You mentioned that you improved the efficiency of the synthetase with mage. How close did you get to the efficiency of the wild-type enzyme? So it's a good question.  So I didn't have this slide that showed the biochemistry data, but going into the experiment we were about 800 fold lower in activity. And now we're about 75 to 80 fold lower. So we improved it by about an order of magnitude. We'll still have more than the order of magnitude to go. So we're getting there, but we're not there yet. And just to give some context, we're working basically with synthetase, synthetase is the derived from archaea. I'm putting it into bacteria. So I think there could be a number of explanations as to why we're still not only to be, but it's still a significant improvement that allowed us to drive many incorporations into proteins. Maybe it's getting too detailed in your question, but did you focus on active site mutations only or the full protein? Right now it was focused just on the massive binding targets and the specific domains of the synthetase that we'll recognize and bind to the anticoagulants of the tRNA. So what we're looking at now is expanding beyond those, as well as going deeper into those regions as well, because I think both of those two strategies need to be pursued. So being able to go beyond, so in those experiments we talked about 12 residues in the amino acid binding pocket, but if you do the math there's no way we can sample that genetic diversity. So we're coupling that also with confidential protein design as a way to better inform the new genesis as well and then going to other domains across the protein. Yes. May I ask you a little bit, a more general question, not technical, about the safety and a little bit of a strike of what you're saying. Maybe I didn't understand. You said that you increased the resistance to virus, T7 virus. That is one factor because there was an infection and there was a company who lost a lot of money. And then you were speaking about, over seven days you checked, seven days there, and so you have long term stability. What do you mean by long term stability? You have not the hindsight of the nature of billions of years, and millions and trillions, somebody spoke about trillions of micro-articles, so for me that's not scientific, absolutely not. Okay, so you're touching on, I would say, excuse me just to be direct. That's fine. You're focusing on two points really. One is the first is on genetic isolation, in terms of the virus experiments. So what I try to do is motivate those experiments both biologically as well as thinking about how they can solve real world problems. So the Genzyme example was a real world problem, and it's a problem that is actually common to all biopharmatization processes, where about 15% of biopharmatization processes are compromised by phase infection, okay. So that's a real world motivation to create organisms that are going to be resistant to viruses. And so what we showed is data that, where T7 infectivity was produced, and some data that didn't show where that actually expands to other viruses. So that, what it does is it shows two things. It addresses that problem I described, but it also shows the notion, which is scientific, that if you have organisms that have alternate codes, they are now incompatible with genomes of that exist in nature, and those genomes can come from other species, or they can come from viruses, which have been evolved over billions of years. And what we're showing is that by creating organisms with alternate codes, you can create barriers to the facile transfer of genetic material, okay. So that is scientific. The second is on biocontainment. Again, that goes after a different, motivated by, I would say a complementary problem, which is now thinking about engineering GMOs that go beyond biopharmatization processes. So there's a lot of people, and I think we'll probably hear a little bit about this later this afternoon, about thinking about engineering microorganisms as new types of probiotics to treat disease, for example, or for bioremediation. So when you think about applying these organisms in open system applications, what you want to do is endow safeguards into these organisms. One of those actually is genetic isolation. Another is restricting these organisms such that they can't grow in the wild, or in other words, you limit their growth to defined synthetic environments. And what we've shown is that you can basically, by virtue of recoding, link the viability of these recoded organisms to synthetic amino acids, which don't exist in nature. Of course, what you said, they are compatible, so they can be exchanged. And then, secondly, the containment, I think if I understood correctly, it's 10 to the minus 12. But if you have trillions of trillions of trillions, that's it. Now, it's a general question. It's valid. It's not personal. I'm not...  Yeah, so I would like to hear your answer. Sure. So with regard to those experiments, we pushed the limit of what we could really achieve in the lab. So if you're growing up trillions of cells, that's quite a bit of cells. And then being able to test those on plates and liquid culture is a big experiment. So that's the limit of what we could do in our lab. To go beyond that, and address the point that you just raised, what happens if you go to trillions and trillions and 10 to the 15th cells? We haven't tested that yet. And so I can't really speak to that. But it's something that I agree needs to be done. The quantity and the time. There's reasons for that. Thank you. Right. But we did test it over time. Over time. Yeah. We basically tested these over the course of three weeks. That's a long time for a graduate student to be a tracking experiment. It's not nature, you know. No. But... Come back when you have to, Billy, and you're later. We do. We do. We do that with the experiments. It has resources. One can be very astonished. You're absolutely right. And I would say this is important. It will be important in two centuries, you see. I would say this is an important first step, okay? And there's more that can be done. That's it. Okay. That's it. Okay. Danielle. So I guess, building on that, can you do a back of envelope calculation on how long it would take to revert or overcome changes, or even adapt by introducing new changes into the genome.  