Family Theatre presents Harold Perry and John Lund. From Hollywood, the mutual network in cooperation with Family Theatre presents Mr. Harrison and the Lady Racketeer starring Harold Perry. And now here is your host, John Lund. Thank you, Tony LaFranco. Family Theatre's only purpose is to bring to everyone's attention a practice that must become an important part of our lives if we are to win peace for ourselves, peace for our families, and peace for the world. Family Theatre urges you to pray, to pray together as a family. And now to our transcribed drama, Mr. Harrison and the Lady Racketeer starring Harold Perry as Bill. Billy Boy, didn't you hear the whistle? Hi, Phil. You were going my way tonight. Why, you need a lift? Yeah, afraid so. Cars still in the shop. You going my way? Sure thing. You don't mind waiting a few minutes? Tucker again? Yeah, that's right. Oh, brother. What now? That's CO2 thing, I suppose? Who knows? Billy Boy, that's a good idea.  Well, no use Kelly-sledding. Harrison! Yes, sir? Come on in here. Well, here goes nothing. Good luck. Thanks. Yes, sir? Mr. Harrison, you have a wife and child, haven't you? Yes, sir. Then you should have some awareness of the meaning of responsibilities, isn't that right? Yes, that's right. They expect certain things from you, financial support, I imagine? Naturally. In order to provide that support, then it is necessary for you to keep working, isn't it? Yes, sir. Now, you'll forgive me for asking all these questions, but I wanted to get a few things straight in my mind, because I seem to be under a mistaken impression. Perhaps you could correct it for me? I can try, Mr. Tucker. Fine. I'm sure United Automatic Fire Control will appreciate it. Now first, I am the foreman of what department? Plans and drafting. That's what I thought. And second, you work in what department? Plans and drafting. That's what I thought. You find enough to keep you busy, do you? Oh, yes, sir.  Mr. Tucker, in certain cases, water damage is just as costly. Mr. Harrison, have you been with this company 20 years? No, sir. Nine. Nine years next month. Well, until you've been here a while longer, I don't think there is much you can tell me about water damage and fire damage. But, sir, I've checked it through, and that CO2 primer would effectively lower the ignition points. That will be about enough, Harrison. I suppose you are perfectly aware of this, but I regard you as something of a bottleneck in my department. Bottleneck? Bottleneck.  Yes, sir. Furthermore, you are slow in your work, and now I know why. You've been spending the company's time on harebrained schemes like this. Mr. Tucker, I did that in my off hours at home. Well, you know what I think of this idea? I'll show you. Oop. There. What do you think of that? Does that give you a rough idea of how I feel about the latest of your ideas? Well, does it? Yes, sir. But what? Nothing. Nothing. Now, in the event you should forget again, Harrison, I am the foreman of plans and drafting not new inventions, and you work in my department. Is that understood? Yes, sir. I am a charitable man, Mr. Harrison, or you would be looking for another job. Your work is second rate, and both of us know you can be replaced with no discomfort to unite at automatic fire control. Don't we? Yes, Mr. Tucker. Don't push my charity any more, Mr. Harrison. Just do your job.  I understand. That will be all, Mr. Harrison. Yes, sir. Good night. Oh, Mr. Harrison. Yes, Mr. Tucker. As long as you seem to find time for extra work, I shall expect those fall book plans by Friday. Friday? But they don't have to go to Mr. Morgan till the following Wednesday. Friday, Harrison. Yes, sir. Oh, I'd like to punch that guy's nose for him. That super- You threw the grinder, didn't you? Hmm? Oh, Phil, I forgot you were waiting for me.  I feel like it. It really gives you a hard time, doesn't it? This time, he was pretty easy. Only a couple of minutes. Sometimes he works me over for five or six. Someday, Phil, someday he's going to go too far. Yeah, and you'll pop him one and have to hunt yourself up a new job. Why me? Why is it always my hidey-nails-in-the-wall? It's not just you. Once in a while, somebody else gets it, you know? Not as often. Yeah, maybe not. And I think I know why. What? Look at it this way. What's Tucker got? What do you mean, what's he got? So he's the foreman. But aside from that, he hasn't got a thing. He hasn't got a wife and kid like you have. So that makes him mad? What am I supposed to do? Toss my wife and daughter away just to get in his good graces? Look, I'm not defending them. I'm just telling you what I think. It's a small, envious man, and like most small, envious people, he dislikes people who have something he hasn't. And there's something else. Heh. I must sound like the office psychologist. Go on, Phil. You got something else he hasn't gotten. That's what he's really afraid of. What's that? Imagination. Imagination? That's right. Automatic sprinkling systems built in fire-controlling devices. These are pretty imaginative things. They're great. But there's room for improvement. There's room for improvement in everything? Right. I'm not an early boy, but fire-controlling devices like ours are only a few decades old. So the improvements come faster, and the guys who do the improving are the ones who move ahead the fastest. Are you trying to say that Tucker's afraid I'll cop his job? That's about it. Huh. That's a laugh. Is it? Well, no. What could I do this? You could handle it better, and except for one thing, you'd probably get it. What one thing? You're afraid of them. Yeah, you're right about that. Well, why? Why? I'm a very specialized draftsman. There aren't many openings for my specialty fill. I can't afford not to be afraid of Tucker. Well, maybe someday, Billy Boy. Yeah, maybe someday. But I'll tell you one thing. If Tucker thinks I'm going to do any work at home, he's crazy. I won't even think about this job at home from this moment on. Not for the next few days, you won't, but you won't have time. You're aunt. What aunt? Well, didn't I tell you your wife called before you got back from lunch? Sure, I didn't tell you. My wife called? Well, it's the first I've heard. Yeah, I must be getting old. So you're getting old. Now, what's this about an aunt?  She sounded kind of excited about it. Well, I can imagine. I can't see. I could have forgotten it. Anything else? No, it's about Alson talk about her arriving in a Ritzy car, dripping with furs on the long green. She was excited, all right. Did she say what this aunt's name is? Velma or something like that. Well, you ought to know how many rich aunts you got. Phil, I haven't got any aunts at all. Well, I'm really not surprised you haven't heard of me. Oh, that really is a lovely dress, my dear. Thank you. Looks like it's right out of one of those exclusive shops. Oh, no, this old thing. Well, it doesn't look the least bit old. Ladies, ladies, please, I still haven't... Here's the coffee. Oh, Rita, darling, will you move the flowers off the coffee table so I can put this tray down? Sure, thanks. Smells good. Nothing like a good cup of coffee to settle a meal. Tamps down the food, you might say. Please, everybody, sit down. I've got to get this thing straight. All through dinner, we've talked about dresses, the Alaskan salmon canries, my mother and father's courtship. In fact, everything except you, Mrs. Jorgensen. Call me Aunt Thelma. That's what I want to talk about. But Bill and Thelma and I went through all that this afternoon. Sure we did about the scandal. Rita. I'm sorry. You all went through it, but I didn't. Mrs. Jorgensen, since you're supposed to be my aunt. Supposed to be? Heaven, don't you think I would have heard about it if I had an aunt? You couldn't because of the scandal, Daddy. Rita, if it's all the same with you, I'd just as soon hear the story from Mrs. ... from your aunt. And I use the word, advisedly. I'm sure you understand, Mrs. Jorgensen.  