Thank you, Linda, and thank you also, Elaine, for inviting me to chair this session and to share some of our research as well. It's really terrific to see such a great turnout. Eric gave a tremendously insightful and exciting introduction to TCGA, and one of the messages from his talk is that the torrent of data that is coming out of TCGA greatly exceeds our analytical capacity within the narrow TCGA community. So we really need help from the entire scientific community. So I'd like to start by saying that the talk that I'll be giving today is I'm up here, but I really represent, of course, a team of people at the USC Epigenome Center, but also at Johns Hopkins University, where we have a very close and tight collaboration as one of the GCCs within TCGA with Steve Baylin and Leslie Cope and Jim Herman. And so I'm really speaking on behalf of them as well as the broader TCGA community. So during my talk, I'm going to give you a more narrow look and deeper look into the Epigenome that Eric mentioned several times during his presentation. I'm going to be focusing mostly on DNA methylation, keeping in mind that, of course, the Epigenome is more than just DNA methylation. There's histone modifications, how the nucleosomes are positioned, and various other proteins associated with the DNA, and collectively, this structure has marks that influence the accessibility of that DNA to the transcriptional machinery. DNA methylation is the mark that we focus on primarily within TCGA because it's the one mark that survives processing to naked DNA because there's a covalent modification of the DNA itself, a five-methylcytosine modification. And in many talks in the epigenetics field, we use this lollipop depiction of the potential targets of DNA methylation, CPG dinucleotides, indicated here by these little lollipops scattered throughout a schematic of the genome. Now if you look at which of these lollipops are actually methylated and which are un-methylated in a normal cell, you'll see some striking features. First, the lollipops themselves tend to be clustered in islands called CPG islands, and as well as areas of vast parts of the genome that actually have a depletion of CPG dinucleotides, these low CPG areas, and if you look at which are methylated, the CPG islands tend to be close to promoter regions, un-methylated. That DNA is generally accessible to the transcriptional machinery. The low-dense regions tend to be methylated, indicated by red in this figure. And if you then look at what happens in cancer, you'll notice two things. First, CPG islands can acquire DNA methylation throughout the entire CPG island that's normally not present in that normal cell and in that island, the so-called focal hypermethylation. And when that happens, at a promoter region of a gene that's supposed to be expressed, you get silencing of the gene. The gene transcription gets turned on. It's no longer activatable, at least not very easily. Now contrast with that, a more global loss of methylation in the CPG less-dense region, so the depleted regions, where you often see sort of this erosion of DNA methylation, so global loss. So there are two important features of this slide that I'd like you to keep in mind as we go through my presentation. One is this focal hypermethylation in the context of global hypomethylation, and this has really been known for decades. And today I'd like to shed some light on the relationship between these two events. So Eric mentioned BRCA1 and CDKN2A, P16, one in lung and the former in ovarian cancer. This is a different way of showing the data for BRCA1. This is a plot that Huai Shen put together. And it's showing the expression level of each tumor for BRCA1 versus the DNA methylation at the promoter. And you'll see an interesting relationship. On the left-hand side, you'll see that most of the tumors have a moderate level of expression and very low levels of DNA methylation. On the bottom right, you see a group of tumors that have relatively high DNA methylation and much lower expression levels. These are the so-called epigenetic silenced cases. And on the left, you'll also see where the fallopian tubes are, which we use as one of our controls in red, and you'll see eight fallopian tubes there that they have decent expression and low DNA methylation. Now one of the things that was better easily, more easily to see, easier to see in Eric's presentation was the fact that the germline mutations in green and the purple somatic mutations are actually mutually exclusive with the DNA methylation events, the epigenetic silencing events. So really, we have here a beautiful example of this CPG Island hypermethylation, this focal methylation that I was talking about that is clearly functionally significant from the fact that there's this statistically significant mutual exclusivity with a gene that is known to be mutated in a hereditary predisposed cause of ovarian and breast cancer. Interestingly, though, so you may think that they're equivalent, but if you actually look at the survival curves, and we really need even bigger numbers to really confirm this statistically, but there's certainly a trend that appears as if the mutated cases shown in red have better survival than the epigenetically silenced cases in blue, and this is even after adjustment for differences in age of onset between the two. So we'll have to see how they respond to PARP inhibitors and whether they are functionally indistinguishable. So I'm going to now briefly go over what Eric has already presented. That's the glioma CPG Island methylator phenotype. It's been published. We discovered this when we looked at the first 91 glioblastomas in TCGA and compared the samples against each other shown here in a heat map. And on the left-hand side is a group of glioblastomas that clearly has a very distinct profile of DNA methylation changes. It's very easy to recognize, so we called that G-SIMP for CPG Island methylator phenotype following the example that Jean-Pierre Issa Aminorotoyota created for colorectal cancer. Now in the meantime, our colleagues within TCGA, Rulfer Haak and others, had been working on profiling and characterizing and classifying glioblastomas using expression data, and they came up with four subtypes shown here, pronural, mesenchymal, classical, and neural, shown in these four different colors. And you can see that the G-SIMPs all the way in the left are almost exclusively contained within the pronural subset, but there are some pronural subtypes all the way on the right as well. And so it seems as if pronural is a further substratification of the pronural expression subtype. When we looked at expression, first we looked at the different expression subtypes, and these are the four different expression subtypes, and you don't see very striking differences in survival. The only hint is that the pronural subtype seems to have a slightly better survival, a slightly better clinical outcome than the other three subtypes. But remember, the pronural subtype was composed of both G-SIMP tumors and non-G-SIMP tumors. So the question becomes, well, what happens when we split out the G-SIMP tumors from the other non-G-SIMP pronural tumors? And lo and behold, what you find is that all of the survival advantage of the pronural subtype is really represented by these G-SIMP tumors, shown in red on the right-hand panel. And actually the rest of the non-G-SIMP pronural tumors have a worse outcome, a worse survival than the G-SIMPs. So this really indicates that there's some biology here to this profile and that it's not just a collection of passenger events. There might be something here that is indicative of a different clinical behavior. And one of the other really fascinating findings we found was when we started to take advantage of this comprehensive nature of TCGA data analysis and compared where the G-SIMPs to the non-G-SIMPs of what the distribution of point mutations and other genetic alterations in tumor suppressor genes was. And you'll see here that all of the mutations in IDH1, shown near the bottom of the bar on the top there, all of these fell within the G-SIMP tumors. So there was a perfect correlation between mutation in IDH1 and being a member of the G-SIMP category. And you see the 2x2 table there on the lower right. So this is really a fascinating finding. We don't know for sure what the reason is for this amazingly significant correlation association. But the model that has emerged is that IDH1 may actually, the mutation may be responsible for the aberrant CPG island methylation using the following hypothetical scheme. So we know that isocitrate dehydrogenase normally converts isocitrate to alpha-ketoglutarate shown here. And we also know that alpha-ketoglutarate is used as a substrate by an enzyme called TET, there are actually several TETs, that convert methyl C to hydroxymethylcytosine. And it's thought that this is one of the first steps on the pathway to demethylation. So this conversion of methyl C to hydroxymethyl C is a step along the way to active demethylation. Well it turns out that the mutant IDH1 actually takes the substrate of the wild type IDH1 and actually reverses the reaction but creates a novel oncometabolite called 2-hydroxyglutarate. And 2-hydroxyglutarate actually inhibits TET. And so now you have this wonderful hypothesis here that it's the accumulation of 2-hydroxyglutarate that inhibits the TETs, blocks this vacuum cleaner that normally keeps CPG islands clean and you get accumulation of CPG islands. Now it doesn't explain some of the wild type IDH1 G-SIMP cases and it also doesn't really explain the very characteristic gene specificity. So it's only a subset of CPG islands in the genome that are targeted in this G-SIMP phenomenon, but you could imagine that there are accessory proteins that help recruit TET enzymes to certain CPG islands and that when this regulatory process that is normally there to keep CPG islands clean, when that becomes defective because of this oncometabolite that you then get accumulation of methylation specifically in those CPG islands. I'm now going to briefly show you a few slides that from ongoing work from Huai Shen on cross tumor comparisons, one of the great things about being a member of TCGA is the huge amount of data and large numbers of tumors of different types