together and be like all right that's an scp for you you don't understand what's going on well you're not supposed to understand what's going on fucking hell subject the object procedure wait now you've gone the opposite direction from going from way too much information to way too little information wait the result is simply waiting simply waiting i know i said i wasn't gonna talk about tone but come on come on for three and a half days they can't seem uneasy rocking from side to side again you're ascribing motives to this object which up until now this i still don't understand what the fuck was going on in the previous log so up till now i don't understand why you're ascribing any human motives to this egg after seven days the restlessness increased it threw itself off the table shattering the containment box it was held it it was held it yep that's thing it began to roll from side to side build speed as it went i think you're accidentally to word there eventually gained enough speed to shatter the bulletproof glass between itself and the research team having thought of this outcome project lead jim cas caught in his open palm as he had expected nothing happened came to a complete stop in his palm and there was no way adversely affected and walked with it under his arm back to the famous cell side on the table it would seem that during long times of no contact with human skin the object begins to grow restless and do anything and will do anything i'm imagining what you mean to say to meet with human skin once more it seems very similar to scp and then it will do anything to reach its goal mother you know i was thinking of scp 093 as it was going along and now i realized it's probably just how you uh inspired yourself to write that single test log which again has no narrative connection to anything that came before subject the objects it's a collective test of four through 30 no a collective log of tests four through 36 i think it's what you mean to say here for brevity's sake these were all replications of test two as it was through at least now finally finally a narrative thread that actually connects to something that happened before as it was through a larger pool of test subjects was wait what okay let's try this sentence again these were all replications of test two as it was though a larger pool of test subjects was needed for testing thought that's the word that's missing it or not missing but that's the word that's misspelled in such a way as thought it was thought a larger pool listen it still doesn't work really but it explains why my brain was like what the hell's going on here although due to the events described in redacted we have taken extra repercussions precautions i'm pretty sure what you mean we've taken extra repercussions all declass personal work garbed oh wow not clad this time with radiation hazard suits and only their hands are to be uncovered then they're not protected from radiation that's not really how a radiation hazard suit works like ah yes the rest of your body is fine but your hands we're going to expose that to massive amounts of radiation therefore you will only lose your hands because that's how radiation works right of course these 32 tests we had a group of more than 200 unique individuals participate you have a numbers right here the results are as follows okay those aren't results that's a listing of the numbers of people involved which you don't need because you already said more than 200 unique individuals although you could have given an exact number and then directly below it you show some 15 Caucasian males sent the radiation upwards that's half of them non-reached dangerous levels 12 Caucasian females caused the radiation to spike four of these are each dangerous levels that's less than half 16 in one of these mid-race scanners go haywire and the room was filled with flash of light the d-class who this happened to immediately fell unconscious he was removed from the testing continuum 16 Asian females caused the radiation to spike none of which reached deadly levels 20 of these reached unsafe levels there were a total of five bright flashes and unconscious d-class and i tell you that your whole is the egg racist thing probably needs to go like there's nothing about this is interesting and i'm i'm just not sure what it's trying to get at and conclusion the third level is at 3 for deadly encounters 19 for unsafe encounters and 47 chance of increasing radiation after incident audio log was reviewed it was determined that any future in order to be moved to site 88 for better security measures providing provided that there are provided there that we here are okay every time i run into one of these weird center structures my brain wants to try and fix it and then eventually just get lost so let's try this again for better security measures provided there that we here at site 64 he's changed he's been acting the special container procedures and is to be and are are plural changes be strictly followed with no exceptions after the prisoner break incident also prisoner break incident what oh it's because in the audio i guess in the audio log it's considered a prisoner break incident i love your quotations those make things way easier for me to understand what's going on can you tell that i'm being sarcastic if not i'm being sarcastic i also get a visitor remain on high alert when near it or any of its sub anomalies the fuck discoveries have been made recently addendum new discoveries discoveries nice opening good to know it was found in the plains of southern england during an archaeological dig near stone hinge an ancient worship center was unearthed this center contain many corridors and objects much of which were non anomalous that's a senate structure was unearthed period this center it's where you need a period right after between unearthed and this contain many corridors and objects most of which were non anomalous and what is in this what is believed to be a worship center there is a room stands in the midst of the corridors and hallways being big enough to approximately hold 200 humanoids this is believed to be the main hall wow your senate structure fell apart you went from at least mostly coherent to completely incoherent in the space of one lock wow foundation was called in a deal with an anomalous object in the center of this main room the object is egg shaped and has engraving and markings of unknown origins being similar in look and in look and properties wow to sv xxx the foundation has classified this as an instance of sv xxx too this instance will be held at site 64 for further study and experimentation all right listen up motherfucker the solution to your problems here is simple you have created a boring object and because it's boring to begin with three sentences long in the description are you out of your fucking mind you cannot have eight addendums for an article with a three sentence description at least you can't do so if nothing in the description explains anything about why it's why is this why should this why should i read more what about that first what about this draws you in that you can think of like come on think about it you're looking at this article you're reading it you read the first you read the special containment procedures which are very seldomly the part that's going to hook people it's it's where a lot of people find their hooks but more often than not it's not what's going to hook them what's going to hook somebody is a sentence in the description something that makes them go away what and then continue to read nothing about this an oval shaped container resembling an egg with markings engravings of an unknown origin it's currently known to only be active when touched by human skin it's undergoing testing that's it that's your description i mean and it's been a while around for a little while because the test logs indicate at least several months worth of testing so they should know more about it and of course they do know more about it because what what are they the description has to cover everything it should cover the xxx-1 instances it should cover the xxx-2 instances everything in the description should describe the object why is it anomalous and then you go into your test logs and the first test log is pretty simple and in fact okay the first test log gives you something to go off of although the test is incredibly strangely constructed they're like all right let's let it let's let it just kill this guy as far as i know it doesn't kill him but like they just let it the sags sit on him it's like ah i'm dying i'm dying it's and then they just they're just like mm-hmm mm-hmm yep you just imagine like they're behind the glass screen like stroking their beers going yes yes take write that down yes he's screaming he's screaming in pain yes yes let's write that down it just whatever it's for some people that's what the