Welcome to MOOC course on Introduction to Proteogenomics. In previous lecture, you have heard Dr. Henry Rodriguez, he gave you very nice and broad overview of the field of proteogenomics, especially cancer proteogenomics, the major milestones which have been achieved and what kind of challenges which lies ahead for the community. Now, we are going to talk in much more detail in depth about first genomics module. Then proteomics and then we will try to integrate the big data and proteogenomics to make meaningful insight. In this slide, the first lecture today is going to be by Dr. Kelly Rogels. She is assistant professor at New York University in USA and she is going to talk about genomics, one of the major aspect to understand the comprehensive view of any disease or any system. Dr. Kelly will talk to you about the diversity of omics in biomedicine and especially the milestones which have been achieved using genomic technologies, various type of mutations like hereditary or acquired mutations which affect different type of diseases especially in context of oncology. What are the publicly available where one could try to study and find the mutation studies and little data sets which are publicly available. Along with that, the basics of gene sequencing and methodologies will be covered as well. Okay, hi, so I am Kelly Rogels, I am an assistant professor at NYU and I am going to give you an introduction to genomics. Just to start, I wanted to just give you an idea of what my lab does to give you a little context about who I am and what I focus on. So our lab really is interested in applying multi-omics integration methods across a lot of different questions and diseases. This includes cancer, the human microbiome and I do a little bit of work with PopHealth. I am obviously just going to talk about the cancer stuff today but we do sort of think about the integration across not just cancer but lots of different scientific questions. And really what we are interested in is looking, taking a systems approach to human disease. So looking at combining omics at the cellular level, so understanding how proteogenomics within molecular networks interacts and how that impacts disease. Also thinking about intercellular multi-omics, so not just within one cell but across many different cells and then in some cases if we have the data, which is of course always the limitation, if we can look at interorgan multi-omics, so if you have many different organs and many different omics, you can really have a very large and comprehensive view of human disease and I think this is really the goal and we are starting to get there as we are able to generate more and more data. So I think everybody here is going to eventually touch on many of the things in this slide so I wanted to bring it up in the beginning. So really we are going to be talking about all levels except not metabolomics, I don't think anyone here is going to be talking about that but in terms of genomics, epigenomics, transcriptomics and proteomics and there is many different data types that we can data that we can gather from these different omics data levels and so today I am going to touch specifically on the genomics, epigenomics and transcriptomics data and go through an overview of how we collect the data and then how we analyze it. So as I mentioned there is a large diversity omics that we are currently studying in biomedicine so this slide was taken from the TCGA which I am going to talk a bit about and then I added some extra slides to represent proteomics and phosphoproteomics here but there we can look at the genome which is really the long term storage information of the cell, the transcriptome which is the retrieval of this information, the proteome which is the short term information storage and then how the signaling networks interact and the interactome which we will also touch on. So here is just a lot of the different levels of data that we can gather and at this point and so in terms of next-gen sequencing we are really covering all from the micro RNA up through the mutation calls and that is what we are going to be focusing on. There has been a long history of studying the genetics of cancer which predates the proteogenomics of cancer and so the reason why genomics and cancer have become such an enormous field is because it is known that at the molecular level cancers cause by mutations that result in a barren cell proliferation and these mutations can either be germline meaning that they are inherited or they can be somatic meaning that they are acquired at some point in life and these mutations if they are occurring in oncogenes they can cause over expression of these oncogenes, oncogenes meaning that they increase tumor proliferation, they can be fusion genes, they can be an altered gene product so there are many examples of this that we will cover some of them in the hands-on such as ERBB2 it is just one we are going to talk about specifically in the genomics hands-on session and then there is tumor suppressor genes so these are genes that normally regulate cell differentiation and suppress the proliferation of the cell. So if there are mutations in these genes there is an increase that would reduce them, there is an increase in proliferation so you can we look at both tumor suppressor genes and oncogenes in terms of the mutations in the cell and as I mentioned there are many genomic drivers this was in 2010 there was a I think this is in nature yes in nature there was an article about the cancer genome and the TCGA which is the cancer genome atlas which I'm going to cover in a bit of more detail later really was one of the projects that spearheaded this so they sequenced actually this is an outdated number I think it's more like 11,000 cancer genomes over 33 different kinds of cancer so it's a really wonderful data set that everyone has access to and there's also the international cancer genome consortium which is another large project that has worked to collect lots and lots of genomics data for cancer that you can all also access and then there's what let's call there's a typo there and I apologize cosmic which is the catalog of somatic mutations in cancer this so this is just cataloging all of the mutations that have been found to occur in tumors as well so this is another really good resource that's publicly available so now I'm going to jump into genomics I think a lot of you probably know this but I realized I should probably have a slide in there just because you know just in case otherwise you'll be completely lost after this so the chemical structure of DNA and RNA so DNA is double-stranded RNA single-stranded and there's these nitrogenous bases that make up nucleotides they differ between DNA and RNA in that there's a thymine in DNA and a uracil in RNA triplets of these bases encode different amino acids so that's something that we're going to go into okay so just two slides on the history of sequencing just because I think it's important to start start there so Sanger sequencing which how many people have heard of Sanger sequencing is a great wonderful so this was developed by Frederick Sanger who received the Nobel Prize in 1980 for these methods and it was the most widely used method for until next gen sequencing came around and we're going to spend most of our time talking about next gen sequencing so what they what this method did was use these modified nucleotides which attach to the DNA strands and each of them was tagged with a fluorescent label that identified which nucleotide it was so I'll show the schematic of this so here we have our DNA template so the double-stranded DNA was denatured to get a single-stranded DNA and then you add in these nucleotides that have either non fluorescent or fluorescent tag on them and then you have a DNA polymerase so it allows the strands to grow and becomes double-stranded because DNA polymerase is adding on these these deoxyribonucleotides and whenever it gets to one where there's a fluorescent probe it stops so it keeps growing and then these these fluorescently tagged CDNTPs are randomly added so as soon as they're added on it stops and then so you know that the the length this what is it six nucleotides up is a C and seven is a G and etc and then you run this on a poly acrylamide gel separate out the strands and then you can use a fluorescent detector to figure out at what length each of the different nucleotides is at so this worked really well it just took a really long time so eventually next-gen sequencing came along so this was established in the mid to late 90s and it was based on this Sanger method but it incorporated some new innovation so how many people are you have used like a luminous sequencing for example okay so there were more Sanger sequencing people here in the Lumina yeah so so now what happens is you still have this DNA template so it's a single-stranded DNA template and it's fragmented and there are adapters that are put on the template and we're going to talk a lot about these adapters because we can do some cool stuff with them and then what happens is the these fragments are attached to some a solid support like a flow cell we'll talk about that as well and then there's an amplification that occurs so that you stick your fragment onto this this flow cell and then you amplify it so you end up getting a cluster of the same exact same sequence that's stuck in a certain part of your flow cell and then you so this is what's called library prep so this is how the library is prepped from your DNA template and then what happens is we do what's called sequencing by synthesis so it's similar to what I mentioned in the Sanger method except now these fluorescent label nucleotides you can actually you can when they when they bind to the DNA they stop the synthesis but then you can remove the fluorescent probe so that you can continue to grow it so you don't in the Sanger sequencing once it hit there it stopped now you can take that floor off so you can keep growing instead of having to do all of the different lengths and then running it through a gel now you can just keep adding more and more on and just taking a photo every time the floor is put on you take photo you remove it etc. etc. until you grow it all the way up the strand and then the data is exported as a text file so it reads out what cluster it is what read it is and then the actual sequence so this is a much faster and more efficient method than the Sanger sequencing what we're going to talk about is a lot of different methods okay so genomics we have de novo sequencing mutation discovery exome and whole genome sequencing and copy number alteration or variation detection epigenomics we have assays to look at transcriptional activity protein DNA and interactions and methylation analysis and then the transcriptomics level we can look at mRNA expression alternative splicing and micro RNA expression and there's more these are just some of the basics so I included some current next gen sequencing technology that's being used the moment and sort of the newest instruments so the most common one at this point is Illumina high seek so the this one I'm going to talk about why it's the most commonly used and what technologies they've come up with that have made it the most popular so Illumina high seek it's commonly used for the whole genome and exome sequencing targeted sequencing RNA sequencing chip seek and it's really you can parallelize a lot of samples at once it's pretty fast and it's highly sensitive and has a high output and then there's Illumina my seek which I wanted to introduce but we won't talk about it much because it's not used much for cancer it's mostly used for metagenomics so microbiome data small bacterial sequences so or 16s ribosomal sequencing and so the cost is higher compared to the high seek but it's faster and has longer read lengths which makes it good for these these other smaller genomes that are less annotated there is