that we can start to look at. And so here's a bird's eye view of 2,275 different TCGA cancer specimens with 409 normal tissues and this is just a simple hierarchical clustering across all tumors. And on the left you see the matching normals which have a fair overrepresentation of kidney samples, but all of them are in there at different levels. And you'll see a few interesting things. First, the normal tissues for these probes, these probes were selected to represent cancer specific methylation. You'll see that in the normal tissues there's relatively little difference among the different tissues for this subset of probes. So among the different tissues the cancer specific methylation actually does not seem to target the same sites that are tissue specifically differentially methylated. And on the right hand side you can see that mostly these cancer specific methylation profiles break down across different cancer types, different tissue types, different cells of origin for cancer. Now you may think that that's obvious, they're different organs and therefore different expression profiles and that that is why we see differences in DNA methylation patterns among the tumors. But remember this is looking only at the cancer specific accumulation of methylation. Again on the left there's not much difference among the normals. So even though all of this methylation or most of it happens in the process from a normal cell turning into a cancer cell you get these characteristic differences in DNA methylation profiles. Now one of the things you can do with this data is to look at correlations among different tumor types. And Hui did this actually for most of the probes, about 18,000 on the 27k alumina infineum platform. And this shows a broad overview of all the two by two correlations, scatter plots of every combination of tumor types that we had enough samples on plus Hui also split some of the cancer types into say SIMP versus non-SIMP, G-SIMP, etc. And in breast cancer she split out basal carcinoma. So what you see is that several interesting things. First the gastrointestinal malignancies, so stomach, I apologize for the jargon of the TCGA tumor types, STAD is stomach adenocarcinoma, colorectal adenocarcinoma, rectal adenocarcinoma, those all cluster sort of in the middle together, but the SIMPs are even more similar to each other in gastrointestinal SIMP than they are to their respective tissues. So there's clearly probably a common molecular defect that arises in the lower GI tract that can cause this very characteristic SIMP phenomenon. I didn't have time to show it, but we found that this is highly significantly associated with BRAF mutation. Secondly, you see at the bottom several female hormone-driven malignancies.  And there you see some interesting things. First of all, that they cluster together, which is of interest. And secondly also that basal carcinoma of the breast is more similar to endometrial cancer and ovarian cirrus cancer. There are other things in here, it's fun to explore this, looking at germ-layer origins and things like that, it's really a fascinating set of data to work with. But I need to move on to discuss going whole genome, and I'm going to show you some examples of whole genome bisulfite sequencing and comment on what we think that that might tell us about some epigenetic origins of cancer. So today I'm going to share with you four TCGA cancers, tumors that have been fully sequenced by whole genome shotgun bisulfite sequencing. We aim to cover about 20-fold coverage, that's enough with the high correlation of CPG methylation locally to get a very good picture of the DNA methylation profiles genome-wide. So we tend to cover about 90% of CPGs at least five or ten times, which is really quite significant. We're talking about 25 million CPG dinucleotides in the haploid genome. And we've also sequenced the normal adjacent counterparts for each of these.  And this is actually one we knew from our infineum data that there was actually relatively little CPG island hypermethylation, I'll come back to that, and a colorectal adenocarcinoma. So this is a genome-wide view of all five adjacent CPG windows showing on the horizontal axis the methylation level in that window from low to high, left to right, and on the vertical axis in the corresponding tumor. And this is really a map of the read density. And so you can sort of see this as what part of the genome, what fraction of the genome is present in methylated in both normal and tumor, which would be at the top right, or un-methylated in normal and un-methylated in tumor, which would be the bottom left. And on the top left, you see anything off the diagonal is either hypo or hypermethylated in cancer. Well, let me start with the hypo-methylation. So anything below the diagonal has less methylation in cancer than in normal. And you can see this sag under the diagonal on the right-hand side. So the vast majority of the genome is actually fairly heavily methylated. These are a lot of intergenic regions and intra-genic regions, but excluding the CPG islands. And you see that that sort of loses methylation in the tumor. But there's also this focal hypermethylation that I told you about in the beginning shown on the top left. And you see that little yellow blip there. Those are the CPG islands that are acquiring abnormal methylation. Let's look at some other cancers. It's not advancing. There we go. So here's a breast cancer. And you see something similar with respect to the top right, although we don't see as much hypo-methylation clearly. And we also are really lacking most of the CPG island hypermethylation. And the bottom left here, we see the endometroid cancer. And you see some CPG island hypermethylation, but not as much in the colon. But you see quite severe hypo-methylation. And finally, lung cancer, we actually didn't have the normal sequenced yet, so I'm showing it here compared to the normal endometrium. But again, severe hypo-methylation. And on the top left, some hypermethylation. Now, I want to focus in on this CPG island hypermethylation on the top left. So these are what Ben Berman describes as methylation-prone regions in the genome. And what Ben did was look at various different chromatin and genomic features of these methylation-prone elements and found that they were heavily enriched for marks that there's called polycomb repressive marks and poised promoters, bivalent promoters in embryonic stem cells. And this is something that we had found with simpler technologies a few years ago. So genome-wide, if you look at the very specific CPG island hypermethylation, there's a huge enrichment, more than 100-fold, for these poised promoters. So let me say just one or two things about this. The trithorax and the polycomb systems were first discovered in Drosophila, and they really counterbalance each other in early stem cells in development. And the trithorax marks are activating marks. And these are modifications of the histone H3 tails. And the polycomb is a repressive mark indicated by histone H3K27 lysine-27 trimethylation. And there's a subset of about 1,000 genes present in most multicellular organisms, including Drosophila and humans, that are targeted by both of these marks in stem cells, such that they're not actually transcriptionally active, but they're kept in a poised state ready to be turned on when the cell needs to start differentiation. And these targeted genes, targeted by these two marks, are actually mostly transcription factors and differentiation factors. So they're very important for lineage differentiation and development. Now this is an overview of about 1,000 of these targets compared to 16,000 non-polycomb targets. And what I'm showing you here is the methylation level in stem cells, embryonic stem cells on the horizontal axis, and in the normal colon on the vertical axis. And in yellow are the polycomb targets. And you can see that the polycomb targets are mostly to the left, which indicates that they don't have DNA methylation in embryonic stem cells. But there's already some acquisition of methylation in normal cells. So these poised promoters that are needed to differentiate and develop for differentiation and development are unmethylated in stem cells. They don't have DNA methylation. They just have this poised state. And there are some of these targets that have acquired methylation in normal colon. Now what happens when we look at colorectal cancer? What I'm going to show is I'm going to transition to the cancer and watch what happens to the yellow dots. And what you see is that the yellow dots move up. And so a process that has started in normal cells becomes exacerbated in cancer cells. So a methylation of what should be normally a reversible repression in stem cells acquire some irreversible silencing in normal cells, and that becomes exacerbated in cancer. So what does that mean? Well the model that we put forward a few years ago is that stem cells have these very important genes kept in a poised state. And the stem cell renews, of course, but of course also spins off differentiated cells. And if you look at where the polycomb group proteins are, in yellow, these are actually removed in the differentiated cell.  