Well, good afternoon, everyone. If everyone would take their seats, we will start this symposium. I'm Eric Green, Director of the National Human Genome Research Institute, and I want to welcome all of you to this modern code symposium, Genomics of Model Organisms and Human Biology, where we hope to showcase for you insights from the modern code project and NHGRI-led initiative. I want to welcome all of you. I hope you're enjoying the lovely, cool confines of this auditorium in the Natural Conference Center, which is far cooler than what is currently outside in the near 100-degree Washington, D.C. area weather. We are here today to celebrate and to showcase the modern code project and, more broadly, to showcase the important role model organisms play in the biomedical research landscape. What I wanted to do in this opening talk, if I can have my slide, is really to set a context for the talks that are going to follow later today and tomorrow. And in particular, what I hope to accomplish if I ever get my slide, and there it is, what I really want to accomplish is really to set a landscape view for all of you, so you can really appreciate the role that model organisms research, especially genomics research, has played and will continue to play across the broad swath of genomics research activities. In doing so, I want to tell you a little bit about the past. And then in particular, I want to emphasize sort of the present as exemplified by a strategic plan that is really guiding the field of genomics in a particular NHGRI in terms of its research pursuits. And then also give you a little bit of a glimpse of the future, especially with respect to the trajectories that we're trying to put in place through our strategic plan. Now, going to the past, lots of places I could start, probably the most relevant one for this particular symposium, and for the field of genomics, of course, would be the Human Genome Project, which began October in 1990. And I dug out a slide that I have been using since I was a postdoctoral fellow working on the Human Genome Project. And the slide really emphasized the fact, it's a slide I used many, many times over the years, that the Human Genome Project, its name was a bit of a misnomer. It wasn't exclusively focused on human, but rather a carefully selected set of model organisms were chosen. Their genomes were sequenced, studied, and then eventually sequenced. And in particular, they were chosen because the unique contributions in terms of insights that genomic knowledge would provide about different aspects of biology. And this group, Security Council, if you will, of organisms really, of course, augmented knowledge we would gain about the human genome through the mapping and sequencing of the human genome. And the Human Genome Project, of course, was remarkably successful in its pursuits, including model organisms. If we take a brief walk-down memory lane, if you will, you would recall the first eukaryotic genome sequence to be established was that of yeast reported in 1997. A year later came the first animal genome sequence, C. elegans, ably led by individuals in the field, and particularly Bob Waterston, that you'll be hearing from shortly, and John Sulston, and really was a tour de force study that in many ways laid the foundation for sequencing larger and more complex genomes, including the human genome. A couple years later came the sequence of Drosophila's genome, and then one year later came the draft sequence of the human genome, this landmark publication in nature reporting the first mammalian genome sequence. And then remarkably just a year later came the publication in 2002 of the second mammalian genome sequence, that of the model organism, the mouse, which has played such a critical role as a complement to knowledge about the human genome with respect to having a model system for doing genetic studies. A year later came the end of the Human Genome Project in 2003, and with it, of course, came lots of activities to pursue new research avenues that were facilitated by knowledge of the genomes of human, mouse, and these other model systems. Now, genomics has gone in various directions with the kinds of technologies and the kinds of opportunities created by the Fruits of the Human Genome Project. The ones, of course, that we focus on here at the National Institutes of Health, and in particular at the National Human Genome Research Institute, are those that focus on health, disease, and medicine. In particular, NHGRI, which is now an Institute, I have been the director for a little over two and a half years, I can tell you that a significant amount of our effort is now focusing on developing a path towards an era of genomic medicine. Medicine would have been tailored to the individual based on genomic information of individual patients. But of course, that's a very long, complex journey. It's one that our Institute will focus on, I'm sure, many years ahead, but we regard that mission as sort of critical for the reason why we sequenced the human genome in the first place. So in thinking about that journey from the base pairs of the genome project to bedside of patients, or if you prefer the metaphor, from helix to health, when the genome project ended, in fact, precisely the day that the genome project ended from this podium, I can tell you, was the declaration of the genome project coming to an end. And at that point, we also unveiled this new strategic plan in 2003, which a number of us, the leaders of the Institute, put together with help from the community. But at that time, Francis Collins, I know, stood at this podium and described the set of activities that would be pursued now with the sequence of the human and other genomes in hand. And one of the initial steps and a key part of this 2003 strategic plan was the recognition that the human genome project delivered a lot of sequence. And it was good sequence, it was accurate sequence, it was important sequence, but at the same time, one of the next steps that absolutely had to be pursued would be to try to understand the function of that sequence, whether it be the human genome sequence as shown here, but really more broadly, we were thinking about needing to understand genome function in general, and that would in particular inform the human genome sequence and knowledge of its functional components. It was really just a short time thereafter that NHGRI decided that indeed a focus effort to pursue this was critically important, and that led to the birth of the ENCODE portfolio, the ENCODE portfolio, which goal was fundamentally to elucidate genome function. The first component of this was the ENCODE project, Encyclopedia of DNA Elements is what that is short for, which as a project focused on getting a catalog of functional elements of the human genome. But even at the earliest stages of planning the ENCODE project, and I can recall because I was involved in the workshops leading up to this, and I even recall the council discussion, our advisory council when they discussed the ENCODE project was a recognition that to really be effective at this, and to really understand the human genome through the kinds of efforts that ENCODE would pursue, we needed a complimentary effort, as has always been the case in genomics as part of the human genome project, for example, with model organisms. And so shortly thereafter, the MODENCODE project was born with a particular focus on flies and worms, but in addition, of course, since then there's even been MODENCODE components that even include mouse. And it's this MODENCODE effort that we're here to celebrate and the MODENCODE effort that we are here to also showcase. Now what I will tell you is much like the human genome project and many major projects that have been pursued in genomics since the end of the genome project, ENCODE and MODENCODE are very much large consortium team efforts that whereby the efforts really only come about to fruition through collaboration, through extensive teamwork, shoulder to shoulder, shoulder on shoulder in some way efforts that just has proven to be critically important. And in many ways, this NHRI is distinct among most of the other NIH institutes in that this is the style of science that we foster and this is actually what we think we do very well. And I think what you're gonna see for the next day or so in a series of talks that really are showing the accomplishments of the MODENCODE project is in fact that consortium-based science is critically important for this area of research. And what I will predict right now is that the majority of the speakers that you're gonna hear from, just look at their acknowledgement slides at the end and just remember this image and you're gonna see the parallels because what you're gonna quickly learn is that so much of what's been accomplished in ENCODE and what you're gonna hear about is MODENCODE really has been massive group efforts that have required expertise of many people, multiple disciplines, coming together with a shared goal and ending up with the accomplishments that are gonna be discussed. So where are we with ENCODE and MODENCODE? Well, what I will tell you is that we shouldn't recognize these as done projects by any means or done efforts. While the sequence looks amazingly simple and in the case of ENCODE, for example, focusing on the human genome and well underway, I am quite convinced we will be pursuing a complete understanding of the functional landscape of the human genome and these other model organism genomes for many years to come. In the case of the human genome, I sometimes joke that maybe at best we have a Cliff Notes version of it, but decades from now we will still be interpreting, re-interpreting all of these genomes. I think you will hear in the talks that will follow surprises that have completely caught us off guard even in the four or five years that have passed in recent days with respect to thinking we understand all the functional and complexities of a genome and recognizing that there's even more complexities there than we had previously appreciated. So that's a bit of the past, but what I want to tell you is a little bit more about the present and in particular, this strategic plan has guided us well certainly since 2003, but several years ago we recognized that especially with technological advances and the data influx that came with those, that new opportunities were on the horizon and it was time to sort of put another stake in the ground, if you will, with new strategic plan and that's exactly what we did in completing this a year ago and I'm hoping that many of you have seen this strategic plan published in the 10th anniversary issue of nature that commemorated the draft sequence of the human genome 10 years earlier. If you haven't seen this strategic plan, it's a very easy URL to go to, you could easily download a PDF and share it widely and hopefully read it critically, but this strategic plan in many ways captures the present and also looks to the future and that's what I want to spend my last few minutes describing to you. For those of you who have not seen this, I also want to sort of set a context again for where modern code and efforts like it fit into this. In this new strategic plan that really guides, we think the field but certainly is guiding NHGRIs thinking about genomics. What we heard from some very helpful advisors and colleagues that we invited into various workshops and planning sessions was that we had an opportunity to be far more