The aim of my presentation today is to basically present some really satellite view of the microbiome. So we basically have an understanding and the same wording, the common language that we're going to speak. And also I'll present to you a little bit what's coming up. What are the teachers, the TAs that are doing the courses, just to remind you some of the very important people that helped us, great tailwaters for all the outfall bio K plus, this lunchtime to redo all your microbiome while you're here. And the big people in front of us as well in the process. So when we talk about microbiome, we also met that genome if it's in the environment, but here we talk mostly about humans. As humans we have 10 trillion cells and 23,000 genes. The microbiome and the microorganisms are the microbiome that kind of our friends get 100 trillion cells and 3 million genes. So essentially for every human cell, for every human cell you have 10 bacteria, you're more bacteria or microorganisms than humans. And this is basically a super organism that you interact with it. Essentially the microbiome is another organ. So what does it do? It's very influenced by the environment. And also there's some host genetics to it, so we'll show that to you as well. Some of the microbiomes basically digest the food that you're having. Essentially, I like the body phenols, that's not you doing this process and it's a bug. But sometimes things go awry and you may have toxins, so it's still in others. It's important basically for two things, it defends you against bad bugs and it helps you feed yourself, get the nutrients. And basically the equilibrium between this really controls some of the health and disease states. And it does a lot of function. It supplies nutrients and energy and if you have too much nutrients, obesity and the double-edged syndrome, so there's a lot of microbial products that work in controlling this balance. It also prevents cancer, pituitary protection and all of these and toxin and cross-nutrient. And if you have chronic inflammation, it can favor the promotion of cancer. It also inhibits pathogens, so it's there to defend you, essentially.  For instance, C.G. Steele and autochloroquine and the likes. And it's also a source of pathogens, so you have to be careful. It's also a source of antimicrobial resistance. So this, because there's a lot of exchange between these microorganisms in this environment. It's also involved in your normal gastrointestinal and immune function.  And you have inflammatory bowel diseases. It's involved in the motility. So again, IVS, constipation, diarrhea, bloating in your eyes. And it's also involved in cardiovascular health and controlling the amounts of lipids that you have in your blood and stuff. So essentially, it's very well involved in cardio and metabolomic diseases. When we talk about the microbiome, it's not just that gut microbiome. We have microbiomes everywhere. So hair, nostrils, skin, colon. And they all, it's just one human here. And all of them have different compositions in bacteria. There's even somebody who did the microbiome of bugs that you find on your windshield in the summertime. So essentially, we are covered with microbiome, and all of these are fairly different. Something you should remember as well is that the microbiome, it changes with age. So when you're a baby, you have a certain microbiome. If you're fed by a formula, so that's the environmental component, or if you're fed a breast-fed, it's very different. Well, somewhat different. As soon as you take solid food, there you go. You've got your microbiome changes. As an infant or a toddler, basically, if you take antibiotic treatment and change, if you're malnutrition or you all have the same ones, and then if you're healthy, it goes through a certain progression. As an adult, if you're healthy or obese, you have different microbiome. And as you get older, your microbiome also changes. It evolves with you in time. And also, one thing, and you'll see that we have a small presentation from somebody from C.I.C.A., but your microbiome, if you're a woman or a man, is very, very different. So essentially, at puberty, you can start having differences between a male microbiome and a female microbiome. This is hormonal, but it's also due to food intake in some ways.  But some people do it. So we fought our way at the top of the food chain is not to eat tofu. And this is shown here in a little bit more detail also that if you're the BMI here, how fat you are, basically, body weight index, it changes as well, and it's different for men and women. And I think that's not surprising. So in some ways, when I started doing this work, I write grants, but I didn't think, you know, I should have the same amount of women and men in my studies. I think this is essential now to control for diet, age, and also food intake. So we sequence a lot right now. There's a cute little baby, you can read it. It showed us there's a lot of... We started to discover, we sequence and sequence a lot more. So there's aquatic microbiomes, animals, soil, and sediment, and waste, plants, and others, and we have all these bacteria. So recently, the sequence they put into NCBI, a great deal more of sequences. And what's very interesting is that this is a power of discovery in some ways. These new genomes, I think there's a little over a thousand, they have biosynthetic gene clusters of different metabolic processes. And each, basically, each of these bacteria is around two million bases. A lot of them have these biosynthetic gene clusters, and essentially some of them have a lot of them, even if they're not that big. There's a series of DNA segments and basically clusters that codes for enzymes that process different molecules. So there's a great deal of new chemistry and biology in these, and it's also something that's very interesting in terms of bioprospection. And I say that because right now there's a lot of efforts that are being done to essentially look to generate some of these databases. And I think you should, I just put a few there, there's some obviously on the Human Microbiome Project, lots of data there that if you want to download, sometimes you say, I'm going to do an experiment, but listen, why not go check if somebody else did something, or they could be your controls for your study, or if you may test your own hypotheses by using somebody else's data.  You just need it. But in essence, there's also, if you're working in an environment, there's the same, you have a lot of tools everywhere. We're going to go over some of the tools in this class. So that's very interesting to know. And there's also this new one that just came out. There's a lot of microbiome data here, and it's a little bit more cleaned up than some of the databases that you can find out there. So what happens to the microbiome? So it changes a lot. Supposedly in this room, maybe 40% of our microbiomes are in common, and the rest is very specific to you. So that's one thing you'll have to remember. You are the best control for yourself. My microbiome looks a lot like mine during time. So doing these types of studies with the repeated sampling of the same microbiome. And there's a lot of interesting things that happen in some ways. We did a lot of studies treating healthy people with antibiotics, and you see a real shift in essentially in the bugs that are there.  It's all basically the level of sequencing as well. I don't remember that when we sequence, if you do that 10 times, the DNA will be sequenced 10 times. If you do that one time, the DNA will be sequenced one time. So if you change this, you have to go really, really deep to find species that are not there at very frequent ways. But it can change really rapidly. Obviously, antibiotics is a big kick in some ways, especially depending on the antibody. But let's say if you take somebody's anemic and takes iron pills, it's going to change a lot because bugs live iron, and it's very dynamic. It changes quite quickly. But it has a tendency to come back to some sort of homeostasis ground for yourself. I mean, because you're in an environment, you have your own genetics, you have your own food habits, it has a tendency to go back to normal. But when we did this particular experiment, we'll go over this in detail a little later when we do a more scientific presentation, we actually gave antibiotics to healthy people because we wanted to see just antibiotics. So we selected them for all sorts of processes in a sense that they didn't work in a lab or a farm. They were normal people, so none of them were scientists. And then essentially, we tried to basically control for a lot of variables. And then we gave them an antibiotic. And this is what happened, basically. This is a PCA, a principle component analysis. And this at the back here, this is the blue, the little gray here, this is where they all salt. Then we gave them an antibiotic for seven days. And at seven days, this is where they are. Basically, they all change. It's very distinguished. And then we came back 90 days later and asked them, that's kind of the paradigm. After 90 days, your microbiome is back to where it was. It's mostly there, it's a pale blue, but it's a lot bigger. And then some of these people, for instance this person, never came back. She's one who, in the course of the study, became anemic and we gave her iron. This is where she ended. So it's very dynamic. It can go really quickly. So in terms of doing microbiome work, it's a little bit difficult. So you have to think about these concepts. One other concept, they always say that brown bread is better than white bread. Is that true? You have to think about it. It's actually true, depending on your microbiome. Some people, the white bread will be better than the brown bread won't be. So you have to think a little bit outside of the box in some ways, because this is happening right now. Just a little foot for thought here. There's some really wonderful things that are happening in terms of the microbiome. We have this process where we can transfer healthy microbiome to people with specific infections. So these usually affect elderly people. Average age is 80.  And it's a lot of people. It's 40,000 people in the U.S. a year. But we have a cure rate of nearly 90% with this repopulation, basically reintroducing healthy microbiome into these people. Tell me about drugs that work that well. It's very, very interesting. There's a bit of a yuck factor, but in a sense this has been worked out right now and it's been done in our own hospital. So you have to just validate the pill that you're going to give to these people so you don't give some bad stuff into that. There was a very interesting paper. It was in a bio archive. It's not public shit, but they took a chili fish. It's a teeny vertebrate fish. And they took the microbiome of these younger fish and then gave them to older fish and then it lived longer. So it's also something that's really interesting in terms of what's happening with the microbiome and what we need to learn about it. There are even now companies that you can send your little poop to them and basically they will, not sure about the quality of the service, but they will tell you maybe you should eat this, maybe you should eat that. It's quite interesting. I'll see how long they survive. There are some ideas here about the power to drive co-evolution. So in some ways the microbiome works with us, our dyes change, so the bugs co-evolve with us as a human species. That's very interesting. We'll have a section also on the responses to drugs. There are some drugs and some bugs that don't go well together. For instance, if cardiac patients that have heart trouble and they give them digoxin, there's a bug called Ericatela lenta. If you have that, it will not work very well. You have big side effects. So we have, the bugs have a lot of effects in processing some of the drugs. And also some of the drugs will also control the type of microbiome you have. So it's a two-way combination. And as I said, and this is what interests me the most in some ways, I think it's a very new source of interesting metabolites in those biocytic gene clusters. There's plenty of opportunity to do big data in there and do machine learning and stuff. And we'll talk to you about that as we go along. So I didn't want to take, I want to do this pretty quickly so we don't get too late. I just want to tell you what's coming. So after me you'll have metagenomic, how to approach it. So we'll talk about the tools of the trade, time, 16S profiling, how we do the reprocessing. And this will be done by Robert. Now he has a beard so we didn't want to be recognized, I guess. But in some ways some of the tools of the trade will be shown to you. And some of these tools are always, in some ways, some sequencing. We do a lot of sequencing. I'm just showing you what the way we do it. But there's other methods to sequence DNA that's quite efficient as well. In essence, it all starts with the reads we get from the sequences and the unit called the camer. The camer is 21, 31, 41. In vectors, usually that range is good. And what we do is we assemble these reads with the room graphs. And then do the assemblies. And remarkably, if you're there about 1%, you'll be able to assemble 80% of your genome. So it's pretty good. And then what you can do, these are just a normal assembly. You can take a reference database. Let's say it's other species and basically cameraize it. So each one, you can see that there are thousands and hundreds of thousands here. And each one is assigned a different color.  