All right, welcome everybody to the November 16th hyperledger technical oversight committee call. I think all of you have been on the call before, but just as a reminder, two things that we have to abide by. The first is the antitrust policy that is currently displayed on the screen. And the second is our code of conduct, which is linked in the agenda. For announcements today, we have the hyperledger definitely developer newsletter that goes out each Friday. If you would like to include anything in that newsletter, please do leave a comment on the wiki page that is linked in the agenda. The second announcement is that today there is a workshop. I think it happens two hours after this call. If I get my, no, an hour after this call, I think it is. So if you still do want to attend, please do click and register and attend the meeting or the workshop on atomic cross ledger transactions between hyperledger base and corda ledgers using hyperledger cacti v2. And I feel like there was another announcement I was supposed to make, but I cannot remember what it is and I did not write it down. So maybe somebody else might have an announcement and I can think about what that was that I wanted to say. I have nothing. Okay. Well, the other thing that I think I wanted to say didn't come to me either. So maybe it will come to me later. It will. I'll let you guys know what it was. The maybe there's no meeting next week. That's probably what it was. That is probably what it was because that went through my head this morning. So yes, there is no meeting next week. Just as a reminder, we are canceling because next week it is Thanksgiving here in the U.S. And so there's a number of people who will not be on the call anyway. So we canceled the meeting. Thanks. Right. Quarterly reports. So for quarterly reports, we have the same reports on the calendar or on the agenda that we had last year. Last week. Where is my brain this morning? And I don't think there's any new comments that have come out that I have seen. But if there's any comments or questions that anybody would like to bring up now, now is your time to do so. Okay. So we did get the hyperledger bubble report that came in last evening. So if you haven't had a chance to look at that, I know I have not. Please do have a look at the bubble report and provide your comments and feedback to that. And then for next week, we have due the Solange and the transact report. As you may recall, the transact maintainers have not submitted a report for the last two quarters because they have been moving the code into Saatu. So we will probably want to check in with the transact maintainers and see where they're at if they're ready to move the project to an end of life state or or not. So yeah, just I'd like to keep that on the agenda just so that we remember that we need to have a conversation with them every quarter. All right. Any questions on the quarterly reports? No. Okay. So we do have two discussion items today. The first one is maintainer events for 2024. The second is our badging life cycle task force. So for the first item on our discussion, wanted to have a conversation with the folks here on the TOC to talk about, you know, desire to have events for maintainers in 2024, what those events might look like. I know we had some past discussions in the TOC about maintainer events, but I think we were still in kind of the COVID phase of life. So now that we're kind of beyond that, wanted to see what people have ideas around what they would like to see done in 2024. This will obviously help the staff as they put together their planning for 2024 to make sure that we can satisfy the needs of the maintainers. So any thoughts or ideas from anybody on the TOC about the sorts of things that they would like to see, the sorts of things that they thought were useful from past maintainer events that they've been involved in, or yeah, just really any ideas that you might have is what we're looking for at this point. So these are, just to be clear, these are events of groups of maintainers across the project. Is that what you mean? Yes. So in the past, we've had two different types of maintainer events that have occurred at the Hyperledger Foundation. In the early days, we used to have what we called Hackfest. Those were open to more than just maintainers. They were they ended up having a lot of new folks involved, but they were on conference style where the maintainers could get together, discuss whatever it was that they wanted. It's very similar to IWC then in the way that those things happened. And then the last type of event that we had for maintainers, they were called maintainer summits and they were more closed as far as the attendees to really just maintainers and the discussions there were two full. We did have kind of that on conference style, but we also had a bit of specific driven content where we would make sure that the maintainers across different projects knew about each other, knew what the other projects were doing in case there was any sort of collaboration that could happen. And then obviously, there's also the events that happen like the Indie Summit or the Airy Summit and things like that, that haven't necessarily been open to everyone. And so, yeah, I think the question is, do you like any of those type of events? Are there specific things that you would like to see out of events containing maintainers for the hyperledger community? You know, just any sort of ideas of things that might work for you as in as a maintainer as an individual or things that you think might work for your projects that you're involved in. So, yeah, I think at this point, just really looking for different ideas about things that might occur in 2024 to help with the community and specifically the maintainer community. Yeah, I think one part of it could definitely be sort of low effort, high reward, things that projects have found. So things like the, you know, walking through how you can do a make doc site to get much better documentation, samples of, you know, good getting started material and tutorial things, CI, CD things that people have found. So sort of leave it open. But the idea would be things that we've discovered that proved valuable. And here's how we did them, if you will. Not great, kind of a sort of a learning event for the best practices that the different projects have discovered. Yeah, which is the same thing we talked about through this a lot of this year, best practices for automated pipelines, best practices for documentation and things like that. And then with that, the tools that, you know, making sure all the maintainers and all the projects are aware of the tools that Hyperledger has. I mean, there's there's a ton of things and it's hard to know all of them. So I think that's another good topic, a summary of those. So those are just general interest ones. The other one would be overviews of the projects, maybe, or some of the lesser known projects and how, you know, with that idea of leading toward a collaboration across projects, I don't know how much that's needed. I've not participated in such things. So I don't know if it sounds like that has in the past. Yeah, definitely in the early days, I think there was a lot of that. Yeah, I don't know that we're doing as much as we used to. Probably a lot of the the virtual events that are happening are, you know, potentially a little bit deeper dive instead of high level of reviews. But yeah, there's there's probably some some stuff there. So for the the first sort of idea that you had with the the learning events, you think that's better done in person, virtual, hybrid. What was your your thought on that sort of thing? I think I would do it as either a maintainers event where we put together a an agenda, but do it remote or at most tied to some other event. I don't think you could have an in person for that purpose. I don't think that would be powerful enough to draw. But I think it could be, you know, a three hour session, you know, a full a full chunk of day, because you never know what time of day it would be. But chunk of day type where you have a series of of presentations or or or discussions. OK, great. Thank you. Yeah, Marcus. Yeah, so if I remember correctly, I think I attended the hack fest in Amsterdam and also the maintainer meeting. It was either in Toronto or Montreal, I don't remember. But I think both events were great. I mean, meeting so many people, you are, I mean, on a day to day basis, just interact via Discord or or Slack or whatever we use back then. I think this was for many people, such a great experience to to meet the people in person. And I absolutely see big value in that. And I am in the last few years, we did a lot of remote conference style, which I personally hate, but this is only my personal opinion here. So I would really love to see the people again in person. And I mean, have whiteboard sessions, have discussions during lunch, during dinner, having beers together to basically, I mean, build a good foundation people can actually work on. I mean, also having fun together, right. And I don't know, I think, I mean, a hybrid model of this hack fest and maintainer summit would be nice. So for the hack fest, make it open so that also users or potential new maintainers could come and learn about, I don't know, the core technologies or the core code of the different projects, but also get the maintenance room to sit together and basically, I mean, discuss things, which is maybe much easier to discuss in person and things get resolved in a one hour slot rather than discussing it in the form in over two weeks, something like that. So if such an event could happen in person, I would definitely would like that. Right. Thanks, Marcus. Yeah, I completely agree, right? Seeing people face to face interacting with them in a different manner does bring a different sort of connection to the people that you've been working with closely anyway. Right. So I appreciate the thoughts there, Marcus. Absolutely. And I think you see the benefits, the actual benefits of such a meeting after, I don't know, or the first few weeks after such an event because then you start collaborating with the people again using our usual tools and then you will notice, OK, it becomes for some reason much easier now to collaborate. Yeah, probably because you've seen that person and know who they are at a deeper level than you did surface wise with the discord communication. All right. Thank you, Marcus. Bobby. Hi. So again, I didn't run for the TSC next year, TSC next year. So I'm just giving my two cents for whatever it's worth for everybody. But it's definitely worth something, Bobby. Thank you. I honestly do believe in the power of face to face meetings. But in this day and age, those are far and few between and very special. I believe in the interim that I am, again, the hugest proponent for that metaverse library. It has all the information logically set up open 24 seven. It could be done in different languages. It can be done, you know, meeting spaces for maintainers with their information. They can go whenever they want. So again, I believe that this community has such important information. And just to make it accessible for people when they need it, I think is where we should go in the future. And my second thing is I do believe in the badging process. And I think it should be gamified learning. I think we have enough