specific and far more sophisticated in describing the research activities that were gonna be needed in moving us from base pairs to bedside. And in particular, this could be organized under sort of five major domains of research activities. Some of these were very familiar to us and some of these would be new for us. So for example, one domain of research activity would involve using genomics to understand the structure of genomes, that sounds very familiar. Or in particular a second domain using genomics to understand the biology of genomes while modern code and code fit squarely in that second domain of research activities. Of course, we're interested in using these advances to better understand human health and disease. And so a third domain would be to use genomics to understand the biology of disease. From such insights, of course, one would imagine having opportunities to advance medical science. And so the fourth domain would be to use genomics to advance the science of medicine. But recognizing that not all medical advances lead to changes in healthcare effectiveness, we also needed to take on the responsibility which we are doing into use genomics to demonstrate that you can improve the effectiveness of healthcare using genomic information. So these five domains provide a framework by which we think about strategically the things that we want to accomplish. But let me also point out and the people in the audience and listening through video cast who think like model organism basic scientists as many of you do will recognize that this progression from left side of the slide to the right side of the slide is not the only way science progresses. And in fact, there's a non-linear aspect to associate this and we don't mean to imply otherwise. And by that I mean discoveries in one domain can often immediately yield insights or new lines of experimentation in a non-adjacent domain. And also the reverse order takes place where you can start at the bedside of patients and work your way back. Or for example, insights that you may gain about the biology of a disease might instantly tell you and give you insights about how genomes work and how immediately lead to experiments that maybe you're done in model organisms to provide more deeper insights than one can get by simply working on human diseases alone. And so there's an interplay of these different domains that's very healthy. You just have to, with the way we represent it in a two-dimensional figure, it ends up seeming like it's progressive from left to right, but that's not really the way we mean to imply the only paths. The other thing that's very useful we have found for these five domains is to use them to sort of think back on what's been accomplished over the last 20 years in genomics and also to look forward over the next 20 years. And the way we chose to do that was by simply representing genomic accomplishments that had taken place at different time intervals and then in different ones of these five domains. So for example, we represent the human genome project as an era with many, many accomplishments shown here as these dots first blue and as they pile up on each other then progressively changing color, eventually becoming red. Fundamentally, the human genome project was efforts that led to accomplishments to understand the structure of genomes. Sure, we learned a little bit about the biology genomes, but fundamentally it was the first domain where most of the accomplishments took place. When the genome project ended, we continued to explore the structure of genomes, of course, but through efforts like ENCODE and MODENCODE and many others, we began to explore and understand much more about the biology of genomes, leading to many dots filling into the second domain. And sure, some advances took place in these other domains, the disease specific domain in the middle and maybe even a few accomplishments out in the more clinical domains, but fundamentally the activities in the past decade or so have been the center of gravity resides in the first two domains. Thinking about the future, well, the future we think first over the next decade or so is gonna see a progression of accomplishments so that the greatest accomplishments we think are gonna reside in the second and the third domain. In particular, as I alluded to before, we have a lot more to learn about genome function and we think a lot more is going to be learned in the next decade, but we also think at the same time this is gonna be a decade of great excitement as advances really do lead us to greater insights about the biology disease. With that will certainly come more accomplishments in the more clinically oriented domains in the far right, but realistically we think the greatest accomplishments in those more clinically more difficult domains and thinking about the things that need to be done realistically are not gonna be happening as much in the next decade as we'll be taking in the decades beyond then. So there's another subtle feature though that I also wanna point out, actually before I do that, let me just also point out to you and you're gonna see this play out in multiple of the talks you're gonna hear is that what is driving this forward over the next decade and in particular beyond that, probably more than anything else if you ask me to name one thing, one issue, one factor that is driving this progression from the left side to the right side. What I would tell you it almost certainly has to be the dropping costs of sequencing genomes. And so in particular, for those who don't think about these numbers, let me just give you a flavor and then we'll try to extrapolate that to what this means for model organisms. If we think about just sequencing the human genome, when we first sequenced that very first human genome as part of the human genome project and when we actually were actively sequencing it took something like six to eight years and cost something like a billion dollars, especially if you round up but that's around the order of magnitude we were dealing with. When the genome project ended, people sort of did some calculations to say just today, the day the genome project ended we went back and tried to sequence a second human genome. The predictions at that time were using the technologies available that would take something like three to four months but still would cost 10 to 50 million dollars. I don't need to tell a sophisticated audience like all of you what has transpired in the last five or six years in terms of these next generation sequencing technologies have been just truly mind boggling. And what's happened now is of course today in the course of maybe a day or two or three for a cost of maybe four or five, $6,000, you can get an entire human genome sequence. Truly astonishing reduction in the cost of sequencing. But then think about how much bigger the human genome is with respect to the genomes you're gonna hear about in this symposium, worms and flies and so forth. And with their much, much, much smaller genomes the cost for sequencing their genomes is just ridiculously small. And what you're gonna hear therefore are some remarkable studies probing genome function because the same methodologies that can be used for sequencing human genome can be used for not only sequencing model organism genomes but as readouts for all sorts of assays that are used to be able to elucidate genome function. This has really driven the encode and the modern code projects forward and you're gonna see how some of these applications are gonna continue to drive these forward because these remarkable technological advances. Very last thing I wanna point out though is that this figure from our strategic plan which is figure two, it's the organizing figure in many ways this is the icon that I can tell you NHGRI looks at and thinks about in developing programs and thinking about our strategic planning going forward has some subtle feature that I think is very relevant to this symposium and by that I mean if you notice it's not all the activities that are gonna deal with diseases and with medical science and with healthcare and in fact if you notice over the next decade and even a decade beyond that a significant coloration if you will of accumulated hypothetical dots of accomplishment a remain in the second domain and the third domain and I can absolutely assure you that the reason we are thinking in those terms is the recognition that so much of understanding the biology disease and so much at understanding the biology of genomes especially when you get to some of these key mechanistic aspects of disease and of genome function are simply not going to be fully elucidated by studying the human system and by that I mean there will absolutely continue to be a key role of all these model systems shown here and probably others and the interplay of these models with what we learned from humans but inevitably we will be looping back and having to use model systems to really understand human disease mechanism because realistically the limitations associated with human systems are so profound compared to the genetic manipulation one can do to these models that we recognize that in so many ways these are gonna continue to be so incredibly important and then think about how the genome sequencing technologies in many ways democratize the ability to study these genomes and how much simpler they then are in the case of worms and flies and yeast and so forth that one could imagine that this not even just being an endeavor that NHGRI is thinking about but indeed as these various disease studies are taking place across all the institutes at NIH and their disease specific areas that the same interplay of genomics model organisms and disease understanding will become sort of just a commonplace as science marches forward. So I really wanna emphasize as you listen to your the talks in this symposium that recognizing that many of these dots that remain over the next 10, 20 years in that second and third domain very much apply to model organism accomplishments. So lastly I wanna point out that NHGRI is holding this symposium but of course symposium tablets don't get pulled together without hard work of staff. I wanna acknowledge in particular the four people at the top, Carolyn and Mike and Leslie and Elise who have put in a tremendous amount of work to organize this. In addition to the people sitting in this room this is being video cast live to probably many people around the world oftentimes we find we will also be video archiving this and featuring and making it permanently available on the genome TV channel YouTube that NHGRI now has and I can tell you from experience that when we put on symposium like this and bring in all star speakers that are gonna follow me that indeed we get just tens and thousands hundreds of thousands of hits and so this is sort of for the permanent historic archive but it will absolutely be used actively in the coming weeks and months as many people who can't be here today I'll be listening in about these fascinating and important talks about Madden code and also I wanna thank the individuals in the bottom who are some of the individuals associated with our contracting group who helped facilitate some of the logistics associated with this symposium. So with that I will stop I will thank you for your attention and I hope this was a valuable context for you to now hear the rest of the symposium and with that I will turn the program over to Elise Feingold.