And what rate are those appearing? Maybe we don't know what rate they need to appear at, but at least we can compare what rate those are incorporated. Yeah. It's a good question. I would actually say in the course of those experiments, as we were sort of arriving at our solutions that we presented, we did observe, I didn't have time to discuss that, but we did observe secondary mutations that led to escape, and we characterized those. And actually, that was informative in then creating next-generation solutions to actually overcome those problems. And so we observed what you would typically observe. We observed the formation of amber suppressors. We observed mutations in proteins that are important in fidelity at the ribosome, for example. And those were in earlier strains that didn't have the mutations that were targeted at conserved functional residues of those essential proteins. And that's what sort of led to that solution is really going after an approach that distributed the multiple TGs across conserved functional residues so that you wouldn't allow one or two or three, who knows how many, mutations to overcome that sort of degree of containment. Something beyond that I think will require larger populations, possibly a much longer period of time than what we were able to do in the lab. I'm not sure, Jeff, if you have a comment on that as well, because I know you did some of the similar experiments, but. Right, so the other point to make with regard to the trillions and trillions is that there are many different ways to contain microorganisms. So, Ference got a factor of 10 to the 12th, which is probably the world's record at this point, I would say. But we showed in a paper last year that if you use two completely orthogonal containment systems, each one contains to a level of one in a million, that when you combine them, you get about 10 to the minus 12, as you would expect for two independent control systems. So, there's no reason in principle why two, three, four or five orthogonal control systems couldn't be combined. It's a good point. Sure. We actually observed the same results in an analogous system in that period. I can also make a comment on that. A spin-off company at our institute called Actogenics, I think they were the first ones to enter clinical trials really by a contained lactococcus for probiotics. And so, the only thing they were required to do from regulatory therapies to be able to enter clinical trials was to have an oxotrophy, classical oxotrophy for uracil built into the organism, such that the organism had to take a uracil from the gut components in those patients. And as soon as the bacteria were released out of the patient, concentration of uracil dropped so highly to such a low level that they considered this sufficient. This was EMA approved in this clinical trial. I mean, approved for clinical trial is not the same as approval for real use in the end. So, I'm sure they would have to build in our terminal systems to bring that up further. But it's not impossible to get these kind of products approved to enter development in this case. Yeah, I think that's really important. Was that a naturally occurring probiotic or an engineered probiotic? It's an engineered probiotic producing a human side effect. What do you think are the chances that you could actually manage to build in this artificial amino acid and some vital function for the bacteria itself? So, then you would make it really dependent on? Yeah. So, we are looking at that in two different areas. One is to do more molecular evolution of these active sites in these proteins and as well as see if we can further expand and enhance the activity of enzymes by the presence of a synthetic amino acid. Touch them out a little bit at the end and sort of seeing if we can actually enhance their, in some way, function or maybe thickness by encoding these amino acids. Because if they get dependent on it and they don't produce it themselves. Yeah. Maybe I should add, I mean, currently we do know almost nothing about how these synthetic amino acids are taken up. They provide always a huge excess of these compounds in the hopes that somehow they take it up. But currently there's not much known about uptake and I mean availability, I mean the costs are immense. When I talk to our chemists sometimes it's really difficult to produce these compounds and then at the end we get more nuclear. So, there are limitations still. I wonder if there's been any consideration to refactoring, recoding the organelles. We have a much smaller constrained system, basically a translational transcription machinery, very few genes, like 20-odd genes. Like mitochondria? Yeah. We have considered it, we haven't done it yet, but we have considered that. Because you wouldn't have to worry about changing piecemeal because of the whole thing. Possibly. Yeah. It's 120,000. Just like that. Karen, I was wondering if you could comment on the growth rate of these GROs. I know you showed sort of the relative growth rates between RF1 plus versus RF1 minus. Can you comment about absolute growth rates? Sure. So, in the context of doing the experiment we inherited some secondary mutations that reduced the growth rate to about 60 to 70 percent. And the original one that we published that we can attribute to these secondary mutations. And as you mentioned, we didn't see any impairment due to the RF1 knockout. And so what we've actually been doing since that observation, and when that paper came out, is going back and actually using mage to revert some of those secondary mutations to improve growth rate. And we have observed improvement. And is it still like a M-U-S background? Which I presume would also affect growth rate, but I don't know for sure. So, M-U-S knockout does not affect growth rate. What it does is enhance the background mutation rate. Right. And so, we and others, in fact, as opposed to out there, I would point out number one and two, that has shown that you could basically create these dominant negative protein mutants where you can basically transiently silence M-U-S as a way to relax the genome, drive high-efficiency mage mutation, but then remove those dominant negative proteins and then stabilize the genome to reduce that background mutation rate. So, us and others have actually improved that aspect of the mage process. Yes, Victor. Mr. Farron, you have an idea of what happens to your recorded organisms where they are released into an actual little environment like soil or some kind of mesocosm or something like that, because, you know, you may have surprises. You think that this is completely to have a certainty of containment and maybe at the end it would not be like, I don't know. Is there any data on that? So, it's a good question. So, we haven't done that exact experiment. The closest we've done, and we did this in our paper where we showed the containment is rather than taking them and dumping them into the soil outside, what we did is we bought plates that were made from soil extracts and blood extracts and we showed that they weren't able to grow on those so that they weren't basically able to scavenge from the environment and, you know, escape through a conventional type of metabolic cross-feeding. But we haven't yet tried to compete them in nature and I think they would perform miserably, to be honest with you. Same lines. What I was thinking about was, you know, I should have