Hi. Hello, everyone. I hope you have a great time on this observability day. It grown a lot since we started it, I think, first one in 2022 in Detroit, I believe. It's super amazing to see it's growing bigger and bigger. In this talk, we are really excited to introduce you to the topic of Prometheus Kubernetes operators. But you won't be a standard Prometheus operator talk, by the way, because of two reasons. First, we actually introduce you to two operators. You know, one is the official Prometheus operator. We all love to use and have fun with it. And we also introduce you to BitNewer Google managed Prometheus operator in short GMP, which has some pros and cons. The second reason why it's a bit unique talk is that we'll actually focus on metric collection use case on Kubernetes clusters. So only scraping, maybe aggregating, and sending this data straight to remote endpoint being another Prometheus, Thanos, Cortex, or just Venter. So a little bit simplified concept, but still not easy to grasp. So in the next 20 minutes, I really hope you to learn first why operators are really useful in this collection use case, how to configure and use both Prometheus operator and GMP operator, and when to use which. And finally, you'll see, hopefully, a working live demo of both running on a cluster. But before, short introduction, I have Max with me. Hello, guys. My name is Mohamed Amin. I also go by Max. I am a software engineer at Google. And I'm a GMP operator maintainer. And I was an open source mentor for a few projects like GSOC. Fun fact about me is I have 10 patents. I used to be a closed self-developer, but it's more fun to develop in the open. Nice, thank you. I don't have any patents. But I'm working also with Max. I'm actually leading the Google Cloud Management Service for Prometheus team. I maintain Prometheus. I co-started Thanos project. And generally, I love working in open source. I maintain various libraries as well. I'm also active in the CNCF TAG observability. Join us if you're interested in observability. And finally, I also wrote a book called Efficient Go. It's about goal and programming and optimizations. And actually, tomorrow, I will be giving away and signing those couple of dozens of copies for anybody that will come first. So save this date if you want to have a book on how to optimize your software. You're welcome. But let's focus on today's discussion. In our experience, the most pragmatic way of designing your Prometheus collection pipeline or metric experience, in general, is what we call this collection use case, or agent mode sometimes. As you might know, Prometheus is a very powerful project. It's a binary, actually, that has multiple metric functionalities into one binary or into one process.  There's so much stuff that you can put in this binary, simple and convenient. However, while this is useful for more dynamic environments like Kubernetes, especially when hybrid stories into place where you have multiple Kubernetes clusters, but also other environments, maybe other cloud providers, maybe it's quite beneficial to partition the collection logic and the other part. And the best part of the design of just scoping through the collection pattern is that tons of complexity is moving somewhere else, maybe to some other team, maybe to a vendor that you can pay temporarily or do it on your own. And on Kubernetes, what you are left with is really stateless processes, be it Prometheus's, which only scrape your applications, scrape metrics from your applications, group those metrics, possibly add some metadata, group them up, filter, and then stream those metrics to remote backend of your choice. And in CNCF, we have lots of options for that. We have Prometheus actually can be your remote backend. And you will see that on the live demo. But there's also Cortex, Thanos project, but there are many, many other vendors and other projects as well. So do we need to have operator in this case, right? Because we simplified stuff. So before I answer this question, let's have a small disclaimer. I'm generally not the greatest fan of operators, Kubernetes operators, generally. I think we built too many operators for two simple operations. We did a bit interesting stuff around operator actually playing and scheduling CRDs, resources of other operators. And this other operator also scheduled some CRDs of other operators, nested operators. It's kind of getting out of control a little bit. There are certain things you can do in your application instead of actually writing an operator, especially if it's stateless software. So we kind of went overboard. And each operator in your cluster is additional problem. Like it introduces overhead with resources, additional resources, another point of failure, another lag, and kind of delay in whatever operations you are doing. So there is already additional complexity to already difficult systems we run. Despite all of that, I think the answer here is yes. I think a Kubernetes operator for collecting Prometheus metrics makes sense. And I will tell you why. So first of all, first reason why operator is useful is scrape configuration. As you might know, Prometheus requires scrape to be configured in a one-bit YAML, right? So each application can be encoded in SCD visual jobs, maybe. You filter on and reach this with relabeling, which is super powerful. And once you apply this configuration, maybe mount a config map or something, your Prometheus, we know what to scrape done. The three problems with that is that first, you have to understand relabeling and really understand this YAML configuration. And maybe it's kind of complex for you to use. You have other systems to learn as well. Second, if there are different teams, multiple teams on the single cluster, which we already, I mean, we have that a lot because Kubernetes comes with multi-tenancy semantics, like namespaces, for example, you have a problem because suddenly, multiple teams, multiple people responsible for different applications, they come in and change one single file. So there will be conflicts, there will be one team breaking, monitoring for another team, so this can be problematic. Final problem is that to debug any problems with this, you have to really understand Prometheus UI and what is happening. Maybe you go to Prometheus UI, you have to kind of like have a read access to this very critical process that collects your metrics, which is kind of like sensitive. Then also, you break multi-tenancy because you suddenly see all the pods running everywhere on this page. So there are lots of considerations for this to not work well. How operators can help here? Well, there is like this common pattern where operator can expose a custom resource, custom resource definition, that allows to scrape configuration in fine-grained way, for example, per application, per team, per pod. And this is super useful because then you can have a separate file per team that literally specifies per application where the application metric endpoint is, how to select the application, how to filter those metrics, how to remove, add those metrics and maybe how to authorize Prometheus to scrape those metrics under secure environment. So generally, that's useful. On top of that, there is possibility to kind of maybe propagate some status of this scrape, like was this successful, how many targets you actually discovered, and you can propagate those information back to this custom resource. So for example, in the image, you see the status field and you can immediately debug things without going to UI, exposing maybe sensitive information and so on. So generally, it's beautiful because it's way easier, much easier to use Prometheus and make Prometheus collection in a shared environment. And finally, especially on communities, collection ideally scales, right? It scales by the amount of metrics you have, by the amount of applications you have. The beautiful part about using Prometheus for collection is that it's suddenly stateless. So you can totally create another Prometheus and tear down dynamically as long as there is a graceful period for remaining samples to be sent. But that's solved by you in Prometheus project. So generally, you can scale out and back very dynamically to save costs and for ability. While operators are not strictly required for this, they help, right? They can serve as a controller for this auto scaling and at least simplify configuration for kind of complex, maybe hash mode configuration that we have in Prometheus. You literally hide that by, I don't know, specifying number of shards you have. And you don't need to think how to really configure the complex wellabelling for hash mode. So consistent hashing kind of load balancing the scrape targets, right? So to sum up, we should look on either Prometheus operator or GMP operator if you want to simplify your collection configuration, especially if you have multiple teams, multiple tenants. And when you are kind of new or you want to have a very as easy as possible scaling capabilities of Prometheus collection, right? Now let's quickly walk over those two operators. Let's start with Prometheus operator. And I'm kind of grateful to have privilege to work with the team in Red Hat who created Prometheus operator from the start. It was actually one of the first operators, Kubernetes operators, if not the first one. So it was a beautiful journey. I learned a lot from it. So let's walk through it. So kind of for the collection purposes, we can look only on two things. First of all, we can look on the Prometheus custom resource or Prometheus agent custom resource. Both can kind of allow you to specify your Prometheus deployment. And we can kind of specify that for collection. For example, we can specify its name and how many shards you have. Arthur and Nicholas today had a talk about how to make this auto scalable. So that's also an option and it's incoming or already possible as an experimental feature in Prometheus operator. And you specify remote write URL and that's really it. Make sure to put this podmointer namespace selectors even if they're empty because otherwise they will not select any custom resources for scraping. So once that's done, once you apply it, you have three Prometheus running it with hash mode and sending data to remote backend. Now for target scrape configuration, you again have pod monitors for example. There are also service monitors, but I will focus on pod monitor here. And literally you specify what pods they select and what monitoring properties they have. So essentially where their metric endpoint is, what interval do you want from those metrics and maybe what kind of like additional metadata or labels you want to add or remove. So that's all possible. Now let's talk about GMP operator. All right, let's talk about the GMP operator. So what is GMP? It stands for Google Cloud Managed Service for Prometheus. We call it GMP for short. It's a similar to the Prometheus operator where it offers a managed Prometheus experience. It allows you to manage your Prometheus instances. It also allows you to deploy like managed rule evaluators and alert manager. It was developed by Google and GMP operator has a different set of CRDs from the Prometheus operator. I'll show that to you guys now. And it's fully open source and it's available on GitHub. So GMP is different. It's different than the Prometheus operator because unlike the Prometheus operator that deploys Prometheus instances as deployment, the GMP operator deploys it as a daemon set, which means for every node you have, you run a copy of Prometheus. And whenever a new node is added, a new Prometheus instance is added. Whenever you remove a node, a Prometheus instance is removed. And each node has like a dedicated Prometheus for scraping metrics in that node. And Prometheus uses filter targets to ensure that only targets in that node are scraped. And because it's only limited to a single node, that means the number of metrics are naturally constrained to the capacity of the node. So let's talk about our first CR that's called OperatorConfig. It's very similar to the Prometheus and slash Prometheus agent CRD that Bartek just talked about. And it's a singleton that runs on your