And then this colored the room graph, you can see and identify all of these assemblies, which species it is, very, very readily. Obviously, if you give a different reference database, if you give all the ones that say resistance genes, kinase or phosphatase, you can do this the same process and you can get how much in this microbiome are phosphatase present or classmates or genes of resistance. So these are very, very powerful to start asking. Not questions of who's there, but also a little bit, what are they doing a little bit? But it's not metatranspectomy, but that's John telling that. It's a very good indication of what's going on. A little later, the metagenomics, how to approach it. And I say carefully because there's been a lot of problems in some of the metagenomic systems up to now. We'll talk a little bit about the bigger picture, and that's the Morgan, with Metafalan, and Schuyum, and Sam. And Frederic, who's in my lab and loves scales for some reason. We'll talk to you a little bit more about Ray Meta and Pacros. I think the two of them share the process of explaining all of these common tools of the trade so you'll be able to analyze the microbiome more readily. One interesting process is to look at the biomarkers. How can we use it to predict or do interesting stuff? Fiona Breitman is going to come and tell you about this. There's supposedly two big enterotypes for humans. They've got microbiomes. So there's the bacteria assay and pre-botella. And these papers are being revisited in some ways. At one point in time it was even three, if I remember well. So I think most of us now realize it's some sort of continuum, but they can be useful trade-offs to see how it happens. And I'll talk to you about this as we go along. We'll talk about metatranscriptomics. So basically John Parkinson will do functional interrogation of those microbiomes, not just who's there, but what are they doing? I think that will be a nice lecture for you. I'm very happy here in Toronto. And Maxime will talk to you how to compare microbiome. If you have lots of microbiomes, how can you just visualize how to do this and that will be done with Ray-Soveya. We'll talk also about host drugs and the microbiome interaction. So we have some host genetics influences the microbiome that you get. There's some obvious host genetics. If you have cystic fibrosis it will definitely influence your microbiome, but there might be even more subtle ones. And there's a paper recently, I'll get it out to the TAs, that showed that the environment now is more important than the host to control your microbiome. So we'll see. I think it's always a given type. Also, a lot of the drugs you take can influence your microbiome. And it's okay, most of you guys don't take drugs, but it went well, hopefully. And then some of you basically later on who are presently elderly person takes between eight and 10 drugs a day. So we don't know. We know about hepatic toxicity, renal toxicity, but I think there's also some effects now that the drug companies are looking for microbiome toxicity for some of these drugs. And also, one of the problems is the drugs can be processed by your microbiome or influence the microbiome. And the microbiome can actually, this what happens for dioxin, it metabolizes drugs differently and creates some problems for you. And it's right here. So it's kind of nice. Vincenzo's here. We have this, this is kind of a new era in saying that there may be a lot of different control of the microbiome by the endocannabinoid systems. And I think our guest speaker is a Canada excellence researcher in microbiome and talked to us Tuesday or Wednesday. Wednesday. And essentially that will be, that's open to everybody in the whole Tuesday. Wednesday. So it's Tuesday, so we'll, that's open to some of the, to the whole community. We'll see for that. Okay, so I'm in a faculty of medicine, so I see this, and especially I'm in infectious disease, so you can see how I see the world right now is that we have us and our microbiomes, the drugs and the packaging, and there's a cycle now that we just used to do this and now I think we have to include the microbiome into the process because it seems to be a very important regulator of our health and also essential for, you know, staying healthy. So, microorganisms, they're our friend mostly and I think our gut feeling right now is that we should work together. They can help us in some ways. We can recreate states of microbiome that promote health and also there's a state of microbiome that's just terrible and leads you to diseases. So I'll just stop there because I just wanted to thank all the people from our group of machine learners that do some of the analysis and you'll see a lot of them. Frédéric and Alex here and Pierre and Maxim are here as TAs to help you along with some of these questions. I'll stop here because I just want to answer questions and see what are your interrogations about this field. It's a very new field. There's a lot of new questions and a lot of room for young scientists to emerge and start thinking about this type of research. So, thank you. So, any questions? Questions? How do you differentiate the effect of the phage versus the microbe when you transfer it to the animals, for instance? Is it the microbe or the phage that has an effect on it? Okay. It's not the phage. The phage is actually... I don't know in terms of... if it's a lithic phage or is there any difference for you or all the phage in general? In the environment, the biggest control of microbes are phages, bacteria phages. Many times it's an equilibrium. In a human, I don't think it's any different.  So, I'm not sure if I answered your question properly, but you can't... Well, we like phages. We sequence a lot of those, too. And that's in the environment. They are the biggest control of the microbiome, the microbiome population. Sorry about that comment. It's the balsalt metabolism that controls the germination. It's the restoration of that metabolism. That's also tough. And also, it's a niche.  Yeah. I'm wondering if we'll cover at some point things along the lines of data quality, study quality. You've kind of alluded to... there's a lot of crappy data out there and it's important, especially if you're coming into the field to be able to evaluate, is this something that is worth following up on or should the study be completely repeated or things along those lines? Yeah. Well, I don't like to trust a bunch of colleagues, but... It's not... Data cannot be totally trusted. It's good to replicate. That's how we basically make sure that happens. There's a lot of sequence that's not right and, yeah, you should always be very careful about the data use, especially it becomes very problematic in... when we do big data analytics. We do some mass spec stuff. The spectral libraries are very terrible. So that's a big problem. Yeah, I think... Rob, you had a... You wanted to answer that or you had a question? Yeah, we will. I mean... It's not just this field, it's every field, and it's not bad intent. Sometimes it's bad science and sometimes it's just unaware of. But, yeah, you should control the sequences. But just issues, even if I want to do an experiment about what's the proper study design? What's the proper number of... Oh, this we'll talk about. In microbiology, I didn't realize I should be careful to put this the same amount of women and men into a microbiome research. Don't eat the same, don't have the same hormones. So this, now I'm more aware of it and by reading and by... and we have somebody who's going to talk to you about this because it's an important factor in designing studies.  The number of women when you have to recruit children in our study... compared to all states in the development? As you see, the microbiome changes with age. So there's puberty, but there's also for women pre- and post-menopausal. So all of this you have to take into account. Adjustable? Well, yeah, so that means the study numbers have to be bigger. It's just that when you start to do a microbiome research and you want to go to a level where you want to do full shotgun sequencing, you need 15 to 20 billion base pairs. So every time, so you can do a certain number and it's very costly. I mean, every time you press the button on an Illumina machine, it's $25,000 and you can do maybe maybe 20, 25 microbiome. So you need big numbers but they're expensive to reach. So that's some of the limitations but there are tricks to do this puberty as well that might be a little bit cheaper and one of them is go look in the database of some, if there's something there that's okay as well, just to give you an idea. Thank you for that talk. So I was just interested about the cut microbiome. So yeah, I'm so glad to see that there are a lot of things right now, the data information about it. About the fish. Yeah. So in humans, is there any way to transfer the cut microbiome too? Yeah, we do it only for medical reasons and only, this is being done for people that have seeds of silk that's resistant to treatment now and then they do a transplant, a fecal transplant and essentially that works pretty well. It's just that there's some issues at one point in time that I was done that if you don't, some people do it at home, they're so desperate but sometimes if you transfer a microbiome for somebody who was obese to somebody who was thin, then you may have changed that thin person into an obese person. So this you can transfer some lab traits as well so that's why people are very careful in doing this and it's also you're not doing you're not giving a single agent, you're giving a big thing and that gets the authority kind of nervous there's also ethical concerns and legal concerns in doing some of that stuff. Is there someone like doing like a capsule stuff? Yeah, it's a capsule, don't worry. Okay, I'll take a few more questions and I'm here all week so you can ask me a lot of questions. So it's just a follow up on that so what's the when was the first transplant? How long is the pull-up now? It must have been a long time since the first transplant. No, it's been a while. I can't talk specifically about I can't remember the last time but we've done a lot of I can't remember the last time but we've done at our hospital something like 20 of to 20 now and sometimes it works the first time and sometimes we give another