What we believe happens over time, over our lifetime, as we get older, is that slowly there's a crosstalk between the polycomb, the yellow polycomb, and DNA methylation machinery, which turns a transient repressive state into a permanently silent state. And once that happens at enough different genes that are required for differentiation, the cell loses its capability to differentiate. And it becomes stuck as a self-renewing cell unable to properly differentiate. And that is then a sitting duck, really, to turn into a cancer cell with additional mutations in oncogenes and tumor suppressor genes. So this model explains the methylation behavior about half of cancer-specifically methylated genes. It is consistent with the observation of epigenetic field effects adjacent to tumors. It's consistent with the stem cell-like behavior of cancer cells and with the evidence for tumor-initiating cells. And it suggests that therapeutic cloning strategies using human ES cells or IPS cells should incorporate screening for PRC2 or these polycomb DNA methylation abnormalities. And it suggests that in some cases, cancer may start out as a differentiation defect due to epigenetic defects as opposed to necessarily a gatekeeping change in a tumor suppressor gene. This is somewhat provocative, and I'm not arguing, obviously, for a hereditary case. It's quite different, but I think that it's certainly in many sporadic cases this may be the case. I'm going to briefly, in the last few minutes, go over some really exciting data that is actually some of which is in press. And this has to do with looking more closely at where the CPG island hypermethylation and hypomethylation happens across the genome. This just shows you a blow-up of one CPG island that is unmethylated, each one of these little rectangles is a sequencing read, red is methylated and green is unmethylated. Here you see the normal colonic mucosa, and down here you see that this segregation between CPG islands and non-CPG islands has fallen apart, and you get encroachment of methylation into the CPG island. And at the bottom, you see the differential between tumor and normal. So one thing that Ben found, which was very exciting, was that these regions of hypomethylation appeared in contiguous stretches that were of megabase size, indicated at the bottom here by these stretches that undergo hypomethylation interspersed by regions of relative epigenetic stability. And if you plot 20 KB windows now, and the same kind of plot that I showed previously instead of these short focal regions we're looking at big range, longer distant changes, you'll see that the genome is really segregated into two compartments, one part that is called partially methylated domains, nomenclature started by Joe Ecker, and another part that is relatively stable. And if you look at where the CPG island hypermethylation happens, we find that this focal hypermethylation happens primarily within these regions of long-range hypomethylation. So what we really have is areas of epigenetic instability that encompass both the hypomethylation and the hypermethylation. And the most interesting finding we think is that we found, and this is shown here for the TCGA tumors, the partially methylated domains, and all the way at the bottom, we found that these regions coincide with regions that are late replicating and in the nuclear periphery. So Eric talked about how regions of the genome that are near the periphery of the nucleus and are late replicating have higher mutation rates. Well we now find that they're epigenetically unstable. So we really have this spatial view now of the genome. It's not a long linear molecule with all the chromosomes lined up either front to back or in a circle. It's actually a spatial structure and the regions that are near the periphery of the nucleus contain our lamin attached. They have late replication and they have epigenetic instability and the more actively transcribed regions interior to the nucleus are much more stable. So that's it in summary. I'm running late so I'm going to actually just keep this up for a minute and jump on then to the acknowledgments. I really want to point out Dan Weisenberg and Ben Berman who are two faculty members at the U.S. C. Epigenome Center who really helped drive this project so I'm particularly grateful to their contributions. But obviously this is a team effort with many people participating in the data production and analysis. And on the top right again my collaborators at Hopkins, Steve, Jim and Leslie. Thank you.


Right down. So there is a presence of nuclear force, which is very important when we discuss about nucleus. Okay. Let us talk about the nuclear force exclusively. Okay. So several experiments have been conducted between 1930 and 1950. So there is an entire decade of experimentation that is done on the stability of nucleus and there is a graph that has come out between, distance between the two nucleons. Nucleons is proton or neutron. So you are taking two nucleons, you take two protons or two neutrons or take one neutron, one proton. Okay. And you just vary their distances. Alright. If you increase or decrease their distances and you vary it in such a way that their distances go from 1, 2, 3. These are, you know, multiplication factor is 10 is for minus 15 meters. Okay. So this is perimeter. 10 is for minus 15 meter. So when you say 1, 1 is 1 into times or minus 15, which is 1000 times less than the size of item. Okay. So remember that. Now this on the Y axis, you have potential energy. This is potential energy. M E V. Okay. So we have minus 100 over here. We have zero here and we have let us say 100 over here. Okay. Now when this graph is plotted, it is observed that this graph goes like this. Draw this all of you. Now, do you guys remember that the relation between the force and the potential energy is minus the derivative of potential energy like this. Do you guys remember this? Right. We define potential energy like this only negative of the work done by the field, which is minus f dot dr. So if you are talking about the displacement in the direction of force only, so the full derivative becomes partial derivative. So it will be minus of du by dr becomes force. So this is the relation that is there. Now you can see here that the slope of this line, when you are less than r naught distance. Okay. When you are less than r naught distance, slope is what? Positive or negative? Negative. Negative. slope is negative and it is very, very high because the x axis is, you know, this scale is literally stretched. You know, the distance from here to there, you know, from here to there is 10 raised to power minus 15 into 3, which is almost nothing. Okay. So we are stretching it and then seeing it. So this is having like infinite slope. Are you getting it? This is like literally a straight line. Okay. So the force of repulsion will be, sorry, the force will be positive. So there will be a repulsion force before r naught. And then if you go slightly away from r naught, then you will see that this is, this is the positive slope. So it will be attractive force from r naught distance. But then if you move to this distance from r naught, if you travel this much distance, then the slope will rapidly decrease. Here it is near infinity and here it is almost flat, which is zero. So here du by dr becomes zero. So as soon as you reach about 1.2 into 10 raised to power minus 15 meters, the nuclear force goes to zero. Fine. That is why we call it short range force. It cannot be felt beyond a certain point. It suddenly drops to zero. Okay. So just write down a few properties of the nuclear force. Write down the first one is nuclear force is much stronger. You can see the graph. The slope is almost infinity whenever it is applied much stronger than Coulomb force. Okay. Second. So that is why you know two protons, even though they are very close to each other, they should feel electrostatic repulsion. But nuclear force being much larger still holds them together. Okay. So nuclear force is an attractive force inside the nucleus between the two protons. Write down the nuclear force, nuclear force falls rapidly to zero for distance greater than few centimeters. It is very or femto. You guys have any idea? No idea. Okay. Anyways. So what is that for distance greater than something you've written? For distance greater than few centimeters. It is femto. Femtometers. Okay. Fine. Write down the third point. Nuclear force between neutron, neutron, neutron proton and proton proton is approximately same. It does not depend on charge. Okay. So these are the few points about the nuclear forces. Fine. So we have done with the major portion of the theoretical part of the chapter. So after the break, we will start with something called radioactivity. There you will see a lot of numericals. Okay. We'll take 10 minutes break. Right now it is 7. Fine. So next we will discuss about radioactivity. Write down. Ramchar, you're there, right? Yeah, sir. Yeah, I'm just making sure everybody came back. Fine. So we are talking about radioactivity and radioactivity is nothing but it's a spontaneous reaction. Okay. It is spontaneous. Write down spontaneous disintegration of heavy nucleus into daughter nucleases. Fine. So it's a spontaneous reaction that happens. You don't have to do anything like several spontaneous chemical reaction you might have seen, right? That happens on its own. Similarly, this is also a spontaneous reaction. So when a heavy nucleus disintegrate, you can see that, you know, entropically it is favorable because entropy is increasing, number of nucleases are increasing. And also the binding energy per nucleon goes up because for a heavy nucleus, the binding energy per nucleon is lesser. So it is favorable both ways. Thermodynamically as well as, you know, entropically. So that is why this is a spontaneous reaction that happens. And it is disintegration. Okay. So there is just one nucleus that is there. It's not that two or three nucleases are reacting. One nucleus is disintegrating into the daughter nucleus. Maybe one will give three nucleus. Are you getting it? Now, when this disintegration happens, it is a good idea to find out the rate of disintegration. That will actually give us an idea about how much time it will take to totally consume the entire nucleus. For example, you have n nucleases of uranium 238. And it is disintegrating into several atoms. Let us say this is atom one, atom two, atom three. Okay, this has three different nucleases. So this many will disintegrate into these three. And some amount of maybe energy is also released. Okay, it's a good idea to find out how fast this disintegration is happening so that you will know that after particular time, what will be the remaining uranium 235 and how much energy will be liberated or how many daughter nucleases will be there. Okay, so in a way, what is happening is that the uranium 238 is getting consumed. Okay, right now let us say 50 nucleases there after some point in time, maybe 40 will be there, then 30 will be there. So like this, the number of nucleus of uranium 238, they are decreasing. Okay, and you can relate this scenario to let us say a city which has, suppose this city has a population of 1000 people. Okay, and this city has a population of 10,000 people. Fine, demography is similar as in the percentage of people who are to 20 years age, percentage of people