This is Orson Welles, speaking from London, Black Museum. Here in the grim stone structure on the Thames, which houses Scotland Yard, is a warehouse of homicide, where everyday objects, a picture frame, a coat hanger, a file folder, a baby buggy, all are touched by murder. Here's a hammerhead made of cast steel. Well-shaped, extremely familiar. The front end blunt, solid. Designed for driving nails, the clawed prongs at the rear for pulling nails. Very practical, very, very, very familiar. And so very, very, very lethal. Odd one, this, wasn't it, Inspector? Just a little extra patience, a little extra routine work, Cross? That's one way to look at it, sir. My preferred to remember it as the case which began with almost two dozen disappearances, and wound up with one killer who used a hammer with purpose. Well, today that hammerhead can be seen, here in the Black Museum. The annals of the Criminal Investigation Department of the London Police. We bring you the dramatic stories of the crimes recorded by the objects in Scotland Yard's Gallery of Death, the Black Museum. In just a moment, you will hear the Black Museum starring Orson Welles. Now the Black Museum starring Orson Welles. The Black Museum, Scotland Yard's Museum of Murder. Beyond these walls, the Thames seeds with a commerce which is life to London. Within these walls where some of the river's dampness exudes from vaulted stone, there is quiet, very sinister quiet. The kind of silence which inevitably surrounds objects touched by horror and fear. Yes, here lies death. Behind glass doors, peaceful inanimate objects on deal tables. The authorities have provided suitable identification in labels and neatly-lettered cards. The motives, actions, and the reasons why these objects rest here now were all provided by murderers. Here's a calendar. The usual twelve-page printed piece with a picture of a pretty girl decorated. The holidays are marked as usual in red. One other day is marked as well. A day and date of a murder. Strangely, that red circle led to capture and conviction of course two, execution. Now here we are. Here's the hammerhead I told you about. It's an efficient tool. It's hammerhead, type used by generations of carpenters, by millions everywhere for work around the house. Hardly a home is without one. And one would expect that a story involving such a tool would begin in somebody's home. On the contrary, this tale begins in the direct antithesis to a home. It begins in a London railroad station. Let me have my bag, will you? Yes, sir. Your check, please. Right, you are. Thank you, sir. Here you go, sir. Hey, that's not my bag. Mine's a Gladstone. Oh, sorry, sir. Just let me see the checks. What's wrong? Are you sick? No, sir. It's just my hand. Cut yourself? That's blood. Yes, I know. But it's not a cut, sir. It's from the bag. Well, open it, man. Don't stand there. Yes, sir. Doesn't seem like much of a lock on it, sir. What does one do now, sir? When you find part of a body in a police, you call the police, of course. What else? Yes, sir. Please wake up, sir. I'll call them. Yes, call the police. Start the wheels moving, the wheels of police routine, which grinds slowly but inevitably toward discovery. In this particular situation, the call led eventually to the office of Inspector Church at the yard. The information cross, the contents of that police at Charing Cross, belong to a torso found in Brighton. Another one in Brighton, sir? Number 23, 23 girls missing. Just unreported. Photos available, sir? In most cases. Here's the assembled composite of the latest. Hmm. Pretty little thing. To wind up so widely separated as London and Brighton, here's the setup for now. I'm assigning a man individually to each case. Identify any found bodies, trace the known missing. I'm taking Daisy Baker myself. You'll take over here, and all the information will channel through you. Very well, sir. Why the Baker girl for yourself, sir? Well, she is, or was, the common law wife of Jamie Marsden. That one! Remember him? Oh, picked him up in his first conviction, himself. Rather a long record, hasn't he, sir? All petty crimes, short sentences. In any case, the Baker woman's been reported missing by her sister. It might be worth the trip to see the sister. Her name is Crandall, Ruth Crandall. Before I drop in at Marsden, I think I'll visit the lady. A routine call to inquire the reasons for a woman's worry about her missing sister. Inspector Church found Ruth Crabble at home. So, when I plan to go down to stay with Daisy, well, to see her anyway, and the wire came, will you see how it is, Inspector? May I see the wire, Mrs. Crandall? Yes, I have it just here, in the desk. Yes. Yes, here it is. I see. Going abroad. Good job. Sales Sunday. We'll write. It doesn't tell us very much, does it? Well, I tried to call her husband. Well, he wasn't very cooperative. He said she'd upped and packed her things and told him she was bound for Paris for a dancing job. Oh, Miss Baker is a dancer? That's how it was, she was living in Brighton. She was in some show down there. And you feel something is wrong? Definitely. I don't know exactly why, but will you see, the wire doesn't even say love. And that makes it seem strange too, doesn't it, Inspector? Perhaps, Mrs. Crandall.  Except, of course, that I haven't heard from Daisy since the wire came. Inspector was puzzled. None of it felt right, none of it conformed at all to the usual pattern. Ruth Crandall had nothing factual to go on, and a woman's instinct is never evidence on which to base an arrest or a conviction. Still, the Inspector took the train to Brighton and called on Jamie Marsden at 35 Park Road. Yes? You remember me, Marsden? Uh, Copper, ain't ya? Yes, Chief Inspector Church, CID. Well, come in, Inspector. I don't suppose this is a social visit? No, I'm a bit busy for that sort of thing. Oh, well, sit down anyway, Inspector. Just a few questions. Well, go ahead. I hear you married since we last met. Yes, I did. Nice girl. She home? Well, um, no, as a matter of fact, she's, uh, she's gone off to Paris. Her job is a dancer over there. So her sister told me. Yeah, well, she wired her sister. Nothing much my sister-in-law would want to see me about, so, uh, well, there wasn't much sense in her coming all the way down to Brighton when Daisy wasn't here. I assume you have your wife's address. Uh, well, uh, no, Inspector. Well? We had a bit of a dust-up four days he left. She, uh, flanced out of here. All kind of mad, as you might say. Mrs. Crandall knows this? No. Mrs. Crandall don't take to the likes of me, so I saw no reason to tell anything she didn't have to know. If Daisy wants to reach her, she knows where. Well, that's it, I suppose. You'll be here if I want to see you again, Marsden. I'm moving. Three rooms is a bit large for me, seeing as I was on my own these days. The, uh, new places at, uh, Maitland Street, um, number 26. It's a good bit cheaper. More suited to my means. A check of the habitual haunts and acquaintances of Daisy Baker drew another blank.  No one knew where. Meanwhile, reports on other missing girls were equally discouraging. That's the lot, eh, Cross? That's the lot, sir. Well, and, uh, another missing one reported makes an even two dozen, sir. Have they tried the picture of the girl we found in Sharon Cross on this new report? And not the same girl, sir. Too bad. No luck with Marsden, I presume? No luck at all. Edgy's on a fellow, that one. Yes, he ought to be. He's much too familiar with us, and he knows it. Well, there's no help for it. It'll have to be a house-to-house search. The usual district, Inspector. All of Brighton. Rather a large order, Inspector. Finding 14 missing girls and identifying six of 10 bodies is quite an aura cross. There's no help for it. It'll have to be done. Chances are we'll have to lend Brighton... The hard-doll slogging of police routine. Divide a city into sections. Assign groups of detectives in pairs to each section, then walk from house-to-house from cellar to attic. Pausing for the questions. Questions, questions. Try to locate someone who has seen something who may know one of the missing persons by sight. Try. Keep trying. Well, there was nothing there. It's jobs like this, Inspector, that make me wonder why I want it to be a policeman. It's jobs like this, sure, that make good policemen out of ambitious young men. Well, next address. 26th, Mainland. I expect Jamie Marsden who won't be looking for me this quickly. Marsden? Who's that? Oh, Petticriminal. His wife was reported missing by a sister. Turned out she'd gone off to a job in Paris on her hub. Knock on the door, sure, will you? Yes. Sorted kind of story, even a touch of the dope rack in it. Yes? My credentials. CID. Also a search warrant. Well, your men did something getting wasted any time. The police come in. Waste any time? I called the police about five minutes ago. They said they'd sent someone over. Who's the landlord? I am, Inspector. Well, we're here on the matter of our own. However, what's the trouble? Notice anything, sir? I do. How about you, Shaw? Yes, sir. I do. It's from this room. The tenant is out this now. Left his door locked. Name of Marsden. Well, is that so? Just as well, we have the search warrant. Try your shoulder on that door, Shaw. Yes, sir. We've never had anything like this before, sir. Well, nothing much here unless it's on the walls. There's a truck in the closet, sir. Drag it out. Cut those cords. Yes, sir. Of course. Good Lord. May I stay outside, Inspector? Yes, of course. I wonder, Marsden isn't home. Well, Daisy Baker didn't go to Paris after all. Took quite a beating, didn't she? Looks like a blunt instrument did the job. Call headquarters, Shaw. Pick up order for Jamie Marsden. Today, that hammerhead can be seen. Here, in the Black Museum. In just a moment, we will continue with the Black Museum starring Orson Welles. And now, we continue with the Black Museum starring Orson Welles. The wires were alive with a search for Jamie Marsden. Somewhere in England, the little petty thief was hiding. And sometime he would be found, according to Chief Inspector Church. The man almost undoubtedly killed Daisy Baker. And there's no question that he had a body in that trunk moving it with him. An inquiry into the whereabouts of missing girls had blossomed into a full hunt for a murderer. The premises at 26 Maitland Street, Brighton, were