cluster and it's like a top level view where you can configure special configurations for all your Prometheus instances. Some of that is like remote write, like you can see here or collection, what kind of compression you want for your metrics, what kind of filters you want to use, et cetera. So our main CR, which is similar to PodMonitor that Bartek talked about, it's called PodMonitoring. And PodMonitoring has a strict namespace tendency. That means it can only scrape workloads that exist in a certain namespace and you can't scrape targets in other namespaces. As you can see in this example, you can see in the bold namespace one is highlighted and we're scraping app A. So app A and nodes one and two are getting scraped but node three app A is in different namespace so it's not getting scraped. So the next one is called cluster PodMonitoring. It's the same thing as PodMonitoring except it's cluster scoped. And this allows you to scrape from apps all over your clusters without namespace. This is an improvement on PodMonitoring because if you have many similar apps that exist in different namespaces, you don't need to create a PodMonitoring for each of these. Also if you're an admin, this is a very powerful tool if you want to query across namespaces and look at what your apps are doing. All right, let's talk about optimizing GMP operator for daemon set deployment. So all the GMP CRDs are a Taylor set for a daemon set. It also optimizes Prometheus configurations for daemon sets. And this is the complex engineering that we're hiding from the user. And some of these technical challenges were utilizing the Kubernetes API WatchCache which keeps an index of all the pods that exist in every node name and this is a cheap way for Prometheus to know what pods exist on the node that it currently resides in. And this all happens without impacting Kubernetes performance. For the same reason we don't need service monitor abstractions like Prometheus operator. If you're interested in more details you can watch this talk by Danny Clark called Stateless Collection for Stateful Data Collection and from KubeCon 22. So an upcoming feature we have is called Secrets Management. This feature allows the GMP operator to handle your secrets without exposing a Prometheus that doesn't need access to that secret. And this is really challenging engineering problem and it's very hard to implement in a secure and efficient way. We have some ideas on how to implement it, so stay tuned. All right, demo time. So for this demo we're gonna show you how easy it is to deploy GMP operator and Prometheus operator and we're gonna have a sample app that we're gonna scrape metrics from and we're gonna do all that at the same time. Pretty ambitious. All right. Let me mirror my screen. All right, so I have a clean cluster running right now and it has three nodes. So for GMP operator it's gonna deploy three collections, three Prometheus instances and for the Prometheus operator we can configure that. Sorry, let's configure a metric source. So we're gonna configure this app called Avalanche. Avalanche is basically an app that emits metrics and it's scaled over time and let's configure a Prometheus remote write that you can write metrics to. All right, so this is how you install a Prometheus operator. This is provided to you, bundle.yaml, it's on there, GitHub, you could just use it and you just apply it right away. And then the next step is you can figure the Prometheus CRD that Bartok was telling you about. So as you can see here, we're gonna have two shards. We're gonna have a remote write and we're also gonna add an external label called operator, Prometheus operators to mark that this came from Prometheus operator. That was Prometheus operator created, Prometheus instance. All right, so we're gonna apply that and yeah, here we go. We see the operator came up and the two shards of Prometheus are coming up as we speak. All right, let's also install GMP operator as well. So this is how we set up the CRDs for the Prometheus operator. This is all provided to you on the GitHub. It's the first thing you run. And then the second thing is just install the operator also provided to you on the GitHub. So also similar to what we just did for the Prometheus operator where we configured the Prometheus agent CRD, let's configure the operator config which is its equivalent for GMP. So we also have the same thing remote write, same endpoint and we add an external label operator GMP so we can know that this came from Prometheus created by GMP. You don't need charting. We don't have that because we exist in every node. All right, let's apply it. All right, so as you can see, like remember we had three nodes so three collectors are automatically created and you have the operator. So yeah, that's how easy it is to start Prometheus operator and GMP. All right, let's do some interesting stuff. Let's start scraping. All right, so this is a pod monitor. Walter introduced us to it and we're just scraping this endpoint metrics every 15 seconds and our app is called metric source. So let's apply that and let's do the same thing for the GMP operator. So we have a pod monitoring GMP, same endpoint metrics every 15 seconds and pod monitoring is our namespace scoped but since there's no namespace here, it's gonna use defaults. All right, let's apply that as well. And let's see, all our apps are running. All right, let's try to see and Prometheus if I can find it. All right, so click to execute. You can see Prometheus operator come up. There's two avalanches that we're using and GMP operator is starting up also. The Prometheus operator we started up first. So as we query, GMP operator should start up and you can see that I'm aggregating by operator. So Prometheus operator has that external label and GMP operator also has that external label. You can explain what this backend is. Let's explain what the backend is, like receiver, for the Prometheus receiver. Yeah, so our backend is essentially a Prometheus receiver and we are sending these right requests via remote write. And so it's gonna come up slowly over the next couple of minutes. But yeah, all right, let's, yeah, Bartek will give us the TLDR. Amazing, thanks for the demo. Went almost smoothly. So we will have two choices and probably you're asking, okay, which one you should choose? It's not like one is better than another. There are essentially pros and cons. So let's go walk through them very quickly. So generally, Prometheus operator really focuses on hash mode deployment. Like that was the first deployment model Prometheus operator offers and it's really good at this. And it has, again, like benefits. One benefit of hash mode is for example, when the Prometheus running on the node, you know, you have Prometheus per node as a demo set. If the target is to be on one node, you might have a problem. You have to kind of vertically scale that. But in practice, you know, we found that's a good trade-off to have. It's also worth mentioning that Prometheus operator is working on more deployment models. In fact, it's incoming the demo set based deployment model and we are kind of helping contributing this to Prometheus operator will come eventually, right? However, the CRDs will be still kind of like tailored for everything else. It's not gonna be like fully tailored for demo sets. Which comes, this is where another point comes, right? So Prometheus operator is really good at running Prometheus. It's not only for collection, but also for all the other stuff, like literally as a full metric backend, right? So you can scale on Kubernetes Prometheus' for hail availability, you can have queries, storages, alerting, all of this. It's combined with Thanos processes and so on. So it's kind of smooth on that flow, on that stage. For our GPU operator, it's a little bit different because we only support a demo set intentionally, right? So we can have simpler CRDs, simpler pod monitoring and so on. So you kind of like, yeah, you don't have a lot of choices. You just, you know what you're doing and it's optimized for that model. Finally, Prometheus operator has just all the knobs that you might need from Prometheus, like literally what Prometheus offers as a flags. You know, Prometheus operator has as well. For GMP operator, we don't show all the options. We have opinionated, Google opinionated version of your configuration. Watch you, in our opinion, you should kind of like know about. So it's much simpler. But then if you're more advanced users of Prometheus, then maybe you'll be missing some option. And still it's open source, so let us know. Maybe there is some important option to have, but we keep it limited so it's easier for users, but it has some trade-offs again. Prometheus operator has service monitors, right? It's not easily possible to have service monitor in a pod monitor, in demo set deployment, although we can kind of like try to hack it through. So, yeah, we drop it. And to be honest, to be fair, like it's really not that big change. You just switch to selecting pods instead of selecting your services, so it's not that a big deal. And GMP operator, for example, has target status propagation. So it kind of tells the YAML back. Essentially tells the CRD pod monitoring what actually is scraped, what targets they discovered, and so on. You have to enable this feature manually in operator config, but it's worth a while. So, generally, TDR, Prometheus operator, more options, more useful if you want a local querying capabilities. And GMP operator, perhaps simpler stack, and also it is enabled by default in GKE. What I mean is that when you create a new cluster, GKE cluster in Google Cloud, you have this installed, and literally you can start using pod monitors, and you will see your metric in Google Cloud monitoring, or you can configure a custom remote write endpoint to send it to your whatever else cloud, or Thanos Cortex, and so on. With that, that's all what we wanted to cover. Thank you so much, and yeah, we're open for questions. Yeah, I think there was a mic somewhere for questions, and... First of all, thanks for the presentation, awesome. My first question would be about the pod monitor in the operator of Prometheus. You can do relabeling and metric relabeling as well. Are you able to support the relabeling config on the pod monitor provided by the operator? Yeah, so you have metric relabeling, right? So you can do whatever you want after the metric is scraped, but for relabeling that is before metric is scraped, so this relabeling is used for service discovery, we locked that in, and we offered a simplified, opinionated filtering, and a way of adding labels and removing labels, right? So literally you have like add label and remove label. And just simplify the logic, but of course you cannot do all the magic that you can do for relabeling, right? And then I have a, I don't know how to name that type of question, but the open-temperature operator, we discussed about it, has a target allocator that discovered the Prometheus CR by default, so if you have any pod monitor, it will scrap it automatically. Are you planning to release like a Google open-temperature operator supporting those CRDs instead of the traditional Prometheus versions? Yeah, that's a good question. I don't know what I want, what I can share, but we are definitely working on some open-temperature, you know, like managed experience in some opinionated way, but yeah, stay tuned, there will be something. And last question is the Prometheus operator provides a Grafana, and there's an option to say, to deploy config maps with your actual JSON file of your dashboard, do you support this or are you planning to support this? No, again, we are only collection focused, which makes us, makes this operator much simpler and easier to maintain and for everyone, so no, it's only collection, yeah. All right, thanks, thanks. Thank you. I think we have to finish, but one thing we have a ContripFest, which is essentially a workshop on Friday, where we will be literally with you on your laptop, we'll just deploy Prometheus operator or GMP operator if you want and we'll try to stress it, so come and we'll help you to run it on your own laptop, yeah. Thank you. Thank you.


