[User] Please transcribe this text

[Assistant] You can see this free phosphate on the signal end, which is, includes the RSS and is the DNA we're gonna throw away.


[User] Please transcribe this text

[Assistant] You can see that nucleophilic attack, so that the coding end ends up with this weird hairpin. The signal end ends up with a double-strand break, basically. And the signal end just gets pasted together and


[User] Please transcribe this text

[Assistant] lives happily ever after as a signal and no one cares.


[User] Please transcribe this text

[Assistant] And how we resolve that hairpin on the coating end.


[User] Please transcribe this text

[Assistant] As I introduced last time, we have this enzyme, artemis, that cuts open the hairpin.


[User] Please transcribe this text

[Assistant] Artemis is fantastic! It can cut open the hairpin and allow this process to happen. But it also is not perfect because


[User] Please transcribe this text

[Assistant] But it can actually reach up to five base pairs in either direction from the base pair where it is cutting. If it happens to cut the right,


[User] Please transcribe this text

[Assistant] Phosphodiester bond, then we get the same product that we had started with.


[User] Please transcribe this text

[Assistant] However, if it cuts too far towards the five prime end, we get this overhang on the bottom strand.


[User] Please transcribe this text

[Assistant] If it cuts too far towards the 3 prime end, we get this overhang on the top strand. Uhm, you can see that here at the bottom as well.


[User] Please transcribe this text

[Assistant] And that will get filled in by DNA repair enzymes to make sure that that DNA is double stranded.


[User] Please transcribe this text

[Assistant] I went through the specific examples with this sequence last time on the board.


[User] Please transcribe this text

[Assistant] And if you remember, we looked at the sequence, we saw that we still have the TC that was present in the original germline sequence. So usually when I say germline, I mean the normal sequence that's in every other cell of the organism and is also in the eggs and the sperm.


[User] Please transcribe this text

[Assistant] Uhm, so that's kind of the original germline. But you can also see that at the end, we've added two new base pairs of sequence that were not present in the original germline.


[User] Please transcribe this text

[Assistant] There was no GA after this TC before. We've now added it.


[User] Please transcribe this text

[Assistant] Uhm, in this process. And those added nucleotides are called p-nucleotides.


[User] Please transcribe this text

[Assistant] Uhm, because they are palindromic nucleotides. Uhm, and they're palindromic because if you actually look at them in going forward and reverse, they read the same way. So it's T, C, G, A.


[User] Please transcribe this text

[Assistant] One way and TCGA on the other strand. Uhm, so it reads the same forward and reverse, just like many different words in the English language.


[User] Please transcribe this text

[Assistant] This addition of p-nucleotides is one of the two forms of junctional diversity that I mentioned. So we might be joining together our J,


[User] Please transcribe this text

[Assistant] Uh, Kappa 1, RV Kappa 21 that are shown in pink and in yellow.


[User] Please transcribe this text

[Assistant] And the final cell that does that.


[User] Please transcribe this text

[Assistant] Could end up with slightly different sequence than this original germline sequence.


[User] Please transcribe this text

[Assistant] Uhm, if you remember that was part of how we were getting to the math of the huge diversity of different antibody genes.


[User] Please transcribe this text

[Assistant] Talked about the sprinkles on top of the, uh, VDJ diversity.


[User] Please transcribe this text

[Assistant] The p-nucleotides that you just saw are one of the two types of junctional diversity. So one of the ways that some of these


[User] Please transcribe this text

[Assistant] Uhm, in the third CDR3, or the third CDR region, that third little loop that's touching the antigen, so this junctional diversity is really letting us get some good diversity there.


[User] Please transcribe this text

[Assistant] Uhm, exact same process in this figure from your textbook. So you see that we have the hairpin being opened asymmetrically, uhm, and we can fill that in. This is actually, I was showing you before an older version of it from your textbook, or version from an older textbook, but it's exactly the same, uhm, with the sequence here.


[User] Please transcribe this text

[Assistant] Sometimes people also want to go through, like, for some people it makes sense to actually see it on the sequence as well. So here's my sequence. So what you can see is here's my V, and here's my J. The V and the J are in black. The RSSs are in red.


[User] Please transcribe this text

[Assistant] And so I've got my heptamer, the seven base pairs, the random 12 and then the 23.


[User] Please transcribe this text

[Assistant] And RAG1 and RAG2 first kind of line those up next to each other. So bend around the DNA. So it looks kind of like this. There's a long ton of DNA in between.


[User] Please transcribe this text

[Assistant] So the first thing that happens is, rag, oops.


[User] Please transcribe this text

[Assistant] Bragg one is gonna, Bragg two is gonna make that nick and give us our free three prime hydroxyls.


[User] Please transcribe this text

[Assistant] You could imagine pretty quickly that it's gonna get messy if I keep drawing both of them. So instead, I'm just gonna draw one.


[User] Please transcribe this text

[Assistant] So now I have my nicked DNA. I've got my three, my free hydroxyl here.


[User] Please transcribe this text

[Assistant] Uhm, and you can see that I still have the intact DNA on the other strand.


[User] Please transcribe this text

[Assistant] This free 3' hydroxyl is going to do a nucleophilic attack.


[User] Please transcribe this text

[Assistant] We're gonna get a little hairpin that looks like that because there's a bond between that T and that A. Uhm, now what could happen is that Artemis could cut here for one, two, three, four, five,


[User] Please transcribe this text

[Assistant] Or one, two, three, four, five. So Artemis has a lot of choices of places it could cut. Uhm, we're going to assume... I'm not sure I know how to do this. Hold on. Momentary, uhm...


[User] Please transcribe this text

[Assistant] Alright. There, I got rid of my drawing. Uhm, so, we're gonna assume that we cut right here. So that's kind of the most, one of the most extreme places that I could cut my hair from. So in the N, I'm gonna have, the T is gonna end up down here. The A is gonna end up here. T, A, C.


[User] Please transcribe this text

[Assistant] Just because we've cut at that spot where I've shown you. And so now we have this kind of overhang and


[User] Please transcribe this text

[Assistant] Our DNA repair enzyme is going to come in and fill in the base pairs.


[User] Please transcribe this text

[Assistant] As you can see here, uhm, all of the things that are written in my little pen were not in the original sequence.


[User] Please transcribe this text

[Assistant] So those are all added sequence that we've added through this process of p-nucleotides. And you can also see that we've got C A T A T A T A T.


[User] Please transcribe this text

[Assistant] And, er, all the way to G actually, and C-A-T-A-T-A-T-A-G. And so we've got basically the same sequence forward and backward, uhm, which is our p-nucleotides, or palindromic nucleotides. Uhm, did you have a question, Carame?


[User] Please transcribe this text

[Assistant] This isn't the RAG2 NIC. The RAG2 NIC was here no matter what. The RAG2 NIC is always between the minigene sequence and the RSS.


[User] Please transcribe this text

[Assistant] Then we get the hairpin. Here we're talking about Artemis opening the hairpin.


[User] Please transcribe this text

[Assistant] So Artemis could open the hairpin at one of, I guess, 10 locations, 11 locations, something like that. So this is different than the original NIC. This is how we're kind of dealing with processing the NIC. Okay? Yes?


[User] Please transcribe this text

[Assistant] The p-nucleotides are what I drew in red. They are, because they're the new sequence that was not present in the original. The stuff that was typed was present in the original. The stuff that I've drawn was new sequence. So you can see it's kind of related to what was in the original. It kind of came from what was in the original.


[User] Please transcribe this text

[Assistant] And that's in fact why it's palindromic, but it is in fact new sequence that if you sequence this cell compared to another cell, this cell would have this new added sequence that wasn't there in other cells. Okay?


[User] Please transcribe this text

[Assistant] We have a nice piece of double-stranded end DNA per the RV and


[User] Please transcribe this text

[Assistant] It would be messy to draw, but we could draw the same thing for the RJ that was down here as well. And we have this nice even double strand DNA.


[User] Please transcribe this text

[Assistant] Before we had a hairpin. We had two hairpins. We can't s- If I ate together two hairpins, that would be a disaster!


[User] Please transcribe this text

[Assistant] But now you've got two nice double-stranded ends of DNA that you could ligate together. Before we ligate them together,


[User] Please transcribe this text

[Assistant] Oops, one more step happens. So here you can see we opened with the hairpin, we filled in some, we can fill in some base pairs.


[User] Please transcribe this text

[Assistant] But we also have another enzyme that will act here.


[User] Please transcribe this text

[Assistant] Uhm, that enzyme is called TDT.


[User] Please transcribe this text

[Assistant] And TDT is a type of DNA polymerase, but it is a unique DNA polymerase. It is different than other DNA polymerases that you have learned about in one important way.