who are 60 years age, like that it is similar, male number of percentage of male, percentage of female, everything is similar. So if I say that here, the number of deaths that are happening here is five deaths per day. So how many will be there here in this city, 50, right? So this number of people who are dying here can be related to the number of nucleases that are decreasing. Are you getting it? So you can say that the number of nucleus that are decreasing at any moment is proportional to the number of nucleus that are present at that moment, isn't it? If number of nucleases are more, then more number of nucleus per unit time will be decreasing. Are you getting it all of you? Yes, sir. Okay, and since number of nucleus, they are going down, so dn by dt will be a positive or a negative quantity? Negative. This will be less than zero. So if I have to bring a correlation between dn by dt and number of nucleus, number of nucleus will be a positive quantity, right? So I have to write down like this, dn by dt will be equal to minus of some positive constant multiplied by number of nucleus at that point in time, okay? So this is the relation which we are going to use to derive several things, all right? So this is purely probabilistic in nature and you can solve also this particular equation. So if you say that if we consider at t equal to zero, when time is zero, number of nucleus that are there, they are n naught, then how many number of nucleus? So is it equal to n naught into e to the power minus lambda t? All of you getting that? Yes, sir. Yes, sir. This is a simple linear differential equation. You can just take n in the denominator of the left hand side and this is equal to minus of lambda into dt, okay? Then lambda is constant. So when you integrate from zero to t time, number of nucleus goes from n naught to let us say n. So you will get log of, natural log of n from n naught to n. This will be equal to minus of lambda times t. So when you put the limits, it becomes ln n minus ln n naught. So it will be ln n divided by n naught. This is equal to minus lambda t. So n divided by n naught will come out to be e to the power minus lambda t, right? So n will be equal to n naught e to the power minus of lambda into t, okay? Now you can look at this expression and make out that when t is equal to zero, n is n naught only and ideally when t tends to infinity, what should be the number of nucleus present? It should tend to zero, isn't it? After infinite times, the number of nucleus should just vanish. Are you getting it? Yes, sir. Okay. So now see, this is rate of disintegration as a function of how many number of nucleus are there at that point in time, okay? You can also write down rate of disintegration with respect to time. So this will be lambda n naught e to the power minus lambda t, okay? This is the second equation. The first equation gives you rate of disintegration as a function of n and second will give you rate of disintegration as a function of time, okay?


Okay. Let's start. Let me share my document. Can you see my sharing of the document? Okay, good. I think today, I think in last meeting, we have addressed the most comments. Any new comments? Yeah, we forgot to. So in the next CSF, somebody's work group meeting, I'm going to ask Alex to see what's his comment on that. Any more comments on that? So, Nahiro, I see that you have this comment, right? Is this new? Or are we already addressed? I think we already addressed. Yeah, so is this resolved? I think my understanding is right. Because I think if possible, I think I expect Cassie to add some use case. Do you remember? Oh, okay. Yeah. Okay, I see. So for the use case for what? For all, for the parallel? Parallel, not parallel state, but parallel that one. Okay. Yeah. Okay. Now I got it. Yeah. Sorry. I haven't got chance to add that yet. So I'm going to do it. Okay, so this is that I need to do that. I think, I think this one, this Kansas case sensitive. I think we decide it is case sensitive, right? So this, this was last comments by Yvonne. Let me see any other. Okay, I think this we discussed it. Okay, I think that's pretty much it is, right? So I think most of the comments were addressed. So I have an action item to add a use case for the parallel action, right? Nahiro? Yeah. Okay. So that's your price. Okay. And this one, I think you already replied to Roy's comments. We also discussed this. And so for the people, let me see who will participate. So I need comments from other people who missed last time's meeting. I think most people are in last meeting. Except Rachel. Yeah, I think Rachel, you. Yeah, I wasn't here for the last one. Yeah. So you have any more comments on this document? No, I think I think my main question about this is really about extensions. And that's a bigger question. Oh, that's more on the cloud event side. Right. Okay, so, so I think today probably I'm thinking we, I'm thinking about writing this up. So I'm going to add a use case for that parallel, the parallel action per Nahiro's comment. And so I think, you know, we have gone through many iterations of this document, many comments and then many sessions basically. So I'm thinking maybe we should put this into a PR and then, you know, as a first draft and then later on, people can, you know, more people can read on it and then comment on it or update it. I think add more and add more things to this document or modify, you know, some sections. How do you folks think about that? So Kathy, when you talk about a PR, do you mean a PR to the cloud events like repo? I would not think I think this is a parallel to cloud events, right? So this is what with the Solaris World Group discusses the next work item is related to cloud events because it's going to use cloud events. But I don't think it's part of the cloud events. Right, I would agree. That's why I was thinking maybe if we have time on this week's call, we could talk about the next steps on what to do with this. So for example, my initial thinking is that we should create a new repo for this work and have this be at least initially the only document in there. So we could do exactly what you said, right, open up pull request to make modifications going forward. I think I agree with that. So probably, you know, maybe that's, I think this is a parallel work to the cloud events, but it also shows how we are going to use those events, right? So I think we agree with you. We pull a new repo. So I can do a PR pull to that new repo. And then this is as a first draft. And then later people can add more, modify this, you know, pull more PRs on this, or even add other, you know, other documents, whatever.  And then we have a link that we have a link to this new repo. Add this link to this new repo into the work group webpage so that, you know, when people ask for that, we can just point it to, you know, the work group webpage or the link. Actually, when I joined the connective meeting, the eventing meeting, they were asking, you know, some things on this. So what do other people think about this? Sounds good to you, to everyone. Yeah, I think it's definitely the way forward. We definitely need to have a put into a repo. Okay. Sounds good. So let me, so if that's our consensus, let me write down this agenda so we can. So, dog, I might need your help on how to, I mean, which repo and then to put it in. Yeah, that's the easy part. We need to first discuss it on one of the weekly phone calls to make sure people are okay with creating a new repo to host it. And then we just figure out the name later. That's minor. Okay. Okay. That sounds good. Okay. And then we'll put this in. And then I think we, I'm thinking about writing up on this work group meeting, this subgroup meeting. Unless we, of course, we can, you know, have another meeting if it's needed. So what's other people think about this? Or you have any more suggestions on how we should, I mean, any, any additional work we should do in this work group? That seems great to me. Okay, good. So I think that's, I'm going to just, so that's our consensus, we wrap this up. We would like this, we think it makes sense to put this into, I'm going to put this into the meeting minutes. To put this into a repo of the service work group. And then we're going to discuss this to the service work group and then to get, you know, a sense to get, you know, other people's opinion. Yeah. That's, that's about it. I think this is a short meeting. Of course, I'm going to add that use case. And then people can still, you know, you know, give comments and even we add it into that repo, people can still pull new PR to modify it. This is just, this is a backup open document for, for better, you know, polishing and modifying to make it more useful. Yeah. No other, any other topic you would like to discuss? Okay. Not for me. Not for, okay. How about others? Any other, if no, I, if no one have any other topic. I guess we can end this meeting. Unless you, but we can also communicate on the slack, you know, all the different channel, even the CSF or group meeting, the crowd events were group meeting. Kathy, are you going to prepare something short to summarize this ahead of Thursday. You mean summarize. So because, so I'm going to summarize, you know, what we discussed with what we would like the decision we make today, so you would like to wrap this up, put into the repo. But in terms of the document, it is a long document. It's, you know, it's, it's very comfortable. I think it's kind of very comprehensive. Unless you think it's helpful. Yeah, I can summarize, you know, the reason is that we're going to like we'll need everyone else to say yes this is worthwhile and we should create a repo and so if we take a few minutes before that meeting and prepare something to give them, and I think it will, maybe that will go more easily. Oh yeah, I think that's a good suggestion. Okay, I can do that. I'll try to maybe write some site to talk about this so that people, yeah, and kind of stand it better. Okay, I know it's hard to summarize. Yeah, but okay, I think that's a good suggestion. Yes, sure, I can do it. Yeah. Okay, if that's it. Thank you everyone. Thanks everyone for your feedback for your participation in this work. I think we have done a great job on this. Bye everybody. Okay, thank you. Bye. Bye bye.


