Good morning everybody. Thank you for joining us this morning. Please enjoy the wonderful breakfast. My name is Helge Zitzen. I'm the president of SID. I just wanted to welcome you this fine morning as you get ready for an exciting day. Before we get going though a bit of the excitement I would like to thank Corning who is sponsoring all the food here and you should you know give a moment of thanks to the glass people otherwise you wouldn't be eating. So thank you and hopefully that food puts you in a good mood because you have one hell of a day ahead of you. You know those of you from the press and from other parts of the the media we have a record breaking this play week. Look forward to record breaking really at every single dimension really in SID history. So not just better than last year or better than the year before but better than anything that this 54 year old society has ever done. So already last night we surpassed 7,000 registrations just to give you a sense of context. Last year final registration at closing end of the week was 5,300 so we're a 1,700 up and the show hasn't even started yet. So I have reasonable hope that we'll get you know 7,500 possibly even 8,000 by the end of the week. Every other metric is up as well. The exhibit space is the largest ever in SID's history by a significant margin depending how you count meeting rooms where somewhere between high 50,000 square foot to low 60,000 square foot compared to 47 I believe last year and that sort of was the stable line. So tons of exhibitors here and tons of beeping. We have you know you can go all the metrics down. There's a record number of papers being submitted over 700, 722 when our historical averages were sort of 5,600, 650 or so. So across the board I won't belabor all this. There's sessions where we literally yesterday at the poll extra tables and chairs in because they're overcrowded. It's exciting time. It's good to be back and say that's obviously a major contributing factor but it's also good to be in a vibrant industry and maybe from your perspective I'm sure you don't writing articles about you know just numbers but there's some exciting stuff happening. After you know after a few years of kind of you know somewhat incremental process and progress in the display industry we now have some really cool stuff. You know we have foldable displays in production. We have advanced OLED configurations. We have a whole bunch of cool things that are happening on the show floor in the convention in the paper sessions. For some of you might have attended yesterday. This yesterday's award dinner apart from obviously giving deserved awards to all sorts of wonderful people that you can read in the documentation. You could see the sort of palatable excitement in the room in part also because the record numbers have also attracted some really high profile people so I encourage you you know those of you who are more snoopy or press people to seek them out. For example yesterday we gave the David Sonoff award a new award we created for industrial achievement to the founder and chairman of BOE. This is the largest display panel company on the planet by by every measure and every market category and so you know multi billionaires like this don't normally walk the show floor so I'll give a price to you whoever hunts them down for an interview. Similarly we have you know CEO CTOs of Samsung LG some of the largest companies on the planet here all walk in the show floor for the first time really in a long time because you know this sort of level of senior level attention is a novelty so good hunting to all of you. It's a great show not to be here I'm glad to have all of you here enjoy breakfast I'll hand it over to Sri for the logistics of the day but I just wanted to encourage you to write wonderful stories of what everything we're doing because we want to have 8,000 attendees next year and you're a key part of that strategy. That's really what we're feeding you. Thank you all. Bye bye. Okay I know we started a little bit later than we like but this is I think a slightly better time than 7 a.m. so as usual my style is I know in breakfast it's a little bit harder but we're still going to try this what I'd like to do is see if we can get everybody to stretch a little bit and I will get started so I can finish well in time so we can all go to our next meeting on time. With your permission for those who are willing and able if you would kindly stand up and step away just a little bit from your table. Thank you very much. Steve Atwood says I hate this thing but I'm gonna do it anyway because I've known Sri for so many years. Jennifer and I actually did something like this in Brazil a few years ago I didn't feel Jennifer. So here's what we're gonna do I'm gonna put some oxygen in your blood okay so hopefully this is very good for you the rest of the day. Go put your hands up in the air and we're gonna go up and down I'm only going to do 20 usually I do 30 or 40 we're just going to 20 okay let's do this 1 2 3 come on guys you can do it 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 thank you please sit down trust me this this is better for you it's good for your heart. So this is our usual press and analysts breakfast meeting I'm gonna go through this very quickly so you get a glimpse of what's happening for those of you that are new to SID and display week here's a little glimpse on who we are we are headquartered here in this area we are volunteer led you just heard from Helga he's our president he like me and many others are volunteers there are probably about 400 of us that do various things for SID and we are probably the only dedicated society for displays at our size and we believe we provide a tremendous value to the industry by doing this conference and a whole host of other things we have in this slide we put together the slide a while ago we have way over 5,000 I'm hoping this year we might even cross 6,000 members that are members of SID 28 chapters worldwide the Japan Beijing and the Silicon Valley chapter are our biggest and all three this year will exceed 1,000 members which has not happened ever in the history of SID this chapter five years ago the local chapter was maybe about 500 or so we've literally doubled even though there's no display company per se in the local area but end users and so on and we have 12 student branches around the world this is our 57th year started at UCLA in 1962 so tomorrow we will distribute these awards Samsung won the award for the wall their LED wall Apple watch Sony crystal LED and then the display applications of the year were JDI for the displays they put in the dashboard and automobile and then Lenovo for the dual display LCD and e-paper display components would be dexerials for the AR film and then shot for their real view product so those are those will be distributed tomorrow we put out a press release there's details there and if you need any additional information Anna in the back will be able to help you get that so this is a part that I usually forget every year so now I remembered let's do this so my marketing team where's my marketing team if you would kindly stand up Neil Lisa Anna put your hands up because there are other people standing so we know who you are and then where's Lucy Lucy disappeared okay okay very nice very nice so we are volunteers thank you very much for everything that you guys do okay today you know we have an announcement coming up at the end of this presentation from Corning and then they will also invite you to their booth I won't go any more details because we're going to cover that in quite a bit the end of this presentation keynotes are from BOE Google and Samsung that starts around 8 20 in the morning ribbon cutting at 10 30 after which people get to go into the exhibit floor to see the different exhibits floor opens at 10 30 and goes until 6 30 today we have a networking event which is the first time that we are doing this which is at 5 30 in the evening I believe they are going to serve beer for the first time at SID I'm sure that was a challenge getting it approved at SID the investors conference starts at 9 o'clock and this is produced by DSCC that will also be very exciting they are expecting a whole host of both venture capitalists as well as companies presenting that are looking for funding there is a press luncheon right here in this room then there'll be an announcement I won't go into details about that now technical symposium obviously runs through Friday and this year the emphasis is on these foldable bendable displays and then AR VR I zone we've you know we started this I zone as a way to get young companies to participate where they couldn't afford to have a booth to give them a free booth and we'll have a sponsor pay for that whole area I remember I was working for E Inc at that time and we were the first sponsor this is probably six seven years ago something like that and we barely we had like 20 tables and we would get like 24 companies apply right this year I can tell you we probably stopped we've got like 75 applications and and I believe about 45 companies were chosen and so these you know will be very good opportunity for you to take a look at some interesting technologies and the few companies that were in the eyes on last year graduating they have boots on the show floor and then there's a exhibitor forum which I was told by our convention chair eras that it's getting much better every year and he would really encourage people to go and join the forum as well on Wednesday we have a press breakfast