foundation is weirdly enough that that's their view of what the foundation is it's three guys standing behind glass one two d class die in a room going yes that's quite interesting scribble scribble scribble scribble scribble uh yes there's blood everywhere and you see how far over winter there yes it's uh let's write that down that's some people for some people that's what the foundation is like there's not an interesting story it's not interesting people just yes death destruction it's so normal which i get i get the draw that it's just all right let's keep going here the problem is your test line you then and then you just i don't know where you're just like i wonder if this egg is racist yeah let's take that yeah let's check it out i'm like that's your thought that's your that's your like oh and where does that come from it doesn't come from anywhere like i do not suggest you follow this light of inquiry but if you do your first test log could have been between two people of various whatever's and like radiation could have done and then you do another test and the opposite way and no radiation comes off of it and you go huh why did one of them cause radiation one of them not cause radiation and then you do your radiation test and maybe you check to see if it's male or female and maybe you check to see if it's Caucasian or Asian or African or red hair or red hair like look how red hair to separate it out like it's its own ethnicity that's that's just fantastic i don't understand this whole aside by the way this whole side is strange and needs to go let's just move on i'm not even gonna worry about it and it doesn't connect anything like the urgent top secret addendum there's a person walking around you don't tell us what the bash two instances are just for the stupid audio log that still doesn't tell you anything i love the idea though that they do just say what happens if we don't do nothing then it just starts going i want to touch people and then shoots through the window oh man and then they're like no but really is it racist with the next logs we're gonna test this 32 more times to check yeah but is it racist you have no strong narrative through line you have no characters that stick around ah you've got nothing like you yeah nothing at all all right the first thing i will always suggest when i tell people how to fix a thing is pick especially in flash fiction pick one character and focus on how the object affects them and that is always your best bet for a flash fiction piece like this especially since you do introduce a doctor Emma twist he's a researcher at site 64 use her tell her story how is she affected by the weird possibly racist egg oh my god i am just out of my you know what i feel sometimes like you people are not even trying i feel like you're wiping your ass with a draft and tossing it to me like i'm the f*** and told it to flush it down and the weird part is i know that's not true it feels like it every time i read one of these things because it doesn't feel like they're trying but i know they are not only are they trying they're tossing it to me not to throw it away not to get rid of it but to try and make it better but there's nothing here three sentence description you can't do that you give me a draft with a three sentence description what the f*** am i supposed to do with that you don't describe your scp object there's nothing here but a set of eight logs with completely random things going on in it there's nearly no narrative structure at all and by the way your clinical tone throughout the piece is bad and all of the ways that i've explained it to you i can't help you people until you learn to help yourself are you not listening to me are you listening at all to the previous things i've said in previous videos i honest to god want my viewers and subscribers and this isn't everybody by the way but i want all of you to get better at this but if you're not going to listen i don't understand what the f*** i'm doing here so come on please for the sake of my sanity f***ing stop doing this and this isn't just about harsh critique by the way i choose to do this because i find it particularly entertaining for my audience and i think you guys enjoy it mostly is it just about your drafts in general like okay get out of your own head that's the best bet here you know why this description is three sentences long because the writer knows exactly what the f*** is going on and rather than communicate that to the audience they assumed that the audience understood what was already in their head and then they wrote their article that's why this article has a three sentence description and that's you can't teach that i guess you can't teach people to stay out of their own heads you can't teach people that what's you know and what the other person you're talking to that's just basic empathy understand that other people have thoughts different than your own okay i don't know what the f*** this article is about i know for a fact that the writer knows what the f*** is going on and wants to communicate it to the audience and this is what they came up with and it is incredibly disheartening so anyway that's me taking down something that paid me twenty dollars to review their article oh my god what do you people do this to yourselves and me i don't know i don't know oh my god all right i'm gonna i'm gonna calm down i'm gonna settle myself and then i am going to thank people from my patreon and and i'll do my outro just give me a second all right if you like the video please hit the subscribe button hit the notification bell out next to that so you get notified when a new video comes out and i'd like to thank two new patreon backers one the twenty dollar pledge of logan peterson and the five dollar pledge of salvator lodado thank you guys very much for helping support me it's the kind of thing that makes videos like today sting a little bit less i appreciate all my patrons quite a lot and everyone else in the audience as well even if sometimes i don't sound like it i love you guys you're the guys helping me get closer and closer to doing this for a living and that is an amazing feeling regardless of how i feel right now i'm going to pin a comment in this video and i will give you guys an opportunity to submit new drafts to me for the next harsh critique don't worry it doesn't hurt me physically to do these just emotionally and mentally that's all so and plus people like them if you want to join my patreon like everybody else on the screen right now you can head on over to patreon.com forward slash d samarian thank you very much for watching and i will see you on tuesday


In this video, we'll give some tips on better searching using and, or, and not. The technical term for these words used in searching is boolean operators. You can use them to combine keywords in your search to get quite different search results. Here's how they work. Let's say you're researching the effects of coffee, especially espresso, on the study habits of university students. If you search the library catalog for coffee or espresso, your results will include all materials that include at least one of these terms. That means all your results will contain either the term coffee or the term espresso, but not necessarily both together. If you use and, your search will only find items that contain both terms, coffee and espresso. Since both terms need to be in every item, this means you'll get many fewer results than using or. If you use not as in coffee, not espresso, your search will retrieve items that contain the term coffee, but will exclude any items that include the term espresso. You can also combine multiple operators in your search. For example, you might want to search for something with more than two search terms, like coffee, students and espresso. You can combine the operators differently between the different terms to get different results. If I search for coffee and students and espresso, I get a small number of results that contain all three search terms together. If you search for coffee or espresso and students, you'll get results that have the term students and also have either the term coffee or the term espresso. Using or this way lets you include synonyms for your search term, which increases the number of results. Most databases let you combine multiple operators in one search. I'll show you how it works in ProQuest. Here I'll enter coffee or espresso in the first box to indicate I want anything that mentions either coffee or espresso. Then I'll choose not from the drop-down menu beside the next row of search boxes. Finally, I'll type beans in the search box beside the not to exclude anything that has the term beans. Each of the search results will contain either the term coffee or the term espresso. None of them should contain the term beans. If you have any questions, ask us at library.wlu.ca.help.askus.