Our first topic covers rates of reaction. Without doubt this is the central idea in chemical kinetics. There are three main aims of this topic, or three things that you should be able to do by the end of this segment of the lecture series. Firstly, you'll be able to state which factors influence the rate of reaction, but more importantly, you'll have to know how they influence it, and you'll need to consider this from the perspective of both macroscopic and submicroscopic levels of chemistry. For instance, we know that macroscopically an increase in temperature should increase the rate of reaction, but at the molecular scale it's really the speed of the molecules as they move that causes a reaction to speed up by giving them more collision energy and a higher probability of actually forming a reaction. And don't just think that more temperature means more faster is an adequate explanation, we'll need to see some way of quantifying this as well. Secondly, you'll be able to explain reaction orders and construct rate laws for each. At the end of the day, you can treat this as an exercise in memorization and just learn a few equations, but it helps to be able to drive them mathematically. It also absolutely helps if you know where they come from in terms of how molecules interact. After all, relating what happens at a molecular level to the equations that predict the observations we see in the lab is the very reason we have physical chemistry. Thirdly, and finally, you'll be able to use the initial rates and pseudo first order methods to calculate reaction orders and rate constants. These methods, despite their odd sounding names, are simpler than you might think. And we'll cover this in two different ways, by being able to plot a graph by hand and also since this is the 21st century using a spreadsheet and a computer to it. And we'll also cover how to simulate a reaction and solve a rate constant using an integrated rate law. These three objectives cover everything you need to know about rates of reaction as an undergraduate chemist. It might seem simple at first, but there's a lot buried in these topics.


Enegi data is a hard bit of modeling. You can do modeling without good energy data.  If these models can help us realize these plans, then it will help our people to get access to killing energy, hence better lives.


Item number SCP-2578 Object Class Keter Special Containment Procedures Global email networks are to be monitored by the Foundation for indicators of SCP-2578A. If the counter on a confirmed instance of SCP-2578A reaches 24, a response team from MTF-Iota-10, damn feds, it is to be dispatched to the location of the corresponding instance of SCP-2578B in no more than 10 hours. Over the last two hours, the team will monitor the situation and await further instructions. In addition, the response team will escort one D-Class Foundation employee scheduled for termination, the scapegoat for the purposes of contingency 12 Azazel, along with ampules of low-grade hypnestics. In the case of an in-progress and paler event, the response team is to carry out contingency 12 Azazel as soon as possible. CONTINGENCY 12 AZAZEL 1. Through the use of hypnestics, the response team will implant the scapegoat with artificial memories of assassinating SCP-2578B. 2. The scapegoat will be handed over to the law enforcement authorities of SCP-2578B's government. In the case of an aborted and paler event, the instance of SCP-2578B is to be detained and released after amnestic therapy. Due to the potential for civilians to communicate with SCP-2578D, instances of SCP-2578C are to be excised from global email servers upon detection. At this time, due to its location and destructive potential, containment efforts of SCP-2578D will focus on non-intervention and repeated attempts to negotiate. DESCRIPTION SCP-2578 is the collective designation for a series of phenomena related to the deaths of at least 100 ████ human subjects since 1995. Prior to death, all victims referred to as individual instances of SCP-2578B shared the following characteristics. SCP-2578B was a political figure, or was due to hold office at a future date. SCP-2578B intended to engage in all the following political activities at a future date, and had the adequate military, financial, and political resources to do so. Estimate Cleansing The Establishment, Continuation, or Reinstatement of Government-Sponsored Slavery and or Child Labor, The Violence Suppression of Peaceful Protest and or Descent, War Crimes Against Foreign Powers, The Establishment of Absolute Control of the National Press, Media, and Religion. SCP-2578B was relatively unopposed in his views by his constituents, and dissent or rebellion was curved in such a way that, had the subject not died, all of its plans could have been successfully implemented. 72 hours prior to its death, the instance SCP-2578B will receive a message, SCP-2578A, on its primary personal email client. The sender will only be identified by a set symbol, shared with all instances of SCP-2578A. The symbol appears to be three crescent shapes next to each other. The contents of SCP-2578A is consistent throughout all instances. 6. Semper Tyrannus Latin, thus always the tyrant, state motto of Virginia, also notable for its use in the assassination of Abraham Lincoln. Subjects Latitude and Longitude A number, which is 144 in the first message. I never miss my mark, abdicate and you will live. This part of the message is then repeated in Spanish, French, German, Russian, Ukrainian, Arabic, Farsi, Mandarin Chinese, Japanese, and Tagalog. After 30 minutes, the message will be re-sent to SCP-2578B, but the value of the second number will decrease by 1. Once the number reaches zero, an impaler event will occur 72 hours after the initial SCP-2578A. The corresponding SCP-2578B can stop the countdown in a variety of ways, including, resignation of their post, rescinding any pending orders that correspond with the aforementioned political activities, surrender to a war crimes tribunal or a resistance movement, and or suicide. Impaler events are characterized by the sudden appearance of a borehole in the targeted instance of SCP-2578B, which usually begins at the top of the head and ends at the groin, though alternative locations such as with SCP-2578B-429 have been noted. Though these incidents bear evidence of a high-powered gunshot, no bullets have been recovered from these events, and the holes will appear even when the instance is on an airplane, underground, or in a building, with no damage to the surrounding area. SCP-2578C refers to a set of emails sent to various politicians, civilians, and other human subjects at their successful or aborted impaler event. The content varies and can be personalized, but will usually include a declaration of victory and or words of encouragement, such as this message sent to a stenagogue scheduled to be bombed after the election of SCP-2578B-429. Three Crescent Symbols Is Victorious Yoan Lepescu successfully terminated May 12, 2009 Aim it due for services rendered Abandon your fears of tyranny Know that Three Crescent Symbol will always watch over you Three Crescent Symbol will always protect you And Three Crescent Symbol will always love you This part of the message is present in some capacity in all instances of SCP-2578C The entire content of this message is then repeated in Spanish, French, German, Russian, Ukrainian, Arabic, Farsi, Mandarin Chinese, Japanese, and Tagalog. SCP-2578D is a metallic spacecraft approximately three meters in length. It has been identified as the source of all impaler events in SCP-2578C and SEED Whether SCP-2578D is a manned or unmanned spacecraft is unknown at this time. The origin of SCP-2578D is unknown, but its design has been noted as similar to that of a horseshoe crab. This is believed to be an aesthetic design choice rather than a serve of definite purpose. These painted decals of the triple crescent symbol associated with SCP-2578A and SEED have been identified on its side from satellite photography. The tail of SCP-2578D can be positioned from three points of articulation. The tip of the tail contains what appears to be a projectile weapon system used to carry out impaler events. The mechanism behind this weapon is not currently understood. In addition to this weapon, it also contains an unknown amount of surface-mounted energy projection devices. See Incident 2578-1427 for more information. The location of SCP-2578D varies as needed to carry out its objectives and avoid detection, but it will rarely descend lower than 4,000 km above the Earth's surface. The propulsion mechanism of SCP-2578D is unknown. Addendum excerpt from the log of recorded