pill it's not a long treatment and the person it modulates really quickly and it chants to me the person The follow-ups are not that long but the reason they might not die from this but the average age of the people who get this so they die from something else sometimes Okay, two more questions So my issue is data collaborative at the national level because I found that like creating a research now we are doing a lot of micro miles that our data collaborative approaches really little and I don't see very obvious people are very segregated working but we never compare our data and we still do our data very well and I think that is happening in the U.S. as well but they are very hard working in terms of data collaborative at the national level but how about our Canadian research where are we now and how are we doing? Well I was in the U.S. for like 15 years so people have a realization that you can pay it by the public so the data is public and there are also rules and regulations when you receive grants now you can deposit the data and now CIHR adds the same rules and most of the funding agency want you to deposit the data the patients group or foundations they are like really crazy about you so it's happening it's a change of mentality and it's great that you think like that so I'm sure you're going to deposit your data and your colleagues will too Okay, last question I have a follow-up to one of the questions on the data quality so I was wondering whether bootstrapping because the data is what we have and that's going to be limited by the ability of the machine so it introduces biases and there are other steps beforehand so whether bootstrapping would be a good approach to use on building analysis together for vast results Okay bootstrapping always scares people if you do too much we have techniques to know if you're overfitting of the data I think we'll talk about that it's a complex issue but yeah it's a consideration I mean I can't if the data is not really good it doesn't work and you can't salvage it if you're lucky enough we try to do a lot of high throughput data so we can generate lots of data so that's statistical power but if you don't it's just inferences that you can get but we'll have a section in the machine learning to see that and also we can also compare we have comparisons of microbiome with others at large scale and you can see if there's some outliers out there and tease them out that's another possibility Alright, we'll stop here


How is it even possible this thing was? It was so clean like literally two days ago.  Yeah, dude Um shit's been hacked.  That's gonna be cool And then tomorrow is actually formal and then we'll be back by Sunday So it's like a three-day thing. It's kind of cool. Oh, yo, so I was gonna wear if you guys watched these sneaker tub Dot com semi-sponsored video wasn't really sponsored. They just took me out with some shoes I was gonna wear those white NMD's. It's white NMD's they got me these sick-ass white enemies. I'll show you guys right now.   Ah, they're there.   So if I hadn't got my mom the Lincoln I would be taking her soccer mom van So it's a really good thing I got her the Lincoln and this washer's so low. No lie though boys I'm be looking fresh as hell that formal I just got a new suit because I actually don't have any suits or ties or really anything I'll have a lot of dress clothes.  This is cool. I don't know how to do keys. I don't know how to do this. Hello Very very nice.  Very nice Where's Christian already, yo, this is kind of nice. Look at these rooms.  This is just this is literally just the downstairs too. All right, and now he's upstairs What's up motherfuckers? Yeah, where's your date? Oh wait, you're getting up Just finding from Asia That's kind of funny. Wow. This looks really nice. He was at two fridges only pop in here lots of pop Oh my god. I love you Jumping We're going grocery shopping So we do that all our trips. All right, we're getting we're getting groceries and we're taking this Dad push me. Can we make it? Yay. Thank you so much Legs broke and it's got to jam and hit the other egg and machine. Yo, Chicago targets have Starbucks in them I've never seen such a thing I'm 245 pounds and Kaylee's like 70 niggas. Oh my god, you're so right. We had we had Billy in our last room What do we name our pet? We had Billy on spring break with the turtle named Billy What do we name this one six nine song game gumbo gumbo you mean I think No, this is gumbo minus. This is our room pet. This guy goes everywhere with us now.  Um, it's just the weird thing is that this camera is literally like this camera is twice The size of me. It's half the size half my weight. Okay Look for like makeup and stuff. Anyways, we're running some errands They're behind me. I want to see I want to see something wicked 42 these are priorities here. We need our oreos.   I just whipped on these other things. I thought it was you guys Kayley No, not for gushes. Well, I'm not six years old.  Yeah, we almost forgot Yeah, it's not low enough I'm not counting that Fancy dinner and we are going to have a lot of pop at the fancy dinner Almost like a mob another party. Well, listen up gummo gets so many girls.  We know what happened It's called a mini-dad Thank you town He's to my favorite fight beast nation boys Am I gay now? I got so cold that I'm buying a switcher in the night. Oh MMG Oh It's Elena guy just came over and asked us if he said are you guys a YouTube channel?  Okay, it's not about taking the easy way out of the journey. I Got really cold. So I bought this jacket It's cold. This is not a primal day for Chicago here Yeah, we have another vlogger to I'm such a gentleman. Oh my god, look at me Kayley Kayley brings a stepping stool everywhere Wait, why did you have to get up to even look at that?  How am I better nice Which one we lost another one that faces my face How is he pregnant day two Fucking whale This is literally half of our mess. We're gonna clean all this up. Where are you go? Welp Chicago's Alright guys, Chicago is awesome. I gotta do some cleanup I think everyone's still gonna be sleeping for next like hour and a half. Thanks for watching as always. Peace out I'll still hope you enjoyed


So, good morning, lectures and participants, we are formally starting our school, joint ICTP, IAEA school on nuclear data measurements for science and application. The school will continue two weeks, so part of the lectures are here, and as a second part of the lectures will come next week. So, this is the web address of this event, and Aganizer includes two persons from the International Atomic Energy Agency. So, my, I'm, and Dennis Ridicus, I will be here this week, Dennis will come for the next week, and local organizer, Professor Joni Miller and Liza Anita, who just talk you about administrative details. Maybe it is a good, it will be good practice for the lecturers if they will say a few words about themselves. So, as concerning me, I worked last five years in the International Atomic Energy Agency in Vienna. I'm a head of the Nuclear Data Service Unit. It means that our main task is distribution of nuclear data among member states of agency. We have more than 160 countries. Before that, I worked 10 years in the Foshen Center in Karlsruhe, where I was involved in the nuclear data and the neutronics simulation for the fusion applications. Before that, I worked rather many years in the Institute of Physical and Power Engineering in Obnius, together with Vitaliy Krychkov and his students. I was involved in the measurements, analysis of different type of neutron and proton induced reactions, transport and so on. So, I would like to say about the aim of this school and prehistory. So, this lecture aims to introduce and deliver concise and the most recent information on nuclear data, in general and specifically on the measurements, which are required for fundamental research and various applications. So, before this event, there was some prehistory. So, in 2012, sorry for mistake, I notice now it's rather far future. Okay. So, Nuclear Energy Agency organized a technical meeting on the use of neutron beams for higher precision nuclear data measurements. Proceedings are available as a report. If you click on this link, then you will get this report with additional information, which in principle available as a CD-ROM, but they are included in this link. And one of the conclusion or recommendation of this meeting was the organization of periodical technical meetings, education and training workshops or schools to ensure knowledge transfer and preservation. So, in such a way, present school is somehow implementation of the recommendation of this meeting. So, now I would like to say a few words about the content of the school. It means that which type of data and which type of application will be covered by the lectures. So, this is the basic nuclear physics and nuclear data. So, it's like you see a list of the main erections which neutrons undergo during its collision with the metals, with materials. And last lecture will be properties of neutrino. It's some kind maybe outside, but it's also interesting to write our knowledge, and especially that this year the Nobel Prize was awarded for the determination of the neutrino mass, if I remember correctly. So, and also besides a cross section as a basic nuclear data, there will be several lectures or exercises which will be devoted to the nuclear data for application. It will be included prompt gamma activation analysis and non-energy application of research reactors. So, this is the last topic. It will be done as we will present this. Maybe additional information which will be scattered in the lectures. So, it is important for the nuclear data to know about facility instrumentation, data analysis. So, in this lectures and exercises, there will be covered various neutron sources and facilities, both accelerator-based and reactor-based research reactor. So, it is a very famous and top facility launching Los Alamos, Linux and Rancella, and other facilities in the United States, Gelina in Belgium, facility in Japan, in Hungary, Grenoble, new facility for science in Ghana, which is under construction now. So, Linux Neutron Source in Bariloche, Argentina, Vandegraaff's Neutron Sources in Obninsk, and others. And as a facility instrumentation, naturally several speakers will speak about time-of-flight, standard time-of-flight or slow-down spectrometers. There will be lectures about detectors for neutrons, fission chambers, digital charge particles, spectrometry in gaseous or fission detectors, BRCA, counter for charge particles, and others. So, another essential point of learning is real practical exercises. How data taken in experiments, how they preliminary process and analyze. So, it will be a topic of several exercises which will include modern energetic neutrons of properties, neutron flux measurements, matrix analysis of cross-section and uncertainty propagation. And also, essential part for all who are doing research is working with data already accumulated. It means X4 as a database of the all measured experiment, all measured cross-section, not only cross-section, SIG targets and many other quantities, and evaluated data cross-section, which we usually design as evaluated neutron data files. So, here is important data search, retrieving, plotting, intercomparison, and so on. There will be special two exercises devoted to this topic. So, another member from nuclear data section, Viktor Zerkin, he will come here and make such exercises. About how this event was organized. So, main organizer responsible for it was this ISTP center. Then nuclear data section and physics section of International Atomic Energy Agency. Then we collaborated rather tightly with the neutron time flight facility in CERN. They recommended lectures. And as a cosponsor is University in Seville, which has such a project like European project for neutron size and Europe and Spain. So, the total school will