Alright, I'm going to get started. So good afternoon everyone. My name is James Stewart. It's a pleasure for me to be here. That's a picture of me on my bike. For many years I was a cyclist. And as you'll learn in my talk here, I'm a person living with multiple sclerosis and my life was changed pretty dramatically because of it. I wanted to give you a little bit of background. So what I'm going to talk about is about multiple sclerosis, and then also the mechanism of how they believe the disease of multiple sclerosis is working. What happens with it, how I'm going to talk about disability and how the disease affects people. And then I'll get into some of the medicines that are used for treating MS. And then I'll talk a little bit about the advocacy that I do to help find a cure for MS. And then I'll finish up with a few interesting research projects that are using those stem cells that we saw just a few minutes ago. My background is that up until the time I was 45, I had a very active career with a number of different things I studied at UC Davis and studied fermentation science, which is the art of making wine. But I used that and worked at Genentech, which is a pharmaceutical company. And early in my career, I help manufacture tissue plants, manage an activator, which is used to dissolve blood clots in the heart. So one of the big ironies that I experienced in my life here is that as my life evolved, I ended up becoming a patient that uses product that is made by Genentech. But in any case, I had a great career. And now it's about a quarter of my life that I've been living with multiple sclerosis. I was diagnosed in May 11 2007. And since then I've been working with not really employed, but helping to do advocacy with the National Multiple Sclerosis Society, and participating with Americans for Cures, which is an organization associated with CERM, which is the California Institute for Regenerative Medicine. And now I am serving on the UC Berkeley Stem Cell Research Oversight Committee as a patient advocate. So I'm able to look over research that is geared towards curing not only multiple sclerosis, but a number of different diseases. I wanted to clarify that you can see on this slide that I don't have, I'm not a doctor. I'm not a scientist per se. I have a little background in science, but I'm mostly a person living with multiple sclerosis and what I'm going to share with you today is really what I know about the disease from my personal experience. So, I don't know if any of you may have experienced or know somebody that has MS. But one of the things about multiple sclerosis is that it presents itself in many different ways for many, for different people, we're all different and we experienced the disease in different ways. Some of the common symptoms are that, in fact, one of the first symptom is a visual symptom where oftentimes people get blurry vision commonly in one eye. And it could be heat related, but you might also find difficulty just with with seeing what you're looking at on a computer, for instance. The other common problem that people first experience is what they call foot drop where your toe just doesn't quite pick up as you're walking like it normally would. And people end up tripping or sliding on this gravelly surface and not realizing why that's happening. But it's just that your muscles aren't coordinating. And so you end up tripping and falling. It could lead to walking difficulties. But as you see, some people might just experience depression, or some numbness, some people the first symptom, they experienced numbness in their face. And so it all depends on where the disease is affecting them. So primarily multiple sclerosis is a disease of the central nervous system. It affects the brain and the spinal column. And, you know, so that's where the disease resides and we'll get into more of that as we go along here. So it's, I have this point here is any one of these or all of them, it could be many of them, many of these symptoms that people have. And it's really the doctors concerned to figure out what's going on when a person experiences this and decides that they want to go to the doctor to figure out what's really happening. So one of the big things that also happens is fatigue. Many people, one of their first symptoms is just that they don't quite feel as energetic as they used to be. And you can see the dialogue here where someone is talking with a cyclist who's just really having a tough day. And, you know, it's what's what's wrong, and it's my multiple sclerosis fatigue. Someone else is saying, Well, maybe you're just tired, I get tired sometimes, and we all get tired. But this guy responds, I'm tired exhausted really, but it's, but it's more than that. His friend says, But you haven't done anything. He says, Well, thank you, I know this. That's, that's just the frustrating part of that. Oops, I'm sorry, I've hidden my screen here. There we go. And he says response a nap is needed your eyes are closing and the guy responds I'm not sleeping my eyelids are just heavy. It's hard to hold up. And that says I understand and he says no, no, you really don't. And I can really relate to this, the fatigue is something that it's just really hard to describe, because it'll hit you at any given day, or any given hour of the day. And it's really almost just staggering in its effect, it really is. It will slow a person down quite dramatically. All right. Multiple sclerosis was first described by this fellow Jean Jean Martin Charcot in 1868 and he realized that that it has something to do with with heat. And the problem that most people experience with MS is that when their body gets warm, the nerve conduction doesn't happen as well as it normally would, and it causes that fatigue that that I was just talking about. And they would test this in patients that they thought they would have that they thought would have had MS by asking them to sit in a warm bath. And if after 15 minutes in a warm bath their legs were weak, and they had difficulty moving them, then they would diagnose them with with multiple sclerosis. And then they described it as lesions disseminated in space and time. And really what that means is that you would have an attack or a lesion happening in one place of your brain or your spinal cord.  Because it's disseminated in space and time, then they would be clear that it was multiple sclerosis symptoms that they were that you're experiencing. And now, nowadays they use a spinal tap or an MRI picture of your brain to look for the inflammation that happens in the brain as a signal that you would have multiple sclerosis and because the MRI is recent, more recent development and technology, and it's becoming more widely used more and more people are being diagnosed with MS. There were other criterias for diagnosing MS that over the years and the more current one is this McDonald criteria that physicians use. The McDonald criteria, really, it's the best way now to describe or diagnose the disease. And because it presents differently from one patient to another, really what they're doing is trying to ascertain the difference in space and time. And they do that in this, there's a link here if anyone's interested. It's a pretty complicated process because they're looking at different parts of the body to see where the disease might be affecting them to come up with a diagnosis. So there's what's considered four types of multiple sclerosis. The clinically isolated syndrome or the early stage of multiple sclerosis is where a person would have their first attack. And that's where they would have that first instance of inflammation in the brain. And they would experience those symptoms that I was describing, you know, maybe a blurry vision if it's an optic neuritis in the optic nerve of your eye. And really what's happening with the clinically isolated syndrome in the past up until just a few years ago doctors would say, well, we can't really diagnose MS because we haven't had a second event in a different, in a different place in your body. So they would just describe it as a clinically isolated syndrome and they might treat it with some steroids. But then they would let you go and, you know, oftentimes the body is able to repair this damage. And so that symptom would go away. And things would be fine for a period of time. And it would rear its ugly head and come back and we would have another event. And at that point they would start to describe it as this recurring remitting MS where you have, you have an attack. And then the issue goes away. And I'll, I have more slides that'll share more information about these different versions of MS in the coming up. Then there's another version of MS that they describe as secondary progressive MS. This is where you would have an attack, it would resolve, then you would have another attack. It would resolve, but you might have a third attack and it was resolved but unfortunately the disability starts to increase. And the ability, the recovery isn't quite as good as it would be in, in recurring remitting MS. So the disability starts to add up and they describe it as secondary progressive MS. And the fourth type of MS is this primary progressive MS where people experience just a continual degradation in inability where they might have an attack that doesn't quite resolve, but things just generally get worse over time. And so that's described as primary progressive MS. And these are defined by lesions in the central nervous system. And right now, there's not really a clear understanding of what causes of lesions. They have lots of theories about what causing MS but really they do not know that the actual cause, and they're thinking that it may be related to stress or some infection. And there could be, they've studied genetic predispositions and they've learned that there are 200 variants of genes that that increase the likelihood of having MS. So, so as I mentioned, there's really don't know what causes MS. And there, this is a picture actually a self portrait of my, my brain with arrows pointing to some lesions that developed for me.   