SCP-2578B instances. Designation Name Title Impaler event Notes SCP-2578-B-013 President of the Republic of Srpska Occurred April 19, 1996 Note from Dr. Nysmith As of July 21, 2008, the current procedures are to take president over all former containment procedures. I'm sorry, framing D-Class for killing politicians isn't pretty, but our alternative medicine guru cover-up after SCP-2578 caused the disappearance of Karajik wasn't just unethical. It was silly. SCP-2578-B-326 Mohammed bin Salman Deputy Crown Prince of Saudi Arabia Aborted For a detailed list of the 230 Aborted Impaler Events so far in Saudi Arabia, please refer to Document 2578-K SCP-2578-B-429 Yeun Lepescu President-Elect of Romania Occurred May 12, 2009 The borehole was discovered through Mr. Lepescu's chest. Eyewitness accounts claimed that approximately five minutes before the Impaler event, Mr. Lepescu grew increasingly agitated for unknown reasons and insisted on letting his four-year-old daughter ride on his shoulders. Incident 2578-1427 On April 19, 2016, after the Aborted Impaler Event of SCP-2578-B-832, the Foundation used to computer terminals that received several instances of SCP-2578-C in China that triangulate the origin of the messages, leading to the discovery of SCP-2578-D. Email contact was established with SCP-2578-D by the Foundation shortly thereafter, requesting information about its origins. In return, SCP-2578-D sent the following. Very interesting. With regrets, I must ignore these irrelevant questions completely, and thank you immensely for the indirect access to your database, which was very informative about the impasse I have reached in North Korea. For a while, it felt as if I were talking to a wall in the back and forth with Kim Jong-un, but a bronze steely is close enough. It seems a more direct approach is needed for liberation. With love, triple crescent symbol. Two hours after the above message was received by O5 command, SCP-1427 was declared neutralized. Research into use of SCP-2578 as a means of neutralizing difficult to contain SCP objects or SCP objects of political origin is pending O5 approval. Incident 2578-1427 Timeline 1715 Containment staff of SCP-1427 terminated in a simultaneous and paler event without warning. Emails of apology sent to the containment staff's families from SCP-2578-D. 1729 SCP-2578-D sighted in the stratosphere over Pyongyang, descending rapidly from high Earth orbit. 1731 SCP-2578-D infiltrates the containment area of SCP-1427 and begins direct bombardment with projected energy weapons on the ends of its tendrils. 1732 1427 sustains heavy damage and snaps in too. SCP-2578-D begins to retreat, apparently leaving the steely neutralized. 1734 As an apparent defense mechanism, SCP-1427 begins to exhibit higher than usual outputs of electromagnetic energy, causing irreversible psychological damage to all those who were previously under its control. 1736 SCP-2578-D returns, latches onto both halves of SCP-1427 and rapidly ascends into the high Earth orbit. 1753 The two halves of SCP-1427 are seen by a Foundation satellite, drifting in the direction of the Sun. At 2012, Dr. Nysmith received a following message from SCP-2578-D. 3. Crescent symbol is victorious. Regrettably, I could not stop this steely from delivering its cowardly parting shot towards its slaves. Even so, their current plight is better than life as it had been only a day prior. I thank you for your assistance, friend. Also, I have sustained heavy external damage from expending this much energy in a short period of time, so if any tyrants come up while I am in auto-repair for the next week, I'm afraid they'll have to wait a bit longer.


Hey guys, my name is Els Marshall and welcome back to Hey Guys. The first story we're gonna be talking about is Logan Paul.  Basically, Logan Paul did, you know, he had a tent on top of a bus. On top of a bus, he had a tent on top of a bus. I was riding it. Yeah, no, great health and safety, you know. You know, great example to the kids. Now, that's gonna be like you, man. It obviously has to pass on five individual parking spaces, yeah? Obviously, you know, the sheriff was like, da, da, da, but I'm not having that. You know what, like, nah, but there is he who's Logan. Logan Paul then got questioned by the sheriff. The sheriff was really like, why is this being so stupid? You know, this is dangerous. He was like, no, I saw my responsibility. He's calm. They let him go because he said it's his birthday, yeah? Next time I'm getting in trouble, yeah? Please come up to me. Man, say it's my birthday and they let me go. I'm gonna use that trust me. Next time I'm in trouble with you, actually, I don't get in trouble with you just to get that straight, but you know what? You get to fix up a little bit, you know what I'm saying? Two in a news, bro. Yeah? Just focus on your boxing match with KSI. Get training, yeah? Another one. Basically, Conor McGregor has been arrested in New York. Yes, you heard me right. He's been arrested. So what he did, he went to, you know, the USC Press Conference. He was like, you know what? Man's gonna go to 30 of my guys, yeah? Run up in there and go and dash stuff at the Tour Bus. Conor McGregor dashed a trolley, yeah? A trolley dashed it into the Tour Bus and the windows smashed. And some fighters actually hurt. Like, there's a few fighters actually cannot fight on Saturday because of this. I don't even know what's going on. I don't even think he's gonna come back to USC after this. He might do, he might not. Dana White saying, you know, doing business with him right now, it's not the best. And we're gonna lie, it's not the best. Of course, there he is today. So we're gonna have to see what happens to McGregor and what charges he actually gets. So I'm at like Marshall, Aaron the Streets, and we're gonna see what people think about McGregor and how his title got stripped. Let's do this. McGregor, Conor McGregor. What do you think about his title being stripped? Do you want to keep me in into it? I don't like him. He was gonna make the winner of this fight the champion. I thought I would probably be good for him. But he never technically said that he would be stripped. Like runs off of the kind of pipe around him and that's just gonna generate more hype for him. You don't like him? No. Why? I like Joshua. Yeah, he is though because there's only one champion. The one thing you gotta know about the UFC is they do what they want, when they want. That's how you cheat. What's going on? Oh man, oh man left. If McGregor and Mayweather did a fight in the UFC, who do you think will win? As far as I know McGregor, he's not MMA or something? All right, listen. I'm away round.  McGregor? He's a chicken Mayweather. He's a chicken. He's a chicken. Fifty and always a chicken. You make a lot of sense. McGregor, he always runs. It just is round. I think it would be McGregor. McGregor? Yeah. And what? Because that's his domain kind of thing. Conor McGregor? Yeah. McGregor? Yes. And boxing, Mayweather, everything. How are we beating? You said we make techniques. Yeah, you're waffling him. If Conor McGregor came out right now, how would you react? I'd just say what's the crack, man? What's the what? What's the crack? What's the crack? I say dude, you're the man. You're the best. You are it. Yeah. What do you mean what's the crack? He wouldn't understand. Oh Irish. It's here, it's here. Look, look, look, look. No joking, don't do this. So Skepta has just been made chief in his family's hometown in Nigeria. So technically, I apologize if I say this wrong. Skepta's new towel is Amuludun of Adu Eje. So Skepta went with his family to collect his award in his hometown. I'm going to say Skepta, legend, yeah? He's done everything and this is just like top everything off for real. Skepta said this is a great honour and a great achievement to his career. Thank you for the chiefs of Adu Eje keen for presenting with my chief in Tau today. I am Oyn and we'll continue to put time and love into Nigeria, especially community of Adu Eje. Skepta has been in the music scene for so long but now he's getting recognized more outside, you know, the music scene. We saw Skepta in the cover of a magazine with Naomi Campbell. While Skepta was out there in Lagos he actually performed a show it was not, yeah? I don't know. Pretty better when you perform in the real world. They're going to lie to you, but. So I was at MTV here where he was Skepta all the best through his new job in Nigeria. Next. Thank you guys for watching today's episode of Hey Guys. My name is Mitt Els Marshall. Make sure you check out my social media at Els Marshall One. Make sure you check out at MTV UK. And I'll see you guys next week. Peace.


