In a nutshell, the NAPLAN test is assessing students' basic literacy levels. It is important that all teachers contribute to developing those literacy levels. So as a teacher, we can use the content that we're so passionate about to deliver basic literacy skills. It's not about anything extra, it's about incorporating effective strategies into your teaching and learning practices that students will benefit from. These are skills that they will use for the rest of their lives. So it's your responsibility and teachers' responsibilities to make sure that the students are exposed to those skills that they need for their future. So it's definitely not about an extra thing that we have to incorporate, it's about delivering our content through the skills that they need. Well, NAPLAN data is a great way for us to also see the different programs and the different things that we're implementing within the classroom and within the school, whether they're working efficiently and whether they are actually increasing our student outcomes. So it gives us that map of progress. The other way that we're able to use the NAPLAN data is that it gives us those future directions. So for example, at a staff meeting, after examining the NAPLAN data, staff made connections about some of the things that some of the patterns and some of the things that they saw occurring and then from that they were able to create as a staff questions about where to next. So how could we, and for example, one of the questions was how could we increase our Year 3 students' interest level reading or our Year 3 boys' reading interest levels or how can we implement what we do very well in spelling? How can we get children to transfer those skills within spelling to everyday writing? So the NAPLAN data provides us with the information that we need to start at the point at which the students are and to provide better pedagogy and better curriculum for them individually. NAPLAN data is helping informed teachers about their students, about their strengths, their weaknesses. In terms of the NAPLAN data itself, we take things in a very literal sense in terms of creating data walls for all our staff. So the idea is we have this collection of data from NAPLAN, obviously in Year 7 and Year 9, that we can actually put a face to that data. And we put displayed in a very prominent place in our staff quarters so that in terms of becoming a highly visual tool that teachers can use to identify students that might ordinarily be slipping through the gaps or fly under the radar or putting their face in terms of their name front and centre, we seem to be able to alleviate those issues. The key area in which it's helping us to improve student learning outcomes is the tracking of growth of each individual student. We have a personalised learning agenda at our school so that individual feedback provided on teaching programmes through the item analysis that allows us to corroborate where every kid is at. And if we teach them at their identified point of need, that's the key to making rapid progress. And we have seen the proof of the pudding because that process has worked for us. It has lifted the student gain tremendously from years 3 to 5. And it's a simple formula for us, but it's one that we found that works. See where the gaps are. Build teacher knowledge of the precursor and skills that support that gap. And teach to that gap and assess and then I think we generally find that we fill those gaps. And that is our key to driving student learning. The NAPLAN data, whilst it's great for assisting us at our own school in terms of classes and their specific literacy and numeracy needs, is also beneficial because we can then feed back to our feeder primary schools the areas of weakness, particularly for our Year 7 students. And they can then build those areas of concern into their teaching and learning programs as well. We have a very strong community of schools link, so we try to minimise the gap between primary school to high school. So that's one way in which the data is useful in that respect. Within our own school, just the ability to look at the class need and build up those skills within our everyday teaching and learning program. And just making sure that we are progressing from what the child's already at to where we want them to be, identifying them on the literacy and numeracy, continuing and ensuring that we're moving them along. That's just one of the benefits of the smart data NAPLAN package. In terms of the school, it allows us to ensure that we are teaching and ensuring that there is progression and it's not just teaching for teaching's sake. It's there to ensure that our students walk out the school gate being literate and numerate as a member of society. Aries' use of NAPLAN data to improve student outcomes also can be used with raising expectations of teachers. It allows us to look at where our children are and where they can go and also how we can get there. It also provides the school with a shared goal. It's not about A teacher in A class, it's about the school. It's about the school understanding the context of the students, what their needs are, what the individual needs are and what their group needs are. And we can use that data really well to map forward to get more positive outcomes for our students. One of my previous schools, a very low achieving school, which consistently was underachieving in a wide range of tests, was a very difficult school to work in. It had a lot of behavioural issues and teachers felt disempowered by finding some focus areas that teachers could use to implement, to make improvements in teaching, their teaching, but also in the student outcomes, provided us with success, small success. Not success, it was out of the range of that particular group of students or teachers, but success which we were able to build on. And indeed over periods of years, that success translated into more than just the classroom, it translated into behaviour, self-esteem, creative and performing arts. So those fundamental things that happen in a classroom, the success of children, are very important for the overall well-being of students. It's enabled us, the NAPLAN data has enabled us to actually focus our teaching. It's informing us with the areas that our students perhaps are not doing as well in, also those that they are doing very well in. And so we can see where our programs are working and for those other areas where they're not, it means that that's what we need to incorporate into our teaching. And by doing that we're giving our students a very comprehensive education and they should come through then with all the skills that we want them to.


Think Tech Hawaii. Civil engagement lives here. Hey guys, this is the Prince of Investment with your host, Prince Dax. Coming to you guys all the way live from the beautiful state of Halu'la, Hawaii, via Denver, Colorado. So it's always, I don't have a lot of time, and I definitely, you guys, don't have a lot of guys and girls, don't have a lot of time, so we're going to jump straight into it. So this video, we're going to talk about water reach and how do they work, as you can see in the description box. But what are people that are catching this for on the playback, the podcast, all that's catching this live right now. Thank you for tuning in. Don't forget to hit the like, subscribe, comment, share button, drop some comments if you've got questions below and all the other great stuff. But to think about it, we're going to talk about water reach and how do they work with me, your host. So water reach, reach are, is they asking them for real estate investment trust. They was created in the 60s to give ordinary people an opportunity to be able to invest into real estate. Now I'm not going to sit here and tell you today that, hey, I'm the best real estate person in the world. I know every single thing about reach, but the thing about it, what I'm going to do in this episode is we're going to talk about water reach, what are some of the advantages, the disadvantages, how to be able to get involved with them, a general understanding of how they work, and I may do something a little bit more detailed later on. So water reach, a resource, real estate investment trust, right? We all know what real estate is.  But to average everyday person to be accomplished, not to accomplish, to be able to get involved with real estate, you have to have a good credit score, you may have to put some money down, all types of things you may have to do. Now, I'm great, I'm not going to get into, I'm not going to unwrap the ravellings of all the different ways you can get involved with real estate and how much money you need with no money and things like that. But we're going to talk about, we're going to talk about the simple ways for you to get involved into real estate. So this will create in the sixties just four people to have the opportunity to be able to, to be able to profit from real estate. So essentially a real estate or a resource, you can purchase them from, well you can purchase them from, you can purchase them from places like brokers, TD Ameritrade, E-Trade, Scottrade, things like that. Those are the places you can purchase them from. You purchase them just like a stock.  Inside that bucket, they may go out and say, hey, we want to raise money. They IPO, they are an initial public offering, they raise money. So when you purchase the stock or you purchase the read, you're turning your money over to a group of investors. Those group of investors, depending on what type of read it is, they may go out and buy houses and look, you know, they may go out and buy houses or they may buy particular mortgages. And with those, you know, there's other ways to do it too, but to give you prime example two ways, houses are mortgages.  