Bill, have to roll. He's right, Helen. You married yourself a smart man, one of the brightest pennies ever turned up in the family. And he got that way asking questions, right? Right. Mrs. Jorgensen, why haven't I ever heard of you? Well, it's a long story, but I'll give it to you, short version. We'll have plenty of time to go over it in the next few days. You see, I'm the black sheep of the family, the skeleton in the family closet. Go on. Shortly after your parents, God rest their souls, were married, I don't suppose you remember your paternal grandfather. I heard he was a hard man, but I can't say that I remember him. A very hard man, good enough in his way, but stiff and stubborn. Well, as I was saying, shortly after your folk were married, I chance to meet Mr. Jorgensen. Boy, wait till you hear about him. He was a gambler. Please, my dear. A good man. A little mixed up when I met him, but a good man. And they fell madly in love, didn't you, Anthem? Oh, we did. Oh, your grandfather raised a terrible ruckus, told me he'd disinherit me rather than have a professional gambler in the family. But they were married anyhow, and they'd probably never... Aunt Thelma tell it, darling. That's right. We were married. Your grandfather, I mean your grandfather, took it pretty hard. He did disinherit me, and he vowed that never again would my name be mentioned by any member of the family. Just because you married a gambler? No, he was a hard man, your grandfather. He must have been. Well, Mr. Jorgensen and I moved to Alaska, where in the course of a friendly game one evening, Mr. Jorgensen chanced to get himself shot through the hand while dealing some cars. Oh. Naturally, that ended our gambling days, and we were forced to go into another kind of business. But from appearances you did quite well. Well, up with one thing and another, we did manage to put a little buy. Tell him how much, Aunt Thelma. My dear, you don't ask questions like that. Oh, it's all right. I don't mind. Oh? Well, then how much did you put by? Last accounting, I believe it was around 23 million bucks. 23 million? Oh, but money won't buy everything. And since Mr. Jorgensen passed away, I've had a yen to seize some of my own kin. Spend a little time with you, and of course I'll pay my own way. Oh, no, you won't. You're our guest. We won't hear of it, will we, Bill? 23 million dollars. I wonder if I might use your phone. Sure. But of course, it's in the den. Oh, Rita, darling, show your Aunt Thelma to the telephone. Bill and I are going to reheat this coffee. Right this way, Aunt Thelma. Are you going to call Alaska? Oh, my no. Just a business acquaintance here in town. Here's the phone, and the phone books are under the table. Thank you, dear. You want me to dial it for you? Oh, that's all right. I can do it. Aunt Thelma? Yeah? You'll have to pardon Daddy. He's not usually like that. I think he's having trouble at the office. I think that's what it is. Oh, that's all right, dear. If you need anything, just call. Thank you. Oh, Rita? Yes? Is there an extension phone? No, that's the only one. Oh, thank you. Well, you'll close the door like a good girl, won't you? Yes. Hello? Oh, hello, Will. Thelma. I'm in. No, nobody suspects a thing. Well, my nephew isn't quite sure. Oh, but then I think he's just been seeing too much of Rackett's squad. That about the first? Sure, I'll take him back to the store tomorrow. I'll just tell the family. I'm putting them in storage. Now, you know what you're supposed to mail to the house each week. That's right. Four or five copies of Wall Street Journal, Shippers Report, and at least two of those envelopes with the important-looking letterhead. How's that? No, no. Don't worry about running out. It shouldn't take more than a month. Sure, it's a gamble, but I think it'll play off. Remember, I've been figuring the angles on this deal for 12 long years. And I've studied this family till I know it better than mine. They'll be eating out of a hand in two weeks. Don't worry about a thing, though. I'll have this guy paying for the rest of his life. At last, I found the foolproof racket. Yeah, honey, I'm home. Hello, Aunt Thelma. How do you like these, honey? Nice. What are they? They're going to be new drapes. I was downtown, saw the material in the window and we've been sewing up a storm all afternoon. Oh, is that the mail you have in your hand? Oh, yeah, all for you, Aunt Thelma. Anything that looks important? Well, let's see, Wall Street Journal, Alaskan Tidal & Trust Company, and the Merchants Bank of Greater Manhattan. Looks like it might be a check. Just put it on the side table, will you? What? Aren't you even going... There's a phone. Oh, Rita will get it for you. Ma'am, Tucker's giving me a hard time again. Wait a minute. I'll go see. Dad, Guesser's on the phone. Who? Oh, no, not at home, too. Speak up to him, Bill. Sure, I will. Well? Yes, sir? Tomorrow morning. But Mr. Tucker, that would mean... Yes, of course I do. I'll try, but I don't even know if it's possible, sir. All right. All right. Yes, goodbye. Not good, huh? Oh, didn't see you there, Thelma. I followed you in to find out what was going on. Well, that's Frank. Tucker gave you a time of it? Yeah, gave me an impossible project to finish by tomorrow morning. Sit down, Bill. I want to talk to you. Mind if I close this door? Be my guest. Tell me why I don't stand up to Tucker. Nuts. I know why you don't stand up to him.  Not exactly correct. I know I'd lose my job. He's only a foreman, isn't he? He didn't hire. No. Wilbur Morgan hired me. And Wilbur Morgan's number one top guy. You know, once in a while you use very strange terminology. Am I right? Yeah, you're right. But what if he is? Wouldn't he have to do the firing? I don't think it would work quite that way. Listen, Bill, since I've been here two weeks today, I've had a chance to read the articles you've done on that, uh, trade paper. What do you call it? Pacific Fireman, that's it. I've looked over the plans you've drawn up for fire control apparatus. You mean you've been through my desk? Well, you don't make 23 million without keeping your eyes open. Yes, that may be true, but still I... Can it, will you? If Tucker tries to fire you, you can demand to take it to Morgan. Storm his office if you have to. Yeah, that would do it for sure. Well, after seeing what you can do, I believe you could hold your own against anybody. I've read a little bit about Morgan, too. And from what I've read, he's a reasonable man. Yes, to a point, I suppose, but if I burst into his office... You wouldn't lose a thing. And if you take those plans with you, I'll bet you gain a whole lot. Maybe even your own department. Oh, now I know you're out of your head. They're good plans. And it would take a new department to develop them. That's true enough. Why don't you give it a try? Helen and Rita, that's why I don't give it a try. It all comes back to this, though. I can't afford even risk getting fired. Oh, I thought you'd say that. And I figured that angle, too. Now, how much would you say that company's worth? Worth? Oh, four or five million dollars, I suppose. Good business? A fine business. Good enough for me. If you're fired, I'll buy You what? Well, when you've got 23 million, four or five isn't much of a gamble. Besides, it sounds like it might be fun. Oh, brother, I gotta think this one over. Why? The way it looks to me, you don't stand to lose a thing. I'll do it. Yes, sir? I'll do it. Good boy. And you know something? I think I'm going to enjoy this. Hey, Billy Boy, wait for me. Phil, you're late for work. Man, I might say the same about you. Yeah, but I mean to be. You mean to be? You haven't seen anything yet. Hey, I got a couple of extra excuses if you want one. I don't. Well, I wish you luck. You want to see some fireworks? Don't get too far away. Fireworks? What are you talking about? Mr. Harrison, you are late. Mr. Tucker, what are you going to do about it? Hey, Bill, what's the matter with you? What did you say? I said what are you going to do about it? That work I gave you last night I didn't get around to it. You didn't get... You didn't get around to it. Mr. Harrison, I should like to get a few things straight in my mind. Oh, fine. I'll help you.  Harrison, you better get to your desk before I lose my temper. Get to my desk? Did you say get to my desk? I thought you always wanted an excuse to fire me. Well, I'm giving it to you. You know why? Because I don't care whether I lose my job or not, and something else. I've been waiting for years to tell you what I think of you and your methods. That will be enough. I will accept your resignation. I didn't offer it. Oh, well... Everybody in the department feels the very same way I do. We don't like your jump-or-out-you-go policy. And I intend to bring it out in the open by forcing your hand. Well, now, Harrison, there's no use getting emotional about this. Why don't you fire me? As a matter of fact, Harrison, I never had any intention of firing you. Every department head has to exercise his own kind of discipline, you know? So you keep me worrying about my job for years? Well...  