Is that something wrong with me? So YouTube team keep it clean what's going on it's engraving here with another video and I come to you a little bit concerned about Myself and I feel like I may be a defective Ravens fan But before we get into why I believe that special shout out to my god, David Me and my family we went out to eat the other day and David had came up to us and he was like a man I watch your videos. I appreciate the videos So David is a part of team keep it clean and he worked at the restaurant that we ate at sent us free dessert Okay, shout out to David man. So but seriously we appreciate you We appreciate you watching the videos and appreciate you being willing to do that for us Also special shout out to all the team keep it clean patrons appreciate y'all supporting despite What we're getting ready to talk about now I'm a Ravens fan Been a Ravens fan for a while We've of course made a lot of videos on YouTube about those Baltimore Ravens and different thoughts that we've had concerning the team Over the years It's a lot of fun. It's been a lot of fun It still continues to remain a lot of fun and we appreciate everybody that does watch the videos and support the videos but one thing that has just been a constant and It's made me feel like man. Am I off? It's something wrong with me has been when it comes to the talks of adding a quality wide receiver and the reason I say that is because We've brought this up several times as you all already know y'all know how we feel about it I feel like the Ravens should add somebody who is that guy either somebody who like We've mentioned plenty wide receivers already before but more recently. It's been a DK Metcalf But we've talked about plenty of them in the past and we will continue to talk about them Or whether it happens in the draft in the first three rounds It's good. It would be either or it probably wouldn't be both I wouldn't mind if it was both but it's gonna be either or but Whenever we talk about The Ravens potentially adding a significant wide receiver A lot of Ravens fans when when they discuss it. That's that's something that that's like frowned upon or something and I'm like Why? And so many people they they they say a lot of the same thing One they'll say hey, we don't need that. We don't need another wide receiver We have enough wide receivers as is. We don't need another one I'm like. Oh Well, nobody ever said that about the linebackers Nobody ever says that about the cornerbacks Nobody ever says that about when Ravens at a defensive lineman. No one ever says that when Ravens at a safety No one ever says.  Oh, yeah, bring him to oh, yeah Let's get that guy. Oh, yeah, let's acquire him. Oh, yeah, let's sign him but then When you talk about the wide receiver position Ravens adding more and adding quality to So many people like no for what why and I just get so confused at that like What's the problem? Why wouldn't we want to do that? I See so many conversations of people just Wanting to make everybody's job on defense easier wanted to make everybody's job on defense more simple Wanting every to make everybody's job on defense that much more effective and impactful and I got no problem with that I got zero problem with that. I mean, I want these Ravens to be the most well-rounded team that they could possibly be But it's always so weird to me that when you we have these same conversations about the Ravens doing these things on offense It's talked about like it's a bad thing and I'm just like, huh? I don't understand and The the Ravens can dish out these big contracts to guys on defense and people will be like, yes, let's go Let's get it. Whoa. We moving baby. Yes, go But then when it's even talked about it when the possibility is even mentioned on offense People cringe and they're like, no, we shouldn't pay that guy all that money No, Lamar should take a hometown discount No, why would we get a wide receiver? Why we trade for a wide receiver? We're gonna have to pay him And I hear that stuff from them like eel. What? What's happening in my ears? This is gross Because a lot of Ravens fans are they seem like they're afraid afraid to Do something significant on offense and that scares me and that's made me feel like me. Maybe there's something wrong with me Maybe I'm a defective Ravens fan I'm just off You talk about the possibility of paying a Hollywood Brown. It's a no You talk about the the possibility of Lamar Jackson getting pay lots to say No, you talk about the possibility of the Ravens drafting a wide receiver very early No, you talk about the possibility of the Ravens trading for a significant wide receiver. No And What a lot of them do they they'll point to the market say, why would we want to pay wide receiver that look at the wide receivers they got paid that They are those guys and they are difference makers on their teams You look at a Tyreek Hill you look at at the Vonte Adams Those are just last year those are guys that the Ravens they had experience with and over the years, too Now Tyreek Hill last year the Ravens they took care of him last year, but over the years he has been a Ravens killer Well, you can