Hey everyone, we have a nice conversation to have here about Skyward Sword and how it's actually a bigger improvement Performance and visual wise then maybe we initially thought and even I initially thought When watching the trailer now throughout this video we're going to be having side-by-side comparisons of Skyward Sword's Wii version versus what we got with the Skyward Sword HD trailer Obviously caveat. It's an advertisement trailer who knows if it's really Representative of the final product. We obviously hope it is or hope it's even better than what we got in the trailer but I want to get into this because honestly there is still a massive debate over the pricing of this game and I Don't actually think despite it looking better Then you might think it does or be a bigger improvement than you think it is That that debate is gonna go anywhere, but we'll talk about that in a moment. First off Thank you so much for tuning in. We are giving away $99 Nintendo Switch eShop gift card head on to the description or the pin comment without further Do that's gonna do our first comparison now all of these comparisons are gonna be coming from other people's YouTube channels I'll be linking to each comparison if you want to hear any of their commentary on it Or any of their music or sound that they play along with it This is just not because I'm trying to be lazy over here one I just want to show you multiple different comparisons to I no longer own a Nintendo Wii or Wii U So I don't actually have the ability to capture my own Skyward Sword footage and unfortunately I didn't really make a video walkthrough for this back in the day when I ran Zelda Informer So I don't have any local footage Even from back in those days to try to create a comparison of Visuals so thankfully the rest of YouTube has already done this for us quite easily and get multiple angles from side to side Partial screen views to whatever we end up going without Throughout the conversation that I decided to hold here. So one thing I came away when watching all these different videos is The resolution bump actually matters now I talked about how the Skyward Sword art style was created in a way to look good on blurry screens because at the time The Skyward Sword came out and a ginomo knew this most people at that point had an HD television at least 720p most people at 1080p and remember this was happening about a decade ago and At that point most people had converted off of their CRTs and we're now into flat screen you know HD TVs so that had become kind of the standard in the home by the time this game came around and Ijinomo knew this so what he wanted to do is put an art style in this game that made the backgrounds Look good. Despite it being blown up So I take it a 480p image and blowing it up to 1080 you wanted it to still look good So you went with this painter-esque art style that made it where it didn't really matter if the game was HD or not The background was still going to look basically the same and for the most part when you look at these comparisons the background We're talking the sky objects way off in the distance for the most part don't look incredibly better But honestly side by side The difference is much more pronounced than I expected now. I've seen skyward sword in HD. I've seen it on Emulator, I've seen it up to 4k even so I know how much crisper an image can look just by increasing resolution on it And you know updating textures to take advantage of that resolution increase And while I don't really feel like there's been much texture work specifically done with skyward sword because They're likely already were HD assets that were being down sampled to 480 I do think that it's interesting seeing that the differences are more pronounced than I expected the game Definitely looks significantly better in my opinion In 1080p than it ever did in 480p now. This isn't to mean it's going to look Incredible this isn't going to be the kind of stark differences we saw with say well the wind waker back on gamecube versus the remaster or re-release hd of it on The on well We you why because nintendo actually went through and replaced all the character models And redid some of the looks use the new engine on it or at least an updated engine It was still technically the same engine, but it was an updated version of the engine And they had a bloom and all these other effects first-person mode technically And they did all this because they were experimenting with hd zelda development at the time So they were trying out a bunch of different techniques that obviously would lead into the next zelda game Uh, which was breath of the wild So the interesting thing is they used the wind waker as an internal testing ground Hence why it actually has a lot of different things going on in it compared to say twilight princess hd Which nintendo tasked tantalists were doing which literally it was like a retexture hd port Yes, they technically added new content without an amiibo all that jazz we know but for the most part It was a rather simplistic port jobbing comparison to the wind waker And now we get to scourge sword hd where to be honest it is maybe the simplest port job they have done yet Kind of so if you think about the twilight princess And how they brought that over and they kind of tantalists kind of re-textured things in a way Well, it's really hard to re-text your skyward sword Beyond character models and as you're seeing some of the models here You can definitely tell that there's been some slight alterations to the models to make them look a bit better in hd So there's definitely been some texture work done on the actual character models But it's hard to do much about the blurry Painter style background without just completely changing the art style So you're kind of stuck with it In a sense it does look better in hd, of course, but You're not going to be able to massively improve it without fundamentally changing the art direction of the game However, this is the first zelda game and this is just I don't know why people aren't Paying more attention to this because they talk about how there's no quality of life improvements, right? Well, they added More accurate motion controls They have taken the hud and massively shrunk the hud to actually make it Usable if you guys remember in the original we version of skyward sword and maybe you don't you didn't play it The hud was huge. It took up a majority of your screen It was like over 50% of real estate was spent on the hud It was insane and yes There was an option to turn the hud off But people often needed the hud to be reminded of what items they put on which button on or which thing on the d-pad and You know What buttons attack and what a shield like people needed reminders and that's what huds are for Are to remind you it was nice to be able to turn it off But still people also just turned it off either to record a really clear slow clear gameplay session or to get a screenshot um I like the fact they shrunk the hud down I like the fact that they did technically work on improving the motion controls and they did Map it to a controller and do all the testing necessary to make that work as well So nintendo did do quality of life improvements there But the biggest quality of life improvement is Did you guys know? Factually, this is the first traditional 3d third person perspective over the shoulder Zelda game to be in 60 fps Breath of the wild didn't do it. Breath of the wild struggles to maintain 30 When they ported the wind waker hd and twilight princess hd to we eu They also still ran at 30 fps Oh, what about ocarina of time 3d and major's master 3d 30 fps They have been using a 30 fps target for zelda games for a long time Now the original nes zelda back in the day was 60 or 50 if you were in those 50 hertz days Out in europe back when they were using a different standard for some reason but Reality is zelda hasn't met at 60 fps very often nintendo did bring it back with some of the handheld entries So only between worlds is a crisp 60 fps But the thing is 60 fps matters It is a massive difference and from what we saw in the trailer it looks Like a locked 60 fps. We were not going to know for sure till the game is in our hands But it's probably a locked 60 fps. And so instead of taking some of the capabilities of the switch and Really pumping a lot of work into redoing every minute detail of the world They chose to take the performance increase going from a we to a we you and put it into the frame rate It is no small feat to just double the frame rate of a game and have it run smooth at that given frame rate In fact, there's a lot of things you need to adjust in the code base to actually make the gameplay Work well because the gameplay was built with 30 fps in mind to bump it to 60 Sometimes the timings on things are slightly off So they would have had to fine tune the game to even run at 60 And the thing is I have to start to think do we really want them to do You know, here's here's where I'm kind of stuck in this conversation Nintendo had a choice tantalists or whoever did the port had a