And the cerebral spinal fluid, you know, is, is really a clear liquid it's, it doesn't have any blood in it, it, but something crosses over that blood brain barrier, and gets through that, that cerebral spinal fluid and gets into the nervous tissues that are really your axons and, and nerve cells that your brain is, is consisting of. So they're thinking that, you know, again, exposure to toxins might be a cause. We really don't know what the trigger is. And there's lots of research going on right now about the gut microbiome connection, where they recently came up with the idea that this type of perfringions toxin is a bacteria that may be living in the gut of people, or that is infecting in the gut of people living with multiple sclerosis. And that toxin apparently has fingerprints that look a lot like the myelin that coats the axons and then in the nerve cells. So they're able to that toxin is able to cross over the blood brain barrier and cause the infection that may be happening in people. So, and there's also some role of, you know, the B cells with MS the idea is that the body is an autoimmune disease, and the B cells are crossing over this blood brain barrier to attack the the whatever the infection is caused by, and that's causing this inflammation. And so they're thinking that possibly B cells are just randomly getting through the blood brain barrier and just starting to attack myelin, but they're not sure exactly why that happens so that's where they describe it as B cell dysfunctionality. And then the other part of our body that happens, this is normal where we have a ligand endocytes that remyelinate our nerve cells. And that's a process that happens. So, if there is damage, there's a process to fix it. And that maybe that process isn't working as well as it should be, possibly the ligand endocytes are being held back from remyelinating by astrocytes that are also cells that are in that area of our body. And there could be other T cells and T cells are part of our immune system, and they could be having a role of identifying the myelin that's coding the nerve as as an invader, and possibly they're signaling to the B cells that there's something here that needs to be taken care of and the B cells are honing in and doing the damage that they're doing. And there could be also a role of microglia as as we're when we're born we have just trillions of brain cells and there's lots of connections that are made and over the years that we're growing in our youth. Those connections are are are trimmed, if you will, and microglia are doing that they kind of kind of snip areas of the brain that are not being used so it kind of explains for instance why some people are able to, and when they're younger years or it's much easier for them to learn a foreign language, our language areas of our brain are developing in that period of the years of our life, but after the microglia have clipped those sections of the brain where if we're not using that foreign language says well we don't need this area of the brain and then it goes on and saves it for other other use. It's an interesting process our bodies are capable of doing. So here's some multiple squozes interesting facts. There's over a million people in the United States living with MS. And it affects women, three times more frequently than men. So there's something going on with the female anatomy that is potentially influencing the disease. There's I mentioned earlier the MRI sensitivity is showing that there's, it's being used to find more people living with MS. So the, the rate of MS has risen but possibly not. It's possibly just because we have the tools to help learn which people are affected by the disease. I mentioned those four types of MS, but there's a, the European Committee of treatment and research in multiple sclerosis ectroms. They have proposed a new way of classifying MS and they think that it's, you know, basically, one disease process that's happening, just showing itself in different ways in different people depending on their body makeup. So to further complicate things, scientists at Tisch, they're in New York. They think that primary progressive MS is its own disease, possibly immunoglobulin G driven. And that could be why people with with primary progressive MS have a more severe disease course. And each of these different exhibitions of the disease kind of lead to the need for personalized medicine to help people that are affected by by MS to be treated effectively for their own personal symptoms. So recently, just in the last two years there's been a lot of learnings about MS. And one of the more exciting studies that was done. And Science Magazine published the data about this was that they did a study in the military. People when they joined the military they have to have their blood sampled to make sure that they're healthy. So they're able to take blood samples from just thousands of people. And what they did is they studied those patients over the years. And they were able to follow them. And some of those patients ended up with Epstein virus, and, and then they followed they continued to follow them. They learned that those people that did experience Epstein virus, many of them went on to develop MS. And so they're that study really found this link between Epstein virus and MS, which is a very important discovery. And the idea here is that the, you know, the Epstein by virus is somehow your body is fighting it off. And it's somehow entering into the B cells. And part of that Epstein bar virus RNA, if you will, the rabbinic acid is incorporated into the B cell. So that B cell then starts to look like it has that Epstein bar virus in it. And that same protein is what's involved with the myelin. And so our body ends up becoming a little confused as to where what is the myelin and where is the Epstein bar virus and, and it essentially starts to learn to attack the myelin because the Epstein bar virus presence in the B cells. So that's kind of the theory. So, and you can see that the medium time from the first EBV positive sample to MS onset was five years so it took a while for the body to develop that sensitivity. And one of the things that they learned also was this this biomarker. They call it neuro filament light chain is something that can be used to monitor this Sarah conversion where they're able to see that that Epstein bar viruses is is infecting in the in causing an infection or a reaction in the in the central nervous system. And as you see this is very recent study 13th of January, just last year. Just this is a slide that just kind of shows the epidemiological dispersion of MS, and it's more happening in the northern and southern latitudes. So you can see in the red here. And then also down in New Zealand, where more people are at high risk and the theory here is that possibly vitamin D or exposure to sunset sunlight, or lack of that is is really causing our body to be more sensitive to that infection. Well, in the middle part, the middle latitudes here don't experience MS as much for some reason, and they don't really understand why that is. So switching gears, I wanted to talk about some of the people that have MS. Here is a list of a lot of famous people that that have MS. One person that I'm particularly interested in was Selma Blair, she, many of you, she was recently on the cover of Vogue magazine actually, or one of the covers I guess they have many covers, and she was brave enough to do a stem cell study where her body was ablated of the immune system and then they re-injected stem cells into her that they thought would help her and she claims that she was helped by that, but I have another slide later in this presentation that shows how that affected her. But so she's a more one of the more famous people that have lived with that are living with multiple sclerosis. And, you know, so a lot of people that are famous are affected and otherwise some not so famous people as well. So this slide here is a slide that shows some data that is really my own personal experience with MS. You may have gathered by the earlier images I was a cyclist when I was younger, and I enjoyed cycling to a great degree I live here in Sonoma County in Northern California and we just have a wonderful place to ride bikes. Lots of hills and just beautiful vineyards. And I really took advantage of that when I could. I was able to do these century rides so I would ride a century ride is where you're riding 100 miles and I was able to do that I, but, and then I also rode my bike to work. And this graph here is really a graph of how many miles I rode in a given month. And so you can see I was a really active cyclist some months I would ride over 350 miles and in one month. There were a few times where I experienced some issues that I was thinking maybe I was riding my bike too much and this turned out to really be one of the first symptoms that I experienced with multiple sclerosis. This arrow here indicates where I was riding to work. And, and I would, of course, when you're riding a bike your body temperature heats up, and I would get to work and I noticed two things one, I would look at stops lights in the distance and out of one I would see the red and and yellow lights changing but out of my right eye, I would look for the red and the green and they were kind of gray. So the color perception wasn't right. And then, by the time I got back to work I would sit down and take a shower and get it, get over to my computer and look at my, my emails and I couldn't really read out of my right eye so well there was blurry. And so I went to the doctor and I said something's not right and they said well it's central serous retinopathy. And which is a leaky retina. And they said it just causes this blurry vision and it'll go away and sure enough it did. So you can see for about a year later in the latter part of 2003. I also had, I was cycling and I noticed my leg cycling up one of the hills nearby, and I noticed my leg was tremoring in a funny way it was just really shaky. And so I thought something's not right. I just blamed it on cycling too much. So then I got excited to do another century ride. That was this one over here. But then I noticed things were getting a little bit more difficult. And I actually ended up changing my job location. So instead of writing to my workplace that was about 12 miles away. I started writing to a workplace that was about seven miles away. So that's where my riding distance started to diminish. And I ultimately ended up changing jobs at this point, where I started working on the Boeing 787 aircraft with a company that supplied conduits for the landing gear. And it was about that time when things really got rough for me, because I was experiencing this new job it was a stressful change for me. And I started to experience some depression, maybe because of my job change. But, but really what was going on, and I didn't know it at the time was that I was living with multiple sclerosis. And at this point, I was diagnosed, and two days after I was diagnosed I started the first treatment, which was an injection, a daily injection of an interferon that tightens the blood brain barrier, basically making it more difficult for B cells to get into the central nervous system. And then I, you know, continue to do some rides. I really thought that cycling would would help me feel better. Exercise is a, is a recommendation for, you know, if you want to maintain your body in a good way. It's good to exercise and I really tried hard to do another century ride this one here I wrote about 50 miles I couldn't do the hundred. And then I was on this medicine for a long time, steel experiencing difficulties with just my ability to get around. And my doctor realized that my disability was increasing even with that medicine. And they changed my medicine