My name is Andrea with Foodimentary Adventures in Food.  On our channel, you'll find simple and tasty dinners using everyday ingredients. So for dinner tonight, Howard grilled some pork steaks that I had in my freezer, and here they are, and they're pretty big, so we're actually splitting them. So this is our dinner. We've got pork steaks, and then on the side, for the sides, I should say, I made this Posteroni, which I also had in my pantry, and then I had some fresh Brussels sprouts. So Howard grilled those for us as well, threw them on the grill, and this is the seasoning that I used for the Brussels sprouts, and I just tossed them in some olive oil as well. So this is what we are having for dinner tonight, and we will see y'all next time. So for dinner tonight, we are having shrimp. I am going to be using this packet of seasoning that I have used before, Howard and I really liked it. I found this at Walmart, and I think it's like $1.33. It's in the Ethnic section, and it says Cajun Shrimp, but Howard and I really think that this kind of tastes more like jerk seasoning. It is very good. So I'm just following the instructions on the back of the package. I've got one pound of shrimp that I've cleaned and drained, and then it calls for onions. I'm using frozen onions because that's what I had, and then I'm adding in the seasoning package. That is Harrison, and then it calls for two tablespoons of Worcestershire sauce. The recipe also calls for onions. I'm sorry, lemons, but Howard is not a huge fan of lemons, so I'm not going to add them. I'm just going to give this a stir, and now I'm just going to move over to the stove. Okay, I've got my butter melted in the skillet. The instructions actually said to add your shrimp to the skillet and then add butterpats on top, but I just decided to melt my butter, and now I'm just going to let all of this cook down. Okay, so here's our dinner. I decided to add in some green onions.  I just sauteed it with a little bit of grape seed oil, and then I used this to season it with. So this is what we are having for dinner tonight, and we will see y'all next time. So for dinner tonight, I am making my version of a patty melt. So I did a haul a while back ago. I went to Costco and I bought these for the first time because they had them out at Samples, and I thought they were really, really good. So this is what the box looks like. You get 12 in a package, and like I said, they are fully cooked. I'm getting ready to open these up for the first time. I've got some oil and onions going in here, and then I'm getting ready to add in my patties. And then I've got some bacon that's ready to go. I've got some sharp cheddar cheese, and then I've got some white bread. So I'm going to just grill these up once my patties are done. Okay, so here's dinner. Here is my patty melt. All I have on there are the onions, cheese, and bacon serving it with a side of cheesy puffs. And I actually got these from Bucky's, which is a convenience store. And I got the jalapeno puffs. And then this is Howard's plate. He does not like his sandwich is grilled, but he added on avocado. He didn't have any condiments this time, which I'm surprised. And he's having some cheese puffs too. This is actually a pretty good size bag and we just split it. And then I forgot to show you all on the burgers what's in the burgers. I normally don't buy these pre-made burgers because they have a lot of additives and things in there. But these, as you can see, just beef, water, and spices. And like I said, they are very, very good. Let me try to get in so you can see them. They're really good and juicy. So anyway, this is what we are having for dinner tonight and we will see y'all next time. So I am trying a new recipe for dinner tonight. It is called one pot taco spaghetti. So in my skillet here, I have browned up one pound of lean ground beef along with some onions and garlic. And I just added in some water and I'm adding in taco seasoning right now. Of course, I'll make sure to leave the recipe in the description box. And now I'm going to add in some diced tomatoes. And I'm just going to stir it all up until they're combined. Until everything is combined. And then I'm going to add in my spaghetti noodles. So there it is. That's all stirred up. And let me add in my spaghetti noodles. So it says you're supposed to add them in and then just make sure that they're covered up by the liquid. I may have to break these in half. Let me see here. I thought this pan was big enough. Maybe not. I don't know. Okay, I'm going to have to work them in. It looks like they are going to fit. I'm going to work them in. You're just supposed to cover it and then let these cook for about 15 to 20 minutes. Okay, so I managed to stick all of my spaghetti noodles down in there. My skillet is an 11 inch skillet. I would probably use a larger skillet next time. If you have an 11 inch skillet or smaller, I would definitely break the pasta in half. But it says to bring it to a boil. So it's just now starting to boil. And then it says to cover it with the lid and then cook it for 20 minutes. And then once it's done, I'm supposed to add on some cheese and then cover it and then let the cheese melt. Okay, it's been about 20 minutes and the noodles are cooked. And I tasted it. I feel like it's a little bit bland. It was a little bit bland. So I added in some of this chicken bouillon. Because when I originally read the directions, it said to add in two cups of water and I thought, man, that's going to be kind of bland. Maybe I should add some chicken broth or beef broth and I didn't. So it is a little bland. Just be aware, even though there's taco seasoning in it, I think that the water kind of watered it down. So now I'm just adding in cheese. It calls for cheddar cheese. But in my freezer, I have this bag of half used nacho taco blend, which is Monterey Jack and Cheddar. So I decided to use that instead. So I'm just sprinkling it on top. My burner is off. I'm going to cover it up and just let that cheese melt. Okay, so here is dinner and it is pretty good. I think next time I make it, I would probably make it with some low sodium chicken broth or beef broth just for more flavor. I'm serving it with a side salad and I'm going to be using this Olive Garden and Howard is going to be using Thousand Island. So this is what we are having for dinner tonight and we will see you all next time. So for dinner tonight, Howard and I decided to try this Vietnamese restaurant that is near our house. We both wanted to try it for a while and for whatever reason, we are just now trying it today. So Howard got a brisket cheesesteak. It's a banh mi sandwich and here it is. You can get a combo, but he just got the sandwich and then I decided to try their creak fried rice and it has bacon in it and shrimp. It has the cucumbers as you can see and then those are pickled carrots on top. So this is what we are having for dinner tonight and we will see you all next time.


The latest weapons, coupled with the fighting skill of the American soldier, stand ready on the alert all over the world to defend this country. You, the American people, against aggression. This is the Big Picture, an official television report to the nation from the United States Army. Now to show you part of the Big Picture, here is Sergeant Stuart Queen. Quite a few members of the Army who go overseas are permitted to take their families along with them. Furthermore, the Army sees Stuart that the children in these families are provided with an adequate American type of education. Our first report will show you the kind of educational opportunities now being offered to children of American servicemen stationed in Germany. This is a future playground for a new school in Germany, a school that is being constructed for the children of Army, military and civilian personnel stationed in this area. Recently in Germany, the housing situation has eased and more servicemen have been allowed to bring their families overseas. As Americans, we consider it vitally important to have troops here, but the military urgency has not kept us from remembering the importance of a good education and providing good facilities for it. The Army is in charge of this program of education. Under its direct supervision, through the office of the Adjutant General, school sites are selected, schools are built, and the program of education is administered. Well qualified teachers and principals are recruited from the United States. In effect, the Army plays the role of Board of Education. It helps the teaching staff to do its job by working with it on many problems. Not only how the three Rs can be taught most effectively, but other practical problems like how youngsters living at some distance from the school can be given regular bus transportation. Usually one school must serve for a large area, and so each morning the bus covers at least as much ground as a country school bus in the States. Sometimes a group of youngsters may have as long as an hour's ride to school. But the scenery is attractive, and of course the bus is a good place for chatter before the teacher takes over, so the time passes almost too quickly. Here in Kaiserslauern, Germany is a new American school for children of elementary and high school age. Once at the school, the children would hardly know that they are on foreign soil. The teachers, the classrooms, and the activities are greatly similar to those found in any town or city back home. But back home means very little to some of these kids who may never have seen the inside of a school in the States, because their fathers have had continuous work to do for Uncle Sam in foreign lands. Although most subjects are the familiar ones, there is one here that is a bit unusual, especially for children at the elementary school level. A foreign language, and naturally German. It is not difficult for children to pick up a second language rather quickly, and here under expert guidance, they do. Back in the States, these kids are going to seem awfully bright when they go to high school if they decide to elect German as their foreign language. Everything is up to date in this new elementary school, and although the kids like it, they like to be outside it just as much as possible. It's time for the playground now.  And after a little while, they're all playing together. These girls do pretty well on the overhead bars, and the boys, well, they take to the air, perhaps to prove that there are some stunts that girls can't do. High school, as you might expect, has a much more serious aspect. Here, students preparing for college can be assured of receiving full credit for their work overseas. This mock-up of the human body used in a biology class is typical of the desire of the Army to utilize all available resources to make instruction vital and effective. After working under the close supervision of the instructor, the science student is expected to develop methods of observation and study, which will help him to proceed ahead on his own. Laboratory exercises are a fundamental part of the science curriculum. Chemistry, like biology, is approached with the intention of developing an understanding of the method of the scientist. The scientist tries an experiment. He sees whether what he has in mind is really true. He or she submits the theory to a practical test. Like the laboratory, the library is a place to track down knowledge, and many an assignment can only be fulfilled by going there and looking it up. Of course, the library is always open to those who want to go there for the pleasure of finding themselves a really interesting book. Classes must be set up each term to fit the changing needs of the always changing student body. There may be a class in typing one term, but not the next. Teachers are usually required to have experience in teaching in more than one subject, and sometimes in more than one field. Although the student body changes, there's always one like this. In the home economics field, a girl learns not only basic sewing, but keeps up with changing American fashions. Some of these young ladies studying here in Germany have already seen quite a bit of the world, but are rather anxious to know just as much about being well-dressed as the girl's back home. Not only what to wear, but how to create it. The balance between practical and theoretical subjects is very much the same in these overseas schools as in the States. To a young lady, learning how to look one's best is easily one of the most interesting subjects