comprise, comprises 25 lectures and eight practical exercises. So, there will be additional a poster session, I'm not sure one or two, with voting of prices and certificates to the three best posters. So, I would like to thank for contribution to the ISTP staff, especially to the school secretary, Lisa Yanity. You contact with her, I guess on many occasions, also housing and IT offices of ISTP. Then, as I would like to thank in advance lectures for coming and for the transfer of knowledge in the form of the lecturing, tutoring, direct communication with the students. And to the students, we wish to learn intensively the subject of the school, be active during school and establish partnership with the leading expert and labs. So, this is what I would like to say. If there will be a window, I can make presentation, technical presentation about what nuclear data section, how it develops nuclear data and how it distributes nuclear data. So, thanks for attention. If no question for such a formal introduction. So, then next lectures. Hello everybody. Good morning. Sorry. So, first of all, while I'm switching on the other computer, I would like to thank the organizers for the invitation. My name is Nicola Colonna. I'm from INFN, National Institute of Nuclear Physics in Bari. Since the beginning, I'm involved in the end-top, sorry, just a few more seconds for the preparation. Okay, should start now. Perfect. So, as I said, I'm involved in the end-top collaboration since the beginning. And before that, I used to work in fundamental nuclear physics and neutron-induced reactions, AV ion-induced reactions, and nuclear medicine. So, right now, I'm mostly concentrating in the end-top project. And I will discuss a little bit about the activity going on on fission, but before I will give an introduction. In fact, I will describe the motivation for measuring fission, a neutron-induced fission cross-section. A few words about the neutron beams that can be used. A little more in detail about end-top, the end-top facility. Just a few words about the experimental method. And if there is time, a few examples of measurements that we have done at the end-top, which have led to improvements in the current knowledge of neutron-induced fission. And then, of course, a few conclusions. So, I will not go into detail. For those of you that are not very familiar with fission, just a few words about the process. Initially, the process is governed by a barrier. So, when you have a neutron that is captured by AV nucleus, for example, uranium isotope, it produces a compound nucleus with an excitation energy that is given by the neutron binding energy, neutron-separation energy plus the available kinetic energy in the center of mass. Then, when the neutron-separation energy is higher than the barrier, fission can occur at any energy and attain neutron energy. For this reason, this is referred to as a fissile isotope. Otherwise, you have a threshold, minimum energy, minimum neutron energy, typically around 1 MeV, above which fission can occur. This is often referred to as a fertile isotope. Now, important observables when studying fissions are, of course, the energy differential cross-sections, the fission fragment mass distribution, the fission neutron multiplicity and spectra, the total energy released, and also the delayed neutrons. Now, just to give you a visual example of what I just said, look at uranium-235. This is the fission cross-section of uranium-235, and the neutron binding energy is 6.5 MeV. The barriers, the two barriers that you saw before, are around 5 MeV. So, essentially, the energy available is always higher than the barrier, and the fission occurs at any energy. If you look at uranium-238, instead, the neutron separation energy is much lower, it's 4.8 MeV, and the barrier is much lower than the barrier, of course, which is 6 MeV. So, the fission occurs above, let's say, 1 MeV, but of course, you can have some sub-threshold fission with resonances that can provide important information also on the structure of the nucleus. Now, why is it important to study, to measure fission? Of course, because you need to get data for applications or also for fundamental studies, but also, mostly, to implement and to improve models of fission, so you can predict fission cross-section, for example, of isotopes that you cannot directly measure. So, let's see now the motivations in terms of technology applications. So, what happens? Mostly, these are related to the working of nuclear reactors. So, what happens in a nuclear reactor? So, you start from, as you probably all know, you start from uranium-335, you capture the neutron, then from the uranium-336 compound nucleus, and this fission produces long-lived fission products or other fission products, which often, let's say, have to be somehow disposed. You can also produce neptunium-237 because you capture uranium-237 decays quite quickly, produces neptunium-237, which is a long-lived isotope, and this is again part of the nuclear waste. Then, more nasty things are produced starting from uranium-238, a series of neutron capture and beta decays produce a lot of actinides. In fact, essentially, plutonium-239, which is also used as a fuel in nuclear reactors, but you produce also americium isotopes and curium isotopes, and all these are the typically long-lived isotopes, which, of course, you have somehow to isolate from the environment. Another possibility which is now being considered is the use of the so-called thorium-uranium fuel cycle. How does this work? Essentially, in this case, the fertile element, the fertile isotope, is the thorium-232. The thorium-232 captures the neutron, then beta decays produces uranium-233. The fissile isotope, which could be used in reactor C, is the uranium-233, but you can also produce, again, as a result of successive neutron captures, you can produce a little bit of neptunium-237. But the interesting feature of this fuel cycle is that you don't produce any of these AV-minor actinides that you have seen before. So, this is a very interesting cycle, and this is one of the reasons why it's being considered as a possible fuel for the future reactors. Now, if you look at the nuclear waste, you have some fission fragments that I mentioned before, but they typically have lifetimes of the order of a few hundred years. So, after, let's say, one thousand years, the radio toxicity that is the, let's say, the rigativity produced by these fission fragments is essentially decayed to the natural level. On the contrary, if you look at the transuranium actinides, deuteronium, plutonium, americium, and curium, in particular, you see that the radio toxicity, the dangerous feature of this waste decays much slower, and it stays on for thousands of years, hundreds of thousands of years. So, although this only represents 1.5% in mass of the nuclear waste, they essentially provide the biggest radio toxicity contribution after 100 years. And most importantly, the problem persists for, like I said, hundreds of thousands of years. On top of that, some of these isotopes are also fissionable, which means that they pose problems of criticality and proliferation issues. Okay, so, at present, the only way you can manage these waste is to put them in geological repositories. But if you do that, of course, this is, for example, a calculation, you would need, you see, if you have current reactors, they are called once through because the fuel goes only once through the reactor and then it has to be disposed. Then the amount of waste increases, and just to give you an idea, this is the capacity of one of the geological repositories that have been considered in the U.S. now, I think, is stopped. But in any case, you will see that at the current rate of use of nuclear energy, you would need a geological repository, like Yucca Mountain, every 20 years, and we still don't have one. So this is really a major problem of nuclear energy, the fact that you need to find geological repositories for long-lived waste, essentially actinates. So another possibility is, as I mentioned before, this is a problem related to the current technology, which is called once through. The fuel is prepared, goes through the core, the reactor core, and then eventually has to be disposed once it is spent, but it cannot be used anymore. Of course, there are other problems, apart from the radioactive waste, that is also the fact that you don't use very efficiently the fuel, and pretty soon this is also going to be, as to, cannot be available anymore. So another possibility is to recycle at least part of the waste, in particular the actinates, and in this case you, first of all, use more efficiently the uranium resources, and secondly, the amount of waste that needs to be disposed of in geological repositories is much smaller. So clearly you need a new generation reactor to do this, and these are the so-called four, generation four reactors, mostly fast reactors, we will see. There are also other possibilities to use the so-called the seleniton-driven system. It will be a little more specific in a minute. Of course, the main advantage will be the higher efficiency, lower production of waste, but of course one aims also to improve the safety and the nonproliferation aspects, and possibly also to lower the costs and construction time. Now probably many of you are already aware that there is a large activity going on, an international collaboration also, an international effort, I would say, towards generation four reactors. There are several types. I will not go in the details of the, let's say, the technicalities of the reactors. We'll just mention that most of them are fast reactors. Before I go to that, as I mentioned before, there is another possibility that has been considered for some time for burning nuclear waste and transmutating nuclear waste, and this is the so-called the seleniton-driven system. So how does it work? Essentially you have an accelerator, a proton mostly, high current, high energy accelerator of the order, let's say, with GV. Then the proton beam is injected on a spallation target, which is typically lead or some AV material, we will see in a minute also. This is of course surrounded by a subcritical core. So you produce in this case, in this spallation target, the neutrons that are just enough to sustain the reaction. And then of course this produce energy. The energy goes to produce electricity. Part of this electricity of course has to be supplied to the accelerator to make it work, and part of that can go to the grid. But the important thing is that in this core you can put fission fragments and minor actinites, and the reactions that will occur here will transmute them. This will essentially transform them from long lived to short lived radioactive isotopes. So of course this is intrinsically safe because if you turn off the accelerator you don't have any more reactions going on. You don't essentially, you turn off the reactor here, the chain reactor, and you can incinerate nuclear waste, but you can also use also the different fuel cycles like the thorium uranium that I was mentioning before. Of course what are the, in order to make such a device, such a reactor, subcritical reactor with an accelerator, you need to develop this kind of accelerator which has to be high current, high stability. And also you need to somehow get, let's say design the core, and for this you need, since you are putting in the core of the reactor fission fragments and minor actinites, you need to know the cross sections of these isotopes in order to calculate the behavior of the reactor itself. So let's look a little bit at the physics of these new reactors. Essentially, as I mentioned before, the main innovation concerns the possibility to use, and at the same time burn, minor actinites like nectonium, mameritium, and curium, which right now you cannot, you have to just put somewhere for underground. Hundreds of thousands of years, hundreds of thousands of years. Now, if