[User] Please transcribe this text

[Assistant] Uhm, in fact because it has this unique ability,


[User] Please transcribe this text

[Assistant] There are a whole bunch of different experiments where molecular biologists use TDT.


[User] Please transcribe this text

[Assistant] Uhm, non-immunologists are like, oh, this is a cool enzyme, it has this cool function, we're gonna use it for stuff.


[User] Please transcribe this text

[Assistant] The func- the thing that TDT can do, unlike all the other DNA polymerases you've learned about, is that TDT can add base pairs in a non-template directed fashion.


[User] Please transcribe this text

[Assistant] What that means is it doesn't have to base pair with some other strand. It doesn't say, oh, I'm adding a T cause there's an A opposite me. It says, I'm adding a T cause I feel like it.


[User] Please transcribe this text

[Assistant] It just adds whatever it wants without having to match another strand.


[User] Please transcribe this text

[Assistant] And so it adds just totally random nucleotides.


[User] Please transcribe this text

[Assistant] Because they are random nucleotides, we call them N nucleotides. Because they're so random.


[User] Please transcribe this text

[Assistant] And so after we add those P nucleotides, we also add, have TDT that just adds some other nucleotides because it feels like it.


[User] Please transcribe this text

[Assistant] And so you can see we have some more nucleotides that can get added just cause TDT felt like it. They don't have to match anything. There's no relationship with the original sequence, but they're more of that bonus sprinkles sequence to give us more junctional diversity.


[User] Please transcribe this text

[Assistant] Then we're going to have our, you know, we're going to fill in our gaps. We're going to like it together. Your book correctly shows here.


[User] Please transcribe this text

[Assistant] That, uhm, there are some, there is also some cutting of some base pairs by an exonuclease. I'm not gonna focus on that. Don't get like hung up on


[User] Please transcribe this text

[Assistant] The exonucleolytic cleavage part. Cause I'm just not gonna like hit that very much. But your book is correct. Yes, there is sometimes exonucleolytic cleavage here.


[User] Please transcribe this text

[Assistant] Uhm, and so, uh, once we have these ends processed, finally we can ligate them together. Yep, Michael.


[User] Please transcribe this text

[Assistant] Because basically we're going to add them randomly and then they're going to get complemented and we're going to get back to that situation of two perfect double strand pieces that are going to get added together. So again, TDT is just going to add what it feels like.


[User] Please transcribe this text

[Assistant] Uhm, and this is gonna, and that, so here you can kinda see.


[User] Please transcribe this text

[Assistant] We've got a bunch of proteins that are really important for binding, uh, to


[User] Please transcribe this text

[Assistant] Free DNA ends. We don't want to let our free DNA ends like float around the cell and go and, you know, mess the other stuff up.


[User] Please transcribe this text

[Assistant] We've got a bunch of DNA binding proteins. We open the hairpins with Artemis. TDT can process those ends. And then the ligases will finally just ligate it all together. Giving us our coding join.


[User] Please transcribe this text

[Assistant] That is our say V and J segment or whatever. Maybe with a little bit of.


[User] Please transcribe this text

[Assistant] Spice added from junctional diversity, which you can see here in addition to the original red and yellow, uhm, pieces of DNA. There was a question.


[User] Please transcribe this text

[Assistant] So the big reason, so, uh, really it's, it's another way of getting more junctional diversity and giving us more diversity in the repertoire.


[User] Please transcribe this text

[Assistant] Uhm, someone actually did an experiment once where they made mice that didn't have TDT to ask that exact question. Uhm, and it's really just about increased diversity of the repertoire.


[User] Please transcribe this text

[Assistant] Uhm, so this is kind of all of what happens in processing that coding joint.


[User] Please transcribe this text

[Assistant] So, as I have told you, uhm, this process is very dangerous and we need to think a lot about how we


[User] Please transcribe this text

[Assistant] Regulate it, or we make sure that we don't get recombination errors.


[User] Please transcribe this text

[Assistant] If we get recombination errors, that can lead to things like leukemias and lymphomas, as are shown here.


[User] Please transcribe this text

[Assistant] Uhm, or as Dr. Duttaway might say, uhm, you get dead.


[User] Please transcribe this text

[Assistant] So, we need to make sure we limit recombination errors. And we can look back at the process that I just talked through, and we can see some places where we are able to limit our recombination errors. One of the things that happens


[User] Please transcribe this text

[Assistant] Is that the enzymes that we are thinking about, like RAG1 and RAG2, as well as Artemis and some of those other DNA binding proteins, all act together as a complex. In some views, like this view from this textbook, it just kind of shows them as one big blob.


[User] Please transcribe this text

[Assistant] And that's actually a whole bunch of enzymes in that big blob.


[User] Please transcribe this text

[Assistant] Uhm, here you can see, uhm, all of those enzymes as purple dots that are sort of all bound together. All of those enzymes are binding to each other and working together.


[User] Please transcribe this text

[Assistant] And the idea for this is that as we're cutting the DNA, the...


[User] Please transcribe this text

[Assistant] Cut pieces, the DNA ends, are not gonna get lost and fly around all over the place and potentially undergo some other weird chemical modifications.


[User] Please transcribe this text

[Assistant] We're gonna hold them all together and do all of this in one little location.


[User] Please transcribe this text

[Assistant] And so the fact that these enzymes are really good at working together and hold on to the DNA.


[User] Please transcribe this text

[Assistant] Through this whole process until it is completed is one way that we can limit the potential for recombination errors.


[User] Please transcribe this text

[Assistant] Big way that we limit recombination errors.


[User] Please transcribe this text

[Assistant] Their ability to make the RAG1 and 2 proteins.


[User] Please transcribe this text

[Assistant] So most cell, all of the cells in your body, of course, have the DNA to encode these enzymes.


[User] Please transcribe this text

[Assistant] But most cells do not transcribe that DNA and thus do not translate and make those enzymes.


[User] Please transcribe this text

[Assistant] And that means in all of those cells, your skin cell, your eye cell, whatever, the DNA is safe. Because...


[User] Please transcribe this text

[Assistant] These cutting, these special cutting enzymes are not even present to do the cutting.


[User] Please transcribe this text

[Assistant] When our B cell actually starts its life as a stem cell, it doesn't make rag one and rag two.


[User] Please transcribe this text

[Assistant] It only turns on RAG1 and RAG2 twice in its life. So it turns it on for a little while, then you can actually see it turns it off, and then it turns it back on, and then it turns it off. And once it's turned it off there at the end, it's off for the rest of the B cell's life. The B cell's never turning it back on again.


[User] Please transcribe this text

[Assistant] Uhm, these are going to be important events that we see in B cell development. But the basic idea here is that the cell is regulating when is this cutting enzyme present in the cell. So that.


[User] Please transcribe this text

[Assistant] The DNA that isn't supposed to be cut cannot get messed up.


[User] Please transcribe this text

[Assistant] Uhm, you can see that there are two


[User] Please transcribe this text

[Assistant] As you will see next week, this one, this first time that rag is expressed is when the B cell makes heavy chain. And the second time is when the B cell makes light chain and that's it.


[User] Please transcribe this text

[Assistant] Uhm, someone also asked me a really interesting question after class on Wednesday.


[User] Please transcribe this text

[Assistant] Uhm, and it had to do with DNA replication.


[User] Please transcribe this text

[Assistant] When the cell turns on RAG and is doing all this cutting of DNA,


[User] Please transcribe this text

[Assistant] It absolutely does not do DNA replication. There is no cell division then.


[User] Please transcribe this text

[Assistant] It's like you have a brief period of time, the cell is not dividing, absolutely no replication, you just cut the DNA, cause if you tried to cut it and you tried to replicate it at the same time, disaster would strike.


[User] Please transcribe this text

[Assistant] So in fact what really happens here is we cut the DNA, then we have a little pause where we can do replication of the cell, and we can do DNA replication, and then we turn it back on.


[User] Please transcribe this text

[Assistant] Again, so we make sure we keep those processes as separate as possible timing-wise. And again, we'll see this when we go through B-cell development next week.


[User] Please transcribe this text

[Assistant] Uhm, and then for the rest of the life of the B cell, no more rec. Uhm, cause we do not want that B cell to get messed up.


[User] Please transcribe this text

[Assistant] So we can think about the sort of timing of what we've been talking about.


[User] Please transcribe this text

[Assistant] Uhm, in relation to the immune response and to this general clonal selection theory as well.


[User] Please transcribe this text

[Assistant] Here you can see in grey the stem cell that is in, that is starting out this process.


[User] Please transcribe this text

[Assistant] Uhm, has not yet done VDJ rearrangement and you can see this generation of diversity.


[User] Please transcribe this text

[Assistant] What you can notice is that this process of diversification, this is really our VDJ recombination we've been talking about, is happening in the primary lymphoid organ.