to this or the moon is I started taking copaxone, which was another injectable. That drug is one that instead of tightening the blood brain barrier, it is putting a mile and like protein in our in your body, just everywhere so it's a decoy. And the idea is that your B cells of fight will go after that that mile and like protein that's injected in you and leave your nerve cells that are coded by my own alone. And so that's the idea of that medicine. But, unfortunately, they're about they, I actually stopped working because of my disability started to really ramp up. And actually this is a good point for me to point out at the bottom of this slide, I'm showing the EDSS scores that I had. And here's another slide that I'll explain this a little bit further but my EDSS scores were going from from zero to one to two to three, and all the way up to four here. After I stopped working, I switched over to guess what a medicine that I didn't have to inject myself with. This was a pill. And they that was really hopeful because boy, not having to inject yourself every day is a real treat. So, but at the same time, I was, you know, really hopeful that that would make a difference in my life. And that's when I did the last bike ride fundraiser with the MS Association. And we saw the picture of earlier of me cycling. And I was able to ride, I lived near a park and I would was able to ride for quite a while. Just a 12 mile loop, if you will, that I did consistently every day thinking that that would really help me, and it did. I think it really delayed any real further disability. But unfortunately, it just got harder and harder for me. You can see this bottom graph here is then the frequency of rides and it my frequency went up there was actually one year here that I wrote every Monday, Wednesday, Friday, for an entire year. And that 12 miles and it did help, but at the end here towards the time when it was started to rain and in January of 2015, I realized that it was really more dangerous for me to, and I could injure myself pretty seriously. And coincidentally, so that's when I stopped riding and coincidentally that's when my doctor said, gee, this Jelenia is not working for you. So I wanted to start taking an infusion of this medicine called Rituxin, and that's the medicine that that Genentech manufacturers. So I'm going to move on off of that. And just talk a little bit more about the theory of what's happening to explain the MS progression. You can see that it really affected me in my ability to do things. So they're thinking now, and this is just really recent thinking over the last two years is that the Epstein virus causes that immune response. The blood brain barrier breakthrough. It causes mitochondrial injury. There's these inflammatory events that happen that activate the B cell response. The allele activation decreases the immunosuppression and causes cytokine production, which causes inflammation. And then the other thing that happens is these ion channels start to not work so well on the ion channels or what's transmitting our nerve signals. The nerve signals are just not getting to where they need to be. And that it would explain why when you're walking the signal to lift your toe every step you take is just not happening. And it just gets there a little bit too late. And so it's because of this ion channel deficiency that's happening. Dendrocytes might be in secreting cytokines and that's inhibiting the oligodendrocytes from remyelinating the cells. And then there's other structural issues that are happening causing that inflammation to become more, more real. And then the loss of my own induces what this axonal degeneration where really the axons aren't working anymore. So I'm going to show you a few slides here of again more pictures we saw the self portrait of me, but here are more indicators of where the grain matters changed in the brain when that inflammation starts to happen. The idea is that the inflammation starts and the demyelination starts to happen. And then it leads to this axonal loss that's indicated. These are nerve cells. And then there's another picture of this model that kind of explains what they think is happening. This Epstein virus, bar virus infection, getting into the B cells. And then this molecular mimicry that I described where the body starts to think that the myelin is part of this B cell infection that it has a desire to, to fix. Parts attacking the myelin that's where these little ridges here that are kind of oddly shaped our parts of the myelin that have been impacted by the B cells. And there was also a paper just describing how primary progressive MS might be a little bit different. They're, they're just realizing that there's a lot of differences with primary progressive MS, and they have a lot more to learn about it. Because there's something else going with primary progressive MS that's not clear with the recurring remitting MS. So I'm going to assume that the scientists have come up with to kind of show the picture of what's happening. The yellow is a nerve cell. The blue is in the liquid dendrocyte that's remyelinating or myelinating that nerve cell. The B cell sends out antigens they started attacking that myelin and the astrocytes have a role. You can see that up here. The blue here is depicted in this part of it. And here's where the nerve signal transmission is just affected by the, by the sodium and potassium signaling that our nerve cells do. And this is more description of that what I just showed you on in the pictorial form. I highlighted this one section because it really explains that fatigue that happens in so many people with MS. And it's just that the energy requirements increase due to disruption of that, then myelin loop that's caused by the beast cells that's attacking the myelin.  And you can imagine that happens every second, millions of times every second as we're moving around. And is that disruption that's happening where our body senses that it's being disrupted and so it sends a little bit stronger of a signal to say put your foot when you're walking be sure to lift up that foot and it gets very tiring. So I mentioned earlier about the expanded disability status scale. And here's really what they're what the physicians are looking for. This steps of one through four. It really shows people that are describes people that are able to walk fine. But they're also seeing where, you know, the doctors are observing other other deficiencies and so one of the things they might do is just ask you to close your eyes and, you know, touch your nose. It's a coordination issue that they're checking or another thing they would ask you to close your eyes and stand on one foot. And these are things that most normal, normally, people can do these things but with a person with MS, because they might have a little bit of loss of balance. It shows that it's not quite working quite right. And that's where they start to realize that that something's not not right. They start associating an EDSS score with that. Unfortunately, the MS disability in many people it kind of continues on so it starts out in this area here where everyone's able to walk just fine, but they're, they have the disease. It slowly but surely affects them and I showed that in that earlier slide with my cycling endeavors where the EDSS score would increase and ultimately it got to the point where I was using a cane and that's about when I started to when I stopped cycling. And unfortunately for me it's gotten a little bit worse still after even though I am taking medicines, Rotexin medicine to do, this is a disease modifying therapy that slows down this disease. I'm at a point where I need to use a walker and I'm trying to stay away from having to use a wheelchair, because you know if you, my thinking is, if you, if you don't use it you're going to lose it so I try to keep walking even though it's very difficult for me. And a little bit further on that EDSS score. This is what they're looking for, and what I kind of just described. So you can kind of guess. I'm over here at about six and a half requiring I need to walking aids which means two canes really to for me to walk without without a walker. And I'm trying to stay away from this seven where I would be in a wheelchair. And unfortunately it gets worse for for many people. And this is even with the disease modifying therapies that that we take. So I wanted to go a little bit further into the descriptions of those four types of MS, just so that we know a little bit more information about each of those symptoms. The first one was clinically isolated syndrome. This is where you would experience those those problems that we've been talking about. Maybe a walking difficulty or some people might have a bladder problem. All of a sudden they have this urgency where they have to urinate, or they might have a dizziness problem. All of these things are where you would have these symptoms lasting for at least 24 hours. And it's just one episode of this. And the now that they have the MRI they might show one area of myelin damage. And then they would see, you know, where there's more myelin damage, if there's more than just one area that would indicate that they're more developed or further along than this clinically isolated syndrome. Here's relapsing remitting MS, it shows where you would have a relapse, and then it would remit. So the relapses are where there's exacerbations. And then you would have a problem so maybe one is an eye problem. Another one is leg weakening another one is numbness in the face. And the idea here is that because you are taking these medicines, these disease modifying therapies, the conditions are improving, and it's kind of delaying the worsening of it. And ultimately, this could continue to get worse. And it develops into this secondary progressive MS. And this is marked by these frequent exacerbations where, you know, just problems are happening more frequently. And, you know, also steady progression of the symptoms. So, you know, this is a steady progression, primary progressive MS where things just slowly but surely get worse over time, you might have one attack or an issue with something else that's happening. And, but generally it's slow and steady progression with no remission periods, so it's not returning back to what it used to be like. It's just continually getting worse. And without these relapses. When they happen, they're generally what doctors will do is prescribe steroids, and they slow down the inflammation, and they make you feel pretty good about how you're feeling so that reduces that inflammation that kind of puts a halt to the inflammation. But it's there. The disease is still happening in the background. And there's something they call pseudo exacerbations. And this is where you would have relapses and that are related to heat or exercise or, or even illness that if your body temperature gets raised by by a fever it really affects people with MS. And there's no cure for MS. And all these desired disease modifying therapies they slow the progression of MS, but unfortunately it doesn't stop the disease. I wanted to show you a little bit more about the medicines for MS. Over the years, they, they started out thinking that it was inflammation related to our diet. In the 1950s, they gave suggested that people go on to the swank diet, and we're still seeing that diet is an important factor in in helping people live with MS. When I was on bed of serum that was developed in 1993. So, most of these medicines have are currently just recent developments, Rituximab I mentioned I took that one and also copaxon you can see that these are really recent developments. And some of these the big thing here all these were injections. And the big news, as I mentioned when they came out with gelinia and that was a big treat for us to put on these injections that suddenly we could have medicine that what didn't involve injections. And then they came up with the Rituximab is an infusion but they started realizing that that infusions might help people in with the disease and they came up with some more medicines that are infusions. And only in 2017 that they came up and approved a medicine called a crevice. This is also a genetic product that is for primary progressive MS up until this time there was no medicine, or disease modifying therapy available for people with primary progressive MS.  