Stevenson falls to Mary Washington tonight Glen Clark with head coach Kathy Rayleigh You know coach that the errors right like that. It's particularly the unforced errors. I know it's a young team We talked before the game. This is what you're working through But you know, I feel like that was kind of the story tonight, right? Well, you know, it's so funny We we have a game two games ago or clear was just not good at all And it really hurt us and and then we we changed the clear and we go 17 for 19 And then very next game. So we're thinking all right, we got the clear under control. Well done team We don't really make any significant changes and we come back and we're 10 for 15 and it felt like we were about 10 for 70 in the clear today That's what a young team is a young team just has to learn to persevere and get better the next practice and get Better the next game and this team does that we put together some Fantastic defensive effort today. We took 10 shots in the fourth Quarter today 10 shot there have been games. We haven't taken 10 shots in in this early part of season So to take that many shots in a quarter that shows me that we're we're starting to put together an offense We're starting we won the draw battle, which is one of the things we wanted to do We played great defense at times today We caused so many turnovers that when we need it when we when we needed to Regan in the in the second half just save after stop after save after stop after cause turnover We're doing all the right things We're gonna just keep trying to get better and and we got to get in the win column because it you know that we need to Validate all the hard work we're putting into this I wanted to ask about like how how this team because you've talked so much about how coachable they are and all that like The spirits can easily be brought down by a tough start to the season by just the results not going your way How how has everyone handled it and how have they not allowed it themselves to be down? Just because you start feeling sorry for yourself when you're not getting result Well, I you know, that's just not the way that I coach I you can't feel sorry for yourself you put in that much hard work It can be a little sad if you don't win a game that you that you know You put your heart into but that maybe is one individual and it's the job of me as your teammate or me as your coach That when you're having a down day, I've got to bring I got to loan you my energy and when I loan you my energy I'm saying, you know, I'm gonna put you on my back and you're gonna be okay until this next game I just really think that this group just works so hard and they want the best for each other I don't know if you could see but we were you know, we did not have a good first half and The energy on the sideline came out better in the second half And we were louder and we were more supportive and we We're really trying to teach this team to celebrate the little things and and they are and they're gonna get the wins And they're gonna start surprising some people We just have to put it all together. You know, you mentioned Reagan my word Like what what did you see what was thought process and it wasn't just like the total of saves It was one was low one was you know While that you had an attacker on the crease like it was doing a little bit of everything Well, I think that she practices very hard. You know, she she does individuals just trying to get herself better her stick speed has improved so so much we've Gone to the drawing back to the drawing board after last year and really changed how she was gonna make some low saves She hated us for she hated us for it for a little bit and and today I'm gonna say we're forgiven, right Reagan forgiven today You know, we we thought that maybe We could throw them off with a right-handed goalie and then you know having the left and then the right and and it did it through them off a little bit But what turned in what was a short-term plan turned into be a long-term plan and and we kept her in until we ran a special defense that that Sophie's just a little more experienced with but I'm I'm you know, I'm so happy for her because she does work so so hard and Glad to see that her have that success today. Give me one goal for spring break Give me one goal for when we come back from Arizona. I want this to have happened We need to put 60 minutes together We're gonna turn the ball over, but we can't let one mistake turn into two So I know that's not an easy goal for me to say. Hey, we accomplished that I want a game where we have double digit goals. I want 12 goals When we get 12 goals, we'll start winning games. Okay? Okay? Okay? Counting on it. Let's make that happen coach. I know it's tough, but always appreciate a good seat. Thanks. Thank you All right, she's Kathy Rayleigh because we're talking about her will go Reagan first come on in join us on the hot seat After an unbelievable second half tonight Were you feeling something when you you came in to start that you know what was about to happen? No I was hot I had a really good warm-up at halftime and we were just trying to get ourselves through that third quarter energy that We've been dipping down the last couple games and we had 60 straight minutes of a hundred percent energy all the way through And it just kept me going as well. So the coach mentioned the work on the low shots Tell me a little bit about what that looked like and did you feel it paying off? It definitely paid off I've been I've been sitting more. I'm a lot more explosive to the ball She's been making me in practice literally drop all the way to my knees and As old as it makes me feel it's definitely Show it show it show us show us show us come on. We got to see it. That's the work That's the work and it pays off. Yes How good does it feel I know you'd rather come in a win I understand that that's the way that you want things But how good does it feel for all of that work to have paid off the way that it did tonight? I it's great. I mean it that was my first real good Collegiate game and I had 11 other girls in front of me that I had trusted a hundred percent and we just put I'd say we put a good 58 of 60 minutes together. We played really hard all the way through and Just our our issue right now is a clear and we're gonna fix that All right now we need to get know you a little bit. I want to know what's the last show that you've binged Give me Okay, I watched it if it's embarrassing by the way No, my all-time favorite show is NCIS I've watched it through beginning to end Probably four times now and I just got my roommate and I we watched it all the way from beginning to end She's never seen it before Are you like an amateur like do you feel like you could solve cases? Do you feel for sure? Yeah, but I'm gonna be the nurse. I'm gonna be the nurse. No, I'm not the investigator Who can we shout out who's maybe watching this you want to say hello to thank them for your their support? Definitely my parents and my in my younger siblings They've been with me from beginning to end since second grade since we started this They're not here tonight But I know that they were watching the whole time and it just means a lot that they've been behind me Congratulations on a great effort. Hopefully next time we're talking about a big win on top of it But really incredible performance is a lot of fun to watch. Thank you. Thank you. It's Reagan Torbert now Let's bring in Kelly Ann one more Kelly and Kosa with us here after Stevenson suffers tough loss to Mary Washington Kelly. Let me talk through We were just talking with coach about how you guys have kept your spirits up It would be easy to feel sorry for yourselves and be down after this type of start How have you guys prevented yourselves from knowing you're a young team you're working through things from feeling too down? I wouldn't say it would be easy to feel down, especially with the team that we have it's easy to not feel down with the girls That are surrounded by us everybody's out there. You can tell everybody has heart Nobody doesn't want to be there and you can tell everybody works for their teammates It's super easy to go out there and practice in games every single day Knowing that I have however many teammates behind my back and like I'm behind their back at all times Knowing that whatever happened in the last game, we're gonna go out there and give our all the next game And whatever happens. It's because we put our heart onto the field Coach brought up the draw us right it was a big part of the game The night take me through and you're kind of involved in every aspect of that How important was it and how good did it feel to really put together a solid performance there tonight? The draw is such a it's an up in the air 50-50 mine game for me I mean to like actually grab the ball get in your stick It's like you're on cloud nine like you know what's gonna happen like you're trying to talk to your teammates Like the ball goes up you grab it and you're like something that we did and practice together And we communicated and worked together just worked and it's awesome to know that Everybody else on the circle is giving a hundred percent and you did too and it all happened to work out It was working tonight. There's no doubt about it How close do you feel like this team is to putting everything together one game? I mean one practice like it's there. I fully believe it's there like Reagan said 58 minutes I think we had a 58 out of 60 minute game today We just need that last puzzle piece and it's gonna click very soon I'm gonna give you the same question. I just gave Reagan.  Okay. That's actually very cool Wait now wait a second. I'm 40. This is my world, right? How did you discover friends? My mom and I have been watching friends since I was young. I've probably finished the season eight or nine times now Yeah, I like my mom and I like will recite lines and stuff. Well, that's a little embarrassing Now we have to ask the question are you more of a Phoebe are you more of a Rachel like do you identify with someone in particular Phoebe? Sure everybody would agree Like everybody on the team would agree with that I think so Who are we shouting out? Who's watching who do you need to say hello to and thank for their support? Probably my friends back home at Abingdon Abingdon fire company I know that they will follow and support me and they as much they miss me that I know they're cheering me on from home Yeah, Kellyanne. Hopefully next one again. We're talking about a huge win. Enjoy the trip out there, Arizona. Thanks for coming up here