choice They could have focused on making it Possibly a little bit better visual looking some more blooms and more of this things that make it look more current, right? They could have focused on that And gave us 30 fps just like we got with with twilight princess hd and the wind waker hd Or they could give us a smoother gameplay experience and give us 60 I think all of us can agree 60 fps is Way more preferred than something that maybe is a bit more visually stunning In fact, I think what's so great about a potential switch pro coming Is that while breath of the wild 2 is going to be on the og switch one of the big differences between the pro model And the current switch and switch light is that it could be at 60 fps for that game instead of 30 Which to me makes a massive gameplay difference 60 fps gets more accurate controls more crazy things can happen The game just feels smoother feels tighter And it just ends up being a better gameplay experience So fundamentally scoured stores the first 3d zelda game at 60 fps Which means it should be one of the tightest controlling zelda games to date So they they did that improvement, which is a massive Massive quality of life improvement that people are just overlooking in addition to yes The game actually visually looks a lot better in hd than it did on the we I think people are just seeing still screenshots and being like hey look at this still screenshot Ha ha doesn't look that good, but watch the game in motion. It definitely is a marked improvement So this obviously comes back to the conversation of hey scoured sword hd is 60 dollars Is it really worth 60 dollars? And we've had a number of conversations on this and I think the grand takeaway from this is It's worth 60 dollars if you're willing to spend 60 dollars if you're not willing to spend 60 dollars It's not worth it. There is no right or wrong answer to this. There is a what you would prefer You could try to make it a question of morality, but this is what nintendo has done it only Honestly feels bad In light of the fact that mario galaxy Which to many people should be even a higher valued game from nintendo was given hd treatment and tossed on A collection pack for 60 bucks getting two other games to go with it And in hindsight.  Yeah, skyward sword hd feels overpriced when you consider mario galaxy had two other games packed with it But at the same point I'm going to spend 60 bucks and i'm spending an extra 80 dollars buying zelda joy cons skyward sword to me Is one of the best zelda games ever released. I recently did a listing uh through live stream of all 35 zelda games I had 35 zelda games not all of them are can in but all of them uh were licensed by nintendo basically Including things like you know just just to toss it out their cadence of hyrule was on that list Twilight princess pic cross anyone remember that game? That's on the list. Thanks crossbow training all of the cdi games were technically licensed by nintendo So they're on the list. So yeah, it's a rather big list 35 games for 35 years of zelda So I didn't even realize When I was first collecting all the data for it that there was that many games even though I've technically Tried every single one of them in one form or another I mean we got online zelda games back in the 80s and bs zelda and ancient stone tablets So like there's just some crazy stuff in zelda's history that I went through but I'm not so sure there is a good answer what I can tell you Uh about the 60 dollar price tag is Nintendo isn't screwing anyone over nobody has to buy games buying games is an optional entertainment medium We all want games to be cheaper It's one reason why I love game pass on the xbox series x because it fundamentally makes playing games Cheaper, especially if you're interested in the games they put on that service. It's just like netflix. Why did netflix blow up? It's not just the convenience of live streaming. It's it made consuming Autonomedia cheaper than traditional cable combined with hbo and renting movies at that time They made it cheaper And that's exactly what game pass is doing So fundamentally we all kind of want things to be cheaper, whether we're okay with spending 60 bucks on skyward sword hd or not But at the end of the day What really matters Is do you have a great time playing the game you choose to spend your money on whether you spend five dollars ten Get it for free free to play fortnight Spend 60 for a port hd remaster By breath of the lot to You know spend what was it 50 or 40 bucks? Whatever it was for miles morales Or unless you got like the 70 dollar edition or 80 dollar dish. I can't remember where it came with the playstation 5 version of The original game no matter what you end up spending on your game So what matters is are you getting enough entertainment value out of that game for the money you spend? And that honestly is a question that is entirely up to the individual Nintendo is going to do what nintendo does other companies are going to do what other companies do The only anti-consumer practice nintendo really has going on right now is a noble Fixable issue with joy con drift that nintendo is refusing to do anything about at least up to this point And have barely acknowledged in many cases and sometimes even denied it before the lawsuits started landing So at the end of the day that's nintendo's giant Asterix of an anti-consumer practice right now Charging 60 dollars in valuing their games at a certain valuation. That's not anti-consumer It's just Not what some people feel they should be doing Maybe because of the pandemic Maybe because of mario galaxy being packed in with two other games Maybe because they don't think there's been enough done with scobber sword hd to justify a 60 dollar price point Which we should know the game doesn't come out till July. We don't really know Everything they've done with the game. I'll give you a prime example Amiibo functionalities included, but we did not see any amiibo functionality in the trailer. We also did not see Uh, you know Any mention of amiibo functionality in the original game because there wasn't any amiibos there was no functionality back in 2011 so There could be more to the puzzle that we don't know So until we get the full picture until the game's here until we could decide for ourselves if it was if our entertainment value Was worth the money we spent on it or didn't spend on it Uh, I feel like that conversation is something best that we return to after the game comes out Until then I am Nathan Robeljansford in center, but I hope you enjoyed this fresh look at skyward sword We version, uh hd version side by side the conversation I had along the way And you know, am I here to convince you that to buy the game? Am I here to convince you uh, what to do with your own money? I just like talking about zelda and if you made it this far in the video I guess I might as well tell you I am going to attempt to have a zelda video come out every single day, uh Either until Breath of the Wild 2 releases or until we get to the 36th anniversary. So Potentially 365 straight days of zelda videos Um, you might think that's insane But keep in mind I used to come up with conversations about zelda every single day for four years straight Doing it for one year won't be too bad Maybe For now, we have so much to talk about with Breath of the Wild 2 I could theorize Um, I can bring in conversations Thursday. I already know we have a zelda Episode of the podcast coming out. So like that video is already taken care of it's monday So I gotta come on two videos before Thursday. I think I can pull it off. All right, folks. I'll catch you in the next video


Bothered by the DuPont Company, makers of better things for a better living through chemistry. Starring Virginia Bruce. Tonight's DuPont Cabotade, Lady of Johnstown. And here's our star, Virginia Bruce, as the real life heroine of our story, Rose Noff. I want to tell you about a birthday party. It was mine, and it didn't seem at all unusual to me. But all my friends and my family, my son-in-law, my grand-son and granddaughter, and my great-grandson and granddaughter too, they all seem to think it's quite remarkable there.  Happy birthday, Mrs. Knott. First 90 years of the hundred. Make it nice and more, Mrs. Knott. Thank you. Thank you. There's cake and refreshments in the dining room, everyone.  