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MLA Full: "Molecule Architecture: SciShow Talk Show with Dr. Orion Berryman." YouTube, uploaded by SciShow, 3 January 2018, www.youtube.com/watch?v=0qpZdri0zEc.
MLA Inline: (SciShow, 2018)
APA Full: SciShow. (2018, January 3). Molecule Architecture: SciShow Talk Show with Dr. Orion Berryman [Video]. YouTube. https://youtube.com/watch?v=0qpZdri0zEc
APA Inline: (SciShow, 2018)
Chicago Full: SciShow, "Molecule Architecture: SciShow Talk Show with Dr. Orion Berryman.", January 3, 2018, YouTube, 38:21,
https://youtube.com/watch?v=0qpZdri0zEc.
Dr. Orion Berryman talks with Hank about the cool chemistry going on in his lab, and Jessi from Animal Wonders brings in Prickle the Hedgehog!

Animal Wonders Montana: https://www.youtube.com/animalwondersmontana

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Sources:

 (00:00) to (02:00)


(Intro)

Hank: Hello. Welcome to SciShow Talk Show.  It's that day on SciShow where we talk to interesting people about interesting stuff.  Today, we've got Dr. Orion Berryman.  Did I get that right?

[ORION BERRYMAN]

[Orion Berryman - Molecular Lab]

Orion: Nailed it.  

Hank: Assistant Professor of Chemistry at the University of Montana.  You have a group, the Orion Berryman group, and we have talked to people from your group before.  It's pretty cool to have a group.  Like, how does that happen?  Do you like--

O: It's like a bunch of groupies following you around.

H: Yeah.

O: No, it's like--

H: Just graduate students doing your bidding.

O: Exactly.  Like slave labor basically.

H: That's way better than groupies.  Do crystallography for me.  Make a molecule.  Go.

O: That's right.  Certain benefits, anyway.

H: Yeah, you've littered my coffee table here with molecules.

O: Yeah, sorry about that.  

H: No, it's fine.  I accept.  You--so you're doing organic chemistry.

O: Yeah.  We call it physical or organic chemistry, or supramolecular chemistry.

H: Supra?

O: Supra, yeah, so the chemistry outside of a molecule.  

H: Wait a second, 'cause isn't all chemistry just molecules?

O: Yeah, so, I mean, typically, when you think of organic chemistry, a lot of organic chemists construct molecules or figure out efficient ways to synthesize or make a molecule, and that's really important for the applications that we do, but we're also interested in once we make that molecule, can we study it and learn how it interacts with other molecules?

H: So, I mean, isn't that just all chemistry?

O: Yeah, so--

H: I don't mean to harsh your buzz.

O: No, that's really great.

H: But molecules interacting with each other.  

O: Yeah, so that's the really cool part of being a supramolecular chemist, is that you can apply research in supramolecular chemistry to any chemistry field.

H: Yeah, and you've got these 3D printed molecules here and these all look basically like the same thing, except that, so these two are the same, except for whatever this is.

 (02:00) to (04:00)


O: Mhm.

H: I don't know what this is. What is that?

O: That's purine (?), which is an anion. So this thing that you're pointing at is important because we synthesize the rest of the molecule- this is just a model of it, obviously, the molecules themselves are much smaller--

H: I think we were all there, at least.

O: You said that your chemistry was really rusty, so I thought I'd start there.

H: Thanks, appreciated.

O: So, we're interested in targeting or selectively sensing these anionic portions or anions. So how this molecule interacts with these things, chloride in this case or purinate in this case, is important to us.

H: And purinate... no idea what that is.

O: Purinate is a tetrahedral oxoanion; there's four oxygens around a metal. And so why people are interested in purinate is because it's very structurally and electronically similar to protecnotate (?) which is radioactive and nobody likes to play with protecnotate(?). So we use that as a surrogate or a model for protecnotate, basically.

H: And why do people want to do chemistry with "protectonate?"

O: They want to know how it can be a contaminant, so how you could remove radioactive--

H: Pull it out of stuff, okay.

O: Yeah, exactly.

H: So you're creating all of this whole thing except for the anion and using this to influence the anion.

O: Yes, so we study how strongly we can quantify- how strongly this molecule, once we've made it, interacts with different anions. Now, this gives us a sense of how efficient our molecule is or could be at extracting a contaminant or something of interest.