Ja, het mooie deel in de wereld en deze mooie conferentie, ik geniet er veel van aan het doen. Ik ben een biophysicist, ik werk meestal op soft-matterfysieken en ik probeer er wat op te doen op biophysieken. En ik ga vandaag meestal over wat werk ik in het gebouw heb gevolgen met tijdens een sabbatical leave in Keltaque, terwijl ik met oud-vrienden van UCLA een collaboratie heb. Dus het officieel titel van Baitalk is een dynamisch of in vivo bacteriopage ejectie, genome ejectie. En de populaire titel is hoe je in de kruid gaat. Want ik zal je laten zien dat in vivo ejectie van een genome, van een vijf genome in een live bacteriopage. Er is een short term, dus er is een short range behaviour, het is gedreven door de pressie in de vege, maar er is een lange tijd behaviour ook. En dat behaviour heeft te doen met de groepen van de cytoplasm. En die groepen is het meestal kruidendes, zoals we in een minuut laten zien. Dus dat is waar de populaire titel komt om hoe je in de kruid gaat. Alright, dus dit is de kruid. Dit is de kruid ik ben werkenen met. Missie Rue, ze was een groot student wanneer ik werkte in Keltaque. En Rob Phillips, ik denk dat hij veel van jullie wel is, wrote a beautiful book about physical biology. Deze zijn twee oud-vrienden. Hij ging terug, meer dan 20 jaar geleden, wanneer ik een postdoc in UCLA was. En hij was ook aan de virus werken, dus dat was echt leuk. En een inspirerende collaboratie. Maar om te beginnen, feestjes, waarschijnlijk zijn de meeste van jullie ergens, dus ik zal jullie een introductie geven. Het is ook mijn probleem om je te houden, na de lunch. Ik hoop dat ik je wil houden, om je te houden met iets wat je al weet. Maar ik wil jullie een introductie geven. Het is altijd goed, hè? Hier is een feestje, een proteinecapsitie die genetische materiaal heeft, het genome, het ligt op de bovenkant of het stem van een bacteriën, waarin het bindt op typische proteinen of sugars op deze stemmen. En dan ejecteert het genome. Dus hier is een scherpke foto, hier is een reale foto. En de lifecycle is eigenlijk, je hebt deze feestjes die lopen op het bacteriën, ze injecten hun DNA, het bacteriën, gebruiken de reproductie, de machinery van het bacteriën. Nieuwe protein, feestproteines worden genererd, nieuwe feestjes, en je krijgt nieuwe feestjes. Op een gegeven moment, de bacteriën ligt of explode en de cycle is klaar. Nu, Dennis zal zeggen, in de volgende seizoen, zal de DNA weer in deze feestjes zijn. En nu gaan we over hoe het gaat uit, oké? Dus, waarschijnlijk, dit is een historieke ding, het is een hele bepaalde experiment.  En het is een heel smarte experiment. Een lange tijd geleden, in 1952, about a year before Watson & Crick wrote, they published their paper on the alpha helix structure of DNA, but still at that time there was still some debate whether DNA constitutes really the genetic material of organisms. And the argument, the counter argument of that, was in fact that DNA is so simple. It couldn't code for these complications that organisms display. Not even bacteria, but particularly higher organisms. But this is typically a proof, I think a very nice and elegant proof. So they radiactively labeled the sulfur groups in the proteins of these phages. And they also radiactively labeled the phosphorid bits in the DNA. Then they could show that the DNA is in fact in the bacterium and the proteins outside the bacterium. Dat was a really additional confirmation that DNA is really the heritair material and not protein. I'll get back to the Hershey chase experiment in a minute. I will talk about the easy part. How DNA gets out. Initially it's pretty easy for DNA to get out, but because it's highly pressurized. It's wrapped inside the phage head. We have, for example, a delta DNA. The contour length of 50,000 base pairs, 50 kilo base pairs of DNA is about 17 micron. Then these phage heads are about 30 nanometers. So it's like if you have a cable and you spin it over the golden gate bridge, you try to wrap it into a van. And it's not the very thin cable. So there's a lot of pressure involved in stacking of having DNA packed into these phage heads by 56 atmosphere. So this is a robotically lysed phage. And here you see all the DNA that's supposed to be in the phage head. So it's enormous disparity of length scales in that sense. So this is what you can call a single molecule Hershey chase experiment. So this is stuff we'll be mainly talking about. The question we addressed or what Rob and his collaborators already addressed is what the mechanism is of phage DNA translocation. So it is proof of Hershey chase indeed that DNA is the carrier of genetic information. Now the question is how does it work? What is the mechanism? Can we quantitatively describe that? What are the time scales, for example? And I think the experiment that they did is really elegant and smart. So what they did is they labeled phage DNA with so-called cytox orange and that's dye that cannot penetrate the bacterial membrane. So the inside of the bacterium only gets fluorescent if DNA penetrates the membrane by other means, right? It's not a spontaneous process. So at the beginning of phage infection there will be all the fluorescence will be in the phage of the bacterium. En on a later stage the bacterium will continuously become more fluorescent and the bacteria and the phage head will become less fluorescent. So this is a grammatical picture of how that's supposed to go. Yeah, so... And then a priori. So for some people this is probably a familiar picture, right? So a priori you could think about how this affects influence the dynamics of phage-action over the speed of how DNA is translocated from a phage to a bacterium. So of course it's a stored energy in the... So it's like the very closely packed DNA that constitutes a huge driving force for ejection and I think it's safe to say that in vivo ejection is the main driving force, right? It's almost all there is. En then of course there are other things that are the properties of the solvent or the cytoplasm like the osmotic pressure, other macromolecules, salt, you know, divalent ions, you name it. All these things are important. And there's also something... Potentially there's also something else and that's so called regiting proteins. So the idea is that at the first stage of DNA ejection the process is relatively fast even by the internal pressure. But then after a while when the driving force becomes comparable to the turgor pressure in a bacterium it gets slower. And the idea is that there are so called regiting proteins that very strongly bind to the DNA that comes out of the phage so that it doesn't get back. So it rectifies in fact the motion. I'm not going to defend it in detail because this is a spoiler but we're going to show that we'll at least let the phage but they could be there. This is one of the aspects that could be important in the phage ejection or in DNA ejection by phages. So this is a typical and I have to learn to show it. So this is a typical movie if it worked, yes it does. So it's a little fast but you see that in the beginning in the beginning all the fluorescence in the phage had so this is a phage that sits onto a bacterium here's the bacterium so all the fluorescence in the phage had, there's no fluorescence here and then after a while in order of minutes there's a redistribution of fluorescence and you can tell here that it's on the order of minutes so let's say in 5 minutes most of the DNA is out there's also a lot of noise but that's a different story so schematically it looks like this so at first all the fluorescence in the phage had and then gradually there's a redistribution of fluorescence that coincides with the redistribution of the DNA and these are some typical stills now in vitro the situation is much faster and I'm going to show you that as well because here you see it really goes over let me first stop what the idea of the what the what I'm actually showing you so the setup is that you have phages adsorbed onto a microscope cover slips and then there's a flow of gold particles that stick to DNA so they're being visualized the idea of the flow is that it kind of stretches the DNA that comes out of these phages and this lamb B initiates let's say the uncorking of the phage so it binds to the it's like a receptor that binds to the phage tail and that induces ejection of the DNA so that's the setup and here are some typical movies this is a typical movie you see it goes very fast I'm inviting you to look over here because here you see how it triggers and how it here goes and then so it's like seconds right in vivo it's extremely fast