given a thorough going over. Detective Shaw reported... Nothing, sir. Not a trace of anything except that trunk and the body. To which Inspector Church replied... Very well. Now I'll give the same treatment to 35 Park Row. There, the young detective reported. In the backyard, sir, in a pile of junk, we found a hammerhead. It's been given to pathology, Inspector. There is stains on it. They might be blood, sir. And as Inspector Church said to his deputy, Inspector Cross, some 48 hours later... Pathology report, Cross. That hammerhead did the job. The stains of blood and the type conformed. Good enough, sir. Not quite. Good enough. The handle is gone. There's no proof who used the hammer. And pathology also reports that the autopsy shows enough morphine in the Baker woman's body... to establish unconsciousness before death, if not death itself. Any record of dope-handling in Marston, dossier, sir? Nope. We haven't been able to tie him into that yet. Well, we'll see after we find the gentleman in question. Meanwhile, have them get me Brighton and the wire. I have a routine job for Detective Shaw. Too many loose ends in this one... The car was made to Detective Shaw in Brighton. Armed with a postcard, a file number and a hand-lettered menu... Detective Shaw invaded a certain telegraph office in Brighton. Yes, sir. Always glad to cooperate with the police, sir. Can you find me the original of this wire? I think so, sir. Just a moment, please. This is it. I assume, sir. It has the same file number. Yes, that's it. Going abroad, good job. Thank you very much. Now, if you'll just let me compare the writing on the blank... with these samples I have with me... Detective Shaw noted his comparisons and went to the telephone. A few moments later, he put a call through to Inspector Church at the yard. Go ahead, Shaw. What have you got? They had the original, sir. I compared it with the postcard, with the Baker woman's writing on it. I'm no expert, sir, but it's obvious that two writings are absolutely different. That's that, then. I had a specimen of Marsden's writing, too, sir. Where did you get that? From a restaurant where the man worked for a while as a waiter. The menus there are handwritten. It was part of his job to write them out. Good man. There's no question about it, sir. Marsden wrote that wire and signed the Baker woman's name to it. Another link in the chain rapidly forging itself around Jamie Marsden. But still, no Jamie Marsden. Every policeman in England's carrying the man's picture and description, sir. How long is it going to take to bring the picture and the man together? Not too long, Inspector. In fact, within 24 hours. Here, you. Just a minute. You want me, Constable? Stand over there, in the street light. No weapons. Now, why should I be carrying a weapon, Constable? I'm just an ordinary citizen. Let's have a close look at you. Yes, I'm sure of it. You'll have to come along to the station house. You're being taken in charge. What for? You're Jamie Marsden, unless I miss my guest by a mile. Don't you know there's an all-stations broadcast out for you? You're the most wanted man in England this minute. That was in Manchester. Very shortly thereafter, Jamie Marsden faced Inspector Church and Deputy Inspector Cross in their office at the yard. All right, Marsden, let's hear it. All of it.   But you knew she was dead. If you mean, did I put her in the trunk? I did, but you didn't kill her. No, sir. You've got to believe that. Apparently, you seem to understand that it's somewhat difficult to believe. Well, that was the whole thing from the beginning. All right, let's go back to the beginning. Well, me and Daisy got together down in Brighton about a year ago. Oh. Oh, she was dancing in a coop show, and I was barking a booth a little way up the sidewalk. Well, sort of got into the habit of meeting her after closing time. Then, well, we reckoned that two can live as cheaply as one, so, well, we put in together and started housekeeping. Were you pushing any of the stuff her way? I didn't know she was on the stuff. No, not for months. Inspector, you've got to believe it. Yes, it seems that a lot of things we've got to believe. You heard, Cross Marsden. I am, shall I say, skeptical too. Keep talking. I'm honest with you, sir. I am. Keep talking. Well, Daisy's sister came to visit. We didn't get along. If I'd have killed anyone, it'd have been that sister. What she came for, except to be nasty and snoop, I don't know. Back to the story, Marsden. Yeah, yeah, yeah, all right, sir. Well, like I was saying, we got together and everything was fine. Oh, we had a couple of fights, but, uh, oh, nothing much. Then Daisy said, as our sister was coming down again, I got real mad. I slammed the door. You didn't slam Daisy. I may have cut her a bit, sir. Nothing, nothing serious. Anyways, I went out and I stayed out for a couple of hours. I'd come back and the place was awful quiet, and I thought, well, maybe Daisy had gone out or taken a shot or two or something. I walked into the bedroom. That was at 35, where we had the three rooms. You walked into the bedroom and let her have it, right, Marsden? No, so wrong. She had it. Oh, it was awful, Inspector. She was real bashed up. Why didn't you call the police? Me? With my record? Who'd have believed I didn't do it? You don't believe me now. I never killed nobody, just been put away for small things, but I got a record. Nobody had listened, I reckon, so... I got real scared. I did the first thing it had in my head. Which was, Marsden? I got an old trunk and I stuffed her in it, and then I took the sheets and all down to the cellar and I stuffed them in the furnace. Well, the rest you know, Inspector, and that's the truth, so help me. What did you do with the hammer, Marsden? Hammer? Oh, what hammer, Inspector? The one you bashed her with, Marsden, the hammer that killed her. I don't know about no hammer. I didn't kill her nor nobody. I didn't kill her, Inspector, and that's the truth. They worked on Jamie Marsden for three days. They tried every trick, every question they could think of, but no one could shake his denial. Jamie Marsden insisted he had not killed Daisy Baker, and that was that. Weary and exhausted, Chief Inspector Church faced his deputy. You know, Cross, I am almost beginning to believe Marsden myself. He did kill her. It's completely out of the pattern. His kind of criminal almost never kills. I know, but somebody killed her.  Well then, where do we go from here, sir? Well, we do doubt there were. There had been other men in this woman's life. Have you any doubt about it, sir? Do you suppose the sister would have any ideas? Well, it's a place to start in any case. Jack, then let's get on with it, Cross, and ask the Brighton police to work on that angle. The sister, Ruth Crandall, is the start of the new angle at any rate. The two CID men paid their second visit to Mrs. Crandall. I suppose, Inspector, you've come to ask me to testify at Marsden's trial. Nasty little man. As a matter of fact, we haven't. We don't have enough evidence yet to send Marsden to trial. You've booked on suspicion, that's all. Not at all evidence. Hardly seems possible. The papers were full of it. The newspapers aren't the police, ma'am. Of course not, Mr. Cross. When I met my sister's body with him, he did run away. I know, Mrs. Crandall, but there's been no weapon that relates to Marsden. No weapon? The hammer's head? Well, after all that's a weapon? Did you say a hammer man? We came here to ask you about another man in your sister's life. Have you any ideas? I know this much, Inspector, but my sister was no better than a reputation. Heaven knows I tried. All my life I tried. When my husband died, I offered her a home even. Knows she persisted in the disgraceful kind of life she was leading. She even boasted to me once that she liked it. As for knowing the kind of men she went around with, really, Inspector, you see how I live? How would I know anything about things like that? I see. Well, Mrs. Crandall, if you think of anything, which may be of help, we'll appreciate your letting us know. Two men with a purpose left the neat suburban residents of Daisy Baker's sister. Shortly after the return to Scotland Yard, the teletypes, the telephones were all busy. Reports were swift in coming in. Here's word from the hardware store, sir. A hammer was bought. The janitor at 35 Park Road did see someone that day. They found a taxi driver in Brighton who remembers. One of the neighbors places the date exactly. So she remembers the house was empty because her little boy was ill and she wanted to borrow something. Here's the final touch. Local bus driver remembers the trip from out there to the railroad station. The final touch. And once again, two men from the CID went visiting. We've traced your movements all that day, Mrs. Crandall.  The bus driver remembers how you asked if you'd reached the station on time. A taxi driver in Brighton remembers taking you to 35 Park Road. The janitor saw you there and the hardware dealer right round the corner from here has a record of his sale of a hammer. To you. You shouldn't have mentioned that hammer, Mrs. Crandall. It was about finding it in the backyard at Brighton. I was right. She wasn't fit to live. They would have unpitted me on account of my sister. They looked down on me. I never felt better in my life than when I hit her and hit her. I then broke the handle off the hammer and burned it in that furnace at that awful house. If only I'd been a little more careful. Then you'd have to have tried that mountain fellow. You'd have to have hung him. Perhaps. Now then, Mrs. Crandall.  And today that hammerhead can be seen here in the Black Museum. Orson Welles will be back with you in just a moment. Now here in person is Orson Welles. In due course, Henrietta Crandall paid the usual penalty for premeditated homicide. The purchase of the hammer was sufficient evidence of the intent to kill. As for Jamie Marsden, product of the London slums of bad company and evil ways, Jamie went free. But not for long. Six months had barely passed before Marsden was picked up for possession of a deadly weapon and sentenced to serve 90 days for simple theft. And as for the hammerhead, well here it is in its usual place in the Black Museum. So until next time till another story about this same place I remain as always obediently yours.