H: So, basically, creating a place that an anion wants to be, [unintelligible] negatively-charged ion of some kind.

O: Yeah, so we're essentially like molecular architects, where we're trying to design a molecule to complement the size and shape and electronics of another molecule.

H: So this is a pretty active area of research for you right now?

O: Yeah, it is.

H: I'm assuming because there's only four things here on this desk. Three of them are this.

 (04:00) to (06:00)


O: Well, so this happened to be, you know, when we were interested in figuring out if we could 3D print our crystalline structure, so this happened to be one of those new structures that we had, so we just sent a bunch of different samples out for printing.

H: Okay, cool! So you're making stuff frequently, new models?

O: My students are. I unfortunately don't.

H: You just supervise.

O: Exactly.

H: Does this have a name, this structure that you've built? Are you trying to figure out the IUPAC name in your head right now? 'Cause that's gonna be really long.

O: It is gonna be. I would have to go to ChemDraw or something and look it up. So what this molecule taught us, really- so this was kind of our first generation receptor- and this taught us that our design was probably more flexible than we wanted it to be.

H: Flexible, like, physically?

O: It has lots of conformational--

H: Like it can bend and wiggle--

O: Yeah, it can move in a lot of different conformations, more than we wanted to. If you really want to design something that's very selective for something, one way to do that is to make it pre-organised or to already be complimenting the shape of whatever you're trying to target. And so this design taught us that these alkyne bonds, these carbon-carbon triple bonds here-- you know, you have essentially energetically free rotation around that bond.

H: But double bonds don't have that, but triple bonds do?

O: The single bonds adjacent to them, yeah.

H: Gotcha. So you're getting wiggles?

O: Yeah, so basically this led us to creating more rigid molecules so that we can complement other things and make them more pre-organised. And then that led us to building larger structures like these molecules over here.

H: This is a big old thing!

O: Yeah, so this is an extension of this piece, this little binding motif, we've essentially just elongated it. And so then we have nine aromatic rings instead of three.

H: And then this is when you do the crystallography, this is what it looks like.

O: Yeah, that was the big surprise for us. So we take one of these strands which has three different binding sites now, and we dissolve it in solution and something really complicated happened, we could tell by NMR spectroscopy.


 (06:00) to (08:00)


O: We couldn't tell what that was until we got a crystal structure and it turned out to be this really cool triple helix binding around two iodides. That's kind of some of the power of X-ray crystallography is that it gives us atomic resolution of structures. And then we can go back and say now we have the coordinates and we know the symmetry of this molecule, we can go look at our other data and say, wow, that really does fit the symmetry that we see in the crystal structure as well.

H: Right. So somewhere in there there's your iodides.

O: Yeah, so if you look there's a pore here and you can see that middle atom here, that's an iodide. And there's one on the other side. So we think- now we've done some preliminary studies where these ions are fluxing in and out, and so this basically just looks like a small ion channel. So that's one of the areas of research we're pursuing is extending this into a larger structure.

H: Yeah, I mean my background, if it is that anymore, is in biochemistry, and so when I think about this there's obviously lots of biological enzymes in your body, in my body, that do similar things. Like when you need an oxygen or an OH group, you need a place for it to sort of go to increase its energy level so that a reaction can proceed, lots of things like this, but obviously much bigger than this.

O: Right, yeah. So in biochemistry-- you know, we're a very collaborative university, when I talk to other professors that are biochemists, they kind of look at our molecules and say "oh, that's cute!"

H: That's super cute, I mean, this is adorable! It's symmetrical, yeah, super cute! Whereas this is getting to more what biochemistry is. 

O: They'd still consider that cute.

H: Yeah, this is tiny still, but, you know, it's a messy clump of lumpy stuff that's gonna be moving around a lot. Even when you do crystallize it, you might not know what it looks like in solution.

O: Right, exactly. But to me it's fascinating because for three of these strands to come together and bind two iodides in a very specific, higher-order structure it's really pretty amazing, the things that have to come together to do that. You know, there's over 50, I think 58 pi-stacking interactions that are contributing to the energetics of the stability of this, as well as these very directional halogen bonds and that's what we're kind of excited about.