so there's a huge difference or huge well there's at least a magnitude difference in timescale of the ejection process and there's more I will show you later there's some more pictures over here just because I like them so here are some stills of the process you can see how it goes eventually in time so this is seconds so it's relatively as I will show you later this is fast compared to I'll show you here it's fast compared to in vivo experiments and also there are differences because depending on the the kind of ions in the in the evitro system it goes faster or slower so it's very sensitive to the counter ions and a lot of other things alright so this is I think this is a really very beautiful and elegant way to get grip on what the driving force really is and it's using osmotic pressure I'm a physical chemist by trading so I appreciate the smartness of this setup so what these authors did I think many of them are here right Alex is here and Bill is here Avi je was also involved in that in the early stage so the idea is to have a so they call it the osmolite that's a relatively long polymer that cannot penetrate the phage tail so it exerts effectively an osmotic pressure and by playing with the osmotic pressure of the osmolites these people were able to to stop ejection at some point so it stops at the point where the pressures are equal and one of these pressures is being set by the concentration of the osmolites and by that you could where the ejection stops that's a measure in fact for the pressure inside these phage heads I think that's a beautiful experiment now back to where I really want to talk about back to in vivo it's more complicated this is an experiment of two mutants of lepta phage with E. coli a long chain length the blue ones, short chain length and the red ones and this is the ejection velocity so kilobase per per minute as a function of the DNA that's inside the capsid and a priori the idea was that the DNA inside the capsid determines the driving force and that principle determines the ejection speed the curves have the same shape but they're different curves because they're different DNA now if you look carefully so the first thing to think about is what the relevant quantity or the relevant parameter is to study the relevant description and if you look at these curves you can tell that if you translate that red one about 10 kilobase per that's about the difference between these two mutants they coincide now if you do that typically the difference between these two mutants that means that the starting point also coincide and starting point here means here's DNA in the capsid so here's no DNA in the bacterium so the idea is if you translate it first you shift the curves and then you flip it you will get universal for two curves behaviour if you take the parameter DNA ejected right so here's how it looks like so you shift it and flip it so then you plot the ejected DNA rather than the DNA in the capsid and then you see that on a relatively long time these curves coincide at the beginning there's a difference and that makes sense because that larger genome of course exerts a larger osmotic pressure so it's faster but in the longer run it was unexpected so that means that since in fact the relevant parameter at least experimentally is the properties of the ejected DNA as well as the properties of the bacterial cytoplasm that set the time scale for ejection here in these relatively long times alright so and if you look at that carefully there are two regimes right so there's one regime we call that pressure driven I'll get back to that later why I call it that so that's different between these two mutants and there's another regime we call that late stage and I'll tell you where it comes from in a minute so people are know a bit about glassy dynamics they know where short stage en late stage come from but I'll tell you that in a minute so you see that it becomes similar you can also plot it differently you can just plot the the number of ejected base pairs is a function of time take the logarithm for both and then you clearly see two regimes there's one short time regime and it has a slope of one which means that it is it's a driven process and velocity more or less not exactly but more or less and then here there's another slope and that slope turns out to be 0.2 so one of the things we try to do is to find out to come up with a mechanism that explains the value of that slope on the long times alright so let's start with the early ejections well many talk about the late stage but let's we know about the early ejection stage the idea is that at the early ejection stage when the DNA is closely packed into the phage heads and they have a typical separation between the DNA strands of ds of s then the idea is that at these short distances is mainly hydration force that determines the interaction between the particles so here and that's exponential that's exponential there's also electrostatics that's also pretty important but at this point that contribution is small compared to the bending energy bending energy is also large on an absolute scale but it's small compared to the hydration force at least close as these very close packings then what you do so this is typically the force per unit area so if you integrate that over the typical distance to the typical separation you will get the energy that is stored into the system and then if you take a model at least a geometrical model for how DNA is packed and people all agree that it's hexagonally packed you can get the force just by differentiation and it turns out that the force is an exponential force in the length of DNA and it's not directly easy to see increasing function of the DNA length cause it's minus 1 over the square root of L DNA but it's an increasing function of the DNA length it's weakly increasing compared to a real exponent but it's weakly increasing and then of course there's also a friction so there's also a friction contribution and that's typically a friction coefficient times the velocity and we could calculate the velocity just by by force balance and that the friction factor that's also turns out that's also be exponential in the length of DNA but with a slightly different coefficient than the driving force there for completeness there should also be a stokes contribution cause you could think of the blob of DNA being ejected that also has a friction effect but at this point that we ignore that it turns out to be a pretty small effect I'll get back to that later cause in lake stage it becomes very important alright, so you get the injection speed but you do compare to so this is all known this all worked by Bill and A-legs and a lot of other people and the only thing that we did is we add or we subtract the turcopressor of the bacterium and then you get a pretty good agreement for the short stage, for the early stage injection it's not totally perfect if you choose the quantities that are in the theory for reasonable values it more or less qualitatively describes what's going on so this is the ejection DNA and this is the speed and it goes to a maximum that's because of the competition between so the friction factor decays faster than the driving force so that's the reason why you have a maximum here so that looks reasonable like let's say acceptable in terms of the simpleness of the model but there's a big problem and the big problem is that at some point when almost not even, well a bit more than half of the DNA is being ejected there's no driving force so purely mechanically the process should stop at that point but still it goes on and that has to do with the two so that's consistent with these two length scales they show that first the fast regime and the slower regime back to the question that I'm addressing now so we understand more or less the fast process now let's get to the late stage process and what I'm assuming is that it has to do with the dynamics or with the diffusion dynamics of a blob of DNA the ejected blob of DNA of cytoplasm we've already seen experimentally that at some point the relevant parameter experimentally the relevant parameter is the amount of ejected DNA inside the bacterium so the only quantity that may go into this description is the properties of the DNA as well as the properties of the cytoplasm nothing else so that's what we assume so we need to know what approximately the hydrodynamic radius is because we want to calculate at some point whether it is diffusion coefficient or friction coefficient we know it's not simple self diffusion a priori because the pretty large blobs of DNA at some point I will show you that in a minute and we know that the cell cytoplasm is classy it's a crowded environment and we start simple by just assuming that there are no ratcheting proteins so this is the idea so there's a blob of DNAs already out and what we are pursuing is that the dynamic properties or the diffusion of these blobs determines the ejection speed so what we need to know the ejected DNA in a number of base pairs we call it n the function of t then we need to know what the hydrodynamic radius of that blob is which depends on n, it depends on t and then we need to calculate what the diffusion coefficient is and it depends on n, it depends on t and then you need to close to the story well first of all about the size this is more or less a sort of proof but it's more like an argument by reductio at absurdum I think that's the most beautiful argument in mathematics personally so it's not stretched because we know that the size of a bacterium is about 1 micron and we know that the contour