in school, and so important as preparation for the future. Here's another phase of the future that hasn't been neglected. These home economics students use dolls as subjects while learning how to care for infants. Each student has a chance to try her knowledge. Someday, the facility and ease these girls are learning, will do much to keep a new child healthy and happy. Students at this high school have an excellent opportunity to study a child's later growth and development. Many of the girls take charge of youngsters from the elementary school. In this way, they not only learn the ways of the small fry, but at the same time aid the school program by giving the younger children a full share of attention and encouragement. In many ways, life in these dependent schools overseas has a tendency to develop community spirit, with everyone lending a helping hand and everyone a little happier because of it. A lively phase of the school program is the work being done in the art room, where many students find a means of self-expression, which is apt to stay with them for the rest of their lives. Music too offers long-lasting enjoyment. There's keen interest in this group, for example, just look at the expression on those ankles. Musical enthusiasm is understandable here in the land of Bach, Brahms and Beethoven. The high school has a physical education department. One of its objectives, the development of good health for all students, is carried out in some measure through group games, such as volleyball. Volleyball is a natural for these girls, whose fathers in the army usually play the game and are encouraged to play it, not only for exercise, but to develop the sense of teamwork and cooperation. Football, the game between two American high schools, is scheduled for Saturday at 1.45. Overseas, the high school game is big league stuff. The routers are devoted and the refreshments are all American. Team captains toss up. The Nernberg Eagles win and decide to kick off. There's a good cheering section at work here, and if you just happened to be passing through this part of Germany on this particular day, you'd be willing to bet that this was Saturday afternoon in a typical American town. For the players and the students, it's an afternoon full of team spirit and the determination to win. Fight goes on right down to the one-yard line. There's plenty of inter-high school competition here in Germany, but under army supervision, all athletic events are carried out with the objective of reaching the American attitude of fair play. More important than winning or losing is the respect you hold for your opponent. When the races won, the winners take their places in true Olympic style. It's a great feeling to be up there on the stand. Recreational facilities of many kinds are available to the students. Teenage activities after school are again just what you might find back home. A few of the boys and girls sing the good old songs, mostly there's keen interest in the latest hits from the states, with Crosby and Sinatra holding their own against the newcomers. Sooner or later, the mambo may be the big dance here, but right now the youngsters are sticking to the good old-fashioned jitterbug. From the standpoint of education and just plain fun, sightseeing is the big plus for the American student who goes to a dependent school overseas. On the streets and in museums, there's an altogether different world on display. A world many centuries older than ours in America. Yes, outside the walls of the regular high school is a classroom of another kind, rich in history and the arts, with a bit of geography thrown in for good measure, a living, exciting laboratory available all the time. After inspecting the statue of the Greek goddess Pallas Athene, a group of sightseers continue along the Carl Theodore Bridge in the ancient city of Heidelberg. Throughout Germany, one sees layer upon layer of history, a series of rulers and ways of life, back through kings and princes to the days of the Romans and the Teutonic tribes. When you become just a little tired of sightseeing, there's always the movies, not only for resting the feet, but in this case for refreshing the mind on things American. What about it? Shall we see bomb winde wear it, gone with the wind for the umpteenth time? It's got gable and it won't be exactly the same, because this time the ladies and gentlemen of the Confederacy will be speaking in German, which these students will understand. As in the States, fathers and mothers play an active role in guiding student affairs by participating in the Parent Teachers Association. There's a large turnout for every meeting. The PTA has found that by sponsoring a German American Teenagers Club, much can be done to foster mutual understanding of the interests between German and American youngsters. Not all of these meetings are intended to be serious, but when there is something to discuss, parliamentary procedure guarantees all members the right to speak their mind. Conversations are, of course, in German. These get-togethers are valuable practice in international understanding. Finally, a day arrives that formally culminates the four years of high school study for these young men and women. Graduation provides a feeling of accomplishment. High school has been a task. It has not always been pleasant, but now it is over. There is a feeling of sadness, too. There will be a break in long and rich associations with teachers and fellow students. But what is unusual in this graduation is that something of great significance has been woven into the lives of these young men and women, a wider experience with people and events, a greater perceptiveness of the world about them. As they grow older, they will value more and more the experience of going to school in a foreign country. In winning their diplomas from an American school abroad, these graduates are personally most fortunate. But their country, too, is fortunate because with their families, they have proven themselves outstanding as representatives of America abroad. Heidelberg, with its renowned university, a seat of learning attended by students from all over the world. Perhaps this graduate will continue on here, or perhaps he will return to study in America. Whatever his course, he has already gained valuable understanding and background in an American school abroad. The Army is making possible an American education in a foreign land with all its advantages. For the children of American servicemen. The mother of an American serviceman inspired our next subject by writing this letter after she had visited her son at Fort Bragg. It is an exceptional letter, picked from a great many written by civilians to military commanders. We think it expresses very well, very simply, and honestly, a mother's feelings. We have asked the mother who wrote it that she would allow us to quote her words on the big picture. She has kindly given us this permission. And so, here is her letter, addressed to the commanding general at Fort Bragg, North Carolina. I have just returned home from a three-day visit to Fort Bragg. And I hope you'll not mind my writing you, to express what I imagine many mothers must feel after spending some time in an atmosphere that is altogether strange and foreign to us. From the very first, when I drove into the fort, the visit taught me a great deal that I did not know. It had always been my impression that an army post was a cold, desolate and unfriendly place. And this is what I suppose I expected at Fort Bragg. But instead I found it to be a beautiful place. And an experience I wish more civilians might have. It had been quite a long drive for me, and frankly, on arrival, I felt tired and lonely and wondered whether I should have made the trip. But almost immediately, the hostess at the guest house where I stayed made me feel very much at home. She extended every courtesy. And when I was shown to my room, I was altogether grateful that it was immaculate and most comfortable. After I'd been settled, I set out to observe some of the training activities in which my son was involved. My son is a paratrooper. He chose to be one, knowing it would not be easy. Here at Bragg, it is far from home. The work is hard and the tension is great. But there's been a great change in my son. It seems just yesterday that he was a very small boy. Still remembering some of his small boy fears, I find it difficult to grasp, but very wonderful. He has suddenly been made a man. I watched him jump from a training tower and dangle like a marionette on a string, like some toy he might have played with, only what seems to me like a few years ago. I think all of us mothers would like to say thank you for these men at Bragg. We have sent you boys, and already you have made them men. Of course I was there to see my son, but I saw thousands there exactly like him. Men aware that they were not alone in the job they had to do. Men working together to gain the strength and the know-how for doing whatever the job might demand. I got a feeling of an esprit that is incomprehensible to a woman, and that leaves her very humble and proud that her son is a man.  But when my son entered the army and later came here to Fort Bragg, all of it was with my full blessing. I had brought him up to believe in a way of life, not only freedom and democracy, but memories of things at our home and in our town, and above all the difference between right and wrong. I tried to give him something that he would love enough to preserve it, for himself and others, against whatever danger might threaten, from whatever water. And now, in these times, the danger to our country seems very clear. To hope for peace means nothing, if we do not have men who have the courage and the strength to fight for it. I was glad that my son was here in training, becoming strong for his own sake, and for the sake of America. I watched the lowering of the flag, a ceremony both simple and moving. I had one more day to spend here. I was looking forward to it.  An M.V. gave me very explicit directions on how to get to a good vantage point for watching the jump. Incidentally, may I say that throughout my visit, every soldier to whom I spoke was courteous and helpful and cheerful. I'm pleased to tell you of this, because I know that sometimes our servicemen are criticized harshly on these matters, and I, for one, would like to report how favorably I was impressed. I was impressed with the size of Fort Bragg. I learned that an army post is much more than a cluster of barracks and administration buildings. I drove from miles and miles past one craning area after another. I suppose there are some mothers who would not want to see their sons jump from a plane. I think I am one of those. I'm afraid. And yet, I would not miss the experience. I tried to think of him in the plane, preparing for the jump. I knew, he had told me, that very few men can look forward to a jump without fear. Butterflies in the stomach, or just plain fear in the mind. Fear that at the last moment is overcome. This capacity to conquer fear. This is what my son now has, and because he has this, I am grateful. I tried to pick out my son from those tiny specks in the sky. It was no use. I prayed for the safe landings of all of these men, wherever they might make them. I came to Fort Bragg rarely to see my son, but I saw much more. I saw all those who were side by side with him, other sons of other mothers. I wish that all of them could see what I have seen. Not only their individual sons, but all of our sons together, proud of being together. None of them wanting war, but all of them ready to fight for the kind of life we mothers have taught them to believe in. I saw them marching together gallantly, and I'm grateful that our safety and our future is in their good, strong hands. You have presented this letter which shows not only the deep affection of a mother for her son, but a fine understanding of the role her son must play in the defense of his country. Now, this is Sergeant Stuart Queen, inviting you to be with us next week for another look at the Big Picture, the United States Army in action. The Big Picture is a weekly television report to the nation on the activities of the Army at home and overseas, produced by the Signal Corps Pictorial Center, presented by the U.S. Army in cooperation with this station. You can be an important part of the Big Picture. You can proudly serve with the best equipped, the best trained, the best fighting team in the world today, the United States Army.