So reads can be set up that way to where they capitalize on someone paying their particular mortgage. On the other end, with what reads do is they go out and do the traditional way. They go out and get an apartment, a house and they rent it out. And when people pay their rent, that creates cash flow back into the reads. So the thing about the SEC, they're regulated by the SEC, the securities change submission. And what the securities change submission does is they require that 90% of the holders inside of a read must be inside of real estate, right? So what it does is it goes out, it takes some money, it buys things, buys all types of real estate, houses or whatever the case can be. A lot of them set up different. You have to read and, you know, I'm not telling you everyone of them set up the exact same way, but they go out, they purchase particular homes. And when they purchase homes, just like anybody else who pays their mortgage or who pays their rent, the money is fed back into the funds. And when the money is put inside the funds, the money is distributed back out to the shareholders. Almost kind of like the concept of a, almost like a real estate group. The thing, now this is over some of the advantages of a read, right? The thing about it is some reads go for 30, 40, 50, 100 bucks per share, right? So someone who only has 30, 40, 50, 100 bucks a share, they can now take advantage of a read. So an average everyday person actually has the opportunity and chance to be able to be involved with the read, like someone who's listened to this now. And also it's a great way to diversify your portfolio without having to make a big, you know, commitment or purchase. We all know most mortgages are 15 years, 30 year mortgages, right? So you don't have to make that big of a commitment. And if you want to diversify your portfolio, you want to add real estate to your portfolio, instead of going out having to buy a piece of land or property or whatnot, you can look into something called reads. I hope I'm saying this right, a real estate investment truck. So it's a simple way that you can get involved. That's the advantage. What are the disadvantages? One of the major disadvantages that I see with a reach, they don't gain the value that traditional real estate earns. For a prime example, I live in Hawaii for a couple of years.  And with that being said, if you bought a house, let's say for $400,000, and Hawaii three years ago, and you just held on to it, and you can sell it for five or six hundred, you know, a few years later, right? Most, you know, you're making 25, not 25%, between $100,000, almost $400,000 investment that you didn't even put up. You just made the commitment for it and walked away with, you know, a nice piece of money, right? The things with real estate investment trust, they usually don't grow like that. You know, you don't really, I don't see that I know of that I see, I don't see too many real estate investment trusts just doubling and tripling and quadrupling over themselves. It may be some amount there, but they have a, they typically move like a stop. So when they move like a stop, for someone who goes out here who has good credit, who has the income, who can afford it, and who has the know-how, they may go out, they may rent a property, right? They may buy a particular property, they may rent it out, right? They may buy these properties, rent it out, the property may cost them $400,000. You know, they're not paying it. They then, they may have to put some money down or didn't put some money down. They can turn around and sell the property for $500,000, $600,000 a year or two later. And you know, their property is going in $100,000, $200,000, also just, you know, making a commitment, taking the risk of making the commitment to be able to pay that. The thing about it is with real estate investment trust, you don't see them move like that. They typically move like the stock market. Now, let's go back to the advantage side of the house. Earlier I spoke about one of the advantages of that, anybody, not any anybody, but a lot of people have access to real estate investment trust. And with that being said, because it's so cheap to get into, right? It's almost like buying a purchasing on stock. So the other positive side is that, is that most REITs pay a nice dividend. And what I mean by paying a nice dividend, their dividends are usually something, it can run in between three to four to five percent, right? And it's a very easy way to diversify your portfolio. That's why, you know, that's why the advantage, but the disadvantage that you think you're just going to grab it and it's going to replace, it doesn't replace traditional real estate investment trust, right? Now, the other thing about it is, yes, you can go out and start your own real estate group, but the thing about it is that it's regulated by the SEC. What I mean by regulated by the SEC, the SEC requires that they hold certain amounts of funds inside of the, you know, they must hold a certain amount of funds, or the funds must be in some type of real estate, right? So they're regulated. Every quarter they must put in quarterly reports. So now another way, like I spoke on earlier, I have a detailed video on the investor show YouTube channel. We have a step-by-step video on how to find reach with e-trade and tini Ameritrade. Those are like the top two brokers that people utilize. So I have a step-by-step video. It's not as simple to find them, but I have a video that help you use filters on tini Ameritrade to help you add real estate into your particular portfolio. Now one of the reasons why I say that adding real estate is a good thing, and something that I'm trying to inform the option of doing even more involved into real estate is that it diversifies your portfolio. Like we always speak about having so much money in equities, so much money in bonds, so much money into real estate. So these are ways you spread your money out depending on how the market may move and how things may go. So that's one of the great ways to diversify your portfolio and to get involved with reach and how you can purchase them. Now also with another simple way, if you're someone who doesn't have an e-trade or Scott Drake account, not Scott Drake, I know tini Ameritrade, purchase them, but e-trade account, one of the ways you can look into doing a read is, you know, one of the ways you can look into doing a read is you can get inside of a reach and now one of the ways I'm kind of lost my little chance out there, but one of the good ways of actually utilizing a read to your advantage is it's a great way that you can look into or an easy way for tears to start out and to get a little taste of real estate. So if you have a five to nine plan but a brokerage account for your child that you opened up and you want to kind of give them that little taste in real estate, this is the way to do it. They also pay nice dividends. Now one of the disadvantages I just thought of that I forgot to mention earlier is that reach usually pay a nice little dividend, you know, talking three or five percent dividend because they're collecting money from their tenants paying or they're collecting interest off mortgage. That money is falling into your account. At the end of the year, Uncle Sam's going to want a piece. That's just how it goes, right? So if you're paying taxes on money that you probably didn't even utilize. So depending on your taxes, depending on the way you're set up in taxes, it could increase the tax liability because of the dividends that you're collecting out of the reach. Even if you have those dividends reinvested, those dividends are still being reported and you still are accountable to pay taxes on them. So that's another, some people consider that as a disadvantage depending on your tax situation depending on your tax bracket, all that type of stuff. So those are things you must consider when you are looking to purchase a real estate investment trust. I will advise you to do your own particular research to learn more about real estate investment trust. And what I lost my train of thought on earlier, I was trying to, I was speaking about if you don't have TD Ameritrade, E-Trade or Scott-Trade account, one way you still can look into reach is you can just Google, just use the word Google, reach stock numbers, not numbers, but reach stock symbols. And those symbols will return you particular, those symbols will return you particular investments that you can go off, symbols that you can look up and do your own research and look into other reach. All reach is not the same. Some reach have different objectives. They're equity reach, they're mortgage reach and there's another type that I can't even remember reach. So look inside of them to find out more about them. But it's an easy way and a great way to add real estate to your portfolio without the traditional way, a non-traditional way to add real estate to your portfolio. Also, it's very cheap and inexpensive to get into and it doesn't require commitment because it pretty much trades like stock. So I hope that helped you guys. You know, we talked about what are reach, how to purchase them. We talked about some of the advantages. We talked about some of the disadvantages. We briefly spoke about how they worked, the different types they are. Who they were regulated for, why they were created. Why they were created is very important to me.  And you know, from what I read in research it was created in 60 to give people a chance with real estate investment trust. Here this is 2018, I don't know too many people even brought up real estate investment trust. So look inside of that. That's a quick and easy way to add real estate to your portfolio. So as always, we've got state tuning here. Next week we'll be coming in live all the way from Omaha, Nebraska. We'll be airing there and showing some stuff here on Think Tech Hawaii at the great Berkshire Hathaway, Warren Buffett's Berkshire Hathaway, 2018 meeting. If you haven't seen the cover to the 2017 meeting, please stop and take the chance. Go look at the seven minute documentary because I will be making another one this year. So as always, my name is Prince Dykes. I'm not going to be here for too long. My name is Prince Dykes. Thank you guys for tuning in. I hope this video will help you. Don't forget to hit the like, subscribe, comment, and share button. Until the next podcast cartoon, or whatever you seem to do crazy around the globe, peace, be safe, amout, and safe.