 (08:00) to (10:00)


O: Those halogen bonds force the assembly of this complicated structure rather than a simple one-to-one binding like we would see in these more simpler cases.

H: Right, but it's still functional. So are you looking at catalysis here or are you looking at cleaning up radioactive spills?

O: Yeah, so the smaller stuff we originally wanted-- we were looking at building catalysts and anion sensors based on halogen bonding interactions.

H: Anion sensors? So just telling you stuff's there?

O: Yeah, so if you could determine the concentration of, say, protecnotate in a solution it could be of value to someone.

H: To someone, we're not gonna say who.

O: Not somebody walking down the street, but yeah.

H: So you were talking about pi-stacking, I don't know what that is.

O: Yeah, so that's the wheelhouse of supermolecular chemistry are these non-covalent interactions or how molecules interact with each other. And so pi-stacking is one of the types of non-covalent interactions and it occurs when you have something with pi electrons or two things with pi electrons. And then, in certain orientations, that could be an attractive interaction. And so all of these small interactions in concert can lead to really a large enthalpic or large energetic contribution to the stability of the structure.

H: Sort of base level chemistry, usually talking about covalent bonds but also hydrogen bonds, which are non-covalent and a huge deal when you're figuring out the structure of a protein, but then you've got a lot of other kinds as well.

O: So I teach sophomore organic chemistry and we talk about synthesis, making molecules, and then we kinda just brush on hydrogen bonds and trying to explain the importance of those, but there's a whole another really cool world out there--

H: Of non-covalent bonds.

O: And if you really delve into the chemistry major, you get to experience these things and I highly encourage it.

H: When did you graduate from-- when did you finish your undergrad?

O: I graduated in 2003.

H: So right around me.

O: Yeah, we're both ancient.

 (10:00) to (12:00)


H: Yeah, ancient! How long ago were you doing this?

O: That was probably a year and a half ago or so.

H: And then you've been moving on to these [intelligible] structures.

O: Well I have one student, Casey Massena, who has been working on that project. And then I have other students that have been basically been working on the second generation of these molecules, other ways of how we make them more pre-organised, like sticking intra-molecular hydrogen bonds, or hydrogen bonds within the same molecule.

H: So what are the characteristics of this that's making it really good, like a nice, happy home for an anion?


O: Well so, I could tell you maybe what I'm excited about or why we use halogen bonds or why we're excited about them.

H: Okay! And these are the halogens?

O: Right. So, typically, when we teach sophomore organic chemistry, you think of halogens as being electronegative, so they pull electrons towards them. That's not the whole story, halogens have lots of electrons that are malleable or polariseable. If you put electron-withdrawing groups you can polarise that electron density around halogens.

H: So it's like this big, squishy cloud of electrons around them.

O: Exactly.

H: So you're not just pulling electrons to one side of the atom?

O: It's hard to quantify the location. We can see relative to that original, without the electron-withdrawing groups, that there's electropositive distal end of the halogens, what we call the "sigma hole" in the chemistry jargon. And that electropositive region is attracted to negative things or Lewis bases, things that have a lot of electron density. That's one of the bases of this halogen bond or this attractive interaction. So why is it cool? 'Cause hydrogen bonds, we know, are ubiquitous and have a myriad of important applications. But a halogen bond is similar to a hydrogen bond but there's other characteristics. So, for instance, because we're dealing with a polariseable atom as your donor, the halogen, we can expect complementarity with really kinda squishy or polariseable Lewis bases or anions. So that's something that's tough to do with hydrogen bonds, right? They prefer a tight point charge.


 (12:00) to (14:00)


O: And so we can expect some complementarity with large, squishy anions. And also the directionality of the interaction is such that it wants to be 180 degrees. If you deviate from 180 degrees, you get electron pair-electron pair repulsion with the other electrons around the halogen. And so, while the hydrogen bond is very directional, the halogen bond is much more directional. So from a design standpoint that's really cool because you can say I want the substrate to bind right there, so I'm gonna point my halogen right in that direction. So those are kind of the two properties.

H: So this carbon backbone, you're basically creating that just to give these two a place to be and point them where they wanna be.

O: For me, that's kind of the fun part of the job, is we get to think about the design of a molecule, what's the best way to orient those two halogens in this particular angle and direction.

H: And this makes sense and is easy, this - I guess you kind of know in your head, you got a picture of how it looks, but - once it starts to fold up... it's a mess.