I'm going to talk to you about another new frontier to complement our explorations on Earth and in space, and what I want to talk to you about how we can together manufacture the future. Everything that we do in 3D is disruptive, it's transformative, it's impactful, and it's going to touch everything, it's going to change the way that we design, it's going to influence what and how we create things, and it's going to bring about, I think, an era of localized manufacturing in big ways. We invented it, believe it or not, 30 years ago this year, Chuck Hall invented 3D printing because he wanted to help an ailing car industry in Detroit compress their time to market and regain competitive advantage. It took 30 years of innovation and perseverance to invent it, to advance it, and now we are democratizing it by actually opening access to everybody through manufacturing systems, school children type systems, and cloud printing so that everybody everywhere could harness the power of 3D printing, and so, you know, to us now it's your turn. What's the big deal about 3D printing? The big deal is that when you begin to deposit material one layer at a time, complexity is free of charge. There is no burden, there is no overhead, you are not anymore bound and constrained by any of the traditional manufacturing processes, it's sustainable because there is little to no waste, it gives you the opportunity to create millions of one-of-a-kind items without any tooling and inventory, but even more importantly it allows you to mass produce highly complex shapes that could never have been produced in traditional manufacturing. Shape of a turbine blade and where the holes go and what the coating is, that might be the difference in one or two points of fuel burn in the way a jet engine works and that's billions of dollars for our customers in terms of performance. Now the way that's made today is kind of subtracting, right, you get a block of something and you weld it and you arc it and you take the scrap and it goes someplace and that's how you make those parts today. And 3D printing allows you to make that product right the first time, it allows you to make it from the core up so you basically don't have as much waste, the tooling's cheaper, the cycle time's faster and that is the Holy Grail. And that is the Holy Grail and this was in a panel that we did together with the Atlantic magazine on the future of manufacturing a few months ago and you don't have to go all the way to the turbine blade. We did a little exercise that if you only printed your safety belt buckle on an airliner through the lifetime of an airliner, you can save up to 3 million liters of jet fuel. So we can start just by weight reduction. Automotive has been one of the early adapters because we started by wanting to help automotive and what we're seeing today is the migration of our systems from the design and prototype labs onto the manufacturing floor and opportunity to begin to put high impact, low weight, high temperature, very durable and complex structures that allow the manufacture of performance vehicles in a way that could not have been accomplished before and the opportunity also to begin to create flexible agile bridge manufacturing that overcomes any unintended interruptions in supply chain and it's going to production. There is no question about that. The area that is the fastest growing for us is the manufacturing of patient-specific medical devices. Every in the ear hearing aid today that goes in the ear canal is printed. Most of your dental restorations are printed and companies like Conformis are leading the charge in patient-specific implants and the big deal is that not just the implant is printed but all of the surgical tools that are now planned and manufactured specifically for each procedure. When you stop to think about that, that significantly improves the outcome, removes the variability and enhances the quality of every medical procedure. And so you might ask, okay, Avi, what's the big deal? We know that this has been around for a while. We know we use it in prototyping. Does it really scale? Can you really think about the factory of the future that makes millions of complex shapes or better yet millions of one-of-a-kind? And one of the examples that I like to cite because it's really unique is Invisalign, the clear aligners that you have because just last year alone in a room that is about the size of this ballroom, aligned technologies manufactured over 17 million one-of-a-kinds in a factory of the future that exists today that was fully mechanized and automated to deliver 17 million one-of-a-kind items economically, affordably, and in the here and now. Manufacturing, innovation institute in young style life, a once shuttered warehouse is now a state-of-the-art lab where new workers are mastering the 3D printing that has the potential to revolutionize the way we make almost everything. There's no reason this can't happen in other towns. So tonight I'm announcing the launch of three more of these manufacturing homes where businesses will partner with the Department of Defense and energy to turn regions left behind by globalization in the global centers of high-tech jobs. And I ask this Congress to help create a network of 15 of these homes and guarantee that the next revolution in manufacturing is made right here in America. We can get that done. So I want to talk to you. I mean, it's amazing that, you know, when you have an attractive business, even the president is auditioning for the VP of Business Development role. But what I want to talk to you about is how we're going to reinvent the future starting today, how we're doing it already. So let's start with retail. This is a project that we have done with Disney to begin to reinvent the retail experience so that it becomes immersive, personalized, customized. And on an emotional level, when you think about brand equity and what this brand equity really means, the opportunity to empower millions of people to co-create a unique experience with their brand. It takes advantage of all the converging technologies that we're talking about, sensing and cloud computing and artificial intelligence. To bring home in the most powerful way, a completely personalized experience. You can see it with the Disney Princess, and you can see it with the carbonized experience. And that's only the tip of the spear in retail. You