Why narcissists don't end up together? Narcissists don't tend to end up together They don't tend to end up in abusive relationships Because they don't put up with it They don't allow people to treat them badly Because they can recognize bad behavior they can recognize mistreatment, but we don't recognize it We think it's normal because that's how we were treated by our parents So we don't see anything wrong With being treated that way We think it's what we deserve But a person who is self-absorbed and lacks empathy Does not need to watch these types of videos They don't need to learn about narcissism Because they would already instinctively know that something is not right They would recognize it without conscious thought They would feel it by natural instinct They would feel like it's unfair They would recognize that they don't feel good But because we have weak boundaries, low self-esteem and high empathy We don't tend to call people out on what they're doing Instead We give other people priority over ourselves We let them do whatever they want to do Even if it harms us Because we've been trained to be this way since childhood It's a result of our programming It's all we know and that is why we end up with a narcissist Because we don't see that something is wrong until it's too late Until the damage has already been done But narcissists are wired very differently They've been taught that their experience of the world Is the only one or the only correct one Which is why they're so sensitive to criticism or devaluation Which is why they don't end up with other narcissists Because they see it from the jump Thank you for watching I hope this video resonates with you Please like, comment, share and subscribe If you would like to donate My paypal link is in the video description Coaching inquiries You can email me at coach.narc-survivor.uk Thank you for watching and I'll talk to you soon


Well, and welcome. This is the script we wrote in the last video that calculates the days until Christmas. Actually, the days, hours, minutes, and seconds until Christmas. And originally named this XMS underscore one because I was going to make a second script, but I'm just going to modify this script instead of creating a whole new script.  I'm going to put a note at the top of this script here, like so. We are going to be using a program called toilet. Check out my videos. I've done videos. There's toilet and figlet, which are both very similar applications. And toilet has to be installed to use it. But to put it simply, if I make sure toilet is installed by running this command, I can then say toilet and I kind of use it like echo and I can say hello world. And in this case, it's kind of ugly. That's the default, but you can do different types of ASCII style text on the screen. Figlet and toilet both are useful. I felt like toilet. I think it was, even though it's a funny name. I think some of the default or the presets they have look a little bit nicer. You can do colored stuff, metallic looking stuff, all with ASCII art in your shell. Let's go back into our script here. So I'm just putting a note in here. I've done in the past where the script can check since I'm not creating like a dead package for installation. This is just a self script. In the past I've done check if this file exists. If it doesn't, then try running apps install this, which would work on Debian based systems. But if you're using something other than app, it won't work, blah, blah, blah. It's just what I feel like doing today and I don't feel like doing that. But I am going to now check if the user, so basically this script is going to work like the previous one or you can tell it to use toilet if you want fancier text. So you can have plain text or the ASCII fancy art. So basically the way we're going to do this is real simple and just say, hey, if the user gives an argument toilet as the first command, the first argument after they run the command. Well, then we are going to set toilets equal to true. Perfect. Okay. Now we're going to then go into our main loop. And right now our main loop prints out this text. We're going to move that to another function. Let's go ahead and grab this starting here. Oops, we'll leave the sleep command there. Let's do D to pull those lines. And then I'll go P to paste them here.  So when you run this command, it is going to get the time and that text output. But we want to put that output into a variable. We'll call it output equals. And as we talked about previously, actually all the time, if we wrap our command in a dollar sign parentheses, now it's running that command and putting the output of it into that variable. Great. Now let's go ahead and run that command inside our main loop here. That's actually let's put our clear and main loop up here. And then I'm going to say get time. Perfect. So we're looping, we're going to get the time. And then we're going to have another function in here. And I'm just doing things in functions. Lots of times people don't do the shell scripts. I didn't for years. I'm starting to get in the habit of it. Now we're going to do create another function called print output. Okay. And here we're not going to do an if statement. We're going to say if. And again, spaces are important here. Make sure you have them where I have them, or this will not work properly. Then, and it will say else, it will say if. Great. And what we're going to do is, if toilet is true, which is set by the user at the beginning of the script, we're going to run the toilet command. Again, toilet has to be installed. We're going to do filter, metal, and we're going to do dash F SMB lock. And we're going to pass it the output text. This is going to be rough. Obviously, you can play with this to get the look that you want. But we're going to do another filter of border. And we're going to do metal for that. So this is saying if toilet is such true by the user, use toilet. Otherwise, just echo the output. And we have to add that. So after we get the time, we'll run our function of print output. And I think we're good. I think I got everything written properly. I'll run that script now. And you see, if you don't tell it toilet, it gives us our plain text here.  Now, toilet is an unrecognized option filter. Ah, I typed filter. I forgot the T there. I'm like, I know I have the toilet installed. Let's try that again. Filt our command with toilet. Not the prettiest. It was just one of the templates they had in there. A little hard to read. But you can see now we have 90 days, 14 hours, 16 minutes, 42 seconds until Christmas. And of course, you can play with that again. Look at toilets options to get a better look at that. But if you wanted to have your countdown timer look a little bit nicer in the shell, this is one way of doing it using toilet or figlet. But I thought I'd share that. You know, things that we added or changed from our previous is we split some things off since we're going to be doing the output in two different ways to ping on the user. We did a check for what the user gives us up here. And then we split our getting the time and outputting it to two different functions, which makes it nice for, you know, again, you don't have to use functions. I just think it's a little bit easier to read when you're, when you do that. Anyway, thanks for watching. Please visit filmsbychris.com. That's Chris the K. There's a link in the description. As always, I hope that you have a great day. Support me on Patreon. Please.


Welcome everybody. Today I'm going to show you how to make some brown butter. Now what is brown butter? Well that's where you take typically unsalted butter and you put it in a stainless steel pan and you melt it and you cook it until the water evaporates and the milk solids sink to the bottom of the pan and they turn brown. And what that does is it gives the butter a great flavor. It's sort of like a nutty flavor that's maybe even a hint of toffee. And it just adds so much flavor to so many dishes. You can use it on your pasta, you can put it on your vegetables, you can make sauces with it, you can even bake with it. I have a recipe for you on how to use brown butter in making ginger cookies for example and they are delicious because of that. So I'm Rockin' Robin and I'm going to show you how to make it right after this. So typically everybody talks about using unsalted butter but recently I have been using salted butter with great results. You can use salted butter to make brown butter, no problem. You just have to watch it. It's a little bit harder to make only because it seems like it foams up more and it's harder to see the butter as it's browning and that's what you want to avoid is burning your brown butter. But we'll talk about a way to help remedy that if you do happen to burn it. Okay but for now let's talk about our butter. I have been using salted butter like I said. Kerry Gold is my favorite. It comes from the butter comes from pasture raised cows which I think for whatever reason the butter just is easier to work with as opposed to like clover organic butter. I've tried that it foams up a tremendous amount makes it more difficult to see when it's done and you're more likely to burn it if you can't see it. So I recommend using this whether it be salted or unsalted. So what we do is you want to use a stainless steel pan as opposed to a dark colored bottom pan right because you want to be able to see the butter so either a white bottom or stainless steel works the best and wider is better than more narrow and deep because it's just easier to see the butter as it's browning. This is the largest pan I have so that's what we're using today and I'm just going to brown up a little bit just to show you. Okay so I'm going to place some butter my Kerry Gold butter into the pan over medium heat. We'll start it there. Now I'm using a spatula that is heat resistant that we can use to just keep stirring the butter as it melts. Now all together this will take just a few minutes. It's already starting to bubble up pretty good. I might turn it down a little bit just until everything melts but you can see using a light colored pan it makes it very easy to see what's going on in the in the butter. Now like I said the milk solids will start to separate and fall to the bottom. The water there's always water in butter some brands have more than others and that's what you're going to see bubbling up and you want to have a dish ready.  