O: Yeah, unexpected and hard to characterise, but really it points to the exciting part. The discovery part of chemistry or any science are these serendipitous discoveries that you can then lead to new applications and new discoveries.

H: Yeah, I mean, definitely, to me, this feels like organic chemistry and this feels like you're getting close to how natural systems create enzymes and catalysts, which is very interesting.

O: And it's important to have that link between, very simple, we can fully understand, hopefully, this process, to more complicated. And now that can lead us to why these really complicated systems work in [unintelligible] as well.

H: Right. And also these complicated natural systems, they work very well, sometimes better than anything that we can - well, usually better than anything we can do - but they don't have access to all the same tools and intentionality that we have access to.

 (14:00) to (16:00)


H: It's not like my body can just throw a chlorine atom into an enzyme. It doesn't have access to chlorine atoms because they're poisonous and they're not hanging out in my body; it's not a nutrient. Whereas you totally can incorporate halogens, metals, all this stuff into doing chemistry that a natural system wouldn't normally. Though, there are always exceptions, weird ones.

O: Right.

H: And, of course, metals are a very important part of my chemistry, because of hemoglobin and such. You know, breathing.

O: I appreciate breathing these days too.

H: It's very interesting to me because when I studied organic chemistry - and I didn't a lot - it felt like there was a very tight distinction between what was being done in organic chemistry and what was being done in biochemistry. And this makes me feel - even though it is a cute little molecule - that that line is getting blurrier.

O: Yeah, it is, certainly.

H: Well, what's going on in your lab?

O: Well, you were talking about metals. We are designing ligands to extract particularly arsenate and uranyl from contaminated sources.

H: Bad stuff.

O: Yeah.

H: That's sort of a Montana problem.

O: The arsenic is, the uranium not so much. Turns out you could be rich if you could extract uranium from seawater.

H: Ah, yes! You could be rich if you could extract a number of different metals from seawater.

O: Exactly, exactly!

H: So that's what you're thinking with that then.

O: Yeah. You have to fund a lab somehow, right?

H: I hadn't had that thought. That's an exciting one, sucking uranium out of seawater.

O: It's three parts per billion, pretty consistent throughout the ocean. So there's a lot more uranium in the ocean than there is terrestrially.

H: A number of chemists have gone down the hole of trying to extract gold from seawater and how rich they would be if they could do it.

O: Yeah, the Japanese have actually developed processes where they can extract kilograms of uranium from seawater. It's just cheaper right now to still mine it.
 


 (16:00) to (18:00)


H: There's this economic idea that there's no upward limit on the price of gold, it's just whatever the demand is. And I'm like, "no, the limit is how much it costs to extract it from seawater." That is how much gold will ever cost, it will never cost more than that. It just happens to be more than it currently costs. Somebody should know what that number is and I don't know that anyone does right now, but there is certainly a number. Wow, and they have extracted kilograms of uranium from seawater?

O: Yeah, over the course of months.

H: I hadn't thought about that application. What other weird things are you gonna try to do to blow up the world?

O: We're also working on designing oxyanion-hole mimics.

H: Sure, which is like a biochem thing?

O: Yup, but looking at it from a small molecule approach. I mentioned earlier one of the projects we're working on is developing catalysts or trying to make more efficient organic catalysts. Nature does this very well, oxyanion holes stabilize negatively-charged oxygens in enzyme active sites through hydrogen bonds, ion pairing, all sorts of things. These are high-energy states that the enzyme is really good at stabilizing. We're interested in doing that from a small molecule approach and trying to learn what they do in enzyme active sites and apply it to small molecules. And it's a similar strategy to what we use for our other projects - we're designing a molecule and trying to manipulate its interaction with another molecule. So we have a catalyst and we have a substrate, say this is a carbonyl compound that we're interested in catalysing, so a carbon-oxygen double bond or something containing a carbon-oxygen double bond. Energetically, it prefers to bind coplanar with whatever you're interacting with, say it's a hydrogen-bonding organic catalyst. What it looks like enzymes do is they actually bind orthogonal so they raise the ground-state binding energy of this complex.

 (18:00) to (20:00)


O: So then your difference in energy between your high-energy transition state and your molecule that you're trying to react is smaller. So that's what we're trying to do with small molecules, it's just sterically control how this catalyst reacts with this substrate.