information. I think we have more information that that gamified learning would challenge people to, you know, maybe you get something if you learn about three projects instead of just one or, you know, whatever. So I do believe that we could step it up again, like Stephen said, with the learning section of this and getting the information where it needs to be. So thank you for letting me speak. Yeah, thank you, Bobby. And Bobby, just because you brought it up, you are going to be missed next year at your voice on the TOC. I do hope that you can attend at least some of the meetings, you know, obviously, even though you're not on the TOC, it doesn't mean you can't be here. So please don't hesitate to bring your voice to the community. Well, I intend to definitely keep that hyperledger library operating in the metaverse. And the only way I can be effective of that is if I know what's going on. So you haven't heard the list. Perfect. Very, very good. Very good. All right. Any other thoughts or ideas about things that you would like to see out of the events from 2024? David, Sean, Ray, any particular questions that you have that you might not have been already talked about or things that you'd like to to see if the group might be interested? My main question was the one you already asked about, you know, if you would want to do this in person. And if so, you know, what would be compelling? I think, you know, people have touched on this. But if we did do an in-person one, what what would it need to include to really compel, you know, people to go to it? It sounds like there is definitely a desire for in person is what I heard. And then just, you know, the details, it sounds like maybe we need to do this attached to something else, because maybe there's not enough draw for a standalone. So that that just sort of, you know, is very helpful for our planning to know to know what would it be? What would it need to look like for people to, you know, show up? And attend? Yeah. And if anybody has any ideas of the sorts of things that it could be attached to. Yeah. Well, that might be useful to have attached to. Is there an event we're all planning to be at next year? Right. Well, I guess for many people, we need some kind of business justification to travel these times. I mean, if the TLC, for instance, would say, OK, we do the end of the year project review in person at a maintenance summit. And that would be kind of increasing pressure. Yeah, I mean, that's a good point, Marcus. I mean, it's one thing for you to want to go, but it's another thing for you to get approval internally to go. I guess, yes, there's two layers there. So yeah, what would make it compelling for you to want to go? And then what would make it, you know, justifiable internally to get signed off for? Right. Rama. Just wondering if it's going to be a global program next year, because the world is on the field. Is a good question. I don't actually know the details myself either. You know, I think, as Tracy said, we're in the we're kicking off the 2024 planning process and that has not been finalized. So I don't know the answer. I think maybe one thing we can do either sometime in December or very early January is come back, you know, and report back what our 2024 planning, you know, is so that everybody here is in the loop and we stay coordinated about, you know, what the TOC is planning for next year and what the staff is planning for next year. So, you know, we're happy to do that. Thanks, yeah, I mean, it's also a response to Marcus's question. The global forum is the kind of thing you might get to report. Yeah. Yeah. So as far as global forum is going, yeah, again, I think we can report back on that maybe in a few weeks or very early January and then, yeah, if that's a compelling time to plan for this or if it not, then we could find something else. But the problem I see with the global forum is that this is, I mean, a conference style and I mean, people maybe think, OK, they need to present in order to participate there. I mean, for maintenance in particular and then many companies have the policy. OK, you can only go to conference if you present. Something. But I don't know, maybe then the global forum can the next edition of the global forum could also have a, let's say, let's say maintain a summit included where we do some reporting on projects, something like that. In order to, I mean, trigger really everyone wants to come to the global forum. I mean, the global forum has another interesting aspect that it connects the community with potential clients or more end users from different industries. So this is for the companies, I guess, also a very interesting thing. Yeah, Marcus, I think that's a it's an interesting point, right? I think if you think about the early half fest that we had, you know, some of the concerns there was that the maintainers wanted to actually do some work and get some something accomplished. And sometimes when you had the the users or the the newbies, right, showing up, the first thing that you needed to do was obviously educate people about what the projects were. But at the same time, those events gave us the opportunity to cross paths with people who want it to use it or potential clients, right? Which obviously is a a compelling reason for businesses to want to send their, you know, their maintainers to these different events. So I think, you know, David, kind of the thinking there would be there's got to be a reason that businesses want to send the maintainers to an event and what would those reasons be? And we could maybe do some brainstorming about that sort of thing. I wonder maybe this is not the time to do the brainstorming, but I wonder if maybe doing a multi part thing would maybe it seems like the workshops were really compelling at Global Forum in Dublin. And that would be maybe, you know, that compelling reason. You're you're on the agenda to give a workshop and then people maybe even new people, we could open that up to new people. New people want to go to that workshop. And then before or after those series of workshops, maybe we do the maintainer only part. So that's my thought on brainstorming for a compelling reason. Yeah, I agree. I thought one I hate to say recent, but the event that we had in Basel was really good.  The member summit was there. The, you know, we had the Global Forum and. It was we had a big buff area, right? So you if you were interested in fabric, you could go sit at the fabric table. It was it was really nice. So kind of that multi part event where, you know, it's more open to the public on a couple of days and then or on a single day. And then the maintainers have like two days where it's more gated. I think that would be really great. Thanks, well, any other thoughts on this topic before we move forward? All right, well, I'm sure this isn't the last time that we'll be talking about events for 2024 and what those look like. But it was a hopefully it was useful. David, Sean, Rai, to get some initial thoughts on this. Yeah, for sure. Thanks for adding it to the agenda. Yeah. All right. So the next item on the agenda is the task force discussion on the badging life cycle. Rama, I think this is off to you now. Thanks, Tracy. So I had mentioned last week that I would have a document for people to vote on. Fortunately, I haven't quite finished it yet. I have made have something to show you. Let me just show you what I have. And I also want to discuss a couple of things. And I can finish the document pretty soon. And then we can go about the voting process. That's right. It's your stream, right? Yes. So one bit of a cop. So I thought it would be best to put this into the TFC repository. So I created a file in the government document folder called logic badging. This is in my book at this point. Ignore this part. This is just notes, which are removed. I'm going to have a list of different badges and classified into either very unimaginative names. Because we have different name suggestions open to it. It's called the life cycle type of badges and quality indicator badges. Just to show you what the shows I'm referring to. Let me go to the... Yeah. So, I mean, here we call the mandatory in optional. But that doesn't really describe the badges, I mean. It's not mandatory to have a badge. Just that the badges we listed here are the ones which are relevant to a project's life cycle, state transition decision. Whereas these badges are not. But both these badges are... Both these kinds of badges are good to have and important to have. So, that's all I'm calling them. Again, if you have any suggestions for what you should call them in the paper, just open to it. And I will... I mean, put list them and that's the needy task. I just haven't got onto it. I made this slightly different diagram. Because what I was trying to do with this was trying to figure out if he had covered all the state transitions in the life cycle. And the diagram by itself, by the way, I added another arrow which I showed in the last time I covered this topic. Maybe that was three weeks ago or something. Which is an arrow from graduated incubation. Note that the life cycle original diagram does not have that arrow from graduated incubation. But during the discussions on the badges task force we determined that it would be good to have such a transition. So, I added one. That's the only one added. And then there's also this sort of a dashed arrow that just comes into the proposal stage. Which is just how it's like a better known qualification for any project to be accepted as a portal. So, I counted 14 arrows. And the collection criteria, collection bucket, each of these is a badge. The green indicates the acquisition of a badge or going from a badge in one station or another. That is, say you have the decentralization badge. You'll have like two parts to it. One is it's either a two plus or a three plus. Which means you're okay with the project being maintained by after two companies or after the institution as long as the incubation stage but you need at least three for the graduate stage. So, that's the decentralized badge. You may just call refer to them as separate badges. And we formally accept this. The red boxes that indicate the withdrawal of particular badge because the criteria for that badge as the project is not meeting the criteria for that particular badge. As you can see, I tried to put the numbers in the different boxes. And of course you can review this. What I wanted to just discuss at this point was that I was able to fit in all the numbers except for 8 and 11. What are 8 and 11? 