[User] Please transcribe this text

[Assistant] This is happening before you ever get infected before you see antigen. By the time


[User] Please transcribe this text

[Assistant] The B-cell leaves the primary lymphoid organ. It has turned rag off. It is never having rag ever again. We're done with that.


[User] Please transcribe this text

[Assistant] And we now are looking for antigen and having that cell get ready to expand.


[User] Please transcribe this text

[Assistant] You can see that as well in another piece of this. So all of the events that we've been talking about are happening in the primary lymphoid organ. They are happening all the time.


[User] Please transcribe this text

[Assistant] My poor mother, uhm, has two daughters with PhDs in immunology. Uhm, and so, you know, when she's like, why are you sitting on the couch doing nothing? We can be like, mom.


[User] Please transcribe this text

[Assistant] We're doing VDJ recombination in our bone marrow to make new B cells. What do you mean? Uhm, so because you are in fact doing this.


[User] Please transcribe this text

[Assistant] Diversification of these B cells right now to keep making more.


[User] Please transcribe this text

[Assistant] And then those B cells are turning off RAG forever and ever. Yep. Jumir.


[User] Please transcribe this text

[Assistant] So, great question. Uhm, all of the parts of this are really kind of...


[User] Please transcribe this text

[Assistant] Random and math based. And so I told you that what happens is you make one of every kind of B cell, and that's kind of what's implied here. You know, one pink one, one blue one.


[User] Please transcribe this text

[Assistant] Uhm, people have actually figured out some really sensitive ways to do some experiments, and we now know that it's actually about 10.


[User] Please transcribe this text

[Assistant] And they are all randomly picking. Because you make enough, you make at least one of every kind. But sometimes there will be a duplicate, certainly.


[User] Please transcribe this text

[Assistant] So as I have sort of said and implied a few times, remember that this process is happening in a B cell.


[User] Please transcribe this text

[Assistant] Uhm, and that B cell is going through VDJ recombination to both make its B cell receptor and eventually to make its antibody.


[User] Please transcribe this text

[Assistant] Sometimes we can think about sort of B cells as different kinds of B cells. We can sort of subdivide them up. There's one kind that's really good at making antibodies that's labeled here as a plasma cell. Uhm, that plasma cell is something that we see out here.


[User] Please transcribe this text

[Assistant] Circulating through the body, not something we see in this primary lymphoid organ. That's like a later step of the B-cell's life.


[User] Please transcribe this text

[Assistant] Look at that, I didn't even have to go backwards because I had the slide there to go forwards. Uhm, one other thing happens.


[User] Please transcribe this text

[Assistant] Uhm, when we are doing this part of BDJ recombination that, uhm, I'm gonna mention now, it's gonna be one of the things that's gonna make you be like, wait, wait, wait, wait.


[User] Please transcribe this text

[Assistant] Get that? It's gonna come up way more with B-cell development and B-cell selection, but I want to at least mention it now.


[User] Please transcribe this text

[Assistant] If you think back to when I started telling you about the V, D, and J segments, and the V and J segments of the light chain, on one of the slides I mentioned to you what chromosome they were on.


[User] Please transcribe this text

[Assistant] The heavy chain loci is on chromosome 22. You don't need to know that it's on chromosome 22, but here's the thing. All of your B cells, this stem cell that was developing,


[User] Please transcribe this text

[Assistant] I don't have one. It has a copy of Chroma Heap, so I'm 22. It got from your mom. And one it got from your dad. So actually you have two big sets of


[User] Please transcribe this text

[Assistant] Heavy chain Vs and two heavy chain, big sets of heavy chain Ds and two big sets of heavy chain Js.


[User] Please transcribe this text

[Assistant] And from, like, one side from mom, one side from dad. So in theory, your B-cell could do this and make a mom heavy chain and a dad heavy chain.


[User] Please transcribe this text

[Assistant] And it could make a mom light chain and a dad light chain. And then it could mix and match them all together. And if it did that, it would have tons of different receptors on its surface. It would look sorta like this. So if we think of like,


[User] Please transcribe this text

[Assistant] Mom's heavy chain is blue and dad's heavy chain is green.


[User] Please transcribe this text

[Assistant] You could get different receptors, you might even get some mix-and-matchy ones, and you'd get, this is showing up only having one kind of light chain, but you'd really get mix-and-matchy light chains too, and it'd be a great big mess!


[User] Please transcribe this text

[Assistant] You'd never get strong binding because you'd never get like the same antigen binding in multiple places.


[User] Please transcribe this text

[Assistant] The B cell would be very confused. Like, what is my antigen? I have like 20 antigens. It's a problem. That does not happen.


[User] Please transcribe this text

[Assistant] Instead, we also see regulation of which chromosome it's used, whether it's mom or dad's chromosome.


[User] Please transcribe this text

[Assistant] So that each B-cell only makes one heavy chain and one light chain.


[User] Please transcribe this text

[Assistant] When we think about different chromosomes, we sometimes talk about alleles.


[User] Please transcribe this text

[Assistant] And so the way, this thing, this process is called allelic exclusion.


[User] Please transcribe this text

[Assistant] We are going to see allelic exclusion in B-cell development and how that happens. What goes on with allelic exclusion. But you should just already be realizing that we need to start thinking about the whole chromosome and the whole cell now and not just be zoomed in.


[User] Please transcribe this text

[Assistant] On that. So like I said, we're gonna see much more lolik exclusion.


[User] Please transcribe this text

[Assistant] But I wanted to introduce the idea here.


[User] Please transcribe this text

[Assistant] Sort of pieces to this that I want us to think about.


[User] Please transcribe this text

[Assistant] I'm going to mention these partially as ways to answer questions that students sometimes have.


[User] Please transcribe this text

[Assistant] I, some, in some cases you might be like, oh my gosh, I can tell there's a whole rabbit hole of detail here. And you're right, there is. I'm just saying these are things that happen. The rest, more parts of that are a not today problem. So it's going to be okay. Um, so one thing that we've talked about is the fact that our B cell has the ability to make


[User] Please transcribe this text

[Assistant] The same basic protein as a B-cell receptor and as an antibody. And so we might say, well how in the world are we gonna make


[User] Please transcribe this text

[Assistant] Sort of two versions of this protein off of this same genetic information.


[User] Please transcribe this text

[Assistant] The reason is that, you remember when we, I've mentioned the constant region stuff, in terms of the genome.


[User] Please transcribe this text

[Assistant] One that allows for a transmembrane domain and one that doesn't. So we can do this.


[User] Please transcribe this text

[Assistant] Uhm, at the level of the mRNA, we make our changes to the DNA, then we transcribe and make our mRNA, and we can splice our mRNA in two different ways.


[User] Please transcribe this text

[Assistant] Uhm, and we can get both a form of the protein that doesn't have a transmembrane domain and a form of the protein that does have a transmembrane domain.


[User] Please transcribe this text

[Assistant] What that means is that it is, when the cell decides to make secreted antibody, it's not a permanent change. It's changing the RNA. It's not changing the DNA.


[User] Please transcribe this text

[Assistant] So if it would like to switch and make different mRNA tomorrow, it can do that.


[User] Please transcribe this text

[Assistant] If it wants to switch and make a different VDJ pick tomorrow, it can't do that. Cause that was at the DNA level. It's not reversible. We threw out the leftover DNA.


[User] Please transcribe this text

[Assistant] Unless we like, go through embryonic development again, we're not gonna get new beginning chromosomes. Once we change the DNA, we're stuck with it.


[User] Please transcribe this text

[Assistant] But if we're, we think about things that we modify at the level of mRNA, we can pick and choose when we want to make those changes. And so the B cell can sort of pick and choose, do I want to make B cell receptor right now? Do I want to make secreted antibody right now? By just splicing the mRNA differently.


[User] Please transcribe this text

[Assistant] We also have to talk a little bit more about the constant region stuff.


[User] Please transcribe this text

[Assistant] So here, uhm, you can see that we've got all our V's, D's and J's of the heavy chain.


[User] Please transcribe this text

[Assistant] And you can also see that we have the exons of the constant region. Oh, it looks like it was chromosome 14, not 22. Oh well. Guess what? I was never going to ask you that on the exam anyway.


[User] Please transcribe this text

[Assistant] So you can see, you know, we've got the, uh, mu constant region that encodes IgM. D, G,


[User] Please transcribe this text

[Assistant] E-A-M-Ds give everyone apples. Just like I told you before.


[User] Please transcribe this text

[Assistant] Uhm, they encode the different parts of the heavy chain to give you the constant regions.


[User] Please transcribe this text

[Assistant] Uhm, but you can also see one other piece of this on this slide.