We need to clarify that the tourism levy bill is not targeting Airbnb's, but it's for the entire accommodation sector. So both the large hotels, which would range up to about 450 rooms, and a one-bedroom apartment which might be operated by a local St. Lucien or an expatriate national, that the bill really is targeting those guests that are coming to those hotels, like they do in Barbados, like they do in Belize, like they do in Jamaica, like they do in the Bahamas, and a number of the popular Caribbean destinations that you know are already charging the Airbnb fee. They have partnered with various platforms to ensure that they're collecting the monies on behalf of those respective governments. What it does is that it reduces the onerous task of governments year after year, having to find about $35 million to market the destination of St. Lucia, so that we remain competitive in the tourism business. What it does then is make more monies available for schools, more monies available for roads, and more monies available for sporting infrastructure, and all the necessary government services that we need to elevate and advance our country. It must be made clear that the Village Tourism Incorporation Inc. will be established in conjunction with the Tourism Levy Bill. What this does is that it will give the Airbnb properties the opportunity to get concessions, so at present, only hotels that have six rooms or more are benefiting from concessions. Now we are saying that everyone should benefit from concessions, that everyone should participate meaningfully in the tourism sector. And so we are asking everyone to get registered, we are asking everyone to participate, so that you can receive marketing help. At present, only big hotels are assisted by the tourism authority. They are the ones that go on trade shows, they are the ones that are promoted. Now we want to promote authentic St. Lucia. We want to promote little inns and cottages and apartments and villas that are owned by St. Lucia people, so that St. Lucia can participate more meaningfully. There is a lot that you can do on your own, and we will leave you to do those things by yourself. But just consider that if you have just started an apartment, in five years' time, you have to replace the drapes, you have to replace the furniture, you have to replace the sheets, you have to replace the towels. The television might be one that is outdated and might be in need of replacing. You may need to put other amenities in the room so that you can stay up to date with what's happening in the industry. If you are not registered, then you will not be able to get concessions like large hotels do. So what we are simply trying to do is to create a better management system for you. A lot of the bigger hotels can afford to put a reservation system in place. They can afford to set aside a marketing budget. They can afford to get legal help to advise them as to how to apply for concessions. They can afford to do a lot of things that smaller inns cannot do on their own. And by the setting up of village tourism incorporated will help the smaller properties to get established, to get advanced and to be more competitive within the industry. I think it is disingenuous for anyone to take just a very small sentence in an entire seven or eight piece amendment to a legislation to say that that is the true representation of what the bill is. It is reckless. It is irresponsible. And it is political maneuverings only to cause scare. But we have seen this in the last four years. We have seen whereby instead of coming and reasoning and giving the solution people the truth that the opposition solution Labour Party, all they have done is to present themselves in a manner that is scaring the people. So I want to debunk this. I want to say it is absolutely false. The likelihood of someone violating them or causing a violation that will amount to the maximum penalty being an Airbnb operator is very nil because the Airbnb platforms are the ones that will be collecting the taxes for the government of solution, not the owner of the apartment. So therefore the chance of him violating the tax is one that is very, very, very slim. Now I think it's important for me to also note that the government is trying to work with you. The government is trying to empower you to participate in this business. Now many years ago there was a tax called the hotel accommodation tax and in that tax even today the former prime minister of St. Lucia, Dr. Kenny Anthony is on record of saying that hoteliers owe millions of dollars in this tax and the reason why we have had to ensure that the penalty is at the strictest that it can be is to send a very strong signal to the hotels that we are serious about collecting or them collecting the monies on behalf of the government to ensure that this tax is remitted to the government so that we can then fund the marketing activities of the tourism authority. I hope I've made myself clear. I just want to ensure that I speak to all the Airbnb hosts. We support you. We want to lift you and elevate you and we're not here to cause any mayhem or any harm to your businesses.


This study has identified three potential candidate genes for diabetic nephropathy, DN, diagnosis, and therapy. These genes are C1QB, IgM, and ITGB2. Additionally, this study has also proposed potential RNA regulatory pathways adjusting disease progression in DN. This article was authored by Yongjin Hu, Yan Yu, Huidong, and others.


Alexa, play TWIT podcast. Getting the latest episode of TWITLIFT specials. Here it is from TuneIn. It's TWIT. Bandwidth for TWIT specials is provided by CacheFly at C-A-C-H-E-F-L-Y dot com. Alexa, stop. Alexa, play NOCILICAST podcast. You'd like to play the program called NOCILICAST, right? No. Alright. Alexa, play NOCILICAST podcast. You'd like to play the program called NOCILICAST, right? No. Alexa, play NOCILICAST podcast. You'd like to play the program called NOCILICAST, right? No. Alright. Alexa, play the NOCILICAST podcast. Alexa, stop. Alexa, play the NOCILICAST podcast. You'd like to play the program called the NOCILICAST, right? Yes. I can't get the program the NOCILICAST from TuneIn right now.


Yeah, we on boss talk one-on-one. Hey man, that was my boy, man. Like I said, I used to love listening to him. I was hurt when he was locked up, you know? Let's talk about that a little bit because that had to take you by storm. When he got locked up, yeah, I gotta have that. Like that's a core thing, a core moment for me because I was with him. You know what I'm saying? Kind of close me off to the music because I cut for him so much just to, I listened to UGK, that was my thing. I met Vaughn a couple of times, like I always say, but I never had to get to meet him. I don't know if he was with me at the car show. I seen him perform at the car show, but I never got to talk with him. Right here in Dallas? Yeah. Oh, I was there. Yeah, I remember that. We had the dickie suit on and coming through walking, just walking in the states, man. You mean right after he got out? Yeah, that's it. Yeah, I was happy about that. Yeah, I remember that. Yeah, yeah. So how did that end up happening? What was going on? You can talk about it now. I'm no longer with us for as high he ended up getting jammed up and all that good stuff. How did he end up getting jammed up? Oh, what happened that made him? Yeah, and then what? I'm going to tell you what he told me. Of course, that's what I wanted from your standpoint. Okay, this is what he told me. Initially, you mean the, what put him on probation? Yeah, yeah, yeah. Okay, this is what he told me. He said, I'm in the mall. I'm in a certain store. Okay. He said, I'm talking to the store associate, okay? And the store shows, you know, he's being friendly. He knows who I am. Yeah. You know, everything's cool. So he finishes helping me and he goes and starts helping two girls. And then his excitement, he says, hey, y'all know who that is over there? That's PMC and the girls. Of course.  Wow.  And the Chad, I know.  And with it being high-pitched, he cutting you with every word. Yeah, yeah. And so he rip him up with his words. He leave out the store. And so he said, I go into a different store. And as I'm in this different store, it's like 15, 20 minutes later, he said those same young ladies walk in with three or four guys. So in his mind, they go get some guys to come out to him.   Put it down.  They go to a mall security. He says, by the time as soon as I hit the door, bobo, bam, they grab him, hit his head all on the door. You know, they grab him. It's two, like two of them grab him. Hit his head all on the door. They say, hit his head on the cop car, everything. Yeah, cause you know. Hell in it. Yeah. So he go to jail. And this is what I learned. A lot of things I learned from that situation. Fast forward, Christmas, Christmas time. So this has to be Christmas 2000, 2000, 2001. I'm at my mom's house. I get a phone call. Well, excuse me. Nah, yeah, I get a phone call cause I got a cell phone there. Yeah, yeah, yeah. It is pimp. Is he's like, bro, you know, my album is already out. Right? With the biscuit up off me. He's like, say, man. I won't talk about that too, but. We got a show tonight. Chocolate City, first show UGK has done in four years. First show in Houston then since I was there. You know what I'm saying? He said, we need you to open. Wow. I said, we in. Right now. So I gotta go tell my family that I gotta go. So I call up all my people, we hit the road, we go down to Houston. It's a beautiful situation. Come back. Okay, let me tell you, this show is Mobile Luciano opening in the middle fingers and then it's UGK.  She said, baby, talk to Chad. We just got this dirty city tour booked. Okay. I said, okay, wow.   But it's, it's one thing about. It's lucrative. Oh my God. One thing about Chad and that whole family, UGK family, they were not stingy with the money. Yeah. You know, when I was the hype man, they paid me like a, like I was out there. Like an artist. Yeah. Like an artist. You know, I had my own room.  None of that. None of that.   After the show, go in mama's room and get the money. So yeah, so, so we do this show.  So we're gonna do 15 shows, get the bread, come back to Houston and we're gonna shoot look at me video.   Boomtown. Yeah. Oh. So Boomtown living up here. I said, that's gonna be wild. I said, well mama, since the camera's gonna be there and everybody gonna be in present, this gonna shoot Biscuit of Papi video at the same time. She said, let me call Chad and ask him. She called Chad, she called me right back. He said, that's a pfft, genius. So next week, he went to, for his court apartment and never came out. Wow. And never came back out. Well, never's a long word. Four years. Yeah, four years later. Yeah. So that hurts. And I know it did hurt you. Did you, you did take trips down there? Where? I never, he told me, he told me don't come. Okay. He told me, I rode him almost, I rode him once a month at least. And he rode back. Oh, every, yeah. Yeah, I got, come on now. You know, so, and every time I said, boy, let me put some money on your books. He wouldn't take it. He wouldn't take it from me at all. He's like, I got people putting money on my books, but boy, I know you're trying to make it. I said, okay, you need it. Let me know, I got it. And that's how it was. Wow. That's dope, man, that he understood because I can relate. Chad, you know, I hear a lot of people on, cause I watch you, I follow you. And people say this and you've heard this from everybody and it's true. There was a difference between Chad and there was a difference between PMC. Yeah, yeah. I'm one of the only people that I know. That's what runs, runs, runs special state. I know Pimp as Chad Bartlow. Okay. Now, this is the thing that Pimp did that he didn't do around a lot of people. When we were, when I was on the tour with him, we would, you know, do our music and get off the stage and do, he would always call me and say, and I was marking. He would always. She said that. She would always, he would always come in. Hey, Ryan, what you doing? I said, man, I'm just, man, come on down here. Let's go to the Waffle House. I need to eat some steak and eggs. I said, okay, steak and eggs. I said, yeah, we're going to get steak and eggs. I don't want nobody else with us just going to be me and you. So he still got his Pimp feel talking to me.  So that was him all the time. He never turned on and off?  So it's like, when he get ready to go to the show, well, I put it this way. When we together, he's like real calm and just say, hey, man, come on, man, let's go. Go chill, go to the mall or something, buy some stuff for the next show or something. Cool. The character ain't out yet, but soon as we get out the car, the character kick in. So we getting ready to go to the mall. We don't realize how early it is. It ain't over. So the security come to the door and this the first time he talked. So he say, I wonder why y'all don't open the door for me.  I'm trying to spend some money. So I'm looking and I'm saying, he didn't change. You know, so he didn't change. He say, you know who I am? I'm Pimp C, open the door. I got money. So I do say, man, we ain't open.  Open the door, open it. So I'm like, man. So I'm just sitting back and saying, what you waiting on? Come on in. So I said, all right, see, come on in. I come on in and he kind of, he said, we just gonna win the shot. So he got his hands and he do his mouth like that. We just gonna win the shot.  Cause I perform and I'm like, man. So he say, Ronnie, what you want? I say, man, whatever you need of me to be in. He said, get what you want. Cause I'm paying for it. I got money. So I'm like, man, so the security go, okay, yes, sir. Oh, yes, sir. I'm gonna go get my manager. So we gonna open the door. Go get him. So I said, man, I'm looking at this cat. I'm like, man. What city we all in? He really, we was in Chicago. I'm chilling. I'm like, man, he really in myself. I'm sending myself. He really is then turning to the character again. So you know what I'm saying? So after we got all our stuff and then we get back in the car, he said, all right, man, we gonna win the shot. It was different. I'm one of the only people that, I don't think Chad ever went out for him. Really? Yeah. Everybody goes. You and probably running, because running said the same thing, because of you all. Yeah. And I was older. That's what it is. I was like that. No, don't do that. Don't do that, bro. Bro, you tripping. Yeah. I was that on his shoulder. That's why he always liked me around. Because when he got to tripping, I, you tripping, Pio. Chad, you tripping. And he'll listen to you. Oh, what? What? Yeah, it was different. So when you, when you, when he was down there and he gets ready to come home, you know, I know now this is where the celebration begins. But I know it's hard as y'all go through it. Yeah, we on Boss Talk 101.