length of DNA is 17 micron no deal also it's not just purely a random log or it's not purely a self-avoiding chain self-avoiding chain the hydrodynamic radius is given by the so this is the persistent length times the number of base pairs to the power gamma gamma is about 3 over 5 that will give you for that typical DNA about 1.5 micron no deal either so it should be more condensed than either of those two and what I'm just assuming simply is just like it's close packed it's close packed on the scale of the persistent length and then you get something reasonable that's about 300 nanometers so it could be that it's even closer than that but then you have to bend it a little bit but I don't think that's not necessarily problematic it could be a little bit less closed it's also fine I will show you later on at the end that the result is not very sensitive to gamma so that's good because this is kind of a gas and you could have that smaller the denser state just by the so-called nucleic associating proteins we already heard about that rapid proteins whatever so now about the cytoplasm so I think this was you can say that if you are a large maker molecule and you are in a cell cytoplasm what you may call diffusionally challenged because diffusion is not easy if you are in such a highly viscous crowded environment and this has been shown not too long ago by this group is Christine Jacob-Parker and Eric Newfrain and they showed that relatively large maker molecules say larger than 30 nanometer if you are a typical protein you are fine in the cell cytoplasm it is self diffusion within a couple of seconds it is relatively fast but if you are larger than 30 nanometers you have a problem you see this is the mean square displacement this is time it is not linear even over more than an hour it is sub diffusional here you see the same thing they effect show that if you switch off the metabolism completely so you can do that by some chemicals and you stop all the ATP hydrolysis you can just temporarily put the bacterium sleep so to speak then everything stops so at least for these large maker molecules it is a typical glass so there is no movement at all at that point so you may say that just summarizing anomalous diffusion anomalous diffusion means a slope smaller than 1 if you plot the mean square displacement it is a function of time when the cell metabolically active in a rest when it is inactive so this was something I wanted to share with you because I like that I understood that there are also students here there is something you want to hear so this is just in writing what all scientists know that is if you start studying something you usually find something else or it doesn't work usually the other thing that you find is often much more interesting than what you were really looking for these guys just put it in writing because they start their paper that study began with something else and now I am going to talk about what they actually discovered so I like that so I just wanted to share that with you typical solid fraction we have about 3 million proteins in E. coli their volume is typically about 100 cubic nanometers so your volume fraction is about 0.3 and then I don't count the hydration layers and all these kind of things if you count that you may be close to about a half and we know that for example studies of hard sphere hard colloids that behave as hard spheres at about the volume fraction of a half things really become slow and that is probably what is going on here as well so this is some other so we just checked some other relatively large molecules so this is the logarithm of the mean square displacement this is the logarithm of time so this is self diffusion so these are some typical so these are plasmids this is lab.dna here and there are some other proteins relatively large proteins here and for all these components these slopes are pretty close to about half so it's self diffusion with a coefficient of about half it's something that I don't understand it's something that we apparently see I will get back to that in a minute so the idea of that sub diffusion is that for example here if you have a so this is this typical cytoplasm here is a relatively large molecule so at short times at relatively short times before any collisions with their neighbors has occurred diffusion is itself diffusion even shorter times there is a ballistic regime but I'm not going to talk about that but at very short times it's diffusional because there is no it doesn't feel the neighbors yet then intermediate times these particles are temporarily caged by other particles and that's called so that gives rise to anomalous diffusion and it's typically transient behavior because in these systems if the system is fluid like after a while these motions randomize again and you will get diffusion again but now it's long time diffusion so this is typically an intermediate regime and there are also experiments because these are hard sphere colloids and you see that at relatively long time so this is the log of the mean square displacement this is the log of time so at short times it's linear at long times it's more or less linear and at intermediate times intermediate times it's a region of anomalous diffusion and you see here that it could be everything and the slope in between in between 1 and 0 and what we find in the cytoplasm it's typically a half and I don't know where that comes apparently these densities and these interactions between proteins in cytoplasm are such that it leads to an anomalous diffusion coefficient die is around a half I think that's the most reasonable explanation I can come up with at this point so it's still transient behavior but transient can be very long because we have a good long life and we are all transient alright back to phase DNA so we assume we have anomalous diffusion so that the mean square displacement of the blob of DNA is proportional to time to the power of a half where a half is to the power of alpha where alpha is equal to a half and then we assume that the diffusion coefficient still has a stokes eindzine form which is that it's kt over 6 times pi times the viscosity times the hydrodynamic radius which as we see as we saw depends on the number of ejected base pairs which depends on time and just put a delay factor in the larger viscosity effectively and it should have a unit of time to the power of 1 minus a half in order to have the mean square displacement being square nanometer so whatever it means it's something that is on the order 0.1 so that's about the difference in viscosity between cell cytoplasm and water so now couple the dynamics of the blob by the ejection of DNA but just assuming that this is the mean square displacement of the blob given by this and here and that's related to the amount of ejected DNA in the system so the blob dynamics determines how fast the DNA is being ejected at long time that's actually all I'm assuming here so then you combine everything you get an expression for the diffusion coefficient which depends on the hydrodynamic radius which depends on the number of ejected base pairs the number of ejected base pairs itself depends on the mean square displacement which depends on the diffusion coefficient and time the diffusion coefficient itself depends on n you solve for the number of ejected base pairs and you get something like some constant times time to the power alpha over 2 plus gamma and here you see as long as gamma is around 1 over 3 you always get the same coefficient so in effect that I was assuming gamma is 1 over 3 it's not very sensitive for the result as long as it's not 1 or 3 over 5 that will give you a difference then you just plug in the numbers we predict that the number of ejected base pairs function of time should be proportional to 3 to the power 0.21 and here that's what you see because here I plotted this you've seen it before but this is the fast regime so this is the short time regime so this is the long time regime and you see that the slope is indeed 0.2 and also the pre-factor because in this case I would think that even with ridiculous models you may get a reasonable coefficient but the pre-factor is also reasonable so in this case that's also important to check that of we just take a viscosity of between 10 times 200 times more than in a simple solvent you would get a reasonable value for A that we get here so you can also do it in terms of velocity it's just a matter of differentiation and it's a bit more noise but you will get to predict minus 3 over 7 and we find with an error minus 4 so that's all pretty okay so this is discussion well conclusion indeed so the late stage ejection seems to be quantitatively in agreement and just with a simple diffusion scenario and at this point we don't need to invoke the properties of ratcheting proteins it could be that the dormant stage bacteria also have a dormant stage so they can get into a kind of hibernation at some point and it could very well be that that stage it should work as a defense mechanism against phages because we know that diffusion stops when there's no metabolic activity so in terms of phages phages will only be able to to insert about half of its genome into bacteria and then the process stops so it may be I don't know it could be a mechanism er are also other things that I didn't talk about one of them is that ejections also often it's often observed that ejection goes on for a while and then it passes right and then it goes on again etc so the ejection process is kind of irregular in some cases and that could have to do with so-called dynamic hydrogenaties because we have already seen that at these length scales the molecules that are so large as these blobs of DNA that are half or totally ejected then we have glassy we know in glassy systems that they're dynamically heterogeneous and that's because they're pretty closely packed so they hardly move but when one particle turns out to be able to move it will just cause a cascade of other movements so it's a collective process and that could be the reason of why these pulses have been observed alright I think with that I'd like to stop and maybe there are questions