[User] Please transcribe this text

[Assistant] Which is the distance in DNA between some of these different, uh, constant region sections. So you can see the IgM constant region is pretty close to the VDJ stuff.


[User] Please transcribe this text

[Assistant] You can see D also still pretty close.


[User] Please transcribe this text

[Assistant] And you can see again between each of these, it's a pretty, it's a decent sized amount of space. So now let's imagine.


[User] Please transcribe this text

[Assistant] That we're doing our VDJ recombination, okay, so we're gonna put our V and our J's close together, and we're gonna cut out the intervening DNA, we're gonna make this short DNA.


[User] Please transcribe this text

[Assistant] Remember that puts our promoter and enhancer next to each other and lets RNA polymerase come along.


[User] Please transcribe this text

[Assistant] So now RNA Polymerase is going to do some transcription.


[User] Please transcribe this text

[Assistant] An RNA polymerase is going to start transcribing. It's going to transcribe V. It's going to transcribe D. It's going to transcribe J. It's going to keep going. It's going to transcribe this constant region. It's going to transcribe this constant region.


[User] Please transcribe this text

[Assistant] The RNA really only has the M and the D constant region.


[User] Please transcribe this text

[Assistant] And then there was just too much work for the polymerase to go all that long distance.


[User] Please transcribe this text

[Assistant] IGM constant region stuff. Here it's expanded a little bit. You don't need to know that it definitely, all the expanded parts. But in fact, it does have those two polyacites I told you about. You'll have the D.


[User] Please transcribe this text

[Assistant] That B cell can say, huh, today I want to make IgM. Here, let me finish splicing my RNA and use the IgM constant region.


[User] Please transcribe this text

[Assistant] So a B cell could make IgM and IgD versions of the antibody at the same time.


[User] Please transcribe this text

[Assistant] Or it could switch back and forth, like today I'm an IGD- Em, to tomorrow I'm an IGD.


[User] Please transcribe this text

[Assistant] Uhm, and in fact there are, but like I said, there are in fact some times where B cells are making both. So that's cool. We can do all of the cool IgM, uh, effector functions this way.


[User] Please transcribe this text

[Assistant] But if you remember, we talked about some pretty cool effector functions.


[User] Please transcribe this text

[Assistant] We don't have their mRNA here. The polymerase fell off.


[User] Please transcribe this text

[Assistant] So how the heck we're gonna make those, uhm, is a sort of different issue. Uhm, those are made...


[User] Please transcribe this text

[Assistant] With class switch recombination, we have another event where we cut and paste the DNA.


[User] Please transcribe this text

[Assistant] Now throwing out the constant regions we don't want.


[User] Please transcribe this text

[Assistant] Uhm, so there is this whole process where we get another change at the DNA level.


[User] Please transcribe this text

[Assistant] It sort of wants to make IgM or IgD. It's making that change at the RNA level. It doesn't have to commit.


[User] Please transcribe this text

[Assistant] It has the RNA, it can make different mRNA the next day, because the DNA is not changing.


[User] Please transcribe this text

[Assistant] It does not have the choice to go back to making IgM ever again. It has passed that point of its life. And it is now at a later point.


[User] Please transcribe this text

[Assistant] We al- I also mentioned that over time our antibodies can change their binding strength for antigen.


[User] Please transcribe this text

[Assistant] At the DNA level, where we're actually going to have enzymes that come in and give the cell more mutations in its DNA to help it change its binding strength.


[User] Please transcribe this text

[Assistant] So again, because this is a change at the DNA level, the cell can't go back. If it does this and messes up, for example, it gets dead. Um, cause it can't go back in time, like it sort of can with the, uh, RNA.


[User] Please transcribe this text

[Assistant] Both this process of mutation to change the cell's affinity as well as class switch happen late in the life of a B cell. Not early in the life of a B cell.


[User] Please transcribe this text

[Assistant] Uhm, they're usually happening, uhm, more like in a secondary response instead of in a primary response.


[User] Please transcribe this text

[Assistant] Uhm, and so the reason why this is sort of important,


[User] Please transcribe this text

[Assistant] Is that I've mentioned those outcomes of those things to you.


[User] Please transcribe this text

[Assistant] And those are important things to kind of understand that happen to B cells.


[User] Please transcribe this text

[Assistant] As we talk about B-cell development and selection next week, we are focused on the details that go on in the primary lymphoid organs.


[User] Please transcribe this text

[Assistant] We will learn about the later life of the B cell later in the semester.


[User] Please transcribe this text

[Assistant] Uhm, so, none of the, so the class switch, the affinity maturation, that's a later problem. That's outside of the bone marrow problem. It's a totally different process. So yes, it does happen, but we're not gonna care a ton about it right now. Yep.


[User] Please transcribe this text

[Assistant] So uhm, Jameer asks a fabulous question.


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[Assistant] Which is, do all B cells start with MND antibodies? And in fact, yes they do.


[User] Please transcribe this text

[Assistant] And so, uhm, every new B cell is M, uhm, and then becomes M and D.


[User] Please transcribe this text

[Assistant] And so we actually can think about stages of B-cell development based on if they're M or something else. Uhm, so if you recall, I said, uhm, I like to use MDs give everyone apples. Not only does that help you remember what the five isotypes are and the order of them on the genome, it also kind of helps you remember what order they get made in the B-cell's life.


[User] Please transcribe this text

[Assistant] Uhm, so that's why I kinda like to go with that one a lot.


[User] Please transcribe this text

[Assistant] Uhm, so this is just a general summary of some of the changes that are getting made with the immunoglobulin genes. So we're going to, uhm, put together our Bs, Ds, and Js by recombining the DNA and because it's happening with the DNA, it's not reversible.


[User] Please transcribe this text

[Assistant] Uhm, we're going to, uh, that putting together the V regions also makes the promoter enhancer close together, which is what it's saying is number three. Again, that's a change of the DNA, because we threw out DNA. That's irreversible. We're adding new sequence.


[User] Please transcribe this text

[Assistant] With the PNN nucleotides, that's a change at the DNA level. It's not reversible.


[User] Please transcribe this text

[Assistant] We can however have M and D and we can sort of switch between membrane bound antibody and secreted antibody based on processing RNA differently. And so that is something that the cell can reverse and that the cell can regulate.


[User] Please transcribe this text

[Assistant] Later in life, the B cell can, uhm, switch which class it's making and can change its binding. But again, those are gonna be things that are gonna be DNA problems and they're not gonna be reversible and they're gonna be things we care about later. Uhm.


[User] Please transcribe this text

[Assistant] This table is also just showing some information about B-cell development. Uhm, you might look at it and think it's sort of a meh table.


[User] Please transcribe this text

[Assistant] The reason why this is a nice table, uhm, is because it really, I'm not showing you some of the table. It actually is a compare and contrast of B cells and T cells.


[User] Please transcribe this text

[Assistant] Uhm, so when we learn the T cell stuff, we can see the compare and contrast on this. So you can see, you know, we use V's, D's, and J's in B cells.


[User] Please transcribe this text

[Assistant] We have a light chain that's either kappa or lambda that will come up in B cell development.


[User] Please transcribe this text

[Assistant] We've got, you know, the VD and J heavy chains. We need reg 1 and reg 2. We get P and N nucleotides. Uhm, we can't have a D.


[User] Please transcribe this text

[Assistant] Fuse with another D because of the 1223 rule.


[User] Please transcribe this text

[Assistant] Uhm, we get a lullic, we have go to lullic exclusion. We secrete the product sometimes as an antibody. They're constant in regions and they do stuff.


[User] Please transcribe this text

[Assistant] Uhm, and we can make changes later in life to those B cells. So that's really what this table is getting at.


[User] Please transcribe this text

[Assistant] And again, part of the reason why that's important is that it will eventually be a nice compare and contrast.


[User] Please transcribe this text

[Assistant] Uhm, so just a sort of couple of other interesting things. Uhm, there are diseases where people are unable to do BDGA recombination, so there are a few different


[User] Please transcribe this text

[Assistant] Uhm, sometimes also some other proteins involved in VDJ recombination. Uhm, and these generally result in these people have no T cells or no B cells. They still have an innate immune response, but they have no adaptive.


[User] Please transcribe this text

[Assistant] Uhm, and they usually have, uhm, extreme susceptibility to a lot of infections, uhm, and this is lethal, uhm, without treatment. Uhm, I will, I also told you, uhm, about, uh, thinking about, uhm, evolution of the immune system.


[User] Please transcribe this text

[Assistant] And having RAG1 and RAG2 is sort of, is in a lot of ways, there are immunologists that would like kick me for the statement, but for our purposes it works.