I can see now on my screen that we might be able to bring in our participant from Israel. Yeah, look at that. I do see something great. Excellent. I'm really happy about that. Just to tell you guys, I'm wearing my headphones. Maybe this is for the technical crew because the monitors, it makes it very difficult for me to understand what people at the other end even next to me are saying, so I'm just wearing this for my own benefit. Thank you very much. Now, Itamar Rabinovich, can you hear me? Yes, I can. Excellent. Can you hear me? We can, and we're so glad that you're with us because your voice in this conversation is essential. Can you tell us where you're joining us from? We can see you're in a vehicle. In a vehicle, we had some understanding about the panel, so I'm not at my home as I plan to be. I'm in my car, but speaking on my phone, but here I am anyway, and delighted to be with you. Excellent. We can see and hear you very well, and it's just fine that you're in that car. We're very glad that you can join us today. Would you like to offer a few comments? We've just been getting underway. I did an introduction of our guests, including yourself with the hope that you would be joining us. We've heard from a couple of speakers so far. We've touched on some of the themes. We've been in email contact with one another, so we're staying pretty much on track with what we discussed. Would you like to offer some comments to the plenary at this point over the next couple of minutes before we move on to the next speaker? Yes. I think that we need to look at the so-called the day after. We must have a vision of where we want to take the region and the Arab-Israeli relationship to, which means dealing with the larger Palestinian question in the Israeli relationship with the Palestinian Authority. I heard the reference before to the West against the rest. It doesn't have to be that. I think that several countries in the Middle East do not see the problem with the West but see the problem with Iran. Our host itself, Saudi Arabia and others, have been the targets of violence by proxies of Iran. I see that the current war is not just a war between Israel and Hamas, but between Israel and Israel is targeted or threatened by five Iranian proxies. And in order to organize the region to deal with these issues, there will have to be a plan for dealing with the Israeli-Palestinian relationship. It's difficult to envisage it. We're in the middle of a war. We have the wrong government, the wrong Israeli government for doing that, but the need is there. The debate inside Israel today is, do you deal with the political issues domestically in the middle of a war? Do you wait for the end of the war, whatever that end may be? But I hope that at the end of it there will be a government in Israel that would be willing to look at the larger picture and to fit into a scheme that would help organize the region, including dealing with the larger Palestinian question. Thank you very much. If you don't have anything to add, we'll move along. It didn't take you very long to get to Iran and Iran's proxies, the role that they're playing in this war. I think that's a hugely important part of this, of course. We need to discuss that. It's also important what you mentioned about the political context within Israel itself and the ability of the Israeli government or willingness of it to address this problem in a constructive way. These are question marks that you've raised. Thank you. Thank you for now. If you don't have anything else to add, I don't want to interrupt you. Our connection seems to be stable. I hope it will stay that way. So we'll continue then here on the panel bringing in voices.


Ken's chart, unfortunately Ken couldn't make it today, but I'm going to probably draw this in yellow and all seek capture pain relief is is understanding where typical support and resistance traders have been caught in their positions. So let me just try to move this up one second. I'm going to do a different color. So in this example, we have probably just off the screen, but we have can you guys see the yellow marker by the way. Yeah, yeah, yeah. Oh, Leonidas for COT data, right? COT, I kind of stopped COT and the reason why I stopped COT was because it really wasn't providing that much of an edge to our fundamental analysis. Yeah, so I kind of I did I did stop COT but I do include it I do include ING's analysis of COT so there is still COT in there if you want to use it by a Dutch bank called ING and they're pretty good. So anyway CPR right capture pain relief. What we're seeing is a typical or typical price action where support becomes resistance resistance becomes support. Yeah. And so what we're looking at is failures in that in the typical what you know all your YouTube Instagram traders do. Yeah, and the strategies that they they technical strategies that they that they use with we're trying to use them against them. Yeah, because what we know in the way that I was taught by my mentor was in order to make money you have to take money. Yeah. The money is transferred from the loser to the winner. And the simple concept of waiting and seeing where your opponent is is invaluable. So if you didn't know that this was coming and not many people did know that this this large candlestick here was coming, you know, because of the Bank of Canada. And their decision today. What do you think is the expected move to the downside. It would have been for price to continue going lower correct everyone would agree with that. Yeah. Yep. No. Yeah. Okay, brilliant. Yeah. Right. And so once traders get involved in a trade like this where they get some price action and first of all you've got you've got breakout traders, you've got retracement traders, and you've got level traders. Yeah, level traders. And they had to trade around levels anyways, you've got the breakout trader who would have got involved in that very bearish candle stop above the high right stop above their cast that's where you have to place your stop over there, or just above there. And then you've got the retracement trader, right replacing their stop losses there. Right and they've seen it's nice engulfing candle and traders are getting involved in there right now none of them has made enough from a risk award perspective. Yeah, to make any really real amount of money because if you've had to enter on this candlestick here, and that's your risk price hasn't really moved at far right as an inverse risk award traders at least go for like one to ones right. So they haven't then I know for a fact that they haven't exited that trade is the same thing with these guys right these guys, even though some of them might enter here, prices barely went to a one to one barely. Yeah. So for me, if that's your risk, and you've got a little bit of reward. Yeah, these guys are still in their trades. Why would these guys still be in their trades because of something called loss aversion bias. Right. So first of all, they've been they've committed capital and they've been captured in their position as prices go against them why would they be captured. Why wouldn't they just, you know why wouldn't prices trigger their stop losses and it's because, as we know, and many of you here have done this is that there's something called loss aversion bias, right, lab loss aversion bias. And it's where pain feels worse than gains feel good. And it's just a natural thing normal human bias right we tend to really focus on the pain, rather than the good rather than rather than pleasure. So pain feels worse than gains feel good or pleasure feels good and it was done by some it was actually an experiment by some scientists. So it's a natural thing that we do right and how that manifests itself in in trading is that traders don't want to realize the loss. So what they do is they move and remove their stop losses because the pain of losing is just too much. So let's say for example they've been on a two or three trade losing streak maybe they've over leveraged they've you know risked, you know 5% 10% on the trade right they don't want to realize this loss. So as prices start to go against them. Right so they've been, they've committed capital, and as prices go against them and they start to move their stop up right so these guys the retracement traders who stopped losses above this resistance level, the breakout trader who got in on this breakout this nice bearish candlestick here. These guys are moving and removing their stop losses because as price goes against them they don't want to realize the loss. They don't want to. And in the short term we get emotional with traders we shouldn't really but we all do. And we make these repeated mistakes and you move and remove your stop losses right. And as you're starting to do that now you get caught in your position because rather than risking 5% and getting stopped out or 10%. Now you're down all the way up here maybe you're down 20% or 30% or 50%. Yeah, so now things you just dug yourself a hole you're kind of caught in your position I only really meant to lose 5% of my account on this one trade now I'm down 25%. You're hoping and praying. Yeah, that prices come back because the pain. Yeah, so the pain there. Yeah, so it can be captured as prices go against them is more and more and more pain because now you're thinking to yourself.  I put everything I had to put my children's you know, school funding there I put my, my Mrs, you know wedding funding there. And I cannot realize this loss. Yeah. And the more that prices go against traders. This is the pain that they suffer and this isn't a phenomena for retail traders this is all traders because traders river your institution of course you have risk managers in institutions but we know that institutions can trade their way out right they have sophisticated or more sophisticated in hedging strategies that can hedge their way out right whereas the retail trader doesn't but regardless of whether you know institutions and retail are hedging their way out. The point is, is that traders are caught in their positions and they fill in a lot of pain and when you're feeling a lot of pain. The only thing you want is pain relief, right. It's pain relief. And the only relief that you're going to get or some sort of relief is if prices come back down to this area right there. That's it. Because then you can get out for your original loss or somewhere there are thereabouts and express trade in the book is what a break even trade or a small loss or your original loss especially if you were down like 50% you're seeing your unrealized loss.  Right and let me just clear this chart up a little bit. If you sold here. Yeah, to get sure to exit your trade you've got to do the opposite thing you have to buy. So yes a buy order. Yeah, traders who new traders who are looking at this level of what support support resistance if prices come back down here going to do what what are they going to do what would you do if you saw that. Buy that's exactly it so more buying so more demand what is buying is demand right by orders of demand and then you've got traders who would have shorted up here maybe wrote it down. Yeah, it's to certain areas taking take profit areas tend good take profit areas tend to be areas of support and resistance because you know where price it's known I call it a trouble area right. Prices have been rejected from there so you're probably going to take profit there if prices break through more traders are going to take profit where around here and if you sold up here then you're the opposite to take profit you have to do what buy to exit the opposite. Yeah, so there's so from a technical analysis perspective. Yeah, we understand why there should be more buy orders than sell orders the question you always have to ask yourself at a level is why is there likely to be more sell orders technically. Not the sentiment wise but technically. Yeah, as to why you want to be a buyer or a seller. Yeah, and we know pretty much the actions of all mark technical analysis. Market participants, because pretty much 99.999% you can trade as there's thousands of different strategies out there, but they all get grouped into breakout, retracement and level traders. I don't know of a strategy and I haven't I don't know many strategies I don't know hundreds of strategies but the point is is that every strategy that I've ever, you know, I guess looked at on YouTube, you know, eight from over seven eight years ago, all involved support and resistance because that's where the turning points are. So that's where there's going to be a lot of potential liquidity and a lot of trading activity. And this in fact turns into an intraday demand zone. This is this is what I know is an intraday demands and CPR zones can be obviously can use them on the daily but intraday demand zones that whole area there is demand. From the top of that support support resistance zone all the way down because none of us know where within this zone, right where prices are going to turn around. No worries john no worries, no problem it's being recorded so have a good one. Anyways, so, so the point is is that this, I'm just giving feedback and I just this was just the educational purposes I know we've got some new guys in here but Ken's chart. Yeah, for me this is fantastic. This is what I would class and a one set up and it has that added bonus of fundamental analysis. So with the Bank of Canada. Yeah, announcing Bank of Canada announcing that they will say announcing but first of all inflation went higher. And they are reducing their buying of bonds I think it is or purchases. So that is positive for the the Bank of Canada and I guess the Canadian currency. And so what you have here also is if prices come back here this is now going to be seen as an absolute bargain if the rumor is that they are going to hike rates sooner rather than later. Because anyone who missed out here all the big institutions that didn't manage to get their orders filled in and around here now know. Yeah, exactly so there you go. Thank you so they've also upgraded their GDP forecast. So now when you think about the CAD versus the Swiss Frank. Yeah, Swiss Frank negative interest rates. They're not even close to raising interest rates and even talking about raising interest rates. Yeah, now this looks like an absolute bargain if prices ever come back down here, knowing what we know GDP, inflation, interest rates, everything going in the right direction. This now looks like an absolute this is what you would I would class as a once out. This is a one for sure. Yeah. So for me doesn't get really much it doesn't get much better than this because you've got the fundamentals behind you. You've clearly got the rest of these other traders who have been caught in their positions. So yeah, this is this is a this is a fantastic trade setup for me. I want it to go a bit higher. I want to maybe break another level or so just to add more pain. I'm very sadistic like that I just want more pain more pain for them and then I want relief I then I want it to trickle back however it comes back and in the in the time that it comes back. Yeah, don't don't think to yourself oh why why why is the can Canadian dollar falling look at it as this is my opportunity to buy again because you know what the financial institutions are looking at that as their opportunity to buy they might manipulate prices to come all the way back so that they can actually do more buying at this price point at this 73 knowing that in the future they want it at say for example 80 in the next you know three to six months. I think I absolutely bargain now unless you know the Swiss National Bank pull a rabbit out the hat. I can't or unless obviously there's some sort of risk sentiment or risk off sentiment or for example even the can Canadian dollar let's say or the Bank of Canada you know maybe say something or do something or maybe there's some really bad news around Canada. I don't see nothing is perfect right anything can happen in this world, but the point is and as I was saying at the beginning of the video is all about probabilities. Right, probably. I don't want to try to type it out with the on my trackpad or probabilities the probabilities of this going in this direction if it pulls back is very high considering all the boxes that we're ticking.  So price can do what it wants to do in the short term medium term but we have to take these trades, but anyways, brilliant trade set up that and let's see how that develops anyone got any questions on that by the way.