You want to get it out of the pan so it doesn't continue to cook and possibly burn. Okay so now you can start hearing the bubbling going on. It's starting to get you know you can see the milk so things are separating a little bit and depending on your stove if things start getting too crazy bubbling too hard you can always turn your flame down. You can even take this off the heat as well so don't be afraid to do that. So that water is starting to evaporate those bubbles that's what that is. I tried using that other brand clover brand and I did make brown butter with it but it foamed up a tremendous amount made it really hard for me to see the bottom of the pan and see what the butter was because it was so much foam but I was able to tell enough that I was took it off at the right time and it was it was all good. Now let me turn this down just a little bit because I can already see that it's it's starting to brown up just ever so slightly. You can see how this is starting to foam up a little bit. Just give it a stir and keep stirring and you just want to look to the bottom of the pan because that's where all the milk solids go to the bottom and those are what are going to brown up and if you can't see them that's more of a problem that's problematic right. So when I'm doing this right here I can see that it's starting to turn and if you want to take it off go ahead lift it up a little bit you can see the brown color coming through. All right you see that you see how I'm whipping that around and you can see the bottom and it's just about done. Okay I would say this is done I take it off the heat. Let's turn that off. It's going to continue to cook so that's why we got to get it out here you can see it now right. So we're going to pour it into this dish hopefully I can get it all in there going overboard. Can you see right here at the bottom that brown stuff going on you want to make sure you get all that out because that's the flavor and that happened very quickly. So that's it right pretty simple it only took me literally probably less than five minutes to cook it on the stove I mean it went quick and you just want to be right with it don't leave it stir it up really well so you can start you can start to see that brownness coming in and it comes quick so man turn off the heat take it off the you know take it out of the pan pour it into a dish and you're good to go and you've got a nice flavor enhancer for a lot of dishes and you're gonna love the flavor. So thanks so much for watching everybody don't forget to subscribe to my channel I've got a lot of videos coming out you know every week I put one out click the subscribe button and the notification bell next to it so you'll be notified when they come out and leave me a comment as always I love hearing from you so thanks again we'll see you next time


I'll thank you very much. I'd like to thank all the organizers for this opportunity to speak at such a great webinar series. Just want to make sure everyone can hear me. Yes, I've been at NIST 10 years. I'm going to talk about some of the modeling efforts for monoclonal antibodies and high concentration formulations. I don't know if I can get this slide to change. There we go. So just really quickly, when I mentioned any commercial or trade names in this talk, it does not imply endorsement by NIST. So there were a lot of scientists involved in various parts of this work I'm going to talk about today. So I'd like to start by just acknowledging a number of people, both at NIST and IBBR and three joint postdocs that we've had with IBBR over the years, who have done some collaborations with NCNR and Lynxis and CNRS. I'm going to present two case studies with pharmaceutical antibodies done in collaboration, one with AstraZeneca, as well as the Stevens Institute. This is the beautiful map included with the Lynxis NIST webinar and Kale did an amazing job with this. So just reminding everyone we're stuck maybe fortunately or unfortunately in the pits of course graining today. So this is the outline of the talk. First I will motivate some reasons why we need multiscale antibody simulations to address challenges in the pharmaceutical industry. And after introducing a few examples of the kinds of experimental data that we're hoping to compare with to validate our models, I'll introduce a few different kinds of models, both isotropic and isotropic models with flexibility in the hinge. And then I'll present these two case studies with real world pharmaceuticals trying to help rank order them using these course graining models. And if I have time at the end, maybe five minutes I'll briefly talk about the software that was used during all of this. That's available to the community. So what is an antibody and why do we care about them. So, on the left here is a molecular dynamic simulation of the NIST mad by Christina Barganzo that you may have seen earlier in this series, and in case you missed some of the previous talks. So it's that antibodies have these three domains that are connected by this relatively flexible hinge region, and they have this characteristic Y shape, where the arms are what we call the fabs at the top here have variable regions that bind to antigens. And the bottom is the, what we often call the FC is more conserved than the fabs. Antibodies are in about, if you look at like pharmaceuticals just in general and rank them by sales you'll see that they make up almost half of the top pharmaceutical products here's a couple of examples. And they're used to treat things like cancer arthritis psoriasis and asthma. So they're very important in industry, and the very large complex molecules we'd like to be able to understand them better and simulate them and help with, with screening pharmaceutical candidates. So, they're big molecules so one of their problems is that they suffer from physical, some physical stability issues so here's an example of viscosity of two different maps as a function of their concentration. And you see as you increase their concentration, the viscosity can go above this subcase injection limit. And that means that they then have to be delivered to patients by IV, which is costly and time consuming so we'd like to be able to predict. So, between map one and map two, we could have predicted this without having to make them first, which is really expensive or make large quantities of it to do the experiments. And also the companies don't really want to share exactly what map one and map two are these are often like highly guarded sort of secret secrets and it's not just the viscosity at high concentration, we also have to think about issues with liquid liquid face aggregation, as well. So, if we want to study antibodies at high concentration and study their interactions with each other, at minimum we have to simulate at least two, which is already 40,000 atoms. And if you want to look at phase behavior and viscosity, that's collective behavior of our long link scale so that would actually require something like a 10 million atom simulation, which is simply not feasible with the standard molecular dynamics kind of approach. We need to develop multi scale and coarse grain models that capture the essential physics of the antibodies, but they have less interaction sites so we don't look at every, we don't have every single atom interacting. We need some kind of more coarse model than that but still captures the flexibility of the hands and specific patchy interactions on the surfaces. The coarse grain models also need to be able to capture the effects of the solution, for example, how they behave as you change the salt concentration, or the pH conditions, as well as if you add the crowders or excipients and the solution. And these are all things that we're, we're working toward. So now I'll show some examples of the kinds of experimental data that we'd like to look at to validate our models. And one thing you're going to hear a lot about in this talk is the second osmotic Vera coefficients. So a quick vignette on these. This is a, the formula for the second Vera coefficient of an isotropically interacting particle, where you have R is the, as the interaction is a function of separation distance. So you can see that it's essentially an orientationally averaged metric for the interaction between two particles. And it's a very, it's very readily calculated in theory simulation as well as measured in experiment. So it's a very nice direct comparison between the simulations and theory and experiment. So what we're going to use in this relatively famous. Noron Frankel, it's corresponded extended corresponding states to collapse phase diagrams. It's very efficiently calculated with mayor sampling Monte Carlo, which integrates these mayor functions in a efficient way. And so we will be using this for the, the models. We also recently published experimental data on the NIST map at low concentration, we have examples of charge as a function of pH for both the full map and the different fc and fab domains that was measured by electrophoretic light scattering. We have a second automatic beer coefficients that were also measured with light scattering, both for the fab arms as well as the whole map, and also how they, we have these values over a range of ionic strengths, as well as pH is, which is a is a great resource for trying to build models that hopefully capture these, these kind of solution effects. At finite concentrations, some of the most informative experimental measurements are small angle scattering. So here is the scattering intensity for the NIST map at using x rays from two milligrams from a liter to 193. And so we'd like to use computer simulations to be able to calculate these compute these, these skirt, these scattering curves, and interpret these interesting features like we would call these interaction peaks. And we can also get effective structure factors from these by taking one of these scattering curves and dividing by the, the, the high dilution curve and getting an effective structure factor, which we can interpret these peaks and fit to them to models, as well as we can readily calculate these with our course grain models and compare. All right, so first I'm going to introduce these isotropic models that capture flexibility and the maximum packing of antibodies. So remember that antibodies have these three domains that are flexibly connected by this hinge. And so one of the simplest models that we could think of for modeling antibody would be besides just modeling it as an entire sphere is modeling each domain as a sphere and connecting them with a flexible hinge region. And so we could improve this model by by modeling each domain as a collection of spheres. For example, here, one of the domains is modeled by two spheres instead of one. And we can see that if we look at the scattering at infinite dilution that's the black curve here for the experiment. The red one is the seven bead and the blue is the four bead model, and you see improvement as you increase the number of spheres to model the antibody, you see better comparison with experiment. But that comes at a cop at a at a big cost that it, it adds, you know, the number of interaction sites means is twice as slow, as well as more complicated bonding potentials and things like that. So look using these kind of models, though is is informative we can see that and and I think I mentioned I should have mentioned again that these are mostly hard sphere like excluded volume interaction models. So we're mainly focused on high concentration so 175 this is pretty high concentration for these antibodies. And we see for the scattering intensity, when the domains are held as far apart as possible. That would be like this red curve here and when and the blue curve is when the domains are as close as possible. And so we see very different scouting intensities we see that the intensity increases, as the domains are closer together. And that's because of the improved molecular packing, so they have a smaller sort of effective size. And you can see that the position of these interaction peaks also changes. So, for the more open structure to the more close