[User] Please transcribe this text

[Assistant] Having reg 1 and reg 2 is sort of the definition of having an adaptive immune system. Basically at some point, uhm, there was a change about 550 million years ago where one of our ancestors got reg 1 and reg 2, uhm, and every


[User] Please transcribe this text

[Assistant] Uhm, organism that's come from that common ancestor has an adaptive immune system because they can do VDJ recombination. Uh, so that's kind of the big difference that happened between these, uh, organisms in the jawed vertebrate.


[User] Please transcribe this text

[Assistant] Uhm, and when we define adaptive immunity,


[User] Please transcribe this text

[Assistant] The ability to do VDJ recombination is actually one of the things that's often used as the definition of adaptive immunity. So with innate, we often say we have germline encoded receptors. That means they're the same DNA that's in the normal rest of the cells. Whereas in,


[User] Please transcribe this text

[Assistant] Adaptive immune cells, we have this, uh, these receptors that are coming from this special recombination process. So we actually use this process as part of our definition, uhm, of, uh, adaptive immunity.


[User] Please transcribe this text

[Assistant] Uhm, so I love talking about the story of what happened 550 million years ago to give us rag, but I'm actually going to skip over that for time's sake, though I could geek out hard on that front.


[User] Please transcribe this text

[Assistant] And instead I'm going to, uhm, think a little bit about some of these problems, uhm, just to help you guys out, uhm, in terms of thinking about stuff on the problem set.


[User] Please transcribe this text

[Assistant] Uhm, there's one problem I really want to make sure I get to. So I'm gonna do these in a weird order. Basically the one I definitely most want to talk about I'm gonna do first. And then we'll come back to some of the other ones as we have time.


[User] Please transcribe this text

[Assistant] This is the problem that everyone gets very confused about.


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[Assistant] So in this scenario, I'm telling you about some B cells that were studied and we sequenced their genomes.


[User] Please transcribe this text

[Assistant] And the B cells that were studied in this problem, uhm, used a particular V, VH2, uhm, and they used a particular, look at that, D, H2, D, that's a D.


[User] Please transcribe this text

[Assistant] Uhm, so that, that, and that's what they look like in the normal genome before anything gets changed, anything happens.


[User] Please transcribe this text

[Assistant] And then if you actually look at the B cell after it has undergone all of these processes.


[User] Please transcribe this text

[Assistant] That's what the DNA looks like. That's what the sequence looks like in the B cell.


[User] Please transcribe this text

[Assistant] So what I ask you here is to label the origins of the nucleotide in the rearranged locus above.


[User] Please transcribe this text

[Assistant] If the nucleotides could be p-nucleotides, you must label them as p-nucleotides. Because one time somebody labeled everything as N and gave me this really good explanation of why they were N. I was like, alright, you're kind of right, but...


[User] Please transcribe this text

[Assistant] So, I've got a bunch of nucleotides here, and I have to say where they came from. Some of them are really easy.


[User] Please transcribe this text

[Assistant] Those four are either P or N nucleotides.


[User] Please transcribe this text

[Assistant] And we have to look at them to decide which ones they are. When we do that, we look at each one individually. So we're going to start by looking at this T. Okay?


[User] Please transcribe this text

[Assistant] So, if this T had been a P nucleotide,


[User] Please transcribe this text

[Assistant] Once we, if you remember the steps, we have the p-nucleotides, and then after that's all done, we do the ends.


[User] Please transcribe this text

[Assistant] So what we can see is there were no p-nucleotides added on this side, because we look, as soon as we get to a no, we know, alright, we're done. So that is not a p-nucleotide. Alright, so now we're going to actually do the other side. Let's look at this T. Where did this T come from?


[User] Please transcribe this text

[Assistant] What are sort of options for this T? Is this, could this T be a p-nucleotide? So I see some head shakes, yes. Why?


[User] Please transcribe this text

[Assistant] So I'm going to say, because if you notice it says, if it could be P nucleotide, you have to say it is. It's P. Alright, now let's look at this T.


[User] Please transcribe this text

[Assistant] Yeah, so this T would have had to have been bound to this next A over here.


[User] Please transcribe this text

[Assistant] Cause remember, this would have been a hairpin and it would have kind of looped back around. So could this second base be bound to this one? Yeah, it could. So that also could be a p-nucleotide.


[User] Please transcribe this text

[Assistant] Now you might say to me, well Dr. Barker, I don't understand why you just did one on the left side and then stopped. Why didn't you ask the same thing about the C? Well the answer is because if this one wasn't looped around, it couldn't loop around like


[User] Please transcribe this text

[Assistant] Not loop around and then do it afterwards. So once you get to a no, you're done on that side. All right, so now let's go to the C.


[User] Please transcribe this text

[Assistant] What's up with the C? Could the C have been a p-nucleotide?


[User] Please transcribe this text

[Assistant] Yes? So yes. Yes, because this C could have gone with this G. I'm still doing this I. Okay? So that one could be P.


[User] Please transcribe this text

[Assistant] Alright, now we're gonna look back at this T. Could this T have been a p-nucleotide on this side?


[User] Please transcribe this text

[Assistant] No, cause if it had, it would have been bound to this G. T's don't go with G.


[User] Please transcribe this text

[Assistant] So now anything that's left over and that can't be a p-nucleotide is an n. Is a random n-nucleotide. Because n-nucleotides aren't really anything, they're just random. So this is how you would address a question like this.


[User] Please transcribe this text

[Assistant] And I know this is one that people are always confused about, so that's why I wanted to go through it so that you could see how we would, uhm, look at this. Yep.


[User] Please transcribe this text

[Assistant] And then basically once you've kind of done both sides for P, any nucleotides who you have not assigned are M. Okay?


[User] Please transcribe this text

[Assistant] And that's because of the order of the steps that we saw today. Yep, Carney.


[User] Please transcribe this text

[Assistant] It could also, it could be a P. It could also, if, if it for some reason matched over here, sure, it could be a P and there are no N's in this case. Uhm, but yeaah, that's not how I wrote it. Uhm, I was tricky on this one.


[User] Please transcribe this text

[Assistant] Because of this C, this C could bind to this G, and so if you didn't know that you had to like, stop after you did the nos, you could get really confused about this C.


[User] Please transcribe this text

[Assistant] Uhm, so, that's my trickiness. Uhm, alright, any other questions about this?


[User] Please transcribe this text

[Assistant] Okay, so I'm just going to show you a couple other of these sample questions and tell you some key things I'm looking for, because I don't know that we have time to go all the way through them, but I just want to point out a couple of key points. Uhm, so here I'm asking you,


[User] Please transcribe this text

[Assistant] Uhm, about drawing the germline DNA sequence.


[User] Please transcribe this text

[Assistant] First of all, I, I do one thing that's kind of tricky in this, is I put them in alphabetical order, not in the order they are in the genome. So I wrote D,


[User] Please transcribe this text

[Assistant] And then I wrote V and then I wrote J. That's not alphabetical order. Good job, Solve. In any case, I tell you that these sequences


[User] Please transcribe this text

[Assistant] These are there. I expect you to know that V comes first.


[User] Please transcribe this text

[Assistant] And that J comes last. And that I have a really weird chord, so I can't draw where I want to draw.


[User] Please transcribe this text

[Assistant] I'm expecting you to be able to give me the RSS's. I don't care that you know which one's 12 and which one's 23, but I care that you give me two different kinds.


[User] Please transcribe this text

[Assistant] And so in, I expect that you know that there's a, there are RSS's here that they are touching. There's not like a space between them and the gene segment.


[User] Please transcribe this text

[Assistant] So here's my DNA connecting this whole business together. Drawn extremely poorly.


[User] Please transcribe this text

[Assistant] And then I'm also asked for the appropriate constant regions, which again, I wrote in an alphabetical order, and I'm expecting you to know what order they are in. So here's my, so then I'm going to draw constant regions.


[User] Please transcribe this text

[Assistant] So that's kind of what I'm expecting for this kind of a question.


[User] Please transcribe this text

[Assistant] Uhm, so if you look back at what we were talking about with the D's, the D has the same kind on either side. So it could join to a V, it could join to a J, but you can't have a D join to another D. So if you look back at the slides, this is kind of how they were depicted.


[User] Please transcribe this text

[Assistant] Exactly, if I, if I was asking about a light chain, there would be no Ds, and there wouldn't be these same letters of constant region. There would just be, like, constant region.


[User] Please transcribe this text

[Assistant] Uhm, I often will then ask about the DNA segment.


[User] Please transcribe this text

[Assistant] Uhm, I'll ask you to join three, and what I'm specifically looking for is that, you know, the VD and J are touching. We got rid of all the intervening DNA.


[User] Please transcribe this text

[Assistant] But then I'm also looking for the outside DNA to still be there.


[User] Please transcribe this text

[Assistant] So anything that was outside, like v1 or j3,


[User] Please transcribe this text

[Assistant] Or all of those constant regions, M-D-G-E-A.