Play as eight straight wins over the Brooklyn Nets Seven straight over them in this building. How'd you get it done tonight? Man, Katie was magnificent the ball in the sand same as when cook, you know, we go from playing Almost no minutes to seven up again 27 everlessly like he did Which shows up as a testament to what kind of player he is.  It's huge It's about what your bench can do. I mean strengthen numbers We've been doing it for five years now and give a credit to our front office We're finding these type of guys like this who are hungry and ready to compete at any given moment Three rings back-to-back NBA champions. What's the key to staying hungry for you guys shoot? Maximize your potential realizing that Windows like this rarely ever come around especially for franchises. So and you just see the electricity in this building It's so fun to play in front of these fans every night. I'm gonna give credit to the Nets They got a lot of town over there. They've been building up over the years. I got a great system in place So they got a bright future.  Thanks a lot


If we don't invest in what goes on in this building, we're cheating ourselves as Pennsylvanians, all of us. And so that means we need to figure out a fair way to raise the funds to fund education, which is why I'm calling on us to move away from this undue reliance on the property tax to a much better, healthier mix between state funding and the property tax. We need to make the way we raise the money fair with the way we allocate it, so that they're going to get more money to do what goes on in this building and all the other buildings in the Downingtown School District and this kind of building all over the state. We need to have a shift. I mean, we've been talking about property tax reform and property tax relief for decades now. And it's high time we actually deliver on that promise. Our constituents, the voters have said, this is what we want and that's what I was trying to deliver yesterday. Yes, oh, I know, trust me. The goal is to have some public education, the key pieces along the way as well. It's, um... It's lucky to see which material will reduce the cost of impact the most. There you go. Yeah, it's like... I got you. It's nice to meet you. Come on in, come on in. How are you doing? Governor Wolf, this is everybody. It's nice to meet you. The power of the products and the questions. We're going to get a splatter from one of the reactions right here. It's not as fast as what it was before. Right. So you guys are, you know, the theory and, you know, both theory and practice. Yeah. In the student comments, it was more of like our lunchroom, but also during class, as you saw a lot of kids, I'd wander around and work. So, right now, they're going to be a lot of students just working down in the studio. All the courses are digital. Everything's online. Access all-force materials. All-force materials. So you guys are working. So we're in a really important front. Nice to meet you. How are you? Yeah, I'm in chorus. I'm in chorus. I'm so tired.


All right, so we are going to be talking about managing open V-switch in a large heterogeneous environment. I am not Andy Hill, that is not Joel Priest. Use the slide and you can figure out the rest. We are both systems engineers at Rackspace who have been working on the public cloud for about three years now in total. So some quick definitions first. What do we mean by large fleet? Tens of thousands of hosts, yeah. Lots of hosts, obviously way more instances on top of that which equates to lots of logical ports and everything that you are managing with open V-switch. Hundreds of thousands of instances to be exact. Heterogeneous, tons of different hardware manufacturers, more than is probably saying. We have several majors in server versions, differing kernel versions within those and servers, multiple hypervisor vendors within those, sorry, hardware vendors for our hypervisors within those different hardware revisions there of all of those kind of tweak the requirements and behavior slightly that you get when you are working with anything really and by extension open V-switch. We have six production public clouds stretching from DFW or IAD, US, London, Hong Kong, Sydney, et cetera, et cetera. Six internal private clouds. So that would be we run OpenStack on OpenStack. So that's our internal OpenStack deploy that we refer to as Inova as well as any of our pre-production environments, CICD, Dev, all that kind of stuff. So this is a quick OBS introduction on sort of the flow of open V-switch and where it's going. I'm just familiar with that. Essentially you potentially have a control and a management cluster that is talking down to your OBS which in turn has a local database that it has reads and writes going to and from that both to the OBS process and to the control and that all exists in user space and then there is the open V-switch kernel module existing below that. So the main takeaway as far as our presentation which you need to know from this slide is basically user space, not as fast. Kernel space, super fast. So you want to be operating as much down on the kernel space as you can to get the most performance out of V-switch. History. Rack space. We have used OBS since, I don't know, it was probably just V-S at the time. We've been on open V-switch for a very long time, pre-1.0 I believe when we launched our next-gen OpenStack cloud we were running <IP_ADDRESS> of OBS around there. Been using it before that. We were using it before OpenStack even launched. Some towards the tail end of the old old legacy cloud, slice host days if anybody remembers that. We were using OBS. Power is 100% of the next-gen cloud and we have upgraded OBS nine times in the last two years. So this is my favorite slide. If you get nothing else from this talk, if you are a package maintainer, if you are using Open V-switch, upgrade OBS. We are on very new OBS, like, as new as we can get for the most part, try to, yeah, if you're, you'll see and you'll go into extensive excruciating detail on that in a moment. Like you, yeah, you want to be on newer versions of OBS. We've talked to people who have not gotten expected, like, what they would consider expected performance out of it and a lot of times when we dig deep on that we find out that they are using way old versions. So please, please, please upgrade your OBS. So why upgrade OBS in the first place, right? These are the summary of the reasons that we've upgraded OBS. The main ones around performance, we also did some upgrades to make upgrading less painful. They've made a lot of improvements into how the in place upgrade of OBS happens and makes it more palatable for us to do very often, like we have done in the past two years. We also upgraded OBS because we needed to upgrade our NSX controllers. So anyone who's ever upgraded NSX, one of the components of that is to upgrade open V-switch. So we had to do that a couple of times. There was also a really nasty regression in OBS 2.1 that made us upgrade once more. This one was around certain types of VMs whenever they would plug the first time they'd be okay. But then if the tenant reboots the instance, it would no longer get data path flows. So we've upgraded OBS for a few other reasons, but the main driving reason behind all of this is performance. So some of the things that can impact your performance are some of the things that we've seen impact performance for public cloud use case. Largely around broadcast domain sizing and specific attention for broadcast related flows. Just take some real care and make sure that that's behaving the way that you want it to behave if you're crafting these flows. A lot of times what ends up happening is the broadcast traffic goes to every node, goes to every VIF, and instead of OBS dropping the flows dropping the ones that it doesn't need to, it just goes all the way to each VIF anyway instead of having a little more control over that where you don't have to spend the CPU cycles to even consider that traffic that's not going to be relevant to your host. So we monitor OBS quite a bit. This is just a big, big chart of OBS CPU, OBS vSwitch DCPU utilization. This was in a cell that had one of those large broadcast domains that I'm talking about, but then somebody started doing something a little interesting, and we see this. So OBS CPU went through the roof because of all this broadcast traffic going to all the nodes. Some of them was basically port scanning and doing, generating a lot of this traffic that ends up being particularly painful for OBS. This was kind of in the olden days, and that's a picture of Chad. He's one of our systems engineer. And this was just a really, really bad situation. So we had to kind of take a look at what we may have done as an operator and kind of examine the flows themselves, but vSwitch could have handled this bad situation a better way anyway. So around performance, I'm going to go ahead and just say there's three kind of eras that we've experienced with performance. Pre 1.11, I'll call it the dark ages, it's really rough. You don't get performance on a lot of workloads. Just the typical workloads sometimes have problems. Megaflows, and then I'll say ludicrous speed. I'll get into each one of these. Let's go ahead and do the dark ages. So how many people in here have seen this flow eviction threshold setting and had to tune it because there's a workload that's unhappy? So by default, pre 1.11, flow eviction threshold can cause some problems. So flow eviction threshold is the threshold in which OBS attempts to start evicting unused data path flows. So Joel mentioned earlier, the data path flows are the fast path. But if OBS is kind of managing that and trying to keep those to a minimal, you may have some issues where a lot of those data path flows get generated. Then OBS has been CPU cycles managing those data path flows, and it just turns over and over and over again, causing that CPU usage to go way up. It was also single threaded. This didn't get changed until a later version of OBS. It also was doing some very specific matching on the traffic that comes in. So it's like a 12 point match, source port, destination port, all the little details in an open flow connection. It was very, very specific matches. So some workloads that may require a brand new connection from a client to a server that gets a brand new source port on every single connection. Well, that's another flow. That's another thing that OBS has to keep up with. That's one of these situations where OBS really had a tough time. And there's a couple of other things a little lower. But basically, the more bridges that you had, you also had a penalty for that. The more bridges you had to traverse, you kind of also got hit for that. So then OBS 111 happened, and we got mega flows. And we felt really good about it. We were like, all right, mega flows. There's been a whole lot of activity in the community about just wait, mega flows is really going to help you out. And really, for the most part, you were less likely to hit that flow eviction threshold that I mentioned earlier because instead of doing a very specific 12 point match, OBS