know, we think that there is an opportunity here to completely reinvent retail. And there is an opportunity to also create completely new exchanges in marketplaces for people to begin to upload designs, share designs, customize them, monetize them, and create apps. You can see on the left of your screen an example from a startup in London. It's called Makey Labs. They created apps that allow girls to basically design their own dolls. What's the big deal? The big deal is that you begin to unleash little girls' creativity when they think that they can actually design it, create it, make it, and shape it. On the right, you can see some of what we do on cubify.com that Peter mentioned. It's a completely new revolutionized way to think about how we can infuse gamification and creativity and open all of our sophisticated manufacturing systems for the benefit of kids and adults and educators and inventors. Healthcare, you saw a little bit what we do with patient specific. That's only the beginning. We're now using Kinect sensors and turning them into medical scanners. We're using sophisticated feature recognition software to stitch it together and create a variety of prosthetics, fairings, braces, and allowing people to reclaim their symmetry and to celebrate their deformities in a fashionable way like beautiful tattoos instead of hiding them and isolating from them. And we see that as a life-changing experience. And this is what's next. What's next is fracture and scoliosis and the opportunity to do it in a way that's cost-effective, fits under existing reinsurance reimbursement codes and allows you to function and celebrate a condition instead of hide, isolate, and be encumbered by it. Interactions are going to change. We have amazing technology now in terms of sensing and scanning engines that are going to redefine how we speak. And there is an opportunity here to develop a whole new language of creativity through gesturing, as you can see with some of the early works that we're doing with the lip motion devices. And as the prime sense type categories are progressing, it's going to completely redefine how we digitize everything around us and how we manipulate everything around us, creating new creativity languages. And I want you to save that thought because that's at the heart of my challenge. Food creations are going to change. I'm personally passionate about chocolate. So what you see on the right is my own skunk works creation. I want to create the curing printer with dark, spicy, chili-based chocolate that I could print for myself. So that's my early creation. Probably will come to a market near you sometime later this year. And with all that good news, there is always the unintended and the most celebrated cases of what happens when you can point, click, and counterfeit, or easily come to illegal possession of weapons because you can now print in an undetectable material. The lower case of an AR-15, the thing for me here is that craftsmen could have done this for decades. The tipping point here is that with 3D printing, craftsmanship is democratized. And so now if you have the file, anybody can do it. And those are the things that we need to understand as we challenge the entire social and legal system with all this disruptive technology. 3D me, who do you want to be? So now you can do it with two pictures. Oh, cool. I made it, mom. 3D me. And you don't even need to scan yourself. 3D me. I hope I look this good on my wedding day. 3D me. Wild East, Wild West, 3D me, bring out your best. I can slay dragons. 3D me, who do you want to be? So no longer scanning, just pictures. It's going to change the way that we think about how we accessorize ourselves and other fundamentally human condition need to differentiate. So you'll see more and more of that happening. You're going to see it in bio printing all the way from bone replacements to organ replacement. The research and the startup work is quite advanced. And you will see us continuing to democratize access and price points all the way down to a sub $500 for the next generation of these little beauties for eight-year-olds and bona fide industrial manufacturing platforms that will reside on every factories floor in the future. But we live in exponential times. And my concern is that not everybody is coming along for the journey, because in exponential times, we are experiencing an exponential divide between the closed-minded and the open-minded. And I think that that represents us with a real challenge and a real opportunity in education. And this is my plea to you. I'm absolutely passionate about education. And to me, education is a more important bottom line, even for a public company, than the EPS bottom line. And the question is, how do we unleash kids' creativity? And how do we impart this important language of creativity to kids so when they get to the workplace, they are fully equipped? My name is Caleb, and I'm eight. My name's Lauren, and I love music. I'm a sleeper and a teaser. So this is a project that started by Singularity University summer program students that we now decided to incubate inside of 3D systems, because we are investing hundreds of thousands of dollars to make good, to find new ways how to create the platform, the infrastructure, the ecosystem, the learning, the curriculum, and we can't do it alone. We need help. Kids get it instantly. They understand it. They want to use it. And the insights that we're discovering is that there is a new kind of literacy that needs to be born out of it, which is not necessarily about reading and writing. It's about a world-less universal language of creativity. And so there is an enormous power here to be unleashed. There are opportunities, I think, for some real X prizes. In my dad's brother, I invented a safer football helmet. I invented a robot companion and a system.  We're already doing all of the democratization that we can on the device and the affordability and the accessibility. I'm willing to do anything that I can to put it in the hands of children. I need like-minded people that help create the ecosystem, the platform, the social networking, the universal language of creativity that could potentially transform how we create, make, and give our kids a better chance for sustainable entrepreneurial shape in a different economy than what we live in today. So thank you for giving this video so much. Thank you.