you look at the cross section of some isotopes of these elements, well, you know that like uranium-235 and plutonium, they are fissile materials, so the cross section essentially is quite large at all neutron energies. This is the neutron energy scale here, but many of these actinites are threshold, they fission above a certain threshold, typically 1 MeV. So clearly you cannot induce fission unless you have a neutron flux in this energy region. And this is the spectrum that you see here, it is what typically should be for a generation 4 or an ADS reactor. So it's typically a fast neutron spectrum. In current reactors, the so-called thermal reactors, the neutron energy is much lower, it's a thermal energy. Here you have a neutron energy which is centered at a few hundred kV and with a tail that extends to several MeV, so you can burn also, you can induce fission also on threshold isotopes. Now, okay, so they require energy of neutron energies above 1 MeV and of course if you want to design such a system, you need data with the high accuracy in that region. So for the design of new generation reactors and the generation 4 or ADS, you need and also for safety parameters, you need accurate data on fission and capture. And other quantities, fission capture cross-section and other quantities that regard these minor actinides. So data on minor actinides are essentially fundamental. Just before going on, I think everybody knows in this room what is between high accuracy and high precision, but just in case there is somebody that doesn't remember the difference, I will show it just with a plot, this is a target and a phrase that says it is better to be roughly right, which is close more or less to what the real value then precisely wrong. So the difference between accuracy and precision is that accuracy, measurement with high accuracy means a measurement that gives you a data which is close to reality. Precision may give you always very good data but not which is systematically off from reality. By the way, this phrase apparently comes from Keynes. So it is fundamental when you measure any kind of cross-section, when you make any kind of measurement to have a good control of the systematic errors. And we will see that in fission cross-section measurements, this is one of the most important, let's say, and most difficult tasks. Okay, so just to summarize what I just said, we need new accurate data for uranium, plutonium, minor actinides. And all this is needed for increasing the fuel burn-up even of current nuclear reactors, but also for future reactors. Of course, to use the plutonium that is being accumulated, for example, or also for the plutonium that is around from, let's say, nuclear weapons. We need data for recycling of nuclear fuel in the closed cycle generation for reactors or for transmutation of the nuclear waste. Now, you can find a long list of needs of data needed in a compilation. For example, there are several, but one of the most important is the NEA, Nuclear Energy Agency High Priority Request List, where they essentially keep up a list and they update very often a list of requests that are important for, let's say, nuclear technology. By the way, I saw that there is a session later on in this school. You will learn how to retrieve data, experimental data, but also evaluated nuclear data. I will just mention here that there are several libraries that contain data of evaluated cross-sections, for example. This is ENDF, now it's version 7.1. ENDF is the evaluated nuclear data file from, typically, U.S. GENDL is the Japanese evaluated nuclear data library. JEP is the European one, BRONDEL is the Russian one, and there are also the Chinese and so on. So there are several libraries and hopefully they should contain data which are consistent to each other. But in many cases, this is not so. The data, some of them are incomplete or they show differences, they are discrepant between each other. And this is, of course, because often there are not many experimental data available. So the evaluations are made based on experimental data and if they are not available, of course the evaluations cannot do. They try to do the best with models, but of course sometimes they cannot provide very accurate data. Evaluations. So in many cases these are clearly inadequate for the requests related to advanced nuclear technology. And, of course, evaluators are always asking for new data so they can improve their evaluations. And not only for long-lived, but also for short-lived lives. Here short means tens or hundreds of years, of course. Now, just to give you an example, this is a table for some specific isotopes and some specific reactions. What is, in particular neutron energy ranges that you see here, what is the current accuracy, which is, let's say, estimated on the basis of available data. And this is what would be the required accuracy for the design of new generation reactors. So you see that, for example, look at plutonium-242 fission, right now it's of the order of 20%. It should go down to 3%. So it's a huge effort that you need to do in order to decrease the uncertainty in these cross-sections. By the way, I'm putting many slides, some references where you can find additional information so you can find more details on the tables or the plots that I'm showing. Now, I will go very quickly in Europe. For example, there is a big effort which is financed by the European Commission in order to essentially stimulate new experimental activity, not only experimental activity, but theoretical activity aimed at improving the current knowledge of fission, neutron news fission, neutron capture or other reactions that are important for the development of new generation reactors. Essentially, there is a long list of reactions that need to be measured. And just to summarize, for the fission, you need to measure fission cross-section of actinides all the way from thorium to curium with a half-life from a few years on. So essentially, this is a big problem because look at some cases, some experimental challenges. Look at plutonium-241, this is only a lifetime of 14 years, but still the uncertainty right now is of the order of 10-20%, it should go down to 2-6% in the neutron energy range between 500 electron volts and 2 MeV. So it's a huge, wide energy range where you need new data. And the same thing for mediation-241, mediation-242 metastable, curium-244, curium-245. So these are not so easy to measure essentially because of the short half-life, which means that they are half emitters, it's a huge background in the detectors as we will see later, and it's not so easy to have high accuracy. But nevertheless, there is this strong need and this requires improvements in the experimental methods, in new facilities, neutron facilities where these measurements can be made. And in some cases, it will never be possible to measure directly neutron induced fission of these isotopes. So another possibility is to use surrogate, so-called surrogate methods, a technique that allows to measure, let's say, indirectly the fission cross-section. If there is time, I will give a few words on that. So now, let's go to the neutron sources. So you have several, of course, types of neutron sources. The most common one, the most, let's say, famous ones are the low-energy neutron beams from nuclear reactors. This is typically a neutron spectrum, a thermal neutron spectrum, around 25 milli-electron volts. And this can provide very useful, extremely useful data of thermal energy. You can also produce low-energy neutrons from accelerators.  Then there is a whole bunch of accelerators around the world that can produce mono-energetic neutrons. Now to do that, you essentially use protons or neutron-induced reactions on a thin sample, a thin target, let's say. Typical reactions used are DD, KB, DT, but very commonly used also for other purposes are the lithium PN reaction and the beryllium PN reaction. So you produce neutrons at a given energy or with a given spectrum, let's say. These require only low and medium-energy accelerators, a few MEV, let's say. You can change the energy of the neutron energy by changing the energy of the primary beam, primary charge beam. And you can go many cases up to 20 MEV. Then there is another set of neutron facilities, the so-called time-of-flight facilities, in which you produce neutrons with a wide energy spectrum and then from the time-of-flight you try to reconstruct the energy of the neutron. So you can study the cross-section, for example, as a function of the neutron energy which you determine from the time-of-flight. Of course, there is always a trade-off in these kind of facilities between the flux that you can get and the resolution of your neutron energy. Because to get a higher resolution you can go farther away from the source but you lose flux in this case and vice versa. In these cases, of course, you require pulse accelerators, so typically they produce lower neutron flux anyway. Now, again, you can have different kinds of time-of-flight facilities. Like I said before, you can use PN or DN reactions with lower medium-energy accelerators, pulse, of course. You can use a thick target to produce a wide neutron spectrum and also a higher flux. And then you can, of course, put some moderation in order to get energies down to thermal region. You can also produce another very famous, let's say, other famous time-of-flight facilities are based on electron beams. Typically, in this case, you produce neutrons through the gamma-N reactions. First, you have, of course, to produce gamma rays in a target with the IZ material, for example, uranium, from the electron beam, of course. And you can put also some moderation spectrum. So, the most famous facility of this kind is Gelina, that you will hear in the next few days here. I will not spend much time on this, but there used to be also orella in the United States. But, okay, right now, the most productive one is Gelina. And then there is the spallation neutron source. So, spallation neutron sources are based on high-energy protons, let's say, of the order of GEVs, which pinch on large blocks of AV material. And then, of course, you need also some moderation to increase the spectrum, the neutron spectrum. So, spallation neutron sources, the most famous ones are LANSK in the U.S. and TOF, J-PARK in Japan, GNEZE in Russia. Now, for those of you that are not familiar with the term, spallation is a series of reactions that occur following, let's say, the high-energy proton impinging on the material. So, you have intranuclear cascade in which, essentially, nucleons are at each other. And then, at the end, you can produce some nuclei with some excitation energy that evaporate. You can have some pre-equilibrium emission also. Of course, for these reactions to be effective, you need, first of all, the high-energy proton beam, but also you need large volume spallation target. By the way, if some of you are interested in spallation, which is a very interesting process, I would suggest this article from Goldenbaum. You can find it on the Internet, I think. Now, in spallation neutron sources, the neutron production depends, essentially, of course, on the proton energy and on the atomic charge and density of the spallation target. Of course, there are also other, as usual, there are other considerations that enter in the choice of the spallation target, like, of course, the radiation resistance, the cost, and so on. Now, just a few words on the Los Alamos facility, the LANSC, the Los Alamos Neutron Science Center. This is essentially based on an 800-mm proton on tungsten targets. There are few targets. If you send the proton beam on a target without any moderator, you produce neutrons all the way up to, let's say, 200-mm. If you put moderator, then you populate the low-energy region up down to, of course, thermal energy. So you can use two different targets, spallation targets, depending on what kind of neutron spectrum you like. Of