How's the Paris experience been so far? I mean it's been great. You know, our flight over was smooth. Obviously eight hours, but pretty simple in general. We got over yesterday. So what we did, we did recovery, a little sauna. So it was a pretty light day. Just in terms of the time that we got in, I got a good couple of naps. And now we're about to have a pretty normal day with hopefully a good practice and start setting up to try to beat the Cavs. Seeing the Eiffel Tower taking photo with the rest of your teammates, what was that like? That was dope. Obviously I think one of the big pieces of a trip that's this long and obviously overseas. And kind of away from the normal routine is we get a chance to really build some extra camaraderie that other teams may not get to do.  So the Eiffel Tower was a part of that.  I think it was cool. About the Eiffel Tower, the whole experience, like, do you get some free time with the schedule to try to enjoy, to get away from all the NBA in the game? I mean, this is only our kind of like first real day. So we'll see. We started with Eiffel Tower, we're gonna have practice now. I'm pretty sure we'll have, you know, obviously different activities and things that kind of immerse ourselves into the Paris lifestyle. But we're all looking forward to the trip as a whole. The game against Cleveland, that's like Cam said, we need this one, even if it's in Paris, it's different, we need this win. Like, is there any extra motivation with all the experience this week? Of course. I mean, I think the energy of the fans and playing a game that's a little bit different than usual adds extra motivation for sure. But, you know, we need the win, regardless with where we are in the season and just understand that every game matters. International game before maybe Mexico? Yeah, I played in Mexico. I was at the China game too. That's probably it. But yeah, no, I mean, those were fun as well. And everyone's a different experience. I'm excited to be here and for taking this. Cool.


Okay, we're back at NAB day two. Wrap up here inside the cube. This is our flagship telecast, siliconangle.com, siliconangle.tv. Now we're going to wrap up today's segment and we're going to go into afternoon presentations that Intel Studio Experience has a slew of demos. If you're here at NAB or you're watching on Twitter, tweet Intel Studio and come by. I'm here with my co-host. I'm Dave Vellante of Wikibon.org and John, we've seen the themes come together. We heard Eric Jackson talk about evolution today. He's a consumer of all these cool technologies and basically seeing evolutionary technologies and things like cameras and other, you know, whiz bang toys, but not a shock, you know, not a shock and awe to him. It's relatively shocking and aweing to me as someone who's relatively new to NAB, but for a practitioner like Eric, not so much. And we heard Tom Joyce talk about, you know, storage, how it's different in this industry and tape and then Autodesk with some really great innovations and a lot of other great guests today. I mean, obviously the theme today for me was the software matters. And then, you know, we're seeing a lot of innovation with software, you know, Autodesk, we heard from Adobe yesterday, we heard from Magic. So, you know, software really is the mean, the proxy for the innovation in the core hardware because you can see the benefits and that's where the applications really shine. The other thing that has clearly come out here is that Thunderbolt is not integrated into HP. I thought that was pretty interesting that it's not fully yet into their high-end workstations. You get a lot of Mac-like competition given the whole emphasis of multi-platforms, so I think that's a big deal. Well, I wonder if I could ask you about that, John. I mean, you were, I think, pretty clear and you, at least I inferred from your comments that you'd think that would be a mistake if HP didn't adopt Thunderbolt. I think it's an HP mistake if they don't put Thunderbolt into the machines. It's just clearly, I mean, again, I have to look at the actual performance. Is it reliable? Obviously, it's as expected pretty as reliable. So I'm assuming it will be reliable. But at those speeds, it's clearly a superior product. And if you're going to have a high-end workstation, you got to have the most superior products. I just think from an HP standpoint, it's just the big battleship of HP. I got to redesign the motherboard. I got to have the connectors, negotiated price with Intel. But it looks like they're following Apple, right? Well, they should follow Apple. I mean, Apple's stock price is higher than HP's. They got to get over that, right? So, you know, but the thing is, it's about Mac competition. Mac had a lot of success at the high-end, the creative, general-purpose creative market. But, you know, you had workstations owning the higher, higher end of graphics and rendering. And I think the big epiphany here is that Mac basically is a UNIX workstation. So what you have here, HP, and now you see with Dell, it's mainly HP. They're UNIX guys. So I think HP's smart to move into that workstation business. Go head-to-head with Apple and say, hey, we have workstations too, and make the fastest car they possibly can. It's for these app subscribers. It's just amazing to see how much love, you know, Apple's getting inside of the Intel booth, you know, 10 years ago, that was in the case. Apple made a major transition to Intel. When it hits someone at HP and Dell, they're just going to give us laptops so we can get, our tactics not working by having Macs on the desk here, Dave. Now, but seriously, it's fun to watch. I think I'm really bullish on the tech companies. I think they all get the impact of the media and how they're enabling the massive change. We've heard about SSD, how that's changed the game. I mean, you can see it on the face of the Autodesk executive, how impactful the performance has been for his job, his company, and ultimately his customers. I think the other thing that's a key point out of today is the democratization of media, and it's kind of cliche to say the democratization of media, but in reality is the tools are out there. There's a zillion different lights, there's different cameras. They're all got the same cars. I think Eric talked about the cars, GM Ford, pick your general car, and then you get the high end, you got mid-range. So you have all the tools out there. To me, democratization puts the tools in the hands of everybody. That's individual corporations. That's also broadcasters and the people. And so software will make it all happen. So to me, my walk away here is looking at the software innovations, and that's going to be my action item this afternoon, is to go out on the show floor and look at the actual software, composite software, and see if I can get a hand on some demo units. So it's a tech rally today. IBM and HP are leading it. Apple bounced back today. So some good things going on tech. And Zynga actually told the street that it's going to start a acquiring company. So Zynga's down significantly, down 5%. And so Zynga's got, as you know, almost $2 billion in cash. So I mean, what do you think about that? Zynga going to be more acquisitive. Well, I think it's the sign that they don't have any confidence in their product leadership. So obviously anyone who knows about Zynga and played Farmville knows it. That horse is not going to stay around for a while.  You don't play Words With Friends? You know, Words With Friends is just a different experience. So I think the gaming business is all about experience. It's like a nightclub. It's always good. And then all of a sudden it gets stale and then people move on to something else. So good move going on, start acquiring companies. I think OMG Pop was an amazing deal for Zynga. They paid $189 million. I think that's the number I heard. Some people are reporting about $200 million for that deal. And clearly that was a fantastic deal. So they paid a very low price relative to what they're getting in terms of value, in terms of users, et cetera, et cetera. How about it, Zynga's got a $7 billion market cap, Instagram, one seventh the value of Zynga. Well, Instagram is a fluke. I think that a lottery ticket, really, ultimately in my opinion, but I think it just goes to show you that the way the market's going is if you put out good software and it hits that thermal, hits that growth, you can have that massive tsunami. And I think ultimately, in order for them to actually compete, they would have done, have to do a monster round of finance, even though they raised $50 million. They still got to hire the engineers and do all that work. And ultimately, I think they're looking at a road saying, hey, I'll take that offer any day of the week. I think they would have taken a half a billion dollars easily. So again, it's very bubble-ish in the sense of the markets, but that's Silicon Valley. Well, and like I said, so tech rally today, IBM HP, IBM's pushing its 52-week high, not quite there, but IBM's market cap's now 239 billion, John. HP, by contrast, which is a larger company, is a market cap of under $50 billion now. So lower than EMC slash VMware. Certainly significantly lower than SAP. So that's something that we've been watching pretty extensively. Other news on the page of siliconangle.com, top story today right now is Oracle execs thought Sun acquisition was a mistake. My first and very interesting story that's coming out. So this is on Silicon Angle. I got to read that story. We've got some big data stories. Nacera had a great article in Wired Magazine around the whole open-stack buzz. They're really a software networking company innovating like a Cisco-type environment in software. So I think we still haven't even seen the embedded killer software yet in some of the networking side of this. I think Thunderbolt is an absolute telegraph move around where the networking business has to go, has to hit the performance levels. That meets video. And then just a lot of other tech news and IT news going on at Silicon Angle around open-stack, but ultimately, earnings are happening. Hulu's got an article in New York Times, adds original programming. So again, back to here. Content is the key landscape change