here about the same time maybe a little bit earlier 715 from arm and then we have a market conference on foldable displays by DSCC and DSCC founder Ross Young told me yesterday that they've got record number of registrations for this conference so that's going to be very interesting hot topic there's an automotive market conference that is personally led by Rashmi Rao who is our general chair this year and that's also going to be very exciting we did a job fair last year and it was only for students this year we opened up for other industry people and that we've already got 15 or 16 companies that have officially signed up there may be more and then probably about a hundred students have also signed up to attend that's going to be very exciting the eyes on winner will be announced later on that morning and then we'll have the award ceremony at lunchtime the companies that I just mentioned will formally receive the awards I will be moderating the CEO forum this will be the second year in a row we are doing this and women in technology follows the CEO forum for me this is a very big deal you know when I agreed to volunteer for SID and serve on the board and be the chair for marketing for me the big criteria was find a way to have more women in every aspect of SID particularly leadership bring more young people into the organization and we're making progress and this is one of the ways by which we do this I really really really appreciate particularly those of you in the media if you could come to both the CEO forum and the women in tech and write about this we really want to make this a mainstay because the rest of our programs are much more aligned towards you know people with technical background where this one offers something for probably everybody including technical people networking event again at 5 30 on Wednesday and then exhibit floors 9 a.m. to 5 p.m. and then on Thursday it's obviously much shorter it go the exhibit floors are up to 3 p.m. and then we'll have poster sessions from 5 p.m. to 8 p.m. which you know in past years they have been really wonderful a lot of excellent posters that will give you more idea into what's happening in the industry okay here's here are the three women leaders that will be part of the panel Lee Epting Samantha Phoenix that some of you would know she's from our industry she works at planar as a VP of technology and Consuelo Valverde she both Consuelo and Lee are new to our industry and they will bring a new perspective and Jenny Donnell and that many of you know will be moderating that session and the CEO forum we love Dave Dutton from Silvaco Rob McIntyre from LG and then Andrew Scully CEO of Imagine will be the three CEOs these are all the different sponsors and you can find their logos also on the different posters that we have all on the show hot topics for this week or automotive AR VR TV market flexible OLEDs reflective displays digital signage and the eyes on obviously the reason we bring up eyes on in this category is because there's so many different technologies not even easy to categorize some of them here are some highlights and obviously this is you know of the 250 exhibitors plus probably 40 50 companies in the eyes on we are not going to cover all 300 here these are only companies that did submit something to us that want to highlight what they're doing areas materials for a micro fabrication film they are in booth 319 I'm not going to go through all of this but clearing I will be showing a e-paper technology there are two companies C3 Nano and Cambrios that will show a silver nanowire based products Jennifer here is a subject expert on that on this area Corning we're going to talk much more about Corning they're going to be showing the astra glass in their booth ink will show a whole bunch of e-paper applications including their color displays Fujitsu will show resistive touch panels arm will show some processor obviously I'm sure process iris tech interesting company out of out of Montreal will be showing their technology that adapts to the view adapts a display to the viewer under different circumstances and then interest spec technology will be showing a analyzer product conica Minolta spectral radiometer analysis obviously next-generation quantum dots that is their expertise and nano comp I'm presuming they're from Finland and they'll be showing a light guide for reflective LCD and radiant would be the longtime support will be showing a near infrared lens for facial recognition measurements SAP blocks will be showing a quantum dot color convention technology for micro LED and micro LED as you know is also another very hot topic this year multiple companies talking about next a bit again Shenzhen China star will show also a micro LED product a lot of these products these slides will not do justice you really have to go and see these products play with it and even threaten to break it so that will get a little bit excited TNMAS got its SLT technology and you can see their comparison of the images very obvious what their technology does vision ox once again we actually give an award to vision ox last year for some of their products this year they'll be showing a bi-directional foldable AMOLED display synaptics will show the next generation VR displays via uptronics a disc interactive display system and those are some of the highlights of what you can see and here are some other logistics particularly from a press room perspective we open 7 a.m. to 6 p.m. today and tomorrow and then 9 a.m. to 3 p.m. on Thursday we are going to be bringing lunch breakfast lunch and snacks into this room for the media and we really encourage you to use this rather than the ones in the other conference rooms or session halls we have tried very hard this year we actually tried to do this last year as well to see if we can bring more healthy food right and we would love to get your feedback to see if we have met that goal wireless access available there a display week 2019 is the network name and then there's a virtual press office and inquiries go to press at SID org or you can contact Lisa and our Neil or somebody on my team I believe okay the on social media we are focusing on display week rather than on SID those are some ways by which we can connect I really appreciate I noticed yesterday there were a whole bunch of posts on LinkedIn where people are saying display very very happy to see that happening and then next year it will be June 7th through 12th in San Francisco as Helga mentioned we tend to get a lot more people when we are here in the Bay Area in spite of the fact that Bay Area is a little bit more expensive and particularly for Asia visitors hotel rooms are also quite pricey and some people had a taste of our traffic as well recently okay with that I'm gonna introduce Corning to me you know I'm gonna go off script with Corning and I actually threatened the Corning team that I will actually do this first let me introduce the Corning speaker and then I will tell you something that I learned about Corning recently which was very fascinating to me and I'll share that Hanim from Corning is here and he's the business director for high-performance displays at Corning and he will further talk about Corning and what they are showing in their booth as well as what their company is all about but here's something that I learned from a friend of mine and she has a CEO club here locally and she sends these weekly updates and as a coincidence she said check out Corning and they're doing something really great and this resonates with many of the things that are my personal reasons for why I'm associated with SID and giving my time to SID 40% of their employees are women I don't think a whole lot of companies in the space can say that being in marketing I notice a lot of marketing agencies majority are women right but that's rare but in our industry if you go to almost any LCD maker or a OLED maker or any you know so-called highest technology within our industry you don't see this they've achieved something really magnificent to me that's a very big deal 42% diversity in their management team that's pretty amazing you know for those of you that are followed in Silicon Valley as much as we tout as we are Mecca for technology innovation and so on we're not there 100% pay equity for men and women as well as minorities and they achieved this in 2017 to me these three statistics are the reason why young people should go work for that company with that hand welcome and thank you can you hear me okay all right thanks Siri for the introduction and good morning everybody for those who are not familiar with Corning I'd like to spend a couple of minutes introducing the company so our company is one of the world's leading high-tech material science company we have a world-class expertise in glass science ceramic and optical physics and with that we introduce many innovative products that transfer the industry and change people's life our headquarters is located in upstate New York a small city called Corning but however our footprint is very global our RD center our lab our sales office and our manufacturing starts are truly scattered across across the globe our last revenue is a little bit over 11 billion dollar and we were ranked at 293 of Fortune 500 so one of our earliest innovation and I believe was 1879 is the glass envelope for Edison's light bulb right and that kind of transform evolve into CRT2 right and then that also later transform into the first class substrate for the LCD industry and along this path we had been in the cutting edge