I was one of the facilitators to talk through one of the groups during lunch, so the idea was we would have a working lunch and engage with the specific groups. Each group was paired with one or two people who were experts in the field or had a particular interest in it, so I was paired with the big data team. The people who are looking at edX and different initiatives around MOOCs with Harvard and I do a lot of work around data and privacy. So the idea was to brainstorm, give them feedback on what they've done, talk about their presentations and maybe inspire them a little bit with real life examples of what we've done, help them along, identify questions they may want to look at, different areas of research or help fine tune what they're already doing and I guess really just to have a dialogue about their work. So I think one of the issues was around consent, so we were talking about people having their data that is held by an educational institution be shared for research purposes and the assumption was well of course if you ask people they'll say yes I'm very happy for my data to be used, nobody would say no and I sort of immediately jumped up and said well I would say no which sort of seemed to come as a surprise to the person working on the project, she's like why would you say no, you know kind of this immediate assumption that all data, all research is for a good purpose so why would you not want it to be shared and I was talking about a developing country perspective which is what I'm more familiar with and how often the consent that you give isn't fully informed consent, there are issues around people not having the education, the literacy, the knowledge of what might be done with their data to be able to even make informed choices so sort of adding that slightly different perspective around how if you start a program or if you design an interface working off an assumption that yes of course people are happy to share why wouldn't they, it already sort of designs a certain path you're going to go down and it's not flexible enough and maybe looking at the sort of devil's advocate side of the spectrum and saying well why would people not want to give their data and then allowing people genuine choice and having that consent be meaningful is something you do need to think about so that was something that sort of came up which I think they hadn't quite thought about.


アプセス?OKOKSoOK, soI'll start.So far, I talked about some...SoYesterday, orZip-SawThis is overdifferentchemical species.So this is kind of averageyeahovercells.So this abundances abundances of chemicalsfor instance messenger RNA.So that is somewhat power law behavior.And that is often appear in statistical physics as a transition point.And alsofor cell-cell fluctuationvariancewe have seenlognormal distributionand thenwe discussed some kind of kind of reproduction of cellsand what the nature of reproduction of the cells.And thenI discussed some kind of sleeping state.Actually, this is also shownin this othertalk in this kind ofsowhen you put this bacteria intokind of in new entrainresource condition, nutrient conditioninitially takes some timeand then exponential growsthe number grows exponentiallyand then comes toso they cannot grow anymore.And then finally it goes down.And then the question I discussed yesterdayso how this kind of sleeping stateappears.And thenthen Idiscuss this kind of model.So basically this is a kind ofactive protein.So thatso this isautocatalytic.autocatalytic means that this numberincreases by itself.So for instanceso this increases byproportional to this itself.So that givesusual exponential law.So this kind of behaviorexponential law.And then how it sleeps.So that's the question.And then we consideranotherdifferent molecule species.Andthat is some kind oferrorfrom the original.So this does not have functionto catalyze others.Soand so in some sense if this is largerthis growth is suppressed.And thenif you have some kind ofcomplex between A and Bthen consider such model.And thenif this nutrient islower this fraction is increasedand thisfraction increased.And then it goes to this kind ofyes sleeping state.So the growth ratefor examplethis growth ratehow this increasesthisshowsfromthis growth ratechanges fromthis growth rate muandthis musogoes downat some point drastically.So this is10-9or something.So this is almost zero.So it goes down.So the cell cannot grow.And thenyeah.So we have seenthis behavior.So that meanswithin this nutrient rangeso the cellcannot grow.Or it does not die.So this muis nearly zero.So the reason for that is thatso active moleculeisso trapped by this complex.And so thatwhen it's trapped by this complexso catalyticactivity cannot work.So it cannot grow.So this is so far a model.And we are not completelysure if this is really true or not.But there are some discussioneven in the present cellthere is some kind of such inhibitorfor the growth.And so that may work as B.So probablythis kind of basic ideamay be okay.Of course in biological detailsthere are much morecomplex nature.But probablythis kind of behavior exists.So that'sactually so hereit's trapped by thisactive molecule AA is this one.So active one is trappedby this inhibitorso Bor erroneous onebad one or something like that.Sothis isand anotherinteresting pointis thatokay in experimentso this isso when these cells put into astubbed condition there is no nutrient.So the growth rateso goes downto nearly to zero.And actually one can measurein thisso just lookingat this microscopeand or someplate or something.So this cell stopsthe growthwithout nutrientand stays there.Sometimes they form a kindof strange form or something like thatbut they stay there.And then theyagain put nutrientand theoriginalpicture of thisthis lag phase meansthat when youput nutrientto recover the growthit needs some time.So that's a kindof common nature.So even though youhave put nutrientsit'sfinally this becomes positivethis becomes positiveand it can grow.But it takes some timeto recover thatand actually this issomewhat rather large.And another interestingpoint.So thislag timebefore thisit's okaybefore it recovers the growthand then itstarts to growagain.So hereand this isthe lag.And actually in this experimentor in most experimentsso they put into the starved conditionand how long itis put into the starved condition.So maybeso thisso they put a kind ofso here they start nutrient.And before thatokay no nutrientsometimestarved time.So withoutyeahwith nutrient it grows thisand they cut thisand they are going to this state.And how long itis put to this starved condition.And interestinglythe experiment showsthatthislag timehere it's put lambdalag timeandstarved timethis lag timeincreaseswith the starved time.So this is some experiment.So how long itis starvedand thisis lag time.So in somesense cells rememberhow long I'mstarved.So this is a bitkind of interesting behaviorbecause if this starved conditionis a given justsingle statethenmaybethis lag time isindependent of thehow long I'm starved.If I'monly one bad stateif I'm starved stateif I reach hereit's a single statethenyou need same time to recoverthe growth.But the experiment showsthatsomehowthis lag timeincreases with thisstarved time.So if I'm starved very verylong timeit needs more timeto recover.So that meansmaybe slowly in this starved conditionslow change occurs.And if it goes slowlyto a much worse statethen you need more timeto recover.So that kindofexperimental resultisknown.And howit depends onthis dependence of this and thisthis increaseswith this.Solamda increases of T starvedsomehow increasesmaybe.How it increasesthis dependence is not maybeyet soaccuratelyobtainingexperiments.But anywayincreasing function.Andsome data show thatthis is roughlysquare root ofstarved time.But some experiment showsmaybe it's almost linearof the starved time or somethinglike that.So thatthat point is not yet so clear.But maybe something like that.And actuallyin this simulationwehave seenkind of this kind of square rootin this simple model.Andthe basic mechanism thatit showssuch kind of dependence isso as I saya andb.Soactive one andb.Soit'sslowly this part is increasing.And active one isyehdecreasing.Andin thismodel basicallyb is produced by a.Sowith the aid of a.Soroughly speakingincreaseofbad oneisproportional to a.But a plus bsee.Andat some stage this complexreaches some value.Thenseesome seesproportionalto a,b.Andthat meanssomething like that.This is a kind ofrough estimate.Of course in the simulationwe show this behavior.Sowe try to understand why this kindof square root appears.And so assuming thatthis process is rather fastand it's equilibrated and thisis roughly constant valuethen this.Andthen so wehave this.Sothat meansthat meansb increasessquare root t.Soif you have starvedsothe amount of bis roughlyproportional to t starved.The fraction of bbad one increases with thissquare root t.Andthen tochange the growth.Firstthis is attached to this.Soif you put a nutrientagainthenthis a start to workmaybe this becomesdetached anda starts to be activeagain.Andthen the time neededfor this isproportional to this.Soin this argumentroughly we have this.This is a kind ofrough estimate.But anywaywe have seenthat kind of behavior here.Andmaybe the otherone isthere are other interestingpoints,but maybe Iskip that.Andsorry,I have a question about the experiment.Soall the experiments are done wherethe nutrient supplied beforeand after starvationis the same.Yeahsame nutrient and soit grows and thencut and thenwait sometime.Andthenactually there isthis is theaverage starvation time.Averagelag time.Andactually for each cellsome cell can wake upearlier.And some cansleep longer.Sothere is a ratheryeah,long taileddistribution for this.Soeach cell lag time.Andthis is also,thisprote is something like this.Soandactually if we doa stochastic model for thiswe can have this kind oflong tailed behavior.Andbutfor such experimentyou need to measure asingle cell.Sothat's not so easy.Andactually tomorrowYuichi Wakamoto will talk abouthis beautifulexperimental technique tosee such behaviors.Yeah.Okay.Maybe if you're interested indynamical systemsand thissleeping statefixed pointis somethingso you have twonull clients.Andif it goes there.Andso if it goes tofinally approach,itgoes to thisfinal sleeping statefixed point.Thesetwo null clients are almostin parallel or tangential.Soit takes very long timeto go there.Sothat's this time.Soso relaxation toover this process in thisstabation condition isanyway very very slow.Theslow,the reasonwhy it's slow is thatanyway A isthe active one.Andeverything in this cellis processedby this catalytic molecule.Andthis catalytic molecule number isvery small.Theneverything is slow.Soeverything is slowed down.Sothat's how this kind ofprocess occurs.And if you areinterested in dynamical systems,maybe youcan see two null clientsand how these are.And if you'reinterested in,please refer tothis original paper.Yeah.Okay.So there are some otherinteresting issues in the origin ofrelated to the origin of life.ButI guess I don't havetime to go into detailsto each topic.IfI do this,I needmaybe two or threelectures for this.Andso I'll skipthis.Butmaybe I justsay the topics.So oneis whywithin each cellthere are so manydiverse components.Andactually in this modelor the modelI talked yesterday,justone active molecule,oneactive catalyticspecies.And that producesitself.Andto grow,maybethat is simplest and maybeit works much better.Because othersdo notnecessary,not so necessary.Sobut stillin our cellthere are so manymany components.Maybejust for the growththis will not be souseful.Sothat's a kind ofvery