You're emotionally, mentally, and, for my money, spiritually, poverty-stricken. Get your things, Harrison. You are through. Get out. Don't know, Mr. Tucker. Not that easily. Wilbur Morgan's the man who did the hiring. He's got to do the firing. I'll have you black-bold in the entire industry. Let's go see Mr. Morgan. All right. Have it your own way. You people! What are you all ducking at? Get back to your work at once. You are through in this business, Mr. Harrison. I suppose you know. Not yet. I'm not. Miss Bevins? I'd like to see Mr. Morgan. Is he alone? I believe he is, Mr. Tucker. But the meeting of the department heads isn't for another hour yet. This is another matter entirely. Mr. Harrison here. Yes, Mr. Harrison. I received a message for you just a couple of minutes ago. A message for me? Yes. I told the woman it was little strange and that she should leave it with the receptionist, but she insisted that I take it. Said to give it to you just before you went into Mr. Morgan's office. Let's see it. Let's see it. Dear Bill have decided not... have decided not to buy the place. You've got the ball now. What are you going to do with it? Love, Auntie. Got the ball. What am I going to do with it? Bad news, I hope. Oh, Mr. Tucker, I... Yes? Nothing. Then shall we see Mr. Morgan? Wait a minute. I'll have to announce you. I'll announce myself. Mr. Morgan, I'm Bill Harrison. I've got a few things to say to you and a few things to show you to make you a lot of money. Now, first of all... Where is she? Where is that old double crosser? Oh, Bill, you're home from the office so soon? Oh, there you are. That's right. Here I am. That was a terrible thing to do. Did you get what you wanted? Yes, but no thanks to you. How much of a raise? I'm afraid to think about it. You can't do this to me. How much? Well, how much? 25,000 a year plus royalties. 25,000 a year? Plus royalties. Oh, I'd better sit down. But when I think of how close I came... Aunt Thelma, did you have to send that note when you did? Yep, I did. Standing on my shoulders wouldn't make you any taller.  That's a very pretty platitude that I own. I'd have to send you the message when I did to give you time to back out. What made you change your mind? I didn't change my mind. Here, Bill, this is for you. What's this? My bill. For what? Read it. For services rendered, I, Bill Harris, and agree to pay Mrs. Thelma Jorgensen $100 a week for the rest of her natural life. Who? Huh? What's this? What services? I helped you make a man of yourself, didn't I? But what will $100 a week mean to you while to me? Well, you forget about your raise. Yeah, but... But nothing. You asked what it would mean to me. I'll tell you. It can mean security, that's what. Security. But $23 million. I don't have $23 million. Everything I got is borrowed except the clothes I'm wearing. And you know how I paid for them? Well, I'll tell you. Working in a prison laundry. That's how. A prison laundry? That's right, a prison. And I'm not your aunt. I served for 12 long years for working confidence games. For 10 of those years, I worked on this. A foolproof racket. Foolproof. Because there's nothing illegal about it. Believe me, I don't understand. I'll lay it out for you. The world is full of bright young men, right? Right. And a good number of them will never go anywhere. Because they think they can't afford to take a chance. Right? Right. So all I have to do is pick the right man and make him think he can afford the chance. Cut myself in on the profits and I've got it made. But tell me, why me? Oh, you were an easy mark. You published a few articles, so I got to know you and a little about you. No living relatives? That made it safe. You worked for an outfit I could check up on. Why, a lot of things. But what if you'd been wrong? I took a month to look you over. You learn a lot about character and the confidence games. If I had thought it wouldn't work, I'd have pulled out and still been ahead for the boredom room. Smart? Besides, well, I got to worrying about the set up. So I wrote Morgan and asked him if he'd be interested in seeing plans like the ones you had. He wrote that he would. Oh, it was in the bag a snap. Why didn't you just tell Bill that? Oh, really, Aunt Thelma? Oh, no honey, the service is rendered. That's right. Fixing it up so he can be his own man again. Kind of fixes it so I'm earning my pay.  Shoot, Bill. Oh, I knew that. Well, now that I'm financially independent and nobody's aunt, have you kids given thought to taking in a ruble? I think it can be arranged, don't you Helen? Well, in our new income bracket I don't know that it would be proper, but I'm sure we'll always have room for dear Aunt Thelma. Right. This is John London again. The other day when I was supposed to meet a movie producer friend of mine for lunch, I happened to arrive early. I went into his office right in the middle of a story conference he was having with two of his writers. They were outlining a very spiritual scene, the crucifixion of Christ on Calvary. In that conference I got quite a shock. These two writers were talking about this scene, about the way that you and I might rehash a prize fight. The language was blunt, to say the least. When the conference was over and the producer and I were having our lunch, I said to him, say, isn't that a kind of a strange way of dealing with something spiritual? Sounds to me like they were getting very familiar with it. He shook his head. I thought his answer was pretty good. He said, they've got to try to understand how the soldiers felt when they pushed Christ toward Calvary. And if they can, try to understand how Christ felt being pushed. If they're going to make the picture look real, they've got to get close to the subject matter. They've got to be familiar with it to make it good. Well, that really applies to us too, you know. We should have reverence for the things of God, but we should make them familiar too. We remember that God is infinite and all-powerful, but we must also think of Him in intimate terms as our Heavenly Father. That kind of familiarity doesn't breed contempt. It breeds love. We should always remember that God wants us to be close to Him. That He's even asked us to bring our needs and desires to Him through prayer. Ten minutes a day, devoted to prayer, will bring us closer to Him and gain for some of the blessings that could only come from an infinitely powerful God. Who, thank God, we can approach simply as our Father. And when you pray, pray together as a family for the family that prays together stays together.  Family Theater has brought you transcribed Mr. Harrison and the Lady Racketeer, starring Harold Perry. John Lund was your host. Others in our cast were Herb Vigran, Polly Bear, Marjorie Bennett, Gigi Pearson, and Gayan Kelly. The script was written and directed for Family Theater by Robert Hugh O'Sullivan, with music composed and conducted by Harry Zimmerman. This series of Family Theater broadcasts is made possible by the thousands of you who feel the need for this type of program. A virtual network which has responded to this need and by the hundreds of stars of stage, screen, and radio who give so unselfish leave their time and talent to appear on our Family Theater stage.  This is Tony LaFranco expressing the wish of Family Theater that the blessing of God may be upon you and your home and inviting you to be with us next week when Family Theater will present The Seven Sun, starring Ricardo Montalban. Bing Crosby will be your host. Family Theater is broadcast throughout the world and originates in the Hollywood studios of the world's largest network. This is Mutual, the radio network for all America.


The study develops a strategy to design and evaluate high entropy alloys, HEAs, for structural use in the transportation and energy industries, using pallets of elements chosen to meet target properties of each HEA family and methods to build HEAs from these pallets. The study shows that intermetallic phases are consistent with HEA definitions and includes both single phase, solid solution HEAs and HEAs with intentional addition of a second phase for particulate hardening. A thermodynamic estimate of the effectiveness of configurational entropy to suppress or delay compound formation is given and a three-stage approach is suggested to systematically screen and evaluate a vast number of HEAs by integrating high throughput computations and experiments. Key components such as materials libraries with microstructure gradients and high throughput tensile testing are currently missing and suggestions for future HEA efforts are given. This article was authored by Daniel B. Miracle, Jonathan D. Miller, Oleg N. Senkov and others. We're article.tv, links in the description below.