8 is the arrow going from incubation to end of flight and 11 is the arrow going from graduation to end of flight. So, it doesn't fit any of these because when you were discussing the project life cycle we were always thinking about what should happen to a project that's in an incubated or graduated stage should it fail to meet particular criteria and we were always thinking about okay maybe we should go into the government stage or to the deprecated stage. It seems rather drastic to move them directly to the end of life but maybe there's a good reason for that. So, I just wanted to ask if anybody remembers what was part of creating this diagram in the first place what did you think of the criteria to move from incubation to graduate directly to end of flight and if you can't think of any criteria maybe we should remove the arrow and just have the extra step before the project is pulled to end of flight. Sorry, I can't see any... Yeah, so maybe, sorry I didn't raise my hand maybe one of the things that we could think about here is just let's say that you've got a project it does something right let's just call that X and then another project comes along that also does X but does it better and you're like well let's just move our work over to that or let's say that this project shouldn't be used any more in favor of this other project that does whatever we were doing much better that could be one reason that you might move straight from an incubation or graduated to an end of life you know it could be that the maintainers are going away and they don't have any plans to maintain the project moving forward right so they're not even going to maintain security issues or they're not going to do any sort of bug maintenance that would be probably required in the dormant and the deprecated phases right the dormant phase I think says that we're going away but we're still going to be you know doing like the security bug fixes I think the deprecated one is we know that this is headed towards end of life and the end of life we're going to say is in six months or a year whatever that number is and so you know therefore we're going to do that but if the maintainers have completely gone away and there's nobody to come pick it up then it would it should go directly to an end of life state and I think we've had a couple of those projects where we've sent directly from incubation to end of life whether or not we've had any that have gone from graduated to end of life I don't think we have I think most graduated projects have either gone to dormant or deprecated before they go to end of life but yeah I do think that there is at least a potential right that that line should exist but it really has more to do with the fact that there's you know either something better that's come along and I can replace it or that the maintainers have completely gone away No that makes a lot of sense I wasn't actually thinking about projects that just for which there was good reason to just end because of either replacement or because nobody wanted to do anything more anything useful I think then yeah this isn't even a badging criteria I mean at that point it's sort of I think it will be clear to everybody that the project needs to move to EOS I guess the bad that we modeled as top-level versus labs that's the top-level bag we can just say with all top-level batch means either an incubated project an incubated stage or a graduate stage just to complete the picture Does that make sense? No I think that makes sense Hello? Yeah I mean it's a bit of sidetracking maybe but you know when I was looking at this I thought man this is really complicated and you know I went back to the beginning page of this task force which had this parallel graph of you know the life cycle we have and the one that's exist for LF networking and I think there are two aspects to this first by calling end of life end of life we made it like sound like it's not recoverable at least in this world and you know I just went through this with the OpenSSF so it's quite familiar to me if instead it were called archived then that's not necessarily an absolute end you can recover from archived by unarchiving and so I think we have created a deprecated endowment because it seemed so lethal literally to go to end of life that we would need to be very cautious about it and not call it too soon but maybe there is a simple way to simplify this to rename end of life to archive and then we can probably you know simplify this graph get rid of dormant and deprecated because there is no real harm to going to archival even if it's temporary or not yeah sorry no I realize this is not probably a bad badging but I think this graphic really illustrates the complexity of our life cycle and I think you know we should also consider you know possibility of simplifying this no thanks everything you said makes sense I mean we did discuss I mean if you go to the first document I created in the project badging life cycle I tried to raise these points I was asking about enquiring about whether we need all these states and these sort of complex lags and also the end of life as you mentioned yeah the LS graph just has been archived maybe we can call it suspension life and I'm asking this question about whether we should have an arrow from this state what do we call it back to the polls Tracy yeah I know I like this idea I don't know that you have around kind of combining these three states if you will into like an archive state I do think that it will make things easier not only in this life cycle but also as we think about these badges and the transitions between them right I think we see a lot of things on this like four and six right if you think about four and six they could very well be well I guess they'll still be four and six but I think there's ways to go from that archive back to an incubation state and there's there's you know even though we don't really show that because we basically say it has to go back through the proposal state again you know which is a line that's somewhat missing here I guess if you will but I think there's you know there's ways that even then the spadging could potentially be simplified to reflect you know we won't have all these numbers and have to think very hard about this I think the other piece of this that comes to mind is that there has been a lot of confusion for people who weren't involved in the original discussions about this life cycle about what's the difference between dormant and deprecated and end-of-life and what you know do I go do I have to go to dormant before I go to deprecated do I have to go to deprecated before I go to end-of-life do you know what's what is this certain life cycle that I could follow and so I think that yeah I like I like the suggestion I guess is what I'm trying to say so Tracy what do you think we should then go back and maybe make this make a simpler life cycle diagram and then come back to the budget yeah I do think that could that would work Rama okay do you think we should merge all these three into one or do you think okay I mean if end-of-life is just meant to be an archival state run like a death state then yeah we can probably merge them all I mean if end-of-life is meant to be something more drastic then you can probably and so I think my earlier thought was you can probably merge these two dormant and deprecated I mean that could be an option and then I don't know maybe end-of-life becomes yeah I don't know it's you know is there really a need for an end-of-life I think is the the question or is it just everything is archived and then at some point if somebody decides you know what I want to bring this back then it would come back I think it serves to remember what you know why we have added those right and so we have specific scenarios where we say okay now we're in you know where do how do we capture this state but I again I think you can get re merge all of this if you will into one archived because all the other ones are kind of because we were afraid to call it end-of-life when people said but I might come back like dormant right we had a specific case where somebody said oh I'm not going to be able to work on this for the next six months or a year just put us on the pause and if you had archived you can say okay no worries we'll archive your project for now and when you come back we can easily unarchive it so this is why I mean I think the other cases become moot we don't need those other states I think we can address all the scenarios we address by adding those by if we had first renamed end-of-life archived or deprecated archived and you get rid of end-of-life it all comes down to the same the graphic is going to get simplified in the same manner I agree okay so Tracy then you think you should that should be the next step then maybe yeah combining compose the diagram combining these three into one and then create a much simpler diagram yep I think so thanks Argo okay I had one more question so I had some list of criteria for evaluation and decisions for either issuing a bag or withdrawing a bag so I thought this could also be done using PR because we use PRs for so many other things if we require a bag the project maintenance must submit a request to the TOC via full request and only the TOC may issue a bag by approving this kind of PR this is a question for Esmeralda and should we all vote for it as well as we do any comments on these two everybody think is it's fine to have a bad issuance process via PR and second question should we all vote on it as well or just approve the PRs might be approved or there are certain badges that we think can be automated and is this yeah some of the can be yeah some of the can be to create an action to check for the presence of a particular file and also sort of cosmetic check to see whether it has something substantial some of them we cannot we don't have to decide right now I'll keep this up here and people can think about it that's all the discussion points I had so now I will fix this document and then just submit a PR so next week of course I think we don't have a meeting for time being right and I will be away the following week as well so I'll be back the first week of the month that's I think the 7th anything else or I'll stop sharing any other topics for today that anybody would like to discuss no okay well then we will see you again in two weeks when we come back on the 30th and I hope that those in the US have a great holiday week and yeah for everybody else just a great couple weeks before we meet again thanks everyone thank you


Hi, my name is Pete.  This is pretty good stuff. Let's import this back home and They really steeped themselves in it Young schoolboys in ancient Rome would have learned ancient Greece and many of them traveled to Greece including Catullus Atticus the famous Friend of Cicero lived in Greece for many years Cicero himself brought over a lot of Greek philosophy and made it available for the Romans. So I felt that by teaching myself ancient Greek I would have a greater understanding of Latin and thus I would make myself be a better teacher through having done that and of course it turns out that Ancient Greek is rollicking fun. Well, if you're into that sort of fun I'm not a professional athlete. So I've got to do something else for fun Teaching myself ancient Greek turns out to be a little bit of fun So that's essentially why I taught myself ancient Greek thought it would be advantageous for my Latin teaching and Having done it. I don't know. Maybe it is maybe it isn't But that's why