pack bio and I'm going to go into each of these in more detail which produces very long sequence reads but it has very high error rates it's at this point frequently used in combination with Illumina because they offer different strengths and then there's the Oxford nano poor Minion which is super cool has anyone seen one of these okay they're like usb's which makes them pretty exciting and they're also really good for long reads they're ideal for that reason for this bacterial viral genomes they're very small they have historically had very high error rates but they are trying to improve this we'll talk about that a little bit more too so for Illumina we talked about the library prep so it happens in the same way that we discussed before where you fragment them so here I found I found a couple different here it says 200 to 500 but I've seen different quote numbers for how long these fragments are and then so you you then do this cluster generation on this flow cell and the flow cell is really what I think made Illumina the top of the market for this so they created this pattern flow cell so you could get really clustered high high cluster density and this increased the output of the actual sequencing analysis so once you do this the cluster generation on the flow cell and I'm going to talk a little bit about what this solid phase PCR is on the next slide you do the same sequence the sequencing by synthesis that we talked about before where you just keep adding on different nucleotides and just taking the picture of them as you go okay so the solid phase PCR which is also known as bridge amplification what happens is you have your DNA that is fragmented and then you have these adapters so again the adapters are put on so that you can attach it to the flow cell and then the DNA is denatured into single strands so you break it into single strands and then you attach it to the flow cell and then the single strands they have these other adapters on that are sitting on the flow cells so what happens is the single strands end up bridging over to attach to the complementary adapter sequence so it creates this bridge and then it's elongated by using DNA polymerase so it creates this a double strand and then it's denatured again so then it creates single strands again and then it bridges over again and it keeps creating these more and more of these clusters yes yeah correct so you're saying why not just put like all five prime adapters on and all so I don't think you can control which ones are going to stick but the adapters themselves attached to the plate regardless oh I see what you're saying why do you not I think it's actually because you want it's a good question I look into it more but my guess is that because you want to get both if you do single stranded you want to get it from both directions so paired end versus single reads which we'll talk about I have a feeling that that's why but I don't I'll actually look into it so thank you that led me perfectly to my next slide so um so paired end sequencing versus single end sequencing um paired end sequencing is now really the norm for sequencing um but I think some people likely still use single end reads as well so I figure we should talk about it um so what it means is that you're sequencing both ends of the fragment so as I mentioned the fragments are let's say they're 500 base pairs long um typically when you based on the reagents that are used for Illumina you only measure 50 to 200 of those base pairs so you're not measuring the full fragment you're just measuring the ends of the fragment um so if you do it just from one end right you're only going to be measuring let's say those 100 base pairs on one end of your fragment the first let's say the three prime end um but if you if you read both the forward and the reverse right 100 on both sides then you have a 300 base pair gap but you have three two you have 100 and 100 on both sides and you know that they're from the same strand so you know that that gap exists but you can get both you can get more information from that cluster than you would normally if you just did it from one direction so really you're producing double the reads um for the same amount of time so it's a little more it's more expensive which is the limitation but if you can do it it's it's um it's a better use of your sample and your time and the alignment is much more accurate we'll talk about alignment so when you actually take these reads and you try and align it to a reference genome you have a lot more information on what how to align it because you have even though you have that gap you know exactly what is on both sides of that gap so how this is done and you sort of alluded to this in your question there's the there's a sequence primer that's specific to the three prime and the five prime end um and um that's included in this adapter uh yeah so that is how the paired reads and reads work any other questions on this yeah say sorry say that again specifically is that in the left yes yeah so the adapters oh no so that the the fact that it only reads 100 or 150 is based on the actually based on how much of the it's like the aluminum gives you a certain amount of ddm tps to actually make the reads so it's more about the um reagents you use than the primers it's not random it's not random it's not random no but no no it's not random the 150 is not random because you you tell the alumina how many times to the instrument how many times to take a picture right you're going to say take 150 pictures and then stop because i know that my reagents can get me to 150 yeah yeah that's not random you'll always have 150 if you decide to do 150 so another thing you can stick in the adapters is a way of actually multiplexing your samples which means you're you're pooling lots and lots of samples together so you can run them all at once instead of just running one sample at a time so um what is done is there's a unique sequence that's added to the adapter that indicates um what sample that that sequence came from so during the library prep you add these these unique sequences on um and then that way when you mix them all up and then you do all of your your library the library prep done and then you do your sequencing after you have your data you have this sequence that identifies so the blues came from you know sample one and the pinks came from sample two and then you can just in terms of the bioinformatics you can go in and pull out which ones came from which sample so um this is a very common technique at this point as well paired n would be better for targeted i think pareden's always better right if you can afford it this is always the limitation for these things right is that your question yeah yeah pareden's always better if you can swing it yeah yeah so i did want to touch on the two other sequencing um platforms that are not as commonly used but i think they're going to become more and more present so i wanted to talk about them a little bit so there's this pack bio um may use um this what's called a smart method that um can produce really long reads so the limitation with alumina is um as we mentioned that it will only go up to about 200 base pair so you you when you're aligning and you're trying to figure out where those sequences belong on the genome you don't have a lot of information you only have those base pairs but if you have four you know 40 kb then you have a lot of information and you can do de novo sequencing you can you can get a lot of information about let's say you have an unknown um species that you don't even know nothing about you don't have a genome so you can gather these long reads and then try and do de novo alignment and and figure out the actual reference genome of a new species so that's where these things um typically come in and um another so i'm not going to go into all the methods behind this i did include if you're interested there is this paper that goes into a lot of the details on it but um it doesn't require this pause between the reading of the steps so in alumina you know you have the floors added on and you have to take a picture and you have to take the floor off and then you put a new one on and you take a picture so there's this pause step every time that you add a new one on so in this method that's not that does not happen so it's a lot faster um so unfortunately though it has a very high error rate so 15 percent's pretty pretty bad um so i think they're likely working on lowering this but it's something to keep in mind but it is still really good for de novo assembly of small genomes um structural variant identification um and you can actually directly identify epigenetic modifications without having to do another completely different type of omics analysis which is very cool um and then the other one which is actually quite similar in terms of some of its benefits is this oxford minion which again is this usb science sequencer um and it can do really ultra long read lengths so up to hundreds of kb and what happens is the way that they do this is there's this protein pour that's actually a e-coli mutant um of a csg g protein and they figured out that if you put this on a membrane you can actually read the the dna strand through this pour and the different bases depending on what basis coming through the pour it disrupts the current in a specific way that you can read electronically um so i think this is super cool um i think that the problem that i've heard from people who are more involved in the actual instrumentation of the field is that it actually goes too fast so the reason why there are high error rates is because it's moving too quickly um and they're trying to figure out how to slow it down and i think it's from what i've read um it has gotten a lot better and there was a recent paper i included here that came out this year that actually used this to assemble a reference um a human reference genome so it was just kind of a proof of concept paper to show that you could use this to do some of the stuff that we've previously just used aluminum for so um i think that this is a very exciting um development in next gen sequencing especially because you can just hold it and take it to places and sequence i guess whatever you want to so um there are a lot of different file formats that we'll talk about uh just because um i you know i sit in the data analysis side of most of this so i don't typically do i do work with people who do sequencing and i work with the with the the um the genomics technology center at NYU a lot and so i'm familiar with what they what they do but i typically just get the data after um that's what i prefer uh so i wanted to talk a little bit about file formats so um the raw data is typically in what's called a fast queue format there is a gen bank format which is an sra there is alignment formats which are sands and bams there are these genome browser formats and then there's genomic variant formats and we'll talk about each of these in some level of detail so the fast queue has anyone seen a fast because everyone's seen a fast queue who's seen a fast queue okay some people okay so um this is what this is an example of what it looks like so it just starts with information on the actual um instrument and then run number um and then it has information on the flow cell this is an alumina of fast queues it depends on the instrument just showing you the aluminum aluminum fast queue because i think that's again the most common for cancer genomics so the flow cell id the lane and the tile so you can see here if there's a flow cell contains eight lanes and then each lane has two columns of tiles so you really get exactly where um the sequence was in terms of the flow cell coordinates and then you also get an x and a y coordinate of the cluster on the tile you get a read number so if it's um single reads you'll only have a one if it's parent and you'll have a one and a two and then um if it's filtered out for quality reasons you get a yes here if it's kept you get a no and then there's a sample number and then there's the actual sequence and then you get this quality score which is a it's an encoded score using ASCII characters um to represent the quality score of each of the bases so it ranges from zero to 40 in terms of quality um and you can use there there's a key that goes along with the alumina that just shows exactly what each of these corresponds to so in today's lecture you go to the overview of genomic technologies and especially its relevance in context of cancer and how it could actually provide a broader overview to understand any disease or clinical conditions you also learned why in genomic sequencing two side reads are important as compared to the single reads and how it can affect the accuracy of sequencing you also learned about gene sequencing how it has evolved over the years and now we have not only achieved much higher accuracy of sequencing in a much shorter time frame and in a very very cost effective manner but also the instruments have become much more miniaturized and one could see the examples like Oxford Nanopo Technology Minion which is very easy to carry and transport anywhere as per the requirements Dr. Kelly has also introduced and made you familiarized with availability of data sets and how to obtain different type of raw files and format them for various parameters for further analysis let's continue the next lecture in the same flow of genomics where Dr. Kelly is going to talk to you about the sequencing alignments and various factors which affects that thank you