So, I say that well let us I have obtained an equal I have obtained some sort of a mean length n right. I can calculate what how much time does it take for a microtubule or an actin sort of to reach this mean length ok. And how do I do that? So, I just look at time scales of fluctuations. So, for example, if I were to add a monomer and let us say a monomer has size a right size a. So, this I did not say. So, for a G actin typically has a size of around 4 nanometers and this tubulin heterodimer this alpha beta tubulin that has a length of around 8 nanometers. So, that is the order we are talking about. So, whenever you add a subunit you increase your length by a. So, this probability of increasing my length by a is my on rate. So, k on times whatever is the monomer concentration C naught times delta t the rate is k on the probabilities k on times delta t into the C naught. And the probability of losing a filament and therefore, shrinking your length by a is simply k of delta t ok. And if you are doing this equilibrium model at equilibrium I have that this C star or k d whichever way I write it that is this k off by k on right. So, if I put this k off by k on over here what that means is that at equilibrium p of plus a is equal to p of minus a right which is why basically you get the dp dt is equal to 0 on an average nothing grows or shrinks. But given that I can now calculate just like I did for the random work I can calculate the first couple of moments. So, I can calculate what is average x which is a times p of plus a then minus a p of minus a which is 0 in this equilibrium approximation because p of a is equal to p of minus a and I could also calculate what is x square right. So, that will give me 2 a square k on C star delta t this is a square p of plus a plus a square p of minus a. And if I took so, this is for a single step this is for a single step if I took n such steps. So, I have a polymer of length n let me write small n then that is nothing, but 2 n a square k on C star delta t. But this n if each step takes the time delta t n delta t is nothing, but the total time that you have you have taken to sort of sample this n. So, this is like my 2 t 2 a let me write 2 a square k on C star let me just write k of t ok. This is a simple sort of a random work that x square grows as t. So, it tells me what is typically a time to sort of generate a microtubule or an actin of length L that is 2 a square k of L square by 2 a square k of that is my variance. And if I now put in these numbers that my k of I said was 1 per second my a was how much 4 nanometers let us say for actin and I choose a filament that is around 1 micron. So, if I use this typical numbers again if I use these typical numbers that let us say my I am looking at a filament which is roughly a micron in length with a subunit that is around 4 nanometers and with the off rate let us say which is 1 per second. I can calculate what time it takes and that time if you put in these numbers comes out roughly around 9 hours ok. So, in order to generate sort of mean length of around 1 micron through this sort of a process through this sort of an equilibrium process it would take around 9 hours which is simply too long if you think back to this microtubule dynamical instability plot they grew and shrink shrunk in a matter of minutes. So, this was of the order of a few minutes right. And similarly for actin if you had to wait 9 hours to sort of generate length scales that process would simply not be biologically feasible. So, although this sort of an approximation generates the correct distribution which is an exponential it gets the time scales completely wrong. So, the equilibrium model is not good enough to explain the time scales as it should not be in fact, there is no reason to assume that this is an equilibrium is yes was 1 upon alpha yes. Did I do something now? Let us 1 upon 1 minus. So, in this in terms of these parameters ok let us just do it once this is this part is fine right. If the probability distribution is that then this is e to the power of minus alpha and dn by e to the power of minus alpha and dn 0 to infinity 0 to infinity. So, let me just do e to the power of minus alpha and dn 0 to infinity this is e to the power of minus alpha n by minus alpha 0 to infinity. So, this is what 1 upon e to the power of minus infinity is 0 minus the number of 0 is 1 minus plus 1 upon alpha. That is that and the top part is integral n e to the power of minus alpha n dn 0 to infinity. So, I will do it by parts first function into integration of the second 0 to infinity minus integral of differentiation of the first function into integration of the second. Tell me if I am making a mistake. So, this is this is 0 because infinity will give 0 here and 0 will give 0 there. So, that I do not care. This is a plus 1 over alpha of this and this I know is anyway 1 over alpha. So, this is 1 over alpha square. So, then this is 1 over alpha square by 1 over alpha. So, 1 over alpha. You are saying the continuum approximation is itself making a check that. So, in principle it is true that this is a discrete sum. On the other hand the n is so large that I do not assume that a continuum approximation would make much of a difference. So, maybe one can show that in certain limits that will come back to this 1 over alpha answer. So, that one can think about. At least in the continuum approximation I think the 1 over alpha is correct ok. So, let me do a slightly more involved model that takes into account the fact that this concentration of monomers itself is a variable quantity. Yes, the concentration of monomers right because P n plus P 1 is it will give your P n plus 1 right. So, this on rate k on is some number per concentration units per time unit, whereas the off rate is just per time because you have to have a monomer coming in and meeting this for it to give you the n plus 1. So, it is it has a constant per concentration unit. So, that is the monomer concentration yeah some monomer concentration which I just took as C star. So, we will relax that. So, now let me say that. So, like I said that often let us say for microtubules you will find that there is this microtubule organizing center from which the microtubules start to manipulate. If you are doing this experiment in vitro then you will generally have to wait until some of these monomers come together to form a sort of nucleus a nucleation sort of a and then it starts growing. So, generally if you were to do in vitro there is a lag phase there is a lag phase where this sort of nucleus forms. In vivo that is not the case because there is already this microtubule organizing center from which it nucleates. After the lag phase there is a growth phase where this thing sort of elongates and then there is sort of a steady state where it does not change too much anyway. So, let me say that I consider a system that has m, m nuclei from which these polymers will sort of nucleate ok. And let me say that the number of number of monomers in the filament is n of t. So, this is a function of time and so, this is number or this is the size of the polymer size of polymer. And I have some concentration of monomers some initial concentration of monomers some initial concentration of monomers ok which is c naught. Now, I no longer assume that to be a constant ok. So, now, what should I do? So, let me say I want to write dn dt right. How does that change? It is. So, there is a k on term ok times the concentration concentration of monomers at time t minus a k of term. Let me move all of these out. So, this is essentially what I did even in the equilibrium model except there I had taken that this c naught is whatever the concentration of monomers was assumed to be fixed. Now, I say well as things polymerize of course, this is going to change. So, that is some c naught of t right. So, how will that depend on this initial concentration? What should I write? So, if I started off with some initial concentration c naught over here after time t how many monomers have I used up? I have used up each polymer uses up n of t right that is enough that is the length of the filament. There are m nuclei. So, there are m polymers that are nucleating. So, there is m into n of t and this is a concentration unit. So, whatever is my reaction chamber I need to subtract the volume of that divide by the volume of that to get the concentration. So, these many polymers remain at time t. If I started off with c naught after time t where I have m filaments each of length n in a volume v this is the number of monomers that remain to me and then of course, this k of term ok. So, now, I have an equation now I have a differential equation d n d t d n d t plus k on m by v times n is equal to k on c naught minus k of this this c naught now is the initial concentration. This is the first order differential equation you can solve this whatever way you want. I will write down the solution you can write down and particular solution in a general solution, but you can solve this and you can write down what this n of t is going to be.  So, again if you solve this first order differential equation you should be able to show that the complete solution is that this is my n of t. This is a constant which you need to sort of put in some initial condition.  These are all constants this is the only time dependent one minus e to the power of minus some beta t. So, basically if I were to look at how the length of the polymer would behave in this case if I were to plot l as a function of t versus t and remember if n is the number of monomers l is nothing, but a into n of t each monomer has length k. So, it is just a into this thing and this is 1 minus e to the power of minus something like this. So, that will just go and look something like that right. When t is very large then you will go to this object whatever l star you want to call.  