of the industry evolution for more than 80 years and speaking of the glass substrate actually 12 years ago or 13 years ago to be exact at SID we introduced the ego XG brand this glass since introduction has been the industry staple enabling a lot of transformation in the display industry for example from at that time a small laptop size a panel all the way up to a TV size and also for TV specifically from standard resolution to high resolution 4k and beyond now as you know that consumers demand for more lifelike viewing experience continue to increase right and this also always creates a challenge to our customer panel makers they need to figure out how to serve and capture this opportunity but at the same time in a cost-effective way and then one of the solutions a lot of our customers are adapting is called a new back playing technology called IZZO or Oxide and as our customers adopt new technology that naturally creates new challenges and requirement for the upstream players like us and us just like any other high-tech companies we love technical challenge we love to tackle tough questions and as part of that as a part of that we are looking in we actually spend a lot of time looking into what opportunity we can get out of this and that lead to a development of the new glass and that is right reason why really here today we'd like to introduce you to our new glass product Corning Astraglass. Corning Astraglass is optimized for various high-performance application specifically using Oxide TFT back playing technologies. The development of this glass actually required a lot of deep understanding of our customers technology processes and challenges and based on their challenges and based on their understanding we were able to identify four key attributes that customer really value one is a low total pitch variation another one is a low total thickness variation lower sag and specifically for mobile devices optimized and balanced the action performance and what is really special about this glass is and for those who work in the analog kind of world you know we try to move something here then definitely compromise the others other area and what really try to do is create an optimal balance of these four attributes to maximize the value to our customers and that's what's really special about this astraglass so we truly have a high confidence that the astraglass will be a very key component of the current and coming high performance applications going forward so with the launch of astraglass today astraglass will join our glass portfolio along with our industry favorite EXG Slim and truly premium high-performance Lotus NXT glass we ask you to join as we join us as we work with our customers to define the new chapter of the display industry together and again I'm very excited to share this news with you today so immediately after the breakfast session and throughout the duration of our show in our booth we have an astraglass team ready to help you answer any questions you might have and also share the story around the development of the glass and the science beyond the glass again I think that's three kind of introduce our booth number is 1119 and especially especially for interested in one-on-one interviews please contact Brittany here right I'm sure help us range of time for that thank you very much


While 99% of breast cancer is diagnosed in women, one person can also occur in men and being a woman and getting older is the most important unmodifiable risk factor for breast cancer and that's going to happen to all of us, whatever we may do so. So the incidence of breast cancer will also increase as the population increases. Now as I said, potentially every lady is at risk of development of breast cancer but then there are some modifiable risk factors and some unmodifiable risk factors. The unmodifiable risk factors are gender, age, family history, age of menstruation, age of menopause which we can't do anything about and there are some modifiable risk factors. These modifiable risk factors are obesity, diet, lack of physical activity, tobacco and alcohol consumption and usage of some types of hormones. The most common symptom of breast cancer is a painless lump in the breast or underarm region. This may be or may not be associated with changes in the skin of the breast, there may be associated retraction of the nipple, there may be dimpling of the skin, there may be a blood stain spontaneous discharge from the nipple, sometimes there's a rash-like appearance of the skin of the breast. Any of these changes if you see please visit your doctor. Once a diagnosis of a breast cancer is made we have to know as to what stage the disease is so for that to happen we do something called as initially we do a mammogram to make sure we don't miss out on any other lumps in the same breast or on the opposite breast and for doing a proper staging we do something called as a pet CT to look for disease elsewhere in the body and once this is done based on the size of the tumor the location and the patient preference we give the patient options of surgery like a lumpectomy where in a breast is conserved the entire breast is not removed this is also called as a breast conserving surgery versus total mastectomy. So these are the precautions and once the surgery is done then we tell what next to be done. What do we mean by reconstruction? We take out one part of the breast either it is a lumpectomy where in a specific part of the breast that is lump along with margins is taken out so we need to rearrange the breast to get the best possible functional and cosmetic outcomes. This is called as oncoplasty if it is done it can be done by two methods one is called as local oncoplasty where we use the native breast tissue and rearrange it in such a way that the breast contour is reached again the second method is called as a volume replacement surgery wherein we use tissues from other parts of the body which can be from the surrounding areas like the back or from the abdominal wall that is specifically tram flap and df flap or implants also can be used yeah it depends on the patient's preference if the patient wants it to be done at the same setting we can do it then and there which is preferred if the patient decides to get it done later we can you know schedule it later at the end of the complete treatment. Well breast cancer is the commonest cancer in India both males and females combined as per the globe book and 2020 data so around one in eight women have a lifetime risk of developing breast cancer so that is an appalling figure the incidence of cancer in India overall is 100 for one lakh population and breast cancer it is 30 to 35 per one lakh population and most of it is in sixth or seventh decade post-menopausal women however younger women can also get breast cancer and in men also out of for every hundred females one male can get breast cancer. Around five to ten percent of breast cancers are hereditary and some features indicating hereditary breast cancer are aged less than 45 years multiple cancers on the same side of the pedigree in the family multiple cancer is in the same individual like breast and ovulation cancer in the same individual certain ethnicity like Ashkenazi Jewish population they have a higher incidence of mutations some specific types of breast cancer like triple negative breast cancer an unusual presentation of breast cancer like breast cancer in a male or bilateral breast cancer in a female these indicate hereditary breast cancer and there are very simple blood tests available nowadays which cost only a few thousand rupees which can determine whether it is a hereditary breast cancer and gene targeted therapy is also available nowadays well yes definitely the survival the quantity and quality of life both can be significantly increased even in stage for even though cure is not possible with newer treatment options such as targeted therapy hormonal therapy immunotherapy biological therapy so every patient deserves treatment not every patient require radiation after breast cancer surgery however all those patients who undergo breast conservative surgery would require radiation those patients who undergo mastectomy either as a choice or because of their disease pattern some of these patients may not require radiation those patients who have spread to the lymph nodes after mastectomy or those who have risk factors those would require radiation treatment even after mastectomy usually radiation does not cause much of side effects when we treat the chest wall or the breast region generally they have either heaviness of that breast or the tenderness in that region and they would be some skin darkening and pigmentation and patients typically they take radiation for 15 minutes and then they go back to work after completion of radiation even if they have some pigmentation of the skin it takes around a month for the side effects to subside by itself generally breast cancer treatment is a multi-modality treatment involving surgery radiation and chemotherapy so we generally advise these patients to wait at least for two years before they consider having a family the mastectomy is removal of the entire breast tissue so there are specific indications in breast cancer when the entire breast has to be removed for example when the breast cancer involves the entire skin or which we call as beauty orange or an ulcer is formed because of the tumor on the skin another indication would be if there are multiple sites of breast cancer in the same breast multiple cent multifocal disease as we call