Welcome to the NHGRI NIH wide Workshop on sequencing and cohort studies and large sample collections Apologies for taking up your your Thursday evening on the other hand It did seem to be a good way to make use of the time of the people who are traveling So so we'll defer to them Just a couple of quick administrative notes so Wi-Fi is available and I think most of you are hooking up Jarell there will be helping you with with that as well During the meeting sorry during the discussion if you could mention your name and affiliation before commenting So that the transcriptionist can can get you I think that the people at the at the table They'll probably be able to figure out who you are It's a little harder to see the names of of the folks who are not at the main table And in closing transport will be waiting for the sponsor participants to return to the hotel So you head down to the first floor lobby and they'll gather you there And I think that's all I have to say So again, thank everyone for being here why don't we begin by going around in folks at the table introducing themselves Chris would you like to start? Chris O'Donnell with National Heart Lung of Blood Institute Dan Rodin from Vanderill Julie Bering from Harvard Medical School Lynn Jordy University of Utah Trisha Hart she cancer Institute Rory Collins University of Oxford Maynard Olson the University of Washington Thomas Lane Thomas Lena and I'm H Steven Chanick National Cancer Institute Francis Collins NIH Eric Boerwinkel from the University of Texas Health Science Center in Houston and also the Human Genome Sequencing Center at Baylor Terry Minolio NHGRI Eric Green NHGRI Stephanie Chisler, GlaxoSmithCoin Winnie Rossi National Institute on Aging Peter Donnelly from the University of Oxford Rick Wilson Washington University Mike Murray Brigham and moments Hospital Michael Knowles University of North Carolina Chapel Hill Judy Cho Yale University Daniel MacArthur Massachusetts General Hospital Allison Mandage NHGRI Thank you everyone Also, I would like to thank the staff for a long day and staying over that around the side Thank you for attending if anybody would like to introduce themselves But seriously thank you it makes for a long day I realized that could you put on the first intro slides for me? I have it just a couple of slides so we're all kicked off on the same foot


Welcome back to Think Check. This is Movies You Can Learn From. I'm Jay Fiedel. Today is reviewing Killers of the Flower Moon, which is a very, very interesting movie. It will captivate you. There it is Leonardo DiCaprio, Robert De Niro, and a woman called Lily Gladstone, who you will meet. Okay, so let's talk about the historical background. It's a novel, but it speaks of true events and a true circumstance, a true moment in the history of the United States and the history of the Indians in Oklahoma, the Osage Indians in Oklahoma. So joining me is Stephanie Stahl-Galton. I'm so happy to see her. Welcome to the show, Stephanie. Nice to see you back. Nice to be back. Yeah. Thank you. What's the historical, can you paint the picture of the historical tableau on which this movie is based? Well, I think that, as you said, it's based on the real thing. So this actually is an experience of life for this part of the country, which is Oklahoma. And these are the Osage Indians who have been moved there. They were actually forced to make that move into a territory that they were unfamiliar with. And then they settled themselves into the best situation they could. And this was probably in the 19th century and the 1880s, post-Civil War, but not so much at the end of the century. Actually, if they came west along with the Cherokees, who went from Georgia also to Oklahoma on the Trail of Tears, Oklahoma was some of the worst land in the Zen country. And I think the government was sending Indians to Oklahoma thinking they weren't giving up very much because this was really marginal land. That's why you have the Trail of Tears under Andrew Jackson in the 1830s. That's why later on you have the Osage Indians coming from Missouri, Kansas, and Arkansas, I believe. And so they wound up in what the government considered really bad, useless land. And everybody is in Oklahoma. And this movie is set, by the way, in the late teens after World War I and in the 20s. Go ahead. Hey, that's a little bit later than I noted. And of course, the cruelty of the President Andrew Jackson at the time was astounding, along with some other themes in the movie. But he did have them escorted into this new territory and lost lots of people along the way. There was no mercy. It was a forced march into this territory. But they went with all that they brought with them, whatever they could carry, but they themselves were strong and they established themselves as best they could. But in a very poverty-stricken situation, there was nothing there that they could really do agriculture with and be very successful. So it was very tough times. But then the irony is, of course, that they did then have the discovery of a will. So the point is the cruelty and the lack of responsiveness of the President Andrew Jackson and those that moved these people hundreds and hundreds of miles that they had to walk to, there were many efforts to keep some mercy in this picture and give them that nothing happened. And then, of course, as I was saying, the irony was that the land had nothing on its surface that these people were familiar with or could use as means of producing their benefits in their lives. But they did have something underneath, which was enormous oceans of oil, which then were theirs. And they were able, they became very rich because of the explosion of oil that they discovered under the land. But I think that the story what was already very, very sad, but with the discovery of the oil and the riches that they then purportedly had access to, they still were left in a position of subjugation and oppression and inability to manage it and to make it work for the betterment of their own lives. And this is where we get then the entry of other people into the situation who were there to on the surface help these people out. But what the movie is about is the theme of how the oppression was made to be systematic and systematic about making sure that the money was not theirs and that the money could be obtained by other people who were not looking out for their best interests, but rather coming in to take advantage of them. And I think that what has happened in this story that is, again, based on real facts, is that these people who were portrayed in the movie as the scoundrels who came in to help them, but really were helping themselves, were able to be so duplicitous and bring themselves into the situation and were mostly white men and looking for resources such as these people had. And they were able to manage these people in ways that put them in the worst possible position possible. And they were unable to in any way take charge or control of their own resources. And I know Jay was talking about earlier that issue of incompetence. They even labeled them because they didn't have skills, they hadn't been educated. So they were looking for help, but the help came in and took advantage of all that they couldn't do. So I think that I think the Indians were legally treated probably under the laws of Oklahoma, but maybe under federal law as less than competent. And I guess that was because they were Indians. It was pure racism. And they were wealthy. They owned large tracts of land, you know, reservations that they'd been given. And at the time they were given these reservations, somebody realized what oil meant and that there was lots of oil under them. But in the, I guess the teens, John D. Rockefeller was discovering all his oil holdings, you know, and people were, Ford was building cars and oil became very valuable. And all of a sudden the Indians found oil and they realized what it meant. And they invited, you know, these oil companies in on the land to drill for oil. And they had a scene there. I wondered how they got that scene. A scene there were virtually hundreds of oil wells, wooden oil wells. As far as the eye could see it, it was all owned by the Indians. They were wealthy, but they were treated as incompetent. They could not take, legally take control of their own affairs. So they had to have a, you know, a guardian, that was the term, to do anything, including draw money out of their own account. And you saw some of that at the beginning of the movie and you realized that these really, you know, these really bad guys were controlling the money and dipping into it. And the Indians were getting what was left, even though it was all theirs. So you began to get the sense of how the Indians were being mistreated. But it got much worse. You want to talk about that? Well, I'd see it's coming up in my mind and very painfully because of the way that they were managed by people that themselves really had nothing in mind to be helpful to them, but really came in and took