mean you can say that about really any cheese wire see but anyway Then step on digs to that's another one like these guys They're getting paid But they're getting paid for a reason because they are that high quality product It's like and you get what you pay for So many Ravens fans. They don't want to pay for and To me that sounds like a problem That sounds like a problem And I know the Ravens they paid Ronnie Stanley. That's been a little rough recently, but they paid only took care of them No Ravens they paid Mark Andrews and oh, okay, let's go That one worked out quite well because had they not paid him and then he went off and had the year that he had last year Prices would have went way up boy Ravens got him at a still right now But when it comes to the wide receiver position, it's always crickets it's crickets and You get more wise than anything Why should we do that? Well, we shouldn't do that. No, we don't need that That's when so many fans they start penny pension They start being extra frugal They start being downright cheap When it comes to why see the tap and it's so weird man. It is so weird and I just I Just don't get it Like what is so wrong about wanting to pay a high-quality wide receiver money? and I It just it blows my mind So and I'm very curious as to what's gonna happen What's gonna happen? Well, I mean they could be in they could be in contract talks right now with Hollywood Cuz he um, he's in his fourth year So they could sign up to a contract extension if they wanted to or even if he wanted to And we're a sharp Bateman when that time comes on. I'm just curious Cuz Hollywood is clearly the best wide receiver that the Ravens have ever drafted He's the best one And he doesn't have much competition Of course Ravens when it comes to drafting and developing wide receivers That's another thing. So he's been the best wide receiver that the Ravens have drafted and developed Because you know, you know that track record and we done talked about it a lot of times before it ain't pretty But what Hollywood it's been so much better than a lot in the past and Hollywood has continued to improve every year But when that conversation comes up, oh when the Ravens gonna pay Hollywood How much the Ravens gonna pay Hollywood so many fans like oh, no Wanna pay Hollywood. No stinking money. No, we don't want to do it. He doesn't deserve it We could go out and draft somebody instead. We could replace Hollywood And it's like Why? So I'm almost scared. I'm scared for when Rashad Bateman If he Progresses as we expect him to progress. I'm scared for when his contract time for him What Ravens fans are gonna say? Oh? Oh No, we don't want to pay her shop even any money. Yuck. That's unheard of. What are you thinking? I'm worried about that like seriously Because that's been so many Ravens fans think and I know the front office has ingrained in a lot of Ravens fans this way of thinking like on Defense. Oh, yeah, we bringing out that checkbook But on offense, especially a wide receiver specifically We ain't got it right now But then I take you back. I Take you back to the last time The Ravens traded for a significant wide receiver Let's go back a couple years It's when they traded for Chris Givens from the Jets. No, I'm just playing not him Well, no, he was on the rain was before anyway, not him they traded for when they traded for Chris Give us though. I know y'all some of y'all do and Quambo and Quambo and they gave up. I believe it was a third and fourth round pick for and Quambo What did he do? Oh Nothing just came over to this Ravens team and really helped take them over the top That 2012 Ravens team They had an and Quambo So they had a possession receiver a guy who was that guy Established guy at wide receive he had already been established But he wasn't old and hobbled and Quambo to know and Quambo then was still like that They had a Tory Smith young guy, he was in his second year 2012 he was in the second year and he was in his second year and He was a quality downfield threat Burner and he was the reason that they were like I Lee Evans. It's cool. But no, thanks No, thanks And you know what's crazy?  Okay, if he if he can't beat him join him and if he can't beat us will have him join us Jacoby Jones Decent wire was he the best wire seeper? No, no, he was more impact guy on special teams though But he still made plays at wire see remember when he caught in nom de asa more slipping Oh, even though they call that touchdown back I think they called it offensive passing the field and it was such a terrible call too. Oh, it's so bad But Jacoby Jones, he was decent as a wide receiver, but Ravens already had this that they had to establish one in two Guy, but they still added to that They still added to that Why can't they do that now? I don't see what's the and you sit but my point is you see the impact that it had You see that? No and Quambo then no Super Bowl and we know that no and Quambo then no Super Bowl His impact was so significant Ravens needed that and they got it Because the Ravens have been close for so long year after year after they were close close close Why can't they do that now?