here. And so if you're in the content business, a big deal. Yeah, so that's interesting. I'm reading the Melissa's article on Silicon Angle. Evidently, as part of the filing, some of the Oracle execs said that they thought this was a mistake, which is different than what I thought. So we'll have to dig into that a little deeper. Final thoughts, Dave, for day two here. We had some pretty good interviews. Thunderbolt was interesting. Autodesk was, I thought, my favorite. I really like the special effects, and I can't wait to see the demo of the 1,000 people marching in in the Intel logo. I think that's going to be pretty cool. For me, I think you've underscored the whole democratization of the media business and the tools that are coming into the hands of the masses and enabling people like us. We talked about Leo LaPorte broadcasting, really creating this new form of media. It reminds us of cable back in the late 1970s. So we're seeing the tools come down in cost, the economics are so compelling, and it's just enabling a huge number of people to get creative and provide production values that are much more consistent with what you typically see at high-end studios. And for the folks out there who don't know siliconangle.com, siliconangle.tv, we're going to be launching a 24-7 tech network this quarter. You'll see 24-7 programming from Silicon Angle. We have theCUBE desk here, doing morning and evening news wrap-ups, and as well as CUBE specials, as well as program specials, NAB special, big data special, disruptions of media specials. So we're going to go out there and compete, I guess, with the CNBCs of the World, Dave, and go out and create a tech programming channel to serve the audience, and they are out there on social media. So if we can get that going, that'd be a goal of ours this quarter. You'll take a look on that, keep an eye on that. Other news here, Dave, that you're excited about? Well, I think I want to go by and see that new camera. You have a 7D, right? Yeah, I have a 7D, yep. And so it looks like it's going to get outdated shortly here. All right, well, that's a wrap from day two at NAB with Silicon Angle's theCUBE. We are headlining Intel's studio experience with all great interviews from people here showing off their amazing solutions inside the booth and from the folks out watching. There's a whole afternoon sessions of folks doing demos on this amazing screen behind us, this technology called Sight Deck. We call it the Epiphany Wall. Fantastic, great setup here by Intel, and I want to say thanks to the Intel team. I want to say thanks to Marcus and Hopkins, our producer at SiliconAngle.tv, and an amazing stage here. Very big presence at NAB, and we'll be following the pound NAB show hashtag and we'll be walking the floors. And I'll see if you want to find us on Twitter, you will. And I want Dave to say thanks for day two. It's been great. Yeah, thank you, John, appreciate the collaboration with Silicon Angle, it's always a pleasure. And that's a wrap up for us here at theCUBE at NAB, and we'll see you tomorrow.


Well, I promise to talk really fast, no seriously, the bedside. And do we have a pointer here? Yeah. Is this a pointer? So in the upper left here, I'll be talking about work done in our group at the University of Oregon. And the rest of the people listed on here are clinical groups that we have collaborated with and funding is listed as well. You'll note that essentially all these clinical groups are from Europe, one group from Canada. So we're looking forward to U.S. collaborations, and that's part of the issue that I want to bring up. So as I understand it, my task here today is to provide a perspective from the bench. I'd like to do that by describing two case studies that we have, oh, thanks very much, Carol. Two case studies of successful examples of collaborations with clinical groups. And then I'd like to discuss some of these gaps that Carol alluded to based on our experience working with clinicians. And then at the end, I'd like to touch on the Undiagnosed Disease Network as an example of a way that I think we can have very successful collaborations between clinicians and basic researchers. So the first case study is regarding Usher syndrome and gene discovery. So Usher syndrome is the leading cause of genetically-based combined deafness and blindness. The deafness is congenital, so present at birth it's due to sensory neural hearing loss and the vision loss is due to retinitis pigmentosa. So it's a relatively late onset progressive degeneration of the retina. This is a multi-factorial disease. We know of 11 different genes in which if there is a mutation, this causes Usher syndrome. It's a classic Mendelian recessive disease. Importantly, however, there are still many families that are unlinked to any known locus. And gene discovery is extremely important for genetic counseling in Usher syndrome. If you have a child who fails a hearing test at birth, you'll get some counseling. You could raise that child in the deaf community, which is a reasonable choice, but you may also want to consider cochlear implants. And obviously if this child is later going to be blind, sign language will be insufficient form of communication. And so having this knowledge up front can really help inform the decision by the family about whether to move forward with the cochlear implant and obviously would elevate the child on the priority list for receiving a cochlear implant. However, because the vision loss is very progressive, late and progressive, we don't have good means of testing vision in newborns. And so really the only way to know that this child is later going to have Usher syndrome is through genetic testing. And if you don't know what the genes are, it's pretty hard to test for them. So gene discovery is still extremely important. So we have developed zebrafish models of all the known Usher genes and are studying their functions. And I had a postdoc who was presenting a poster at an international conference. And a clinician, Hano Bolz, came up to our poster and said, I've got a bucket full of patients and families, and we're trying to discover what the genes are. Do you want to collaborate? So this is really sort of a one-off, happenstance interaction that we had. And this led to gene discovery. So they, that group, had done a whole exome sequencing of these families and came up with a candidate, the PDZD7 gene, which was a completely unknown function at the time. And they had picked up variants of unknown pathogenicity in several different families. So how do you move forward from this? How do you try to show causality that mutations in this gene can cause the disease? So we cloned the ortholog and zebrafish. We showed that the protein co-localizes in the retina and in the inner ear with other known Usher syndrome proteins. We showed that in the mutant loss of function of the, or in this case of morpholino, loss of function of this protein results in defective stereocilia and deafness in the zebrafish. And we also showed that it can lead to retinal degeneration. So interestingly, of the families that we've identified, in every case, the PDZD7 mutation appears in a heterozygous form with other known Usher gene mutations, either in heterozygous or homozygous form. So here we see a family in which the son is heterozygous for a known Usher gene, GPR 98, which normally would have no symptoms at all because this is a recessive Mendelian disease, but this patient presents with Usher syndrome. This family is even more interesting. They have two daughters, each of which is homozygous for a known Usher 2 mutation. One of the daughters carries an additional variant allele of PDZD7, and she presents with much more severe symptoms than her sibling. So these types of data suggested to us that PDZD7 may actually be acting as a genetic modifier. So to analyze that, we could use the zebrafish to model these genotypes using morpholinos. So in this experiment here, we use a half-dose, in other words, knocked down about 50 percent of the protein activity of the GPR protein and the PDZD7 protein. And of course, there's no phenotype. It's heterozygous. But when we combine these two half-doses, we see retinal degeneration as in the patient. And this would be the genotype of the other family where we have a homozygous, a full knocked down of Usher 2a, a half-dose of the PDZD7, and this exacerbates the phenotype, as we saw in the patient family. So this suggests, again, a genetic interaction. So we were able to show with pull-down assays that these two Usher, well-known Usher proteins bind to the PDZ domains of PDZD7. And currently, the model is that these proteins actually form a quaternary complex.  And unlike Howard's example, shortly after this work was published, PDZD7 was added to the panel of genes that are tested in children who are potentially, who have Usher syndrome in which genes, they're trying to identify what the actual variants are. So this is a really successful example, I think, of how you can go from the bench, from the bedside to the bench and back again. But there are still some gaps. I think that this successful example illustrates. First of all, where are the missing homozygous and compound heterozygous patients? Is this simply the fact that it's embryonic lethal? The model organism data would suggest not. We've subsequently made mouse mutants. They also are perfectly healthy, happy animals. So it seems to us more likely that there are probably, that the patient pool is just too small. So there are patients out there that we haven't found yet that are homozygous or compound heterozygous for mutations of PDZD7. So why haven't we found them? Well, is it because there's limited access to patient data? Is it perhaps that the clinicians are not telling us about the patients that they have? They're not testing them? Or worse yet, are they actually acting as silos and hanging onto their patients and not sharing? So let's move to the second case. This is the opposite type of experiment in which negative results can actually reveal incorrect diagnoses. And this example is Jubeir syndrome. So here we had a family, a consanguous family, that have three children with deafness. Due to the consanginity, we thought we could do mapping