So, I'm sure you heard by now, but if you haven't, last week there was a shooting at a school in South Florida and for those that don't know, that's where I'm from and it was at a school that is very close to where I grew up and it's actually a school that my cousin attends and she was actually involved in this horrific event but she was luckily one of the ones that was unharmed but some of her friends were killed and it's just a tragedy and I just want to do the least that I could do which was bring awareness to this problem. I don't even really know how to address it but what I do think is probably part of the reason that these things happen is mental illnesses and depression and things like that and I just want to try to bring awareness to this for the people who aren't having those struggles to try to help those who are and just to be more aware I guess is the word but just to be more aware of other people that are having struggles in their life and just to be more open to them and understand that their actions may not be directed towards you. I'm not talking about the actual shooting I'm just talking about in everyday life when people have or having struggles and they're depressed or and they act mean or very negative and things like that. I know it feels like you don't want to be around that person but there's probably underlying reasons for that or if they're acting in have a bad mood all the time things like that there's just try to be more open to understanding what their problem is or reach out and try to help them to fix the root of their problem or if you're depressed yourself because I've had down times myself throughout my life not nearly to that extent but it's very helpful to try to find the root of the problem and not just try to mask it or dull the symptoms of whatever causing your pain things like that it's very even though you don't want to if it's something you don't like about yourself or something you don't like about your life or feelings you have or just situations you in you're in you can take small steps to improve it and if you don't know how then there's people out there that can try to help you or reach you can reach out to and that's what also I want to do is try to tell people that sometimes all people need is a tiny little boost of confidence of just encouragement to get them started and it can go a long way for people that are really struggling and feel like there is no hope or there is nothing positive in their life a small just appreciation for that person could go a long way and I guess that's pretty much all I wanted to say on this but I just couldn't really not speak my mind and bring it to your attention that I definitely think that it's something that we can all contribute into helping with and I obviously wish it wasn't as bad as it was but just I don't even know why this happened but it just I've heard of different things other instances and other shootings there was depression or is a lot of times it's mental illness or loneliness that leads to these type of things and I'm sure some kind of form of that manifested itself into this person to lead them to do these acts so I just want to hope to prevent more of these tragedies from happening in the future and I think it starts with the people just coming together and everybody loving one another and at least showing care and understanding that some people have problems that they can't control or that they were born with or anything like that but that you can do a lot more and try not to if you are not struggling or even if you're struggling less than someone there's someone struggling more than you the littlest thing can do a lot and I just want to try to push that message to just help people help others so that way we can all work together to not harm one another and to stop these things from happening because it's just too much all right well thank you for listening I appreciate it and I'll talk to you guys soon


Let's start with this first problem. It says a coffee cup is filled with 100 grams of water at 25.0 degrees Celsius. A 5.00 gram piece of metal that has been heated to 100 degrees Celsius is added to the coffee cup and the lid is replaced and the water is stirred until the temperature of the water remains constant at 28.0 degrees Celsius. What is the specific heat capacity of the metal that was added to the coffee cup? So, how do we do this type of problem? Well, the thing you have to remember is that the heat that's flowing out of the system is flowing into the surrounding. So once you figure that out then it should be pretty straightforward. But let's just go ahead and write down all the variables that are all the stuff that they give us in the problem. So they give us the mass of water. They give us the initial temperature of that water at 25.0 degrees Celsius. They give us the mass of the metal at 5.00 grams. They give us the initial temperature of that metal at 100.0 degrees Celsius. And then they give us the final temperature of the water, which is 28.0 degrees Celsius. And consequently, of course, since it's equilibrated, that's the same temperature as the final temperature of the metal. That's about Tf of the metal 28.0 degrees Celsius. And this is, I should write, you really should label these as metal and water because it will get confusing in a second. Okay, so remember when we're doing the heat capacity equation, we need to find the difference in temperature. Now we go ahead and do that right now. So the change in temperature, of course, is going to be the temperature final minus the temperature initial. Write it out. So 28.0 degrees C minus 25.0 degrees C, which is 3.0 degrees C. And let's do the change in temperature for the metal. 28.0 degrees C, 72.0 degrees C. Okay, so we've got that. It's wondering what is the specific heat capacity of this metal. So that's what we're looking for. And given to you always is going to be the specific heat capacity of water, which is 4.184 joules per gram degree C. So you won't have to remember this. I just know this because I've done so many of these things. Okay, so essentially you're just going to set this side equal to the negative of this side and go. Okay, so what's happening? So the metal, if you want to think of it this way, is losing heat like that, right? So the water is gaining that heat. Okay, is everybody okay with that? So all we've got to do is set both sides equal to each other. So remember Q equals MC delta T, if you guys recall that formula. So M of the metal, C of the metal times delta T of the metal. So we're solving for that variable there. So C, is everybody okay with that sort of rearranging of the equation? If not, stay here. So let's just go ahead and do this. So we have all this stuff. So we have the mass of the water, the C of the water, delta T of the water, mass of the metal, and delta T of the metal. So we should be able to do this, just plug and show it. So 100.0 grams, 4.184 per 1 gram. And we've got Joules per gram degree C, right? Is that a good specific heat unit? Joules per gram degree C, yeah. So if you didn't know that, that's specific heat units. So negative times a negative down here, the whole thing is going to be positive now, right? So 100 times 4.184 times 3, where I got, or the specific heat capacity of this metal, it's got to be 2 sig figs because of this number here. It's going to be 3.5 Joules per gram. So is everybody okay with that? Everybody get that answer? Did you get that answer this time? So any questions on this one? Again, I think the real thing, there's a lot of these types of problems. You'll probably get one of these on your exam. You've got to remember this relationship, okay? And of course Q equals C and delta T. You know that already. Again, questions? Nope, okay.


A strike was scheduled to commence on Saturday, September the 18th, 2021, but my health care workers have come together to suspend that strike and give the federal government a 14-day break, a 14-day automaton to go ahead and implement all the agreements that they reached in December 2020 and we're discussing that now with a doctor, Dr Ifani Kasme. He is a former spokesman of the Association of Medical Lab Scientists. Good morning, Dr Ifani. Dr Ifani, can you hear us? Okay, we'll try to reconnect with Dr Ifani there, but what we're seeing with Juhisu is something that has been dragging on for far too long and they basically have gone on strike many times over the implementation of the agreements that he had with the federal government December 2020 and that really seems to be the bone of contention when will the federal government implement the demands. Dr Ifani, can you hear us? Loud and clear. Yes, I want you to first of all let us know, like put this on the table, what exactly is Juhisu asking for and what's the challenge with the federal government getting it done? Thank you very much. I must posit that the most patriotic health workforce we have in Nigeria are members of the joint health sector, you know, since after our meeting with President Muhammad Buhari sometime last year and he did appeal that wish. Yes, just following up on what he said, yes, the president did meet with Juhisu and appeal to them that there should be more patience, more understanding with his government, his administration, that they were on top of the matter and that they would definitely make sure that all the demands are met. But the issues now came about when we have Chris and Gige come out in the media to make statements about according to him saying that no doctors were being owed salaries and the fact that the NMA came into the situation and there was, you know, there came to be a conflict between who should be negotiating with the federal government. Dr Ifain, can you hear us? Seems to struggle with connecting with Dr Kasmeir Ifain this morning. The conversation really centered around what happens next with Juhisu and the federal government, you know, there of course have been the legal, you know, aspects of it where they were seemingly ordered to go back to work. The NERD of course didn't respond to that. The Minister of Labour, like you mentioned, he just said in the news that one of the stories that we took this morning saying that they are threats to go back on strike is on scrupulous or something like that. So of course this all of these conversations really, really affect Nigerians the most because there's Nigerians who get to be at the hospitals and have less medical workers attend to them. What will the next 15 days bring? You know, and if the NERD is on strike and Juhisu intends to go on strike also, it means that the whole healthcare system, you know, is going to be on, you know, snail speed and almost nobody working except private hospitals that a lot of people cannot afford to go to. So what will be the federal government's approach? What is important? How urgent is that approach? Some of the important questions. Dr Ifain, once again, can you hear us? Good morning. So just to bring us up to speed with what's on the table here, they're asking for a review of the 5000 error hazard allowance. And I don't think doctors, you know, feel that this is commensurate with all the work that you do, all the sacrifice, all the health risk, especially in light of the COVID-19 pandemic, they have to be in those hospitals, offer care to those who are suffering and go back to their families, you know, a heightened risk of, you know, dying. There's been reports of lots of doctors who have passed on in Nigeria because of the COVID-19 pandemic. And, you know, they have also come out to protest these health workers and their unions that, you know, the families of these people have gotten no compensation from the federal government. So this hazard allowance is one thing that's on the front burner in addition to salaries that have been owed to these workers. And one question really that I have to ask is how many more 15 days automaton would continue to be given? It's something we've seen time and time and time again at the end of the 15 days automaton. What happens next? Another 15 days, another extension. Let's