basic question.Andso there are manypossible answers,maybein a different environmental condition.Ormaybeyeahin aif this resourceis limited,then it's better to havemore diverse chemicals orsomething like that.Sothat's one problemand we are discussing.Andwe discussed thatokay,thisbasic start point is thatthese components arein this membrane.Andthis is compartmentalized.Sothe originof this such kind ofcompartmentalization.Thatis a kind ofverybasic issue.Andanotherimportant issue is thatalways.Soin thisorigin of life,information moleculeand functionenzyme moleculeis separated.Soprotein works as thisand DNAworks as this.Andso this mutually helps each other.Sothat structurethat is also known inCentral Dogma.Sowhy this exists oris this a kind ofessential oralwaysuniversal naturefor a cell system.Sothat's also a kind ofvery fundamental question.Andwe discussed somekind of model for thisthatby symmetry breakingthis role separationoccurs.Butthis is stilljust onepossible solution and maybewe are notyet in this final answer.Sothat's we needsome kind of coherent theoryfor these kind of things.Andso maybe I'llskip this.And if you'reinterested in this otherslides listed there.Somaybe you can read thisoriginal paperor you can cometo discuss to me.Andactually maybeI just want to say onepoint here.Thiskind ofbehavior.Justsay a little bit.Maybe Iat least thiswhy theythis kind ofcompartmentalizationisnecessary or goodisokay.Thisproblem.Youhave catalytic molecule.Andthenit's mutuallycatalytic.Sofor thisXI growsto XIsome J moleculeis necessary.Sothis is catalyst.Sothey have some kind ofcatalytic activityKJ.So thisKJ.Soif KJ is large.Sothis catalytic activityis large.Sothe molecule helpthe growth of othersreplication of others.Butthat is good for others.Butit's why I'mworking as a catalystfor others.I'mnot replicated.Sofor eachmolecule's sakedecreasingthis catalytic activityshould bebetter.Soif you consider thisfitness or some growth ratefor each moleculethenfor each moleculeit's betterto decrease this catalyticactivity.Andso I'm alwayssoreplicatedby the help of others.Thatwould be better.Soif you just consider somereplicating molecules set of hereand then mutuallycatalyzing and then catalyticactivity can changethrough evolution orthen probablyevery moleculestarts to lose the catalyticactivity.SorryI did not understand one thing.Sowhen you say that it starts to lose the catalytic activity means thatit's advantage forJ not to catalyze the reaction.Soyeahthis yeahit's mutually catalyzing.Sothis I catalyzedthis other molecule.Yeahbut the assumption here is then that somehowthere is a constraint to the total number ofso that molecules are competing forsome finitepull of resources so thatthe total amount ofmaybe yeah,finite resources.Yeahbut as timegoes onit's usually better to losethis decrease the catalyticactivity.And actuallyif we dothe simulation of thisok,some model took,somutually help thisok maybe.Sorryyeah.I don'tget this.Soessentially selectionselection of each molecule.Yes.Selectionaxa at the level of the whole cell.ok,so that'sthe point.Herebeforeif cell does not existand then justmolecules there.Thenfor the selectionof each moleculethey lose catalyticactivity.Sothat's a problem.Wethis system cannot continuethe growth.Sothen,as Mate alreadymentioned,if these cellsareput into ayeah cellsome kindof.And thenthe catalytic onethese catalytic moleculeshere.So of coursefor each moleculereplicationthey may goto the direction to decreasethis catalytic activity.Butif everything does thatthenas this cell.Sofor instance,if every molecule losesthis catalytic activity.Thiscell,as a cellthiscannot grow.Sofinally this cell dies.Butif you consider the situationthatok,maybeyou havethe numberof moleculesnot solarge.So probablysome cellsthey havethey keep some kindof catalytic moleculehere.Butfor some other cellsthey lose all this.Sothenthese cellsremain to grow.Andthese cellsdie out.So basicallyin this case initiallythe selection works of moleculesbut nowif we go to the cell levelthis selection works as a cellthenthose cellsthat somehow keep the catalytic activityremains.Sothat's howmaybethis is not taken bythis non-catalyticmolecules.Yes.I have a question because I thinkthis is the core of the chicken egg problem.Soyes.Yes.Sothis just exists.Soexactly.So the questionwhat I don't understand the question isgiventhat a cell exists.Thatis possible to have a cell.So that 12 compartmentswhat isadvantages?Is this the question?Orthe question is why it'sadvantages to have cell compartments?That's the good answer.OK.If you have compartmentsof this structurethis can remain.Butmaybeotherwiseif you have justbigthis kind of special structurethen maybe they will finally die out.Sosomehowin thissomeplacethey have some kind ofcell.Soinitially maybe not cell.Butif you have some kind of smallholes.And thenwithin this only enmoleculeshere.And thenif you compete with thissmall structureof these holes.Thenthis guy can grow.So the question isyeah.OK.Yeah.Sokeep in the structure.Yeah.Sothenmaybe it's importantif n in this moleculein the cell.The numbern is too largemaybe they finally losecatholic activity.But if n is notso large.Yeah.There isyeah.So thiscan keep this structure.Andactually yeah.Wesome simple modelwe have a transitionto this kindof yeah.GrowingandOK.Nongrowing.If n isso OK.This isn.And m is thekind of mutation rate.Sothis is how thiscatholic activity for eachmolecule changes.OK.Istill don't understand theselection acting on themolecular level.Becausethere are two aspectsthat I don't understand.One isthatwhat is thiscompetition.Whereis this coming from.Because it's amolecule.It's essentially a proteinand it's doing its job.Andthe second thing that I don't understandishow does it sensethis competition.Becausea cell is a collective structure.Ithas the ability tosense competition andmodify its DNA orhave a mutation tospecifically modify themolecules which make itfitter.Butwhen I'm thinking ofa specific single moleculeI don't know how it sensesthe competition and where is thatcompetition even coming from.OK.Sofirst this moleculeso moleculereplicate.Andif thisgrow this replication rateso it's higherthen this moleculedominate.So iffor example a moleculeand b molecule and a moleculegrowreplicate per 10 minutesand this moleculereplicateby 1 minute,then this numberdominate.Andso for instanceif a and b mutually catalyticand ifa hashigher catalytic activitythen alwaysa is helping the replicationof b.Butb has no catalyticactivity thenb grows this ab does not help a.Soby that b increasesmore and a increasesvery little thenb dominates.Sothat's the molecular levelselection.Andthen the cell levelselection is thatput these kind of moleculesin a cell.So it's a veryprimitive cell.You don't needto consider DNA or anything.So put these.AndthenOK.If such bdominated cellsOK.Initiallythey start tosome a moleculeexist.Butb is dominant.So finallymostly this isb.Sothen thisthe total number cannot increases.Butif you keepsome cells happened towith some fluctuationhappened to keep amore.Thenthis number increases.Andfor instanceassuming this total numberof molecules increases,thenaccording to these cell devicethen these cellscan divide.Sothere is some kind ofsomolecule levelselection and cell levelselection.Andonce you make cell.Sothere is cell level selectionappears.And the interestingpoint is that cell levelselection and molecule levelselection may go intodifferent direction.Soin a molecule levelselection may go intodecrease K.Butin the cell levelselection may beaverage K overthis within the cell shouldincrease or keep some value.Sothat's in a differentdirection.Yes.SoI mean it'sit's right tounderstand thisin the sense thatwhen you think about moleculestalking about proteinsthat essentiallyare subject to mutationso thatessentially you losecatalytic activity.Yeah.Okay.Yeah.Sosothen mayben is important.Andthen how K changesso pereach replication.Somaybe the rate of losingK.Somaybe K itself changesgoing up or down randomlyby mutation.But maybeas a result K decreases.Butthis is some kind ofmutation ratemutation ratechange rate of KM.So basicallyyou have two parameters.Thenumber of molecules in a celland mutation rate M.Andthen the resultsays that suggests thatokay if n is smallerthey can't survive.Butif n is largerfinally every moleculeloses catalytic activity and dies.Andso this is thephase diagram.So this isthe kind ofsurviving region.So ifn is small,okay.Soforget about this Sthis is some kind ofselection pressure or something.Soanyway,sofor instance this,yeahifn is smallerthen you cansurvive.Sothat's some kind ofimportance of this multilevelselection process.Sothey,soand that isimportant whyso K compartmentalizationor cell structureisnecessary.It's good.I'm sure it'snot sure.Butanyway,so this is,yeah.But is this quitehow to say intuitivethat the,so if Ithink about this nand the state ofthe moleculeas some kind of alignmentprocess.Soifn try to maximizethe K,thebehave in the same way,right.Soas a connectiveincrease nrequirehigh selection pressure for allalign.Decrease nit easier for them to align.Increasingincreasing n means thatmaybe,so basicallyifn is largeso in thiskind of multilevelselection and this isone,so which iswhich property is importantfor molecular levelmoleculeor cell.Andfor moleculefitnessK activity goes downand cell levelaverage K increases.But this is average.Soif this is all of Kloses that,this should decrease.Andifn is largethisifn issmallso beforeeach molecule losesthis catalytic activitycell device.Socell's importance is morerelevant.Sothis kind of structure.Yeah.Andactually this kind ofproblem isquitemaybe general inmany system.Youhave multilevel system.Sofor example,if you considera company andI do not work.I do not workbut somebody other works then the companyso can beokay.Thenso butif this total numberis small,then everybodyhas to work ormaybe.Thenso howthis kind of parasitemolecular parasiteworkerdisappears.Depends oris not dominant.Depends onthat kind of total number.Yeah.Sosois there anotherway of seeing what you are saying.Sothat essentiallyso the typicalvalue of K decreases.Butbecause you have anexponential increasing populationthen there isa large deviationof small moleculeswhich have a largeRHK.Yeah.Andthese are those that aredominating growth.It's abalance.Yeah.This is atouch balance.Yeah.Actuallywe can do some kind ofsome calculation to showthis kind of where thetransitional occurs or something like that.Yeah.But maybe.Yeah.Idon't know.Soanyway this isunimportant.Maybegeneral important problemhere.Then.Yeah.Okay.Sothat's one exampleand then.Okay.MaybeI'll skip this.Okay.Then.But thenmaybe you cannotmake a very large cell.So only thisif n is largeeverythingso this molecule,this cellreproduction does not work.Andthen we discussthat when n is largemaybesymmetry breaking that onegroup of moleculesloses this catalytic activityand they workas a kind of informationmolecule like DNA.Butother type of moleculesremain to workand keep catalytic activityso like protein.Soif that is the casesoif n islarge maybeat some point there issymmetry breaking thatfunction molecule andinformation molecule issplitted.Sothat is theorigin of central dogma.Soproteinworks as enzymeand helps the growthand DNAworks asinformation carrier.Andactually that kind of structuremaybeseems to bequite commonas long as you have multilevelstructure.Soin this case I discusscell versus moleculebut in our bodythere is multicellarso this is multicellar organism.Soin our body casewe haveour bodytotal multicellar organismbut you have many cellsand in this caseagainsome cellworks as a kindof information carrier.Sointhis in our case of spermand egg cellcan