And that's how it's working. All these other medicines do the same kind of thing depleting the B cells. It's about 10 minutes to noon here I'm going to go quickly through a few slides. There's, these are more, more medicines that I wanted to show you just the pricing of these medicines. It's very expensive these treatments $111,000 for the for the beta serum. This is an annual price. So, people that live with MS have a huge burden. It's just, it's not just the disease modifying therapies, but it's also, you know, the medicines that are prescribed to treat the co symptoms that happen with MS. So I'm thinking and idea of those. These are all those symptomatic medicines I just mentioned. So, you know, some people have depression so they're having to get some paxil or some balta. You know, for fatigue they might get pro pro vigil or riddling different medicines for different problems that they might also experience. So it's just not the, it's not just the disease modifying therapies they're needed to purchase they're getting these other medicines as well. So my suggestion if you do have MS or if you know anyone that does please suggest that they take a disease modifying therapy. And what about prevention. You know they're working on a vaccine against Epstein virus and the other idea is to reduce stress there's there's a real thinking that stresses part of it. So, go get some sun. And, and then they're talking about the diets again. This is real recent that they came up with some suggestion to go on a keto, excuse me a ketogenic diet high and omega three is olive oil avocado nets all those good foods, and then the physical diet is still important but they suggest doing yoga massage is really helpful for people that experience spasticity that's muscle tightening that happens with because of the inability to relax the muscle and meditation is also really helpful for people. Okay, and then I just get I'm getting towards the end here of my presentation, but I want to mention the importance of advocacy. I worked with the, I do advocacy with the National Multiple Sclerosis Society really to get funding for for MS research and then also with Americans for cures this is the California Institute for regenerative medicine. And here, here we in California we voters approved at five and a half billion for stem cell research. And I was part of that effort to get that, get that bill passed. So, and this is just showing some of the latest theories that they're looking at. There's a lot of talk about this Bruton's kinase inhibitors. They're still working on more, more treatments. And a lot of them are due to National Institute of Health funding fact almost all the therapies that I was talking about earlier are resulting from from that. There's also funding for research that's done by the National Multiple Sclerosis Society. We're doing this, this project that is essentially looking for cures that are there basically trying to coordinate all the researchers to find cures. And there's some funding. This is shows you what the CERM funding did over over 11 million dollars funding for research at various organizations related to multiple sclerosis. And I didn't need to click on that. I'm not sure how that happened. Okay, let's do that. And then there's from the National Multiple Sclerosis. This is the pathways to the cures. There's just a whole bunch of research that's happening with stem cells actually as well as just other projects. So, just going through these quickly you can see there's just lots of research happening all over the United States. And these are coming up with some, this is a recent study with stem cell reports that came up with this. They're learning that fractaline enhances a ligand dendrocyte regeneration and remyelination. So these are things that really could help people living with MS. And you can see there's a lot of projects, 87 of them just looking at how do we reverse the symptoms and promote wellness. And that's really the issue for people with MS. All those disease modifying therapies they slow down the disease but they don't repair any of the damage that's happened. And that's really where this research is focused is to try and make it so that our bodies get back to normal. I mentioned Selma Blair. This is a picture after she had her immune system ablated really, you know, caused her some challenges. But she says it helped her. And most promising with stem cell therapy is that they have this idea of doing mesenchymal stem cell derived neural progenitors. The idea is to inject these into the space in the spinal canal where people would essentially have these stem cells injected in their spinal canal. And they find that that's really helpful for people. So this is where the latest and greatest research is happening. And there's some great tools for scientists to use to discover more cures and that's exciting for us as well. So there is hope for people living with MS. If you're one of those people just keep in mind that they're doing a lot of work. And they're getting really a lot closer to finding a cure for MS. There's a study in this ATA-188 that's pretty promising. We'll see what happens. There's some citations here just to show where I got that information. And I also want to point out that there's multiple sclerosis support organizations around the country and around the world really that help people living with MS. And World MS Day is coming up on May 30th. So please, please note that and support it in any way that you can. So it's an exciting time of the year. So let me stop here and see if there's any questions in the chat. I know we're running a little short on time but hopefully we can, I can look at a few questions and, and get some responses. Okay, let me, I'll leave this cartoon up there while you're on looking at the questions. So, hi there Nick. I see that you had a point there. Is MS affected more predominantly from environmental factors or genetic? So yeah, Lesina, that's a really great question. And this really what they're trying to figure out. I don't think that there's a genetic component because people that it's not true that people that have MS are going to have children that have MS. So it's not entirely a genetic disease. But I know of people who who have two people living with MS and their family. There's some things going on, and it could be genetic. And they're also thinking, and I showed you in that slide that there is a genetic component that they think might be explaining the sensitivity that leads to susceptibility for environmental influences that could be the cause of MS. So, I, hopefully, I've, I've answered that one. And then, oh, you have more comments here. I believe that T cells, let me sort of, you guys can read it as well. So, okay, this is interesting. I've heard a lot about the theory of T cells being a big part of MS, and the cause of MS. And there is a company that is working on that Atari therapeutics I mentioned, they, that at 188 and the idea is that they can use the T cells to, to essentially fix the B cells that are infected, these antigen presenting cells. So this is a really great question. There's lots of technical details here that maybe I can follow up on this offline. Right. Are there any other questions. Well, I, I suppose there's not. And we're right at the end of the hour here so I think our timing worked out pretty well. I just want to thank you. I also want to thank Shay and shop for setting this up it's been a real pleasure to share my MS journey with you, and I am, and hopeful that we find a cure for MS real soon, and so that I can get back on my bike, and get out there and ride and I wish you all the best and success in your endeavors to pursue your careers and in nursing and doing what you're all doing. So thank you very much, and have a great rest of your afternoon.


Hi everybody, Joe for Jazky's CaseRace.com coming at you with some Panini VIP National Exclusive Gold and Silver Packs, 25 Gold Packs, 20 Silver Packs, all card ship using our college rules if there's players in their college uniforms, and one spot gets you four teams on this big list here.  