course, this is important because in this center, they made a lot of studies, not only related to, let's say, nuclear technology, but also material science and so on for other aerosols, nuclear astrophysics, for many applications. Now, interesting enough, as I mentioned before, this is the neutron spectrum with the moderator. Another interesting thing that they do is in order to increase the neutron flux, they use a proton storage ring in which they accumulate several bunches of protons before they send them under the spallation target. And so you see that, for example, if you have 20 microamps pulse stacking, you have the highest neutron production, of course. So this is interesting, allows to go, essentially, to cover a wide energy range, although not at the same time, from, let's say, thermal to almost, essentially, a few hundred mEV. Another, let's say, this is a device, but it can also be considered a facility. There are some measurements that are very difficult to be performed because they require very intense flux, which is not otherwise available. So another technique is to use the so-called lead slowing down spectrometer. Essentially, here the proton, it's a target, which is surrounded by a big lead volume. So neutrons are produced in the spallation target, but then they essentially go around the lead, which has a very small, let's say, captured cross-section. So they do a series of inelastic and elastic reactions. In each interaction, neutron loses very little energy. So essentially, neutrons are trapped in this lead block. You see a simulation here. For one proton, you produce neutrons that fly around and they essentially are contained within this block. So you can, in this way, at any position inside the lead slowing down, get a very high neutron flux. Of course, there is a problem here because this is, you can still consider it a time-of-flight facility. You can still, let's say, obtain information on the time-of-flight of neutrons. But the energy resolution, the time-energy relation is somehow lost in, at least in, let's say, part of it is lost. So you have a low energy resolution, but you still can make interesting measurements which would otherwise be impossible to do at any other time-of-flight facilities for very small amount of material, for example. For samples of very small amount. Other facilities I mentioned before, well, apart from the low-energy accelerators, there is J-PARC, which is based on 3GV proton beam, 1 megawatt power. And in Russia, there is the GNS in St. Petersburg. Now we go to the end-of-facilities. So this is in the line of time-of-flight facilities. This was proposed in, let's say, 15 years ago, 2000 at Zan by a quite large collaboration for the field. It's about 100 researchers from different institutes, mostly European, but there is also a collaboration with Russia, India, Japan, and so on. Now, typically, the idea of this new facility was to do, was to measure neutron-induced reactions, neutron capture and neutron-induced fission, mostly, both for nuclear astrophysics. And this is, you will see later on, for isotopes typically between iron and lead, which are produced in stars by neutron capture reactions. Also some white elements of interest for nuclear astrophysics. This is also the region where fission fragments, the region of fission fragments. So these measurements here in this region of isotopes are interesting also for nuclear applications because, again, the cross-section for fission fragments are important for transmutation projects. And, of course, then there is the whole activity on actinides, capture and fission cross-section on actinides for advanced nuclear reactors. Now, I will very quickly show the, this will be shown also by my colleague later on. So how do we reconstruct the neutron time-of-flight? We have a proton beam, it's in the spallation target. Neutrons are produced and they fly in a tube for a certain length. You will see what it is now at the top. And then when they, of course, when they arrive on a sample, they produce a reaction. So the time difference between the arrival of the proton beam and the reaction, the occurrence of the reaction, gives the time-of-flight. And from the time-of-flight you can reconstruct the energy of the neutron, of course, with the classical or relativistic formula. Now, at the top, there are two beam lines. One is 185 meters. So this is a very long and which provides measurements with high resolution. And then there is another one at 20 meters that has been constructed just last year, has been entered in operation last year. And it's much closer, it's only 20 meters. So here the resolution is worse, but you have much higher flux. So you can make measurements that you cannot do in this other area. Now the facility at CERN is essentially based on the 20 GV protons from the proton synchrotron accelerator, which is, this is the map of CERN. Then they go more or less in this region, in this area where the spallation target, a lead spallation target is placed. And then there is a tunnel. CERN is like Swiss cheese. There are tunnels everywhere. And we did not have to make a new tunnel for the top. We used a pre-existing one. And inside that tunnel there is the vacuum tube where neutrons fly for 185 meters. And here on top now there is another experimental facility. So this is one thing that I should mention is that 20 GV protons on a lead block produce about 360 neutrons. Each proton produces about 360 neutrons. So you can imagine that you can produce a lot of flux. Now this is a layout of the beam line. So you have several collimators, shielding walls, sweeping magnets we will see later. And then the experimental area is inside the same tunnel.  Now at the beginning when the top was made, it was made very quickly. So we took some lead bricks, stacked them one on top of the other, put some water around for cooling and moderation. But that didn't work so well. So after three years the lead blocks were a little bit displaced and the proton beam had made a hole in the lead. So this had to be, of course there was some release of radioactivity because of oxidation and so on. So this had to be replaced in 2004. So we made a much more professional job later on with monolithic lead cylindrical block surrounded by water. And this is what we are currently using. This is let's say the design, this is the container, the lead is inside here. And this is the real thing that is now being inserted in the proton beam line. So of course to make a good proton beam you need the spallation target for sure. This is quite a big block, 80 by 80 by 40 cm square. This was the old one. Now it's about 40 cm diameter by 60 cm length. And then this is surrounded by water for cooling but also for moderation. Now we also have some different material for moderation, burated water. And then we have the 200 meters, let's say, tunnel. But you need also a lot of shieldings for neutrons, gammas, muons and so on. You need a magnet to deflect charged particles. And again, as I mentioned before, we need collimators. Now here is a picture of the collimator. There are two kinds of collimators, one with a small aperture and one with big aperture for fission measurements. I will show later. This is for example an image of the shielding iron wall for muons. And there are lots of muons and a reactor. So here I would like to show, to take you to a virtual tour of the facility. So we start with the, there is the spallation target which is of course surrounded by lots of shielding. And then this is the pre-existing tunnel with the beam tube. And then we go to 70 meters with the first reduction of the neutron beam with of course some shielding around. Then we fly some more, neutrons fly some more. Here is the first collimator that shapes the neutron beam. Then there is a shielding wall with the chicane to go through. The magnet that sweeps the high energy particles, charged particles out of the beam. And then eventually a second collimator here. And you will see now a wall that defines the experimental area where the devices, the detectors are. If you look at the design, essentially the neutron beam comes from here. The tunnel is a little bit, at the end curves a little bit. So the experimental area is essentially within the same tunnel. This is a sort of a, let's say a small problem, smaller big problem at the end top. Because we don't have much space, especially most importantly neutrons are bounced back and forth through the walls. And this increases typically the neutron background relative to other facilities. So this is the picture of the experimental area. This is the capture calorimeter that probably we will see in the next measure, in the next talk. And this is the neutron escape lane.  Now what is so special about the end top facility? Well, it all starts from the characteristics of the PS, the proton synchrotron, proton beam. This is high energy proton beam, as I said, 20 GeV. But it also has high peak current and a low duty cycle. So each proton bunch is separated by, consecutive proton bunches are separated by more than one second. Which is kind of, let's say, not so common in time of flight facilities. And what you produce at the end in the target plus moderation is a spectrum that has a very wide energy range. All these neutrons are there at the same time, let's say, from thermal to almost one GeV. You can have a flux, a neutron flux that looks like that with two peaks, one of thermal and one around one MeV. If you use normal water, but if you use as a moderator, more rated water, boron captures a lot of thermal neutrons, so you suppress the thermal peak. But this is the advantage is also suppressing the gammas that are produced in the water by hydrogen capture. And so you produce a different kind of spectrum of the neutron flux. Now the main features are the very high instantaneous neutron flux. So this is the main feature of the facility. You have essentially all the flux concentrated in bunches, which are separated by big time distance. So you can have 10 to the 6 neutrons in each pulse, and each pulse again after one second from each other. So this is very convenient, of course, for measuring radioactive isotopes. You can have all the events in a single bunch, very short amount of time, where of course you have a small background, integrated small background. And this is, of course, ideal for measuring branching point isotopes in case of astrophysics, or also for actinides like that I was mentioning before for nuclear technology. Other features are the highway solution in energy because you have a long distance. And this allows you to study quite accurately your resonances in the cross section. You have the wide energy range, as I mentioned before, all simultaneously. So all data at the same time you get from cross sections from thermal to GV. And the low repetition rate, which is another important aspect which one should consider, which is the suppression of the so-called wraparound. I will come back to this problem in a second. Now if you compare to other facilities, you see that Ntoph is not, in fact, as an, in average, a flux which is smaller than Lansk and Gelina. But if you consider the instantaneous neutron flux, that is the amount of flux per bunch, then Ntoph is comparable to Lansk up to a certain energy, and it's much higher, a higher energy. And, of course, it's a little bit higher than, it's quite a bit higher than Gelina. So this is a new facility that allows to measure radioactive isotopes, extend the resolved resonance region to higher energy, and especially measure fission all the way to several hundreds of MEV. And the second area will make things even better in terms of flux, of course. Now, there has been a lot of measurements made in over the years, in these 15 years. I will not go through all of them, of course. I will just quickly, since time is running out, I will quickly go through the experimental devices that are used for fission measurements. So first of all, let me say that, of