advantage of these people. As I said, not only at the level of we know how to do this and we'll take care of it and you, you don't know how to do it. And so you don't have the capacity. And so we will have to control you. And they established these relationships with these men who were, who were these guardians who had to be approached to get any money at all. And then they got to allow the Indians to have the money. But I think that the very, very sad part of all of this and the wickedness that is coming up that's displaying how difficult and how deplorable has been this relationship during the development of our country at that time between the Western way of doing things and the Indigenous people. Well, when I referred it, it got worse. What I mean is, and this is not dissimilar from treatment of the native Hawaiians here in Hawaii. They owned the land. There was no real system for devolving the land of the next generation. And so you had to look to, you know, had to look to the way it worked without a will and who inherited what? Okay. And this was apparently early in the game of this kind of intestate succession arrangement. No wills and it just went down the family. And if you had a larger share because of your place on the family tree, just the way things worked in Hawaii back in the 19th century, then you got more money. And our heroine, Lily Gladstone, a beautiful woman really, I mean, as an actress, she was, she had a full charge. She had a large share. Okay. So that made her a bit of a target by any of these wise guys howly, wise, wise guy howlies that were coming in there to try to launch out into the Indian money. So if you married somebody with a full share and then succeeded that person and survived that person, you were going to inherit her share of the oil. And that was big bucks. So the Indians were not sophisticated about this. They didn't realize that it really wasn't romance at all. It was the law of intestate succession and what, and what their husbands and children were going to inherit from them. And that opens a whole new chapter in how they were abused. And the movie speaks of a sort of history of all these Indians who had died under strange circumstances in that town. I think it was Fairfax was the name of the town, I think. It was Fairfax. They died from, you know, who knows what, but it was like the wasting illness. It was probably poison. Sometimes they were shot. There was a whole, you know, panoply of possibilities about how they died, but it was always, you know, a kind of suspicious. And when they died, some howly guy would inherit. And little by little, their birthright was being conveyed to others, to howly guys. So this is very troublesome. It's one thing to marry a woman and then naturally inherit her wealth in the oil. It's another thing to have her killed early and then inherit everything early. And that's what was happening. And they, the, to see the patterns emerge in this approach that the leaders, the guardians and those that were there to get the money, what they did is that you could see the pattern of the deaths go right along with the inheritance line. So as Jay says, the families were taken out almost one by one, either by the poor health and no support for anything like that. They were suffering with diabetes and all kinds of dilemmas that there was no medical care for and nobody much provided anything. It did come up at the end that they started to do that. But that was very difficult to see people, young people, healthy people, and who had inherited all, who had all of this resource and money and they couldn't get any help.  And then the man that was married to maybe an older sister would come along and then pick up again with the next sister in line. And, and we'd go through the same thing there. And sometimes that was a more pernicious or direct approach to using poison or taking people out, you know, directly with weapons. But then they would move it right on down until they got to the one remaining inheritor. And then that person was in complete jeopardy of being sailed and also being brought around to get into relationship and marry and then give those inheritance rights, not to their own children even, but to this, this usually white man that, or as well as, as Jay said, the Halley types. But they would, it was a fleece. It was a fleecing machine, because the doctors, the medical establishment in that town were all complicit. And they didn't take care of these people. They let them die. Sometimes they provided the poison. The law enforcement officers in that town looked the other way. And there were some really blatant shootings in the town in the middle of the town or in the woods near the town.  And so the whole town was kind of organized around ripping off the Indians. And as, as people came into the town, young men out of other places or with some family connections, in fact, that was how one of the, the Ernest Burke Hart, the Leonardo DiCaprio character came into town and what was, what was done to him as a young man out of the service and trying to reestablish himself and had an uncle living there. And you could see the, the entire game being played with the uncle doing the wink, wink, nod, nod thing about, if you like girls, and you might want to think about some of these here. And if you want to take on the step of getting married, this is a good place to do it.  And this, this, this person that was played by. And you just restart that question, that answer. One chilling piece of this movie is to actually see not only the patterns of the deaths that were directly almost like primogenitor, which didn't involve so many males in the, of the India, they had profiled women too. They, they all had their claim. So it didn't matter what they were women or men, but they would come into the town and they would see what their opportunities were where they thought at first, maybe they could help and beat the oil men, but no, they, there were bigger opportunities that were presented and encouraged. And so DiCaprio, Leonardo DiCaprio came into town as a recently, a recent soldier now out of the service and looking to use his uncle as a way to get a life started and get a job and have some income. And the uncle of DiCaprio that who, who's Robert De Niro was, yeah, it was, that was a fantastic character. And, and you wouldn't even recognize either DiCaprio or, or De Niro, they were, they were so into these characters and so, so tightly identified with them. So William Hale, the uncle, or De Niro would not only play the, the gracious gentleman of the city who he had done very well by that time, but also was the leader for these young, young men who would come and wanted to treat this, this young man as a son. And the chilling part of this more discreet and under the surface tactic was how absolutely it got into the, the intimate and private details of people's lives. So he would talk with his, his nephew who was in town about the kinds of work that he could do. And while he was doing that, he could find people that he might want to consider having relationship with or getting married. And so that, that just laid out and lots of wink, wink, not, not about, you know, having relationship liking girls, getting married, which is such a, taking on that responsibility with the clear message that this is all about, get out there and get us another hook into what is this wealth that these people have and have no business having because they don't know how to end. We're skipping over a lot of content. This is a three and a half hour movie, which is loaded with contents while you want to see it twice to catch it all. But at the end, Robert De Niro character encourages Leonardo DiCaprio to actually poison his wife. And arguably, he had feelings for her. And she certainly had committed to him. She was a really sweet wife. And he would tell her one minute that he loved her. And the next minute he would slip her some poison. Fantastic scenes. But mind you, the character, the rabbit, rather the Leonardo DiCaprio character, was not a smart character. It's like the movie we reviewed before downsizing. Matt Damon was not particularly smart character. He was the lead of the movie and DiCaprio was the lead of the movie. But neither of them played smart characters. And here's this guy trying to poison a wife who was completely dedicated to him for her money because Robert De Niro has encouraged him to do so. And in the end, I find it very interesting this all connects up with the FBI, believe it or not. His wife, a little suspicious of all these strange deaths in the town. She goes gets on a train and goes to Washington, from Oklahoma to Washington. And she looks up the president. And she talks to who was Calvin Coolidge at the time. And she has a moment with him and encourages him to do a little investigation. And he sends somebody from a brand new organization run by a fellow named Hoover, Edgar G. Hoover, back in the 20s, who was was just starting the FBI. In fact, they called it the Bureau of Investigation, not the FBI. And ultimately, to their credit, they sent a team of investigators down to this Fairfax town, who began checking up on things. And they ultimately found at least some of the culprits, not all of them. And it was very interesting that there was a certain level of justice, but not complete. And it shows you, you know, the dodgy experience that federal and this is just like what's going on with Trump these days. The dodgy experience that federal investigators have when some people are lying, and they can't really get the hands on the evidence. But ultimately, our