What about you, Mother? Let me take you in with a rest. No, no, no. Don't give me a moment. I've got a birthday present for you. Me? Well, that's a switch. Yes, I suppose it is. Here, let's sit down. Son, when I took over the management of our business... Oh, Mother, you're not going to talk business, are you? You're supposed to be enjoying yourselves. Do you think I haven't enjoyed myself? Do you think it's all been trouble and hard work for me? I think of the things that have been accomplished. The success of our company. It's been enjoyment for me, just remembering. I know, Mother. Then I listen to that music, and I see your daughter dancing out there. You know that your father and I dance together. Do you think so? I do. You're right, Mother. She has broad shoulders and broad muscles and a hat of good nine and a half gallons bigger than any other fellow in town. And I... And you were the bell of the ball. Yes. Anywhere I can remember one day, right here in Dunstown, in 1882, your father had just come back. The next number's the grand-right and left. Let's sneak out now, Rose. I'm in the veranda. I want to talk to you. Son, I'm surprised you don't care for the grand-right and left. Well, how do you mean? Well, your whole life has been nothing else. Father, Mother, Jack, and when he took his rain... Oh, yes, I guess I had sort of swung from one thing to the other. And the next day? In the infighting for that. Well, I... I was considering accepting a position with the New York Commission House that's selling nit-good. Well? Yeah. Well, why don't you laugh? Because... because Charles, I think he could sell all my things. Do you? Yes, I do.  I'm going to wind up with a business of my own someday. Really, you will. Why, you'll be president of the company and chairman of the board in your own right beside it. What kind of business, son? Well, I haven't decided yet. Oh. Rose, there's one thing I have decided on the role of my partner. I've met a lot of girls in my life. There's only one I've loved. And that's you, Rose. I'm sorry. Darling, I haven't much to offer. No money at all, just a salesman's host and commission. I'd have to ask you to take what comes. They didn't every woman tell me thoughts when she married. The better, the worse. Oh, Lord. I'll take what comes. Oh, darling, I'm home. Oh, she kicked me.  I don't dare leave the clothes right now. Why, what do you make of it? Angel cake with heavenly frosting? Do I have to walk on tiptoe? It'll fall? No. Just plain old pants with jelly. You'll be blessed if you sit again and have to have it. You'll nurse everybody in the neighborhood. You want to know something?  Not only my own, but... Oh, that's rude. Didn't I tell you to tell him I'd make anything? Well, you might turn away from the stove and then let me tell you to my face. But I told you, dear, I can't leave. I just have to say that it must be clarified with the egg whites. Clarified with the egg whites? All that trouble? No. You know that these things have been cooking for two days. When they disintegrate, the liquid has to be strained to see-cloth and knee-cloth.  No, sir. The whole time, you've been away. Sorry, sir, this next door was sick. Performance is good. I suppose, sir, I've heard that there's pain. I came over to tell you how to make it. I'm afraid that's exactly what you're doing. Well, then all I can say is there must be a better way to make it. No, no. Just because you and Sarah don't get along... More in spite of how she and I get along, there must be a better way to make a bold move. Well, if you could think of one, my dear, every housewife in this country would be their eternal brother. Hmm? Are you really serious, Rose? Is it really that important in cooking? I think gelatin might be used in all kinds of ways if it were easier to make. It presides for individuals that might be good for people. Yeah. What do you think, sir? Well, I'm not sure exactly, but I was thinking. I'm no chemist, not even a cook. When you were a good Texas ranger, now you're a wonderful servant. How would it be if I became president of a company? What kind of a company? Well, I watch you standing over that servant, I think. If only I had a factory. If only there wasn't someone one more in the world who could show me how to manufacture gelatin commercially. I could... Why don't you laugh? Because I... I think you could do almost anything, sir. R-r-r-r-r-r-r... R-r-r-r-r-r... R-r-r-r-r-r... R-r-r-r-r-r... R-r-r-r-r-r... R-r-r-r-r-r... Rose, ma'am, what on earth are you doing? Just cooking? Are you cooking on a picnic tomorrow or something? Or are you going on a picnic this rather? No, this is no picnic, believe me. Or if it is, the cooking chefs at the Waldorf would be the ones who'd be out in a good time. Ah, my testing for that new company of your husband. Did you feel it wise, gelatin? Yes, mm-hmm. You have to keep testing and testing. We've got all our savings invested in the process. Well, do you ever get my real life back, anyway? Oh, we've had it a long time. But it wasn't until you learned a method from a Swiss scientist that we started making it commercial. Well, I couldn't get somebody besides you to slave over this stuff they remember us. It's me that always cooking, making up the recipe. Well, I think I'm lucky that I can help Charles in his business. Well, how many wives do you have that time? These are exhibits for the pure food exposition. This is going to be very good for the time. Down-seller on ice, I have tomato acid, and strawberry jamon. I suppose your husband will pick up some pie like a grand piano or something so the person who can identify all the votes to both Brian Paul and Paul, so... Oh, no, some stuff works up, you may be sure. Well, I mean, anybody who could think up the advertising scene for way too little. Oh, well, darling, come on in. Yes, darling. Come out in the back yard. I want to show you something. You've been out in the storeroom over the stable working on some mysterious project all these years. Go! Come in. Come on, darling, keep it real. Um, for heaven's sake, Charles, even if you don't approve, pretend you do, won't you? No, um, I'm tired. For your sake. Oh, darling, I wanted you to see this before I packed it up and send it to me. Oh, hello, Sarah. Good evening, Charles. Come on over by the ladder. Both of you. Ah, just take a look at the steps I've had made. Hmm, it's a bonus sometime. We'll pick you, Brian, McKinley, Charles, be my first time you're going into politics, too. Look again, ladies. We've everything it says on the banner. Oh, Brian wants to win. McKinley wants to win. Let's just stand here. Mark Swarovic always wins. Well, I never. It's going to be strung up across Broadway at 34th Street. What do you think? Oh, I think it's... Oh, darling. Huh? Oh, I think it's quite far. Why, Sarah? Why? It seems it's a long time for the product to become known. Why shouldn't we advertise it? That's the way I like to hear my partner talk. Well, I mean it. A banner like this, well, perhaps it isn't quite the way I do it. It doesn't matter. You'd find some other way that's just as good if I went around. The point is, I consider you my partner, and I want your approval. Say the word, Rose. Does the banner go up across Broadway at 34th? It will, Charles. You know it will. Oh, let's see. Now we've had the horse with carriage, the weight horses, the dirages, all with signs advertising noxiality. And they were good advertising scenes through the years, every one of them. I wonder what I should do next. Rose? Any idea? No. You can take a vacation, Charles, now. Oh, that's a good idea, Dad. Let's go up the town and we can go fishing. Well... Please, Dad. Uh, Jimmy, a ghost sits beside your brother now and quiet down. All right, Dad, but... If we men are going away on this fishing trip together, don't you think it would be kind of nice if your mother read to us a little? Rose? All right. And the signs. Know ye that the Lord is God. We are his people. He thanks the love of him for the Lord is good and his truth endures to all generations. To all generations. It may be that the most comforting knowledge a man can have is that there are sons that we can pass on the fruits of his labor. Rose, I am not thinking of the business when I say that. It's something else. Yes. Oh, well, that may be part of it. Because we've been successful. We've worked hard and saved, and it's a good country that gives one this freedom. I can give thanks simply because I'm happy, Rose. I have many, many blessings. You know what I mean. Now, boys, come on, up to bed with your boat. We start after those fish in Canada early in the morning. Oh. Jimmy, dear, I'm awfully glad you three had such a wonderful vacation. I don't understand why your father didn't come back with you. If he was sick, I wouldn't. He wasn't sick, mother. He just wanted to stay in Montreal for a few days and rest. After two weeks of camp, he wouldn't come in a day or two. He said and would. Maybe that's for now. Maybe he took them up strong. I'll go. Oh. Thank you. It's a pleasure. It's a pleasure. Let's see. What is it say, mother? What is it say? It says. Where are you? I'm at eight o'clock to be here. And where are you going? After. You are listening to the Cavalcade of America starring Virginia Bruce as Rose Knox, sponsored by the Duquant Company. It makes us a better thing for better living through chemistry. Our Duquant story continues. With Virginia Bruce as Rose Knox talking with her son James in the library of her home during a birthday party held in her honor. I'm so embarrassed to say that. You remember more and more of those days when you were still so very young, only 13. Maybe you're not old enough even now to enjoy remembering as I do. But I like to think of the way you looked that day when we came together to your father's office at the back door.  