[User] Please transcribe this text

[Assistant] Uhm, are all still there. So I'm specifically looking for are the right constant, are the right ones together and are they touching with nothing in between them? And are the outside things still present? Uhm, with those kind of questions. Uhm, and so you guys should have a great fall break.


[User] Please transcribe this text

[Assistant] This is the Java 8 way that we saw in the previous unit. This is the Java 7 way. One thing that this has extra is this interface.


[User] Please transcribe this text

[Assistant] In order to implement all this stuff, which is quite verbose in the Java 7 approach.


[User] Please transcribe this text

[Assistant] into the Java 8 approach. It's much terser because we have lambda expressions in it, so it's just one line. But if you think about the interface itself, what did we do? We have this condition here, which had a boolean test method, and it took in a person instance.


[User] Please transcribe this text

[Assistant] This seems like extra work for what we're trying to do over here. We are looking to pass in a condition.


[User] Please transcribe this text

[Assistant] We don't really care about what this condition interface is called as. This could be called foo and it would still work, right? So this we could call this as foo. This is just a variable and this method.


[User] Please transcribe this text

[Assistant] Could be call for us as well and we could just execute it. It really doesn't matter what the name of the interfaces and what the name of the method is.


[User] Please transcribe this text

[Assistant] But we still had to specify a specific method on a specific interface because we had to specify that as the type.


[User] Please transcribe this text

[Assistant] So it feels like we had defining this interface as kind of an overhead. Wouldn't it be nice if we didn't have to do this?


[User] Please transcribe this text

[Assistant] So to just write the lambda expression and somehow create a type for this.


[User] Please transcribe this text

[Assistant] You remember I told you that Java 8 does not have a function type.


[User] Please transcribe this text

[Assistant] They haven't created a new type called function. We are leveraging the concept of interface.


[User] Please transcribe this text

[Assistant] But what the Java language designers have done is they've actually created some out of the box interfaces.


[User] Please transcribe this text

[Assistant] To address some of these common scenarios. See, condition is a common thing. You want to write code which accepts some kind of a condition like this, does a test, takes in an input object, and it returns whether it's a true or a false, right? This is a common scenario.


[User] Please transcribe this text

[Assistant] There are other scenarios like this. Maybe there's a function which takes in an object and it just prints something to the console. So it's basically an interface, in that case, which contains a method.


[User] Please transcribe this text

[Assistant] She takes in an object and returns a white. We've already seen that before. So there are all these common patterns.


[User] Please transcribe this text

[Assistant] Functions. So it's java.util.functions which contain some out-of-the-box interfaces.


[User] Please transcribe this text

[Assistant] Now here is the Java docs for Java.utl.function. You can see here there are a bunch of different interfaces over here. So let's take this example of a predicate.


[User] Please transcribe this text

[Assistant] Which represents a predicate boolean valued function of one argument. It's not very helpful, so let's look at the details. So the predicate interface contains the method called test.


[User] Please transcribe this text

[Assistant] If you were to ever need a lambda expression that takes in an object and returns a boolean, though you don't have to create a new interface for it, you can just use


[User] Please transcribe this text

[Assistant] That's what we are doing here, right? We are doing a condition.test. So the condition interface is kinda like a predicate. It takes in an object.


[User] Please transcribe this text

[Assistant] And it returns a boolean. In this case, it takes an object of type Person.


[User] Please transcribe this text

[Assistant] But since the predicate interface is a generic type, we can have the generic type be person and it still works. So let's try that out here. So rather than have this be a condition, what I'm gonna do is I'm gonna make this a predicate type. Predicate.


[User] Please transcribe this text

[Assistant] I'll call this predicate. Now predicate is a generic type. First let me import it from Java.utl.function. And now since it's a generic type, what I'll do is...


[User] Please transcribe this text

[Assistant] I'll make this off type version. Now predicate will have a method. Let me take this out.


[User] Please transcribe this text

[Assistant] I didn't have to change the code that called this method. You see, I just changed the method itself because the code that called the method is a lambda expression. This is a lambda expression. This is a lambda expression.


[User] Please transcribe this text

[Assistant] And as far as the lambda expression is concerned, it doesn't really care what the interface is as long as the signature of the abstract method in the interface matches.


[User] Please transcribe this text

[Assistant] The signature of this lambda expression. What's the lambda expression doing? It's just taking an object and returning a Boolean.


[User] Please transcribe this text

[Assistant] These are some out of the box interfaces that come with Java to handle some common scenarios. So if you look at the package itself, there are a lot of these out of the box interfaces. Some other examples are something called supplier. A supplier is


[User] Please transcribe this text

[Assistant] Something that doesn't take in any input, but it returns.


[User] Please transcribe this text

[Assistant] An object of type T, so it can be customized to anything that you want. There is also a function.


[User] Please transcribe this text

[Assistant] Which is a, you know, a generic type of two types, which basically takes in an input.


[User] Please transcribe this text

[Assistant] And it returns an output. So this is the only abstract method here. Everything else is, as you can see, default or static. Now it takes in a type, and it returns another type.


[User] Please transcribe this text

[Assistant] So these are common scenarios. Now since these are generic types, they will work for the types that you are concerned with. So you can use them when you have such common lambda expressions and you don't want to create a new interface for it.


[User] Please transcribe this text

[Assistant] So you remember I told you in the previous unit that the first step to creating a lambda expression is to create an interface for it and


[User] Please transcribe this text

[Assistant] Define a method in that interface, which was step two, which has the same signature as that lambda expression.


[User] Please transcribe this text

[Assistant] Which pretty much addresses the lambda expression that you're writing, but you don't have to create the interface as well. You can just use these out of the box interfaces. So let's make sure this works with the predicate, uh, example. So I'm going to run this.


[User] Please transcribe this text

[Assistant] And now we see the things getting printed, all these person objects are getting printed. So it still works the same, but we have not completely bypassed the need to create an interface for this. We just have to find the right interface from the java.util.function package and we can just use that.


[User] Please transcribe this text

[Assistant] Use some of these functions to write more lambda expressions without having the need to declare an interface first.


[User] Please transcribe this text

[Assistant] BatchNorm processes your data one Mimi batch at a time. But at test time, you might need to process the examples one at a time. Let's see how you can adapt your network to do that.


[User] Please transcribe this text

[Assistant] Recall that during training, here are the equations you'd use to implement Batchstorm. Within a single mini-batch, you'd sum over that mini-batch,


[User] Please transcribe this text

[Assistant] Of the zi values to compute the mean, uhm, so here you're just summing over the examples in one mini-batch. I'm using m to denote the number of examples in the mini-batch, not, not in the whole training set.


[User] Please transcribe this text

[Assistant] Then you compute the variance and then you compute z norm by scaling by the mean and standard deviation with epsilon added for numerical stability.


[User] Please transcribe this text

[Assistant] Which you need for this scaling calculation are computed on the entire minibatch.


[User] Please transcribe this text

[Assistant] But at test time, you might not have a meanie badge of 64, 128, or 256 examples to process at the same time. So you need some different way of coming up with mu and sigma squared. And if you have just one example, taking the mean and variance of that one example doesn't make sense. So what's actually done,


[User] Please transcribe this text

[Assistant] is to come up with some separate estimate of mu and sigma squared.


[User] Please transcribe this text

[Assistant] And in typical implementations of BatchNorm, what you do is estimate this using a exponentially weighted average, where the average is across the mini-batches.


[User] Please transcribe this text

[Assistant] So, to be very concrete, here's what I mean. Let's pick some layer L, and let's say you're going through mini-batches X1,


[User] Please transcribe this text

[Assistant] x2 together with the corresponding values of y and so on. So when training on x1 for that layer L you get some mu L and in fact I'm going to write this as mu for the first mini batch and that layer. And then when you train on the second mini batch


[User] Please transcribe this text

[Assistant] For that layer and that mini-batch, you end up with some second value of mu. And then for the third mini-batch in this hidden layer, you end up with some third value for mu.


[User] Please transcribe this text

[Assistant] So just as we saw how to use an exponentially weighted average to compute the mean of


[User] Please transcribe this text

[Assistant] Theta 1, theta 2, theta 3, when you are trying to compute a


[User] Please transcribe this text

[Assistant] Exponentially weighted average of the current temperature, you would do that to keep track of what's the latest average value of this mean vector you've seen. So that


[User] Please transcribe this text

[Assistant] Exponentially weighted average becomes your estimate for what the mean of disease is for that hidden layer. And similarly,


[User] Please transcribe this text

[Assistant] You use an exponentially weighted average to keep track of these values of sigma squared that you see on the first mini-batch in that layer.