Hi everyone, it's Gabrielle with Oxmer Auto Group, so I'm here at Ronald McDonald House. I have Hal Hadley and he is the CEO. So the reason I am over here is that Oxmer Toyota is going to be sponsoring the whole in one with a vehicle for your upcoming golf event, which is on August 9th, I believe. So can you tell us a little bit about that event and how is that going to be helping you all? Yeah, Gabrielle. Thanks for coming out and visiting us at Ronald McDonald House today. So our golf tournament on August 9th at Hunting Creek is one of our signature fundraisers to support Ronald McDonald House. We're a home away from home for families of seriously ill children. So we're standing here in our 56 bedroom facility in downtown Louisville, where we serve families who travel to Louisville to seek health care for their children. And I know I just did a little walk around. This place is absolutely beautiful. Can you tell us a little bit about this place? How long have you guys been in business? Things like that? Absolutely. There are doors in 1984 with 19 guest rooms here. We've expanded several times since then and most recently we completed the biggest expansion in our history last year in 2020 growing from 36 to 56 guest rooms. So it's been a really exciting time for us. We bought the building next door to ours, renovated that, renovated our original facility too. So we've got what's essentially a brand new 56 room facility in downtown Louisville. That's great. And now unfortunately with COVID-19, we're kind of getting out of that now. The last year, how has that impacted you all with COVID-19? Could you still have guests stay here? How did that look? So like everyone COVID-19 did have significant impact on us, I'm really proud to say our doors never closed there though. We did pause new family check-ins for about three months last year. We then slowly started checking in new families and now this week we have over 40 families staying with us at Ronald McDonald House. So yeah, we're very close back to what we would consider normal operations. Okay, well that's good. I like to hear that. Okay, and lastly, how can people get involved with you? I know you guys are based a lot on volunteers. So if someone does want to volunteer, how does that look like? How can they do that? Yeah, we're very much volunteer driven in a typical year. We'll have about 15,000 hours of volunteer time logs. So we've always been volunteer driven. The easiest way to learn more about us, including volunteering, is just Google Louisville Ronald McDonald House. We've got a lot of great information on our website. There's lots of ways to get involved, whether it's volunteering here on site, doing something to help us out from your own home. Lots of opportunities. So yeah, check it out. Okay, awesome. Well, I will have a link to that where you guys can take a look at that. All right, well thank you so much for taking the time to speak with us. Hopefully the golf event goes off very nicely and we'll be out there with that vehicle. Well thanks. And thanks to Oxmore Auto Group. We really couldn't do what we do without sponsors like you and provide all these services to families free of charge. So thanks to you. Thanks to Oxmore Auto Group. Yeah, thank you. It's our pleasure.


The second one, it's a similar effort in redesigning the icon data and T layout. So when we use the icons configured for options in option sets just to enter data by tapping on an icon, it was present in that before, as you can see here on the left side, but now we have included also in the, sorry, redesigned it also. And the new UI is the one you are seeing on the screen, which looks much more nice and again integrated with the style of the application.


The preparations of the heart belong to man, but the answer of the tongue is from the Lord. And then Proverbs 16 verse 1, Proverbs 16 verse 3 says, Commit your works to the Lord and your thoughts will be established. I just wanted us to focus on these two verses. The preparations of the heart belong to man, but the answer of the tongue is from the Lord. Commit your works to the Lord and your thoughts will be established. So we see two things here, man's responsibility and we see God's anointing or God's response. In response to man's responsibility, we see God's response. And the first verse talks about how the preparations of the heart belong to man. So whatever preparations are required for us to be, you know, maybe spiritually prepared for us to hear from God, for us to minister in the right way, the preparation that is required, whatever needs to be done internally, you know, like we go before him with purity of heart, we go before him with diligence and all that belongs to man. But the answer of the tongue is from the Lord. The Lord will respond with his wisdom. The Lord will respond with his power and so on. Verse 3, Commit your works to the Lord. So that's the responsibility of man or the human being to commit the works. Okay, whatever works are there, whatever responsibilities are there, whatever tasks are there to commit it to the Lord. And then the promise and the Lord's response is that and your thoughts will be established, made firm, made strong, made secure. So in both these verses we see that, right? We see man's responsibility, God's response. And it's so important to understand that we have a role, we have a responsibility. And the Lord is faithful to come back to us with his response to enable us to establish us for the task that is ahead. The Lord is faithful to do that. But he's also, we must be willing to do our part in preparing ourselves. We must be able to do our part in committing or laying everything before the Lord, right? And that word, commit, again, the Hebrew, which means to roll away. The picture that we have is that of a camel that is fully laden, fully loaded. All kinds of weights, maybe after a journey. I mean, it's just fully, the camel can carry a lot of weight, right? So it's, let's say it's fully packed, loaded. And after a journey it comes back. And the master, the one who owns the camel or the one who rides the camel would give a command. And the camel would actually kneel down and roll that bird and off its back. Kind of roll it up back. So that's the picture that we have of that Hebrew word galal, which means commit, right?  And what will happen is that our thoughts will be established. Now we need established thoughts in order to have established action, right? So that is what the Lord has promised that if you would just roll on or roll away those tasks, maybe we can do it in prayer, you know, and that's the thing. Or you can just pray and just tell the Lord, Lord, I have this and these are things that are on my mind. These are things that are my responsibilities. We're not, you know, escaping from the responsibility, but we are going to the Lord and saying, Lord, these are things that I have in my hand right now. These are things that I need to do. And the Lord will establish, make firm our thoughts so that our actions are also firm. Okay, let's pray. Okay, Father, we thank you for this day. We thank you, Lord, for these words. We thank you, Lord, that the word says that, Lord, as long as we are faithful, Lord, in cursing you, in taking care of Lord, what we need to do, Father God, what is within our control, God. Lord, we thank you that you're always faithful in your response. We thank you that the preparations of the heart belong to man, Lord, as ministers of God, as servants of the Most High God, the preparations of the heart belong to man, that we will make sure that we don't carry unnecessary weights, that we will make sure that we don't carry unnecessary burdens, that we will make sure, oh God, that our hearts are pure, and Lord, before you, Master, that we don't have any bitterness or offence or any kind of fear, Lord, any remnants of anxiety or oppression, Lord. The preparation that we will come before you in faith, oh God, that we will lay everything aside that needs to be put away, put aside, Lord. And then, Lord, we do that the answer of the tongue comes from you, Father God, the response at every situation, God, the wisdom for every problem to solve the problem, God. That response of the tongue comes from you, Master, we thank you. And Lord, we thank you because your word also says that when we commit, when we roll away, God, our, commit our works to you, Father God, the things that we need to do, the things that we, our responsibilities, or the tasks, oh God, and you will make firm our thoughts, Lord. Right down to the thought level, you will establish it so that our action is strong and firm and are right before you, God. Yes, Master, we pray that we will experience this, Lord, in our own lives, even as we prepare our hearts, even as we commit our works to you. We thank you in Jesus' name, we pray. Amen. Okay, just one second, sorry. Right. Okay, so I just wanted to, as we progress, I think we've progressed quite a bit with our research. And so I just wanted to hear from you all, you know, what is happening? What is the, what is the status? Because I think we have a couple of weeks, like maybe 20 days or so, to finish the report and then start preparing for the presentations after that. So we'll take this time to answer any questions, we'll take this time to clarify any doubts that you might have about the project. And yeah, so it just takes this time. So each of you can take some time to share about what the status is. I mean, like you don't have to, if there's work, a lot of work to be done, you know, there's a lot of work to be done. So you don't have to shy away from saying, okay, from being real. So, so just wanted to open up this time. Okay, each of you can share how the work is, how it's heading, what else needs to be done, etc. Okay, yeah. So we'll go first. Anyone, I'm just opening it out to you. Let's go ahead. Prince, would you like to start? Yes, I think everything we find. So I'm doing collecting the data from the two persons, those who are not believers. So I collected that data. And now I'm going to start. I see. Sorry, Prince. So how are you collecting the data, Prince? How are you collecting the information in person meeting? Okay, okay. So now I'm going to start at two persons, those who are believers. So what about the belief system in my own research? Everything that's fine, but one