it breast has to be entire breast has to be removed another specific indication is known as inflammatory breast cancer where breast entire breast has to be removed after chemotherapy so these are the few situations where mastectomy is definitely indicated in breast cancer so recurrence rate means what are the chances of breast cancer coming back in spite of being treated in spite of undergoing complete treatment so the recurrence rate depends on the stage at which breast cancer is diagnosed so for stage one the cure rates is almost about 95 percent which means the recurrence rates are only about three to four percent so stage two in which the breast cancer could have spread to the glands lymph glands in the armpit or in the axilla as we call it the cure rates are almost about 85 80 to 85 percent which means the chance of it coming back is about 15 10 to 15 percent stage three in which the size of the tumor in the breast is more or it has already spread to the lymph glands so this the cure rates would come down to about 50 to 60 percent which means the chances of it coming back is about 40 to 50 percent the answer is a big yes we have a lot of success stories of women in their 30s and early 40s which is seems to be the age at which breast cancer is diagnosed nowadays who have completed successfully completed treatment and conceived so when they express their desire at the start of treatment to conceive in spite of having breast cancer they undergo a procedure known as ovum banking or embryo banking which will be used following the treatment the same ovum or embryo is used for them to conceive and generally the offsprings will not have any you know complications because the treatment which the mother has undergone due to breast cancer in the past the most common surgery for breast cancer used to be a mastectomy nowadays more and more women with breast cancer are being diagnosed at an early stage and the majority of them are able to undergo a lumpectomy a lumpectomy is also called breast conserving surgery or organ conserving surgery this is because the cure rates in early breast cancer are the same irrespective of whether a woman chooses to undergo a lumpectomy or a mastectomy a lumpectomy is the surgical removal of the cancerous lump in the breast along with a small margin of prestige it was also called breast conserving surgery or organ conserving surgery in mastectomy the entire breast along with the cancer is removed apart from a few exceptions most women with early breast cancer can undergo a lumpectomy rather than a mastectomy you know in addition to the obvious advantage of preserving the breast and therefore having a superior cosmetic and psychological outcome a lumpectomy or breast conserving surgery is also a smaller operation with a quicker recovery does recovery take after a breast cancer surgery the breast is a subcutaneous organ that means it lies just under the skin therefore surgical access is technically easy it does not require any painful or difficult incisions so recovery after breast cancer surgery is quite quick in fact most patients are admitted on the morning of the operation undergo the operation and a discharge on the next day some even are discharged on the same day as the day of surgery after surgery there is no restriction on diet or any kind of physical activity in fact some of our women have gone back to work the day following discharge normally we advise a few shoulder and arm exercises following surgery especially if we have done a reception of the lymph nodes in the abdomen radiation after breast cancer surgery is usually started within four to six weeks time this time period is given for to allow wound to heal and for the normal tissues to recover from the effects of surgery. Radiation treatment can vary according to the stage of disease while the total dose delivered remains more or less the same the area which we cover can undergo a change during early stage disease only the breast is covered for radiation whereas in advanced stages in addition to the breast the lymph node area also undergo radiation radiation therapy differentiates between cancer cells and normal cells by using what is called as fractionation fractionation means total dose is divided into few equal number of sessions delivered over few weeks and every five treatments are followed by a two-days gap during this gap the normal cells recover from the effects of radiation whereas cancer cells are unable to recover that creates a difference between the effect of radiation on normal tissues versus cancer cells the cause of breast cancer is due to an interplay of multiple factors which could be lifestyle factors dietary factors environmental factors acting on the background of genetic factors the common lifestyle factors we talk about others role of urbanization where we are having late pregnancies lesser children less breastfeeding and all these can lead to increased risk of breast cancer dietary factors using fatty diets especially with increased red meat increased use of alcohol also has an increased risk of breast cancer having less exercise not being very active a sedentary lifestyle also increases the risk of breast cancer and then there's always the genetic risk of breast cancer where 5 to 10 percent of patients carry genes mutations of BRCA one and two mutations which can increase their risk of lifetime risk of developing breast cancer and also cancers like ovarian cancer preventing breast cancer involves talking to women encouraging them to have a very healthy lifestyle we encourage them to exercise regularly having a diet which is less in red meat having a preventing obesity which can happen and preventing a lot of weight gain this kind of a lifestyle is protective for breast cancer also regular follow-ups and checkups for breast lumps is important if a woman carries a hereditary BRCA one or two gene mutation then there are a ways by which they can prevent breast cancer which may involve surgery called prophylactic mastectomy and also sometimes we use hormonal tablets to try and prevent breast cancer in this high-risk population


Hi guys, welcome to the ultimate diabetes channel sugar MD today. We are talking about Exercise, but this is a different type of exercise. This is a Exercise that you can do while sitting without even moving from with your legs. So here's the deal I'm an endocrinologist like most of you know, and I see a lot of patients with diabetes. I Asked me the exercise. They say no, I'm like, why not? They'll be like Don't you know my hip hurts? I'm like, how about knees? Oh I have a knee replacement. Okay. Well, how about your ankles? Oh They're like really very stiff. I'm like, okay. So your legs are out. Yeah. I'm like, do you have arms? Yeah, but do they work? Look, yeah, do you use them? Yeah to eat That's not the only reason they have arms so you can actually use your arms to exercise That's what we're gonna do today guys. We are gonna do some cardio while you are sitting using your upper body and arms Let's get started. Hi guys. Thank you for watching Quickly, I have a quiz for you in the description below So after you watch this video take the quiz Answer the questions the more questions you answer correctly the higher the chance and one in three Will win a chapter from my book It's gonna be delivered electronically to you a real chapter from my the ultimate diabetes book So go ahead finish the video take the quiz and win So guys, there's a lot of ways to do cardio and really to be honest with you to be able to do cardio You need some music just like that All right, so guys you gotta have some music some tempo going, you know, like I cannot do cardio in silence I cannot do cardio. Some people do cardio while watching TV and stuff, but Come on, you know, it's if you're walking maybe but did a real cardio to get your heart rate up is Not gonna happen for a long time unless you kind of have a beat going now So there's no, you know, just choose some music that you will like now Let's get started so in terms of like doing something even if you're wheelchair bound Even if you cannot even get up from your seat You can do things to get your heart rate up and this is the key some people say I walk my dogs I'm like that doesn't count because your height doesn't your heart rate does not go up when you walk your dogs Your dog probably stops like every 10 feet You're stopping with the dog. That's not gonna work out You have to get your heart rate up and keep that heart rate up at least, you know I don't know you can if you can do, you know, 10 minutes at a time great if you can do an hour at a time great It's really not necessarily different if you do like 10 minutes in three times a day versus 30 minutes at a time Doesn't make a whole lot of difference. So since upper body and arms, you know May not be as fun as the legs. I would say, you know, you can still stick with 10 minutes But you know what 10 minutes is 10 minutes better than nothing if you can get your heart rate up So let's look at my heart rate right now. My heart rate right now measuring My heart rate is actually is high. It's like at 75. Normally my resting heart rate is at 54 Like when you're in the bed or stressing etc So we're gonna get this heart rate up, okay? So what I'm gonna do is depending on your health and fitness level, of course You should be able to get your heart rate up comfortably at least around 110 120 without really putting a lot of strain to your heart I don't recommend going up to 140 160 kind of heart rate if you're not fit But right now that's what we're gonna do We're gonna watch on the Apple watch see how these exercises can help you now. I have some stretch bands here You know, these stretch bands actually come in different resistance, right? So as you can remember we talked about this before so you can do resistance training And if your resistance is high, of course that that's a good thing, you know, you're building muscle But if the resistance is low and with the high repetition, you can turn that resistance into cardio Because if you're not taking breaks, you know, that muscle movement will give you the heart rate And then there are different resistance levels with these as well.  