already mentioned UNESCO mutations, you might not need it for your technology, but along those lines for, if you were thinking about industrial streams or non-domesticated streams, is there any limitations to your technology or it's able to be used on industrial streams? It's a good question. So, as you can see, as showed early on, the technology is really based on re-engineering the replication fork and because that's basically conserved across biology in principle, you can do that. And so, we have efforts of basically expanding this into some other bacteria as well as in yeast and those are shown to be promising. And I also know of another paper coming out in PNAS and you should go look at the poster outside that actually shows a system that a group from Hungary developed to basically port the mage, certain components of the mage process into some of these undomesticated species. So, you'll actually see some papers come out on this in the coming months. You mentioned that by removing two copies of the tyrosine tRNA out of three, you avoided the emergence of one species of suppressor tRNA. What's the impact on fitness of reducing the copy number of the tyrosine tRNA by a factor of three and is there some way to compensate for that with a stronger motor? Right. So, we were fearful of that experiment before we did it and we only saw about a 10% drop in fitness in doing those experiments. And I do think that if it was more dramatic than that, we would have basically put it under a stronger promoter to compensate for the loss in copy number. But for those experiments, it wasn't striking enough that warranted those experiments. Any questions? One more hypothetical question. In principle, using your method, you should be able to swap columns for normal amino acids, too. So, have you any ideas about such an organism to do with it? Not sure I understand your question. You could use your methods. You have introduced an artificial amino acid. If you repeat this two times, you could actually swap to an amino acid. Yeah, that's a really good idea. It's something that we have thought about and at least mapped out from a design perspective. And I actually think that would create an even greater degree of isolation, if you will, than what we've done. I think it's possible. It hasn't been something that we've initiated yet, but it's certainly an intriguing idea to pursue. And I definitely think that that would work. Because many species depend on things like sex, and today we have a block also. Yeah, it's a way to fundamentally change the meaning of a codon within that species such that not only would you be preventing the introduction of foreign DNA, but you would also genetically isolate the DNA from this organism going out as well. Yes. I have a very naive question. You replace the UAG with a UAA. What happens if you change the UAA to UAG? So, you're right, we convert UAG to UAA. And that was driven by two main reasons. One is the frequency of those codons throughout the genome, as well as how those codons are decoded at translation. And so I showed this during my talk, but I wouldn't try to convert UAA to UAG for two reasons. One, the number of those codons is on the order of two and a half to 3,000. Two, more importantly, is that UAA is decoded by both RF1 and RF2. So then the route to not just recoding, but then eliminating that function from the cell would be very challenging because you would have to probably knock out a release factor and then engineer the other one to alter its specificity away from UAA. So that wouldn't be a natural choice that I would pursue. Could that implementation change the system because you have to be careful? You have to check, but I mean that's for me the most reasonable thing. Clearly, I also would do that, but you have to take into account that you may... Yes, with our connection to the phosphate network. I mean, we just now opened a completely different door. We didn't expect this, but of course when you think about it it makes a lot of sense. Farron, you want to comment on the question? I mean in a lot of ways I sort of anticipated that question with certain things I covered in my talk where if we do want to redesign biological systems I'll just quote what I have up there. We have to do it in the context of evolution and leverage what biology does and does well and is distinct from other, sort of more... like distinct from other, say, conventional engineering systems. And in many ways I think the exercise in recoding was one way to sort of test a sort of permutation on the evolved natural genetic code. So I think in many cases a lot of the work that we're doing addresses your overall question, but I would say that... Yeah, no, I agree. I'm just curious. Okay, so given what you've learned from these experiments what does that mean? Can we draw more general lessons out of it? I would say that really I think the most elegant solutions are going to, let's say, might come through the lens of engineer but are going to be inspired by how biology solves the problem. And I'm a big believer in that. So I know that there was some discussion yesterday afternoon on the approaches of modeling versus more evolution. I think they both have a role at the table because we are talking about... they all have to solubate the laws of physics and chemistry so there are opportunities to model as a component of design. But biology always has some exceptions to the rules. I think we need to appreciate. And that's where their ability to adapt and evolve and find new solutions or landscapes needs to be anticipated. Well, can they even be anticipated? To Kirsten's point about not realizing the links between... We might not be able to predict what the solutions will be but anticipate that they are there. Fair enough. Great. To cut in there, I think to design for evolution we have to consider something that hasn't been mentioned here but there's very few labs working on that which is engineering more than one microbe or more than one species and let them collaborate. That's basically what we see in real evolution is competition with other species and then you have consortia, farming, biofilms and everything. And I think it's not my area of expertise but I think there's a general observation that if you have mixed populations or some fermentists this tends to stabilize the fermentation processes in those clear samples that is done already. So you would have to engineer more than one organism to actually come up with a more evolutionary, stable solution that would be my intuition. And then there is a whole body of theoretical biology of competition and fitness in those replicator systems that have more than one participant. So there would probably be a lot of interesting theory to try to bring on the table as well. Okay. Well, thank you very much for an interesting discussion and with that I think we can go to lunch.