bethiswork as ainformation transferfor the next generation.But othercells of our bodyso this skinor all otherscannot leave the offspringfor the next generation.Sothat structureso one type of moleculecellsworks askind of information groupand most othersare kind of function.Sothat is quite commonto here.Yes.Asfar as I understandyou said DNA worksas information cellsand proteins works asfunction cells.AndI don't have any sense ofwhat is information cells.Does it mean as the history ofthat you said that they don't havecatalic activity.Doesit mean it is the history ofthe cell.That isyou know I don't have anyidea of what does it meaninformation.I see.I should have explained that.What it refers to.Okay.Soin this case sothank you.So maybeyou have learned the central dogmaand so from DNAinformationnow proteins are produced.Catalysedby protein.Sobasically fromthis informationeveryother.Sofor example this DNAand from this DNAproteins are produced.Andthen DNA is replicated.Andthen from thisyeah proteins areproduced.Soprotein cannotproduceby this information from this.Sofor exampleyou have amino acid sequence.Sothat is kind of information.Butit cannotbe transferred.Onlythis you haveDNA sequence.Andfrom this each DNA sequence.Andfrom this some amino acidis produced.Someamino acid produced.Andthen proteins produced.Soalways proteins producedfrom the information ofDNA sequence.Sothat's the informationI mean.Is itokay.It works as a pattern.Itworks as a formula.Youemphasize ontransmission,theinformation.Transmission to this.Yeah.The sake of theinformation.Yeah.Yes.Yeah.Yes.Andactually so alsoin our cellso this our body.Sookayfor instance each skin cell.Butthat is produced from thisoriginalyeah egg cell.Andthen from this informationthis is made fromthis.Buteven if I have this skinthis skin cannotbe transferred tomy offspring.Onlyyeah egg cellor sperm cellproduces the next offspring.Theinformation is transferred only throughthat.Sothat's a quite general nature.Sothat's a veryinteresting issue.Andso wediscuss some kind of model forthat,but it's still quiteopen.Yeah.Sojust to see if I understand the claim.Sothe claim is that if you have areplicating molecule where the informationis stored in the structure itselfthen if there are mutationsthat advantage the moleculeover the cell this replicatesover generations.Whileif you splitthe information content whichis stored in let's say DNAand the molecule that replicatesif you have a mutationin DNA that corresponds to a largerreplication rate of the moleculethat produces a disadvantage for the celltherefore that will notreplicate.Sobasically by decouplingthese,the information spreads onlyvia the oldpopulation of molecules.Yeah.Actuallyokay.Soin this discussionokay,this modelis too complicated.SoI don't want to discuss.Okay.Sobasicallyeach more,soin this discussion of this symmetrybreaking,sothis catalytic activity Kand thenthe property hasto transfer the informationas template informationso thissome kind of property Kand initiallyI assume that K andP are sameamong all moleculesand if you consider two typesof molecule,one types of moleculegoes here and work.Soas I saidthere is general tendencyit goes to okay.Thereis general tendency to goK goes to 0.But actually some typeof,one typeof moleculeinitially losesK.Thenthe other type of moleculekeeps Kandas a kind of function moleculeworks as a kind of functionof molecule.Sothis kind of symmetrybreakingoccurred in some model.Yeah.Sothis is a little bit.Yeah.Themodel is a little bit too complicated.SoI do not go into details.Yeah.Justsee if I have understood likewe needlike the meanKto raisebecause otherwise this cell doesn'treplicate.Yeah.MeanKshould belarger.Larger.Yeah.Butbut each Ktries to decrease.Go down.Thenme it's justaverage of each K.Soit'sconcrete.Someone goes down and they areinformation one and some.Yeah.Sorry.When does thissymmetrybreaking occur?Okay.Okay.This is a little bit.Yeah.Soin thisstudy as N is larger than some threshold.Yeah.Thissymmetrybreaking occurs.Sobut I am afraid that Ito explain that it's a little bit more details.Soit's so you can seethe paper byTakeuchi and myself.And alsomaybe I have other slides to explain that.Soif you are interested maybe I canyeah discuss later.Okay.Sosorry for this.Yeah.InitiallyI thought I should skip this part butmaybe it's yeah.Becauseit's this kind of structure seems to be quiteuniversal.Soin a kind of multilevel systemso molecule cellor cell-to-multicell organism one groupworks as a function and the other group has a kind of informationtranslation to the next generation.Andusually the function parthas a large number.Sofor example in our body onlyyeah just egg or sperm cellit's a very minority.And most othersyeah muscle says all others are majority.Andalso in a cellDNA is usually one or two or somethingvery few number.And proteins are largenumber.So that kind of structureseems to be common.And alsoin a higher levelSo for instance queenbe or queen aunt.So there is auntsociety.In the aunt societyonly the queen produces the nextoffspring.And all the other aunts areworkers.So again this is functionand information groupand information group is very minorityfunction group is majority.Andmaybe this appears when aunt is largeso maybe aunt has many manynumbers.So then the transition occursI don't know human beingsdo not have enough such number tomake such symmetry breaking so thatyeah we can produceoffspring.Everybody can produceoffspring basically.OkayOkay soyeah I thought I just talked this partonly 20 minutes and butyeah.And I go totoday's number fouryeah today's Thursday alreadyso I go to that switch to thattoday's topicOkay so far we discussed the reproductionand can I ask a question about the previous claimso one I mean could wonder whetherit was I mean it's a game chicken egg but it was bornthe membrane before so the compartmentsor the separation between informationand because you could imagine to have these holesand already of these holes at the moment where there is like this sort of group selectionit might become advantageous tolike the separation between the symmetry breaking between informationyeah but maybe at someor maybe initially there is some kind of membrane moleculesin the very beginning I don't know yeahor even withoutmembrane maybe there is some kind of other wayto make these molecules in a compartmentso that isnobody knows yeah soI go to the topic of adaptationsobesides reproductionso adaptation isuniversal feature common to biological systemsand when we say adaptationbasically there are twokind of different aspectsone is that okayso basically adaptation is thatmaybe this biological systemis put to new environmentand we often say okayif we go into a high temperature regionmaybe some kind of biological state of ourschange so that we can adapt to ahigh temperature region or high altitude regionor something like that so thento adapt to that something should changeso that's one aspectso some changes so that thisbiological system can survive wellin this new condition so that'sokay I start fromchange to a fitter state, higher survivabilityand so thisand another aspectis that eventhis change occurs butmost of the cellar stateor most of the variables in our statedo not change so muchor stay at the same levelor come back to the same levelso this is also another natureand actually even if youput this into a kind of different temperature conditionour body temperature remains within a certain rangeand there are many studiesby physiology studiesthen that is studied by the famousphysiologist Canon andthey he called homeostasisso many biological stateremains at the same levelso of course if you put to thisnew environment initially this change occursbut finally most of the variablescome back to the originalso these arekind of two different aspectsthis say changebutmostlydo not change so there aretwo aspectand actuallymaybe this is kind of verybasic issue in biological systemand this is sometimes this is calledplasticity so this can changeand this is called robustnessit does not change so muchso how these two are compromisedthat's the basic issueso in this today's lectureso I discussedfirst changeabilityhow this is changedok so nowthe standard pictureof thisadaptabilityto change to a new conditionis that there is some kindof cell signaling so weput this bacteria into a new conditionand then some changein this internal state occursand standard pictureis that there is some kind ofok externalso we have this nutrientbut we do not have this nutrientor something like thatimformation so external informationcomes into the celland maybe some kind of membraneor something base sense and then cell signalsome signaling process signaling networkthat has been discussedin or investigatedin detail and then leadsto some kind of this changeto gene expressionso that means you have to produceproduce proteinthis protein Aor protein Bor something like thatso for instancein this conditionyou have to produce protein B instead of protein Bso this is the process thatso from this DNAok you have the region to produce Aor B and thenthere is this signal transduction networksays some informationthat in this condition you produce Aor but in the other conditionyou produces Bso there is some informationso that's kind of general picturethat isim not saying that this is notcorrect ok this works inmany examplesmany biologists checked aboutthis kind of cell signaling networkand how this kind of structure in some conditionhow this process occurs and this issometimes very complicated but theyfind outso that'sthat's ok so maybe this cell signalingnetwork can be evolvedafter so many generations soif this bacteria put into this condition okI have to produce protein A otherwiseI cannot survive thenmaybe if some cells findsome kind of specific network then they can surviveand then evolvebut still one question is thatbacteria can survivein various conditionsand sometimes experimenters doput this bacteria into a quite strange conditionthat recently produced environmentso we have many recentlyfound some kind of some chemicalsin somethe kids from the factory or something like thatthen they put this bacteriathey still many times they still can survivebut then it's hard toimagine they have alreadysome kind of historyfor the evolution to survive this and they inventsome cell signalingtransduction networkso they prepareall many differentpossible environmental condition and they preparedifferent cell signal transduction networkhow this can be possibleso that'sa question hereso that means adaptation to a huge variety of environmentsso the question issignal transduction networks are preparedfor all of theseand this may be a little bit hard to imagineso if there is some generaladaptation mechanism that may not beso sufficient as the signal transduction networkin the case of signal transduction networkif you put this new environmentimmediately they start to produce aand all of these cells can survivebut is there some other mechanismthat may be not so efficientbut at least they can work more generallyif that kind of thing existsthat would be quite goodactually there are some experimental suggestionsthat they put thisfor instance this is Elisha Brownin Israelso they did some kind of put thiseast cell into a different conditionand they somehow surviveso the question is that is theresome mechanismthere is kind of change of gene expression dynamicsto switch to a kind ofbetter survivable conditioneven without kind ofdirect external informationso that's the questionactuallyso is there any generalmay be primitive mechanismabout twenty years agoso a colleaguemine worked outsome constructive experimentwhat they