thing is about the paper. I think there's a 25 to 30 pages, but here my own research that will be, I think, 12 or 13 pages only. Okay. The thing is, you know, in that format with that line spacing, etc., it will be, I'm sure it will come to at least 25, you know. I'll try to more explore the things. Correct. And then you can also present some information about like the background of the people, the background in the sense of that community itself. Yeah, that information, the historical background. I'm sure that will be, I mean, that will be useful information as also it will, you know, it will have some, you know, some volume to it. So that is also there. Yeah. So one thing, one more thing is, can I put the picture? Yeah, sure. Yeah. Yeah. Okay. Okay. You want to know whether in the report, you can put the picture. Of course, you can put picture in the report. You can, if there are statistical tables, you can put that graphs you can put. So, yeah, you can use all that. Not a problem at all. Right. Okay. Okay. So what I would say is like you, yeah, make it as a Word document and then convert it into a PDF so that they can be no changes to it once you're, you know, fully finished and then can upload the, you know, the document. Right. Okay. Fine. Any, any doubts, Prince? Anything else that you regarding the work? Not yet, but I'm looking for if there is something difficult. Okay. The idea is like you can even shoot a video of the people. Right. In the sense, you can take pictures if they are okay with it. Right. If they are okay with it, you can even take videos of it. Maybe a short clip when they share something so you can use that for the presentation or PowerPoint presentation, you can use this information as well. So that's just a thought, just an idea as you're presenting. You can say, okay, this is the community. This is where they live. This is where they, you know, worship and or if you're saying these are their beliefs, this is what they do. These are the challenges you can actually show pictures and, you know, if it's pictures that you have taken, of course, you don't have to, you know, cite any, give any credits to it. But then if it's a picture that's already been taken by someone, then you'll have to give credit saying, okay, so-and-so has taken the picture. Right. So you can use that. So you can try that also. And it'll be useful information for you. Especially if you're collecting information.  So you're meeting them and then you're talking to them. So you can even record it. You can ask them the question, record it and keep it for your, yeah. You can edit it and use it. Thank you. Yeah. Okay. So, Dave, any updates there from your side? I can't hear you, Dave. So, sorry. I saw that your mic was unmuted, but I couldn't hear you. We couldn't hear you. Maybe if you're, you can type it out as well. I can read it out. Okay. Who else? While we're waiting for Dave, maybe Kandan can share. Kandan, how are things? What is the status? You can hear me, right? Yeah. I want the data I want. I'm typing. But I also want even more data to, yeah. I want to mention even more data. Yeah, I'm contacting the person who's there in the place. So, yeah, through phone call. Through phone call. Okay. So you're, you're not able to travel there. This is good to lose sight, right? Yeah. I'm trying. I don't know. Let's see if it's possible. If I go there, I can take photos and videos. And I'm sure, you know, I'm sure phone call is effective. But if you're, if you're, if you're saying, right, you need more information and especially if it's going to be information that is not on the internet or books or anything. And if you need to meet with the people and collect it, then maybe a face-to-face interview would help, especially because of the nature of, you know, the kind of people that you're that you're researching. Right. So that's why. Okay. Okay, Dave says I'm still on research phase, got some new resources and schedule some interviews. Maybe after a week I'll start writing the actual research paper. Yeah. Absolutely fine. That's good. Okay. So Kiran, you said I'm still waiting or still writing? Okay. So any, can you just give some updates? What, what is the status? What you're doing? Yes, I'm still writing. I called two, three pastors from Rajasthan regarding Rajput and all this. They said they will update some data and all. Then after that I will try to call them and ask what is that challenges they're facing, like setting the cost between them. So you were able to fix an appointment or you're yet to fix appointments? I didn't fix because I didn't have their data on the numbers. The two, three pastors said like they will send some data but still they're not sent. Today I will try after noon and I'll call them again. Some of senior pastors from Rajasthan. I see. Okay. See if, like you can check on the internet. Is that how you got their numbers? The websites. So I got the pastors number from COVID relief project. Okay. Right. So the thing is, see what I would suggest is that you can go on the internet, you can check out the church websites. When you say churches in Rajasthan or maybe some particular denomination you will get. Yes, sir. I got some demon like old churches like denomination and Catholic also, sir, over there is working. Small like surrounded 300 km like surrounded, the AD also over there, AD church. Okay. And these are okay. So, yeah, so you can, I think you just need to do that quickly. Get information because your research also involves giving recommendations on how to do it better. So for that you need to understand what is currently happening. Right. So and also have a like, like the understanding of what is happening currently. Only then will you be able to, you know, suggest that, okay, these are things that are not happening, which are, which can be effective. And so, you know, you can recommend saying, okay, these are some things that can be done because unless you find out that you cannot suggest any recommendations that you need to know for sure this is what is happening in the churches or in the, you know, predominantly in whatever area that you have chosen, the town or the city that you've chosen. If it's the entire state, then again, it's a, it's a big task. So, so just wanted to tell you that there, you know, you need to do it. You cannot delay. Otherwise it'll be a very shallow research. Right. So because all your recommendations will be very, very general and say they can do this.  So, yeah, I, so you need to do it every day, Kiran. So, yeah. Okay. Fine. So Thomas, any update from your side, please. You're supposed to have little challenges because the grown-up ministries, they won't pass the information over the phone because time schedule, I guess, and because of their, sorry, because of their short time availability. I contact some of the pastors, they ask us to meet in their church, but currently my situation is quite difficult to go out. So that is why I have taken their ink on the YouTube things and collected the, some of the details of their church or the grown-up things and all. Roughly written, I have to make it as a pie. And last I shared Mania as about the missionary. When I studied about his, I received about the missionary from that pie. So I went through that. I don't know how can I use this here because talking about revival of the Lord, the Holy Spirit. But there is more of the social work, very less of the, you can see, healings are, unable to read those kind of things. They fed, they did the social works and because of the love of God, the social work, so many people accepted Christ. Whether, how can I treat here or not? Any solution possible in this? So the thing is, the work was fruitful, but this is the approach they took and people came to know the Lord. I think you can mention that as well. Definitely you can mention that. Because for them to do this kind of work, it was probably, it was very radical, it was not seen in others and then people came to know the Lord. Just make sure that the, them turning to the Lord was something genuine and not because of the material benefits. Just make sure that you can... Yeah, true. They fed the love of God through that act of kind where in his time, they went poverty and food crisis, where the government can provide the food for the people. That time, he, with the help of the government, in his property and household and with the help of the government, and taking care of the orphans and constructing the hospitals like that work. So definitely the salvation is the work of the Holy Spirit. But I don't know how to conclude this or write and put it in the words that ask the salvation. So you can, you could mention that. This is what, this is something that happened and if it's a widespread thing, you could mention that also. In all these districts, this happened that since there was poverty and since there was a real need and the missionaries saw the need and then they showed the love of Christ in action and which, I mean, you can just find out the process and how it was done from these resources just to see, okay, where the people curious that they came and then they said that, yes, we want to know why you do this and how did it happen? So I think that would help as well. So you could just find out the entire process, what they did, how they did. Maybe there will be a pattern that you can pick up from all that they did. They went to this village, they went to this thing and this is what they did. First they did this, second they did this. And then you see that pattern and you can mention that as well. Any update from those two pastors, information that they had shared, not like Pastor Hari and Pastor Yashwant, anything from their side? Any response? Pastor Yashwant's number, his son's number, whenever I try to contact his number, when I went to their church, actually they are very pretty. Even weekdays, people used to come for council, continue prayer, prayer groups going on prayer and all. It's quite tough to get the time over the phone. So it is better to meet them directly. But I have a pastor's interview on YouTube. So some of the information I collected. They started with all numbers. The delivery is very powerful in the beginning stage and the miracles and things and all. They started like this. They just went to pray, family, next their neighbors, some kind of demonic torture to the person. They prayed for the person, like that the church started the fellowship. Today the church has grown up in a very big way. It will be helpful if you can just fix an appointment with him and he might be able to share some information about other things also. Other things that were not covered in the interview, the YouTube interview, maybe he will be able to share. But definitely you need to fix an appointment and go. If you can do that, that will be great. Pastor, I will try to do. Sorry, excuse me. Thanks for sharing all the updates. I just wanted to encourage you to continue to do this work every day. Especially those of you who are in the information collecting stage, those of you who are in the analysis stage, please speed up the work and do it every day. And then the rest of the time can be spent in putting the information together, presenting it in the best way possible and also preparing for the presentation. You will have to do it in a concise manner, 15 minutes. So the rest of the time can go into that. So we will stop here and we will not be meeting next class, which is 30th. Next Wednesday, we will not be meeting. We will be meeting the first Wednesday in April, which is 6th of April. So we will not meet on the 30th of March. We will meet on the 6th of April. So for the e-learning students, there will not be any video upload on the 30th of March. But you can expect a video upload by the end of 6th of April, evening of 6th of April, India time. Okay, fine. So all the best. Keep up the good work and we will catch up next class. Thank you. Bye-bye. Thank you, sir.