So let's get started with, you know, I'm gonna get into this in a second But let's get started without this and I'll show you how to do how to use these as well So simple, right? Even if you don't have a stretch bands, you have your arms you can move So you can actually do march as well.  You're stopping people. Hey, stop Stop, stop, right?  How difficult is that, right? Everybody can do this So you can do that, right? You can move your arms just like that And your heart rate is gonna go up if you don't believe me I'm gonna actually start checking my heart rate Right now, let's get this going here I'm gonna be measuring my heart rate while I'm doing this, okay And all right, so you you can keep doing that now. You're tired of this My heart rate is still going there. Oh, it's already like up to 90 So see it's kind of going up and You know, of course, you can you can you can do this type of movement You know, that's gonna open up your chest And uh, you can you can do that or you can do this Right, so Get some music going on and get this arms moving man. Move it move it move it. All right Now resistance bands these are very nice because that kind of makes it a little bit more fun And also gives you a little bit of a tone on your arms, right? So what you can do is this so you hold it like that, right the simplest way Just stretch it Stretch it you don't you don't have to do like this because that's really You know the piece the purpose purpose so you can stretch it bring it back stretch it bring it back See what I'm talking my I'm not able to almost make complete sentences that tells you that You're actually getting getting to moderate intensity exercise If you can still talk to someone while you're doing all this That means that you're not doing anything so you should be able to Have your breathing cut off while you're exercising. So this is what you're doing right now So another thing you can do if you're not put your arm like this all you have to do Use one hand as the fixing point and the the other hand can do all sorts of movements, right? So this is going up and down you can do this Right and uh same thing with the other arm Again, so if you change the range of motion if you change the position the muscles that you're working also will change So instead of doing this for example, if you do that, right?  You will feel it It's gonna start brooding. So you're gonna know exactly what muscles are working. So You can do that. So what else?  Another alternative to that you can put it right here Like this one one again hand is fixing that and you can lift it up like this. So Again, this is going to give you different type of muscles, especially On your shoulders not a lot of people as we get older and not getting rotator cuff injury either because you're lifting something or Or you're hitting your shoulder somewhere and then you have a permanent damage But if you do this kind of movements and keep your shoulders strong and scapula strong You're going to have much less likely to be injured All right. So what else? So you can actually use your triceps and biceps with these Stretch the band these stretch bands. So how do you do biceps? Very easy, right? So think about like the gym. You're not at the gym But what do you at the gym really you're just doing curls, right? So if you're doing curls what you have to do put that band under your under your foot And then here you go Now you got a curl see that? So if you can increase these Resistance on that, which this is too light for me. Let's just go for something a little heavier with the resistance So you'll be able to do see That gives you more Resistance now. Let's do some triceps. This is biceps and you can do that on both feet Now, how do you do triceps again? You are going to fix one end with one hand And all you have to do is this movement watch So you're gonna hold it like this and then Push it back, right? This is what you're doing When you are at the gym, right? so What else you can do you can actually hold Your hand again like this And then you can bring it down that again works your triceps So you can do the same thing with the other hand So if you do not take breaks like normally people who are lifting heavy They take breaks because they have to because the heart rate goes crazy otherwise But if you are getting your heart rate up to a level and you are keeping at that level Without lifting excessively or putting excessive resistance in the stretch bands I think you will be able to burn a lot of calories.  God has given you Stop blaming the apple. Stop blaming the pear. These are good food You just need to learn how to process those foods that bring you a bunch of antioxidants vitamins and minerals that your body needs So guys, I hope that was helpful and if you like this, please give a like share and we'll see you in the next video Hey guys, I hope you're enjoying this channel so far and I hope you subscribed already If you didn't do it and if you did watch this video right there, I think that will help you too


So you have no idea how to put ads in your game. Not a problem. First go to the description and download these three scripts. Now if you want you can copy the originals from here, but I've made a few adjustments to make your life easier. Inside you will find a folder called ads. Just drag that into your project and drag all three into your canvas. Now go to windows, general, services, ads, and if you see this message click on new link. Select your organization, it should have the same name as your Unity ID, then create a project ID and it'll ask if the game is for kids. You say no because you never want to make anything for kids.  Anyway, then you turn on the add button and set it to test mode. And if it says there's a new ad package just go ahead and upgrade to it. Congratulations. You're done. All you got to do now is copy and paste your game ID. If you're working on Android get this one, otherwise if you're working on Apple get that one. Go over to your canvas and paste it in where it says game ID. Then you got to make sure you switch to the right platform. So if you want to upload to an Android, go to file, build settings, pick Android and switch. If you're making it for the Apple store, pick iOS instead. Awesome. So how do you activate them? Well, let's just say you wanted this button to trigger skippable ads. To do that click on the button and under triggers, drag in your canvas and select show interstitial ads. And while we're at it, let's make this button trigger the reward ad. You can do that by going down here, dragging your canvas and pick show reward video. And if you run the game now you will see your banner down below. If you click the skippable ads button, it triggers the ad and the user will be able to skip it if they want. And if you click the reward button, it will trigger an unskippable reward ad, which will normally close itself after it's over. Cool. So how do you control the details? Well, it's easy. Let's start with the banner. There's really only one thing you ever want to control and that's its position. And you can change that right here. At the moment it's set to bottom center. You can easily change it to bottom left, bottom right, top left, right or center. So if we set it to top center, then save and run the game. You will see the banner now appears exactly where we told it to. Next is skippable ads. We triggered it with our button, but any time you want to manually activate it, the command is just show interstitial ad. If there is an ad available, it will show. If not, you can tell it to let you know. Finally, let's talk about rewards. Any time you want to manually trigger a reward ad, the command for that is show rewarded video. That will initiate the ad if it's ready. Now if the ad finished, you can reward the player with whatever you want in here. If they skipped it, you can scold the player and be like, what the f*** bro here? And if there was an error, you can let yourself know here. Lastly, if for some reason there's an error and you didn't see your ad show up, go to your dashboard, accept the terms and you'll end up right here. Under monetize, click explore, find the name of your game file, go to add units and complete activation and tell them that you just used an unity. Then you will see this. Now what you want to do is make sure that the surfacing variable IDs have the same names as their IDs on the site. So the banner ad ID for android is banner android. The reward ad ID for android is rewarded android. And the skippable ad ID for android is antistitial android. I've done my best to make sure they're the same, but they might update or change the IDs in the future, so now you know where to find them. Alright, well, that's how you do it. Just make sure that before you upload your game to the store, you turn test mode off and change all these booleans to false. Hope that helps and as always hope you have a fantastic day and I'll see you in the next video.