H: So, say, nature is good at this, but we can do it with fewer molecules or fewer atoms.

O: Well, we don't expect to be better than nature at it, but maybe we could do it more- because enzyme active sites can be very specific for a particular substrate- so maybe we could design a catalyst that could be more broadly applicable to a larger scope of substrates. Or we could learn how to do it more efficiently and apply that same principle to other reactions or catalysts.

H: Let me know if you can ever extract uranium efficiently from seawater, I would be interested in investing $40 in that.

O: It would probably be good turnaround from your investment.

H: Yeah, that's all I got for you though.

O: We'll take anything we could get.

H: It's interesting, oftentimes I think of science being done at universities as sort of like, "We're doing the science because we wanna do the science and we wanna learn about stuff and maybe this could be a pharmaceutical someday." But I had not thought of sea mining applications, which is a much bigger industrial thing.

O: Right.

H: Awesome! Do you wanna meet an animal?

O: Heck yeah!

H: Okay!

[TITLE SEQUENCE]

[JESSI KNUDSEN CASTAÑEDA]

[Animal Wonders]

H: So you brought us what is clearly some kind of inorganic compound.

Jessi Knudsen Castaneda (J): It's a Pokeball! This is Prickle. (holding a hedgehog) 

H: It's a Pokeball... Did you do that on purpose?

J: This is Prickle, she is a pigmy hedgehog. These guys you would not find them in the wild, they are kind of a man-made thing. We messed around with nature a little bit.

H: You were like, "Hedgehogs weren't cute enough, we wanna make them cuter."

 (20:00) to (22:00)


J: Right, we want them smaller, cuter and in our homes. So they bred the little ones, they hybridized them and bred the little ones and we got this tiny little thing. So people have them as pets and she was purchased as a pet and they weren't very nice to her.

H: It sounds like it's a familiar story at Animal Wonders. Somebody had a pet and then they were like, "This is harder than I thought."

J: Yeah, "We give up." They ended up abandoning her, they told the pet store to board her and then never returned. The pet store, once they realized she was abandoned, they were like, "Oh, we should probably pay a little bit more attention to her," and found that she wasn't eating. Oh, what does my finger smell like? Just don't bite it.

H: Mealworms?

O: You should probably wash your hands.

J: She has a previously broken leg, so she's a little wobbly, and she was super, super skinny when we first got her. I didn't think she was gonna make it but we got her some really fatty wax worms and she fattened up and she's doing alright now. She's a little smaller than a normal pigmy hedgehog, I think that's just some malnutrition as she grew up or it could just be her. And she's doing alright, she's, we guess, four and a half.

H: How long have you had her?

J: Two years, two and a half years and the pet store just guessed that she was two. So we really don't know how old she is. She was an adult already.

H: This is how you communicate?

J: Yeah, she's huffing and she's like, "I don't like that, I don't like that." But she doesn't not like it enough to be really mad, it's more just a, "Ugh, come on now, stop it." Would you like to hold her?

H: Do you want a treat?

J: Oh, a treat? Yeah.

H: Want a treat? No?

J: Get a little bit closer.

H: Oh what's that? Yes! Oh yes, I love mealworms, that is good, that is my thing, that is my jam!

 (22:00) to (24:00)


J: I love how they eat - nyang nyang nyang! They don't really have very good molars, they have bunch of little sharp dagger teeth, so it's quite inefficient.

H: Oh, come on, finish your food!

J: Ew, exoskeleton! You had a bunch, why are you looking for more?

H: Could somebody peel the next one for me?

J: They are going through a molt, so it probably is kind of a thick exoskeleton that they have on there. So yeah, so they have these sharp dagger teeth. A lot of people think that they're related to porcupines or rats and they're not, they are their own little group. They do not have evergrowing teeth, they are related to moles. And they used to be classified as an insectivore, like the insectivore group, but they have disbanded that and said it's not a thing. So they are reclassifying these guys and we gotta keep on top of it and I don't remember the word that they belong to now. It's a longer one and they made it really complicated and wild.

H: No, they didn't make it complicated, Jessi, it is complicated!

J: Yeah, but they didn't have to name it a complicated name.

H: Oh yeah, they could've called it "Hedgehoggites."