Okay. I want to tell you that this is an art school, so the other, with the total art school, and for half an hour, and this is more complicated, you know? Wow. We are also online, so virtually we are like 100 in person. We are 20. And this is the good of the pro of the Unabrid conference. But in any case, we are super happy because we had the last school here in this room two years ago. So just a few weeks before everything was shut down. And we were, I don't know, 100. We have a group outside. It's huge. And it's super essential to start again. Because actually the in-person school has some benefits that are no way to get when you are hybrid, questions, interaction, and this is something that cannot be done throughout these schools. And this is really a loss for us that wants to visit kind of education. So anyway, so we are back. The Yambo School is organized in terms of lectures in the morning and end on in the afternoon. And then we have plenty of time for discussions because actually we are living together in the same place. We go for lunch and dinner all together. I think there is nothing more to say. There are lots of logistics stuff. So the key for the connection to the, to the, for the end zone, but this will, I think we will sort it out while, while moving along the program. And the first will be Nicola, that is the host, the local host, that is the person at CDP to help us inorganize this conference. And then we will start with the program slowly. I mean, in a couple of days we have to reach, you know, be it as a peer and diagrams and blah, blah, blah. So we have to increase the speed slowly. Okay. So I leave the voice to Nicola. Okay. So thank you. I think I have my microphone. Thank you. I'm Nicola Seriani. I'm the local organizer. Welcome, first of all, physically or virtually to ICTP. So, and to the school. Yes. So in principle, we, the speaker can, I'm so used to use it even during lectures that I don't mind, but anyway, let's, let's agree that the speaker can take the mask away. So, so I will spend a few words about what ICTP is. So you know where you are and, and some practical information on, how, how to move in these days. So what is ICTP? So we are, well, actually the building cannot be seen here, but anyway, this is a picture of the campus and on the Miramara Castle and the park. So it's, it's an institute that was founded in 1964 by Nobel Prize winner Abdul Salam and has basically two tasks. One is to do research in theoretical physics and mathematics at world class level. And the other one is to build scientific capacity in the developing world. So normally we would have the room filled from people from all over the world. Now it's, this happens only virtually for, for now, but we hope that things will change soon. And, and from the, from the governance point of view, it's an institute that was established with a tripartite agreement between Italy, UNESCO, and the International Atomic Energy Agency. So we are an institute which is part of UNESCO, the United Nations system. So we are the place where everybody talks to everybody. So to say, and I hope it will be like this in this time as well. So, and as I said, we have activity in research, in education and in outreach. And we have research activities in different fields of theoretical physics and mathematics from high energy, which is our starting point, condensed matter where I am and where this school is somehow situated. And the more recent activities in quantitative life sciences, for example, and many others, including high performance scientific computing. Well, this is a recap of our connection with the Nobel Prize winners, including, well, our founder won the Nobel Prize for, for the Electoral Week, Theory of Electoral Week Forces. Then, Filippo Giorgis, who's the head of the, of the Earth System section, is part of the IPCC, the International Panel for Climate Change, which won the Nobel Prize for Peace in 2007. And many of our scientists are involved in, in very close to collaborations so they participate in collaborations won Nobel Prizes more recently. One of our main programs is the postgraduate diploma program, which is aimed at pre-PhD students from developing countries. And the aim is to bring them to a level where they can join a PhD programs anywhere in the world. So it's, it's, we, we catch students in a very, in a crucial moment of their career and we open them, we train them and we open new opportunities for them. So this was, this is what we consider our, our most successful program so far. But we have, okay, first a lot of visitors from all over the world. These are bit the numbers from visitors since 1970. And above all, we have a series of, of programs that accompany scientists who have developed their world all over their careers from the, from, from pre-PhD level. So diploma, the diploma is here on the left, joint master's degrees, joint PhD degrees, but we also have programs to support scientists that are already professors, maybe in their, in their home countries, but don't have access to, to the possibilities to do research at high level because they don't have the, the contact or the infrastructure to do research. And we support them in order to help fight the, the, the brain drain from developing countries and including also conference and workshop, as you see here, which, and this is one of them. So, so this is all about ICTP. I think I have a couple of more minutes that I will use actually to give you some more practical information, especially for the people that are physically here at ICTP. So the lunch will take place at the Leonardo building, which is the main building a bit up the road. And I suggest that, so it's, it's a 10 minutes walk. There is a short track and the longer, but much nicer track through the park. So I suggest that today we go together through the park. It will take 15 minutes at most. Tomorrow we have a much shorter lunch break. It's only one hour because of the poster session. So tomorrow we will have some shuttle buses to bring faster. Some of you, because I think we're not going to be able to bring everybody, but the others can take the 10 minutes route on foot and I will be on that route. So, but I think we will see exactly what the need is in case we can, we can arrange. What else? We will have a conference dinner on Wednesday evening, but we will give more details when the time comes. Tonight we have a welcome reception which will be again in the Leonardo building at 7.30 on the terrace. So we will go back after the end of the lectures today. We'll go back again there. And I think that's all. A lot of information was given to you upon arrival, I think, you know, from the, from the info desk. At the, at the, here at the entrance and if there are any other questions, just approach me or the other organizer or the conference secretary. So I think that's all on my side. Other questions? If not, I give back the, the, the voice to the, to the next speaker to start really the school. So welcome again. And that's all. So is it you? Yes. Okay. So I think the best is that you take


Focus on a communication strategy out the gate so everything is extremely clear on what behavior is tolerated and what is not tolerated. The first thing you should do is communicate effectively about your policies in your business. That means extremely clear to the point and consistent newsletters or even text messages to customers, signage if you have a retail location, particularly if there's a mask policy. Communicate that extremely clearly so there's no question that the customer must put on the mask before they come into your business. Make it easy for them. Maybe you actually have free masks for people when they come into your doors or you've set up an almost a pop-up shop outside of your retail location to keep people safe and social distance. Support your employees because we've seen a lot of employees actually catch some heat for simply enforcing the policies of the company and you're seeing these stories go viral on social media again and again of customers who don't want to wear masks and are getting aggressive and angry about it. You can protect your employees by enforcing that communication policy. Just making sure everything is extremely clear that you even provide masks to customers and when things go wrong you support the employee rather than angry customers who are behaving badly. If your customers are trying to drag you into the gutter by causing fights, by not wearing masks and not obeying the policies of your business, it is 100% okay to not serve them anymore. None of us enjoy confrontation but it is important that you protect your good customers and your employees by keeping everyone safe and being very stern on what behavior you will tolerate and what you won't tolerate. I know these are unpleasant emotions right now but if you simply take a deep breath, go for a walk outside, listen to some music, calm down, it'll be good for your teams and for your customers if you're dealing with these difficult situations but you're mentally in a calm place.


Hey, Fabio. How you doing? Hey, Richie. How's it going? Good. Thank you. I'm doing Thanks, you can hear me. Okay. Yeah, I can hear you great. Thank you for we're already live we've already got over 50 on the stream and I'm very excited to speak to you about this news today. This is very big news Can I ask you just a quick question before I get into the news? Yeah, absolutely. One of our members is in Germany and I know you have an American listing and you have a Canadian listing He's requesting a German listing. Is that something right? Yeah, we're gonna we're valued the Frankfurt absolutely Yeah, you're one of you that visitor is that the only one that's been asking so we're valuing it now To do that and we probably do that. I would say by the sometime before the summertime You get that so it's an it's an active but that's simple as a turn the switch on if you will Okay, great Now let's get into this news because I think this is enormous news the title state Pharma Thera announced a successful completion of pre IND meeting with FDA for the clinical development of ketamine in the treatment of Parkinson's disease Whoa That's big Yeah, yeah, that was one of our Actually, that was our first license that we that we executed with the University of Arizona Um early last year, I should say in the q3 of last year and what the purpose is that the The researchers at the University of Arizona, uh, dr. Scott Sherman and dr. Torsten fault, uh, they serendipity You know, they figured That ketamine Uh was helpful in Parkinson's patients to treat their dyskinesia or their their tremors if you will They originally were looking to with ketamine just to treat some of the their Parkinson's patients pain and some And as you know, it's side effects of Parkinson's patients. If anyone knows who has Parkinson's they they do have a suffer from whether different forms of Depression if you will so What was unique about this is that they found this was about several years back that this their dyskinesia Literally halted some patients From four weeks even up to three months and actually there's public as a publication of paper Which you can find in our investor decor on our website If you'd like to read it to show that these these really I wouldn't like to say miracle type cases But you know Another improvement that how ketamine beyond its depression or pain that can help another subset of patients that was never really Being evaluated for so the good thing with pharmac there Is that now we have the exclusive license to advance ketamine in parkinson's disease? So the idea was to look go to the FDA which is um give you a little education to your um to your viewers here is that the Company or sponsor would look to the FDA for guidance on how To develop the clinical program