see what Dr Ifani thinks. Dr Ifani, can you hear us? I can hear you. Yes, please continue your trail of thoughts on the strike and the 14-day warning. Yeah, it's okay. You know, we had that kind of issue. The joint sector, you know, had actually issued an automaton that had last week. And the union is a very patriotic union that take on the sense of the situation in the country, the COVID-19 pandemic, the economic challenges in the country. Anytime the government that thinks was who would listen. But we have to be made the whipping boy. The Jews have made the whipping boy in the health sector, which is quite unfortunate. We issued an automaton and the Nigeria Medical Association became very medusome. They had to join that to the demands we had put out to our employer. One of the things that need to be put out clearly is that medical officers, like every other health profession or professional in Nigeria, in the employment of federal government, we are all employees. It is in Congress and out of place. It's quite nauseating for a fellow employee to be the one dictating the terms and conditions of work for his colleague at workplace. That's why we have issues here. Now, the point is that in 2018, we had a strike action and the government invoked the no-work-no-pay rule. And to date, our colleagues have not been paid that money. Unfortunately, some of the persons that went on strike were paid those outstanding money. Again, on the issue of the hazard allowance, we had made a position clear to government that in the past 20 years and even before then, hazard allowance had been on the flag of it for all persons that are newly exposed to same hazards in the same workplace. Unfortunately, government is not being able to be very decisive because they are being shoved up and down by the Nigeria Medical Association. The current notice we have issued is because we had withdrawn the other one that had expired following the intervention of the Honorable Minister of Health, Honorable Minister of Labor, and I must give it to the Honorable Minister of Labor. He's been top notch as a conciliator. But what we are saying is that enough of the medusomeness of our colleagues in workplace, it is not up to them to dictate the conditions of our work. If they have issues with government, they should get government on their point of argument and allow other workers to negotiate their own terms and conditions with government. It's not the situation where you dictate what we get. Now, why we have given another 15 days after a expanded next meeting is because we have consulted with our stakeholders in the health workforce, and they do feel that government has not been able to listen to us. What is the issue here? We have the common salary scale which was produced, same time secularized, same date with the common salary scale. Unfortunately, because the other people are in political corridors, they've been able to get several reviews, several, about three times a review of the consolidated medical salary structure of, but not even a single review. Whereas the memorandum of agreement we have with government does the place clearly that for every consequential adjustment on the comments, there should be a reciprocal on the common salary structure. That is yet to happen. That is the major demand we're putting out to government. I was saying that what is good for the GIZ is also good for the GANDA, particularly when it is predicated on an extent memorandum of agreement. That is exactly what we're asking. We're not asking for a pay rise. We're asking them, having reviewed the common salary scale three times serially that a consequential adjustment be effected on the common salary structure. Because a lot of other allowances are predicated on percentages of this consolidated basic. And so if you continue to up that of the other colleagues we have in workplace, while you keep an eye on that constant, you're searching our members. Besides, it is not all about enumeration. What conditions are there for our healthcare workouts? We're losing our members in the numbers following the COVID-19 pandemic because they thought for government told us in 2020 that they have an insurance package. But I want to tell Nigerians that people are insured with their particulars. No head worker in Nigeria as we speak today has been insured with his definite particulars, which is a proviso in the insurance act. You cannot tell me you're taking the insurance for $5,000 and you do arise the insurance for the individual beneficiaries. So these are the challenges we have. We are saying that it is important that government comes to the insurance structure to bring it to tune with that of the government. We are asking that government should pay us the backlog of the 2018 three months salary that they withheld following the industrial action because they have had to pay other workforce. You see the weather deletion with invoking the noble club for nationalization of resident doctors. It is only in Nigeria, and I repeat, it is only in Nigeria that students can ground and collapse. I've been here for more than 50 days now, health services and that is because I've only played into their hands. All right, Mr. Dr. Ifain, I beg your pardon. There's so much obviously that you have to pour out, but unfortunately we're out of time this morning. We would have to very likely reschedule another conversation with you so we can look at the different angles concerning this conversation. And what happens in the next 15 days if the government still fails to follow through with the promises made in the memorandum of understanding? Dr. Ifain, we thank you very much, but we have to continue this conversation another time. Maybe see how it goes for the next 15 days if the government gets in contact with you and what the outcome of this would be. Thank you very much again Dr. Kasmere Ifain for your time and we thank you for joining us this morning on the breakfast. It's a beautiful brand new day Monday the 28th of September and we thank you for starting it with us. I am Annetta Felix and I am Osaugi Ogbonwan. See you tomorrow.


What's going on everyone? Sam here with late sports cards. We've been one box of 22 tops, crown, platinum, anniversary, and baseball late for Robert L. Let's go look at Robert. Here we go, buddy. DCPA light. Let's see some good color. Let's see a super. Why not? Why not? Bebert, black and white mini diamonds. Tommy Lassorta. Yeah, Tyler O'Neill, refractor. I know I lost him in fantasy too, which kind of sucks, Anthony. Lorenzo Cain, Maggly Ordonias, pink atomic to 100, black and white mini diamonds, Mike Zanino. Anthony expressed his condolences for Achan. There's Junior, Salvador Perez for you. What? Anthony expressed his condolences about Devon Achan for you. 250, Ryan Mountcastle. What? What's up? Whatever. Oh, he said sorry. He's having long glory. No, he's actually being serious. He doesn't have to be in a bot like usual. That guy. Josh Donaldson. Fine. Yeah, that's true. So, the fastest guy's been a pro. We have an Olympic track team. Royce Lewis. Those old scrambled eggs too, they were in trouble. True. I saw somebody made a, like, you know, I like the Legion of Boom and all that kind of stuff. 2199, that's Miguel Cinell. Well, they called, that was what they called the Chiefs, Legion of Zoom, and then they, they're calling, this person came up with a two-a-side squad. Right? Isn't that kind of cool? There's Eddie Murray. That's pretty cool. I kind of, I was like, yeah, I kind of like that actually. I don't know. But Ducky Matsui, black and white mini diamonds, Frasier and Nick Madrigal. Like that. Royce Lewis. Sasazuki too, 2199 for the Cubs, Tony Perez and Richie Ashburn. I'll do it for your break there. Robert, thanks again for the support, buddy. Get him right out to you, buddy.


Boom, what's up everyone, welcome to Simulation, I'm your host Alan Sakyan. Very excited to be talking about heart and brain diseases and how we can in advance understand the pathologies happening to our body, live longer and healthier. We have Dr. Karunia Kandimala joining us on the show. Hello. Hello. Thank you for coming on. Really appreciate it. It's such a pleasure. Thank you to Kishore for introducing us, your cousin, yes, and you also have your daughter visiting as well into the Bay Area and it's nice she's visiting Berkeley, yes, yes, and your background is very cool. You've been an associate professor in the Department of Pharmaceuticals at the University of Minnesota for the last seven years, also a research collaborator at Mayo Clinic. You were previously also visiting scientists and an adjunct professor in the Department of Neurology at Mayo Clinic and you've been now focusing on macromolecular pharmacokinetics related to Alzheimer's disease and metabolic syndrome and developing nanotech for diagnosis and treatment of cerebral vascular disease. So this is very important for us to understand this affects one out of every six of us by the age of 65, one out of every two of us by the age of 80. So this is a big deal for us to be able to have, you were teaching earlier about the preventative steps that we can take in order to prevent the onset of neurodegenerative diseases. So Karunia, let's start off on a big history perspective. We find ourselves as stewards of Earth, we have eight billion of us now, there's exponential technology happening, we have so much great science that can help us. What's your current take on this state of humanity? I have a very optimistic perspective. I think humanity is progressing and actually moving the frontiers in science as well as in technology. Previously people only used to live up to 50 to 60 years of age, but now we are expected to live about 80, so that's a real possibility. With those advances also come challenges, so because Alzheimer's is one of the diseases of aging. So if a person is above 70, there is a 15% chance, but above 80, there is almost a 50% chance of getting Alzheimer's. So those challenges could be also consequences of the progress we have been making. But at the same time, the science is evolving at a rate to a level where humanity is probably getting ready to face these challenges and solve them eventually. Yes, yes. And the relationship between the heart and the brain to what affects the heart as something that is bad is very much so associated with affecting the brain as something is bad. And that's something that you found with type 2 diabetes and that will continue talking about through this conversation. These are the two of those central organs to our existence and our health. So, Karunia, you're right, the scientific frontier is pushing us in the direction of being able to solve these tough challenges, we're very excited for that. What has been your journey to get to the point of your fascination and your interest with solving these challenges? I think it's the fascination to deal with the unknown. So I have a natural tendency to gravitating towards what is unknown and what's more challenging. So as a consequence, I get myself in trouble every now and then and I still remember one of my professors when I was doing my doctoral study at the University of Iowa. He commented looking at my project, which is to investigate how drugs permeate from nose to brain. So like say for example, drugs of abuse and therapeutic molecules also could permeate once they're in the nasal cavity into brain. So the pathways that they take to reach the brain are poorly understood. So my PhD thesis was investigating what those pathways are and how body can protect itself from being bombarded by these molecules. You know, if it's drug, then it's beneficial, but it could be toxin too. For example, manganese, aluminum, all those metals could get into brain through inhalation. Viruses could get into brain via the nasal pathway. So my thesis was to investigate that and the professor was used to ask me like, so how long do you want to stay here?  