for homozygosity by descent. However, this was uninformative. We came up with no good candidates. So again, we relied on whole exome sequencing, again looking for homozygous snips because of the structure of this family. And we found homozygous mutations in AHI1 gene, which is a very well-known gene that's responsible for Jubeir syndrome. Jubeir syndrome, as you may know, is due to under development of the cerebellum and brainstem. It involves patients present with seizures, retinitis pigmentosa, developmental abnormalities, kidney and liver abnormalities. And these patients were deaf but had none of these other signs. Most importantly, the MRI was normal, and this is the key diagnostic for Jubeir syndrome, the abnormality of the midbrain in which it appears sort of like a molar tooth. So what's going on here? So we look at the mutation, the specific allele is a truncation of the protein right at the beginning of the very important protein-protein interaction domain. So most of us, based on our biochemical training, would argue that this is going to be a loss of function because this protein cannot bind to its binding partners. The mutations in the various databases that are known to be disease-causing cluster in more interminable region of the protein. So again, we made models of this, truncating the protein, introducing mutations in this region that's known to cause disease. And this produced a very strong Jubeir-like syndrome in the zebrafish, which is extreme ciliopathy, very consistent with other known Jubeir gene mutations. However, when we modeled the patient by truncating the protein, eliminating this protein-protein interaction domain, the animals developed relatively normally and did not show any of the traditional Jubeir syndrome phenotype. So this is really kind of a scary result, in a way, because patients that have this mutation would be predicted to get the disease when, in fact, they do not. So I think this has pretty important implications for the interpretation of exome data, particularly in terms of diagnoses, making decisions about treatments, and I think especially for the interpretation of variants of unknown pathogenicity. So we went back to the family on the basis of this, and were able to obtain DNA samples from other SIBS and found that, in fact, one of the other SIBS was homozygous for the same alleles and yet did not have the deafness. So I think together this really points out some of the strengths of even getting negative results. So together, these two studies, I think, illustrate several points, several gaps between the exchange of information, the exchange of information between clinical and basic researcher groups. Most importantly, I think there are very significant barriers for basic researchers to access patient data. So some of these barriers might be sociological. I think Howard sort of alluded to this. It's the different attitudes that clinicians and basic researchers have. Also there can be certainly limited access, and this has been our experience, to clinical records. We have found that it's extremely important to get as much information as possible about the patient phenotypes, and in these examples that I talked about there, it's been sort of haphazard interactions that we've had. So we've typically gotten sort of de-identified clinical records. But really, if we could obtain IRB-approved access to the full clinical records, we could look at the full suite of symptoms that the patients have and thus produce, I think, much better models. And I've touched on the idea, too, that there may just be very limited access to patient data. And I think that's a problem that's difficult, one that we should face and perhaps come up with some solutions. So in contrast, in the last couple of minutes, I'd like to just discuss our interactions with the Undiagnosed Disease Network as an example of a very successful way to move forward. But I think, as most of you probably know, the UDN is composed of seven clinical groups distributed across the U.S. There are two sequencing centers, Hudson Alpha is here at this meeting. There's a metabolomics core, and of course, most importantly, there's a model organism screening center, which flies in Baylor and zebrafish at the University of Oregon.  This network is identifying thousands of patients with undiagnosed diseases. The sequencing centers identify the variants of unknown pathogenicity, and then we generate models of those exact variants using then the wild-type human CDNAs to rescue the mutant phenotypes as a proof of principle for validating these variants of unknown pathogenicity as disease-causing. And this is really, I think, an excellent example of how one can have a free and open exchange of information between clinical groups and basic researchers. But obviously, it's limited just to two basic research labs. So I would say this type of model should really be dramatically expanded and make it available to basic researchers throughout the country. Before the network came along, as I said, our interactions were really extremely haphazard and sort of one-off, and this is really pretty frustrating when one has the best model out there, obviously, and wants to be able to have clinical collaborators to help identify the genetic basis of undiagnosed diseases. So in summary, I've given a couple of case studies here where positive results can help validate genes, where negative results can reveal potentially incorrect diagnoses. And I've brought up some of the issues about gaps, at least from the perspective of the basic researcher, and discussed briefly the Undiagnosed Disease Network. So I'd be happy to take questions. Thank you. Questions. Thanks for that great presentation. I wanted to just ask the question, the context of the negative results. Given the concept of incomplete penetrance, how do you weigh your negative results in the context of what you see within a pedigree, between pedigree, and this concept that some variants may have incomplete penetrance, depending on the genomic context, how do you deal with that issue? Right. Yeah. So that's a really good question. And I think in terms of the animal models, it's difficult. So the examples that I talked about, we're looking at very strong loss of function mutations, and essentially Mendelian inheritance. And obviously, a lot of the variants that are coming, particularly the ones through the Undiagnosed Disease Network, have other modes of inheritance. So I think you have to really deal with that on a case-by-case basis, and have as much information about the human genetics as possible, and then try to develop a model that will be appropriate. There are obviously going to be limitations inherent in any model system. My question is related to the same topic, and it's, for me, I believe in the case of the Jovert syndrome, I probably believe what you presented, and that case in which, despite being homozygous, being expressed is a great opportunity, from my perspective, to look at what environmental factors, for example, dietary fat, from my perspective, could be influencing the expression of that phenotype. I remember something related, like retinitis pigmentosa, in which apoE and omega3 could be playing a complex role there in the expression, so that's a great opportunity to learn more rather than to dismiss that as being a real finding. Right, right, very good point, and I think that's the strength and probably the insight of the undiagnosed disease network to include a metabolomics core, so it really makes sense to run not only the human tissues through the metabolomics core, but also to use the metabolomic cores to analyze the model organisms. So yes, as holistic approach as possible is extremely important, particularly in the case of these negative results. I think it's important to consider or think about the question of causality and penetrance as independent, although when you get decreased penetrance, it makes the study of the causality more difficult, obviously, but in the clinic, one could say, we know that this causes this disorder, we don't know how often it's penetrant, so the information may still be useful to the patient, even though we don't know the complete story on the penetrance. Good point, thank you. Just a quick comment that I think we can't expect that the medical record holds all the phenotype information, and I think we have to remember there's a patient in the bed or a person in the chair, and very often the information we need to correlate with the symptoms that the patient is having, only the patient knows, and so I don't know how we capture that data, but I think it's a very important issue as we go from bench to bedside and back. Yes, that is a good point. I think the point I was making is that whatever patient information is available, that should be made available to the basic researchers, too, because it's extremely frustrating to follow a path when you have only half the information. Dan? I can't see. I hear a voice. The one next. Yeah, so this last discussion sort of moves us a little bit from sort of straight Mendelian disease. When you start thinking about modifiers, that sort of moves us along closer and closer to more common diseases. I think you've already made a compelling case. The UDN might be a great model for how do we think about expanding the basic science clinical interactions for Mendelian disease, but how far down the line do you think we can go with this in terms of complex disease? Right. So it probably depends a lot upon the model. So you can imagine making double and triple mutants in mice, but it gets painfully expensive and difficult as you move along. And so perhaps other models, zebrafish and maybe other, yet other models would have some benefits there when we get to multifactorial diseases. Mark, a quick comment on aquatic cancer. And this is just in response to Deborah's comment about the patient. I think we do have models that are emerging through a Genome Connect and others that are looking at innovative ways to engage patients and families in this type of work. And I think that that's something that also needs to be considered in the context of this discussion. I think we'll stop there. Thank you. And move on to the clinical perspective on need for integration.