could do some wild carding on those flows. And therefore keep the number of flows that were in Datapath much smaller so the performance was much better. But there were still some workloads out there. I mean, 2,000 Datapath flows for some workloads is still pretty well nothing. It's trivial. So we still had some issues, but we saw really, really significant improvements from pre-111 to 111. So this is a chart of the average Datapath flows for one of our regions, you can see they're kind of hovering up there. And then the dip on the right is post 111. We cut almost all of our cases cut in half, right? We're very, very happy with this, but we still could do better. We still could have, we still had some cases where this just wasn't good enough. So then we have ludicrous speed. If you were watching Spaceballs in the lunch area earlier, they did away with flow eviction threshold completely with 2.1 and beyond. So now instead of a 2,000 Datapath flow sort of limit, there's 200,000 Datapath flows by default out the gate with OBS 2.1 and beyond. And this is a configurable value. And we can run all the tests that we want. We can do lots of synthetic workloads, yada, yada, yada. But for the wild, for what we see with public cloud, we've seen over 72,000 Datapath flows with some workloads in 260,000 packets per second. We're really, that's a significant improvement before 2.1. We've been really, really happy with it. This is a chart of the top five Datapath flows post 2.1, just to give you an idea of most workloads are towards the bottom here. This is just a top five, but we've got one guy who's kind of out of control in the 40,000 Datapath flow range. This is a smoke paint chart, if any of you guys are familiar with smoke paint, right? The colors on the chart, the non-green colors on the chart, those straight jitter in the connection. It's pretty clear when we upgraded this environment from 1.4 to 2.1. It was very significant performance. Our infrastructure team, this was for an internal cloud, but our infrastructure team loves this. We have much more consistent performance on the network because of this upgrade. So, mission accomplished, right? We moved the bottleneck. OBS isn't our bottleneck anymore from what we've seen on the networking side. The new bottleneck that we have for tenant workloads is more around the Zen Netback, Netfront driver, which has some significant improvements coming soon. And then there's the guest OS kernel tuning. Some people may have very specific workloads that they need to tune their kernel a little bit, so those are really the things that we're seeing. Just giving you an idea, after we went to 2.1, we have seen no escalations come to us, no problem cases that we were able to go back and say OBS was the problem after going to 2.1. It's all... We haven't had a single escalation since... Let's see, we completed all the upgrades for production in July, I think, and we haven't had a single case that we've been able to go all the way back to OBS, and that's a problem, so that was a huge deal for us. So, I'm going to bang the drum a little bit more here. Please upgrade. So, I hope there's some people who distribute OBS in here. If you do, please upgrade so that your customers who are using package OBS from you can really take advantage of this. Please upgrade, please. And by the way, OBS 2.3 is long-term support, so if there are concerns around that. All right, so now that we've talked about upgrades and the benefits of upgrades, how do you do it? Well, we orchestrated the whole process with Ansible. One of the things that's kind of unique about upgrading OpenVswitch is you're losing the network connection to your host, so there can be a little bit of concern around this, especially in some cases if you're doing a large amount of host at a single time. So, I'll just say take a look at Ansible's async module if you're going to attempt to do this with Ansible. Watch your SSH time-outs in particular from experience in a pre-production environment. I may or may not have taken down an entire cabinet of machines because I wasn't paying close attention to that. And around the impact of OBS upgrades for bonded configurations, we see under 30-second data plane impact, so we do interrupt our customers, but it's a brief interruption and for our non-bonded customers, it's under five seconds. There's still some discussion and fixes going on around why the bonded configurations are taking longer and there's a link in the slide to that, I think.  It's not quite that simple. So when we did our first upgrade, we had something really strange happen. After the upgrade happened, hypervisors, full hypervisors, were just rebooting kind of at random in one environment and this was pretty concerning. It comes back to the OBS bridge fail mode. So by default, the bridge fail mode is a normal fail mode. You can set it to secure fail mode, the difference between normal and secure bridge fail mode. Normal fail mode, whenever traffic hits the host, it acts as a normal L2 switch. Secure fail mode, it's going to drop the traffic. So some really interesting scenarios can happen because of this normal fail mode, one of which was a Zen server bug that we found where the traffic got broadcast to all of the vifts but we were doing some network sharing across like iSCSI and provider network and the iSCSI traffic hit a vif. That shouldn't have happened and it causes a Zen server bug to basically cause a hypervisor page fault and reboot. So it's really, really tough. And you can't just say, I want to switch from normal to secure fail mode. It's not quite that simple. If you do that, it's a data plane impacting event. All the flows on the bridge get cleared. So that's another kind of wrinkle in this whole process. And then yet another one would be the fail modes don't always persist like you think they would. You have to kind of change a setting in Zen server anyway to have that fail mode persist across reboot. Oh, and some more issues around fail modes. So we do use patch ports for kind of moving our traffic along to the appropriate bridge that needs to go to. But if you have some misconfigured patch ports and you have a normal fail mode, this was an incident we had where we had a routing loop because of that. So around this whole theme we really, we had to secure all of our bridges. We had to go to the secure fail mode. Otherwise we couldn't upgrade OBS across the rest of the fleet. And the patch ports don't persist across reboot and there's no construct within Zen servers to make them persist across reboot. So we had to kind of enagle a crime task to happen on reboot to do that. So now that we've determined that we have to migrate from this normal fail mode to a secure fail mode, here's the high level steps that we took to upgrade. We just created another new bridge, had this similar configuration to the old one that all the vifts were plugged onto. Then we moved each vif to the new bridge which got them their new flows. And this was a loss of just a few packets. After that we actually performed the OBS upgrade itself.   We may have had some monitoring kind of flip out because interfaces changed according to the kernel whenever we reloaded the OBS K mod. So we have to like restart SNMP just so our monitoring system doesn't lose its mind. And we did this entire process with Ansible. It was a wonderful tool to use to do this kind of step-by-step process. And I can't really think about using another tool to accomplish such a thing. Okay, so there's yet another got you around upgrading OBS and it's around kernel modules. So this isn't a hundred percent of the time but we don't really risk it. Basically if you upgrade your operating systems kernel through normal patching or whatever like that you also need to make sure that you have a matching OBS kernel module to go with that. There are situations, especially if you're doing these big upgrades where you go from like 1.4 to 2.1 where the mismatching kernel modules if you don't have the matching OBS kernel module with your new kernel you're not gonna be able to have networking on the hypervisor. So this is another one of those things that we learned the hard way. Basically if you're upgrading OBS make sure you have the kernel module and the way we do it is we don't upgrade the kernel module or we don't upgrade the operating system kernel without upgrading OBS kernel module and we don't upgrade OBS without ensuring that we're not missing a part of this equation. So yeah, kernel upgrade equals OBS upgrade is basically what we've taken away from it and since we have such a wildly varying environment this means we have a lot more complexity to manage in terms of getting those kernel modules making sure they're delivered to the right place and if you don't pay close attention to this in your SSH timeouts like I mentioned earlier you can have a trip to the out-of-band management system and try and get networking back on that hypervisor. Okay, and there's still some other challenges around OBS in upgrading, there's a lot of reasons maybe it's maybe it's not your whoever packaged OBS for you maybe it's an organizational thing you can't upgrade OBS right now. This is a problem that a lot of people are facing and we've realized that not everyone can just put the gas puddle down and upgrade OBS as frequently as we do. Other people within Rackspace also had issues with VLAN splinters and the OBS VLAN bug work around. This is not really a problem with OBS so much as it is a problem with some NICs but this is really well documented in the OBS project itself. And I mentioned it earlier but this was a real thorn in my side was some of the components of OBS weren't really tightly integrated with the hypervisor so we really wanted to have those patch ports just be there on reboot instead of having to hack something up via cron. And just kind of a quick summary of the platforms that we've run OBS on. We have some OBS managing LXC, KVM and several versions of Sensor. All right so now that Andy talked to you about all the really difficult stuff that he has to deal with I'm gonna talk to you about measuring OBS and monitoring it. So essentially he's doing all the heavy lifting and I'm doing the stuff going hey, Andy is broke, do something about it. So before I get into the measuring part just out of curiosity how many people in here are actually using OBS like right now? How many of you are in the dark ages? So pre-111, oh thank you. And 111, at least 111. Two plus, at least two plus, yay. So I'm glad we are preaching to the choir on like half of our presentation was just begging you to upgrade when you're already there so that's good. So measuring OBS, I would say in fact all the graphite slides you saw earlier that data was generated from a script that Andy and one of our other co-workers Jason Kolker worked on called Pavlovs, Pavlovs, get it? And that basically is pretty straightforward Python script that's just sending data on packet counts and CPU utilization and all that opening a socket to graphite, dumping it in there and then you can aggregate it there. This is awesome, it gives you a really easy way to look at your entire fleet and