So it was risky, but that's what was the driving force. Likewise, when I moved to being a faculty member, again, I started looking into the pathophysiology of Alzheimer's. Instead of treading the known or well-investigated path, I started a different direction, which I felt is probably what might be the earliest risk to neurodegeneration, which is insults to the vasculature, to the blood vessels. In the brain blood vessels, the brain is heavily perfused, which means there is almost a small blood vessel for every neuron in the brain, because neurons need nourishment and they generate a lot of byproducts that should be cleared from the brain. And vasculature, the blood vessels can do that very well. One blood vessel for every neuron? Every neuron. That's how dense the blood vessels are in the brain, because brain needs a lot of energy, which is supplied in the form of glucose. So that supply is consistently maintained by the blood vessels. The blood vessels are bringing the glucose into the brain. Yes. So we have almost 100 billion plus of these little micro blood vessels, micro vasculature, that brings the glucose up, that powers the brain, and it brings oxygen. Oxygen, which is very critical. So unless the blood vessels are functioning very well, it's hard for the brain to get that nourishment. And also a lot of byproducts are generated, a lot of metabolites. If they start accumulating in the brain, it's very hard to maintain what we call homeostasis, which is the balance in the brain. So blood vessels again remove all those breakdown products into the bloodstream so that they could be eliminated. So this should be functioning very, very effectively for proper brain physiology. Yes, yes. So then simultaneously as our blood is bringing up the glucose and oxygen, it's bringing down the build-ups. The build-ups, yes. Of the toxic products. And this is fat, cholesterol, and then the amyloid protein build-up. Right. Amyloid protein is also regarded as one of those byproducts of brain metabolism. So we don't know what the function is, but we do know that it is there in every brain, amyloid protein is there in every brain. But in Alzheimer's brain, it is overproduced because the blood vessels or the brain itself is not able to clear them, so they start accumulating and cause problems. One of the problems they could cause is killing the neurons. Yes, yes. Okay, so for you, how did it come up for you the moment for I want to be focused on this specifically? Yeah, again while I was doing my doctoral work, one of the reasons we were investigating, you know the purpose of investigating nos-to-brain delivery of molecules is to look at resolving the issues associated with Alzheimer's. Because in Alzheimer's disease, one of the first brain areas that are affected is the olfactory system. It's the olfactory system, interesting for our nose, for us being able to process what we smell. For able to smell, basically. So, an Alzheimer's patient. Why? Do we know why? We don't know why, but we could see some connections and sort of guess associations at this point. So olfactory system is the only part of the central nervous system that's exposed to the environment. This. Right. Is the only... What about taste? Is it not... It is not directly the part of the central nervous system. Taste is not... You have the neurons, of course supplying the nerves that are supplied to the brain. The tongue for the taste perception, but it is not a directly exposed part of the central nervous system. No, we have nerves being supplied to all over the body. But in the olfactory system, the olfactory neurons are actually exposed to the environment. And that's right up here. Right up. These olfactory neurons. Roof of the nose. Yeah. And then... Okay, interesting. Okay. So you can actually trace the area, the olfactory processing part of the brain all the way to... You can trace the... The roof of the nasal cavity. So the roof of the nasal cavity. Yeah. Where the olfactory epithelium is located. Interesting. Yeah. These senses that we have to process our environments are very, very interesting. Right. So... And how we're building new senses is very interesting. Right. Yeah. Now, take us to your teaching... You actually started hinting at what is... If the blood vessels themselves have issues with bringing up the glucose and bringing up the oxygen, that that process can start deteriorating. Actually, you were teaching me earlier, and this is an important point to teach, that it's 90... No, that's 100%. There's 100% failure rate in clinical trials for Alzheimer's disease. And that's because we're not doing it early enough. Right. Yeah. So most of the therapies that went into phase three clinical trials, I'm talking about the novel treatments of Alzheimer's. And our conventional treatments to actually those we call colonist-raised inhibitors that are available on the market, but they deal with sort of temporary effects caused by Alzheimer's disease, but they don't address the root cause. But one of the attempts that were made to address the root cause is to therapeutically remove the toxic amyloid proteins that accumulate in Alzheimer's brain. So and that removal is done by antibodies against the amyloid beta proteins. So many of those antibodies went into clinical trials, but failed in phase three clinical trials. The antibodies are trying to go and remove the amyloid protein buildup, and we're doing it too late in the process. That is sort of the reasoning that scientists are coming up to explain the failure of those clinical trials. But there could be several aspects associated with it. One is amyloid accumulation could be a consequence of some pathological damage that really caused problems. Yes. So it could be a bystander, but genetic data clearly shows that amyloid is a critical part of the Alzheimer's pathology. So it's a, you know, there could be a sort of a shift in the role of amyloid proteins very early on in the disease and then compared to that in later portions. So unless we know and understand what that shift is, it's very hard to time when the therapy should be administered. Yes. Yes. And let's pull up our images that help us explain what we're talking about. Okay. Yes. So these are the stats you were mentioning earlier affecting one in every six people above 70 years and one out of every two people above 80 years now. Interesting. First patient diagnosed by Dr. Alois Alzheimer, 100 years ago, so 1920-ish, interesting. And do you know the story of how Alois Alzheimer, how did, how did, is this a he? Is this a she? Yeah, she used to complain. She? She. Is the, is the professor or is the doctor? The doctor is Alzheimer. Oh, but is the doctor a he or Auguste is a she? The doctor is he, Auguste is she. Is she? Okay. And yeah, and how, yeah, how did she and he, how did, how did Alois understand Auguste's issue? How did he open her to understand that? Yeah, no. So he provided the first clinical documentation of the cognitive loss in Alzheimer's patient. So she used to complain, confusion, memory loss, all the classical changes that we are seeing now in Alzheimer's patients. Then Dr. Alzheimer went beyond just the clinical investigation. He, in fact, looked at the autopsy brain of Auguste. Oh, interesting. Yes. And then he noticed those plaques in the brain 100 years ago. Wow.  And then how are they causing, how are they associated with Alzheimer's pathophysiology? So we've identified now that those plaques are made of amyloid beta proteins. And those beta proteins, they are, they aggregate very rapidly. And those aggregates, the small aggregates, could be very toxic compared to amyloid beta protein that hasn't aggregated, that remains as a monomer, what we call just one molecule. So it's not that toxic. But when it starts aggregating, those aggregates can be very, very toxic. And several scientists have even compared them to be prions, again, that have tendency to aggregate and those prions cause mad cow disease. Interesting. So this is an 100 years ago, we're talking autopsy is what started our scientific understanding of the memory loss of these issues. This is very important because these are those, this is how you get to an edge of science is that you have to take initiative and and do things like do an autopsy and find these these amyloid protein buildups. And this is the plaque is specifically the last 30 years. He's saying we're under state, we're diving into understanding the plaque that's building up and causing the plaque causes the neurons to die because and what's the relationship with the tangles as well. It might not be the plaque that's problematic. It might be those oligomers before plaque formation that are distributed all over the brain that could be causing the problem. Plac, according to many scientists, could be a protective mechanism. So body is actually encapsulating those proteins into a plaque and which is then not that toxic. Plac formation could be a protective mechanism similar to like formation of atherosclerotic plaque in the blood vessels. That could be a protective mechanism, but when it's when it grows bigger, it blocks the blood vessels and cause problems. So it's, you know, as in these cardiovascular diseases, instead of actually removing the plaque, we tend to address issues that promote the generation of the plaque. But in case of Alzheimer's, we might be doing it in a different way. We are trying to deal with the plaque formation and trying to clear or break that plaque down rather than addressing the issues that have caused the problem, that have caused the plaques. So according to our investigations, the cerebrovascular damage could be one of the contributing factors to that eventual buildup of plaques in the brain. Yes. The healthier these billions of microvascular chur that's carrying the glucose and oxygen up, the healthier that that is, the less of the plaque buildup that even occurs in the first place. So this is again, this is coming to preventative medicine. The health care that you're wearing. And how do we then keep the billions of microvascular chur healthy to what's our what's our strategy? Yeah, we have known this for all along, right? It's a right exercise and a right amount of exercise and food. Yeah. And sleep. Huge. Yeah, sleep. But there was a study published in Science that demonstrated sleeplessness can promote amyloid buildup in the brain. So again, suggesting that those are all, the healthy lifestyle is the key to protect the person from these neurodegenerative diseases. Yes. Yes. Ronny, let's go to that next image too. Okay. And this is kind of, as we're talking, you mentioned earlier, the fact that we typically don't think of one little microvascular chur with blood vessel for every single neuron in the brain. That's a very interesting point. So that's called this blood brain barrier. And that's right, you know, that really starts right about at where the initial part of the brain starts. So usually all the blood vessels that are supplying blood to the brain, they have endothelial membrane. What does that mean, endothelial? Endothelium is the cell lining of the blood vessels. Okay. Interesting. All the blood vessels are lined by endothelial cells, a single layer of endothelial cells.  