friend DiCaprio went to jail. And I think he died and jailed me many years later. And the same thing with Robert DiUro character, I think he got out when he died shortly after he got out. They tell you at the end, they get him a radio play, right? At the end, where Margot Scorsese, this is a Martin Scorsese movie, he plays one of the announcers in the radio play. They review the whole movie in a radio play in the late 20s, I guess, in a radio studio. Then Scorsese is part of that. And you say, wait, that guy looks so familiar. That's Martin Scorsese. He made the movie. Well, it's a gift because we know so little about this period of time and these relationships that were set in motion by a lack of any oversight or any federal or anything larger than the local sheriff. And so easily can crime come into that and take over all that is about the good and following the law. But I think that it is quite a statement about the value of a federal bureau of investigation or something to come in and be another lever for these people to call down for some checking on who's breaking the law here. So I found it was a very good advertisement for a little more bigger government. I mean, yes, ordinarily many of you many up these small places, even with tremendous assets such as this can get along and do it themselves. But for the most part, there is usually a little more resource needed to make it all work out for everybody. But the FBI coming in and starting to show how they could go about this technical analysis of the situation when everybody else was just wandering around, how come Joe's dead over there in the barn? They didn't see any patterns. So they brought in that way of detecting whether there was criminal activity going on. And that's what they needed. And that's what I think this woman, the main character woman, Molly Burkhardt, she considered the soul of this movie because she was quiet, not nonverbal, but very low verbal, but very insightful and always watching and listening and knowing what's going on. And she could tell that there was another level of look at what they were experiencing that needed to be taken. Yeah, the Indians are always going to funerals. They were dying left and right. And nobody was doing anything about it. And there was no investigation of any of those deaths. And she decided she had to do something. So she went straight to the top and it worked. For a quiet, diminutive personality, it had a lot of effect, it cleaned up the town. And a lot of guys went to jail. But one thing I just wanted to trip off what you were saying a minute ago, this is a great study of American history. It's a great study of the Indian situation. This is not wounded knee or, you know, Custer's last stand. The Indians were very docile. In fact, the chief of the tribe says, gee, I wish it was the good old days. I'd go and kill some of these people, but it's not the good old days. I can't do that now. They were wealthy, but they didn't know what to do with it. And they didn't know how to control it. And the capitalists came down and ripped them off left and right. It would have gone on forever had Molly not gone to Washington. It's still going on. I mean, the right, the point is also made by some of the reviewers. It justifies this righteous fury and anger that indigenous people have towards the white supremacy and the racism that they've had to endure through all of these centuries and have less just lost incredible amounts of life over it. And that this is one piece of our fabric that we've not picked up the blanket looked under it much at all. And now through this presentation, here's another picture of something that's not a happy picture, but it is a story of how it is that America has grown and hopefully moved on from that sort. Yeah, it really teaches you about the not so much the 19th century, which was bad enough, but the early part of the 20th century in middle America where there was racism to beat the band. There was crime to beat the band. There was the police were corrupt. Even the doctors were corrupt. The whole town was full of corruption. And it's a great concern that as recently as what 100 years ago, that's all it was. This was going on in middle America, which was supposed to be civilized. It wasn't. And by the way, this is not too far from Tulsa, where in 1920, a wild mob burned down the black part of the town of Tulsa in Oklahoma, the same state, either Tulsa or Oklahoma City, I don't remember which which it was might have been Oklahoma City. But by the wine is, it was pretty rambunctious in those days.  And you could get away literally with murder, and robbery, and abuse of people and racism that was just visible, palpable racism. So anyway, it teaches you about that. On the other hand, it is a great movie. Let's talk about the quality of the movie. Let's talk about the acting. We have a few minutes left, Stephanie. Well, as I said, I mentioned before that you barely can recognize De Niro and DiCaprio. I mean, they're so integrated with these these characters and their roles. I mean, it's a beautiful, continuously on on task business that that they're doing, they're both of them. This has got to be some of the strongest work that that both of them have done. And of course, they say Scorsese has taken away some of the phenomenal fireworks that he usually throws in to get more focus on the issues here that are central to this movie's message. And it's these are the kinds of things, the ways to get this information out to the public, to be educated about these things that we're not educated about in school. And there seem to be, there seem to be pressures to not let this into our schools. And yet we need to know about these extremes of of of error and relationships that we've had, you know, with people that are not like us. It's a it's just a part of the whole place where we are now at this time trying to understand how to get along. But I always always watch to see the dynamic and Scorsese certainly capable of that. And he has made unbelievably good movies in his life and his career. But one one thing I noticed is that the copy of I suppose is the lead actor doesn't really change. The dynamic remains about the same. He starts out being a wise guy. He starts out breaking the law. He's he's robbing banks and a mascot and all this, even after he meets this this woman that he's supposed to have a romantic attraction to he's doing a plant a really bad things. And he keeps doing them.   And he's being egged on by the mafia boss. And that is Robert De Niro. And he just he gets worse to Niro as we go forward. So here in these two leading male characters who form an axis of evil. And the Indians can't tell because they'd be really sweet to them. While they're talking to them up nice, they're complimenting them. They're talking about how wonderful it is to live in this town and live in peace and harmony with the Indians. It wasn't that at all. They were killing the Indians and they were stealing from the Indians. So what you have is a dynamical, right? But then the dynamic makes them worse, not two of them worse, not better. Molly, on the other hand, she has a dynamic to she begins to understand. She never fully grapples with the notion that the man she loves is trying to kill her until the very end. And even then, she still loves him. It's a very interesting kind of romance. And he will, you know, say something affectionate to her. But at the same moment, he slips you the poison. I don't fully understand the kind of romance. But she has a dynamic. Molly has a dynamic. She gets wiser, more, you know, able to discern what is going on around her. But the two De Niro and De Caprio, they get worse. And they're beautiful, beautiful acting jobs. They both magnificent in the way they play it. Well, I think that point is so good, Jay, about Molly, the soul of the film is that she was learning all of the time more and more. And the last thing she learned from what I could see at the end was that, yes, she was still taking the medicine from him and believing he was helping her. But, but obviously at the end, she had been told that he had been poisoning her while he was getting her this medicine. And it took her until the very end that she walked, she did turn away and walk away from him when he came to talk to her at the end. And that, that, that was right at the end. And yet she was invested in him and, and, and, in romance with him and in love with him and believing and having faith in him, because that was where she was in that marriage. And he was never even in it to be humane. That scene is just so memorable. There are many memorable scenes in this memory, you know, like at one point he says, what color are you? And, you know, you're red, what are you? And she says, I'm my color. But anyway, at the very end in the scene you refer to, where you, you finally have the confrontation, she says to him, is there anything else you're not telling me? Is there any other crime or bad deed that you would like to tell me now? And he has not admitted that he was poisoning her. And he says, no, no, no, that's it. I mean, I did some murders, but so that's it. And she looks at him and realizes that he's lying to her. And that's when it's a really incredible moment. Without more, without any words, without any accusations, she simply stands up and walks out of the room. That's the end of it. And later, sooner or she divorces him for that. And that's her own life.  