of the said product So in our case we found the pre-indy meeting Requested the FDA to understand what their expectations are for ketamine to treat in parkinson's disease or more specifically to treat the levodopa induced dyskinesia in parkinson's disease levodopa is a parkinson's is a gold standard in parkinson's patients But however over time it doesn't help So there's an there's an unmet medical need for these patients to have a new therapy that can help stop their dyskinesia So we sent out to the FDA on two fronts one Do they accept for us to of our proposal to conduct a phase two study? To evaluate a number of parkinson's patients in the dyskinesia over a three month period Based on the on the parkinson's kind of primary efficacy scales that's uh been validated in uh in the in parkinson's clinical studies To see if we can get agreement on that study Then the second half is do what is the regulatory pathway that we can pursue with our program? To get commercial approval from the FDA. So there's a number of pathways you can take We opted obviously for that what it's called the 505 b2 Regulatory pathway and what that means is that a company like us Using ketamine which is an approved drug for as for anesthesia Is that we don't have to do all the non clinical or phase one and healthy subjects if you will studies we can leap to a phase two clinical study and more so Evaluate in that phase two study all the different endpoints or Or parameters both from a safety and efficacy of these parkinson patients Which would then the data would set up to allow for us to move towards a pivotal clinical study Which that would probably take place sometime in next year. So this is exciting for us because you literally reduce that timeframe for a drug to be to get approval from whether it's say five Even 10 years on the traditional new drug applications or new drug New chemical entities to an existing one and you can reduce that even to say even anywhere between three to five years For approval and we're already ahead of that So this is this is a really game changer in the sense of for a Parkinson's patient And that's and that's evident with the people we have on board with us not beyond beyond the inventors from the university of Arizona We have dr. Robert hauser from the south South to south florida university then dr. Espe alberta espe from the university of sanitary They are you know leaders in their field. So, you know, this is a really You know a a unique program for us to kind of kick off our clinical stage Pipeline to go to the FDA to and to really actually then expand our ketamine Program in depression in pain and all the other even motor disorders that ketamine could be uh Be useful for so really in essence Pharmacare has become it's kind of involved to the specialty Psychedelic company with a particular focus with with ketamine built from use of novel uses of ketamine But also in formulations for ketamine and delivering in a different way such as a microneedle patch, which we announced even early this week with respect to Our license with professor donnelly's microneedle delivery technology that's already shown to deliver as ketamine, which is the The same drug that j and j Markets to patients with depression but in a form of a nasal spray So, you know, we have all these great developments going on and i'm just happy that you know again from our last Interviews that you understand you recognize our value of our company and really sharing our story with your With your viewers and followers. So thank you ritchie for that It's it's important that we find undervalued under depreciated under exposed companies I mean that's what we do best and it's important for the companies to gain the exposure. So we kind of help each other here. It's Something that parkinsons is something that is is destroying families. You know, it's a terrible disease What is it exactly that?  What is exactly what is it doing? Like how is it helping people with parkinsons? Can you explain that? Yeah, so yeah, absolutely. If you know anyone with parkinsons who has parkinsons a lot of it and you can just take the The case of michael j fox. So everyone, you know, well known Parking great great exam patients, right? So everyone can now visualize in that and you see how not only from the movements But the tremors the shaking which is called we call this the dyskinesia of these patients I'd experience on a daily basis at multiple times during the day now imagine a drug that can not only Reduce these tremors and these sporadic movements if you will On a daily basis, but for a longer period of time, but also halting that that's what ketamine is doing And that's just from you know, what parkinsons does to these patients In as a side effect is they're always experiencing some sort of pain There is definitely depression. That's because of being a Socially limited into what they can do now the idea of going to the grocery store going to your car when the grocery store And in shop that becomes a difficult endeavor so ketamine Showing even at these early stage with these patients that's been that's been tested already That they're stopping this kind of these dyskinesia or tremors. So this is a very yeah, so it's it's a game changer, right? So now it's our job is to now look ketamine's out there, right? But it can't be used to treat these parkins because there's no there's no clinical on a I guess you can say clinical meaningful basis to have that approval So that's what we're trying to do in these clinical studies is now to take a larger set of population showing it being statistically significant that it can improve the Or decrease the the dyskinesia in these patients and offer another option And their treatment for for Parkinson's and the spillover or what you like to say is the gravy is You know that can also have help on the pain side of Of these patients of these Parkinson's patients as well as even depression because now you've improved their their way of living with this therapy and that's what we're set out to do Now Fabio we work with so many companies and branding is everything One thing I've noticed with pharma there you've got pharma there, which is your subsidiary But you're operating under new scope capital corp. Yes. Am I predicting the future here? You're going to do a name change to pharma there Yes, absolutely. So that's so so so Richie. This is one of the most painful things that Besides, you know, dealing with fda and what all these other having our name at new scope This is a legacy issue that we had to deal with when we Merge with this company and conduct a non-offering Perspectives to go list on the csc. So we kind of adopted that name So really new scope is the parent, but it's fully operated under pharma there. So Yes, shareholders, we will do that flip where we'll we are going we're in the process of changing our name So that there's a commonality in how we describe our company So this is be quite frankly, uh, and I see now your you know, you explain yourself It's it's irritating to me and I'm the CEO of the company That's why I'm bringing it up because I can see the way you're writing your press releases new scope But then right in the beginning it's pharma there. So it's like it's a little bit of a disconnect for investors And I think by having the name change And I've seen this with other companies It's going to be a major catalyst because there will be no disconnect. There'll be no confusion It'll be pharma there and then that's all you have to put in your press releases. That's all that everyone will be mentioning That's the name everyone will be talking about But a lot of times I'm talking about new scope capital that I'm talking about pharma there So people get confused. They think they're two different deals Um, yeah Right. So, uh, I just figured that it would be a natural progression to just move towards pharma there as your as the name that you guys were operating under Yes, and absolutely that's that's that's that's going that's going in process So that's that's definitely on the top one of the top priorities for our company. That's fantastic Now as an undervalued under appreciated under exposed company that's just getting started that's trending up All this great news coming What else can investors look forward to I know you guys have a lot of things going on Is there anything else that we can look forward to in addition to what you're working on right now with this With this uh, this this deal with Parkinson's Yeah, absolutely. So, you know, right now with the Parkinson's just to kind of Close this loop is that our next stage is to file what it's called is an investigational new drug application to the FDA To allow us to conduct our phase two studies and also set the foundation For the clinical development of that program. So that's like the next catalyst for this specific program Now the next one of them another major catalyst that we're moving towards is our catabit program Which catabit is the combination of ketamine and another drug called betaine that combination Which is pat and it's been past it's been granted and we did we do have the worldwide rights to this program Is that this is a formulation that will allow this combination for us will allow in the treatment for Treatment resistant depression. That's our target. We're going after so our next step with this program Is to file our pre-ind meeting with the FDA to See to to understand the clinical study the phase two clinical study that we're going to be proposing to them For allows to conduct for these treatment to resistance to depression. So in that within that time We're also building our core competency or advisory board in depression so that we can really have a You know a world I guess you can say a a leading expert on this program to really drive this over So that would be the from the catabit program another the the foundational for depression Which is then can also I consider this this this program more of a program a pipeline program for other indications That we can go after such as ptsd Maybe it would be anxiety anything that ketamine could be useful for this combination What it does is that it reduces the side effects and put and at some cases even limit Potentially to eliminate the side effects that ketamine has such as police sedation amnesia nausea all these things and specifically with ketamine using on a chronic basis right and There are other side effects that can that can also happen that would any institutional type disorders as well So we can eliminate that or even reduce the side effects over the long term with this formation So in fact, you know, we we under promoted in terms of what this the potential is but because i'm particularly a more of a fundamentalist I like to the data speak for itself and then let's see audience whether it's the medical community investor community to decide whether This is the the fact or the treatment that's coming to be there's great treatments going as being worked on now I mean you look at even compass with their psilocybin program You have uh, j and j who has their spravado nasal spray and that's as ketamine spray that's marketed right now the differences between hours and bears is that What we're trying to do that's differentiated is that we will allow to give the patient to treat Their ailments, which is say depression at the comfort of the whole home Whether it would be in a micro needle patch Or in a in a in a drug that allowed to take to the use that home on on on on that daily basis as opposed to Other treatments such as psilocybin or ketamine you have to go to the clinic You know do the whole Set up and whatnot and you can stay up to even between several hours to even up to eight hours For the day for that single treatment. So we're trying to change that game to what People are used to to treat their