Interesting. So there are no gaps, they prevent the movement of any molecules non-specifically to get into the brain. They prevent the movement of bacteria, movement of viruses. Interesting. Any extraneous substances, unwanted substances from getting into the brain. Because brain cells, they don't have ability like the peripheral cells to protect themselves. Neurons are highly specialized. They do what they, you know, they do, they functions very, very systematically and with high fidelity. So they don't have the same capacity to handle the abuses like the peripheral cells. So they need protection, they need a certain environment to function effectively. All that is maintained by other cells, other supporting cells. And endothelium, endothelial cell is one of the most critical supporting cells. Fascinating. Endothelial cells are what, they're lined very tightly in the blood as it's going up to the brain. They're very tightly, and that prevents the bacteria and other things that the body cells can fight against. The brain neuron cells can't fight against because they're super focused on activity in the brain, that the brain has to do. This is very interesting. So then in the body, the endothelial. So there are gaps. There are gaps. So that nutrients could go in and out, likewise the metabolites, the toxic substances could get out quite easily. But in the brain, we don't have those gaps. As a consequence, brain needs specialized systems to send material and to send signals in and out of the brain. And then this called blood-brain barrier is then because you can't send a molecule through the blood up into the brain. Unless brain needs it. Interesting. So it won't take molecules unless the body already considers it like an endogenously made substance that then, so you can kind of trick the blood, the brain to taking it. Right. So glucose, you know, brain is 3% of body's weight, but then it consumes 15% of glucose. So- I've heard that numbers as high as 25, is that, could it be? Could be depending on the condition. But at a normal physiological level, on average, it's about 15%. So for all that glucose to get into brain effectively, the blood-brain barrier has glucose transporters functioning, again, with high fidelity. You know, there cannot be any damage to those glucose transporters, otherwise the brain could suffer from lack of nutrition. And this is where insulin is a big key. I would like to, again, make a distinction there. Those glucose transporters, they don't listen to anyone. They don't even listen to glucose. They're independent of glucose. So the glucose transporters in the periphery, in the body, they respond to insulin. They need insulin to act, for them to, you know, actually insulin signals them to take up glucose. Yes. Those glucose transporters are insulin dependent. Like in the muscle, for example, it is insulin dependent uptake of glucose, but in the brain, it occurs independent of insulin because insulin goes up and down in the body, depending on the time of the day, depending on the consumption of food, insulin levels keep going up and down. If the glucose transporters at the blood-brain barrier is listening to insulin, then there will be a huge shift in the amount of insulin getting into brain, depending on the condition of the periphery. So it's a very steady for the brain, but the body is much different in response, interesting. So this functioning is actually regulated by blood-brain barrier, which is the endothelium. Then there are other cells in the blood vessels called perisides. So perisides are like supporting cells to the endothelium. And then we have, that's part of the vasculature. We have the endothelium and then the perisides in the blood vessels. On the brain side, we have astrocytes and neurons. So all those four cells, they function together. So we call that a neurovascular unit. So neurovascular unit communicates and then it actually coordinates all the regulatory functions that are happening between the periphery and the brain. So any damage done to the neurovascular unit could be problematic, and we believe that it could be the earliest damage done to the brain in Alzheimer's brain. For those four cells to be miscommunicating? Miscommunicating. Yeah. Okay. Interesting. CBF means free blood flow? So what is depicted in this figure is the response, the connection between endothelium, the blood-brain barrier, and the neuronal response. So we call this neurovascular coupling. So these are so interlinked that here when the neural response is triggered, it could be triggered by many activities, like even opening eyes could trigger neuronal response in the visual cortex. So once that neuronal response is triggered, then neurons present in that brain region needs nourishment, oxygen, and then they generate byproducts, they should be removed very, very quickly to accomplish that function, the blood vessels are dilated. In that region. Interesting. And then they supply more blood carrying the nutrients and also to bring the metabolites out. So that response is what we call neurovascular response, and that's measured by change in the cerebral blood flow. When you have neuronal response, very quickly you could see changes in the cerebral blood flow. So this is the main signal that's captured on functional MRI to actually relate to which part of the brain is functional under certain stimulation. So this should be done very, very predictably, but in diseases like Alzheimer's disease, that neurovascular coupling is disrupted. Yeah, interesting. Yes. Okay. So then let me see if I can do this. So then the neurovascular coupling, when you're meditating, you close your eyes and you decrease the amount of blood and glucose that's flowing to your visual cortex. And so then the visual processing part of your brain, the neurovascular there, it narrows because it doesn't need the processing because your eyes are closed. It might not narrow, but it stays at rest. At rest. In the fMRI you can see that there's less blood that's moving to that part of the brain. Okay. And then once you open your eyes again, you can see in the fMRI that more blood flows there for the processing. And then in a brain where the cell communication isn't working as well, then it's not as the ability for the blood to move into that part of the brain is it's miscommunicated. Yeah. Okay. So that's the demands of the neurons. So if it's happening over a period of time, then the neurons could die off in that region. Interesting. Yeah. If the miscommunication happens for long periods of time, then that causes the neurons to die. Okay. Okay. Cool. Let's move on. Yeah. This is a good way of explaining the normal versus the Alzheimer brain, yeah. So you have the material transport and the signaling going on or carried on by the blood brain barrier between periphery and the brain. So you have all that communications very well laid out in the normal brain. But then in Alzheimer's brain, that communication system is all disrupted. As a consequence, you could see the, you know, like you see on a highway, you could see the build up. You could see the traffic that's slowing down.  And once the amyloid proteins are together and if the concentration is growing in the brain, they could aggregate. Those aggregates could cause problems in the neurons. And then eventually can lead to the neuronal death. Yeah. Yeah. This analogy is very powerful for, you know, we're talking about diseases of heart and brain. This similarly affects our heart as well as when you see the build up versus this free flowing. The traffic analogy is very powerful. Thank you. Yeah. It's a really good one. And so we want, we want to keep our heart vasculature as well as our brain neuro vasculature. We want to keep this moving like very smooth traffic. And then these things of really powerful sleep, good nutrition, good exercise, these are the things that keep the amyloid build up down. Right. Yeah. The physiological response is robust as a consequence the build up will not happen in the first place. So once that already, once it started happening, then it's, it might be very hard to clear and repair all the mechanisms that are responsible for, for the smooth flow like what you're referring to. Yes. Yes. When you, when you go back to the reason why many of the Alzheimer's therapies might be failing. Yes. The therapies that are focused on getting rid of the plaques might be failing could be due to the fact that the traffic, the build up could be corrected. But then what caused that build up is still not addressed. Yes. In this sense, the neurons might not recover from the damage that has been done a while ago. And it's again very important to notice that now we have clinical tools to see if the amyloid is building up in the brain. So we could use petimaging to investigate the amyloid build up in the brain. And we clearly know now that the build up starts 20 years before the cognitive changes are evident. Wow. So 20 years before. So what damage is done within that 20 years is not clearly understood. So build up could be starting as early as age 40 even really. Could be, yeah. Could be as young as that. If there is familial Alzheimer's disease, it's much earlier. Like usually the subject could suffer from Alzheimer's when he or she is about 50. Yeah. If it's familial, we're caused by mutations in the genes. But most of the disease is sporadic, which means that we don't know what the cause is. Wow. This is a very, very important for all of those that are listening, that are in their adolescent years in their 20s and even in your 30s, really experience life to the fullest now as best as you can because even if we're not even realizing that the cognitive decline is slowly occurring, it really is building up even if we're not noticing the decline. Right. Yeah. Right. Things happening without any notice and then all of a sudden there could be changes in cognition. By then it might be already too late. Yeah. Yeah. Do we have one more? Yeah. We have the one more image as well, the last one that we can pull up to. And this one's actually supposed to be a video, but we didn't get the video so you can explain it as an image. So what this picture is showing is the movement of vesicles, movement of whatever cell, whatever nourishment cell gets that is trafficked from one part of the cell to the other part. So that is handled by what we call microtubules. Microtubules. So these microtubules like each streak is like a microtubule. So microtubule is like a railroad track. It directs that movement from the center of the cell to the edge of the cell. So we can consider this as the center and then moving towards the edge. The edge, yeah. Yeah. So in a normal cell that flows very smoothly. Yes, yes. But when the cells are exposed to amyloid beta proteins, then you could see that those railroad tracks. Oh, wow. This is just crisscross. Yeah, these are way less.  