And this is indeed typically how lengths vary with time. If you neglect the sort of lag phase because I am already starting with nuclei. If you did not start with nuclei you would have you would have a lag phase where nothing was growing and the nuclei were assembling, but then there is a growth phase. So, this is called the growth phase and this is the steady phase. You can do a little better and just even ask that for example, what is this probability to have a filament with n monomers and how does that change with time. So, you could ask what is what is the probability to have a filament with n monomers that is simply the number of filaments with n monomers by n n. And you could write down the relevant reactions for this n monomer filament which is that you can if you have a n monomer filament you can add a monomer to it to go to a n plus 1 or you could take a n minus 1 length filament and add a monomer to it to go to p n right. These are the only two reactions where this p n will appear. So, you can write this d p n d t and again let us say these are kons and kops.  So, this term and this term represents the flow out of the n length filament this and this represents the flow into the n length filament. And given this you can ask therefore, how does this average length change with time? How does this average length change with time? What is L? L is nothing, but a times n of t remember. So, average L is nothing, but a times n into p of n right n equal to 1 to whatever infinity and then you can ask how does this change d L d t is nothing, but n equal to 1 to infinity a n d p n d t and for d p n d t I know what the time evolution is that is this equation. So, I can substitute this and I can do this summation. I will not do this summation you can try to do it yourself or you can check the notes. If you do this summation what you will get is simply that this is a k on p 1 the monomer concentration minus a k of. So, this is basically what we had started off with right p 1 was this c naught minus m k on by v this p 1 is in principle also a function of time. So, if you say that this p 1 is a function of time this that is the equation we started off with. So, if you plot your d L d t as a function of concentration of monomers. So, d L d t as a function of the concentration of monomers then above this whatever c star which is k off by k on you will have a positive growth below the c star you will have a negative growth. The c star is k off yes. So, these are all done in a sort of deterministic not determinism I am neglecting fluctuations right. So, I am saying that yes I have taken m, but I say that each of them will have n monomers. The way to think about this is that on an average each of them will have the same average m, but plus of course, there are fluctuations. So, in principle you should write stochastic differential equations of this and see how important these fluctuations are. So, right now I am not doing that. This is the probability to have a filament of length a n at time t or probability to have more correctly probability to have a probability that the mean length of the filament will be a n at time t. No sorry say that once more we got a expression for the length of the polymer this one yes, but the you have this n of t you can have you have a distribution right it is 1 with a probability p 1 that the mean length of the polymer is 1 with some probability, it is 2 with some probability and so on. So, the average L is going to be whatever a n p n and there there I use this d p n d t this evolution patient that I have written down ok. So, at least I have done a little bit now I can do will make it a little bit more complicated and say. So, till now all my filaments that I have been considering a sort of nonpolar filaments there is no differentiation between the plus n and the minus n. So, I can now relax that and say that well let me consider a structurally polar filament. So, let me draw my monomers like this instead of drawing boxes let me draw a structural asymmetry. So, that one end I will call the plus end the other end the one which looks this is called the barbed end this is the pointed end. So, one is plus and one is minus and what does it is effectively what that means is that what I will say is that I have an association rate which is different at the two ends. So, k of and k on plus and k on and k of minus. So, what it means is that if I write down the rate equations let us say for n plus a monomer that is being added on the plus end that is my k on plus times C naught the monomer concentration minus k of plus and at the minus end dn minus dt is k on minus C naught minus k of minus right. So, basically what this is saying is that what is the rate at which the plus end is growing or shrinking depending on k on and k of this is the rate at which the minus end is growing or shrinking ok dn plus and dn minus and now I can plot these as well. So, let us say again as a function of this monomer concentration C naught I want to plot dn plus dt and dn minus dt. Remember this is basically the if I did not have this plus minus this is basically the model that we just did which grows if your C naught is greater than C star it shrinks if C naught is less than C star. What is C star? C star is this k d basically the dissociation constant. So, k of plus by k on plus, but in a case like this you can show that this also is necessarily equal to k of minus by k on minus that these rates themselves can be different, but the ratios of these rates are necessarily the same. Why is that? That is because let us say I have a monomer like this right and I add a monomer at the plus end ok. So, I get something this structure as opposed to I had this and I add a monomer at the minus end I get the same structure. Once you have this monomer structure there is no way of saying which end you have added the monomer to right it is indistinguishable whether you have added the monomer to this state or this state. Therefore, the free energy difference between these two states delta G is basically the same regardless of whether you add a monomer here or you add a monomer here and that free energy difference is just a function of this. So, k d is basically like e to the power of delta G by k v t right and if the free energy difference is the same regardless of which end you added the monomer to it means that this dissociation constant or the equilibrium constant must also be the same for both these cases which means that this it is a very nice argument it says that this regardless of how different these rates are in a model like this the ratios of these rates must necessarily be the same ok. Another way to think about this yes why do you say at the minus end this will be greater than that realistically that is what you are imagining. So, then that is the point that this this model then says that let us say that the plus end will grow something sorry I should pass it through here that the plus end will grow like this the minus end will grow like this the slopes will be different, but they will intersect at the same c star. So, when something is growing both ends will grow if one end is shrinking the other end will also necessarily shrink which is not a realistic model for example, tread milling where one end is growing and another end is shrinking. So, this is a nice argument which actually precisely says what you are saying that this sort of a model what I have written down cannot be the correct model if I wanted to explain something like tread milling where the plus end is growing and the minus end is shrinking what do I need to do to do that what I need to do is to then say that well what is being added here is not what is being taken out here what is being added here are these GTP subunits. So, I have a rate plus T what is being taken out here are these GDP subunits. Once I have this structural asymmetry this argument no longer holds because now this delta G can be different ok. So, once I have these rates that here it is being added with this what is being added is different from what is being taken off what you could have in principle if you were to draw that phase diagram is something like this again if I plot. So, let us say I will have something like this and something like the two slopes look very similar let me make the two slopes different let us say I have something like this. So, let us say this is my d n plus d t this is my d n minus d t ok. The slopes are different which is what in the earlier case as well, but the c starts are also different this is c star plus this is c star minus right. So, you can have a concentration range a concentration of monomers where one end is growing and another end is shrinking. In fact, you can find exactly a concentration with the velocity of the plus n plus v is exactly equal and opposite to the shrinkage velocity of the minus it which is like the perfect tread milling situation and you can work that out as well. So, the condition for tread milling if I wanted to do like that the condition for tread milling then is that d n plus d t is equal to minus d n minus d t. So, the length of the polymer is a whole remains constant the plus n grows with some velocity the minus n shrinks with exactly the opposite velocity. And then you can calculate at what concentration this will happen. So, if you work this out. So, remember now my equations are these are being at what is being at the plus end or these GTP or ATP subunits at the minus ends or these GDP or ADP subunits. Let us say ADP since this is like tread milling of actin in which case you will get a tread milling concentration of something like k of plus plus k of minus by k on plus plus k on minus. So, the k of plus is a d now the k of plus is a t this is a d the plus is a t this is a t ok. So, if you solve this d n plus equal to minus d n minus you can solve for this C naught which is the concentration of monomers at which you will get perfect tread milling and a model like this will give you a tread milling sort of a scenario. And in fact, you can see actually that if you plot the lengths of the growing and the the plus end and the minus end the curves do look indeed something like this for real actins if you look at experimental curves.