structure, you see that the peak shifts to lower q values. And this also suggests that the, the more open structures are interdigitating with each other between. So basically another domain of a different antibody could maybe try and fit in between here. And we're seeing similar differences for the, the higher resolution seven B model as well. We can also look at the the effect of making these models flexible so this is again the scattering intensity of the the solid lines are the flexible fully flexible models and the dashed lines are the rigid models. And we see the scattering intensity is higher. Again, because the flexible models are able to to pack better, and that increases the scattering intensity and have a smaller effective size. So these were some of the first models that looked at flexibility in in the hinge whereas some of the previous course we models just assumed the antibodies were rigid. However, we didn't include anything more than exclusive volume interaction so we're not able to capture effects of the solution like like salt concentration or pH, or specific patching interactions that that may lead to some interesting clustering behavior that are experimental collaborators have observed. So we're looking to to really improve on these models. So that is the anstropic models that I'm going to show you today. Just to briefly review the some of the course grain models that have have already existed literature. This is the one I just described. You can see that there's a lot of different course grain antibody models in the in the literature. And these are, these are really great models. They've been used to compare with experiments and they've been hand tuned for particular antibodies. They take really a lot of effort from a talented scientists to to parametrize these, because you have a lot of these questions like, where do you put the beads how big are they how do they interact right. And so, one of the issues that we ran into with these with with building on these kind of models is the number of parameters of starts increasing and it makes it harder to screen these. Say if the pharmaceutical company wants to look at how these antibodies behave with like 200 different sequences, and the sequences might only change just a little bit on one of these beads or something. Or it might be you all throughout the protein. They also don't want to share the sequence of 200 different candidates they would like to have a software that we could provide where they could just push a button. And with with less parameter choices and get some results. Right. So, one of the things that I proposed when we first started meeting with the links is simulation working group was going beyond these kind of spherical models, going beyond in the physics community we call these spherical cows. Trying some anisotropic model so here's an example of a model of a monoclonal antibody that I that I showed a few years ago as an example where you could model the fab arms as super quadrics and you can model model the or the fc as super to rights. And this builds on some of my previous work in non antibody applications. But when Sergey shared the work that he was doing and presented last year on this docking based method of simulating proteins I was I was really inspired. So, so briefly, the way I would describe this is, if you treat these two proteins as like a ligand receptor, you can do this very efficient docking algorithm to find the most favorable configurations. And then there's a Monte Carlo move that randomly samples among those those configurations. And this is a really efficient method for simulating hundreds of thousands of proteins that are very crowded where these favorable interactions dominate. Now, in cases where the favorable interactions may not dominate or some of the, the repulsions are just random configurations also play a role. I'm not exactly sure how you would use this method to compute things like second automatic miracle efficiency. Or scattering intensities and cases where there may be less concentrated, or there's repulsions that are dominating. But I was very inspired by the idea and I thought that what if we had represented a protein with an all out of model to begin. And then we looked at decorating the surface with what you can think of as like binding sites so here I'm showing lysis I'm decorate where the surface is decorated with these pink loft beads with a 15 degree resolution and the solid angles. And so I can do sort of an angular scan where each one of these pink beads is a site for looking at how another lysis I might interact. There are many different orientations of the of the particles and if you roll something about the size of a water on the surface, you get for the 15 degree resolution the solid pink surface, and for infinite resolution, you will get the blue. So you can see that a 15 degree resolution the angles is actually not a terrible representation of the of the entire protein. It's a representation of getting the action level at least getting the shape. So what I can do, and what I'm proposing here is that we could take one domain of the antibody and fix it, and then systematically rotate the another domain about it, and calculate those interactions using an all out of model that you store. And then during the course of during the course grain simulation, you can interpolate from that those pre computed interactions. So if you have two rigid bodies there's six degrees of freedom that you search over. If one domain is fixed then the center of the other domain is given by three coordinates and then its orientation is three more so you could think of looking at this in terms of one distance is five angles. So this is a comparison of taking a second all out of approach versus the pre computed in a traffic model. So this all out of model for an antibody domain would have about five and a half thousand atoms or interaction sites, which is feasible for simulating a single protein. If you want to go for the anastrophic approach. This would be a single interaction site that has an anisotropic that has that depends on the orientation of the particles, the relative orientation. So to begin you have this expensive calculation of, of how they interact over 15 degree resolution with five angles which turns out to be over a million orientations. But once that's complete then you have your simulations are about 1000 times faster than the auto model, because it has about the same computational cost of a three site. So the all out of model is as if this had three atoms. And there are some costs involved in this approach though. There's of course you have to store the table could be about 100 megabytes or more, and with with the 15 degree resolution. You also introduce a number of approximations. So the all out of model needs to be assumed to be rigid to make this practical. Otherwise you have to do an ensemble average calculation for every one of the million orientations. And we're also going to make the implicit the solvent implicit, so that we don't have to integrate over the solvent degrees of freedom. And we also assume that we can interpolate between these 15 degrees so if 15 degrees is too big of an angle and you miss some very important patchy interactions, then you're just interpolating between two less favorable configurations and you miss that very important interaction so that's another approximation that we have to consider. So this is the all out of model that that I used in this work. It has excluded volume interactions from amber and auto doc. And it has since there's implicit solvent, it has a screen charge term with this Kappa parameter that is determined by the temperature and, and the ionic strength or the concentration of certain chloride. And the charges also signed by a parse and the pH determines the charge states of the residues. So we can capture some effects of pH and the salt concentrations. It also has a Vanderwall short range attraction with a fitting parameter and front here that's the one fitting parameter from from this work that was published. So here's six different, I believe six or seven different proteins over a range of ionic strengths and pH. So here's an example of the second osmotic virco efficient as a function of ionic strength where black is the Paul Adam model, and the various color symbols are from various experiments. So here's an example of a potential energy curve for two fab domain of the arms of the antibodies that are fixed at just a arbitrarily chosen orientation. And so I'm looking at their, their interaction energy is a function of distance between the centers. So a little less than 60 angstroms is where they overlap so below that point, it would be infinite, exclusive volume potential. And you can see in this case for this salt concentration. There's this short range attraction that goes to basically zero toward a cutoff. And, but if you decrease the amount of salt in the solution, and you, you look at ionic strength of 50 millimolar instead, you see that the the charge interactions aren't screened as much. So now you have this longer range repulsion that's above zero here, but as well as a short range attraction which is an important feature of a lot of these kind of models that you'll see in the in the literature that and this model also captures that. But it also depends on orientation and things like that. So one of the major assumptions that we make in this approach is that the structure is rigid. So here I'm showing very coefficients with ionic strength for a number of different PDB structures of the lysis I'm protein. So these lines here these four different ones are four different PDB structures of lysis I'm. The color symbols here are various experimental data. So here I'm pointing out, you know the effect of this rigid assumption in a way is tested by looking at different configurations and we see differences in the very coefficient, roughly on the order of the variations that we see in this model. I also included this all atom curve here which is it so these were using the coarse grain 15 degree resolution model, whereas this purple curve is the all atom model, which doesn't have the the resolution issue. This is done with a mayor sampling. So, so it's interesting to see that the all item was actually sort of over predicting the viewer coefficient, but through some fortuitous cancellation of errors, the course grain model actually matches the experiment maybe a little closer and some ranges of ionic strength at least. As you get to higher on extreme. Your, your screening the charges more and so an experiment it goes down more than you, but in the course grain model you see it hits this plateau, and that could possibly be because you're of the interpolation assumption where you're missing some very important. The most attractive interactions might be missing in the model, and those contribute very significantly as you increase the salt. So this is only valid in certain ranges of ionic strength you have to carefully consider when you're doing the course training. So when I showed this to Michael and Sergey about a year ago. Michael proposed to look at this lactoferrin protein that he's looked at in the past that has this very interesting patchy interaction at intermediate values, intermediate salt