see what your OBS is doing and see things like we showed you earlier where you can see that dramatic drop in flow counts and CPU utilization with every upgrade. So if you're not doing something like this I would recommend it especially before if you were one of the people who are still in the dark ages or 111 and thinking about coming up do it before that if you're not already because it's just super fun to basically get literally instant gratification the second you're finished reloading Kmod it's like, oh hey look the network is just screaming now, so that's awesome. We aggregate these, we use cells so we aggregate this from the region cell hypervisor so you can get that whatever granular view you're going for and it's really useful for DDoS protection if you're managing hypervisors like with us we have a dedicated backbone team and they're monitoring that stuff at the ingress but it's really useful to be able to see from our side anyways, it's super you just look at who are your top users and if somebody all of a sudden spiked and their orders of magnitude more than other customers there's a good chance they're a DDoS target but that being said when you're at a scale as large as ours we're having problems with scaling graphite and stats D to accommodate because this is a ton of traffic every multiple multiple data set data points for every single port on every single hypervisor or every single instance so we're running some interesting challenges with that in some of our larger regions. And so OBS and compute host lifecycle this script is another script we have internally off-sulate basically this is what runs when we provision a new hypervisor that checks it into our MVP NSX controller evolved a little bit over time back in say when we were in the dark ages rain of things it was just a standalone Python script that we were executing that was kind of dumb that's evolved now it's pretty much strictly enanceable it checks the host end this is kind of almost on the monitoring side of things cause for the most part you're only gonna check something in once if it fails that means that that hypervisor there's only two reasons really it should fail that hypervisor is having a communication issue to your control cluster which is bad and you need to address what is breaking the communication between those two or if say you're re-kicking a hypervisor like it had a hardware issue you failed it out replace that and now you're re-bootstrapping it fresh it has a new host certificate and it gets a conflict when you check into your controller especially if you're using a consistent node name and all that management IP that it has in the NSX controller so you have to catch that error condition and then work around that to either update the host certificate separately or delete the node and then re-add it from scratch so what are things that we monitor these are the big ones we use Nagios for our monitoring and most of these are passive SNMP checks so the first ones we do is connectivity to the controller so just simple the OBS VS Cattle commands in my do I have any controllers that I am not connected to that should always be no the main cause for that for us that can happen after the fact after something has been successfully deployed is generally routes we're connecting to the controller via an overlay network and so we have to have routes directing that traffic to the controllers correctly and thus from the controllers back so if something were to happen that made those routes get out of whack or what not we need to address that SDN integration process so for us running as a server this is the OBS SAPI sync process the TLDR on that is it's basically just the process that is reporting up to the controller the status of the different OBS parts on the hypervisor so it knows where to plug in the little bits that it's in charge of there's some interesting challenges for us specifically on that because we're basically using a fork version of it to handle some internal rack space sort of Byzantine logic stuff on our SDN side so we're not using the stock so whenever we do these upgrades for OBS we have to check and make sure that our custom version wasn't stomped by the upgrade so part of our upgrade process is to write in our correct one and make sure that's the running one so we have our check is just a simple bash script checking A is this process running is it sim link to ours and does that file that the sim link is pointing to actually exist to make sure that it's got all the little bits that we're expecting there and routes that kind of goes back in not just to talking to the controllers but routes from say cell to cell so that hypervisors can talk to other hypervisors and this is gonna bridge look at our bridge networking job look at our setup so as you can see here the blue line is the direct line between two hypervisors that's the one you will end up taking the majority of the time but on your first connection you gotta go down to the control cluster node the orange line and it establishes that tunnel at first so if you break the blue line or that orange line you're gonna have a bad time you've broken your tenants isolated network or your OBS connected activity between those two nodes so that's why we're monitoring for routes and we're starting to do stuff now that not just monitoring we have some rec space projects that have been brought up in a few of the rec space talks here auditor and resolver which are along in the same vein as the entropy project and we're I think having some discussions with those people about that about kind of not duplicating work there but essentially we have some checks put in where if a host for whatever reason does alert for not having the correct routes that it needs then resolver can go and run a job on it and say hey run the task that we have the Ansible task that we have that fixes all the routes on this and fix this connectivity so hopefully that doesn't come up ever I mean ideally but when it does we've got tasks to react to it for us. One of the other reasons this is kind of an issue for us is we have a brownfield IPv4 deployment so we don't really have the luxury to say this is all the tunnels are going to be established on this very large network we have to do kind of right sizing and we have to pay close attention to our IPv4 deployment it'd be really nice if our tunnel endpoints could just be v6. Yeah and reboots as Andy mentioned with the mismatch kernel version when you reboot ideally when the host comes back up you would like it to still have networking I don't think I should have to explain that too much but that's the goal that we're going for and if you go to the link family that goes to your blog post on the blog post from Andy a little bit more detail about the kernel mismatches and stuff but you would think this would never be like a big widespread thing it's not like anything's ever going to happen that we're going to reboot the entire oh god if anybody in here is a rack space customer you got this email very soon this was from the reboot apocalypse as I tried to get people to call it but I don't think anybody joined in other than me so this was the Zen server bug that went around this is why Amazon had to reboot a non-trivial portion of their cloud and we had to reboot the entirety of our next gen cloud so yeah that's a big deal if you're rebooting literally every hypervisor in your fleet which again tens of thousands of hypervisors you want them all to have networking when they come back up so we were monitoring for the kernel mismatches already so we would have known about any of that it could have potentially been a problem on but when we did our orchestration for all that which again Ansible if you can't tell we're big Ansible fans we put in pre-flight checks for that so it would hit every hypervisor and just double check and say hey, do I have the kernel versions I'm going to need if I don't, we failed that host out immediately from that reboot playbook so there would be no chance that it would get rebooted and then we would revisit it and rectify whatever that was causing that problem so I think that pretty much covers it anybody have any questions or anything? The default Zen server use open with switch bridges for management interfaces, sound connection all connection of the host do you use that bridge in your installations? Can you say that one more time please? The default Zen server pass all traffic including management and sound connection through OBS bridge do you do this? So not the same bridge but yes we use OBS bridges for all of the networks so in dark ages it was most fun part when everything died including management interface there was a lot of fun back then Yes, the issue that we mentioned with the version chrono mismatch it would yes break the bridge that was our management interface That's why we would get hit by that is because OBS was managing that network that's why we had to do the out of band to fix that so that's why it was so critical for us to monitor for that aggressively if we had a 1% failure on those reboots of tens of thousands of nodes that's hundreds of out of band Java console serial overland console we have to log in and fix we had no interest in doing that So yeah From your presentation I got you using the out of tree OBS module so do you since which kernel version would you recommend using the in tree OBS module or do you recommend that at all? We don't use the out of tree kernel modules we the only kind of out of band things that we do are around the OBS ZepiSync process and we use the kernels and we compile those are compiled for the kernels that are shipping with Zen server So the kernel ship with Zen server doesn't include the OBS module because in recent kernel versions main mainline kernel versions OBS is included So this is actually one of the problems that we have with the packaging of Zen server itself is it's packaging in the patches that you download whenever you download Zen server patches is it's packaging OBS 1.4 and we're at a substantially higher version than that and we can't run some of those patches because of the dependency there So the Zen server we compile the OBS 2.1 kernel module against the 2.6 whatever Zen server kernel Oh okay, so you're running a quite old kernel version Sorry? You're running a quite old... The one that we get with Zen server is... Yeah Here Hey, so last week there has been a news release about Terak Space dropping open v-switch support in favor of Linux bridge for their private cloud efforts So could you comment on that? Yeah, I think it comes down to we're doing tenant networks and for a lot of the build-outs they're not using tenant networks so they don't need to have a SDN controller to manage their networking, really Some of it is also around the additional complexity that we have to take on in order to accomplish some of our tenant networking and some of the provider security that we have in place some of the kind of value adds that we do with our hybrid cloud offering So we're using open v-switch from public cloud and I don't really see that going away Okay, thanks Anybody else? Nope Alright Thanks for coming guys