did is something like thisin this bacteriathey put some genesand they cut out some other genesbut they put these genesand so basicallyin this as shown in this figurethere are two sets of genesand there is promoterso from this gene starts to beso transcribedso this set is transcribedso there is two setsgreen and redand thenwhat they put is thatwhen this cellwhen these genes are producedtranscribedthey generate these proteinsso this is hereso in one case, Lacquan GFPGutamin A,Gutaminaseand this is a red fluorescent proteinthat is for Abut the name is not so importantI do not know so muchso biologists should know what these names meansbut maybe for physicists the structure is importantso what they have hereis thatwhen this genethis protein is producedthis suppresses this otherand when this is producedthis suppresses otherand that one structureand the other structure is thatwhen this is producedthis make green fluorescent proteinthis is for measurementif this is expressedwe can see this is greenthe other thing is that this is producedthis is redand another thing is thatthey produce some glutaminaseand this is for A or somethingand that isnecessary for the growth in one conditionso here later we put these cellsinto a different conditionso this is necessary for survivalfor other environmental conditionthis is necessaryso maybe for simplicityyou can call this maybe red conditionand green conditionso this is glutaminasesome condition or somethingbut for thisthis is necessaryso the question hereis thatthis isso we put this gene artificially producedso there is no wayinformationso if there is some kind of signal networkthen this is in a green conditionyou can make this green proteinso if some signal transaction network existswe can do thatbut this is put into hereso there is not such structure hereand then can they knowwhich state is expressedand first of allI have to say why this kind of structurewe putso I did not talkin this geneintroduction to dynamical systemsbut basically twoset of genes suppresses each otherand x1, x2and when x1 is expressedx3 is suppressedx2 is expressed, x1 is suppressedand that meansm1, m2and from this protein2 is producedand protein1 is producedthenso you have heard thisheal coefficientin the other lectureand for instancehere we take the case of this heal coefficient2so and this is suppressingso that meansas written therem1is producedwith some ratebut if the other guy existsit's suppressedso for instance like thisand this is something like thisno no no protein2can be different between the twobut for simplicitywe can take this symmetric caseand then from thatokaymaybe degrade itdegrade itand then from m1you can produce p1p1.m1m1-p1and of course you can put some coefficientsbut for simplicityI put this coefficient1and thenso basically you have this equationand then you already heardthat okay in a messenger RNA processyou can do much fasterthen you canideabatically eliminate the messenger RNA variableassuming thatso this goes to the steady state fasterthen this goes to thisand then you solve thisthis equals 0and put this herethen you get this equation herestandard2variabledynamical systemand thenso you need to solve thisbut most of youhave alreadynew about dynamical systemsso if you have this equationthen what you need to first dois to get new clientnew client means that the conditionin this caseso in this dynamical systemsyou have p1p2variableand this dynamical system shows thatokay where it goes here in fixed point or something like thatand then new clientis that p1.equal 0this should be 0so that is one new client is that p1and the other is something like thatsince the model here is symmetricso it crosses at p1 equals p2so you have a new client of thisand okayone new client is thisand the other is something like thisso okay basically thisand if you have new clientso maybe you learned dynamical systemsso you can check thatin which direction the flow goesso above thatso above thatso this goes todown this direction is downand this goes upso right or leftand up or down is changed by thisso maybe as a homeworkyou should write down thisand then check what kind of structureis in this dynamical systemsand write the flow of thisso at each point you can consider p1.p2.and that gives this flowand by writing down thisstructureyou can understandwhere finally this dynamical systems go toand thenso you can see this structureso basically there are three crossing pointsand in this crossing pointsboth are satisfiedthis is a fixed pointand there are two types of fixed pointsone is herethis is fixed point p1.equal 0and p2.equal 0so this arrow goes out along this directionso if you part up a little bitit goes this or thisso that means this is unstableso unless you veryput exactly on this pointit can be therebut any small perturbationcan kick the state to go outso this physically does not existthis fixed point cannot be reachedand on the other hand these twoare kind of stable fixed pointsso this is naturalbecause mutually this is suppressingso either this guy winsso this guy winsand the other guyis almost 0so p1 is much larger than p2or p2 much larger than p1so that means green winsso the kind of these cellshave mostly thisand thenokin these dynamical systemsyou can have both possibilityand maybe if you start fromhere it goes here it goes hereand if you have some kind of noisemaybe it goes here it goes here equallyso the first questionwe addressed hereis that okay dynamical systemsthis butfor a cellif this is expressed in one conditionit can survivebut for the otherif it goes to the other stateit cannot surviveif you put these cells into this conditionmaybe half cells go herehalf cells go here and half can surviveor half do not surviveand they do this experimentand put thisso here so without glutamine environmentand for that they need to be greenmaybe this is green oneand so without glutaminethey have to produce glutamine by themselvesso they need glutaminaseand then it's better to go thereand if the cell goes through thisit shows greenmost cells go to greenso this is a real experimentand for the other casemost it goes to redso now the questionif there issignal transaction network to say thisokay you have to go to green this is naturalbut in this experimentsuch signal transaction networkwas not put so then why isthat this possiblethat challenge to theoryokay maybemaybe if you are suspiciousokay even though we said that there is nosignal transaction network put into thismaybe somehow hiddenthere might existit's very hard to imagine but maybeusually some referees in thepapers would ask okayif that might exist or something like thatokay to check that they didthis promoter genesso that is the initial partthey start this so express genesand if there is a signal transaction networkthis gives informationto thisif there is a hidden transaction networkif you swap this in this experimentand make promoter of this promoter herethis promoter herethen it'sgo to a different statethen maybe hiddensignal transaction network to go to greenbut then it goes to now this other sideand then it should not workbut actually even though they change thisstill it worksso that meansthis hiddensignal transaction networkhypothesis is not possibleso the question is thatokay you have this kind of structureby stable structurebut somehowmechanism that good fix point isselectedgood means that cell can grow fasterso okaythis is hidden hypothesis isdeniedand okaymaybeI can start this simple casein this caseone missing point is that cell growsand as cell growsit's dilutedand if it's dilutedthen to balance thisthe synthesis increasesso instead of this initialdynamical systemswe have this p1there's thisthis is growth rateactuallyso minus mu g x1is dilutionby the cell growthmu g is the cell growthso this is always thisto balance thatthe synthesis is always probablyhigher okaywe discuss this point laterbut anyway thisand then similarly thisnow you consider this dynamical systemsand maybe mu gdepending on the condition maybein green cell this is mu g'slarger green state green conditionand this is smallerso mu g may depend on herebut still this is just overallfactor so that meansmaybe this is largethis is small but still this is fixed pointand this is so if in some conditionif this condition is better okaymu g is large and mu g is smallbut still this is just a factorso basically you have thisstable fixed points hereso only by that nothing changesthen butall these processes are stochasticso you put some noise herethat's reasonable to noisewe can seethat kind ofswitching to a good state occursand that is somehow expectedbecause both are stable fixed pointsbut since with thisso with this condition green conditionthis mu g is much largermu g so this kind ofthis fixed pointgreen fixed point is largerthan mu g red conditionso this is quite smalland this is quite largeand then if you put some noiseand then maybe by noise it can be easily kicked awaybut this isattracting much morethen we may expect that okayby considering this growthdilution and balanceplus noisethen we may expect thatattraction to a good state occursand with this simulation of this modelthisand in changing the environmental conditionin environmental onegreen condition has alarge mu gand the other is small mu gand we have some equation for thatbut anyway for one conditionso one side is 0.99and the other side is 0.01or something so such differenceso very large differenceand if you change the conditionthen it goes to greenthen if you change the other conditionit goes to redso it worksso this could be apossible explanationand actually this is a very simple modeland experimentalist didcomplicated model but basically same ideaof courseyou canyou already expect that okay this worksnoise strength should beappropriate rangeif the noise is too smallmaybe this can be still stableand if the noise is too largemaybe this can be kicked away alsoand then it goes hereso actually we cancheck that noise strength leveland howthe fraction that good state is reachedso we do several simulationshow the fraction that good state is reachedand so within some regionso around this 0.1to 0.3 or 0.4this good region is selectedbut if this is 0.01or something then basicallystill half and halfand if this istoo large again it starts to decreaseand then finally maybeswitch to itso this is a possible explanationfor this kind ofspontaneous adaptationand maybe this is generallywe can discuss that okayin an active stateboth the synthesisso in a good state synthesisof course in a good stateso that dilution is fasterand this synthesisis also large so they are balancedand in a bad state both are smallso then put noisethen good stateis selectedso that's a proposal for thisand actually there is no direct confirmationthat this really works in that experimentbut only manysupporting suggestions thereand one difficulty here is thatit's not easy to estimatethe noise strength in this cellso if we know okayin this cellthis noise level is something around thisthen we can expect thatbut so far we are not surethat's one problem herethen maybe I should stop heremaybe I'll talk abouttomorrowmaybe this is generalized to some othersI hope to mention some beautifulexperimental setup of thiswakamoto's group but maybe you canyou can know thattomorrowok questionsok see you in 24 minutes initially I did not expecthad not planned to talk about this