[User] Please transcribe this text

[Assistant] For each layer, as you train the neural network across different mini-bandages. Then finally, at test time, what you do is, in place of this equation, you would just compute z norm, using whatever value z you have


[User] Please transcribe this text

[Assistant] And using your exponentially weighted average of the mu and sigma squared, whatever was the latest value you have, to do the scaling here. And then you would, uhm,


[User] Please transcribe this text

[Assistant] Compute z tilde on your one test example using that z norm that we just computed on the left.


[User] Please transcribe this text

[Assistant] And using the beta and gamma parameters that you, you have learned during your neural network training process.


[User] Please transcribe this text

[Assistant] So the takeaway from this is that during creating time, mu and sigma squared are computed on an entire mini-batch of, you know, say 64, 128, or some number of examples. But at test time, you might need to process a single example at a time.


[User] Please transcribe this text

[Assistant] And there are many ways to do that. Uhm, you could in theory run your whole training set through your final network to get mu and sigma squared.


[User] Please transcribe this text

[Assistant] But in practice what people usually do is implement an exponentially weighted average where you just keep track of the mu and sigma squared values you're seeing during training and use an exponentially weighted average, also sometimes called a running average, to just get a rough estimate of mu and sigma squared and then you use those values of mu and sigma squared at test time to do the scaling you need of the


[User] Please transcribe this text

[Assistant] Hidden unit values z. In practice this process is pretty robust to the exact way you use to estimate mu and sigma squared.


[User] Please transcribe this text

[Assistant] So I wouldn't worry too much about exactly how you do this. And if you're using a deep learning framework, they'll usually have some default way to estimate the


[User] Please transcribe this text

[Assistant] Mu and sigma squared that should work reasonably well as well. But in practice, any reasonable way to estimate the mean and variance of your


[User] Please transcribe this text

[Assistant] Hidden unit values z should work fine at test. So that's it for Dashthon. And using it, I think you'll be able to train much deeper networks and get your learning algorithm to run much more quickly.


[User] Please transcribe this text

[Assistant] Before we wrap up for this week, I want to share with you some thoughts on deep learning frameworks as well. Let's start to talk about that in the next video.


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to catch on


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to catch on


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to catch on


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to catch on


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Never hang back. Got out there and go for it.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then.


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we, re-hoping for a higher discount


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we're hoping for a higher discount


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we, re-hoping for a higher discount


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we, re-hoping for a higher discount


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home.


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home.


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home.


[User] Please transcribe this text

[Assistant] He pulled some strings and managed to get us front row seats for the concert


[User] Please transcribe this text

[Assistant] He pulled some strings and managed to get us front row seats for the concert


[User] Please transcribe this text

[Assistant] He pulled some strings and managed to get us front row seats for the concert


[User] Please transcribe this text

[Assistant] He pulled some strings and managed to get us front row seats for the concert


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] Would you be interested in going to the movie with us tonight?


[User] Please transcribe this text

[Assistant] Would you be interested in going to the movie with us tonight?


[User] Please transcribe this text

[Assistant] Would you be interested in going to the movie with us tonight?


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to catch on


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to catch on


[User] Please transcribe this text

[Assistant] The idea of glasses being a fashion item has been slow to catch on


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Tomorrow is my day off, so you'd better come after tomorrow.


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Most people go through the same routine, day in and day out


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Many investors were cast down for the bearish market


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] Would you mind repeating that? I didn't quite catch on.


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm dead tired. I'm looking forward to staying in bed.


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap


[User] Please transcribe this text

[Assistant] I'm worried about the quality of this product because it's dirt cheap.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Oh, my god. All my efforts have gone down the drain.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Do me the favor to recall that I told you so, long ago.


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters


[User] Please transcribe this text

[Assistant] Unfortunately, there is nothing we can do to improve matters.


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] It's probably good for you to get some criticism now and then


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] My vacation plans went up in smoke when a crisis arose in the office


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then.


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then.


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then


[User] Please transcribe this text

[Assistant] She was not very homesick. Only every now and then


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we, re-hoping for a higher discount


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we, re-hoping for a higher discount


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we're hoping for a higher discount


[User] Please transcribe this text

[Assistant] Unit price seems fair enough, but we, re-hoping for a higher discount


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] This car is a real lemon. It has broken down four times.


[User] Please transcribe this text

[Assistant] Would you be interested in going to the movie with us tonight?


[User] Please transcribe this text

[Assistant] Would you be interested in going to the movie with us tonight?


[User] Please transcribe this text

[Assistant] Would you be interested in going to the movie with us tonight?


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home.


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home.


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home.


[User] Please transcribe this text

[Assistant] We should probably hit the road. It's going to take us two hours to get home


[User] Please transcribe this text

[Assistant] He pulled some strings and managed to get us front row seats for the concert


[User] Please transcribe this text

[Assistant] He pulled some strings and managed to get us front row seats for the concert


[User] Please transcribe this text

[Assistant] He pulled some strings and managed to get us front row seats for the concert


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] She is such a stick in the mud. She never wants to try anything new


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] He mistakenly believed that his family would stand by him


[User] Please transcribe this text

[Assistant] One afternoon, she set out from the coast in a small boat and was caught in a storm. Towards evening, the boat struck a rock and the girl jumped into the sea. Then she swam to the shore.


[User] Please transcribe this text

[Assistant] After spending the whole night in the water During that time


[User] Please transcribe this text

[Assistant] She covered a distance of eight miles. Early next morning she saw a light ahead.


[User] Please transcribe this text

[Assistant] She knew she was near the shore because the light was high up on the cliffs. On arriving at the shore, the girl struggled up the cliff towards the light she had seen. That was all she remembered. When she woke up a day later, she found herself in hospital.


[User] Please transcribe this text

[Assistant] My wife and I recently welcomed a wonderful baby girl into our family. And as I was sitting there in the delivery room, I had the idea of making a video about the placenta. I mean, how often do you get the chance to make a video and teach people about the amazing placenta?


[User] Please transcribe this text

[Assistant] So after having a discussion with the delivery staff and reassuring them that I wasn't going to be eating it, considering it was covered in meconium, or baby poop,


[User] Please transcribe this text

[Assistant] They were happy to let me have it and that way I can show and teach you today. So, put your forks away and let's do this.


[User] Please transcribe this text

[Assistant] So first off I want to let you know that today's video is going to be slightly different than videos you're used to seeing from us. And that's for a couple of different reasons.


[User] Please transcribe this text

[Assistant] The first is that the placenta doesn't come from any of the cadavers here in the lab. Instead, it comes from my wife and our newborn daughter. So she was born last week, and in the delivery room, I looked to the OB and asked her if I could take the placenta here to the lab in order to make this very video.


[User] Please transcribe this text

[Assistant] So that also means that it's unembalmed, or unfixed.


[User] Please transcribe this text

[Assistant] So there is going to be blood. Now I've done everything I possibly can to prepare this placenta to make it the least bloody it possibly can be, the least graphic it possibly can be, but if that's something that you just don't want to see, I completely understand. I'm not going to get mad at you. This may not be the video for you.


[User] Please transcribe this text

[Assistant] With that said though, we're going to be focusing a lot just, really just on the anatomy of the placenta and mainly the macroscopic or gross anatomy.


[User] Please transcribe this text

[Assistant] In future videos, we plan on doing a whole wide variety of content around embryology, fetal development, the stages of labor, just what happens to mom during pregnancy. There's so many cool things to talk about, and there's a good chance that we may even try to preserve this placenta so we can use it to make future videos. So, with all that said, let's go ahead and take a look at the placenta. But real quick, I want to thank the sponsor of today's video, Wondrium.


[User] Please transcribe this text

[Assistant] You may have heard of the Great Courses Plus before. Well, the Great Courses has evolved into something much bigger and better called Wondrium.


[User] Please transcribe this text

[Assistant] One Dream is where you find the answers to everything you've ever wondered about, and some things you never imagined you would be wondering about. Their carefully curated collection of short and long-form videos, tutorials, how-tos, travelogues, documentaries, and more are academically comprehensive.


[User] Please transcribe this text

[Assistant] Thoroughly researched, relentlessly entertaining, and presented by engaging experts. Personally, I've consumed somewhere around 300 hours or so of One Dream content over the course of my lifetime, and that's just my best guess, but my all-time favorite course is by Robert M. Hazen, The Origin and Evolution of the Earth.


[User] Please transcribe this text

[Assistant] Now, I often talk about this to my students despite it having nothing to do with anatomy. I just find it to be really really cool. And it's the fact that


[User] Please transcribe this text

[Assistant] Older stars have less iron in them and that's because


[User] Please transcribe this text

[Assistant] Iron is formed inside of a star at the end of the star's life cycle, or at least over time through that star's life cycle.