course, in a neutron facility, you need to monitor the neutron flux. So you need some detectors. In this case, for example, we use detectors based on silicon, devices based on silicon detectors. You need capture detectors for measuring capture reactions. And fission detectors can be of different, we have used of different types, like parallel plate avalanche counters, fission ionization chambers, and micro-megas detectors. Now, of course, the basic concept when measuring fission cross sections is to detect the fission fragment. There are two ways to do that, to measure only one fission fragment at the time, or you can measure the two fission fragments in coincidences. You will see that there is, of course, a clear advantage in measuring in coincidences. You can, of course, use several choice of detectors. But one important aspect is that when you measure the cross section, you have to do it relative to another, to a reaction whose cross section is well-known. So you need to measure at the same time one of the so-called standards, which is, for example, uranium 235 in a certain energy region, uranium 238, or there are also other standard, this would be ideal, the elastics scattering on proton, neutron elastics scattering on proton. That would be the ideal measurement, but it's not so easy. Now, so at the end, what you really do is to measure the unknown sample, your actinite, for example, relative to a sample that is already well-known, whose cross section is already well-known. And this is typically a ratio, this is called a ratio measurement. This is very important because it minimizes systematic uncertainties related to the technique, to the experimental technique. And in principle, you can do a good job down to a few percent. If all the systematic uncertainties you remember, as I mentioned before, that is very important to keep all the systematic errors under control. Now, I will go quickly about this cross section. So this is a table of the range, energy range in which the reactions that I mentioned before are considered standard. Standard means that the cross section is very well-known, is accepted by the, let's say, the community as a reference. So, for example, the lithium-6 and T reaction is considered standard from thermal energy, 25 milliliter volts to 1 MeV. Uranium-235, which is the one that we usually use as reference, is standard at thermal energy. And then from 100, sorry, there is a mistake here, from 0 to 50 MeV to 200 MeV. So, from 150 KV to 200 MeV. And Uranium-238 from 2 MeV to 200 MeV. So, typically Uranium-235 and plutonium-239 are used as reference, are used as, let's say, standard measurements. And this eliminates the needs of many corrections and minimizes systematic uncertainty. Now, you know how efficient chamber works. So you have essentially two electrodes, parallel electrodes with some gas in between. Neutron, you have a sample which is attached to one of the electrodes. A sample is the fissile material that you want to measure, the material that you want to measure the fission cross section. So you have a neutron impinging on this sample, produces fission fragments. Or the sample can produce alphas by the alpha decay. So they release some energy, and this is, let's say, the simplest kind of device, but it's also one of the most powerful. Of course, in this case you detect only one fragment at the time, because the other one which is emitted opposite to this one is, of course, absorbed in the backing. It's absorbed in the electrode and there is nothing else to detect here. So this is one fragment detection, but you can still do a very good job. For example, this is the spectrum, the amplitude spectrum. For Uranium-235, you see the alphas are typically very low amplitude, and then you have the fission fragments. Sometimes you should see two peaks, but sometimes you don't, either because the resolution of the detector is not so good, or because the fission fragments don't release all their energy in the gas. But you can easily identify fission fragments, discriminate them from alpha particles. Things become a little bit more complicated when you go to a sample that has a very large activity, alpha decay. In this case, this alpha peak becomes huge. It goes out of scale, and you can have pile up of alpha particles or pile up between alphas and fission fragments. This complicates the picture, so you need to put higher threshold, you lose efficiency. You may also start getting problems of not controlling the systematic error related, for example, to the efficiency itself, or to the pile up. To the contamination of pile ups. Over the years, we have used several systems, certain TOF. At the beginning, we used fission ionization chamber that was in fact produced by our colleagues in Obnitzk, and collaboration with CERN. More recently, we are using micromegas detectors. I will give just a few more details on this chamber, which is a little more convenient. As I mentioned before, we used also parallel plate avalanche counters for measuring fragments in coincidence. Now, this is very interesting, and it's very nice because when you detect the two fission fragments in coincidence, you can reject much easier the alpha particles, of course, because alpha particles don't make coincidence. You have a very good rejection of the alpha background. You also have very low material around, so you have a very low sensitivity to gamma rays, let's say, or gamma flash, which is typical of the spallation. And you have also the possibility to reconstruct the angular distribution of this fission fragment because some of these electrodes are position sensitive. So you can give you the position of the fission fragments. This is a photo of the parallel plate. There is a stack of devices, and in between there are samples that we measure. Recently, there has also been a different configuration, which the detectors have tilted relative to the neutron beam by 45 degrees, typically. And this allows you to have a more complete coverage of the angular distribution. I will not go too much in detail. This is now the tilted configuration. Well, okay, not much time to go through these details. It's just a few words about the micromegas detector. The difference relative to the ionization chamber in this kind of detector is that there is some internal amplification of the essentially electrons that are produced in the gas. So this allows you to have a better signal-to-background ratio, at least relative to the electronic noise. But also, by tuning the gain, you can essentially discriminate better the alpha particle as well. And this I've already mentioned. So one final feature is that in a tent-off, we don't use very complicated electronics for our processing. We just take the signals coming from the device, the detectors with some pre-amplification or amplification, and we put them in a flash ADC. A flash ADC is essentially an oscilloscope where you record the shape of the signal and then offline, really construct it and you extract all the information you like. The timing, the energy and so on. So this is typically, for example, a neutron pulse. So you see the gamma flash which tells you that there is essentially a time reference. This is related to the arrival of the protons on the spallation target. And then you have signals related to fission fragments. This is a zoom of the signal. So then from the timing relative to the gamma flash, you get the time of flight and you can reconstruct the neutron energy. And of course, from the amplitude, you can see if it is a fission fragment or an alpha particle and so on. In data analysis, one of the important features, one of the important things you have to first do is a good time-to-energy calibration. And this is particularly complicated in a spallation facility because during the spallation process, neutrons lose some time. So essentially when they come out, they come with already a certain time delay which depends on the moderation that they have undergone. So you need somehow to correct for this effect and you do this through simulations. And on top of that, you need to also estimate exactly what is the flight path length. And you can do that with some, let's say, resonances, well-known resonances in energy.  One thing that is extremely important to consider is that when you go to high energy, you have to consider also the resolution function, the so-called resolution function of the neutron beam. That is, for a given time of flight, neutrons that arrive at a given time of flight have an energy distribution, an energy spectrum. And so this makes the rest, for example, if you take a resonance of iron, this is a captured resonance of iron, it naturally should look like this. But when you measure it, it is broadened by the resolution function of your beam, as well as by the Doppler effect. So you have to take this into account as well when you analyze the data in order to be very accurate in energy and in resonance strength. And then there is, of course, a problem of a pilup, signal pilup that you need to reconstruct and, let's say, separate possibly, or if you cannot separate, you need to take into account the dead time, intrinsic dead time related to the technique. So some correction is needed. Maybe I should go much faster now because there is, of course, the problem of dead time is one of the main problems in the data analysis. You have some events which are lost. You need to correct for those events with a certain assumption, with a certain formula. Now, typically, in the old acquisition systems, this dead time was of the order of microseconds. Now, if you record all pulses, one after the other, you can reduce this to tens of nanoseconds. And this, of course, makes the correction also much smaller, and so more accurate the cross-sections that you can detect. Now, I mentioned before, this is an important point, I mentioned before that one of the sources of background in fission cross-section, or in general, in cross-section measurements in neutron facilities, neutron time-of-flight facilities, is the so-called wraparound problem. So here is, for example, the arrival of a proton beam on target. And then you produce a neutron bunch. This contains neutrons of all energies, of course. Now, the lowest energy neutrons will arrive quite late may overlap with the fastest neutrons from following proton bunch. So they will appear as a background and will produce some events which are not, of course, real in this bunch. They are not related to this bunch, but they are related to the previous one. So this has to be corrected, and there are several techniques. One can use filters to kill low-energy neutrons, or another possibility is to determine the background by using threshold isotopes, like uranium-238, which does not have low-energy events at low-energy, low-neutron energy. But at the top, for example, this effect is not present because the distance between the bunch is much longer than the neutron bunch itself. The neutron bunch lasts 100 milliseconds, and the distance between two consecutive pulses is one second. So you have 10 times bigger distance between pulses than the duration of the neutron bunch itself. And now let's go a little bit more in detail in the measurement of the cross-section. So typically the cross-section is done, you measure some count rates, you subtract some background, divide by the flux, the number of atoms per bunch of your sample, correct for the efficiency, and also other correction factors for the time or anisotropy or anything you can think of. Now the idea is that if you measure something for your sample, and you also at the same time measure uranium-235, and you make the ratio between the two, what happens is that in the ratio the flux is cancelled out. So you take the ratio of the count rates, which is measured, the count rate for your sample, the count rate for your reference sample, and then you correct for some calculated quantities. Many systematic effects cancel out. In particular, you don't need to know accurately your flux, which is always very difficult to measure, and you also in the ratio of the efficiency is typically much better than knowing the efficiency itself. So the systematic effects are cancelled out mostly in the ratio method. So the measured quantity is the ratio of count rates between your sample, the new sample that you want to measure, and the reference sample, and then you multiply by a calculated quantity.  