Hi everyone, Joe for jasperjasecasebreaks.com coming at you with 2019-2020 Panini Hoops Basketball Premium Stock Edition. One box hobby break. Now, that's really not that important. The important part is you got a shot at winning a $3,500 eminence basketball spot. There's actually another one of these up if you want to try it again. Anyway, let's do the break itself first. We'll do the break first, everyone gets a random team, blah, blah, blah, blah. Team on top at the end with the new dice roll gets the eminence ball, only one winner. Big thanks to all of these folks here for giving this a shot. We'll make you sweat it out by doing this break first. Let's roll it, let's randomize it, three and a two, five times, one, two, three, four and five. The giveaway obviously a different dice roll like we always do. All right, five times for the teams, one, and fifth and final time. After five, we've got the Knicks down to the Timber Wars. All right, here's the first half of the list right here. All right, Shawn Matic with the Heat, Grizzlies for Matthew Shearer, Jay going to the Pelicans. You never know, in a one box hobby break could be some interesting things happening here. All right, let's get all this on one screen. Let's sort by column B. Let's box these up. I will tell Nick that, Rex. You can tell Shawn when he comes. He's an angels fan too. Although they need to be signing like Trevor Bauer or not. Oh, they can tie. Can't pick these up. Yeah, well, I wouldn't worry too much about John Lester though. I think he was, he's at the tail end of a pretty strong career. He's a second year Luka Dodgers. That's not too bad. That goes to Louie and Dallas. These reds are not numbered, but these greens are. There it is. 17 out of 99. John Henson for Detroit, Romeo Langford to 35, and Jared Culver right here. So nothing too crazy here. Jay Goins has the Celtics. I'll have to look at the numbers. Maybe due to longevity he might have the numbers, Rex, but he doesn't, he doesn't, I don't think John Lester's a Hall of Famer. He's in the Hall of Very Good, I want to say. All right. So let's see what's going to be good for these people right here. Louie with the Hawks down to Stephen and the Wizards, and everybody in between in this blank list here. Let's roll it and randomize it. Six and a three, nine times. Nervous. Name on top after nine gets the Eminence spot. One, two, three, four, five, six, seven, eight, and ninth and final time. After nine times, drum roll, drum roll, drum roll. Thanks everyone for getting in. Name on top after, sorry, Mike is going to be Danny Connell. There you go, Danny. Nine times you're up there. You've got an Eminence spot, a $3,500 spot for a fraction of the price. There's another one of the, in fact, I think we're doing two more of these ladies and gentlemen.  Jaspeyscasebreaks.com. I'll see you for the next one. Bye-bye.


Hello, okay, so the thing that I'm going to talk about Yeah, so yeah, that was intentional. I know what I'm doing So the so we have so how many of you use third so everybody is a JavaScript developer, so I'm I'll start with that So how many of you use third-party JavaScript libraries on your website Pretty much everyone right yeah, and how many of you have a problem at times that oh this library is creating some problem in the production and I want I want to switch it off, but How many of you have that problem? There's no way to switch it off right you it's there It's out there in the production and unless you do a production release. It's not it's there You cannot solve for it. So in my team we have come came up with a solution for that and what I call it as a plugin framework for your Website, it's it's a JavaScript framework again It's not using any backbone or angular so So it what you do essentially is the first load of your application You take out all the configurations from the from the server that you want to run any particular Plug-in or any third-party library called Let's say Google analytics or you are running a site catalyst or you're running any other analytics on your website So what you do is you load the configuration in the first load which can be cached on CDN can come from anywhere and Then you based on that all your website code is You have all your third-party plugins are safe coded inside that and when you are running in the website And you see that okay some analytics is breaking your page in the production. You can just switch the The the configuration that is coming loading in the initially you can just switch it off And what will result in that your plug-in will be is off from your website You can fix it in the next release till then your customers are not seeing that issue So you don't have to do an immediate patch release You don't have to do anything all you need to do is load that in the initial con and the configuration pretty much I have taken it from grant file.js I was inspired by a grand file.js and I have written that configuration in that way So you can write it whatever way you want to but the idea was that you have a simple config Which can tell that you want to switch it on or anything on or off and it loads in the first go and You're done. So you now don't have to do any patch releases for this So this is how we did any there's no query, right? I am writing a plug-in npm for that So I'm I want to the intention is to put it on for an npm with the plug-in name of I have not decided the name. My name is Pratik Mandela. You can follow


I do my afternoon coffee delivery. So what's in there? Hold on, hold on, hold on. Dude, you can't open that. Whoa, sorry. Don't open it up, don't open it up. What was the secret? Hey Nora. Can you watch my YouTube channel while I'm gone? Yeah, but I need a million subscribers when I get back. Challenge! So how do you become a leading service design agency in the States? Is it any different to work at a U.S. agency compared to Europe? What's their secret? How did harmonic design do this? I guess we're going to find out. Hey Mark. James. Come on in. You know why I'm here, right? I think so. I want to know the secret of harmonic design. Can you help me out? I can try. I want to see everything. Where do we start? How about right here? All right. Let me show you the wall. This is our wall of harmonicas. Who makes these awesome? We do. All right. Everybody, when you become a full-time employee of harmonic, you sketch within the first week, theoretically. Yes.  