We got Jason down to Sean, two and a three, five times for the teams, one, two, three, four, and fifth and final time. Got T-Wolves down to the Tampa Bay Rays, alright so again I'm not going to read off all these names but I'm just going to show you the list as is, and kind of slowly scroll through it so you can double check it again if you want to when we upload the video, but then I'll alphabetize it by your first name so you can see all of your teams grouped together. So remember there is a all other not on list spot, which is usually the, what's the usual case for that, it's probably the soccer players in their national team shirts. There's a NASCAR racing spot as well, although I think it's all NASCAR, there's no others, not like there's NHRA or anything like that in there. Alright let's sort by column A by your first name, so Alan Matsui, there are your group of teams there, Ben, Chase, Garrett, Jared, Packers, Raptors, Blazers, Tigers, your last spot Mojo teams, Jason, the X-Line, Lawrence, Matinee, Michael P, Nick, Robert, and last but not least, Sean Healey. Alright so trades are allowed, obviously trade at your own risk. We're going to pause the video when we come back, we're going to see if there's any trades and we'll have the break. Stick around, BRB. Alright, welcome back everybody, no deals were done, so the list you saw on the previous screen is officially printed out and remains the same. Thanks everyone for getting in on it, appreciate it, appreciate you. Alright we'll start with the 20 silver packs, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 makes 20, good luck. As you've seen the silver packs are in a paper stock, first card is usually a non-numbered card unless it's a rookie like that Evan Mowley will get to in a second and then the second card usually is a numbered parallel and all cards ship, so we've been lucky enough. Most of these breaks, I mean it's just like any other break, they'll be good ones and bad ones but for the most part these have been delivering some pretty nice hits. And since they're exclusive to the national, you know obviously depending on the player but most of these players, especially the more desirable ones, the hobby hot players, will definitely get a little nice boost in value on the secondary market if you're into that sort of thing. Let's go, let's get on with it, there's Dane, there's David Beckham for that all other spot to 99, Kenny Pickett to 499, Freddie Freeman to 199, Javari Smith to 10, Henry Davis to 199, Mac Jones to 99, Tom Brady to 199, Buccaneers edition of Tom Brady, Javari Smith your what, second or third overall pick, your third overall pick is a rocket that's going to go to Alan Matsui as the Rockets, nice low number there, Kenny Pickett for the Steelers, that's going to go to, let's go, Matinee with the Steelers, nice rookie Kenny Pickett, Freeman, Freddie Freeman, CD Lamb to 199, nice Julio Rodriguez, Scotty Barnes rookie to 50, Justin Jefferson to 199, there's Jabari Smith again to 99, Bobby Witt Junior to 199, Royals that'll be for Michael P with the Bobby Witt Junior, your reigning NBA Rookie of the Year, Scotty Barnes, it's Jared with the Raptors, a little dino DNA to 50 and your presumptive AL Rookie of the Year Julio Rodriguez for the Mariners, next to 499 that will be for Chase with the M's, next group there onwards, Acunha Junior to 50, nice Wander Franco, Jonathan Taylor to 199, Seiya Suzuki to 99, Riley Green to 199, Aaron Judge to 25, he's Raking, Vlad Junior to 199, there's Evan Mobley, John Morant to 99, Steph, Steph another Evan Mobley, nice, even better, who's got the Cavs, that will be for Garrett with the Evan Mobleys, Cleveland, this is for you, that's Evan Mobley to 50 and then this Evan Mobley to 499, 215 out of 499, nice, Aaron Judge going to Lawrence and the Yankees, the Yankees played today, did he hit another home run, I think he's at 45 now, we'll be keeping track of the Aaron Judge, Aaron Judge Homer watch, no Yankees game today, but Aaron Judge went 1 for 2 with a solo shot, Wander Franco Rookie card to 499, goes to Sean Healy and the Rays, alright, and now, let's go for the gold, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1, 2, 3, 4, and 5, to make 25, now the gold packs are canary seed that they use that Prism card stock, ooh, there's a thick card right there too, so the Dreams game onto the background looks really nice, yeah, J-Dog, it's a light day on the baseball schedule today, so, right, another thick card, that's got to be fun, I want to go to one of these field of dream games, whenever that may be, are they doing another one next year, I would imagine, oh that's right, I think Rex mentioned this yesterday, it'll be unlikely to hold a field of dreams games at Iowa site in 2023 due to construction, Frank Thomas, who's part of the site's ownership group, addressed local reporters on Wednesday, blah, blah, blah, the festivities Thursday night will have to hold fans of the event over for at least two years, as the game apparently won't be returning 2023, baseball hall of famer Frank Thomas, part of the complex as an ownership group, told the Des Moines register that construction will mean no 2023, it's a lot going on Thomas said, they don't want to come back if the stadium is not prepared, Thomas is referring to plans of the site to put in youth baseball and softball complexes, construction slayed to begin this year, this does not take with possibility the game returning in future years, so in all likelihood the game will be back on in 2024, you know what Brace for Life, guess what, if you click the break schedule that's pinned in the chat and dropped in the chat frequently by nightbot, you can see where it says click the link for break schedule, shipping info and more, you can click over to the shipping tab and you can know exactly when things are being shipped out, it'll give you sorting statuses, pending statuses, all sorts of statuses that you can get for that, all for you, that way you can check on that every day to see when your stuff is going to be heading out to you, there's to tease junior to 15, nice low number for the Padres, that'll be for Jared, yeah Brandon the Dodgers are insane right now, they've been playing well without a full strength team and Dustin May is supposed to be making his way back by this weekend maybe, or early next week so that's gonna be a big boost wherever he is, long reliever maybe, starter, might get stretched out to be a starter, there's Trevor Lawrence, or I think he is being stretched out to be a starter, so I think he will be starting, it's Walker Bueller that might not be because he's, Walker Bueller may come back in September, nice Trevor Lawrence is by the way for Garrett and so he might be in that sort of Julio Urius role from a few years ago, sort of a, which would kind of be crazy to have Walker Bueller coming out the bullpen, that Damian Lillard giraffe print going to the trailblazers, it's for Jared, but yeah Dustin May should be coming, that should be a big boost for the rotation, it's Kauai Leonard to 50, Kevin Durant, these hyperparallels also not numbered, but that goes to the NASCAR spot, Steph Curry to 99, Warriors, and behind David Beckham is Vlad Guerrero Jr., nice two-color patch, three out of ten, nice low number on that as well, Blue Jays, that's gonna be four, for Lawrence with the Blue Jays spot, nice, that's right, yeah, Gino saying, hey some mobiles, some Trevor Lawrence's can't complain, here's a Mack Jones for the Pat Riots, Matt Ney with that, it's Bobby with year 9-9, and another Trevor Lawrence, rookie card for Gino, there you go Garrett, yeah, I definitely pulled that one, that was nice, that shield, pretty awesome, Danica to 99 for the NASCAR spot, wow, and a hyperparallel Trevor Lawrence, another one for Gino, VIP pack, the hyperparallel, I always think look really sharp, should be a big year for him, got Bryce Harper, Holstein Cow print, we got a Cade Cunningham as well, for the Pistons, there's a Kunio Jr. to 50, and that will be for Matt Ney with the Pistons, Bryce Harper for the Phillies, that's gonna be for Robert, and behind Dylan Carlson is Emanuel, clickly, quickly, not clicky, not clickly, quickly, it's pretty solid, and that is six out of 25 for the Knicks, that's gonna be for Alan with the Knicks, nice, and last couple here, George Brett and Denny Avicia for the Wizards, and there you go boys and girls, I'm Joe for jaspyscasebreaks.com, we got more of those gold and silver packs in the store, so go and check that out, I'll see you next time for the next break, bye bye.


Good morning, we are if you're an arm first of all, thank you all for being here early morning and Well, we are running a ball later from zero we are a theorem arm from Spain Hope you find this workshop very useful for you all and we have a little suppress in the end So I truly recommend you and deeply recommend you to stay till the end So Mr. Diego Lozada and my colleague Fernando they will run this workshop. So let's go for it and work a little bit. Thanks Hello Thank you Thanks for attending Before getting started with the with the workshop a little intro of what we do Yeah This is why we are here. I mean We want people to run notes at home to run to a stake at home where it is By running anything on our min-match or by running an app node or by running a client by yourselves Whatever It's very very important for for the decentralization of the of the network so this ski and That's it if I ask if I may ask how many of you are run a Know at home Not bad Validator right and With these kinds of devices with low power and and resort construct devices is Very good Very good So what we provide we provide a plug-and-play image So it is very easy to start. It's just you just need to flash our micro SD and and start the device and Pretty much it configures everything and you have a valuable all the Ethereum clients for start And you can run on a full node in a few commands. We will see this later Okay, that's how I was saying This is what the the image does so It's quite quite easy Current available for Raspberry Pi and rock 5 Rock 5 is not yet available. Okay. It's Being released this month. I think Why run And if you know on on these devices Affordable, I mean It's cheaper than other other solutions Spends little power There are performant these devices are powerful Particularly now the the rock 5 is is a power super powerful device They are focusing on one task mean No graphical environments no web browsing Nothing just It's focused on running a node. So you have all the resources available for that It's small you can put it in any corner of your of your house next to the router or whatever and It's based on on the RM. So it's good for From our security perspective Running several architectures This is what the image does again automatic installation includes all major clients and the client runs through system D devices, so they are pretty much easy to To manage and we include monitoring dashboard based on Grafana. Well, what happened was much Hardware requirements got a little higher So we are getting some issues with the with the Raspberry Pi 4. Actually we just Being able to to sync a node with get unstable and nimbus. I think this will get better About several weeks because the client teams are working on unimproving the performance and and doing some optimizations we see The rock 5 is running great. I Show you later our validator at home. It's running a best way and take a and it's doing great So this device can run pretty much every client Everything in client. It's it's super powerful Yeah, this is what I was saying Get unstable plus nimbus. This is the only combo that that actually works and The rock 5 see that it's powerful 16 gigabytes of run NBME of course Pretty much amazing so I'm taking over now to Fernando before starting the The node setup because We get a lot of question that is important for us Why should I trust your image is an image? They are bananas. So Fernando will walk you through our report to do to do this yourself if you want How we package All clients how do we make the image so Okay, I think the first question is should you trust us and the short answer is no, you shouldn't You shouldn't trust us. We are going to provide you all the different clients In a way of a Debian package and And you could ask, okay, why I should Trust you How do I know that you are not changing