ailments is go to the pharmacy get your prescription bring it home take it and you know Have it how to make it work so it can control or even treat their their Their disease so that's what we're doing with this with with catabetic and you'll see that progress forward with that now With that not to just gloss over that but you'll see that that's going to be More milestones coming to be we also have our psilocybin program that we're actually working To look at psilocybin for treatment and stroke and then the treatment of traumatic brain injury even specifically concussions Now we're conducting early stage clinical pre clinical research and with that with that Effort is that's going to be taught is going to allow to open up the field And maximize the potential psilocybin But not only with that we have other IP that's involved with psilocybin And we are because we've kind of now evolved this specialty Academy company We are going to and we've signed a binding lli with revive therapeutics that allow them to continue their psilocybin efforts And we're parking if you will our program to to revive And for in exchange for another school's amount fee, which we'll announce once we close it But that will allow for the company to have a non dilutive Funding for the company to allow us to fund our phase two program So this is very unique because a lot of the a lot of the you know the questions in the market is Okay, this company's going to phase two. It's going to need money to to To advance this and whatnot and this is a non dilutive way for us To now advance our phase two without having that pressure on the stock if you say for us to go out to The markets to raise capital. So we are well-primed or positioned To for for pharma there for I guess newscope is to take it to be to become at the next level Which they'll you know with our valuation you can see and your investors are probably more educated than I am in this Is that there's a substantial disconnect between our valuation and Our peers, right? I mean you can see that's evidence, but then you look at our company It's like, okay, they're in this psychedelic sector check How about their patent situation? Well, we have 19 granted patents patent applications that we have for worldwide rights Okay, that's pretty good check. We have a clinical Uh product pipeline that's going into phase two for large unmedical needs Parkinson's depression PTSD eventually even in pain all with our unique formulation that will change the way How these diseases are being treated. Okay, check So now we're on this, you know, this cusp of do you know, we're here now is to make The community understand about our company Um and to understand that wow, okay, we see this this disconnect and you know and to kind of You know move us forward to the next level to allow us to Continue our developments and bring these products to eventually to market So, you know, these are these these these things with the company now we're going through we're a fairly new company as well So, I mean we I founded the company last year, you know early up to 2020 so and things do take time But now the timing is right for us to get to that next level Do you have a goal? uh We're we got a lot of uh members here that that like your company that already own the stock a lot of them A lot of them are interested in getting into the stock. Do you have a goal as far as market cap? Your market cap is a baby market cap right now. Yeah, I think that 100 million market cap is very reasonable I think you're probably around a 35 million market cap right now. If I do my the number is correct Uh, what like 70 million shares at 50 cents about a 35 million market cap so yeah, needed so 100 million market cap. Is that like a goal of yours? I mean 100 million market cap will put you guys at about a dollar 50 Is that something that is reasonable? Do you guys look at that? Is that a goal that you you look to achieve? Is that even matter to you? Is that something you guys think about? Yeah, like we to have some sort of goal I mean it would be foolish for me to say that we would like to have or our goals to be 100 million We're not in the and we're not doing what we're doing to be 100 million market cap company That's just evident We're in the we're the goal is to take this company to a billion dollar market cap Right and how we're going to do it is evident in our pipeline We're we're going after large indications that already had scientific and clinical validation And we're doing a unique way. So if you take a company like like compass, okay Who is in phase 2b clinical says what they're still aside in for tumor resistant? They're at I guess a one and a half two billion dollar market cap American you have a company like mine med who now doesn't have an fda Program they're doing a lot of work out in europe in lsd and mda and I applaud them because I think they're doing a They're doing great work and their market cap that I believe one a half billion Right and then you have these other players who are kind of treading in that say 100 to 250 million market cap range, but they all have different businesses because some may have a A clinic a clinic strategy where they're expanding in the physical clinics to treat these patients Other ones are in the kind of these biotech psychedelic companies, you know, like side and whatnot They have their own little delivery system and they're trying to sell a side and whatnot and they're trading on but they have great backing They have great investors, right? You know, we're just new we came out of we came out of just like, you know, race funds through I guess more of like friends and family and whatnot And then now institutions and now we've kind of built this Quietly this pipeline where if you were to put our company in one of the other companies I've just mentioned, you know That would propel them to another level or even even to even justify those types of market caps as well So again, do I look at the market caps of these other companies? As you can see I do Do I have a set goal of a specific like where we reach one end and we're done with we achieve? Absolutely not but we are shooting for that star So to suggest that we could be a billion dollar market cap a half billion dollar market cap or whatever million market cap That's the investors are going to have to do their due diligence to dig deep and to understand where's that disconnect? We are an open-based company here. You can go on our deck. You can see every pattern We have license you can see all the clinical data we have there's nothing that That's least to the eye of the beholder here and everyone could do their own due diligence on it Fabio super impressed with everything you're doing We're running out of time. If there's one thing you want investors that are watching to know About pharma there. What would it be? The bottom line is we're a young company that's just Or in the cuts of the going to the next level with our clinical or ketamine based Program in in Parkinson's and depression and will be Conducting clinical trial soon which that value inflection point of that of our company will will marry with The other of our peers. So, you know, all I can say is to your viewers is just Continue to follow us continue to try to root for us and even root for everyone in the sector of psychedelics because You know, it's time that the game has to change of how Patients are being treated for their mental health or neurological and pain disease the drugs out there right now The side effects they're just not they don't they're not up to snuff So we're all doing our part to make this world a better place And you know, we we've carved an area that we can we can definitely help in that in that endeavor. So again I thank everyone for viewing and Just if you have any questions, you can call me go on our website at pharma there.com And you can email me at info at pharma there.com or our 1 800 numbers there Have any questions feel free to call me anytime fantastic the CEO of pharma there new scope capital corp symbol ph rm in canada ph rrf Fabio did mention that they will be looking at getting a german listing by the summer So stay tuned get your popcorn ready. Put them on your radar. Put them on I believe this is a company that's undervalued underappreciated underexposed and it's just getting started Thank you for your time fabio and have a great day. Awesome. Thank you rich and thank you everyone Take care. You've upped a good work and we hope to have you on the show soon Absolutely anytime. Thank you fabio. Cheers. Take care. Bye. Bye All right guys, thank you guys for watching. Hope you guys enjoyed the video Hope you guys enjoyed the show. If you guys have any other questions, please feel free to put it in the chat Other than that we wish you guys


I feel like I'm on Love Island. I feel like I'm on Love Island. I feel like I'm on it with this. I actually thought that was a blue band. Do you want to be on it? Yes. Be sure that I need movement. Keep that knee still. I'm just going to calm it down. I don't need to rush it yet. Don't need to do a sidey yet. 3, 4, 5... Yes, wrap it. Again. Again. It's going to be too deny, aren't you? We've all got another 3 months, mate. You ready, mate? Just again, boys. Oh my dirty. I just got a... Boy, he's chaining 2 days.  Exactly, yeah. That is so true. Hold it there, hold it there. Yes. One for one. Ben, do you know how funny thing is? Glad to have played. I was going to drop to my knees. No. So that's gone, Ben. If you missed this one, it's a hard one. There it is! What? You're doing this soon? Doing this? Ben, are you doing a hard one? Yes. Six reps of what? Six reps of 2,400 metres? Oh, 400? One. I'll do one with you, Ben. Yeah. Well, that's my... Here, Ben. Me back music. That's all right. Mate, top in it. Yeah, mate, top man here. Mate, Ben. Ben's funny, man. Ben's funny, man. You're doing it with him, he was so funny. Yeah. Bare tings, though. It's hard. It's hard because then you know you obviously... Bring Sally up. Bring Sally down. Yeah? No, I don't even know. I was just waiting for up. Oh, I'm dying. Seven. No, six, six. Both. In every way. Driver. Good. Less about weight. It's more about speeding up. He sent it down. Horrible. Mate, that was a madness. How much did you do? Mate, I did one I was thinking, mate, you're in big trouble. Yeah. Yeah. It's good though, it's good. If you're able to hit that speed, you can hit it easily, 100%. OK. Dammit, it's Sam's storage, what a pro. Yeah, go on, show how to roll it. I've got it, go on. Yep. 15. Wide grip. Confirmed, innit? Don't make me do it now. That's not the top of the leaderboard. Ben said he could do like 30. You were at the top, see? You're 19. Maybe I was getting it wrong, I think the top of the leaderboard is Dave Gardner. He would get his own whip and face and said... Yeah, it's got a barbecue. I'm a serious. Let's get that mic off.


The study found that there is a strong positive relationship between neutral detergent in soluble crude protein, NDICP, and pre-sequel indigestible crude protein, PICP, suggesting that NDICP can be used to estimate the part of protein that is not available for digestion in the small intestine. Additionally, there was a correlation between neutral detergent soluble crude protein, NDICP, and pre-sequel digestible crude protein, This indicates that the slope of the linear regression line between NDICP and PDCP is 0.9, meaning that the apparent pre-sequel digestibility of NDICP is 90%. Therefore, it is possible to predict pre-sequel digestible crude protein, PDCP, by multiplying NDICP by 0.9. Furthermore, because the literature identifies a similar amino acid profile in NDICP and NDICP within a given feed, this concept may be applied to amino acids as well. This article was offered by Annette Sainer, Susan Kirchhoff, a Susan Beth, and others.