And that gets associated with you on the website. It's on our internal systems and on your business card. What are harmonicas? We are harmonicas. The team early on voted themselves. Was it a democratic process? It was. Patrick and I didn't choose that at all. Which one is your favorite? I don't know. They all have different flair to them. So I like. Please no politics. So which one is your favorite? OK, let me ask you. Which one is your least favorite? That's an easier question to ask. No, I'm not going to say. I like them all. I don't dislike any of them. Maybe mine. I don't particularly love mine. But it's because I'm the only one who actually didn't draw his own. OK, you cheated. I did. Usually the place where the magic happens. Welcome to Harmonic Central. And it's literally because it is kind of the center of a lot of our life when we're in the studio. Where is everybody? Everybody's working from home or distributed today. So I picked a good day to actually sneak around and open all the cabins. You did? Oh, nice. Got a big table intentionally for meals. And often, especially around holidays, when we have a lot of people in the studio, we'll extend that table and we'll have big meals and potluck or we'll have catered events and stuff like that. This is our first big holiday party after we became a company. Nice. And it was a Polynesian theme at Trader Vicks. Part of the tradition of what we do and how we create and maintain our culture is we have these artifacts of our events because those are often the favorite times that we have in team building is that when we come together and just have fun, we enjoy the work. But we enjoy having time together, too. Hidden almost in plain sight. I see one bottle standing quite lonely over there. What's the story of that? Well, somebody has taken it upon themselves to put all of the other booze away. I'm smelling something really good over here. This is our liquid caffeination station. Liquid caffe... Sorry, repeat that. Liquid caffeination station. Like that. As COO, that's my primary role is keeping folks caffeinated. That sounds good. I do my afternoon coffee delivery. So what's in there? Hold on. Dude, you can't open that. Whoa. Sorry. What's going on? OK, so we were approaching, I think, what could be the secret of harmonic. And then this happened. I don't know if we'll be able to keep the footage, but apparently there's something going on with the fridge. That's how the camera will be over. This is what it is. And... And mobs. Yeah, for you. Thank you. To take with you on your travels. I'm sure that this will be helpful in the service design show studio. Thank you. I hope so. Hopefully it will keep you awake during your late night editing sessions. And then, of course, the mega board. The mega board? Yeah, we like to say it's the largest seamless dry erase board east of the Mississippi. You wouldn't expect it to be so empty that you erase a secret. Good. It may have been on here, but it's not right now. We're getting prepped for people to be here. And by the end of the week, this will be full. How important is this to harmonic? Early on, very, very important. We were very much a face-to-face organization. Now we've moved online and we collaborate more digitally. But I'll tell you, when people are in the office and working with each other face-to-face, we're constantly on the whiteboard. People like to draw. People like to illustrate their thoughts and ideas. These are our team rooms. Can we go inside? Absolutely. Right. So what's up with the name? Now retired, the rooms are named after our brand colors. Named by the team, of course. Part of the culture that we've created is that it's really about everybody can contribute to what harmonic is and what it means to be a harmonica. This is probably several different conversations. You look at the color. They're color-coded. Yes. If you're in the studio and you need heads-down time or to be on conference calls, you can just huddle in here. Please tell me more about this special character over here. It's our avocado. This is a formal portrait of the atomic avocado. The atomic avocado. So this is already getting closer to the secret. It's pretty close. Avocado definitely has something to do with it. What do we have over here? This is our big room, also called Dangerine. What happens to Dangerine? Large collaboration space. This is where when we have a team that is mostly based in Atlanta, we often meet here. Even though we can work from wherever, people like to work together still. We've got really great views of Atlanta on three sides of our space here. And that's one of the reasons we got this space. It's just because we have windows on three sides. And designers are finicky. They like their natural light. This is Edgewood Avenue. It runs into Old Fourth Ward and is a historic part of Atlanta. And of course, it's usually a little busier than this when Georgia State's in session, but they're on break.  You'll notice little animals and stuff around the office that people have contributed. I see a sheep over there. We're no sheep, but we have an affinity for animals. That's one of the other questions when people join. It's actually part of the interview process. Cats or dogs. Coffee or tea. Yeah, or sheep. So what's the next space? Where do we need to go?  There's a target. Yeah, we're trying to. Who are you trying to hit? I don't know what that is, actually. Who's there? I like the fact that this has even expanded beyond the walls. Yeah, we never have enough writing space. You never have enough writing space. I would agree. Lots of creativity going on in here, you can tell. So service experience, service management, service operations, and service strategy. Yeah. And in the middle, service maturity. Yeah, we're doing a little business strategy conversation in here. I love it, and other people do, too. And I think one of the things that is kind of thematic is that the times that we have together are those moments that we remember. This is just a making space. What's the thing you miss most when you just meet virtually? It's the after-meeting chat, and just like walking back to where you're sitting, or going to seeing who's around for lunch, and just going to do a random lunch and hanging out with people you don't usually get as a chat with, or you haven't been on a project within a long time. How often do you get together with the entire team? At least three or four times a year. At least that's the intention. It hasn't happened over the past few years, as you can imagine why. But this is actually from before the lockdowns. Really? Yeah, the team was at the Atlanta Zoo doing a service safari and experimenting. Literally a safari. It was. And experimenting with using non-human actors in blueprinting. What's in the cabins? Paper. Legal paper. Hey, we've got all the stuff you need to run a workshop. Colors. What else? I'm going to snoop around. I'm still looking for the secret. You're not going to find what you're looking for. I'm still looking for the secret. We've got our private cubbies here. OK. Somebody left their box of drawers. What's the most precious thing for you inside these cabins? Well, I love the merit badges. What are these? These are merit badges. So when you do something for the first time at Harmonic, you get one of these for your laptop. OK, so what's the dock for? That's the Heck Yeah Rubber Ducky. Heck Yeah Rubber Ducky. When you do something cool.  