anything in the code or you are not changing anything in the package? You are then trying to tell me something or doing anything back But the short answer is you could do it at home using cloning this repository in a very easy way That's our main goal To could do all the same that we do and create your own image With and without need anything from us only ruin these these Sorry, we will document this. Okay. It's it's in our to-do list to Open a develop section for you to to follow our follow-up and and make all of them. Okay Yeah First time we're trying to do all in a very automatic way very easy and we provide a background image I don't know if you know vagrant vagrant things are brought to from Hasikop open-source product Who tries to to create a developer environment in a very easy way in a very programmatic way? I can show you our Not here Here you see anything Okay, that's that's the vegan file the vegan file the only thing that's do is prepare an environment In order to create all the packages. Okay, it's a very easy and problematic way to do so Do you ask to the ground to create a? Wuntu Machine and install all the software that you need to create the image All the packages are based on the work of this guy from Jordan Caesar I don't know if I promise okay his surname But this guy creates a very nice way to create to automate the creation of a devian package or a p.m. Package Or whatever you know, so using his work Is For us is very very easy to create any any package. So if you clone this or repository Do some very simple command big or not You create a bigger machine with all the code inside for example Here you have You will have to enter in this Directory FPM package builder and inside you will be a folder for any client that we support For example, you should see the good Folder here is Very small and simple Make file and with this make file you will create the same package. We are providing you in our repository there is Simplest idea is go to the github and from the people from go ethereum Obtain the version Obtain the Subversion that the package has and create our rpm. The only thing that you are going to do is don't know at the latest binary the last time binary for the For for our arm with this binary and this folder structure you will create a Deviant package the only app for our site is This is more System day unit you are to be more easy to to use to software you could do System start system stop is to restart for the software All the configuration also is included. It's a basic configuration simply you will learn Get and we will launch we will launch a get with This flat metric expensive because we use later Prometheus and Grafana in order to show you the ticket statistics and you could see Later in our Grafana Environment is also good in the image. So you could simply go to a rebel Simple a simple get if the github is not probably the speed of the Wi-Fi is not fast enough to see it But the only thing that is gonna be is open Don't let the latest binary and create a devian package. This event package We will provide you in a form of our devian repository, but you if you don't understand you could do it yourself or you could check if the M if the M think is md5 some is the same from our repository and your Your pockets and we'll see We will not change anything in the in the official binary Okay, let's start. I don't know 14 seconds and The the skip will do all for you will create your your devian package and you could use it offline and not trust our repository it's simpler your Official binary with system D file system D unit Also we provide the same for the for the SD match we went to wait these three seconds Okay, and then you will be we already don't eat before training Here you will have your devian packets for the get Very simple. It's pretty easy. It's not Anything strange here. It's only the devian package in order to create it more easily and for the for the For the wound to image that we're using for all of three devices is almost the same thing a small make package Not make file story that here we will don't know at the latest want to available for for arm and Unzip it Here we disable the automatic categories because If we don't do this the first room is very very slow because one dish will try to great in the first room And probably if the matches are be told We will last for very very minutes or even hours And the only app that we do is at this small city locker in this earthy locale is all the major queries here And It's all the logic we will create a partition for you We will create all the needed users and permissions in order to this package room with the configuration that we made and In I think in a very simple way you could do it at home Do not need us for anything. You could create your own image. You could add your own So far if you want to create your own package if you don't trust Archer repository That's the thing that okay, you shouldn't trust us, but you can see if we are Doing anything wrong or we are cheating doing it at home in a very easy way Okay, okay. Thanks, Fernando Let's fire up a note We will follow the official our official documentation as you can see it's a pretty straightforward Process first you will need to download our image. We already did because you know, it's here We unzip it All these punches are here You see and see we will flash I have a here a A micro SD so Was the was the flash process end You just need to make sure that you Attach an internet cable the DSSD in in the port in the blue port the blue port and You put a micro SD in in the slot and just that pull the device and the on the first boot our Put the street will pre-configure everything and Install all the all the software necessary to run a node and creating the keys for the validator So once you After maybe 10 minutes The the device will restart and you will be on a recent On a machine that is a pretty much configured for for running a and if you know, okay So Let's wait for for it for it to finish or I may be I don't know how much can take this Okay, so We will be connecting to an AWS machine because we need to to connect remotely and it's more comfortable because it's It's more It's more it's it's quicker Sorry, it's faster and but it's arm-based. It's exactly the same that you will Get with this with a raspberry pi or a rock pipe. We also provide AWS image if you want to try or imagine in in your account is a One click away from is just Launching a command. I will show you the config file So you can see all flags that it's needed to run a client again the token The checkpoint scene I was saying Is this URL? So let's launch The service and let's see what happens it's gonna start you see that already Block and state from the checkpoint It says that yes, there's an execution endpoint, but it's not thinking it's not thinking so It's gonna start telling the execution line what to do, okay, and That's it for fire up a note You have an execution layer a Consensus layer you start the both services and Without rematch, it's pretty much what you need to do to to launch a note. Okay Is that easy? Again, like I said in the intro and raspberry pi now just things with Get unstable and like sorry and nimbus because yeah post-merge hardware requirements went went a little higher. So We need to wait. I think a little Fortifications to come from from from client teams and I think It will be able again to sync with other clients, but we'll see we are not sure of that The rock the rock 5 is running fine. I mean Post-merge pre-merge. It's a very very powerful device and it is drawing rate So and Let's go to the validator and as you can see You just need to create the keys and and running a command to import the the validator keys in the In the in the consensus layer so We can go to the second path from the foundation you can see here all the steps that you need to follow and Pretty much everything that it's here. It's already done. I mean an execution client is configured you can choose from from all these four Again You are good You can choose from any any client as well Again, you are done Validators, let's try our one by the top again this You now need a tool for creating the validator keys. It's already installed Actually is Is this one possible? So we can Launch this command straight forward As if you don't account see if you lose it Okay, that's a English English password This is a password for Your key store. Okay Yeah This is these are your keys please don't lose this okay write them down and Keep them because without this you will not be able to withdraw and That could be a problem Yeah, but this Okay, let's confirm. Okay These are as you can see now you can you have the validator keys here The deposit data that you will upload in the 32 is deposit and key store where your keys are okay, so Let's import them So We have the validator keys are raised up So we just need to Start the service at here It's ours. Okay, here it is one validator available. So You just have to go Here know what you're doing a blood here this This file deposit.  I can maybe Copy and paste here. Okay. It's fine. And now the more fun process that it's sending 32 if and pray for to the gods that It's gonna be fine because it's a it's a lot of cash I mean and That's all I mean It's as you as you can see is it's a simple process If you have some Linux skills is is fine, I mean But you can do it without any other skills as well if you follow the documentation and I think We are done with this let's see Running So The rock 5 yes Let's connect to the rock 5 Yes, we are going to show our Validator running in three validator right now with a rock 5 With For five right now is cheaper than the Raspberry Pi 4 even and probably twice or three times powerful. So Okay, I recommend the nation right now is going to for a rock 5 whenever it is available again You can see here the motherboard is running a rock chip and You can see here to java Processes that are basing in teco. So let's see This is a wallet value. Don't you see that it's actually published in the stations? It's running right now. It's running five and The rock 5 is is running both both clients in At the same time and and with no problem at all. I mean, it's a super powerful device You can we can see a bit this as well Now you see it's in sync. It's working perfectly and Again, this device is not yet available, but I think we Have contact with the manufacturer. Actually, this is a prototype from And They are already releasing a batch we have five in its way, I mean I Think that it will be available pretty soon and Super powerful device super a useful device for for running an Ethereum node and Hope they released it this month. Okay, so What's left? The last thing, okay Now I will post it to it Okay As I told you at the beginning of this workshop, there is a raffle right now. So if you want to participate Diego is going to post in Twitter. Are you ready? Oh, you already did. Okay. Thanks If you follow us in at Ethereum