They will all discover it soon enough, I suppose. Are you going to be pressing with this Duquant Company from now on? Hmm. Your father was always going to be both president and chairman of the board. Now I want to make sure for him that his boys will have that talk.  You look very becoming to me. I do. Thank you. I don't know if you can talk it over and hear there won't be anyone getting... Well, I did your part, men. I didn't expect to find you here in your husband's office. Well, that's quite all right, Mr. Simmons. Come in. Thank you. All of you. I was just going to send for you, as a matter of fact. I wanted to find out how you men would feel about working for a woman. Working for a... You mean you're going to take Mr. Knox's case? Well, I'm going to be the best I know how to carry on for him. Perhaps it isn't what I would do some choice, but I feel that I'll have no other. Well, Mrs. Knox, if you want to know I've never been bossed by a woman in my life, and I don't intend to start now. Well, Mr. Simmons, I'm sorry. It's too bad we couldn't work together. I suppose that means you want to go. Expand. I am afraid of that. Goodbye, Mrs. Knox. Gentlemen. Well, I hope there's no one else here who says Mr. Simmons sent him. Uh, yes. Oh, I didn't say it, and I'm bugging myself, Joe. Good. Then I can count on you all to carry on in your job as you would have carried on for my husband. And if you have any grievances at any time, please come straight to me with them. Oh, and one more thing. I've ordered the employees' entrance at the rear of the factory closed. We are all, ladies and gentlemen, working here together. We will all use the front door. That's all. You may go now. May I see you for a moment, Mrs. Knox? Your son, Charlie, told me you were going to try to carry on here. I felt I had become right over. Goodbye, Mr. Griswold. I may need a lawyer's advice. Yes. Now, Mr. Knox... Mr. Griswold, for one thing, I think it's going to be necessary to sell the race for you. But, Mrs. Knox... Well, maybe not, Anaconda. Mrs. Knox did love himself. As for the race, they're expensive to keep, and they've served their purpose for advertising, just as the horses carried in their drogable hat. This is not... It's just not possible for a woman to... You're mean by gelatin. Believe me, Mr. Griswold, I'm also mixed in. They want to feed their husbands and children good nutritious food and at a good low cost. I'm a housewife and mother myself. I feel I can give our customers what they want and need. I agree. But a woman running a business like this really... Mr. Griswold, Charles always called me his partner. This work was our life together. I must keep it for him, for our sons. That's what he wanted more than anything else in the world. And Mr. Griswold, I'm sure you'll understand when I... when I tell you I feel it's my obligation. This is Knox with the Monsignor in his church face. Yes, Alice. I assume they're all worthy extremists here. That's right. American Specialty Manufacturers Association. Really do, huh? Sometimes I wonder if there's any point in our belonging. They're having a convention soon. I think it would be a wonderful opportunity to exchange ideas. Yes. But imagine the havoc I'd guard if I went. The only woman there. Well, why couldn't I? Get the President of the Association for me a long distance, Alice. You're not making a joke. Of course I'm not. Now, go ahead and call him. Oh, and send that young architect in here meanwhile. Wait a minute, please? Yes, Mrs. Knox. Yes, see you now, sir. Oh, thanks. Morning, Mrs. Knox. Great, I'm a little late. Good thing I don't have to punch a time clock. You couldn't find one here if you did. Do sit down and stay. Thank you. As I told you on the phone, we seem to have outgrown our original product here. In the past three years since I've been here, the business has almost doubled. Now, here are the plans I've drawn up for a new building. Well, this is interesting. Who did you say drew them up? Excuse me, Mrs. Knox, but the President of the Manufacturers Association's on the phone. You want to take it in here? No, I don't. Pardon me, Mr. Haines. Uh, look over my drawing then. See what you think. Your drawing? Yes, sir. I want windows, lots of them, and a marble kitchen for testing. Excuse me. Hello? This is Mrs. Charles D. Knox of the Knox skeleton company, Johnstown. I called to tell you that I'd like to attend the Association's convention at the Waldorf Astoria this month. Yes, it would be a great deal to me, sir, if I could be there. Well, certainly you have no objection to a woman attending the meetings, have you? Uh, I see. Well, it's kind of you to warn me. And I'll be looking forward to meeting you. Thank you so much. Goodbye. What are you saying, Mrs. Knox? Well, Alice, I feel I didn't completely convince him I belonged, but I will. Now the question is, what on earth am I going to wear? Well, good afternoon, Mrs. Knox. I trust you enjoyed your lunch and that you found the morning session of our convention inspiring. Oh, very much so. Thank you. As much of it as I could hear back there behind those potted palms. Yes. Well, I hope you understand. We placed you there thinking perhaps you might feel more comfortable the only lady present. Yes. Well, Mr. Chairman, may I make a brief announcement to the floor? I think that I beg your pardon. Well, I'd like to say a very few words to the gentlemen present. Would you please allow me the present? Well, I don't know, Mrs. Knox. Please, I won't embarrass the convention. I assure you. Oh, very well. But, ma'am, please limit yourself to ten minutes. Now, stand right here, now, please. Thank you. Gentlemen, one moment, please. The convention will come to order. Our Lady Delegate, Mrs. Charles B. Knox, would like to say a few words. As gentlemen, it's an unceasingly warm day and you all look extremely uncomfortable. For heaven's sake, won't you? Please feel free to remove your coats and snows. Mr. Chairman, I know that Mrs. Knox will be escorted to a seat right down in the front row. I second the wait. I think I know the rest, Mother. The story in itself. How the company was incorporated. How you put your own principles of saving and sharing into all our company's policies and began our medical fellowships and our research projects. Did you know, Jimmy, it was the women of this country who got me started on them? Oh, now, Mother, you're not going to try to give away the credit to someone else. Oh, to the great many someones. The women who wrote to me as if I were a next door neighbor told me in the big time, gelatin for the sick, adding it to their baby's formula. Letters like that, Jimmy. Those letters are what have made me stay on working with the company as president for 40 years. Seeing our company grow great and our products become a household work. 40 years. Don't you think it's time I retired? Seems to me you deserve a little relaxation. You know your father used to gaze in me. He always wanted to be president of the company and chairman of a company. I told you a while ago that I wanted to give you a present in honor of my ninth year. That's right. I said it was a switch. Well, Jimmy, the time comes when I should step out of the picture and let you take my place with Mark's gelatin. Well, Mother, I'll agree to take over as president if you want me to. On one condition, that you stay on as chairman of the board. That would be very nice, dear, to feel I still had a hand in things. I really love this, Jimmy. But it's your turn now to make your contribution to Mark's gelatin. And you will. Just the way your father would have wanted it. Yes. What was that song you used to read as to all generations? No need to condone. He is God. We are his people. He's thankful unto him for the Lord is good and his truth endures to all generations. Thanks to Virginia Bruce and our Cavalcade players for tonight's DuPont story. Next week, the DuPont Cavalcade will present two popular young Hollywood stars, William Holden and Brenda Marshall. Our play tells of a young engineer who defied the unknown and penetrated the mysterious, great dismal swamp of Virginia to win love and fortune. Be sure to listen. Tonight's DuPont Cavalcade was written by Ruth Woodman and Virginia Redcliffe. Original music was composed by Arden Cornwell and conducted by Donald Voorhees. The program was directed by John Zoller. Next week, the retailers of America will sponsor a nationwide campaign to remind us that we produce and distribute more and better goods at better prices than any other country in the world. Now this is due to the American economic system which guarantees us these basic freedoms. Freedom to work wherever we choose. Freedom to own properties to start an enterprise and profit from inventiveness and investment. This holds fast to these economic freedoms that guarantee us our high standard of living. The DuPont Cavalcade of America comes to you from the stage of the Belasco Theater in New York and is sponsored by the DuPont Company of Wilmington, Delaware. Makers of better things for better living in New Tennessee. Next, Daddy tries to sue the jealous Snooks on NBC.