Oh yeah. Good. So I'm very glad to have come to this meeting because I've learned an enormous amount. I'm not in end code and I don't do end code type experiments. So it's actually been very useful. I've used end code and it's been very useful to use it and to see how people are thinking about using it. So I think I'll be talking about a much more focused topic than many of you have talked about. It's going to be about DNA modifications. And I hope that I can bring some perspectives to what I think so far has been a very small fraction of what end code has been doing. So that's how to move the... Yeah, just this. Thank you. So as probably all of you know, it's a very short introduction to DNA methylation. Methylation tends to be, oops, in CPG contexts and symmetrically methylated. That's about 90% of the... Or more of the CPG's and differentiated cells in the mammalian genome probably saving neurons, which Joe Ecker has done a lot of work on non-CPG methylation. Anyway, the methylated CPGs are in the major groove available for binding by various kinds of metal binding proteins. And the way the standard way for DNA methylation to be erased is in fact just DNA replication, which replaces the methylated cytosine on the replicated strand of the plane cytosine, then DNMT1 puts it back. DNMT, UHRF1 complex. And basically, if you prevent DNMT1 from putting the metal group back, what you get is a slow, progressive, replication-dependent loss of DNA methylation. Now, since the tets were discovered in our lab about six years ago now, it's been clear that while DNMT's put on the metal cytosine, another mechanism for removing the DNA methylation mark involves this progressive oxidation of metal cytosine by-tet proteins to 5-hydroxymetal, 5-formal, and 5-carboxy cytosine. And these are all, they're all epigenetic marks, and of course they can come in combinations so that what you have is you can have, what you can have is different kinds of methylation marks here. So there are 25 possible combinations for epigenetic readers of different kinds to look at. Now, all of these marks, if they're opposite from the methylated cytosine, tend to prevent DNMT1 from doing the maintenance methylation. So they would, in fact, interfere with maintenance DNA methylation and be a way of facilitating replication-dependent DNA demethylation. And there are also some methods that involve base excision repair proteins like thymine DNA glycosylase, which normally takes a base, a mismatched TG dinucleotide and excises it, but in this case can also recognize the perfectly well base paired 5-formal and 5-carboxy cytosine and excise those, and then those are converted back to cytosine by the base excision repair machinery. So there are a couple of other mechanisms that have been suggested for demethylation that I won't go into because they're not as well validated. So where is 5-HMC in the genome? It's highest in gene bodies of the most highly transcribed genes, and I think you can see that over here. That's the top, 25 top quartile of 25% of most highly expressed genes. And you can see the unexpressed genes are really not enriched for 5-HMC in this standard DNA affinity enrichment method, but the lowest expressed genes you can see are slightly enriched but not highly.  And if you look at enhancers marked by K4ME1 and K27 acetylation, the color gradient gives you how much 5-HMC there is in these enhancers, and you can see that it's the most active enhancers is defined by high levels of both marks that have the highest levels of 5-HMC. And these are all highly transcribed regions of the genome, gene bodies as well as active enhancers. It is just heard from Blankingen who just spoke, sorry. It's all right. And this thing that you've shown here in T cells has in fact been shown for neurons and during spermatogenesis, during erythroid differentiation. So it's actually true in many different cell types. So this is also shown in this RNA-seq 5-HMC picture where you can see just called them cell type 1 and cell type 2. They have two different kinds of cells in the thymus, and you can see that the 5-HMC levels and the RNA levels match very nicely. So these two are expressed in cell type 2, and this one is expressed in cell type 1. So basically what we were trying to do was to understand the functions of tetanzymes and mammals, and for the purposes of this talk, I'll try to relate it to what we know about DNA methylation changes. So there are three tetanzymes. We've made mice with conditioned floxalleles of all of them, and we've found that the individual mutations give you relatively mild phenotypes, depending on whether you're looking at embryonic development or particular tissues. And what we do know is that double and triple mutations that we made different types and different cell types actually give you fairly striking phenotypes such as embryonic lethality and ablation of specifically lineages. So for instance, when we delete tetanzymes in hemopoietic cells, we lose red blood cells, we lose these cells, depending on what cre we use. And what I'm really going to focus on today is the relation to cancer, and I'll go through it very quickly. So at about the same time that we were identifying the enzymatic activity of tetanzymes, a different group in France showed by looking at a very small deletion in this 4Q24 region, which is often mutated in milder dysplastics and drones and so on, that one small deletion contained only the Tet2 genes. And this was followed by flurry of whole axon sequencing that basically said the mutations were all across the Tet genes. And we and others have shown that these are very likely all loss of function mutations of Tet2. Since then, there have been any number of papers relating all sorts of cancers, including solid cancers to mutations in Tet1 and Tet2, or to loss of hydroxy metal cytosine, which is a readout for all Tet activity. And so the question became for us, we work with model organisms, not so much to relate the mutations in human cancers to what's going on, but to see whether we can induce an acute cancer of different cell types in a model organism by acutely deleting Tet proteins. And this, in fact, turned out to be true. Basically, we asked the question, is acute loss of Tet function associated with cancer? And the answer is yes. We can't delete just one Tet protein, we have to delete two. And haven't yet been able to do it with three because of the embryonic lethality, but two Tet proteins definitely with Tet2 and Tet3 so far. It's what we've tested because they're present to the highest extents in differentiated cells. And we've taken it out, taken out Tet2 and Tet3 together with either with amyxcite CRE, followed by double-stranded RNA injection, or with CRE-RT2, entomoxifen injection. And the effects of deletion, if we do it either way, which is an acute deletion, is first seen in the hemiportic stem cell compartment. And what we get is an aggressive my lord leukemia. If we delete Tet2 and Tet3 with CID4 CRE in T cells, what we get is aggressive antigen-driven T cell leukemia. In both of these cases, the cancers are cell intrinsic, polyclonal, transmissible indefinitely to recipient mice, and the cancer develops really rapidly. And so we have to assume that the initiating event in each one of these cases is the acute and profound loss of Tet function, which derives from losing this hydroxymethyl cytosine and other oxidized metal cytosines in the genome, or maybe changes in DNA methylation. So that was one of the questions we asked. We took Lsk cells from the hemiportic stem precursor cells, Lsk cells, from mice that had either been either controlled mice or mice that had been before deletion, or mice after the acute temoxifen or CRE-RT2 treatment, and did whole genome-bysulfite