on arm, you just need to post something like No Okay, you have to post I attend to the workshop and I want to win something Okay, that's something is a raspberry P4 okay, and From now on put the counter in three minutes We're going to stop five five minutes really okay five minutes. We're gonna stop and Somebody wins something today He told me five minutes So just only three Yeah, okay, confirm five Yeah, I was going to sell yeah does anybody here I'm pretty sure that Anyone here has any question or yeah, okay? What will the rock five sell for how much would it be? $189 but you need NBMB disk so it will be a little higher and you need Power device and a micro SD. I think it should be between one 350 or 400 I mean cost total cost Well, I have four questions. Yeah, try to be quick. Do you recommend using? WS instance Against running your no, okay. No, no, not at all. No, this this was for for the workshop We don't we don't want People running notes on AWS because that that's not the central way of doing this Okay, and what advantages do you see in running around validators instead of delegating the stake in? Well, because it's very important for the network actually There's a problem with Centralization in these large pools. I mean, it's very important that people stick at home because if one pool or several pools want to take over the network, there is this other army of nodes that it's from the people mean and It's very very important to fight against these kind of attacks to just take at home Okay, and what measures do you take at home to ensure up time to ensure up time? Well, we have SIS AI I I mean one thing that I I Want to say is that it's okay being a lot of line because the protocol is very generous I mean the the penalties for being online offline and sorry are very low So there's no problem for being offline you can be Online 95 for 99% a whole year and you have we are good. So Don't do don't overkill. I mean don't do which I don't don't automate things because You can be slasso It's okay being offline Thanks Sorry One thing that I do that I find is quite good is do this come with Grafana. Yeah enabled Yeah, so in Grafana, you can add the telegram group as a as a notification point And you can set up an alert on like critical log So it sends you a telegram message. I find that's like a really really easy way to just to know when things are up Paul from from lighthouse thing Okay, next one I'm just curious what your experience is if you have Like run on specifically a bit more constrained devices like the Raspberry Pi like which of the implementations are the most efficient in those circumstances on ARM devices on there, but sorry Like which of the node the softwares do you find run the most efficiently on? Okay, yeah Yes, it's very performant. It's very is very optimized and Regarding courses layer. I will say nimbus because nimbus uses Very low RAM memory. It's amazing and but anyway a pretty much Besides Ergon that you know that executes pretty much all the blockchain or blocks And this you and they could that Java base it and they are they are a little heavier The other client prism like house nimbus get never mind. We're running fine. I mean, yeah, I Thank you very much. Love the talk love the work Do you have any plans for saying like MVB boost or anything like that? Yeah, we are we are a We already package made boost, but We are a little concerned because they are not every release, but they are ready sensor in some transactions and We prefer to wait It works. I mean it works fine and you can even have a Raspberry Pi 3 maybe or This kind of devices because it's very light, but we are a little concerned About centralization and sensory and no and transaction sensors Thank you Hey Are you cross-compiling when you see no, no, no official binaries The only exception is Ergon because they don't provide the binaries. Yeah, and sorry So I noticed that you're using swap. How is that impacting the IEO on the You know, I'm the swap for the Raspberry Pi is Necessary because you know eight gigabytes are very tight and it's created on the on the USB SSD. So yeah, it's not the It's not the better solution, but it's needed. So Yeah, it's something that we need to do. Okay, and I'm all questions right there. Okay Thank you on a device like the rocks five Do you have any recommendations about the number of validators that it should should have is there a Recommended limit before you see CPU binding. I had to say we are running free, but I think that It will be able to run a lot. I don't have a figure to give you but I think that a lot I Thanks for presentation. I came a little late so much for if that was discussed Do you know if somebody working on incentive? Program or protocol similar to helium where? Individuals takers that can and approve that they're running in a location that doesn't have high density Gets a little bit of incentive. No I'm sorry. No, okay, because that would be helpful for decentralization. Yes. I guess. Oh, yes, but I Have an opinion about that because I don't know It's You know sometimes you you cannot answer all but always a point to learn. Is there any other question? Yeah Right there So for the Raspberry Pi for you sets you use SATA I'm not mistaken with the computer module you use like SATA over us over USB, right? That's your setup Us be yeah, but for the compute module with the IO board you can actually connect it connect You can use NVMe as well Try it out you can yeah, you can do you can do that help with any of the performance issues You've made it like it's very similar. I mean doesn't make a difference I think what if the if some of the performance issues are because of IO stuff then it might help. Yeah, but you are You know they use B3 is the button here, so No, but so the compute module has Support sorry, I don't sorry. Sorry. I didn't misunderstand. We didn't try the computer model. No, we didn't try it But I guess it will be we'll be better. Yes. Yes Thank you one more there Right now of time maybe one or two questions Just really quick a follow-up on the USB 3 thing. Do you have documented wish USB adapters works? I also wish USB 3 as the modules The best option from our experience is Anesthetic bridge Which is a little device that connect This is a SATA to to USB 3 that works very well You can use use portable usb's Such as crucial or or Samsung t5 t6 7 T7 Has a little uses but Yeah, you you can you can actually a Use a lot of a lot of options, so it's difficult for us to to test everything but Recommendation our recommendation is is that the bridge? Yes, it was great What's your opinion on shared pools taking? We are but if we are big fans of rock pool Actually, we are in contact with Joe clappies from the pool they are running Rocket pool in the rock 5 as well And yeah, this is This is a way of lowering the 32 barrier In a decentralized way. Yes, it's very nice. I am we are big fans of Rocket pool. So yeah, we recommend that We have time for one or maybe two questions anyone Nobody everything is clear share No, it's not in the no, it's not computer. I was asking if you have the graph I know It's Because the port of you know, you have to connect to the three thousand port and we can't okay So as I told you before We're given a gift This raffle so someone in here is going with Something pretty interesting the raspberry p4 for free, of course so winner is And just trash prepare for Preparation prepare something sorry we can see we are running a Random number don't be tricky We can see it in the screen There are nine participants Should all happen and number two just pay them number two and it's cool Arturo Arturo After he's gone, maybe There's not here Okay, he went away for so the next one is Number eight is fingers crossed if you see here Alex Alex mad whoa Winner So first can explain you yeah Yeah Okay, congrats, so Thank you for and and Diego It's been a pleasure to show this Their knowledge and and all of you this morning. I just want to remind you that will be tomorrow downstairs at the booths with our Well, you'll see perfectly if you run on arm. Okay, and we're gonna be there if you I don't know if This tonight comes up any father question will be there The whole day, right? Yeah. Yeah, so thank you all and I don't know if you want to add some words Thank you Okay, thanks guys. Thanks a lot. Thank you. Thank you


Hi, everyone, Joe for Jaspie's casebreaks.com. Happy Sunday, a lot of NBA playoff action happening. My Lakers stealing a win in Memphis. Happy about that. Happy about this break being done as well. Big thanks, everybody, for making this happen. Prison pack number seven. And at the end, we'll re-randomize everybody's names. And we're gonna randomize you a team that's gonna unlock Pick Your Team 11, which is coming up in the next video. Big thanks to Matthew, Ryan, Ben, Brian, Jason, and Ron. Thanks to you guys for making this happen. Appreciate you. Let's do the pack break first. Let's roll it, randomize names, and teams three and a two, five times each. One, two, three, four, and five. And a different dice roll for the giveaway part. You know what, Gabe? I don't know. Gabe's asking, because I was watching a little bit of the Dodgers game before I switched back over here. How did Tyler Hero break his hand? I saw the Yanis fall. He was grabbing his bottom, his tailbone or something like that. Three and a two, five times for the teams. One, two. All right, there's the first half of the list right there. No trade windows in these filler packs, most of you know by now. There's everybody else right there. And let's just print and rip. All right, happy Sunday, everybody. Hopefully everyone has been responsible and have done their taxes. We've got Marcus Morris Sr., hyper parallel. AJ Griffin and Jaren Jackson Jr. He had a great game against my Lakers today. There you go, all right. Let's go to, let's flip back to the screen here. Let's gather everybody's names again, one through 30, new dice, new list. And we're gonna match you up with the team. Good luck. We're just randomizing names, not teams as usual. Let's roll it, randomize it, one and a four, five times. So it's gonna be top 10 after five we'll get a team in the next break. Good luck, one, two, three, four, and once more, fifth and final time after five. So from 11 through 30, sad times, but I appreciate all of you getting in. Top 10, happy times for you. You've got teams in the next break. Matthew is happy, so is Ron, Ron, Ron, Ron, Matthew, Matthew, Ron, Ron, and Ron. Ron definitely had the odds on his side after five times, there's the top 10. Oh, let's just show you what teams you got right here as well. So this is from Prism Pack number seven. So we'll put those next to your names. Ron, congrats, you got the Pistons. You also have the Rockets and Mabs. Matthew, Nuggets and Nets. Ron, Bucks, Pelican Sixers, T-Wolves, and Matthew with the Clip Show. There you go, gang. I'm Joe for jaspyscasebreaks.com. I'll see you in the next video. Bye-bye.