Coffee is for closers only. Purple Heart is for after the US military Purple Heart. Are you still waiting? Do you've collected all of them? Or are you still waiting for one? How is your collection? My collection is pretty weak. Oh, that's not good. They don't let me out of the cage often. And all the things you need to run a workshop, including time timers. My favorite. I wouldn't know how to be productive without one. Yeah, those are pretty cool. So how close are we getting to the secret, James? Because that's why we're here. It's cumulative. Oh, I think it's. So what's what's the next thing that adds to the secret? Well, you've got atomic yoke. Atomic. So we like this like 1950s kind of flair on our color, probably, as you can tell. But also, you know, a great room for hanging out, good view of Grady Hospital and downtown area here in Atlanta. This is probably the room with the most light because you have three windows in it and they're facing different directions. Do they have your own space here? Or does everybody make it all up? Everybody jokes about this phone booth being my office. Yeah, this is I'm going to pull Ace Ventura. You can do all nighters in that one. Well, lots of conversations have been had in that booth. What's one of the conversations you still remember having in that booth, a fond memory to remember? I think the first time we spoke, I was in the booth. Well, there you go. And now we're here. Yeah, because back then, there were probably more people bouncing around and it was probably noisier here. All the rooms were filled because we used to assign each room to an engagement. But this is a conversation with space. Are we going to sit on? With Nicholas Cage, another harmonic or contribution to the space. So what happens here? Just chat, listen to music, read. Because we're adjacent to the library, also called inner depths. What's the music that's usually on? It really depends who's in the studio first. I like just kind of chill like down either down tempo house. Patrick likes indie. Indie? Yeah, he likes indie rock. In the name of Patrick Quattobon, we'll sing this happy Monday song. You mentioned something about the library. Is that still something we need to explore? Absolutely. The deep space? How did it? Inner depths. Inner depths. So OK, sounds intriguing. If you're looking for the secrets of harmonic. We are. That's why we're here. You might find it in a book or two. OK. The team are avid readers and writers. This is actually a working library. So what's happening here? This is a collection of people's favorite design and related books. And we usually have about 50 copies of Patrick's book here that he wrote with Chris Rizden. I see some classics. Yeah. I think this one was one of the first books that I actually read, subject to change. So yes, so Patrick and Steven seeded the library from their own collections. And some of these books are, I think, checked out. These shelves are usually pretty full. But anybody can contribute. And often when we buy books for the company, we'll get an extra copy for the library. But lots of reading and writing going on here, as you can tell from our active blog and social media speaking on the various conferences. Everybody's welcome to contribute to the decor in the office. You can see our pie print. That was designed by Steven Taylor. It is pie to, I can't remember how many. A lot of numbers. How many digits, yeah. Oh, a design. Even more classics over here. I've seen that book a lot of supplies before. So that's a pretty popular one. And funny enough, this is services I'm thinking, sort of at the seed of Harmonic's story. Back 15 years ago when Patrick and I were working together at a large engagement. And trying to figure out, lots of conversation. We were up in Charlotte. And lots of conversation about how to apply UX principles to how people operate businesses. And bring that human centeredness in. And like, lo and behold, this practice is emerging from Europe into the United States called service design. Is there something else to the secret? We could go back to the lobby and look. So we're going full cycle? Yeah, absolutely. And of course, part of the theme is, I think, probably picked up on is that the company is still clay. And we're always evolving and trying and changing. And a lot of what happens here is determined by the people who work here, not just Patrick and myself. We've sort of tried to guide folks in the right direction. But a lot of it is independent. A lot of what goes on here is independent of us. And I think really makes it a great place to work because people are self creating and testing and trying, experimenting. What's the thing that you're most proud of that the team contributed to the sort of the way harmonic has turned out to be? Openness and willingness to share and learn from each other. We're not a big hierarchical company. We're relatively, not to say we don't have titles and hierarchy, but we're relatively flat. And we all play on the same field. So anybody can contribute in any way that they can make of it what they want. It's their job to do it and participate however they want. If it's their internal operations and they want to help out with that stuff, we have internal projects that help push the project, the practice forward. Memorabilia and artifacts in the office. Steven is often contributing these cultural artifacts, which he made as a... I recognize this, but tell us more, what is this? Yeah, this is the iconic IDO. I think it was a medical device. The walls, I think. One of our engineers who wasn't quite satisfied with the discussion at hand leaves the brainstorming session for five minutes, makes the ugliest prototype in the history of IDO. It was like a whiteboard marker with some scotch tape around it and a little clothespin thing. And he brings it back in and hands it to the person who was sitting next to him in the brainstorming session and he says, hey, are you thinking of something like this? And nobody laughed. This medical advisor picked up the device and said, yeah, something a little bit like this. And Steven found that to be inspiring and was inspired enough to recreate it as closely as he could, you know, as a memento and a reminder of it's important to play and have fun, but you can do serious work at the same time. So have we gone full circle? Is this, is this the end of our journey or is there anything left? I can really go for another cup of coffee. Okay, it's time to do the thing that every service design professional just loves to do. Let's synthesize all the things that I've learned through my research in Atlanta and figure out if we have found the answer to the question that we started with. What is the secret to becoming a leading service design agency? Well, there are definitely a lot of clues. The positive spirit of the team, the creative and playful culture, the space that invites collaboration, the longterm vision of the leadership team and of course we can't forget the office dog. There are really some other questions that I still need to ask them. Remember that moment with the fridge? That was weird, right? Well, I guess I'll just have to come back next time. And we'll one big harmony.