I'm going to talk about, yeah, it's titled over here, Structural Biology of Stimulary Responsive Namasellulose Interfaces. That is work that we have done over the past, I would say maybe eight to 10 years. And it is framed a little bit in the motivation to give some answers, some ideas how to fight global obesity. This is a map that is updating, and you see how the work is getting bigger. And the idea of tackling that problem, of course, there are multiple of them. We have tried a lot. Most of the stuff is of the ideas are not really working simply because we are not forcing ourselves to really adhere to the rules. So the general idea is that one has to, or that we try to reduce overweight and obesity. And there's a lot of ideas, as mentioned before, we have ruled out fat as ingredients that is creating overweight and obesity. We have, we came up with artificial sweetness. And then of course also we have the discussion on fibers and fullness. And more recently, people are talking about interaction with mucus and biofilms in the small intestine. And what I would like to come up, or what I would like to discuss over here is actually playing around with the lipid digestion and the lipid uptake. Basically, we're thinking a little bit the role of fat. And that was introduced 10 years ago by Matt Golding and Tim Booster at that time at CSIRO in Melbourne. Basically saying that when we have fat in our food, we actually also are able to, our body is able to induce satiety hormones that are going to stop eating. The problem is that we take our fat, it is digested in the stomach and then it's more than in the small intestine. So the problem over here is more that we have to get the fat to the right place. And this concept is put together in the concept of the iron grate. So that once the lipid is reaching the small intestine, we have the triggering of these satiety hormones. So that is of course happening normally at the end of the meal. We would actually like to do that at the beginning of the meal. So having actually fat going there, not digested. And that is now the problem that we have that basically it will be digested in the stomach and that goes already pre-digested in the small intestine. So it's really just not working when we have the first bite of fat that we are eating. And the idea is now to generate lipid emergence that are going to survive the stomach. So that is an idea that was put up 10 years ago. We followed that a bit and we teamed up actually also with people from the university hospital next door. And when you're going to hear some emergency vehicle coming arriving over here, it's just simply because my office is just next to the emergency room. So the idea was then carried on, as I said, with people from the university hospital in Zurich. And these are images of different emulsions and actually the gastric content volume wise when feeding or when putting people in an MRI device. And what you see over here in the white areas, this is basically the stomach. It is filled with a fatty solution and emulsion system and it's back down and depending on the structure, one has different gastric volume over time. So that is monitored over two hours, three hours. And we see that actually the structure is very much changing over this time and actually also those, the emptying of the stomach. So here we have already an indication that we have a control on the food. Digestion, the stability of the emulsion, controlled by the stability of the emulsion. Good, so that was a little bit of the framing and indication that by designing food, we have a direct influence on, for example, the gastric volume, the emptying of the stomach. Now the problem is how to make these these emulsion systems so that they're stable in the gastric environment, but they're breaking down in the intestine environment. And what we have to consider here is the different pHs, the mechanical stresses that we have in the stomach, even though I'm not going to talk about that. We have mucus in both stomach and intestine. We have changes of joint extension, of course, also temperature is body temperature. So from the food that we take, maybe at 20 degrees or whatever, it is going to be heating up to 37 degrees when we don't have fever. And so these are a lot of boundary conditions to basically have these emulsion stable. And what I'm going to discuss a little bit in the following are actually four steps that we made to go from not only the design of the emulsion, where we actually looked also a little bit more deeper in neutron activity measurements, but we also would like to understand how these emulsion is then stable in vitro environment. And then, of course, also, if the entire idea is actually working in vivo. So here at the very end, I will also present you some experimental data that we have obtained from humans and from rats. Okay, how to make these emulsion? Or let's say the interface of these emulsion. Well, classically, a lot of food emulsions are stabilized by proteins. This is a summary of the adsorption of proteins, conformational changes to network building of a gel or more glassy interface that is stabilizing the emulsion. There's a lot of work on that. I always like to refer to the PhD thesis of Benjamin's from Wageningen University, who really nicely put that together some 20 years ago. But there's a lot of extensive work on that area existing. The other system that became a little bit more popular over the last, I would say, 10 years, as you see also here with the citations are particles. And when you look into literature, there's actually a whole bunch of particles that have been investigated. So starch, flavonoid crystals or particles, ketene, zinc, and in particular, cellulose, and or cellulose nanocrystals. I'm going to stick with the cellulose nanocrystals for the rest of my talk as we, in the beginning of the project, actually screened the others, but found that the cellulose nanocrystals are most probably the most potent candidate for stabilizing the emulsion, in particular when mixing them with proteins, as we will see later. There's a lot of work done in that area over the last 10 years. And I just mentioned to a few articles that are both very recent, that are putting these work together. So the first one is from the Leeds Group, Sakha and Dickinson. And then later on, we also had a review on that. But I also like to mention that others like Kalashnikov I also have written nice overviews on the last 10 years of this research. Good. So what we now looked into a little bit more in detail is that we used crystalline nanocellulose and modified them in different ways. So what we see over here, so this is all work that we have done over the last years, we used unmodified cellulose, we methylated them or esterified them. And the unmodified one is relatively less surface active. So here you do see changes in the adsorption basically by the addition of the salt. With the methylated one in the middle, we see that methylation actually increases the adsorption of the particles at the interface, increasing the surface pressure. And with the esterified material, it's a little bit more tricky because they really just have to spread by solvent and will, as we see later on, build a relatively patchy layer. But that is the zoo of the cellulose particles that we used and we, I mean, modified them in different ways. So basically playing around with the hydrophobicity of the material and looked into their adsorption, their rheology and their structure. And for the first, a very brief introduction to the method that we use for the interfacial rheology. So this is the bicone setup that we have developed some years ago where we basically measure elasticity, viscosity, viscosity of these adsorption layer between oil and water or just between water and air. With all these cables that you see or tubings that you see on the left-hand side, we are changing the environmental conditions. So this is basically our little stomach or intestine that we are using. So here we can change pH, we can add life paces and increase temperature to see what is going to happen with these layers when we are going to physiologic conditions. And one example over here is beta-lactyl globulin. So a protein that we adsorb at the interface between oil and water. So we see G-prime, G-double-primes or elastic and storage modulus as function of time. And we did a lot of now steps that are sort of linked to the two digestion. So we heated up to 37 degrees, we used the pH and then we added pepsin. So you see for all these steps actually the interfacial layer structure is always becoming lesser and weaker in signal. And eventually after a few hours completely is destroyed. So that is something that we actually don't want in this situation, that the emulsion is actually broken and digested already in gastric conditions. So here we're not going to bring these emulsions into the small intestine. And now a little bit closer look to the methylated non-acrystalline cellulose that we have used. So you have here again the plot of the surface pressure as function of different methylation steps. And you see that with increasing methylation the cellulose goes to the interface and reduces surface tension or increases actually surface pressure. Material is normally a few nanometers with and the length is about 10 times of that. So we have work like aggregates that are now sitting at the interface establishing a layer there. And what is also important to see is or actually a benefit for us is that these methylated celluloses they do a thermal dilation normally embark that it is it's around at 50 degrees Celsius at interfaces it's far lower. So it's 22 degrees. And what we see here is when we increase the temperature we see that G prime, G double prime is also increasing. So here we have a thermal dilation that actually also helps us to stabilize the emulsion with a layer of celluloses around. And when we look to the right I think we have over here shows to prime G double prime for the different methylation steps. And we see that these thermal dilation is helping us a lot in particular for the material that has the highest methylation steps. So we start the three, four and five at the very end on the very right end of the graph. So this is a benefit that we have certainly when trying to stabilize the emulsions. And now I'm just showing you the same experiment that we have done now with the methylated cellulose and the better like the globulin together under gusted conditions. So it's the same experiment that we've done with the better globulin alone. But what you see over here is that in every step that we do accept maybe the addition or the change of the pH the layer is actually getting stronger. So we add the methylated cellulose. It builds up the layer that is a composite layer with a better like the globulin temperature increase induces a thermal dilation and the addition of pepsin. So gastric environment is actually not changing things at all. So here we have a nice proof that or at least from the interfacial biology that the material is really resistance against the gastric environment. So the emulsion stays intact. And now let's turn a little bit to the neutron reflectivity measurements that we have done for these materials. So