J: "Hedgehoggite," right. I would've been happy with that or [unintelligible] or whatever.

H: Something cute. 

J: Just not something like 20 letters long that's a bunch of-

H: -weird Latin probably meaning something.

J: Yeah. I gotta be careful with her because these guys do not understand edges and she will rush right off my lap. They do have an instinct for when they do fall off something. Instead of developing a way to not walk off a ledge, they developed a way to protect themselves when they do. So they'll roll into a ball and then their quills will cushion the fall. I tried to catch one once.

H: How did that feel?

J: That was definitely a mistake. Immediate regret and then two weeks of prolonged regret.

 (24:00) to (26:00)


J: My hand was inflamed and... These guys are not clean at all - would you like to hold her?

H: So I've heard you're not clean at all.

J: They love to get as dirty as possible because these quills - you know, if I touch her, it's not like a porcupine, they don't come out and stick.

H: Yeah, they're not unpleasant to touch.

J: Well, she's also calm, she's quite a calm hedgehog. You've met a different hedgehog named Groucho - aptly named - and Groucho would always roll into a ball and get really pokey. But she's quite calm, and so she lays them flat. Even when they are flexing their muscles and their quills criss-cross like that, they have to - is she licking you?

H: She's just getting into a ball.

J: She's just doing her thing. And so, in order to make a predator go away, they will roll into a ball and they will jump towards it a little bit. But even a little poke isn't as bad as a germy poke.

H: Right, a nice and dirty poke.

J: Does she like to smell your finger?

H: Ow, don't do that!

J: Oh yeah, she'll bite you.

O: Are they barbed?

J: They're not, and they don't come out at all. So what they'll do is they'll roll around in their own poop and pee and then if they find some weird new substance like a new plant or something like that, they'll go and chew on it and lick and chew and get all this spit and turn it into this froth. And then they'll arch their back and spin around and lick all that frothy spit onto their back. It's called self-anointing and it's getting all of that, hopefully, toxic substance all over their quills so that when they do poke a predator they'll learn their lesson.

H: The predator will be like, "Boy, I'm not gonna do that again."

O: They'll remember it.

J: Yeah. 

H: Just like you learned.

J: My favourite is the tail.

H: Is there a tail?

J: I usually don't get to see it because I'm holding her, but yeah!

H: Don't fall, don't fall! I wanna see the tail, there's nothing there.

J: It's a cute little nub.

 (26:00) to (28:00)


J: Here you are, there.

H: Oh yeah! Oh, that's dumb! That's a dumb little tail!

J: It's a little nubbin, tiny little nubbin.

H: That doesn't look like it's doing you any good.

O: Does it serve any functional purpose?

J: No, just there.

O: Just cute.

H: Oh, that's the best! Look at its funny mouth!

J: I know, she does that little sneer almost.

O: Cute little claws, look at those things!

J: Isn't she sweet? Alright, she'll walk right off your hands so you have to just keep - whatever she does, she's just, "Hold me, guys."

O: Aww!

J: So what do you think she feels like when you pet her quills? What does that feel like?

H: Like nothing I've felt before.

O: A hedgehog?

J: It kinda feels like a plastic brush quills.

H: Sure.

O: Yeah, it's got some resistance to it.

J: Yeah, and it makes a weird - 

H: Clicky?

J: - clicky noise, yeah.

H: I found it pleasant, weirdly. Like that's a nice feeling.

J: Yeah, they have about 5000 quills on them, which is impressive.

H: It's more than I got.

J: Yeah! What'd she find? She is all into the smells today. I'm hoping that she finds a new smell and does her self-anointing, cause that would be really cool.

O: It must be that mealworm in my pocket.

J: She smells something weird. But yeah, it's just her top half that's covered in quills.

H: Yeah, it's just like cute, soft fuzz on the bottom.

J: Yeah, her little belly is underneath there.

H: Cause it's good to be half soft, half danger.

J: Good to be? Sure.

H: I wouldn't wanna be all danger.

J: But half danger...

H: Yeah, "Half Danger" is my middle name.

J: Yeah, here, if you feel - go like that and feel the top and feel that skin area underneath there.

H: Where are you going? Yeah, okay.

J: Do you feel like it's almost a ledge there?

H: Yeah.









 


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