[User] Please transcribe this text

[Assistant] And what will happen then is older stars that go supernova will actually blast iron into space. And then, again, over time, that will then coalesce into new stars. Meaning those newer stars will have more iron to start out with.


[User] Please transcribe this text

[Assistant] This means that astronomers and cosmologists can actually hunt and find older stars in the universe based on how much iron is in them and the heat and everything they're giving off.


[User] Please transcribe this text

[Assistant] To me that is just so cool. If planetary science and geological formations just aren't your thing, don't worry. One Dream is constantly updating and evolving its library of content so you'll be able to find something that is going to interest you.


[User] Please transcribe this text

[Assistant] Very easily. So if you are interested, go ahead and click the link in the description below or you can just visit Wondrium.com slash IOHA and you can sign up for your free trial today.


[User] Please transcribe this text

[Assistant] Seriously? And I mean this, you won't regret it. So this right here is what's called the fetal surface of the placenta, and we can also see the umbilical cord. Now, as I lift it up, you are going to see, let's see if I can actually get this into a good view in the camera.


[User] Please transcribe this text

[Assistant] And this is actually fetal tissue. So this is actually same tissue that came from my daughter during development.


[User] Please transcribe this text

[Assistant] But attached to it is like I mentioned going to be the umbilical cord. Now the umbilical cord is actually


[User] Please transcribe this text

[Assistant] Uhm, a pretty simple structure. There are going to be two arteries and one vein that are then going to be encased in what's called Wharton's Jelly, which is basically just a, uhm, mucoid, mucus type connective tissue, has a lot of sugars inside of it, but,


[User] Please transcribe this text

[Assistant] This is going to send blood vessels to and from the fetus, and you can see those blood vessels branching out on this fetal surface. This is actually called the chorionic plate, although there is a membrane on top of this, which is called the amnion.


[User] Please transcribe this text

[Assistant] So what would happen is there would actually, and I had to cut this away because it just would have made the video undoable.


[User] Please transcribe this text

[Assistant] So we've all probably heard of the amniotic sac, but the amnion is just a layer that would be on top of this fetal surface


[User] Please transcribe this text

[Assistant] And then what it would do is it would actually come into the umbilical cord and then branch out. So you can kind of picture there would be like this sac that the fetus would be inside of and then the umbilicus, the umbilical cord would connect to the umbilicus of the fetus. So I had to remove that amniotic sac.


[User] Please transcribe this text

[Assistant] All of those blood vessels are going to...


[User] Please transcribe this text

[Assistant] And from the fetus, as well as mom. So as I flip this over, this is going to look a little graphic. So, see if I can do the best I can here. This is the maternal surface of the placenta.


[User] Please transcribe this text

[Assistant] Except, you know, I almost hesitate saying internal surface because there really isn't a surface to begin with.


[User] Please transcribe this text

[Assistant] You have to understand that placenta is a combination of both the fetus and mom's tissues.


[User] Please transcribe this text

[Assistant] When a woman is ovulating, when she has her menstrual cycle, there's an inner lining to the uterus called the endometrium. And that is going to get thickened by a hormone called progesterone. And when it becomes thickened, it gets named the decidua.


[User] Please transcribe this text

[Assistant] The decidua is gonna have a lot of sugars and lipids and fats inside of it, and it's actually gonna have the embryo embed into it and then grow. So what happened was,


[User] Please transcribe this text

[Assistant] As the fetus grew and grew the placenta, right, you had this matching. So you had the fetal surface growing on one side into that maternal surface, into the decidua, and so when this was born, right, because the placenta is actually born, right, this is that third stage of labor, what will happen is once the fetus is born,


[User] Please transcribe this text

[Assistant] And uhm, the blood is gonna stop being supplied, right, going back to that uhm, to the placenta. What'll happen is...


[User] Please transcribe this text

[Assistant] It'll start to detach a little bit, and then the uterus is also contracting.


[User] Please transcribe this text

[Assistant] And so the whole placenta is going to start breaking away, and you're also going to have, you know, the delivery staff, and that OB, pulling on the actual cord as gently as they can, but from what I've seen, it doesn't look to be very comfortable at all. And they're going to then bring it out. And so this is the afterbirth.


[User] Please transcribe this text

[Assistant] And so what's gonna come, so what'll happen is since it's breaking away, you're essentially looking at a wound here.


[User] Please transcribe this text

[Assistant] Right, this is a wound because this would have been merged with the decidua of, or the endometrium of the uterus. But since it broke away, you're now seeing that maternal surface. Now...


[User] Please transcribe this text

[Assistant] The, I should also say the decidua continues to leave the uterus over the next days and weeks ahead, right? There's gonna be a lot of bleeding as the uterus is continually contracting, going down, and everything's getting smaller. Now, what's really cool,


[User] Please transcribe this text

[Assistant] About these is what you're looking at and you're looking to see like these mounds. Let's see if I can actually do this. I'm gonna pull out my probe.


[User] Please transcribe this text

[Assistant] So if you look here, this is really difficult for me to do, but...


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[Assistant] There's almost like these little mounds, like, almost like mountains and valleys. You can definitely see it right around here. Those mountain areas, those are called caudalydons.


[User] Please transcribe this text

[Assistant] And then inside, then you're going to also have these sulci kind of like dipping down. But the caudalidons are going to be where


[User] Please transcribe this text

[Assistant] Is mom's blood supply is going to be coming from the uterus and it's going to go into this space called the intervillous space. Here it's going to empty blood into pretty much just a pool.


[User] Please transcribe this text

[Assistant] But it's gonna be separated and completely separate, I should mention, from the fetus. This is how you can actually have different blood supplies between, uh, blood types between mom and fetus. Say like A positive or A negative.


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[Assistant] Now that creates a whole host of other issues that we can talk in future videos, but just understand


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[Assistant] Will then branch out into little trees.


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[Assistant] And this is the overall function of the placenta is that this is where nutrient, oxygen, and waste exchange can occur.


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[Assistant] Because the fetus isn't gonna be able to breathe inside of the womb, like breathe oxygen in the air, so what happens is oxygen will come in, carbon dioxide will go out.


[User] Please transcribe this text

[Assistant] Right, you're gonna have nutrients like vitamins and some minerals and you're gonna have all sorts of like sugars and, you know, lipids and proteins. Everything that the baby is going to need to grow is going to go in there and then you're also gonna have waste exchange.


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[Assistant] It is also going to leave outside of here. Really, really cool. All of that is going to be happening, and let's turn this back around.


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[Assistant] In those caudalydons, right, those which are just going to be


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[Assistant] When, when I say the maternal surface, this is actually more properly called the basal plate. And then the other side, instead of saying fetal surface, this should actually more be called the chorionic plate. But if you remember me saying there was actually a membrane on top of it, and that membrane is called the amnion. But another function of the placenta besides going to be


[User] Please transcribe this text

[Assistant] Facilitating nutrient exchange and oxygen and carbon dioxide exchange is also an endocrine function.


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[Assistant] You see, every single month, what happens is progesterone levels will drop, and the decidua will then slough off. And in fact, that's essentially what decidua means, is to slough off.


[User] Please transcribe this text

[Assistant] So you obviously don't want that to happen when you have a growing fetus and a growing baby, so what will happen is you have something inside of the, uhm, ovary called the corpus luteum, which is going to help sustain that. But what I want you to understand is that the placenta is another one of its function is to produce hormones to basically just tell mom's body


[User] Please transcribe this text

[Assistant] We're pregnant. We're still pregnant. Don't slough off the decidua. Let's keep all of this going.


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[Assistant] But there's plenty of other growth, uh, hormones, such as growth hormones that are going to be secreted from the placenta.


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[Assistant] I just want you to know that the placenta is an absolutely incredible organ. And that's because, in my estimation, in my personal view, it is a part of the most amazing, incredible, and beautiful process in all of biology, and that is the growth of the human fetus.


[User] Please transcribe this text

[Assistant] That's again why I want to do multiple videos on, you know, just embryological development, fetal development, stages of labor, all of it, because it's such an incredible process. And for me, as someone who never has to physically go through it, but instead I get to observe it, you know, I get to kind of have this very intellectual experience with it, so I get to nerd out with it.


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[Assistant] I may not be able to empathize, but I can definitely nerd out and just find it intellectually fascinating.


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[Assistant] I really hope you enjoyed today's video on the placenta. Again, this is so cool and hopefully the next time you see this it will be preserved and then we can have it, uh, we can even have some more really fascinating and interesting discussions. But thanks for watching everybody and I will see you in the next video.


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[Assistant] So, wow, we've got a lot on these. Just scrolling through here.


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[Assistant] Welcome to this section in learning Elasticsearch 5.0 entitled, What Elasticsearch is Not. In this section,