Most of the time, distances measured in the field are assumed to be horizontal distances. If the distance is long or the slope is severe, the person on the lower end of the tape may not be able to hold the tape high enough to bring it to level. If you encounter this situation, then you must break the measurement into two or more shorter measurements so the tape can be held level for the entire measurement length. The measurements for each section are then added together to estimate the total distance measured. This is why it's called breaking tape. When measuring each section, the tape should be pulled taut and straight, not left slack, but not overly tight to the point of excess stretch. If the tape is not pulled tight, all distances will be too long and a positive bias will result.


Kaduna State Government has expressed its readiness to continue supporting Nigerian armed forces, fallen heroes who have paid the supreme prize of serving their fatherland and protecting the nation. The State Governor, Senator Obasani stated these are the flag of the 2024 emblem to mark Armed Forces Remembrance Day across the country. He underscored the need to support the gallantry of serving military and fallen heroes who have made huge sacrifices to defend the country against enemies of peace. He added that the emblem symbolizes the spirit of patriotism and selfless sacrifice that all Nigerians must embrace and reflect on to serve the nation in truth and fate. Today, gallant members of the Armed Forces are spread in different form, battling bandits, terrorism, insurgents, kidnappers, and other criminal elements. They have been recording successes despite which challenges. Many of them have been away from their families for months and years. Our departed heroes led behind wives, children, and relations that must be catered for. Careful, there are thousands of patrons, some of whom have special health needs and challenges. Let us share a thought for our dear citizens who lost their lives. Let us recommit ourselves to the national pledge to sub-Nigeria with all our strength, defend her unity and uphold the honor and glory. It is in doing this that the sacrifices of our heroes' past will not be in vain. The acting chairman of the Nigerian Legion, Kaduna State Chapter, Major Dandrum Abarren, retired, who was represented by Major Baladamu, said the establishment of core commissioners will assist in intelligence-gathering, insecurity and conflict resolution and other threats to the nation. They appeal to government at all levels to support Nigerian Legion, widows and children of the fallen heroes which have served the nation faithfully. As you are all aware, the Nigerian Legion is a self-sustaining body that depends solely on the goodwill of the people like you. I would like to appeal to the state government and the general public to continue to support the Nigerian Legion to enhance the welfare being of the heroes, orphans and widows among others. As a matter of urgency to consider the establishment of a core commissioners in the state based on the approval of the president of the Federal Republic of Nigeria. The establishment will render services such as provision of security, public and private, intelligence-gathering, school crime, detection and provision of local conflict resolution.


Hello, and welcome to our presentation about ST's MEMS gyroscopes. In this presentation, we will review how MEMS gyroscopes are developed and produced at ST, their main applications, their internal structure and working principles, and details on how to use them for your application. First, what are MEMS gyroscopes exactly? While accelerometers measure linear acceleration as long as there is no rotation, MEMS gyroscopes generate an output signal directly proportional to the angular rate applied to the device. To do this, they measure the force generated by what is known as the Coriolis effect. If you are not already aware of this principle, please check our quick reference towards the end of this presentation. When an accelerometer is rotated, the projection of gravity acceleration is measured as well and there is no way to distinguish between the two different contributions. By using a gyroscope, angular rotations are measured, while linear displacements are not. Accelerometers and gyroscopes can be combined to create an inertial measurement unit or IMU. An ST MEMS gyroscope combines the MEMS sensor itself and an ASIC to process the sensor output integrated in a single micromachined structure. To achieve a very high level of integration, ST uses a system-in-package approach where the ASIC part is stacked on top of the MEMS structure to address applications where small size is a key constraint. The MEMS sensor is composed of a mass, which is kept in a continuously oscillating movement so that it reacts to the Coriolis effect when an angular rate is applied to the device. A CMOS ASIC measures the angular rate of the MEMS element relative to the external world and delivers an analog output voltage proportional to that rate. To give you a more detailed view of our implementation expertise, here we have a detailed view of the MEMS structure of a single axis gyroscope. In the photo, we see the mechanical mass with its two wings highlighted in yellow. The wings move up and down when an angular rate is applied. Capacitive plates surround the structure and are used to actuate the mass. The diagram on the right shows a representation of this structure along with the capacitive plates that are used to create the motion. The cross sections at the bottom show, on the left, wing behavior when no angular rate is applied and, on the right, when an external angular rate is applied. The wing displacement is read by detecting the capacitive variation between the bottom plate and the wing itself. With this structure, we consider that ST has reached the state of the art for this type of product. Gyroscopes were once too big, too power-hungry, and too expensive for consumer applications. Recent MEMS gyroscopes have paved the way to a completely new set of innovative applications. They can be used to implement new advanced user interfaces and give the user an improved gaming experience. For these applications, a full-scale range of thousands of degrees per second or DPS is required to capture the player's rapid movements. At the other end of the application spectrum, image stabilization for digital, still and video cameras only needs 30 DPS and very low noise and high stability over temperature as key parameters. ST's gyroscope offering is able to cover all the main applications with the widest portfolio of single and multi-axis gyroscopes now available on the