Has to come out and get it done on point. But it's UI Goku again, the quick switch! Level 2, please, Gil. Alright, that's fine. This time I'll aim it up. Accuracy! How's it going, everybody? Datsunoi here back with some more Dragon Ball Fighter's rank matches. This time playing the very familiar team of Krillin, Ultra Instinct Goku, and Yamcha. That is right, we are walking the Kame style team at full power right now. This is about the best version of the team. Oh, oh, hold on. Not gapless, but the best we can do without a good assist after we've just got a crack cell wide open. And you know what? Even with no assist, I'm taking the rock. Oh, I could have combo'd off that, but it gives me another shot. And so, you know what? I'm gonna run it right back. Ooh, I'll take a spark. Bait it? Oh, no. Okay, I was not baited. You know what? Let's go UI Goku versus UI Goku real quick. Try something. Oh, it's fine. He wanted the key last. Oh, what a bad reflect for me. Man, with this music in the background, this game is so much more intense. For those that are wondering, this is the Fighters Cup Gojira theme. I, there's probably like only one person out there that was like, what is this soundtrack? Why is this doing so much? Hold on. Can I, can I just get out of here real quick? Yeah, I'm out. No super dashes allowed even against Krillin. I'm gonna take the best level three I can in the corner, Yamcha. Outside of the corner. This level three is not so great, but inside the corner, we got options. I can go low. I can go behind. Let me see both of them. I don't know if this is going to kill the wait UI Goku. No, I messed up the input me and Krillin. Doesn't matter. Super dash is going to clean it up. Whoo. That was that was threatening though. I thought the two rocks would we could get. Oh, no, we're not dead. I forgot he didn't have spark or a third character. But when perfect attack, when perfect attack hits raw like that, usually that's just to the material and there's not too much you can do about it. Hold on, hold on, hold on. Let me just go ahead and get a sliding them. I want to switch out now. No, I don't. He's too worried about the Wolf Fang fist mix. I'm just going to take all the lows I can get in that case. Goku comes in. Oh, the new nerf hurts a lot there. A lot of recovery time added. You know what? I said it before I'll say it again. Let's go UI Goku versus UI Goku. No buttons allowed. Oh, do it twice. So nice. I had to do it twice. Do it a third time. You're dead. Why they let you walk up for so long? I'll never know, but I'm going to take part of it. I'm going to do it every time I can. Oh, I will literally do it as many times. I will do it as much as I have the bar for it. I kind of wish he also did it. That would have been really funny. But instead, he's going to do the right thing and take out our UI Goku. Hard to fault him for that five bars going on six. If we didn't have spark, I would be worried. I'm not going to lie. But then again, I think UI Goku is one of the best characters in the game. Probably number two. I've said that I think when played at his best UI Goku is number two in the game. We're dead. Yamcha is gone.  He gives us level two. Yeah, I thought level one was going to kill for a second. I got very scared. But I think I know how I got to end this. Well, who's better UI Goku or Krillin? It's UI Goku. It's UI Goku. I don't think this is going to kill. That's not so I might as well save the bar. Oh, no. Okay, we got a spark emergency spark emergency spark. Don't level three. Okay. Yeah. And that's not too bad. Again, it is kind of awkward though because now we have to spark. And he hits us again. It's probably over. That's a frame trap. I don't like it here. Oh, I'm getting scared. He X rocks. I don't know what he went for there. It was it was partly the fact that he went for a move. I barely hit him with a jab and also the music was swelling in the background. I that game should not have been as close. I was choking at the end and he was playing really good. That was scary. He's going to perfect attack. No, no reads. There's a reason you're just this is the best. Let's go. The fact that you could extend off that. That's a little while to me. You I Goku says. Oh, hold them down. Give me the Krillin combo. What time is it? Let me peep the clock in the room. It's Krillin time. I don't even want to. Oh, do you just kind of hold it? You got to hold it. You got to hold block. Maybe a raw tag here and there, but for the most part, I want to see defense. You I Goku's coming in. I'm a beam right away. It barely hit him bear. That was insanely close. And again, Krillin's really good at getting the opponent back into the corner. Going to go with a similar strat. Practically forcing sparking. Did it just punch me out of that was sick. I was trying to hold it and make him go for a button, but uh, he just beat me. Do this. I didn't think I would. I did not think I'd get out of that. Get him. Oh, see that right there was what we were hoping for. No trunks assist. He's back dash twice. Now I really got to read that next time we vanish.  That's the read. Just remember the next time he blocks a vanish. We're dashing up. I'm scared though. It's always a hard read to commit to because if they mash out, then that just feels disrespectful. But sometimes that read is the only thing you can do. Our lead is evaporating right in front of us. He erased it completely. Try to read a key blast. It wasn't there for me. Okay. Decent.  I'm going to take a level three. You I go who's got to get out. He blocked the low last time. So I'm going for the cross up. I missed the cross up. I jumped. I super jumped. Oh, no punish on that. No bad reflect as well. Don't switch out. He didn't you I go who a nice tag. I was definitely how and I was I was hoping he would throw something out and change the future. Anything. Whoa. Nice delay. What are you to get back in the corner? I am getting you back in there. I'm panicking. I'm slightly panicking. Be optimal about this. Be optimal about it. Beautiful. You just love to see the optimization. No assists needed. Just take the jumping medium starter get the 4k damage and get out. And now a read by you. I go to. Oh, no. Take the key blast. This character is so cool. Wow, that move is such a cool finisher. I was like, wait, did I win or did I win or did I drop the combo? I don't know what happened, but that is the set of the first set of the video. Let's go ahead and hop into the next one. Hey, we're going up against the guinyu player. It's actually been quite some time since I've played against the guinyu force team. I think the last time was actually double L. But I could be wrong on that. I don't know. Again, it's been a while either way. So come on, man. I wish I would have, I wish I would have been talented enough to convert off that. I would have felt pretty good. The jab, but I will take, I will take the optimization instead with no assist. It doesn't matter. I'm going to get all of this damage. Couple of lights here and there. A sliding to boot. I almost got three bars. Oh, that DPS. This was so good actually caught my reversal and the tag out was nice as well. The UI tech counter just because that was very UI Goku to do. Look at the two age recovery puts me back in range for a man. His two H is really good. You are Goku just has a lot of good stuff about him. All right. Well, I was not in position to do anything about that rocks. No, rocks are not going to stop that. Come on. Oh, no, he stopped me reversal. No, another guard cancel. I'm going to go overhead. Yes, the overhead after that six M on Goku is still pretty strong just because his other light kind of looks like a six M.  But in the heat of the moment, it can really make a deal. No more switching. I'm the ex canceling out of my sentence. Just to say that no more switching. He's going to guard cancel again. No, I'm not allowing any more switches. No DPS. No one's going anywhere. Oh, where's my level one? Oh, the key blast cannon made the rock was a little unnecessary Krillin going to be honest. Even for me, that seemed a little less do a key blast. Oh, no, am I dead? Am I dead? Do I pay the price for that? No, the young justice just stops it. Wow. Is this death here? I yeah. I mean, it is, but is it two bars, two bars? Give it to me for for cheat. Nope. All right. Well, if it's not two bars, I waited too long to go ahead and it's Krillin. So Yamcha, the character I would much rather have on anchor with this team has to come out and get it done on point. But it's you. I go cool again. The quick switch level to please kill. All right. That's fine. This time I aim it up accuracy. That was clean. Well, you know what? I've just realizing now with this game that this ranked video is like the first in a long time that I don't feel like necessarily has a huge point to it. Like we're not trying out to suggest a team. I'm not really going for anything with these specific characters. I'm just playing them because I love this team. I just love this team all together and I guess I mean it does have a point. We are we are getting very close to Master Ultra Instinct rank, which I believe is after God. Yeah. Yeah. It should be the next one. So we are really getting there. I'm going to do it again. So the more wins we get, the higher we get up there and then we can just move on to the next rank. Honestly with the new patch, God of Destruction was not the longest, not the long journey. I thought it would be. I definitely overestimated how long it would take when I said that once we got to God, it was probably going to be a hard wall. But oh, see that's cheap. But yeah, I don't think that was because I was I out performed myself. I just think the new the new patch was a lot greater than I expected in terms of its effect. Why am I talking about stats right now? Let me go ahead and keep playing. Do I go to take a beam and a half? And then we go out in the yoncha because again, we want him on anchor. We don't want him out. So do him second and then Krillin finishes with hopefully just one, but I'll throw two because I'm bad at math. I can't trust myself. If I trusted myself right there, I would have lost the chance. You, I go to come back out. Wow, I can't believe that beat that. First of all, but I'll take sliding. Wow. I can't believe that just happened. I was really trying to read that too. Is that going to hit?  He's not playing no games. There it is. Okay. Nice and opening. Wow. What do I even talk about? Man, I've if you play you, I Goku too much. You're just like, man, this character is good. Talk about you. I Goku is good again. I know we were just talking. Can we talk about it some more though? Oh, please cool or no. I'm you. I don't play by the rules. I should have played by the rules. Sensei being full health. Let's go. That is it. I'm not done with them. The back flip KO punch is going to be enough to get it done. This is what a raid boss character looks like, dude. This is a raid boss DLC character. Yeah, that's the perfect end quote. This here is the power of ultra instinct. Yeah, I don't know guys. I'm going to keep grinding trying to get to master ultra instinct. And I think this team might be what I used to if I play any more offscreen or like off recording. This team will probably be the one I use just because it's so fun. But hopefully you enjoyed this. If you did, definitely let me know down below in the comment section while you're down there. Hit the like button and subscribe to the channel to stay up to date on all things fighting games and fighters. And hey, you can also check out some other videos that should be on your screen right now if you want to watch even more and support the channel even more. Other than that, thanks for watching this one all the way to the end. I have been Dr. Doya and I will see you when the next video is out.