Sup guys, it's Jake here. Welcome back to another reaction video. It's Christmas Eve. It's actually Christmas Eve. I can't believe it. It is officially 8.12am on Thursday the 24th of December. And I'm sitting here with one mission and one mission only for the day. And that is to finish the top 100 series. We've got 18 players to go. I started at 45 yesterday. I got down to 30. I thought, you know what, that's it. Went to the gym, came home, got another 12 done. I was surprised. I was even surprised at myself, honestly.  And an enjoyable goal. I'm not going to lie. You know, I wouldn't be doing this if I wasn't having fun. So seeing as this player at number 18 on the list is none other than the tight end for the Chief, Travis Kelsey. I'm going to pour my first cup of real coffee. And I'm going to get changed because I look far too pale right now. And I'm going to see you back here to check him out. It's three minutes and eight seconds long. It's got 294,092 views. It was brought out on July 29, 2020. He's number 18 on the list. We're in the teens, guys. We're in the teens. Every single player that comes after this is going to be an absolute superstar. And I can't wait to watch. So I'll see you back here shortly. Now, I've got to be honest, guys.  I'm not going to lie. I don't know why. I think I'm a little bit nervous to be fair. I feel like I'm an excited type of nervous because we actually have the possibility of finishing this list today. You know what? I'm not digging the Harry Potter look. I'll be back. Okay. Here we go. The final stretch. The final piece of the puzzle. I couldn't even tell you when I did the first one of this series. It was probably a good two months ago. Two months. Two months. This series has been on my mind every single day. And there's a quote that I have no idea where I got it from, but it is effective and it is true.  You simply have to. It's mental torture for you not to do that, for you not to get that thing done, or at the very least for you not to try. And that's exactly what I've been doing. So guys, one and all, I want to say welcome to Queenstown, New Zealand. This is where I'm living right now. I did two and a half weeks in a van. You guys would have seen those vlogs. It was extremely enjoyable. I learned a lot. I grew a lot. But now I'm living in a nice place. And at the end of the day, you've got to do what makes you happy. And right now, what makes me the most happy is to have a look at Travis Kelsey. Let's go. Oh, that's sick, bro. That is Dad. I thought it was the coach, but it's Papa Kelsey. I'm assuming that was after the Super Bowl. What a moment that would have been. Scholarship to the University of Cincinnati, but I was like a two-star. Never got enough credit for it. Oh, the music, guys. We haven't had backing music. We certainly haven't had backing piano music like that. Shit, that just hit me in some kind of way. It's hard to imagine there was a time anyone had doubts about Travis Kelsey. Fuck, that hit me bad. God damn, that hit me, man. Because the relationship between me and my dad is not where it could or should be. The older I get, the more questions I ask, the more mature questions I ask my dad. And I get to know the reasons why he hasn't been that loving. And it's because he was never brought up that way. And a lot of people that were born in the mid 50s, 60s, they just weren't brought up with kissing and hugging and telling people you love them. Being able to convey your emotions, it just wasn't the case. And my dad has not changed. I have, so it's extremely hard for us to talk. And I've always, you know, I've always just wanted that one moment where I achieve something great, and he tells me he's proud of me, man. You know? He is proud of me, but he doesn't tell me very often, that's all. Anyways, guys, this is not about me. And this is the first tear-off sheet in this whole entire series. Let's go. Because today, it's hard to find a tight end more respected by his peers. Who is the best player in your position in the league? I gotta go with T. Calcy, you know? Travis. Travis Calcy and George Kittle have got to be both up there. I don't know where George Kittle fell, but, you know, he was the tight end on the opposite side of the ball in the Super Bowl, right? So it was like Calcy against Kittle, that top tight end spot. And I guess since we haven't seen George Kittle yet, he must have come out on top.  He probably got a thousand receiving yards, but I couldn't be sure. I'll top the league in tight ends just because, you know, he's a very tactical route runner. His nuance is to drive the game, just knowing what to do in certain situations. He's got the size, obviously. Perfect, perfect tight end. I mean, if a tight end is any, well, if a tight end is any shorter than 6'4", they are undersized. And just to make sure that I didn't just put my foot in it, let's confirm he's 6'5", 260 pounds. And when I see 6'5", I instantly think of Jonah Lummu. Jonah Lummu was 265 pounds and ran a 10.5 second hundred. Travis Calcy ran a 461. But if we just look at his stats, he played three years at Cincinnati. In his first year, he played 11 games, got one reception for three yards in 2009. And here we are, 10 years later in 2019, and he is the 18th best player in the NFL. His first year at college, he got one reception. It's not that way anymore, is it? 461, 35 inches in the vertical, 10'4 on the broad jump, 22 reps on the bench press. Calcy was drafted by the Chiefs in the third round of the 2013 draft with 63rd pick. The Chiefs had hired Andy Reid as the new head coach during the off-season. Reid was familiar with Calcy after he had drafted and coached his brother Jason during his time as the head coach of the Philadelphia Eagles. On June 6, 2013, the Chiefs signed him to a four-year, $3.12 million rookie contract. And if we go down a couple of years, on January 29, 2016, he signed a five-year, $46 million contract extension. He was ranked 91st in that year by his fellow players on the NFL Top 100 Players of 2016. He came in at 26th on the NFL Top 100 Players of 2017. He came in at 24th on the NFL Top 100 Players of 2018. And last year, why is it not telling me? Right. Gonna have to take this into my own hands. This is Calcy, Top 100, 2019. Number 21 in the Top 100 Players of 2019. Not bad at all. So he went 91st in 2016. 26th in 2017. 24th in 2018. 21st in 2019. And 18th in 2020. Now that is not a bad trajectory. Getting him up for a Top 10 finish next year, I'd say. We dig deep. We make plays. This one right here. In the divisional playoffs, the first tight end in history with four straight thousand-yard seasons sparked an epic comeback. Well, I didn't look at that, but I did say that I guaranteed he'd have a thousand yards last year. And that he did. Not only one year, but four years. 10 catches for 134 yards and three scores. See, and he's been with Andy Reed the whole entire time, right? So that coach would have seen him from his rookie season to becoming a Super Bowl champion. Right there. Kelsey was headed to his first Super Bowl and taking some aimless fans along for the run. Shivers, bro. Look at that. Yes, boy. Too easy. Complete and utter respect I had for Travis Kelsey. Let me just confirm what his statistics have been. Came into the league in his rookie season, played one game, but got no statistics. Second year, 2014, played all 16 games. 67 receptions for 862 yards. Five touchdowns. Four fumbles. Three of which were lost. 2015, played 16 games again. 875 yards. Five touchdowns. Two fumbles. Two were lost. 2016, played 16 games again. This is when he broke a thousand yards for the first time, 1125. He got four touchdowns, no fumble. 2017, played 15 games, 1,083 yards. Eight touchdowns, no fumbles. 2018, 16 games, 103 receptions for 1,336 yards, which is a career high. Got 10 touchdowns, which is a career high, but he's already matched that this year. And I haven't even seen what he's done this year. This is about 2019. So the season that this video is about, he got 16 games, 16 games started. 97 receptions for 1,229 yards. 12.7 yards per attempt. A longest of 47 and five receiving touchdowns. He had one rush for four yards and a touchdown. I wouldn't mind seeing that. One fumble and that fumble was lost. So in 2020, so far, through 14 games, he's got 1,318 yards, which is only 18 shy of his season record. So he's most likely going to break that. He's got 10 touchdowns this year, which is equaling his season record. He's most likely going to break that. And with that in mind, guys, with two games to go over the season, I reckon Travis Kelsey is currently stamping a top 10 spot in that top 100 players of 2021. And for that, I want to say congratulations. But with all that being said, guys, in the next video, we're going to be looking at a 49ers player. His name's Nick Bosa. We've seen his brother, Joey Bosa. If there's one thing I want to know about Nick Bosa, it's what does he actually sound like? Because if he sounds anything like his brother, it's going to be very noticeable. Anyways, guys, I'm going to leave it there. If you've liked this video, please hit the like button. We've got 17 more to go. The time is 8.30 in the morning on Christmas Eve. And I want to say Merry Christmas. Have a great day, have a great night, have a great year. Thanks for watching, and I'll see you on the next one. Peace out.


Hi. This is Dr. Don. I want to show you very quickly how to construct this interactive dynamic histogram, as they call it. If you recall, as we recalculate the Monte Carlo simulation, the histogram changes to reflect the output. And the green indicates that we're going to manufacture the decision. The red indicates we're going to outsource. And the colors of these bins change depending upon the results of the Monte Carlo simulation. And it's really pretty easy to do. Let's look up here. This is the data that you normally create in order to build a histogram. What I didn't show you in the other video was that I have two additional columns out here that are actually feeding information into the histogram. And one column I've labeled manufacturer. And that means if the upper limit of the bin is less than zero, that means that the value of the difference is negative, then I want to show the frequency for that particular cell. That says if P2 is less than zero, the upper limit is less than zero, then I show this value R2. Otherwise, I want to show the NA, the NA which is a static function, and it just returns a null or nothing if it's chosen. And the second column, I copied that down. And then the second column, I want the flip side. If P2 is positive, the upper limit on the bin is positive, then again, I want to show the relative frequency. But if it's not, then I want to show an NA. And so you can see in these two columns over here, the upper limits are all less than zero down to here. So we show the actual value of the frequency there. And then on the flip side, on the outsourced side, when they become positive, we show the values in this column. And that's just using these two if statements. And the only difference is, is the upper limit less than or equal to zero? Or is the upper limit greater than zero? Once you have those columns calculated to create your histogram, all you do, I'm going to select this upper limit, hold down my control key, and then select these two columns.  And you will get this funky looking column chart initially. And that's not really what we want totally. All we need to do is to click on one of the columns, right click format data, and we'll get this. We want to set the gap to zero. And then we want the overlap to 100%. And that's all there is to it. That creates the basic dynamic histogram. And all you've got to do is do your editing chart title in order to turn it from this into that. You have to change the color, of course. But that's all there is to it.