concentrations. If you decrease or increase the salt, then, then the repulsions increase so you have this interesting minima and he's sort of challenged me to see if this course grading approach could capture that. So, these orange points are the experimental second osmotic very coefficients, and the red are the all Adam and the black plus symbols are the course grain model with an 18 degree resolution. So you see that the auto model does capture this minima in the osmotic vehicle efficient. And for the course grain model, it does have a minimum but it's not at the right position and that again is likely because I use this 18 degree resolution to model and it may have missed some of the most important patchy interactions. And this is a very big protein this is much bigger than the license I'm. In terms of art angles. This is actually very big spacing between the various orientations that we're looking at with 18 degrees, right. So we could improve that instead of modeling this lactoferrin as a single one single site, we could break it down into multiple sites, for example, and we could even to do something like a flexible bond between those. And even if we did for these smaller collections of the atoms that we assume are rigid. Even using the same resolution, the arc length is now smaller so the, we could see some improvements there. And also I'm just introducing this idea of breaking it down into multiple sites, because that's what we essentially had to do with the maps. And I talked a lot about this is showing a course grain antibody simulation of a single map, and I talked a lot about the interactions between these domains, but how do we model the flexibility of this this highly flexible hinge and link a region. And the way that we do that in the course grain simulations were used confessional bias Monte Carlo to randomly select from the angles and links here in the in the link in the hinge region. But those were informed by all Adam molecular dynamic simulations done by Christina. And let me show an example of that so here we have probability of angles which are for the solid line these are from the all Adam simulations. And they're the angles of these elbows here essentially between. So the black line would be the FC angle from the FC to this elbow to the center of the hinge. And in the course grain model we're going to just assume all these angles are are the same. For the solid line. So the solid lines I'm shown here are from the all Adam simulations which include multiple ionic strengths. And I'm, I'm pointing that out because there's, there could be some very highly specific interactions between these domains that influence this probability of these angles that you're seeing here. But the most important thing that we really wanted to get from the all Adam is what is this minimum angle that we can that we're likely to observe from an all Adam simulation. Obviously, 180 is the maximum when it's straight. And so the what I'm showing here for this course grain curve with the dashed line is having only excluded volume interactions between the domains, when I'm not including the, the specific interactions between the domains those will be included in the simulation, but for getting this this power ability curve. This is essentially like a sign distribution you would expect from randomly picking angles but they were cut off at a certain minimum angle. So the autumn informed this, this minimum angle choice. And we did the same sort of approach for the bond links as well so that's the bond links between the center of this hinge and each of these these red points where it connects to the rigid domain. And so, from the all Adam we get the minimum and maximum bond links and without with only excluded volume interaction the course grain model we see distributions like this. And this is a this is a big improvement on on previous models that either that often would get this information just from like a single crystal structure or something like that. That is the model that we're going to use for these two case studies that I'm going to show with some, some real pharmaceutical antibodies. So, again, this this idea of from from the introductory material. Maps can have very different viscosities. And that can be something that's really important in to the companies that they would like to be able to predict early without having to make a bunch which is really expensive right. The companies have come to us and we can't share too much information on the specifics of the antibodies so we're just going to call them a B and C, but if we did this case study in collaboration with the companies where we have been that they give us this the sequence of a B and C. Are we able to predict which ones are going to be problematic and development. And so, just with given the sequences, we're able to get the structures by homology modeling from the NIST map structure by Christina Burgonzo. And then we apply the course grain methodology I just described to these, these structures, and see if we can predict the which ones would be problematic and which ones were not. So, here is a sort of top down view of the fab arms of each of the candidates A, B and C, and the atoms are color coded by the type of residue if it's hydrophobic or positively or negatively charged. And if I had audience participation I might ask someone, you know if they could tell me which one of these three A, B or C, or to which ones look like they could be problematic or which ones might have high viscosity. You know, maybe someone much smarter than me could could figure this out. But I, I'm going to try and just use a computer to apply this this kind of push button method without any adjustable parameters and see, see what happens. So, here are example simulations of map A and B using the course grain simulations these would be these are 50 grams per liter, six pH, 150 millimolar salt. And so these would be a million atom simulations, if we were using the just a standard molecular dynamics approach. In the course grain model I could run this for a few hours on on a laptop this laptop I'm presenting and, and get reasonable results. So, I would say that I can't really tell much of a difference between map A and B here just by looking at it but we can compute properties the probability of the fab arms coming into contact for example. So, from the center of mass of one arm to the other is the distance that I'm showing here. So around, if you remember for around 60 angstroms is is roughly the contact distance. So the showing the pair distribution. So the map B has a much more likely probability of the fab arms coming into contact than maps A and C. And so, we know that's problematic based on some of the previous course grain simulations this was figured by Marco a few years ago that we find really useful so let me walk through it. The second very coefficient against a lower very coefficient means more traction. And on this axis, the x axis has the basically the ratio of the attractions of the FC versus the fab. So if the FC is more attractive than the fab you get these cases where they form these micellar like structures where when you when you have enough of them, essentially the fab arms kind of crowd out the possibility of adding more. So that they make these finite size clusters, whereas if the, if the fab arms are the more attractive ones, then the antibodies can essentially, there's two arms to these antibodies right so they can hold hands and and form these transit clusters that can span long distances. And if the FC and fab are equally attractive, then you can get things like liquid liquid face separation and anywhere else in there, we would hope would be like a stable solution right. So, these candidates all had the same FC, and they had different fab spoke well if map B has a much higher fab attraction, then it seems that it's more likely in this transient cluster region than the other ones. We can also look at the concentration dependence of these distributions so here we're going from 50 to 200 grams per liter, and we see that map B has relatively concentration independent peak so that kind of tells me that map B is finding the other fabs, regardless of the concentration, whereas A and C are sort of as the concentration increases they're just so happening to finally find each other. We also can look at the vir coefficients of these antibodies, we see that map B again has a low vir coefficient which means more attractions, and a and C seem to be very similar, and much higher. So the are our collaborators were happy to see these results they say. Yeah, this is pretty much what we knew about these antibodies before we gave you gave you the sequences so, so that was a successful first case study so now on to the second one. In collaboration with and quant law. So we looked at in the past 27 different antibodies and this is showing their viscosities at 150 grams per liter for these 27 in this work for within the chat group as well. They use machine learning to try and predict these these viscosities. pink one shared the structures of four different antibodies from this group, including the highest viscosity ones maps 17 and four, as well as low viscosity 10 and 27. And so we're going to apply this course grain methodology I described and let's see if we can make some predictions. So this is showing the vehicle vision again lower vehicle efficient has higher traction. So Mab 17 had the lowest vehicle efficient which is also the highest viscosity, and for had the second highest viscosity and the second lowest coefficient. So these are pretty promising results for this course grain approach maps 26 and 10 are the ones that have the lower viscosity, and they have the higher vehicle efficient so just using the vehicle efficient we've already sort of been able to rank order these in terms of their viscosity by core just correlating them. So, if we look at the fab fab interactions. This is at 150, 150 salt 100 grams per liter. We see, again, the, the interactions between the fabs are highest for the green map 17 which had the highest viscosity. And, and the red was low right, but there's this interesting case here, what happened to have four and and 10. So 10 had a low viscosity and for had a high viscosity but their fab interactions seem to be about the same so so what's going on here what are we missing. So I'm going to go back to this amazing pot that Marco made years ago. And so, in the previous case I kind of glossed over that all the fcs were the same. Well in this case study the fcs are not the same. So we're missing this information we need to know. We've looked at the fab fab interaction but what about the fcfc interaction okay that's going to help us distinguish between the blue and the orange one right the blue had the high viscosity. Okay, so we look at the fcfc interaction, blue is the blue one is down here with red, but the orange one is almost as high as the 17 that the high viscosity. So, what that means is that the orange one is more in the center of this and this axis, because both the fc and the fab were high interaction. So it would be somewhere over here, but in the in the blue map for case, since the fc interaction was was lower it pushed it into this client transient cluster regime. So, to conclude the first part of this