Okay, well as Elise just said, we are not a modern code lab and I'm going to be telling you about our research in a general sense and then getting a little bit into the modern code work. So the question that is of interest to us in a broad sense is how to form organs and how naive populations of cells come together to make a particular structure with defined cell types and very specific kinds of architecture. And the question that I want to talk about today is illustrated here and that is from this classic picture by Waddington to illustrate the kinds of choices that a cell has over developmental time. And so he drew it here where you have a cell that starts its life with many potential outcomes and then through a series of decisions which he suggested would be debinary decisions but just to get the general point that cells ultimately commit to a particular cell fate. And so it's this early, what I want to discuss today is this very early stage where cells have pluripotency or a kind of developmental plasticity and they have multiple choices on what they can become and then that loss of plasticity over developmental time. Now we study this question in C. elegans shown here. We're particularly focused on how the gut is made and I have to say that when I started talking about plasticity in C. elegans people thought I was crazy I think and in part because most people were seeing C. elegans more like this where a cell might have one particular outcome it might not like that outcome but that's what it was stuck with. And of course this perspective derives from the lineage that we just heard about from Bob Waterston and that is this stereotyped cell division pattern that worms have. What we know now is that although C. elegans undergoes this stereotype kind of division in fact that is not reflective of the plasticity that embryos and cells have underneath. And we know that from a number of experiments and I'm going to show you this classic experiment by Jim Priest that I really like and this was what Jim did was he was noticing that these two lineages look very different. They give rise to very different patterns of cells and you can tell this just from the cell division pattern and yet these two cells are sister cells at the four cell stage. So that's ABA and ABP. So what Jim did was the following experiment. He was watching an embryo divide going from the two cell stage into the four cell stage and what he did was to use a blunt needle to rearrange the positions of ABA and ABP. So as the mother cell divides into the two he's pushing ABA back and so now you have ABP in the front. And what this showed is that you could get a completely normal worm out and what this tells us is though the lineages so reproducible that in fact you can get very different kinds of fates out from different cells so they have a lot of plasticity in them we just don't normally see it. So this kind of analysis and other studies that I'm not showing you has told us that the C. elegans embryo and the initial divisions up to about the 28 cell stage or little past have a lot of plasticity and that these cells are capable of adopting very different fates and then what happens over time is that that plasticity is lost and this happens with the onset of gastrulation which is actually very similar to what's seen in vertebrates where it's these early blastomeres that are pluripotent and then with gastrulation cells begin to lose that kind of flexibility. Okay now that's the situation in a worm and of course often when we think about plasticity we think about it in this configuration which is an embryonic stem cell so I just thought it would be good to point out a few differences and similarities. Both have a lot of plasticity the stem cell is sitting in a tissue culture dish of course stem cell ES cells don't exist in the embryo and they can undergo cell renewal and then differentiation of course is controlled by the investigator and that's very different when you're looking at a real embryo where on the one hand we're getting these very rapid changes in cell expression and in fates so there is no sort of stable ES identity in the embryo and then the plasticity that we see is happening despite these changes is happening as I mentioned at this very defined time at the onset of gastrulation. There are differences between the two certainly and for example in ES cells we have these factors that are so critical for establishing pluripotency there's nothing to suggest that worms have anything like this gang of four that have been identified but they also do have similarities for example the repressive transcription complex polycomb. So one aspect that really intrigued us about these early cells in C. elegans has to do with their nuclear organization so these top two panels are C. elegans embryos at different stages of development and so I've ringed and read the nuclei so this is a very early embryo this is kind of a mid-stage embryo and you can see that at the EM level they have they look really very different and in particular the early embryo has very little electron-dense material it looks like it doesn't probably have much heterochromatin and then if you look later there's this clear change in how the nucleus is organized. Now this is not just a feature of worms and so here's some other examples down below this is an ES cell that's the nucleus there but you can see again that the nucleus has this big open look to it and that with differentiation is when you start to pick up this electron dense material and you get a lot more heterogeneity in general and how the nucleus looks and then this is a planarian stem cell an adult stem cell and again you have this big blast cell and it lacks anything that really looks like heterochromatin as you see here. So to begin to look at this kind of nuclear architecture we wanted to develop a way you can't really study things by EM. You can't do a screen by EM. So we've been devising different ways of looking at this and this is the work of a graduate student in the lab Talafakuri and a postdoc Tanya Yuziak and what they did was to take advantage of C. Elegans how it handles DNA. So worms are holocentric as you probably know and if you introduce sequences DNA sequences into the worm it will basically build a big artificial chromosome kind of a pseudo chromosome and so what we and others have done is to adapt the Andrew Belmont system where you can tag the lac repressor and then have it bind to this artificial chromosome and that gives us a very nice way of then being able to visualize this chromosome in vivo and what we like about this assay is it gives a single cell resolution so we know exactly what stage and what cell type we're looking at and we can see the kind of heterogeneity of what's going on and what was immediately striking to us when we did this is that we got this out so what you're looking at here is a panel of cells or nuclei that's what these little purple dots are and black dots and then all these are different artificial chromosomes in these nuclei and what really struck us is how different the morphologies were and just like what we saw in the EM studies we could see a big distinction that happened over developmental time so here we're looking at a single nucleus it's in an early embryo this is this tagged artificial chromosome or extra chromosomal array and what it looked like is it didn't really matter what promoter we put in so these are different lines that we built they all had this kind of very sort of fluffy appearance which we called a floret and by and large the interphase nuclei all had this same behavior however it doesn't last so here we're looking at different cell stages and this is happening quite rapidly so this is 28 to sort of 44 to 100 cell stage and we lose this configuration this big open chromatin look and instead it becomes much more condensed and and these very compacted artificial chromosomes now begin to pick up marks of heterochromatin for example so that was encouraging to us it's it suggested that we could actually recapitulate the kinds of things that have been seen at the EM level and we could see this closing down of the genome so what we think is going on is that there is a global closing down of the genome irrespective these aren't transcribed genes these are just sort of genes in the genome what happens then over time is that kind of opposing this this trend are the so-called pioneer transcription factors or the selector genes and sorry here's the quantitation so this is just to show you that the proportion of nuclei that have one or the other kind of compacted chromatin is increasing over time and so you can see that here so again these are individual lines and just quantifying the number of interface nuclei that have this kind of structure or this kind of structure okay so what we decided to do was to begin oh did this disappear I disappear so what we're going to do is look at one of the selector genes and this is far for so this was the factor that Bob just mentioned it's critical to form the digestive tract in particular the foregut in the worm and it's orthologous to Fox a found in from everything from Hydra to vertebrates and we know a lot about far for and so here is my first modern code slide so I put it up this is was done from Mike Snyder's group and it's looking at the chip data of where far for goes in the genome and then we've done a lot of expression studies and mutagenesis studies and the bottom line is that far for is all over the genome it's in thousands of sites and it regulates essentially everything that selectively expressed in the pharynx so if you make mutations in promoters of those far for sites you will lose or dramatically delay expression in the foregut so it has a very global role now this global role makes sense for a sort of selector gene pioneer factor but it also raised a lot of questions for us and that was that we began wondering how you get specificity if you have this transcription factor and it's going all over the genome and binding to all these genes and critical for their expression and so one way is certainly combinatorial control and I'm not going to talk about that but the other way where far for has a big impact on expression is the affinity for its DNA binding site and what we were able to show and I'm not going to illustrate it since it was published a while ago is that far for has different affinity binding to its DNA target and that higher affinity would promote earlier expression and lower affinity would promote later expression and so you could actually get an input of temporal regulation based just on far for and it's and it's DNA binding affinity and so we've looked at that also by the same spot assay now modified to include both far for and far for promoter to look at the association and the effect of far for on its targets and what we saw was really striking so here what we're looking at these are nascent foregot cells and the purple is the far for Fox a transcription factor and then the green is the lack compressor that just is to let us see this array so in this top panel we're looking at three foregot cells and you can see that far for is clearly binding to the array whereas if we mutate