sequencing on it. And now I'm completing a comment to the students. So one of the things I'm going to be really presenting this data for is to solicit your opinion, whether we're doing it right. And basically what we've done is taken three control samples, three biological replicas of control Lsk cells in three knockouts, and sequenced to fairly high depth, so that's 200 million reads, most of which are mappable, and the coverage in each case is about seven-fold, so that we have an overall coverage of about 21, 20-fold in each one of those cases. And that translates to pretty good coverage of CPGs in the genome. And that was validated, our choice of this seven-fold and so on was validated by this paper, which is a Nature Methods paper, I believe, that tells us that you need at least two replicas, and you need a certain depth of coverage in order to get a sequencing. So what do we find out? We find out that the canyons of DNA methylation, that's a terminology used by Peggy Goodell, or what Bing Ren has called valleys of DNA methylation, or some of these canyons and valleys correspond to CPG islands in the genome, do in fact, if we look at the control versus tech knockouts, do in fact shrink in terms of getting extra methylation of the edges, and this has been called methylation of CPG island shores for what it's worth. And that's true of both of these genes, and if we look at what both of these genes do, both of them are down-regulated in tech knockouts, relative to wild type. The promoter regions of both of these genes are actually present within the valleys, and I think that's shown here. And so one could take this handful of genes which shows this behavior and say, well, we've shown that there are methylation-associated gene-expressing changes, and therefore this sort of explains the phenotype. I would rather say that if you look at the whole genome level, however, the changes we see are really mild. So for instance, here are three replicates. So those are three lines of the controls and three lines of the tech knockouts, and what you can see over here is all across the genome you see an increase in methylation, but it's not really very striking at this average level at all, and that's also true for active enhancers. It's a little higher there, but basically the level of DNA methylation that we see is not change in DNA methylation is not very high. We can also look at this in the previous slide, I was looking at it at all genes, so that's 21,000 genes, a lot of those are not expressed, and we then focused our attention on the differentially expressed genes in both of these cell types, and you can see once again there's a minor change in the average level of DNA methylation. So what Edahi Avalos and Lucas Chavez, my informatic colleagues did, was basically to sum up the methylation at the transcription start site and in the three quarters of the end of this model gene body, and then plot those values in a sort of a dot plot where each dot here then represents one region of the genome, and what you can see over here is if you look at each one of these dots there's as the trend is towards increased methylation in the TET knockouts, but only about a 20 percent change in methylation overall, and if you look at up-regulated genes and down-regulated genes that are about twice as many up-regulated as down-regulated genes, and you can see that in both cases they gain methylation. So we're not seeing that methylation is making any change either at the transcription start site or in the gene body to overall gene methylation. There are some genes that follow the pattern, over here are genes that are up-regulated and lose methylation, and here are genes that are down-regulated and gain methylation, but overall there's really no particular pattern. So what do we need to make of this? I don't really know at this point. Are we to focus on the small subset of genes that just show the kinds of changes in quote unquote expect, or are we to look at the entire pattern and say that we may be changing the metabolic state of the cell? But we don't really know. However, that's probably a reasonable question for later, but what I would like to point out to you is that in fact the measurements that we're making with this whole genome by sulfite sequencing don't distinguish five mc to from five hmc, because what happens is that neither of these gets deaminated upon sodium by sulfite treatment. Similarly, C, Fc and Cac all do get deaminated in terms of deep on sodium by sulfite treatment, and therefore these are all read as C after amplification and conversion, and really since the numbers of Fc and Cac, at least in our CS cells, are very low, what we should at least be trying to do is distinguish tribe mc from tribe hmc. So the recommendations for this first part of the talk are basically to include oxymc or at least five hmc measurements in any of the DNA methylation analyses that in code might be contemplating doing in the future. So as I told you, five mc and five hmc can be distinguished by certain techniques such as tabcic and oxbsc, but these are really too expensive to do and on a routine basis they require about 10 times as much coverage as simply whole genome by sulfite mapping, so one would have to do it at an apricon level. And also remember that we are talking about five new cytosine bases, unmodified, five mc, five hmc, five fc, and five Cac, but the change is binary, whereas what we're looking at when we say a change in methylation level is a change at the population level. And there's some undefined proportion of change state. So the other thing we probably ought to do is include perturbations and kinetic measurements. These changes seem to be much more dynamic than we previously appreciated. And they may happen on very rapid timescales. And finally, I think one really should encourage the development of new sequencing methods to map modified cytosines in unamplified genomic DNA, and that would include ideally long reads, so as to allow unambiguous mapping of repetitive regions of the genome. One small section. Okay, so I want to bring up the idea that one should also be looking at primary cells that are available in small numbers. And in order to do that, what we did was look at a phenomenon called T-cell exhaustion, which is observed in chronic viral infections and in tumor infiltrating cells and appears to resolve for prolonged exposure to antigen. And it's important in the context of certain immunodeficiencies. And what I'm just showing you here is some attack-seek data that are looking at naive cells, effective cells, and exhausted cells in a region. And what you can see over here, looking at these tiny numbers of cells, only about five times than four cells, is that there are, in fact, regions that are accessible to exhausted cells in vivo, in the chronic viral infection context, and do not appear when you stimulate the T-cells in vitro. So I think something like this should be incorporated into the flow for attack-seek. And you can see over here that the same peaks show up in cells that are tumor infiltrating and also exposed to antigen and don't show up in visor standard cells in the tumor. And so I'll skip forward and just tell you about my collaborators. I think Irvind actually is a very important resource on the NIH campus. And these are the people who did the work on the hemopoietic cells. And this is the person who did the work on the T-cell cancer. And these are our prime climatic colleagues whom I've tended to mention. Thank you. We're still 10 minutes away from where we'll be. I guess we need a moment to do some recalibration of the AV. But our next speaker will be John O'Shea, who will ask us not what, well, ask not what you can do for ENCODE, but what ENCODE can do for you.