talk. I would like to say that, given just the map sequence, and some autumn force field taken from the literature, we're able to use this course learning approach without any adjustable parameters to make accurate predictions of the high concentration behavior of the antibodies that were using these pre computed course grain models. So, this approach is actually useful for a lot of complex models not just antibodies, even, and it's a code that I made open source and available to the community. So if you'd like to use it. You can send me an email herald.hatch at this dot gov or visit the software website feast with two s's. And yeah, I'd be interested in using this this methodology and helping the community. So, I'm going to take about five more minutes really quickly to talk about the software that was used and all of the results I just showed you this in this talk. Okay, so why do I even care about software. Well, I've seen firsthand how something as simple as a coding error in what happened to be a sophisticated Monte Carlo technique that wasn't available open source could lead to a seven year dispute. And finally be solved when the, when, when the codes were made available. And this also has a very important role to play for standards in software so so simulations, even play a very important role in, in, in scientific method, because when you compare simulation experiment, you get a handle on the model approximations that were made. So in simulation theory you get a handle on the theoretical approximations. And just as NIST has an important role to play for standards in these experiments NIST also has a role to play for standards and simulations. So in our group. This has been available for I even joined the group we have this NIST standard reference simulation website that I used as a, as a young graduate student, even that provides a lot of well tested data. These are simple models that you can use to to test your codes. Also, why do I make the software available. Well, there's a need if you look at the community there's a need for Monte Carlo software, because if you rank order scientific software by citations. You see there's a lot of well used quantum and molecular dynamics codes, but you have to go down toward the bottom to find the first Monte Carlo rasp is an amazing code. I'd like to see Monte Carlo just use more generally in the community, because it has a lot of methodology available to it. Like mayor sampling gives ensemble five histogram and Grand County go ensemble simulations. So these are made available in the feast code that I've developed and, and it has two S's because I wish it was as cool as Lance. It has the, the anthropic tabulated potentials that I talked about as well as some of the cool conversion bias stuff. I'm not going to go through this whole list I'll just show a few videos in the last couple minutes of the talk. So, here's an example of flat histogram Grand County called Monte Carlo simulations, where the volume fraction is changing this red dollars corresponding with this instantaneous configuration of the new johns particles that are being inserted and deleted from the and we can get, we can look at the, the power ability of transitioning between different numbers of particles, and that allows us to calculate the probability of the vapor and the liquid and rigorously calculate face diagrams that way. Also showing examples of circles that are slowly morphing into squares by random Monte Carlo trials and shape expanded by histogram simulations that we can use to look at how the shape changes the kind of stable structures that would form. And this example had cylindrical colloids that had an attractive interaction due to deplete in the solution, and they, they gel and we had some comparisons with experiment there. We also have cases where, for example, the course brain antibodies might form clusters like these. And so you need rigid cluster moves and Monte Carlo to be able to efficiently sample these and those are available in the code as well as conventional bias aggregation volume bias methods to find a favorable relative orientations between flexible molecules. So to wrap up the talk again I'd like to just acknowledge all the many people and institutions involved in this project, and thank everyone for their time I'd be happy to take any questions.


A Tiger, Financial News Network, News Update. Hey folks, Larry Pesavendo, early morning, or afternoon update here for the stock market. We still got the Dow Jones up 200, S&P's up about 16, and the NASDAQ was down about 80. It's rallied back somewhat. We also, most people don't count this way, but we're actually eight days from the bottom that we made back here, back on February. Let's try that again. March the 14th, and so we've had a pretty good run here, eight trading days. Yes, the statistics on that of going beyond eight days doesn't happen very often, but of course it certainly does. Bonds are down, gold and silver are down sharply, and we have a couple of things going on in the U.S. dollar. It's trying to hold at a really strong level, and especially with the Euro trading where it is now at 108. That's a nice 3-8-2 bounce from the low that we made just a few good days ago. So that'll be the controlling factor here, is to watch that U.S. dollar, because if the dollar rallies, that usually means stronger stocks. So we'll find out if that means that over the next time. One thing I wanted to mention today, we just had the services for Dave White, and he'll always be missed here. I'm doing a show here, but I always, so when you want to, not when you have to, and that's all part of the trading strategy that you have to have. You know when to get out, and that's really all you need to know. As a matter of fact, as soon as you put a trade on, you should actually stop watching the market. And the reason for that is, the money when you see it go by with all these clicks up and down is not a good thing, folks. I mean, everybody thinks that's really cool, but in the long run it really isn't, because people see money going away, and that affects their thinking. And Ms. Hostetter, who I was able to meet a couple times over the years back in the 70s, was really strong with that. And he didn't have computer stuff like we had now. He had a ticker tape, so he had to have a girl do his five-minute charts off the ticker tape to see what was going on. But he didn't look at those every half hour, or every hour. He just looked at them like three or four times a day. That's it. Hey, we're taking a break here. I'll be back in just a few minutes. So<PHONE_NUMBER>.


Hi everybody it's Sam at Mixed Up Craft thank you for watching my tutorial today I'm going to be showing you how to make this twisted easel card so this is how it looks when you take out the envelope and then you have this piece that folds and it will just kind of twist around and sit behind the stopper at the front there. It's a really nice style card I've made the twisted easel before I'll link up here that tutorial if you want a bit more inspiration and yeah it just it's very easy to do it's a simple six by six you know open close card you know side folding card but by just adding this diagonal score line you create this effect here and yeah it just gives a really really nice look and then inside you have lots of room to write your message you could if you want have white paper here and have your message there instead or alternatively you can put it on the back which is I think what I might have done on the other tutorial that's up there so yeah really really nice to do six by six all folds nice and flat to fit an envelope so let me show you how to make it. Okay so I've used a few bits and pieces for this card but I've used my two and a half scallop circle punch I've used my two inch circle punch just the plain one and then I've also used the one and a half scallop one these scallop ones are from Dress My Craft so again everything will be linked below. I've used my trusty Posca pen just to add a little bit of detail and then I'm using my bright rosa kit for this one so I hadn't you know gone actually like used it because Christmas just overtook everything so it's been really nice to sit down and do some crafting with this kit so the bright rosa one is floral and very very pretty so this is the die set that I used for the card that I just showed you here so for those of you that have the kit I've used that lovely kind of center like D tower as the topper here and then these squares this one are all using the dies here you can see where I've cut the silver using that that decorative edged one there these are some of the sentiment toppers and then there's all the different circled punches that I've used to create that stopper so that's the one I've used for this one but then I thought of the other bright rosa dies that I have and the sunflower one I thought that would look really nice is like the topper piece so I use this paper this one here which is the one that I've already prepared and I also use the some of these embellishments on that other one actually if you look a bit closer don't know how I can you see on all of the edges or the little you know bits there I've just used the smallest of those rhinestones it looks really really pretty so that's what I used for that card and then I'm using the happy birthday so that's a thank you card I needed one but then I've taken out the happy birthday here is going to be the stopper or topper depending on where you want to put it for the card that I'm going to show you today also all my scraps are in there as well because I like to keep them within my you know each kit so I know where I am okay so first of all you want a six by six card blank so I've got mine here and then all you want to do is within the left hand square is pop it into your scoreboard find the center all right and just keep your stylus in the track bring this piece in so it's the top left okay within this left hand square you want to sit at the six inches and then that score line you send to scoreline here you want to also be within that track so it sits right within that six inches like so and then you just want to score okay and it might be worth while flipping it over and just relining that as well and scoring again I always put my stylus in bring it down keep it in the track and then lie this down you can follow the track of the stylus so you know the bottom point here is nice and straight but just go over that and score again just so you get your folds in the right direction okay so again you should have all that folding on the left hand side and then you're just going to fold that up just need to make mine a bit straighter there don't know why and just crease that each your bone folder as well I'd already done mine before but now you'll see you get that kind of tent effect but it also will fold flat to fit in the envelope but that's the piece that's going to come up okay so that's all of the scoring needed just for that if it's already a pre-made carb length then you're just going to need your scoreboard just for that score line there so this is the dye this is the sunflower band dye by Broke Rosa and I did do a few samples when they launched it but I haven't actually used it for a tutorial yet I do have another card but I've kind of