far for binding site in a target promoter we still have lots of far for but it doesn't become enriched on the array as you can see here compared to this so it gives us again a very nice assay to look at the single cell level and know when and where far for is binding what really jumped out at us there were a couple things that really were very striking to us and one is that far for can clearly decompact and open up the chromatin compared to when far for isn't there so if you if you look at this dot it looks huge for example and whereas this looks relatively compacted down and we've actually quantified that by just measuring either the volume or the or the area of these regions and asking cells that have far for how do they compare to cells that don't have far for and what happens to these target regions and the data shown here so green are cells that lack far for their outside of the foregut or the pharynx and that's what these green lines are and the pink are pharyngeal cells that have far for and far for is binding and so you can see what it looks like up here so this is a section where you have far for and it's binding and we're looking at different stages over embryo genesis and then out here are cells that lack far for and we're doing this same kind of plotting the area and the proportion of nuclei and what you can see is that the pink line which is to say the cells that have far for have bigger areas than those that lack it and that we take as evidence that far for is leading to this opening of the chromatin okay so here is the normal that I just showed you and you can see it opening up for example here here we've made a mutation where far for still binds but we know we inactivate the ability of D we get a very dramatic opening that's again this pink line compared to the green line on the other hand if we knock out the if we inactivate the far for site now we get rid of that opening so it needs far for and this is a different gene where we can remove the far for site and yet still get transcription and again you can see that the opening is very much reduced so we think there's something special about far for and its interaction with DNA that it can counteract the closing down that I just showed you okay now far for is not static and I kind of implied that by showing you these different stages in fact what far for does is dramatically shown here so we're starting at early embryo genesis and then continuing to the time of hatching and we've quantified the amount of far for within nuclei and you can see this this huge increase over time and so the readout of that then has this implication for the timing of expression and the affinity of binding for DNA and one of the ways that we know that is from actually measuring the association with far for and this decompaction that I illustrated so what we're going to do in this assay is shown here we have a gene that we know is a far for target we also have made a mutation where we lower the affinity of far for or the far for binding site within this promoter and we know that that will delay the onset of expression and so these are two different promoters and we're going to analyze them in two different strains of worms and look at the association of far for with these targets and what we get are these kinds of graphs where we're looking at the proportion of far for that's associated with the target chromosome and we're also looking at the effect that it has on the morphology of that artificial array and the data shown here so this is the earliest stage that we can pick up far for binding and we're looking at either this normal promoter or this mutated promoter already you can see them begin to shift and then within a little while you can see that the wild type you're getting more far for bound compared to this down mutation and it's having also an effect on decompaction on the other hand if you look out here where the gene is actually transcribed they look very similar so you're seeing the same proportion of far for bound you're seeing very similar effects on the chromatin configuration and so the way that we interpret this is that first of all far for combined to these arrays very early in embryo genesis hours before the gene will actually be transcribed and that the effects of the affinity seem to kick in also very early and that at these later stages even when transcription is actually happening that at that point affinity is no longer a player so let me just sum this up for you so what I've told you is that the early developmentally plastic state in the early embryo is accompanied with a very open kind of chromatin configuration and that over time as you lose plasticity that that's accompanied with a compacting down of chromatin and that kind of counteracting that we can watch selector gene like far for which kicks in at this stage and watch it decompact chromatin and what I didn't have time to show you is that polycomb is actually part of this closing down process so this kind of model is interesting but it raises a number of questions and one question of course is that what I've shown you today is mostly on arrays and those are artificial constructs and so one question is what's really happening in the genome and then the other question is really when I say open versus compacted what do we actually mean and you could imagine a number of different ways that the genome could be opened on the one hand there's the nucleosomes interacting with DNA and there's certainly precedent for losing nucleosomes nucleosomes can exist in this kind of beads on a string configuration or they can begin to count compact down its thought into the 30 nanometer fiber so this is another way that you can compact down DNA and then of course these fibers can begin to loop and depending on how you loop DNA that could also have a big effect on the morphology and at the level that we're looking we can't really distinguish what we decided to do was to focus on this earliest point and to think about nucleosomes interacting with DNA and in part we were thinking about that from a work from Misteli's lab looking at the way chromatin proteins interact with DNA in pluripotent cells in this case ES cells and they were arguing that the interaction of these proteins with DNA is hyperdynamic that there's just a lot of motion so we thought we would ask what worms do and when I say we it's May Chen who's a really terrific postdoc who started recently in the lab and Kareem Carr who's a mathematician and you see him here with the biggest gummy worm ever okay so the approach that we decided to take was actually developed by Jason Leeb sitting here and that is fair and for those of you who aren't familiar with fair it the idea is that just as in chip you crosslink proteins to DNA and you sonicate and bust up your your chromatin but then there is no IP involved instead what you do is just remove any DNA that's bound up with proteins in a phenol extraction and you have this released fragments and that's what you analyze and so what you obtain are these sequences of DNA that are open in that they are not bound to nucleosomes and so what we did was more or less adapt this fair protocol to look at C elegans and we decided to do this very carefully staged where we're looking at this early cohort that we know have plasticity and then comparing it to kind of mid-stage embryos that we know have lost plasticity so the first thing that really jumped out at us is shown here so this is from May's preps and it's just three experiments to show you it's reproducible but it was very noticeable that the amount of chromatin we obtained from the early samples was much higher than what we get from the late samples and typically we were getting somewhere close to four times more DNA from these early samples and so here we're just aligning all the chromosomes and looking at our early fair and our late fair against genes and you can see that in fact there is a lot more chromatin in this early compared to the late what that suggests to us is that in fact by this biochemical method we are getting evidence for a more open more open configuration where it's actually the association of the DNA with the nucleosomes and that that changes by mid-embry genesis as shown by the late fair if we look at this a little more closely one thing that jumped out at us was looking at our data as compared again this is more modern code data from Jason's lab and here he's looking at the association of parts of the chromosome with the nuclear lamina with this protein lem2 so lem2 chip you can think of it as as a way of seeing which DNA is sitting at the lamina and what's very clear is if you look at a particular chromosome the middle of the chromosome is not attached to the lamina but the arms or sides of the chromosome are and that tracks extremely well with what we see in the late fair so you can see this is more open and this is less which works quite well with this lem2 region the early has a little bit of this but not nearly to the same degree so in general we just get so many counts it generally seems open regardless of what's going on at the lamina we can zoom in and so here I think we're looking at part of chromosome 5 as I recall and there are what have been called sub-domains for lem2 so there are regions for example here where you pick up lent to and then regions that have less of it and regions with more and these are interspersed and if we look again at the late fair we we see a fairly nice correspondence where it's these lamina free regions have a pretty nice open region and then the regions that have a lot of attachment to the lamina are are lacking late fair and again though if we just look at this level at the early fair we don't see that kind of what's the word we don't we don't see anything like that it just we generally see this opening so here there's a really a very dramatic dramatic difference in the way that the early fair behaves with the late and that fits actually quite nicely with those EM data I showed you where you could see these attachment points to the to the nuclear lamina okay now there were in addition to this so this is where we see perhaps the most dramatic effect early versus late there were also a number of other places that we expected to get nice fair signals and I'm just going to show you a couple of those one is locations that have histone variants and what Gary Felsenfeld showed a number of years ago is that the histone variants H2A Z when combined with another variant histone 3.3 is a very labile nucleosomal configuration it comes off of DNA very easily and that had been seen in a lot of biochemical experiments as regions that lack DNA so sorry regions that lack nucleosomes and we thought we should actually be able to see this kind of configuration and that is indeed the case so here is more modern code data marking regions that have the histone variant H2A Z in three locations and here is early and late fair data and you can see it it lines up very nicely with these two H2A Z regions but on the other hand it doesn't really seem particularly enriched on the third so it's not a one-to-one it works quite well with transcribed regions uh transcriptionally active regions we also see it in