market. Let's have a quick look at ST's family of standalone, multi-axis gyroscopes. ST offers the widest choice of full-scale ranges in the market, from 100 DPS, suitable for image stabilization in digital still camera and video camera, up to 6,600 DPS for improved user experience in gaming and user interface applications. ST OIS gyroscope is the smallest package in the OIS market, offering an excellent rate noise density, top-level performance, and low power consumption. Each OIS gyroscope integrates a temperature sensor for best-in-class temperature compensation for photos with high quality, improving the long exposure time pictures. These charts show ST's family of combo devices with multi-axis gyroscopes. ST's gyroscope in combo devices is an ultra-low power solution for always-on applications combined with best-in-class performance. At ST, we focus on a set of key features to guarantee that we provide the best-in-class design. Let's have a quick look through these features, for example, zero-rate control, sensitivity, and so on, to see how ST performs. So first, a quick explanation of the terminology that we use to describe how a gyroscope rotates in three axes. There are two in-plane axes called pitch and roll, the X and Y axes. The third is an out-of-plane axis called yaw, the Z axis. So linking in with our previously mentioned key features, zero-rate level refers to the analog or digital sensor output value when no angular rate is applied. Sensitivity always refers to the ratio between the output and input of the sensor. ST's gyroscope family provides the industry's best zero-rate level stability over an extended temperature range of minus 40 to plus 85 degrees Celsius. Thanks to this excellent performance, which also applies to the sensor's sensitivity, users can save cost and effort otherwise needed for temperature compensation in their products. A complete understanding of the main parameters associated with MEMS gyroscopes and their representation in the datasheet is very important in order to fully exploit the advanced performances provided by these products. Zero-rate level is the output of the sensor when no angular rate is applied. This parameter is indicated by a typical value and specified over a certain accuracy range. Temperature variation could affect the sensor output even when there is no external stimulus. The temperature characteristic is also reported here to provide the user with a more complete comprehension of possible drifts. Sensitivity is defined as the ratio between the output and input of the sensor. In the case of digital output gyroscopes, sensitivity is usually expressed as DPS per LSB. As for the zero-rate level, sensitivity is also reported both at ambient temperature and over the device's specified temperature range. Temperature characteristic is also reported to provide the user with a complete comprehension of possible drifts by simply subtracting the zero-rate level from the output value and dividing the result by the sensitivity expressed in MDPS over LSB, we obtain the angular rate applied to the gyroscope. The sensitivity of ST's gyroscopes is also characterized by the excellent temperature stability with a variation of a fraction of a percent for each degree Celsius. The third main parameter to consider when dealing with sensors in general and gyroscopes in particular is the rate noise density. This parameter is usually expressed in the form of spectral density, allowing the user to get the actual value of the noise depending on the low-pass filter applied to the output. The output noise will vary depending on the bandwidth. Reducing the bandwidth through low-pass filtering helps improve resolution measurement. The highlighted formula shows that by multiplying noise density by the square root of the bandwidth, the RMS value expressed in degrees per second can be immediately retrieved. Noise is usually expressed in terms of rate noise density, MDPS over square root of the frequency, allowing the user to evaluate, depending on the bandwidth selected, which is the final noise level. The table in the bottom center of the screen can be used to convert this value to the related peak-to-peak level. To summarize, ST's consumer gyroscope family provides the customer with unrivaled performances. The excellent low-noise level makes ST's gyroscopes perfectly suited for applications requiring high-resolution angular rate sensing. So now that we've been through the high-level view, let's check out some of the technical detail behind how MEMS gyroscopes work. This may help you in deciding whether MEMS gyroscopes are the right component for your product. As said previously, ST's MEMS gyroscopes use the Coriolis force to measure angular movement. When a mass moves in a particular direction with a velocity v and an external angular rate is applied, see the red arrow. The Coriolis effect generates a force shown here with the yellow arrow that causes a perpendicular displacement of the mass. The value of this displacement is directly related to the angular rate applied. This displacement is read by measuring variations in capacitance, a robust and reliable technique successfully used across ST's MEMS product lines. In practice, ST's MEMS gyroscopes use two equal masses that are kept oscillating so that they are always moving in opposite directions, much like a tuning fork. When the system rotates, the Coriolis forces on the two masses are always in opposite directions and the angular movement is measured using the difference in capacitance between the two sides. When a linear acceleration is applied to the sensor, both masses move in the same direction, so there is no difference in capacitance on each mass, so the result is zero. Compared to a single mass approach, the differential nature of the tuning fork makes the system intrinsically insensitive to undesired linear acceleration or vibrations acting on the sensor, and so only measures the angular rate. For the Coriolis effect to work, the driving mass must be kept under continuous movement. This is achieved with an oscillation that is regulated and guaranteed by a dedicated portion of the ST-ASIC circuitry. As soon as an external angular rate is applied to the sensor, shown by the red arrows, two separate and flexible wings cut inside the mass move up or down, depending on the direction of the angular rate applied. Note that as one wing moves up, the other moves down. The distance traveled by the wings is measured to provide the angular rate. Thank you for following this presentation. Data sheets and application notes on the ST-MEMS gyroscope and evaluation boards are available online from our dedicated page at st.com.com.