You simply multiply the cross-section of the reference sample, which is well known by this ratio that you have determined in this way, and you get the cross-section. So this is typically what we do at the end of, but also at other facilities to measure fission cross-sections. And as I mentioned before, it's very important to have this reference, this uranium-235 or plutonium-239, which is considered standard with cross-sections that are typically known within 1%. Now, well, okay, there's not much time to go. One thing that I should mention is that uranium-235 is standard only at thermal and in between 015 and 200 MeV. So what happens in between? Well, in between you have to rely on different standards. For example, lithium and alpha reaction in order to get a smooth, let's say, neutron flux. The reason is that in between there are lots of resonances and in the valley of the resonances the cross-sections may not be very accurate. So you cannot get, let's say, this ratio method will not properly work in a region which is, let's say, intermediate between thermal and 150 KeV. So you need a different method there. Okay, so lots of background measurements that need to be taken into account. Electronic noise. The most important one is certainly the alpha particles from radioactive decay of the sample. You can have spontaneous fission and of course you can have neutrons scattered by the detectors which are thermalized in the experimental area. Come back to your sample. You have wraparound neutrons that I mentioned before and you have to take into account also the resolution function. But the best, you can always calculate all these backgrounds and subtract them. But the best is always to try to minimize as much as possible these sources of background. And you do that by increasing the neutron flux which I guess minimizes the ambient background or the effect of the natural radioactivity or minimize the mass of the detector and the surrounding material. Okay, the uncertainty. I will just briefly and then I will stop. So we have measured several reactions at the top all the way from thorium to curium to 245. We have measured also some fission fragment anisotropy, angular anisotropy. We plan to measure some more isotopes now that we have a second experimental area with much higher neutron flux. And this of course will be the short lived isotopes like plutonium 238 which has only 87 years or even worse the plutonium 241 which has 14 years of lifetime. I don't have time to go too much to many of these details. Just a few examples. Look for example at the uranium 236 if I may use only 5 or 10 more minutes. So if you look at the libraries for uranium 236 cross section you see that the Japanese library had only one resonance in the cross section it was typically very low while the European and the American cross section had lots of resonances and the cross section was very high. Now look at the characteristics of the sample. You have some mass and so on but you also have some contamination of uranium 235. Now in our case it was very small contamination. Can you guess why there are so many resonances in these libraries? Maybe I can help you. Does anybody has a guess? They were based on a measurement in which the contamination of uranium 235 was higher and that had not been subtracted. So all these resonances were coming from uranium 235 not from uranium 236. So we measured again with a very low contamination and we found out that the cross section was in fact what Gendel predicted. Very low and with only a few resonances and this is one of the measurement of the symbols relative to the NDF cross section which was too high. So we have to be careful. This is satire energy. So you have to be careful. One of the most important features in the measurement is the sample. Purity, very accurate mass, very accurate homogeneity and so on. If you have contaminations you have to take them into account otherwise you are lost. I will forget about neptunium. See this is another case in which contamination is very important. This is americium 241 that we measured at the top. In this case as well there were discrepancies between libraries and we found out that even our sample contained a very tiny amount of plutonium 239 and americium 242 metastable. But the air cross section is much, much bigger than the americium itself, the americium 241. So you can see that it influences the results. So you need to subtract it in order to estimate correctly the cross section. This is just a few results I don't have time to show but you can see here that the end of results confirm some libraries while some previous libraries were completely wrong. Again in the americium 243 there were only two measurements. One of them was made with lead slowing down spectrometers of very low resolution. But again in this case there were lots of contaminations from nasty isotopes that had to be taken into account. Once you do that you find out the reason why there was a discrepancy between libraries or measurements before. And a very interesting case is the curium 245. So this is an extremely difficult measurement. The curium 245 is a relatively long alfalfa, 8000 years. But there is a contamination of curium 244, 6.6%, which is a much shorter alfalfa and produces a lot of alfalfa decay. And not only that but it produces also some spontaneous fission. So this is a very complicated measurement and this is why there were only few data for example of thermal energy with differences of 30-50%. Now of course in this case for example even at the top we were not able to get a very accurate estimate of the efficiency of our detector. Because we had to put a high threshold to kill all the alfalfa background. But the only thing we could do is to normalize our data to some previous measurement made at thermal energy. Fortunately there were new measurements made at ILL which is in Grenoble close by here and at mall even closer. So we normalize our data to these reactor measurements. And what we saw that there were only two measurements made in the 70s. I think both of them at Los Alamos at low energy and they were completely different from each other. You can barely see white is white, brown is green. Sorry for the colors.  And you can see libraries, the data were completely different. Now we have a better handle, we have a better knowledge. What we found out about this measurement was another interesting feature. At higher energy above 30 electron volt there was only one measurement. And this one measurement was made with a nuclear explosion, the neutron beam of a nuclear explosion. So it would be nice if somebody would volunteer. I could pass maybe the paper and somebody could give a seminar on how to make efficient cross-section measurement with a nuclear explosion. If there is a volunteer then we can give a report on that later on during the week. Anyway we found out that we agreed perfectly. The new measurement at ENTOF agreed perfectly with the old measurement made with the nuclear explosion. So what we concluded was that essentially ENTOF can provide similar results as a nuclear explosion but with fewer side effects. And anyway now it's not possible. There are many other things that we could discuss about. For example there are problems, we think there are problems even in the Uranium-235 cross-section between 10 and 30 KV. We are planning to measure that more accurately in the future. One important recent measurement was, a recent paper let's say, was the measurement of the ratio between Uranium-235 and Uranium-235. All the way to one GEV. There was a problem here because there were only two measurements. One from Lisowski and the other one from Sharbakov and they disagreed by almost 10%. So we measured more very accurately with different detectors, all the detectors we had in particular. And we found out that Lisowski and current evaluations are correct. On top of that we extended the knowledge of the fission cross-section all the way to one GEV. And you can see that some libraries, this is typically the ratio between the cross-section measured at ENTOF and a library. And you see the European library is pretty bad. The Japanese is not so bad. ENDF which is the American is very good. And of course they all stop at 200. This is an extension above 200 MEV, but it's not so nice. And we also have another model for estimating the cross-section and that gives good results up to one GEV. So I will stop here because essentially, well, okay, there are some more details on the angular distribution, but there is no time. I will just say that we have a second experimental area. In this case, the neutron beam is vertical. It comes from below. This is the experimental area. These are the service rooms, let's say. This is the building. The first beam arrived last year in, more or less, July 2014. These are some devices that were mounted for measuring the neutron flux. We also did the first measurement of fission cross-section in this second experimental area. This is a micro-Megas chamber that I was mentioning before. Now, a big advantage of the second experimental area you see here is the flux, which is more than 30 times bigger. On top of that, you also have a shorter time of flight. So you have a shorter duration of the neutron bunch. So the signal-to-background ratio improves by two orders of magnitude at most. And you can see the nice result here. This is the Plutonium 240 fission cross-section, let's say, measurement of the fission cross-section made in the first experimental area is essentially dominated by the alpha background, alpha pile-up and so on. These are the fission fragments. If you go to the second experimental area, now the alpha background is much more suppressed relative to the fission fragments. So it becomes now much easier to set the threshold and determine the fission cross-section. In fact, there will be a poster on this reaction, which is the first time it was measured with this accuracy. So I suggest you to look at this poster by Thanos Tomatopoulos. This is the picture of the experimental detail. We are planning to measure more short-lived actinides in this second experimental area. I don't have much time to talk about the surrogate method, but essentially this is a method that allows indirectly to determine the cross-section using not a neutron beam but a charged particle beam which produces the same compound nucleus. And then with some calculations, other calculations, you can go from this indirect measurement to the direct neutron-induced cross-section measurement. There are several examples. I don't have time to go, but this is a promising and interesting method. Not always, of course, can be applied. You need to find the specific reaction that produces the same compound nucleus, but okay. Sorry, I had to go a little bit faster because it was only one hour. So the conclusion is that of course there is a strong need for accurate new data, in particular on fission, for advanced nuclear technology. And there is a large effort in the international community in terms of improving the neutron beams, the facility, the neutron facilities, also the detection systems, the techniques and so on. Within this effort, we can inscribe also the end-top facility that was built in 2001 at CERN where several long-lived actinates have been measured, both in terms of fission and capture cross-section. Now we have also a second experimental area with higher flux, so this will allow us probably, most probably, to measure also some short-lived actinates. So I will stop here. Sorry for, thank you.