For one heartbeat electrical activity arises in sinoatrial node, spreads to atria via inter nodal atrial pathways, travels via cardiac conduction pathways that is to atrio ventricular node, bundle of his, its right and left branches and the purkinje fibers. The spread of electrical activity is basically depolarization of the heart muscle. Now before going into the details let us see a bit of anatomy. SA node is located at junction of superior vena keva with the right atrium and AV node is located near the inter atrial septum. SA node is connected to AV node by three bundle of fibers arranged from anterior to posterior that is the anterior inter nodal tract, middle and posterior inter nodal tract. AV node continues as bundle of his. It gives off a left bundle branch and continues as right bundle branch itself. These branches and their further small branches run below the endocardium layer of heart muscle. Actually heart muscle has three layers right? Inner most layer is endocardium, middle is myocardium, outermost is epicardium. So the fibers run below the endocardium and meet purkinje fibers. So how the electrical potential spreads throughout heart? Action potential originates at SA node moves via atrial inter nodal tracts to AV node. Now since cardiac muscle cells are connected to each other by gap junctions the potential starts spreading to other cardiac cells also since ions can pass via gap junctions to other cells. So potential spreads via the conduction pathway and also along the atrial muscle cells via gap junction. It takes only about 0.1 seconds for the activity to spread to atria. Now conduction in AV node is slow and there is a delay of about 0.1 second here. This is known as AV nodal delay. After this the depolarization spreads via bundle and its branches first to the left side of interventricular septum at midpoint of septum moves to right and then further spreads down the septum to apex of the heart. Then it turns back and reaches atrioventricular groove. Because of this last part of heart to be depolarized is posterior basal part of left ventricle. This whole process of ventricular depolarization finishes in 0.08 to 0.1 second. Also if we consider the layers of heart remember that these fibers run subendocardially? So electrical activity moves from endocardium to epicardium. During all this process do not forget that heart is a sensation because of gap junctions and electrical activity spreads to other muscle cells via gap junctions. Then you may ask that if potential can pass via muscle cells then what is the need of the conduction pathways? Well there are two things. The spread is faster through this conduction pathway so it facilitates rapid depolarization of heart that is rapid spread of electrical activity. Secondly from atrioventricles the activity can spread only via this conduction pathway since atrial and ventricular fibers are separated by a fibrous tissue ring. This is also important physiologically because it helps in spacing the depolarization of atria and ventricles. Otherwise both of them will contract together which we don't want in heart. These fundamentals we will again consider in another video on ECG and then in arrhythmias but before finishing we will also consider abnormalities in conduction pathways and diseases which may occur. Now remember that apart from SA node each part of conduction pathway is capable of generating electrical impulse but SA node generates impulses at fastest rate that's why it is known as pacemaker. Also in abnormal situations even myocardium can generate electrical impulses. Secondly also remember that one spread of action potential means one heart beat one contraction. Now let us discuss some abnormalities. Diseases may occur either due to abnormality in generation of impulse or in conduction of impulse or both. So it is occurring at various levels. First let us see SA node. Diseases may affect SA node leading to decreased generation of nerve impulse and may cause severe bradycardia. Second there may be conduction block from SA node to AV node and below. Now there are levels of this block. When there is simply slowing of conduction from atria to ventricle it is known as incomplete heart block. Another level is when there is complete block of conduction from atria to ventricle that means no impulse which is generating at atria is reaching the ventricles that is known as complete heart block. Now incomplete heart block also may be of different grades. The first grade in which it causes prolonged duration of conduction only but all the impulses are being conducted to ventricle. Second one there may be missed beats. So like two impulses are getting transmitted to ventricles but the third one may be missed or there may be another pattern like three impulses are getting transmitted but every fourth impulse is getting missed. So these are two different grades of incomplete heart block. Now if we combine these incomplete and complete heart block we can say that heart block has different grades. Only prolonged duration of conduction is known as first degree heart block. When some beats are missed in between it is known as second degree heart block and when there is complete block of conduction from atria to ventricles it is known as third degree heart block. Now incomplete block ventricles beat at their own slow rhythm known as idioventricular rhythm. This may occur either due to AV node disease or a block below the node. The block occurring due to AV nodal disease is known as AV nodal block and that occurring below the node is infranodal block. In some cases rate of heart beating may be so low that it leads to decrease in blood supply to brain causing fainting attacks. This condition is known as Stokes-Adams syndrome. Heart blocks can also occur due to bundle branch block where the conduction till bundle of his is normal but below the conduction is affected. Apart from this abnormalities in generation and conduction of impulses can occur if there is an abnormal focus apart from SA node which is irritable and generates action potential. Now here since myocardium is a syncesium that potential will also spread to the heart causing extra beat. If abnormal focus is too much active and its frequency of generation of action potential is higher than SA node it will cause tachycardias. These are known as peroxismal tachycardias and depending on the location of the focus they can be atria ventricular or nodal tachycardias. Next there can be reentry of potential. See normally there is a particular direction in which the electrical activity travels and you see once a spread occurs it does not spread back because the muscle cells are refractory that is during an electrical activity they do not respond to second stimulus for some time so they are refractory. Now if there is a channel established such that current flows in one direction travels via another path comes to original pace after some time such that the cells are no longer refractory then it will depolarize the cells again and it will keep moving in a round round circle that is known as circus movement of the electric current. That ends our video on generation and conduction of electrical impulses in heart and the abnormalities which can be associated with it so if you like the video please do subscribe to the channel and don't forget to hit the bell button there down.


I just finished an hour-long workshop for teachers at Camp Plug & Play in Tucson, Arizona, and the workshop is called Google Forms and Sheets. Teaching just got easier. You could take a screenshot if you'd like. Learninginhand.com slash easier are my notes from the session. We have some people lingering around in the room, and I thought maybe it'd be a great way to wrap up and reflect and share what we've learned. So what did you learn about Google Forms? I learned about add-ons and just different ways to make my life easier as a teacher. Had you used an add-on before? I had just learned about them this summer, but I've never actually employed them in my classroom. And so the add-on we used today is probably the most popular one called Fluberu. Can you tell us about Fluberu? Are you excited about it? Yeah, I am. Because it's a really nice way to be able to collect all the data from assessments or assignments and get a really quick snapshot of what your students are doing, how they're doing. Yeah, and somebody's asking, is your head exploding right now or it looks like it's intact? It's intact, but inside it's a little sketchy. And you have a great handout. What did Tony Vincent give you when you came to the workshop? A sticker? Yeah, when you come to my workshops, I always give stickers with a web handout. So learninginhand.com slash easier, you've got it there. So what was a surprise to you about Google Forms tonight? Ooh, Google Forms. I think the buzzer was a surprise. Is that Google Forms? Yeah, yeah, that was a form.  Can one of you go to TonyV.me slash buzzer so we can show our 26 viewers how he did that? What I demonstrated was if you wanted a classroom buzzer system to see who buzzed in first, oh, TonyV.me slash buzz, I bet. That's what it is. I have a short URL to it, TonyV.me slash buzz. And it's the simplest form you ever did see. There's a buzzer picture, but then all it asks for is your name. And when you are about to ask a question verbally, students put their name in and they wait to click submit. And if they think they know the answer after it's asked, they click submit. And then on my end as the teacher, I can see who buzzed in first. So it's a makeshift buzzer system. It's one of the unexpected ways we use Google Forms. Yeah, that was fun. All right, how about over here? What's your reflection about spending an hour learning about Google Forms? I feel more comfortable with it now because I've never used Google Forms before. So I have a lot more to learn. So you got to see me create a form live and then send it right out to you. I made it look a little easy, probably, but I've used it a lot. And play with it and try to figure it out on my own. And you have a great handout to help you. And the neat thing is so many people love Google Forms. Like I said earlier, there are YouTube videos like crazy demonstrations of how to use it. All right, got anything to add to all this? No, they kind of took it all. Hey, nobody mentioned Word Clouds. What did you think of that? Oh, I liked it. I like that they can personalize it and make it their own if I were to do it with a class. Yeah, so how to collect text through a Google Form and then just copy that column of text and put it into one of a variety of Word Cloud generators. And you've instantly taken student submissions and turned it into a cloud. A person to pick on, Sarah Crawford. So what was unexpected for you tonight? The buzzer was my favorite because I like to play games. I was really excited about the buzzer. I also am interested to find out more about the other add-on super quiz that works Yeah. So I'm excited that I have this resource to come back to to explore on my own when I have more time. Excellent. Cool. Our pre-show, we had Chocolate Nachos and they look like they are all gone. Were every single, they're in your belly now. All right. All right, well it's late here in Tucson. I think it's 7.30 p.m. and we had a little evening session and all these teachers here are at our week-long tech camp. And so they've got more learning to do tomorrow. So I will see you later.