I'm Adam Navas and I'm here with Liz Wade. Hello, Liz. Hi, Adam. Today, we're gonna be having a real conversation about the program all about the smile. If you haven't had a chance to see or listen to that program yet, you can hear it on YouTube. You can listen to it on our podcast. Or if you visit our website, you can read along with the program there. We recommend that you do that prior to this program, but if you haven't and you wanna listen to it and then go back, I guess that's okay too. Liz, before we dive into talking about the program, what is the program all about the smile about? Well, okay, so in this program, really, okay, I will level with you, Adam. I thought when we kind of looked through this program to have this conversation that this would be kind of like a program that I didn't really learn a lot from or that I, you know, I already knew all the stuff. And I was really surprised that there were a lot of things to talk about in this program that were really interesting. And so first of all, it talks about why people smile. And some of those things were really interesting to me or surprising. So we smile when we meet people. We smile maybe when we're uncomfortable, you know? And I thought to myself, oh, I do smile when I'm uncomfortable, right? Like if I'm in an awkward situation, I'm like, yeah, sorry. And then, but that is for a purpose to form some human connection so that people can understand me better and so that I can like communicate to them that I need help. And there was also a reason that people smile is to make them feel happier, which I also thought was very interesting. And then it talked about the ways that you can tell if someone is really smiling or if they are using a fake smile. So that was really interesting. And then finally, the program really talks about the meaning of smiles in different cultures. So, you know, maybe smiling in one culture isn't as popular or it sends a different message than if you smile in a different culture. And, you know, those things can be, yeah, just misinterpreted if you're smiling in one culture and then another. So really that just went through all the different things about a smile. And I, like I said, I learned a lot in this program.  Yeah, I smile all the time. And then you read it and you're reading through all these different ways that a smile works. And it actually made me think of emojis because there's a smile emoji, right? Hey, it means happy. But there's also like subtle like nervous emojis, like trying to distill the different smile meanings into emojis is really kind of, it was a helpful way for me to think about the different ways people use smiles to communicate different things.  Right. And it isn't that the emojis- Or do you even add a smile emoji? Yeah. Well, and it's not that the emojis determine how we communicate. We need these emojis because they help us communicate. Right. But I think that the, I got really excited or not excited. See, again, I'm struggling for what is the word? What is the, it really made me think about the different people who are going to be listening to this program where they lived what a smile meant to them.  Yeah, and I was gonna say that stuff really changes from person to person, even within a culture. So I think that like probably people in the United States smile a lot, compared to maybe other cultures. But there are still people in the United States who maybe don't smile a lot. And some who smile even more. So yeah, I am really interested, like maybe if your culture is a smiling culture, but you are not a smiling person, like how does that make you feel? Well, and there's also places, I've known people who've come to the United States and they have found people to smile a lot, but they don't get to know people beyond that, what they call the surface level. So they're very friendly, hello, how are you? But if they really wanna go and like have a deep relationship, the smile isn't very deep. Yeah, well, and I could imagine if you were in that position and you were not used to a culture that smiled a lot, that you might be confused about what those smiling messages are sending, right? Like, oh, I see all these people smiling at me, what does that mean? Even if you don't think in your head, what is that person smiling at me for? It might be just under the surface, like, oh, I feel really uncomfortable here and I don't know why. You don't know me, why are you smiling at me? That's weird. Or even as a lady who has traveled before, sometimes I have been told in a country, I don't even know what country it was, but in some countries, you shouldn't smile at people on the street because it sends a message that you're not wanting to send.  So in the United States, when I smile at a person on the street, everybody just usually smiles at each other. Just a quick little. Yeah, exactly, just a greeting, a smile greeting. But maybe if you go to a different culture, like I said, I've been told, don't just smile at anyone because it might be giving a message that you don't want to give. Yes. Yeah. Well, interestingly, I was in the store just yesterday, I think, buying some eggs. And I was wearing a mask. And someone who was working at the store was also wearing a mask. And we were doing that little polite thing, but all we had, we just had our eyebrows, so it was just like. Like that's all, it's just this little, we had to smile, not just because the program talks about smiling with your eyes, right? Like the genuine smile talks about your eyes. And people, a lot of people, at least in the United States over the last year where people have been wearing masks, have said, oh, I can't see people smile, I don't know.  And I think that's an important, it was fun, we had to work really hard to smile, but it can be done, right?  So then, I always think like when I pass someone, I'm like, you know, hi, or even just a smile, like just a greeting smile. But then I'm like, oh, they can't see my eyes. So then like, what do I do? Then I just look super rude, just walking by people. You have to use your whole body. Yeah, exactly.  Hello! How do you smile? Yeah, jazz hands.    No, please. No, I was gonna change the subject.  No, I just, I was thinking about, we're talking about the differences between one country and another as far as smiling. And that reminded me of the program about apologizing. Do you remember that one about how different cultures, different countries apologize and say, I'm sorry for a variety of different situations that if you bump into someone while you're walking, you might say, I'm sorry. Other people wouldn't, you know, that's just life. There's lots of people around. So I think if you liked this program, you should definitely check out that program. I'm not sure exactly what the title is saying sorry. I think it's just called saying sorry. Yeah, so check out that program and let us know. Or the power of apology. Yeah, I don't know. I'm thinking. Let's try to, yeah. See, we're both smiling out of like, are we happy? Yeah, I don't know. Are we happy we can't remember the name of that program exactly? No, but we're like, eh. Like, good enough. I did want to talk about the why people smile part. Because I thought that was really interesting. You know, I don't really think about when I meet people if I smile, but I do. But then also, like I mentioned before, that sort of being uncomfortable and forming a connection, I thought that was really interesting. Like why, you know, instead of using words, it's just this really important, like just facial thing we do without even thinking of it. Yeah. And speaking of other programs, Adam. Yes. That's the face program, right?  Yes. Now, what is that one called? The human face? No, it's not called that. Anyway, so yeah, all of those non-verbal sort of things that go along with your like, sorry. Yeah, the things you're not thinking about that you are. I don't know what to do. Yeah, and just that because we all smile. Yeah. And because we have those expressions that communicate things, that is sort of like a worldwide thing, I think. Yeah. I do think a lot of what we do with our face is we don't think about it. But I do think when we meet babies, Oh yeah. We are very into, like we exaggerate, we're like, Hey! Yeah. And we know those non-verbals because they don't have verbal skills, right? So that we do a lot of it with their tone of voice, but also with our faces and we might lower our tone and hi! You know, so I think that we do know in our heart what those big smiles and smiling with our eyes does. And we can use those. We can be intentional about how we use those. Yeah. Though it's sometimes not genuine. I mean, that's the hard line. But speaking of being, you used an interesting word there that I really wanted to pick up on. And that was intentional. Okay. And so I think actually my biggest takeaway from this program was about using a smile intentionally. And so when, like why people smile is to make people feel happier, but also to make yourself feel happier. So that was something super interesting to me in, you know, if you're feeling down or like I am, maybe you can hear in my voice, I am sick. I am so sick right now. Yeah, I feel bad, but... And yeah, I have a very bad cold and one of the ways to make yourself feel better, probably mentally, but you know, your mental state and also influence your physical state is to smile and you can feel better.  So I thought if we are maybe like down in the dumps, there's another idiom for you. If we're feeling sad or down about things. And I have seen this in sort of like in apps that encourage gratitude to smile and that you can smile, even if you are feeling terrible and even if you are feeling sad and even if something bad happened, you can practice smiling and you just maybe go in front of a mirror and smile 10 times. See how that feels. It sounds weird. Do that a couple times a day. It's like a little exercise. Yeah, it is. It is just like exercise. You know you exercise your muscles to make your body better. Maybe you exercise your smiling to make your whole mental state feel better. Well Liz, whenever we get to do one of these, you make me smile. So I appreciate even though you're not feeling well, we can talk to our spotlight friends and I wanna say that if you haven't listened to this program all about the smile, make sure you go and do that. While you're there, you can subscribe to us. You can smile. You can smile. You will naturally smile. We hope we've made you smile, but make sure you subscribe to us on YouTube. Check out our website, follow us on social media. And we hope that you are having a good smiley day. We hope that until next time you listen, watch, practice and learn. Spotlight out.