Welcome to today's special Christmas edition of Frightfully Forgotten. But what are we drinking today Justin? The Dark Crystal. Today we're going to bring to you 1980's Christmas Evil.  It stars Brandon Maggard. Jeffrey DeMon is in this and he's in tons and tons of stuff but some notable horror type stuff. He was in The Walking Dead. He plays Dale. The movie starts out, there's a mother with her two kids, they're watching Santa putting presents under the tree and eating the cookies that have been laid out for him on the table and like a pig. He's drinking slurping all that milk and everything. So the kids they go back off to bed, the one kid doesn't believe it's Santa, right? The other kid wants to go and see, sort of walks back downstairs, y'all see Santa like going down on his maw, he's all, no sniffing her, he still has his Santa stuff on and everything. The beard? The girl, itchy, your taking it down there baby. So this kind of like almost traumatizes the kid and fast forwards to the present date. We see Harry, who was the little kid, he's like obsessed with Santa.  Harry works at a toy factory, the Jolly Dream toy factory.     He goes to his brother's place, watching him through the window and they all start screwing on the couch and everything. Starts to go to the kid's homes, he digs his hands in the dirt and puts all the dirt and everything on his face and then he kind of leans against the house and like marks the house.   Right in public, no problem. You see Harry start to make his own Santa suit. He also starts to make his own metal toys, like with molten steel and everything. These soldiers, these big sharp swords. Gee, I wonder what those are going to be used for. The work Christmas party for the Jolly Dream Toy Factory. His boss comes around with this new executive and they're talking about this donation scheme and how it's like not really a donation for the kids and Harry's pretty off put about this and he starts talking to people about the tune.   He gets so pissed off, he goes to the factory and starts stealing the toys off the assembly line. So it's now Christmas Eve and Harry's in full Santa gear and he goes around to like all the bad kids' houses he's marked and you can see him taking presents away and putting different presents under the tree.  Oh, I'm Santa Claus, I've come to bring presents for the children.   He ends up at some random Christmas party suddenly, like oh Santa coming soon! Hector Solomonco takes him inside, dancing around, he's giving presents to the kids and giving speeches, finally ends up at his co-worker's house. He tries to be Santa, he tries to go in through the chimney. Yeah, he kind of tries to get down but then he kind of, you see the space that he knows he's stuck. It's a long scene of him like trying to get out of the chimney. You see him like breathing in to like...  Christmas day, the news is all over the town, on the TV, beware!  They start lighting all these torches and they're chasing this Santa through the streets and drives to his brother's place. The brother opens up the front door and is like, Harry, I knew it was you. And that's where we're gonna end the plot point. If you haven't seen Christmas Evil, keep watching the movie to find out what happens with Harry and his brother and the angry Transylvanian mob. One of the best things about this movie is that it's still a Christmas movie. All of the Christmas elements and ideas are still there. And it feels like Christmas, even though it's a horror movie. Yeah, even though it has all the Christmas elements, it more focuses on the main character and his descent into madness, right? Yeah. And using like the Christmas theme of everything, something that should be so innocent but turning it around into something so evil, right? Even though, in his point of view, it's the right thing. And that's the cool thing about this movie is that whole social commentary of like him being so disgruntled with what Christmas has become. Yeah. The commercialization. The commercialization is money-making scheme.  It makes them go off the edge. You do root for him. Yeah. Because you sympathize with him. And he does want to do the good kids justice and do the naughty kids.  Yeah, exactly. He was made this way from systematic abuse. His brother is always berating him and his coworkers are slamming him down. So his mother being eaten out by Santa Claus.  Good lord. It touches on a lot of things. A lot of subject matter for sure. It's not really a slasher movie per se because there's not that many kills in this movie. And you expect it to be a slasher. Halloween had just come out. Friday the 13th. But Black Christmas, all these kind of holiday, real slasher films. And you expect this movie to be on that bandwagon. Nothing like that. Yeah, I know. It's way more deep. And it's more like closer to psycho, I'd say. Yeah. Than it is to a typical 80s slasher. Yeah, a lot of what you see is sort of left up to the viewer to make the conclusion. All the presents left under the naughty kids tree is like, what's in all of those presents? Don't actually see them open them. They're like, oh, what did you put in there?   What just happened? What really happened there? Last year we covered Silent Night Deadly Night. This at face value looks to be probably pretty much the same. Yeah. It's not. Yeah. It's like a completely different movie with the same theme or whatever. But it's a smarter movie. It's a deep Christmas horror movie. Yeah. Deep isn't Santa into his wife. Yes, isn't he? Santa giving it deep. Can he came deep? The curved end first.  Until next time, Merry Christmas and keep drinking. You betcha.