changed it a bit and I do so it's kind of there but I do need to do the video for that one but I've got I do have like I think it's going to work out I'm just still playing around with it because I did change it but it's beautiful this is the big band I've got a few of her band ones and they are lovely but I'm using the smaller one in here so just dye cut that one that one and that one and it's given me these pieces here and then I've also used the circle it's not a circle but just the inner detail that one there as well and yeah all I'm going to do is just shape it a little bit always nice to give any kind of flowers just a little bit of dimension so I always just flip them over and then I've just got this boom and this kind of style no ball bearing is plastic ones they're just a lot of them are for cake decorating I just go under each petal and just kind of shape it will start to curl up and once you kind of do that and then flip it over it just gives a really nice effect and you can just stress them as well and that always adds a little bit of you know more depth to them but now when I flip that over and you push it down you just get a bit more you can see the difference oh stuck there between the two that looks a lot nicer and because where it's creased it gives it again just a little bit more detail and if you add your inks to that it will pick that up even more so I'm just going to quickly flip this one over and do the same okay and I've also just done that piece there as well just to give it a little bit more shape and turn those two over and then I'm just going to use some of my glue and just stick one over the top just kind of you want to offset the top one just so it kind of overlaps like so so you create one big full flower you don't have to you can have one you can also do two different colors as well you know flowers are not perfect they can be anything you want to be but now again what I might do is yeah just kind of give that a little bit of shape in the middle there like so and then I'm just going to add a little bit of glue on the back of that one stick that one down now just put a bit of foam adhesive on the back of that one I'm just going to stick that over the top and then I've got this white one here which again that one's going to be too big I just cut that down again and then I am going to use these ones here from my own stash just because they were really big I wanted something to fill all of that kind of center part so I'm just again going to pop a little bit of glue and just pop that in the center okay so that is my kind of flower all ready to go it looks really really nice I'm gonna leave that to one side and we can get back to the card okay so quite a lot of mats and layers on this one again it's completely you know optional you don't have to have it like that at all but I did like it so what I've got here is I've got this white piece so open up the card ignore all that for the minute then we're just going to concentrate on this right-hand side so I've got this one here so it's six by six this square but this piece here you'll want it to be five and seven eighths of an inch squared so it's just got that very small border okay then I have this piece here which I've used the die from the kit to cut out but obviously not everybody will have that so you'll then want something that is well this is five and a half okay you'll see that sits in there nicely and then this pattern piece was cut with one of the squares from the kit and then I've got this white piece as well but the white is just over five by five and the pattern piece is four and seven eight seven inch square so it just gives you a rough idea of what I've done because I've been working with those dies within the kit but you'll see now when I sit them all over the top on top of each other they look really nice so that's where those are going to go then on the front you want to cut a piece of card stock that's five and a half by five and a half okay and then you're going to well caught then you're just going to cut this one in half on the diagonal so I'm just going to line up those points make sure they're bang on just cut that one in half or I need that again in a second you actually want two pieces that size because I just remembered I also went ahead and stamped my sentiment on the inside so the other half is on the other card so you want two pieces of that size cut them both in half on the diagonal and keep what you know one of them for the inside so these now will go perfectly within the two kind of triangle sections on the front okay then I went ahead and cut this one again which was five and a half and again on the diagonal you just want to cut that in half again and then I did take a little bit more off now the reason I had to take more off this piece is because I didn't want to lose this side this detail so if I go to lay these on top of here now you'll see they just don't they just cover it they just look silly so what I've done is sit this on here but focus on these two corners these two sides here and bring it up like so and you want I guess about 180th of an inch and a border something like that I'm going from the very outer side not those kind of little arches but then you just want to put a little marker here and then trim off that that way you don't lose the detail on the the sides you're just losing that straight edge so I'm just going to line this up in my trimmer and cut that away I'll do the other one in the second but now that sits perfectly and you've got a nice border and that's obviously going to go on the top like so okay so I'm just going to do the same with this one here I'm going to line this one up over the top this is only if you're using this pattern piece or any pattern piece really you'd need to do it that way because obviously it's a die cut so it's already you know the size is set but otherwise if you're just cutting this plane from mirrored card stock you just do this then you'll want it to be a piece of four and seven eighths of an inch squared okay and then just cut it on the diagonal so I've only had to do that just because it was that die that I'd used but now that one's going to go there and that one's going to go there okay and then we've got this piece here which is going to be for the flower to sit in the center of and that's going to be the main feature on the front of the card so the white piece here is four and one eighth of an inch squared and then that lime color is three and seven eighths of an inch squared so again it they're odd sizes because I'm using the dies from that kit but you just want to look at your square dies and anything that's close so if you're lime in my case here it's three and seven eighths if yours is four by four that's fine you know and then just cut your mats and layers if you're doing them freehand and you can follow my size as exact but just work with what you have it's very easy to adapt so I'm now going to go and stick all of these pieces down so the front ones and those mats and layers that I showed you just now inside okay so everything's now stuck down I've also gone and stuck that piece there and now that can come up like so so now I would now do your stopper so I've just gone and pop some foam adhesive on the back of mine you can see there just all the dimension on mine but I like that you don't have to you can just stick them all down but what you want to do now is bring this piece up and it's up to you really where you want it and I'm going to have mine similar to the one before so it's about there and then that will just stop itself there if it's bouncy mine's a little bit of a bounce to it just take your bone folder because I didn't actually burnish this properly and just go along and just burnish that scoreline you see now how flat it is and then it will now be really flat with that which is much better then just close up your card and you want this piece and you're going to line up your well the top right and the bottom left with the that diagonal scoreline like so and then also make sure you got even kind of you know border here but you're only sticking this side so what I would say to do is flip this over so make sure it's all lined up yeah I think that's about right and then and put a pencil mark there and there and now I mean if you've got directional paper you're gonna have to make sure when you flip it over that you're working on the right piece so I need mine to be yeah so I'm gonna add glue now to this car don't go right up to the pencil line leave about 1 eighth of an inch you know a few millimeters just so that it doesn't let any glue doesn't ooze out but you can now stick that half again line up those points onto that scoreline and just stick that all down again just make sure that this is nice and straight and again this kind of corner here is as well just let that kind of do its thing for a minute it's why that's just setting and then gonna bring in my flower and I'm also gonna add a foam pad to the back of this you can use some hot glue just normal glue you want something that's strong and that one there is just gonna stick perfectly in the center like so and then also another thing I forgot it's my Posca pen so this is just a white paint pen so it's just a white paint in there I'm not sure what kind of paint it is but you do need to make sure you give them a good shake when you ever you know whenever you go to first use this and although this is already a stitched die piece I did like you to be able to see the stitching can you see there that white just really love it as like I said in one of my videos when I've done it already I'm kind of on a bit of a thing with this Posca pen at the moment I'm using it so much and it's brilliant but I'm just going around again just kind of following the stitch marks that's already there but I'm kind of doing a double stitch if you haven't shaken the pen enough you'll find it fades it just disappears you can go over it again but do you have to really give it a good shake there's a little like ball bearing inside just to mix everything up because over time it will just kind of settle and split so I can probably give mine a bit more of a shake but I'm just gonna finish this off okay if I just bring out you can see now the difference that that makes I think I also yeah I done it on the topper just around the lime color there and I'd already gone and done it on the pink one there but there is the card all finished there are my two twisted easel cards really easy to make and it's just a nice if you're starting out with your funfold cards and you've just been doing you know your standard top-folding and side-folding a twisted easel ones a nice kind of step into that funfold card and kind of area really because it's just that simple score line yeah it creates such a I think eye-catching card you can imagine when that's you know displayed on someone's mantle side table it's gonna look really really nice so I'm really pleased with how these come out love the colors it's really nice to be working with you know new product and I hope you enjoy them so thank you for watching today as always all of the links to everything that I've used will be shared below and over on my blog please hit the subscribe button if you'd like to see more tutorials and I'll be back again very soon