what you see over here is well the normal reflectivity curve as function of the scattering vector. And we don't have too much features over here. So the curves are relatively flat which we actually all see for protein systems at least food protein systems throughout the way. But what we are going to see is that with the thermal dilation actually also the layer structure is changing. And with, I mean, playing around with fitting we basically can come up with a model on the right hand side so that we have a 22 degrees Celsius. Some of the material sitting at the interface approximately 13 angstrom thick but relatively diffuse layer penetrating into the bark. And when we are now going to the higher temperatures so 70, 30, 70 degrees we have a more compact layer that is thicker about 150 angstroms of thickness. So here we already see the thermal dilation is kicking in and helping us to build a layer structure that is protecting the interface. Now in the next step or in the next graph over here we put together the experiments with the different ingredients that we have. So here we are talking or we have actually the pure water-air interface. We have the better lacto-globulin layer. We have the pure methylated and the crystallized cellulose. Then with better lacto-globulin together and in the final state actually also the compressed one. And depending from the reflectivity curves so the upper right we again calculated scattering density and basically came up with the cartoon in the middle where we have the better lacto-globulin layer about 20 angstroms, methylated cellulose 120, 150 and then the composite layer, the same thickness. So we have indication that the better lacto-globulin is really used is the cement between the cellulose and we can even by compressing not really changing that structure too much. Okay. So that is a little bit of the situation for the methylated cellulose. So this is actually the cartoon over here in the middle. And I also would like to show you the two other materials that we have used the modified and the esterified material and try to give a little bit of a summary what we have observed them. So maybe for the starting with the unmodified material here, we see a relatively slow adsorption. So it really takes hours and that is most probably also the reason why there are sometimes indications in the literature that it does not observe. Actually it does, but you really have to wait hours. You can increase the adsorption by salt. So that is something that tremendously pushes the particles to the interface. But actually it's a relatively discontinuous layer and the coverage is very small. So basically for the idea that we had, it's not appropriate. The middle one, the methylated one as discussed before is a monolayer that we can with a thermal dilation push into a multi-layer structure actually also with the metal lacto-globulin as a composite, then being relatively stable or actually very stable, fugastic environment. You would see that in a few slides down the road. The last one, the esterified ones is we always can spread that with solvent so they didn't absorb from the bark due to the hydrophobicity. And here we have a system that actually has a relatively high contact angle. And as a result, we see actually a system that is more aggregated and building clusters. Interesting, and here again, same system, but now microscopy images. So for the unmodified, you see actually nice distribution but still it's not really a continuous layer. Methylated, a more dense one and the esterified, the clustered one. I mean, in the lower row, we see actually the rheology signal of the material and I really would like to point out to the lower right one for the esterified one. Here we see a Maxwell kind of behavior of the adsorption layer and I think that is one of the very few examples where that is going to happen. So normally it is just a gel structure that we observe for these kind of materials that interfaces and most probably due to the contact angle and we have the situation that the material is behaving as a Maxwell figure. But that is more a little bit of a side note. Okay, and now the question, does that stuff really helps us to survive with a droplet in the gastric environment and the intestine environment? So what we have done here in the first step are in vitro studies, we used lipases, we also used mucus and we looked into the structuring of the food during the digestion. So that was done with a marginal system that was MCT, so medium chain triglyceride at water systems and we also used recombinant top gastric lipases for this experiment. So the first experiment is actually microfluidics one. So we made our emulsion and we kept the emulsion droplets covered with cellulose and beta ducted globulin in little traps as you see in the picture on the right hand side over here. And then we were changing from the generation mode, making the droplet to the digestion mode and we added now different first gastric and then pancreatic lipases to digest the droplets in the trap. And what you see in the lower row is basically a field trap on the left hand side then coalescence the digestion of the droplets and then eventually to the far right disappearing of the oil droplets. So here then the digestion would be over. A little more in a transient way, actually you can see these with now two videos. The first one on the left hand side is starting. So it shows the droplet in one trap. You have the gastric environment when nothing is happening and then in the pancreatic environment the droplet is disappearing. So simply saying that in the gastric environment it survives and once we switched to the pancreatic environment it doesn't. The next movie is more or less doing the same thing. So we have the gastric environment, nothing is really happening. And then in the pancreatic environment is actually the droplet is breaking down rapidly not only having coalescence, just showing the movies again right now in parallel. So you see gastric nothing is happening at least minor things maybe coalescence and pancreatic does dissolve. The pictures put together here in the graph. So you see in the gastric environment relatively small changes of droplet diameter we have a few coalescence effects over here. So that means that the diameter is becoming larger but once we go into the pancreatic environment within let's say 15 minutes or even less the droplet are all digested. So basically the achievement that we survived the stomach and have the release of the fat in the small intestine is given. And now last thing for the last few minutes is does it work with humans and with rats? And so for that we went back as mentioned before to the University Hospital running MRI signals. And what you see here on the left hand side is stomach so the white circled with a yellow circle or circle fence there.  And now with the data processing we actually can also say what is fat and what is water. So the blue one is water. And you see that the fat layer is red on top of the of the emulsion sorry of the stomach and content over here and black again is air. So that is a whole bunch of calculation and procedure. I'm not going to look into that into detail actually also and not really my competence over here. What we have now is in the end these figures. So this is actually the stomach of the first author of the paper that is down there. And she was drinking these three emulsion systems and one stabilized with beta-lactoglobulin methylated cellulose and nanocrystalline cellulose. And what we now can nicely see when we scan through the with the MRE through the stomach that we have for the beta-lactoglobulin decreeming. So here the emulsion is breaking up it is digested with the methylated cellulose we have a dilution effect and with the nanocrystalline cellulose we have a structuring. So here the situation with the beta-lactoglobulin basically is the solution of the emulsion. So we have a digestion going on and for the two others we don't. And we have then now modern monitor that actually also with the gastrointestinal responses. So we look into triglycerides in blood, plasma CCK and the gallbladder volume. And what you see here is a very rapid response to the wave protein isolate. So beta-lactoglobulin simply saying well the emulsion is breaking down. We have uptake of fat, triglycerides are going up, satiety signal is coming up as well very rapidly. When we go to the methylated cellulose it is all delayed and flattened. So basically what we would like to have to see when we go even to these very high methylated nanocrystalline cellulose the signal is almost not there. So that means that here we don't sense any of the material. So it is so stable that it is even not digested in these timeframe that we have. So that basically also says well with monitoring, manipulating the interfacial structure of the emulsion we really can trigger different gastrointestinal responses. So hormone releases fatty acids in the blood and the method I think we can conclude it's showing that with the structuring we can really monitor and control the takeout. Last picture is with accumulated food intake with rats. So you cannot do that with humans feeding them for two days or even more with these emulsions. So we have done that with rats and you see that with the way protein stabilized food intake basically they're eating constantly with the nanocrystalline cellulose, the black one they are eating but then they're not changing or eating more after the two hours or three hours while with methylated cellulose we have lesser food intake compared to the two others but it's actually also relatively rapidly at the beginning and then stays constant. So here again the two cellulose systems basically show in a different way. I mean for individually differently that food intake can be actually controlled by the interfacial structure. Okay, and with that I'm going to finish. So what we, I hope that what I could show you is that by designing interfacial layers with different materials in particular here with proteins and celluloses one can generate emulsions that are differently behaving towards both in vitro and in vivo gastric and interstellar environment and by that helping to structure firstly the food emulsion that we have and by that also controlling their digestion and the lipid take up eventually in the small intestine. And yeah, I think with that I'm going to finish and thank you for your attention. Thank you Peter, it was a very nice talk. I'm sure all my colleagues enjoyed it as well and we have a few questions. So I'm going to start by asking Lawrence, we have a few minutes so I can actually ask the person to ask the question live. Lawrence, are you? Yeah, yes. Can you hear me? Yes. Yeah, Peter, nice talk. It was just a curiosity. You showed that there was a huge difference in gelation temperature at the interface and in the bulk and I was wondering whether you know where it comes from? Yeah, well, I mean the methylated cellulose is gelling at higher temperature. That's an effect that you basically exclude fluid volume in the environment of the cellulose. And I mean that is working in bulk and I think as we are constraining the system to more or less 2D by the adsorption we have less, let's say free