What it's like to teach English online, an online teacher reveals her secret Working as an ESL teacher can be difficult if you live in a western country and you haven't undertaken a certain path during your university studies As far as Italy is concerned, if you want to teach in a public school, you need to hold at least a master's degree in pedagogical studies and or educational sciences No matter how good an English speaker you are, you are required to own those specific degrees If you want to teach in a private school, you have to take into account the fact that they prefer to hire native speakers, which is totally illicit, to a certain extent In addition to that, if you have no experience whatsoever in teaching in front of a class, you are basically hopeless At that rate, you have two options, waiting for a stroke of luck or looking for something else Asia is a wide pond of opportunities in this sense On the other hand, Asia is not just round the corner and deciding to move there can be a hazard I have found my equilibrium for now in teaching English to Chinese kids remotely I have sent applications to several companies and at the moment I am working 14 hours a week during peak time That is, 7pm to 9pm Beijing time, Mondays to Sundays I only teach kids and the number of students per class can vary from 1 to 5 Of course, teaching kids is not mandatory, if you want to teach online, you may also end up having one-on-one classes with adults The demand for ESL teachers The demand strongly varies depending on the country you teach in For example, if you want to work remotely for a Japanese company, you will find that the majority of online schools hire ESL teachers who are willing to teach adults Business English to Japanese businessmen and university students especially On the contrary, if you want to work remotely for a Chinese company, you will most likely end up teaching kids As a matter of fact, many Chinese families are nowadays willing to invest in extracurricular English classes for their sons and daughters So as to enhance their possibilities to study in prestigious foreign universities or work for international companies It is easy to understand that different skills and teaching materials are required for these two different types of students Here is a list of the pros, cons and must have qualities concerning ESL online teaching Please bear in mind that I am teaching Chinese kids at the moment, therefore my observations mostly stem from this experience Pros of teaching English remotely Flexibility Most companies do not hire full-time teachers, meaning that the amount of hours you teach every week allows you to work for someone else at the same time For this reason, their contracts are rarely binding in that sense, so if you end up working for another online teaching company it will not be seen as unfair competition Material Most companies do provide read-made material for their teachers You do not need to produce it yourself, you only need to check it before the class and prepare some useful props and or pictures A different type of experience Since it is a relatively new business, not many experienced teachers can say they have been working as online teachers for the Asian market Fast skills enhancement Teaching online is different than teaching in a classroom, especially if we are talking about kids Catching and keeping their attention throughout the lesson can be difficult and requires you to be extremely creative The supervisor will acknowledge your efforts and you will feel like you have been learning something new every day Company support Perhaps I have been lucky, but the company I am working for provides 24-7 support to their teachers, especially during classes If you face any issue, you can contact them immediately and they will reply to you as soon as they can Cons of teaching English remotely Teaching time Of course, it depends on the time zone you are living in and the peak hours during which you are required to be available, but you need to bear in mind that you might end up working at 5am or 11pm However, companies state what their peak hours are in advance, so you usually have the possibility to make your considerations before applying for the job Flexibility While it can be a pro, it can be a con as well Sometimes you will not be able to teach the same amount of hours each month, resulting in a non-fixed wage No direct contact with the company And, with this, I mean that you are not physically in the same place If you face some issues, you need to communicate through a laptop and, sometimes, it can lead to misunderstandings Strict leave policies and tight competition These schools receive a lot of applications every day, so they usually never run out of new teachers and substitutes It might sound harsh to hear, but the world is not going to end for them if you decide to leave or if they are forced to fire you For this reason, my suggestion is always do your best and always be proactive For example, if one day you are stuck in bed with a high fever and you cannot get up and teach a class, you need to take into consideration that the company might not believe you It is not the rule, of course, but it might happen So, since you are working from home, you might consider the idea of making an extra effort and teaching your classes as well, even if you would prefer to stay in bed The social aspect. There are people who are totally fine with working alone from home As far as I am concerned, I sometimes miss commuting to work and having a chat with my colleagues during the coffee break What you need to teach English remotely Punctuality Enter the virtual class 5 minutes in advance, it will be appreciated Many companies will send you warning letters if you enter a class with a delay of 1 minute without a good reason Creativity Okay, perhaps this point mostly refers to teaching children You need to be funny and creative at all times, otherwise, they will get bored They might decide to leave the class and give you negative feedback Companies tend to be on the student side, so you need to be careful during your performances You need to bear in mind, though, that most companies record the lessons It might sound annoying, while it is actually a great help for the teacher, in case a student gives you negative feedback you can discuss it with the company, referring to the recording Clean and bright environment Some companies do not pay too much attention to that, but some others do Teaching classes in front of a window, with the natural daylight, is optimal, but if you teach during the dark hours of the day or at night you should make sure you have a bright white artificial light in your room Smile, always Even if you are going through the worst day of your life, you need to smile Especially if you are working with kids Take a deep breath and focus on the lesson Singing songs with kids is good medicine, after all Excellent internet connection and laptop Most of the times, companies will let you know the minimum requirements your laptop must have in order to be able to teach for them If you do not own a proper device, they will most likely decline your application Now you are ready to teach English remotely from anywhere in the world It goes without saying that some of these observations are also applicable to teaching in general, both online and on site One final consideration I would like to make is the following, seeing online teaching as a long term and fixed employment can be difficult As I have mentioned, it is a relatively new business and most of these Asian schools are still trying to find their equilibrium themselves This does not mean that it is impossible though As far as I know, there are teachers who manage to make a living by teaching online Like every other job, you need to work your way up the ladder and it is not going to be as easy as some might think However, I believe that if you are interested in online teaching, you should at least give it a try As I said, teaching English online is a great alternative way to find your path in the world of ESL teaching Apply now for your TEFL TESOL certification course and start teaching in a matter of months Speak with an ITTT advisor today to put together your personal plan for teaching English abroad Send us an email or call us toll free at 1-800-490-0531 to speak with an ITTT advisor today