some of these hot regions that you heard mentioned previously so these are demarked again on the modern code website as as hot and you can see we get these whopping peaks here of what seem to be nucleosomal free in in hot regions and then we also get mystery peaks and so this is just an example it's not really sitting near a gene it's not sitting near H2A Z but we're getting really quite strong peaks in certain places and so we're intrigued by by what those actually are so i'm just going to stop there and say what i've told you today is that i think something as simple as a worm is a good way to study developmental plasticity and that one area that we're particularly interested in is the configuration of the nucleus and how it changes over time and we've looking at this both at the cell level where we can do these single cell analyses but then complementing that with this kind of fair analysis and we're really just starting it but i wanted to mention it because the modern code has been really terrific for us as a way of interpreting our data as we begin to compare what we have found and what's up there on the modern code site and and i actually think in talking to other people in the worm community that there are a number of us in this situation we're beginning to look to the modern code as giving us tools that we can use for comparisons as a way of interpreting our data it's not really at the point i think there's maybe one paper that uses modern code data that isn't from a modern code group but i think it'll become more and more useful to see elegans researchers as we as we avail ourselves of that data and then i'll just wrap up by acknowledging tala and tanya who did the initial studies and that's been followed up now by kareem as i mentioned and may and i would like to acknowledge the modern code for their work in particular mike snider who did a lot of far for chip which was great with valerie rynke who is also involved in the transcription factor analysis and jason leeb many of those modern code data spreads that you saw were from the leeb lab they've been really terrific and jason's also given us great advice and this actually reminds me i think i'll put it up as a plug for anyone interested in transcription and development that in a few weeks there'll be a meeting out at facem and we probably still have slots so i thought i would show it to you guys and i'll stop and take any questions thanks i really like this compaction idea i think this is fabulous have you looked in adult self-renewing tissues versus normal tissues in other words is this a would this be a way that would distinguish those two types and i don't know in a worm if they have self-renewing tissues but i guess at least in the germline yeah the only renewing tissue in the worm is the germline and the germline is really very different so you know and we haven't looked at it it would be interesting i think one big difference between the germline and the early embryo the early embryo is really gearing up its whole transcriptional profile is about to just burst forth on the other hand the germline is sort of transcriptionally closing itself down and relies a lot on post-transcriptional mechanisms there's a lot of translational control but i think it would be really interesting because that would help you distinguish it as you say is if this is just a sort of when you need the entire embryo to go off versus individual cells and individual tissues that would be a good way to distinguish that yeah so what i didn't show you and what really got us thinking about this in the first place is there are experiments where people have mis-expressed selector genes throughout the embryo throughout the soma of the embryo and if you do that you can get really dramatic cell fate changes so you can change cells that should be neurons into intestine or body well muscle and what was really striking to us is that the embryos up until the 28 cell stage respond very nicely and they and they respond fairly homogeneously so um i don't have it here so essentially all the selector genes that have been tried were beautifully up until the 28 cell stage and then they begin to falter you know 100 cell stage and on and it was that homogenous response that made us think perhaps there's something changing in those recipient cells and got us thinking about these other experiments so so i think it is kind of homogeneous one thing we do know is for example if we get rid of polycomb we can both change chromatin structure and prolong plasticity they track together but really testing it is in progress so that's yeah uh Susan i have a rather naive question so sorry i don't know i have a rather naive question if as you as you change these you showed this experiment at the very beginning which is very elegant of sort of moving one cell around and get beautiful you know working animal my question is is the gene expression i mean has anybody followed the gene expression patterns to actually understand if the new cell is simply you know leading to the whole new lineage of the cell that was occupying the previous i'm sorry are you saying is the is the is it location the misplaced cell yeah taking on the new expression exactly um it hasn't been done probably to the way you would like it but i think it's fairly strongly implicated put it this way i would bet my one and only beloved child which switch and that's saying something and the reason i say that is for example a b a that front cell makes half of the foregut and that has very distinctive expression patterns and when you flip the but the back cell does not and if you flip the positions of those two cells now you're getting the foregut from that front cell and you're getting on the order of 40 cells from it and that back cell nothing so to have that kind of dramatic change you really need a very gross expression pattern change and and that difference is mediated by notch signaling and then and that's not the only one there are the somatic gonad is very different between the two so there are a number of cells where it would be where to to get those different types of cells out you have to have really dramatic and it is an experiment where you would take a cell from a different embryo and sort of include is that possible to actually get a different genetic background for different so what people have done is they've gotten rid of the eggshell and then kind of mixed and matched blastomeres together and but they they don't you can't make a worm at that point you can see evidence of cell interactions you can particularly see effects of wind signaling on spindle alignment but you what you cannot do is make a chimera take a bunch of different cells and have a chimeric worm come out kind of thing and it's I suspect partly of partly that those embryos those cells aren't as responsive of say a vertebrate embryo and partly it's things like the fact that the egg shell is important for orienting cells but what is really dramatic is this heat shock response where you can mis-express you know a number of these different selector genes and see this complete conversion where you you turn off the endogenous cell expression pattern and you turn on this alternative fate of whatever it is and it and and one thing that's kind of interesting you may be familiar with work of Sophie Giarriot for example or Oliver Hobart and what they've shown is that later in development like in larvae you can convert the fate of cells that are fairly close so for example you can have one neuron cell type become another neuron cell type by mis-expressing um what Oliver would call a terminal selector gene but although you can get those closely related things to switch you cannot get that cell to suddenly a neuron to become a gut cell that seems to be really very specific for this phase of early embryogenesis and it disappears um Susan um so this is great i'm wondering about um when you use the array and you're looking at opening you get the florets um do you have any sense since it's repeated whether there's variability within the chromosome in in how much opening and closing in fact if you look at a floret structure it sort of looks like it's not uniform so i don't know if you've looked at that at all in more detail we haven't looked at it in gory detail but i think you're right so one thing is that when you make um these artificial chromosomes and worms you get different degrees of repetitive dna depending on you know how much of everything you put in and what was shown a long time ago um is that repetitive dna and worms like in other organisms leads to silencing so if you just put in a repetitive array if you build a you would not see this at all i don't think i mean we haven't done it but that would be my hunch it would be much more closed down and it would just stay repressed what we're trying to do is build complex arrays that look more like a real chromosome um and but because of that you certainly see variability whether there's variability in the pseudo chromosome you'd think there would be and actually i was thinking wouldn't it be fun if one could do a like a nano resolution project and and see what's going on there and then i thought it's a worm array like who cares about a worm array so that's when we thought okay we really have to do the biochemistry and prove to people that it happens on real chromosomal dna it's not just some array strangeness and so that's when we started doing all this so the the e-cell becomes committed to a tissue well before any of the other ones and i was wondering if you saw any difference in the in the pattern of those an earlier transition or anything like that um yeah the e-cell is interesting so by the lineage just the wild type lineage the e becomes dedicated to the gut at the eight cell stage and yet at the 28 cell stage you can convert it into skin or you can convert it you know into muscle so even though by the lineage it's only going to produce one cell type already at that early stage you can go later and change it so in other experiments i didn't talk about we actually tried an experiment where we removed pha4 so the selector gene for the foregut and asked is that in fact important for curtailing plasticity so is it really the cell is there a big link between plasticity and cell fate and the surprising answer it was totally not what i expected was no so when we removed pha4 and the foregut cells don't know what to become they still terminated plasticity by that heat shock assay at the same time it wasn't delayed at all and so that's kind of the way i think about it and may i'd be interested to know what what you know if it fits with these networks people were talking about that those very early steps when you establish cell fates whether it's intestinal or foregut or what have you you still are pretty loose and if something else comes in you can switch your fate and it's only as that gets more established you get these feed forward circuits and you really finalize a fate that maybe at that point the cell fate regulators match but at this matter but at these early stages there's still a lot of fluidity and the e-cell it's very happy becoming muscle and it can become skin yeah it's kind of shocking okay thank you