space available and then it actually kicks in earlier. So it needs less temperature increase to do so but that is really speculation. I mean we never, I mean went into that into full detail it's, yeah a little bit, I think that the problem when you go from 3D to 2D that some of them, yeah let's say environmental conditions are changing. So the same thing with, I mean, actually also the viology response that we almost just see less, I mean gel-like or rubber-like behavior but never behavior like a Maxwell fluid. So yeah, okay. Thank you. Tommy also has a question on the reflectance data. So Tommy, when I asked the reflectance data question. So Peter in the first curve that you show on the neutron reflectivity on the cellulose layer it seems it implies that there are two layers. There is a kink in the SLD profile. Sorry to be very detailed but. Yeah, no problem. So do you think that the layer next to the surface is denser or different than from the more extented layer because it seems that there is a difference in there. This is, so that, that one. Well, I mean, you mean this one over here or the- No, that was wrong. Okay, let's see one more up. That one over here. No, I think that was, that's the better like the other one, that one, yeah. That worked one way. It implies to me that there is a, because you see like a plateau layer and then there is something wide distribution. I mean, that is, well, you know that better than me. I mean, getting a final structure out of these needs a little bit of art and imagination. And we basically came up with this conclusion over the drawing in using also these AFM images that we have. And so the layer structure at the top, I think as you said is indeed a little bit denser than when you go into the, closer to the bulk.  I think still there is always a little bit of interpretation left and maybe other ways to say, but we know or we always do these or did that fitting also having the AFM images in mind. And that's the way to do it, I think. Maybe another contrast also could have. Yeah, yeah, yeah. Okay. There's a question from Kirsten. Kirsten, would you like to ask it? Yeah, this is a little off another track, but I was thinking about if these emulsions can be sort of too stable for a quality in the perception and the sensory but this is two things that I have to say over there. The MCT oil that we used in the first experiments, it was sort of a very creamy emulsion.  And the situation with the MCC with the methylated nanocrystalline cellulose, there the emulsion is so stable that you basically just eat a filler. So it's almost, I mean, eventually yes, but I mean, it's almost impossible to penetrate that layer in given time. Of course, we haven't considered any motion and mixing in the stomach. So from that point, maybe it's also different. But I mean, coming back to your question, from the sensory, the stuff is all not nice. And the idea initially or let's say how we actually yeah, we're thinking of using the material is sort of in form of a salad dressing or something that is not a drink that you where you drink 200 milliliters before starting eating or something like that because then I think the meal is spoiled. So we basically have to camouflage that emulsion system in a way that people are still drinking it. And that is really a big problem. Thank you, Peter. There is also a question related to microfluidics and how you did the in situ digestion work. And actually I'm gonna expand it a little bit and we have only one minute left before the next speaker. But if, what happens between the gastric and the intestinal? Do you wash the digested material out or everything stays there? And Tommy's asking also if you had bile salts in the system. I mean, all these experiments, they were done as closely as possible. And I think a big difference to most of the in vitro studies is that we kept the digested, I mean, we wash out the digested material in the gastric situation, but not too much is happening. So everything is still left but structured by the gastric environment before we are going into the pancreatic environment. So it's really not that we do two different steps we do as it is going to happen in real one after the other. So that, and that actually also shows that the pre-structuring that we have of the very stable emulsion in the stomach is has an enormous impact on the pancreatic digestion. So it would be certainly differently when we expose the emulsions individually first to the, or parallel to the gastric and then to the intestine situation. So it's really in one after the other like it happens in vivo. Yeah. Okay, well, thank you, Peter.


Good day, fellow investors. I recently came across a very interesting Bloomberg article about Jim Radcliffe. If you're not from the UK, you probably never heard of him, but he is the richest person in the UK and valued somewhere at around 14 billion. He doesn't have a publicly traded company, so he's not that famous, but I think find it extremely interesting how everybody talks about Bezos, Zuckerberg, Buffett and all the top five richest persons, but I think that those who have between 1 billion and 20-30 billion deserve even more attention because they are closer to us and we can learn more from them. And I went to the article and there are five interesting tips, investing tips for us investors that we can all apply to our lives, our portfolio and to our investing that might help us in the long term. So let's see what the richest person in the UK has to say. So don't worry about starting late. He became an entrepreneur at 40 years old, so he's now what a little bit older, but still at 40, if you are below 40, it's not late. And even if you are 60, you don't need to come to 14 billion. If you come to 1 billion, that's amazingly good. If you come to 100 million, I think still good. 10 billion, for me still good. A million? Well, we can debate on that. I look forward to your comments whether a million is enough or not. Now, number two, make friends with debt, but don't fall in love with it. In 2005, he bought for 9 billion inovine petrochemicals from BP. When the crisis came, the debt covenants were breached and banks made it really hard for him to refinance and made him pay extra charges. So he says that was pretty risky and he has lowered the debt now. The learning lesson is here. Yes, take advantage of that. But please make it in a smart way. Warren Buffett was always leveraged 1.6 times, so he wasn't leveraged 3, 4, 5 times. He was leveraged 1.6 times. So also I'm leveraged, I have a mortgage, but I see too many of you having still the margin debt, buying on margin in this environment, taking crazy loans, investing on credit cards, and that's something crazy that should not be done, because that's really betting that everything that you think will happen in that time slot that you have to repay the debt. And the second lesson here is that debt covenants, debt environments change very, very abruptly. Let's look at what happened with Turkey. Five months ago, everybody was happy. Interest rates very low. Everything is okay. And now nobody wants to give a penny to Turkey. And similarly, that can happen personally, privately. Banks can tighten whatever. So never think that the debt environment currently in place will last forever or that it might not change very, very abruptly. So that's something to keep in mind. Now, to quote, Redcliff is dismissive of 20-something equity analysts, still in short trousers, and pretty averse to non-executive directors. So be careful with equity analysts. I was recently reading reports from all the big investment banks about Chinese toll roads that I also made a video about. And they were all very positive about investing there. All made discounted cash flow models with weighted cost of capital, et cetera, et cetera. And everybody was buy, buy, buy, buy every stock in the Chinese transportation sector. Now, when I see that I say, okay, why would you say that everything is a buy? Oh, yes. So that you can sell it to your clients. And then again, what they didn't put into the models were the long term factors that really put me off from investing in Chinese toll roads, like concessions, expiration, like debt piling, piling and piling, not being repaid in the same line as the concessions expire, expecting something new, something booming and increasing the dividend because you're not repaying the debt. But those are the fine things that an analyst that was just hired, or that simply follows something else that they learn somewhere at the hotel at a weekend training simply cannot really estimate from a practitioner perspective. Red Cliff is a practitioner and 99% of the rest of the world are not practitioners are academics analysts. So they don't have their money in debt. So that's a big difference. So always follow practitioners. Buffett is a practitioner monger. And don't follow really those that are not practitioners, but they don't have their money where their mouth is. That's key. If we just look at targets and ratings for general analysts for the SAP 500, on average, 53% of the market is a buy for them. And then 42% is a hold. And only 6% of the SAP 500 is a sell. Of course, the most cells are utilities, consumer staples, telecoms, and less cells are in information technology materials even less, because everybody expects oil to go to 120 now that it went to 70. When it was to 40, everybody was selling oils or having a lot of holes. So really take with take those analysts estimations with two grains of salt. Number four, something that I have fortunately done with my research platform, I didn't sell equity. I had the opportunity from a big American investor to sell equity in my company, and really make everything big, shiny American. But I would have given 50% of my company forever 50% of myself. And I see it financially, it wouldn't end up positively. So I probably would have destroyed my career. So really, if you really don't need to give up equity, when you own a good business, when you own a bad business, give up equity, take the money and run, of course, like Snapchat did. When you own a great business, you never want to give up equity. And you don't need to go public.  He needed the money. So it's not such a great business. If not, he would never go public. He would have owned 100% of the company. And he would have done greatly. So that's a big, big difference between going public and not and taking up equity. Also for us investors approaching an IPO, why are they are going public? Do they need the money? Are they so good? Then why don't they make the money themselves? And there's always a debate there, whether it's something is good or not. And number five, he says, keep it tight. His holding company has 40 people that work on 6 billion on earnings before interest, interest, taxes, depreciation, amortization. He is not keeping it that tight because Berkshire has 24 people employed. So the message is, of course, this is a joke.  Finances investing is about simple things. So keep things simple, keep things tight. And you, your investment returns will be extremely, extremely positive. Thank you for watching. I hope you enjoyed this. Looking forward to your comments, add some points if you have them. And I'll see you in the next video.