Right. Like it's just being messed up. And the communication here is like looking like smooth. We know what's, we can almost predict where it's going here. It's a disaster. It looks like a disaster. And so then this is where you can see that amyloid plaque buildup. Well, you know, these are actually the blood-brain barrier endothelial cells. And these are the theothelial cells. So these are supposed to move proteins, not only amyloid beta proteins, but also a lot of HDL proteins, a lot of the iron-carrying proteins like transferent insulin. Interesting. They should be moved from the bloodstream into brain. If that's what is going on in the endothelial cell, then they will never reach brain in required proportions. And those are all growth factors. Neurons need them for good functioning. Iron, HDL. HDL, and even insulin. And even insulin. Yeah. Because insulin is a growth factor. It not only regulates insulin, it also regulates the mitogenic activity, what they call is cell growth, self-division, all those are regulated by insulin. So that's the reason why when insulin signaling is disrupted, you could see the cancer cells growing. Yeah. So in Alzheimer's it's the opposite problem because there is problem with insulin signaling the cells start to die. And what other techniques are you using along with your students, along with, you know, University of Minnesota and Mayo Clinic, what techniques are being used especially in the field of nanotechnology to both understand the pathophysiology but also to then go and do preventative because the nutrition and exercise and sleep is a very common mantra that civilization chants. Look in a nanotech perspective what could be done at age 30 to 40 to get us to that homeostatic capacity of like a 15 year old to keep us healthy. So the reason why we started developing nanoparticles for the treatment and diagnosis of Alzheimer's disease and to look at the buildup of those amyloid proteins in the blood vessels is looking at the examples from nature. For example HDL particles, HDL particles are nanoparticles. So they take up, they actually clear cholesterol from various cells and then they carry the cholesterol to liver. So nanoparticles could have the ability to interact with the endothelial surface, the blood-brain barrier, and they might be able to alter some of these processes. They could signal a change. Signal a change. That's one thing. One aspect is nanoparticles could carry a contrast agent for MRI, PET, to show us where the problem is in that endothelium so that we could detect the trouble early on. Interesting. Yes, yes. And then if you can detect where the problems are at then you can then go and target those specific areas and fix them. And then signaling this in young ages, you said in PET scans, and okay, interesting. So we are developing novel probes to see if there is any problem with the endothelial function. Can we spot that early on so that we might be able to repair the damage? And this is where I would like to bring the association between Alzheimer's disease and type 2 diabetes. So there is a clear epidemiological evidence that these two diseases are related, but we don't know how they're connected mechanistically. So we know that in the periphery, in other tissues, type 2 diabetes could cause problems to the endothelium, could cause problems in the endothelial cells. But what it does to the brain blood vessels is poorly understood. So if there is a problem with insulin signaling, you know type 2 diabetes causes insulin resistance. If there is a problem with insulin signaling in the brain blood vessels, all the functions are most of the functions that we've been talking about could get disrupted because they're connected to insulin signaling. So if we manage to find how they're pathologically connected, the type 2 diabetes and Alzheimer's, one big advantage could be we might be able to repurpose diabetes drugs to treat Alzheimer's, at least very early on. So that's one of the motivations behind our work. Can we repurpose, reuse those drugs to treat the neurodegeneration? Yes, yes. Is that because then similarly to how a drug that is assisting with issues with the cardio vasculature, with the heart disease areas and issues can then also be used for similar processes with the brain? Similar processes. So you know with the diabetes, the same problems again, HDL lowering, LDL increase, insulin resistance, all those are very, very, they cause problems to the vasculature. So using the same tools and similar understanding, we might be able to look at neurodegeneration with a different, in a different perspective because instead of just focusing on what goes on in the brain, it might be important for us to look at the aspects that could directly interfere with the brain function. And you know nowadays the National Institutes of Health has been investing resources into investigating the cerebrovascular contributions to Alzheimer's disease. And still the field is in its infancy and more work needs to be done in that direction. Yes, more funding for the National Institute of Health and for the National Institute of Nutrition. We're aiming to set up, shout out to Dr. Jun Yoon in that process because it's very interesting that you bring up this, the connection between the heart and brain disease and how if we understand their connection better we can tackle them together better. This is very important. Karni, this has been such an interesting conversation together and I'm really grateful that we ended up sitting down with you on the show while you're in the area. It's a pleasure. Thank you so much. And we have a couple questions that we like asking at the end of our episode. One of the questions that we like asking is if you think we are alone in the cosmos. Of course we are not and we have known that. But assuming that there are people like ourselves is probably far-fetched but I don't think we are alone in the cosmos. There might be living beings elsewhere in the galaxies but what they are, how they are is probably a frontier that has been untouched so far. Yes, yes. And then the second question we like to ask is if you think we are in a simulation. Absolutely, you know, I believe that we are in a simulation but then is someone else doing it or are we doing it to ourselves? You know, in the sense are we forced to act in a very particular way or have we programmed ourselves to do certain things whether we like it or not? Do we have real independence over our thinking? So all those really, you know, makes me believe that we could be in a simulation but that could be self-inflicted. It might not be someone else really playing with us or might be, who knows, right? You know, I'm open to, you know, after looking at this many unknowns. I'm so open to considering ideas that I'm not aware of currently. So, but you know, whichever way it will be fascinating to know. Yes, correct. Oh, high level of open-mindedness and poking with science at the truth. Yes, yes. And then the last question we like to ask is what do you think is the most beautiful thing in the world? Human mind, I believe, is the most beautiful thing. I might be biased, but the mere thought of the motivation to know actually is what convinces me that it's the most beautiful thing. And that's one of the reasons why I focus on Alzheimer's research because at the end of life, a person, you know, what is he accumulating, he or she? Not wealth, not, you know, fame, name, all those things are very ephemeral. But for that person, what really matters are the memories or the feelings or the connections. But in this disease, it's such a devastating disease that all those are lost. And to me, that's the real loss. So that's the reason why that's what motivates me to really find out if we could do something about it. It's crazy how well these devices keep the memory, almost 100% efficiency.  And on our deathbed, we are typically only remembering just very sparse life events. But if we can be able to remember all of these experiences, feelings and memories that we had and be able to store it for children to be able to access in the future and understand, that's just a very interesting. Well, what about the memories that we don't want to remember?  There's a lot you can't do about the trauma you experienced. Yeah, but we don't want to remember because it's causing pain. But whatever causes pain might not be not everything is bad. For example, there are a lot of painful memories that humanity has gone through. If we forget them, then we keep repeating. We keep getting into those painful memories. So memory, whether it's good or bad to a person or to a community, to society, is a valuable resource and that's all we have. That could bring up the murder rate, though.  And then our self-protective mechanism goes into effect again and we use violent measures to make sure that these memories don't happen again. We have had several guests, like, you know, Coco McKenzie and other people that have said that. On the other side of the traumas are sometimes the greatest treasures. And it's very important to actually integrate the learning experiences into the code of ourselves and the civilization in total. Even at the microcosm, you know, nowadays I believe that, you know, because we mentor graduate students and that's our legacy. And those are our, you know, graduate students will carry through their learning the collective memory of our experience and of our work. So nowadays I feel that they should be more trained to handle bad memories, failures, because if they're handled well, there could be success lurking underneath. Yes, yes. And this is a whole nother conversation on how to best be able to integrate these traumas, you know, maps and other psychedelic studies we've been experimenting with. There's been lots of interesting ways to integrate. And did we get any questions I see on YouTube? Yes, Charlie Sportello, watching in Akron, Ohio, asks if there's any connection between aluminum foil and Alzheimer's disease? Yeah, excellent question, Charlie. I think about 15, 20 years ago, it was believed that magnesium, aluminum, all those metals getting into brain could cause Alzheimer's. And there have been several studies looking at the role of metals in how amyloid proteins aggregate. In fact, amyloid beta aggregates in the presence of metals. But aluminum per se has been ruled out as the prime cause. But metals do play a role, particularly copper and zinc. Then a metal chelator that can get rid of the metals from the brain also failed in the clinical trial. So that might not be the only reason. But we cannot totally rule out the role of metals in neurodegeneration. But aluminum foil is probably, you know, is very safe. Because it's the aluminum that gets into, that's inhaled or that somehow can bypass the blood-brain barrier and gets into brain. It could be problematic. But that has also been ruled out as a major cause. Interesting. That was it. Thank you, Charlie. Thank you, Charlie. Yeah, it's nice everyone for tuning in that. We do have questions. Feel free to ask the questions in the YouTube and Facebook chats. We'll ask our guests the questions live on set. Karunia, thank you so much for coming onto the show. This has been such a pleasure. Thanks for having me. Thank you for teaching us about heart and brain disease and about Alzheimer's disease and about how we can really start tackling this at a greater level. We really want to thank everyone for tuning in. Thank you so much. Let us know your thoughts in the comments below and what we were discussing. 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