I mean, that's not just in this circumstance, but over all these enormous numbers of unfortunate racisms and white supremacists taking it's tricky. It's tricky because they don't admit to racism. They just do it. And they do it in the worst way because they're lying about it. And they're telling the Indians, we love you. And while they got the hand in the pocket. So anyway, so it's three and a half hours. He was too long. No, I never noticed that it was that long. I knew it was before I went in, but it never came up again. I never felt that there was a drag at all. It was very engaging. I mean, we were seeing that, you know, an enactment of huge violence actually within this domestic, these domestic situations as well as on the other layers of interaction in the community. But they came the way the white supremacy could work. It was with just client power getting in there and working it without any regard for humanity or the law or God or anything righteous. Only greed, only greed. Yeah. And that's what the reviewers have said. You know, I think there should have won a lot of awards. I don't know how many it won. It didn't win Oscars. It was nominated, but it should have won a lot of awards. Why, why feel that way? First of all, the production values were unbelievable. And I don't know if you caught it, but on YouTube there's a five or six minute clip. I'll show you how Martin Scorsese was directing and, you know, talk about attention to detail. I mean, Emory Frayn and he would do it again and again so that it was just perfect. And that's what a great movie maker does, you know. And then aside from, you know, the color and the lighting and the entity and all that, the acting was really astronomical. Both Dicaprio, I've never seen him anything as good as this, even Gangster New York, which was good. And gee, look at Robert De Niro's career. This is the top of the line. He was such a character with that slight Southern accent and that moves of unkiller, Masia Donne kind of in his bowl and everyone around him. It was amazing. And it made you believe that you were there and you could see through these guys. You were clinically in a room with him. That's what I call terrific acting. And she, she was lovable. And she was totally Indian. She came from another culture and she was, as you said, quiet and thoughtful and so attracted that you almost believed Dicaprio when he said he loved her. She loves him, but he did not. I'm afraid he did not love her. So it was so intense, as you said, it was an easy three and a half hours because it kept on taking you in places. You didn't know, honestly, Stephanie, it didn't know where the thing was going. That's a little actually there. Yeah.  I mean, I couldn't really tell that he, that the Dicaprio character was giving his wife, Marley, the poison with the medicine, because of course he was distributing good medicine that they had brought to her. So this is again that, that the violence, the, you know, this violence that occurs in this quiet way that they had done on all of this work to bring in the, the diabetes medicine. And then the character William, the William Hale had brought in the, the murderous poison to add to it so that we can get on with this next victim. And yet I couldn't really see what they were doing at that point. It was after the fact that you find it out. You had to watch this movie very carefully, or you wouldn't would miss a lot of things that say you got to see it twice and you're going to be looking at it harder the second time to catch all that nuance to catch the details. So all of that considered, what do you rate this movie from zero to 10? What do you give it? Well, I think we need more of this movie. I put it at the star, the 10, the 10 stars, right, the 10, because of the importance of the topic and the, and the, and the capability of these actors to do these complicated roles. Because we were seeing this duplicity and this evil acted out in layers. So, you know, they're good actors, they're acting the part, but then they were also acting over that it to be duplicitous and to take advantage of people want to commit these murders and keep this whole complicated thing going. And you didn't really see them be themselves in the character going down to level one acting until like in the prison when the uncle William Hale and DiCabrio Ernest, you know, they got together and the uncle begged him not to tell on him. So he did try, he came, he broke out. Even at the moment where his own freedom was at issue, he was suggestible and to the mafia don person. The other thing I found interesting is at this meeting, at this meeting, which the Defense Council phoned up in front of the judge, which was actually questionable. I mean, the judge was questionable too. At this fancy meeting between DiCabrio and his quote lawyer, it wasn't really his lawyer. And they wanted to try to get him to, you know, shut up, not to say anything, not testify against William Hale. At this meeting, there's like five or six or seven oil guys representing at the time, these major oil companies that were drilling for oil in Oklahoma. You never see them before or after that scene, but you realize that they're there running it all running William Hale. They're trying to get their hands on the oil.  And I think that goes to the rating of the movie. Now, some people didn't rate this movie highly. It didn't win as many awards as I thought. But, you know, it's sort of in the eye of the beholder. If you care about American history, if you care about American Indians, if you care about the emergence of evil, you know, people in sort of capitalist clothing in the beginning of the 20th century, then you're going to rate it higher. Because as we say, it's a movie you can learn from. It's an educational experience to be there. But if you rather see Captain Marvel, you're not going to see Captain Marvel in this movie. You don't learn anything from Captain Marvel. And so, you know, you and I would give it a higher ratings than some of the other people. I might add, by the way, there's a rating review in the New York Times in this movie that is just knock your socks off. It is really wonderful. And I'm going to, I'm going to post a link to what I was saying. Anyway, so what would you give it? Ten? What? I'll give it a ten. I mean, the level of action and the latering of the acting actors acting over their characters. It was very, very complicated and very interesting to see the different perspectives that were working through all these layers, those that were taken advantage of, those that were subjugated, those that were oppressed, and then these other guys that were trying to keep it all into control was very interesting the way they, that he laid all that out. The director managed to convey so much like what you say. You can see the movie again to see what was happening. And I'm sure it's representative. This is not a unique situation. It's very representative of the way evil can pervade the situation. And when you have lawlessness and any lack of higher oversight. Yeah. The story of American history, American capitalism, American manifest destiny, you know, lawlessness in this country. It's part of the way the country, as you said, it's part of the way the country, you know, developed. And I would add that all this engagement with other cultures, this was an example of that. It's a clash of the Indian culture, which had a very, which is so sweet and lovable really. And I think that's a true statement of it versus these guys that had no moral compass whatsoever, just ripping them off. And you know, I would say that, you know, we had a movie in, in about Hawaii and the indigenous people in Hawaii. Do you remember the movie, I forget the name right now, a few years ago, and it was very popular. And it was a story of, you know, the descendants, remember? And it was, you know, about the same kind of thing with, you know, going down the chain of descendants and people trying to maybe take advantage of that and so forth. And I find it very interesting that they could make a movie in Fairfax, Oklahoma, about the clash of cultures there. And, you know, that kind of descendancy there. And we have a really mainly worthy movie here. Martin Scorsese should come out and see what he can do for us. And it would be really different, but it would have the same strength. Anyway, we got to go now. I want to tell you, I would give it a 10 when I was negotiating with myself before. And I still, I'm still holding out for a 20. That's so good. That's how good it was. Thank you so much, Stephanie. It's great to talk to you, great to review this movie with you. We'll do it again, Stephanie. That's good. Thanks, Jake. This was great fun. Yes. King and a learning experience too.


Here are the nine types of intelligence. Naturalist intelligence. You may have a knack for identifying patterns in your natural surroundings. Musical intelligence. Can you pick up a new instrument with ease? Do you possibly also write and arrange your own music? Logical mathematical intelligence. Formulas and reasoning skills are your expertise. Existential intelligence.  Interpersonal intelligence. You read others' emotions well and you can quickly tell if someone is being genuine or not. Bodily, kinesthetic intelligence. Do you feel that your mind and body are one? You're great with timing, motor skills, athletics, and dancing. Linguistic intelligence. Can you understand and pick up the subtle differences in the meaning of words and language? Intrapersonal intelligence. Your mind is your safe haven and you understand your thoughts and feelings on a deeper level than most. Spatial intelligence. Are you great with directions and are a strong visual learner? What type of intelligence do you think you are?