Hello, I'm Peter van Hursen from the South African National Bioinformatics Institute and welcome to the tutorial on mycobacterium tuberculosis variant analysis. So mycobacterium tuberculosis is the pathogen that causes TB, which until recently was the world's top killer infectious disease in 2020. It got pushed aside by COVID-19, but still we think that more than a million, maybe a million and a half people worldwide died of tuberculosis last year. The m tuberculosis genome is a 4.4 megabase genome. In the tutorial, you can find out more information about it and the typical reference strain that's used is something called H37RV. There is not a lot of variety within mycobacterium tuberculosis genomics and there is no recombination, but we can talk about that in the tutorial on mycobacterium tuberculosis genomics, which you can watch alongside this tutorial. So what is it that we are trying to achieve with mycobacterium tuberculosis variant analysis? A couple of things that we are interested in. Firstly, which lineage of tuberculosis are we looking at? Because this can be significant for research purposes in the future and maybe in the future we will understand what these lineages mean in terms of clinical outcome. Secondly, what variants exist in the genome that are associated with drug resistance? So mycobacterium tuberculosis is quite complex and unfortunately drug resistance tuberculosis is on the rise worldwide. And thirdly, the pattern of variants that we find within the genome can be used within outbreak investigation where we try and find out which cases are connected to others. So let's get analysing data. I'm going to get the data from the tutorial and I'm going to copy these links that are in the tutorial and I'm going to usegalaxy.eu where I've already created an empty history and I've called this m tuberculosis sequence analysis. So then I click my upload, paste fetch data and paste all of these at which point Galaxy will start to load them for me. So Galaxy has finished processing our uploaded files. I want to first change some names, just remove everything here to call the 00422 fastq.cz and then do the same with this file. So this is read1 and read2 from 004-2. The data in these two files, fastq files was collected from a southern African TB patient in a study which was examining reinfection versus reactivation of tuberculosis infection. First thing I want to do with these files is some quality control. So I'm going to use fastqc to search for it in my toolbox here, fastqc and I'm going to use the multiple dataset selection button and I'm going to choose these two files and then I will click execute. So while fastqc is busy running, I'm going to get ready with my multiqc. What am I doing here? I want to not have two individual reports. I want to aggregate the data into a single graph. So here in multiqc, I say fastqc is my input and then I want the raw data input and I'm going to use control and click to select the raw data from those two files and I can do that and Galaxy will put it in the waiting queue waiting for my other data to process. So my other data started processing once this fastqc is finished processing, multiqc will start. So now multiqc has finished running, so let's have a look. I icon here on the multiqc on data 9 and 7, web 8. Give it a few seconds to load and there it is. I'm going to move my sidebars to the side to give the multiqc window more space that I can look at. I can move my sidebars using these little arrows in the bottom corners of the Galaxy interface. So what we see here, percentage GC is 66 percent. That is what we expect from a microbacterium tuberculosis, quite a lot of duplicate, probably PCR duplicates coming in here, 5.3 million sequences and let's look at the quality. And that is a pretty decent looking quality profile. We see here that the two reads for the reverse both have quality mostly above 30, just dipping here at the end. And then we look to see if it was the adapter content. Looks like there might be some sequencing adapters left in some of the sequences. But it's quite a low percentage overall. So think about like how you handle these sequences, but while you're thinking about that, let me bring my Galaxy interface back. I'm going to move on to some quality trimming. Now there are many different quality trimming tools, but I'm going to use Traumatic. It is one that I know fairly well and I like it. So here's Traumatic and this is paired end sequencing. And there we put the pairs in. Notice that I'm handling these sequence files as individual files. If you're dealing with a large amount of data, you're probably going to want to use a collection of paired end data for this analysis. The average quality by default is 20. I'm going to bump that up to 30 because I saw the quality was quite good on those sequences. So I don't think I'll lose a lot by doing so. And then I'm going to add a second operation, which is that if anything drops below 20 bases, we should discard it. And here Traumatic has started running. You see it will give me both the paired and unpaired reads. The unpaired reads are if it decides to discard a read from one of the files, but not the other then we'll have some unpaired reads left, but mostly we'll be paying attention to these R1 and R2 paired. And while Traumatic is already running, I'm going to do another quality check. So I'm going to use tool called Kraken 2. What Kraken 2 does is it tries to assign a taxonomic label to each sequence read. So I'm going to choose my paired sequences. And I'm going to use the R1 paired and the R2 paired outputs from Traumatic. This Kraken can run after the Traumatic has finished running. I want to use the scientific names. And then down here in the create reports section, I want to print a report with aggregate counts. So what Kraken 2 is doing, of course, I have to select, I want to use the standard database. Let's see the most recent standard database, which is a database of essentially most of the sequences that you find in NCBI across different domains of life. And what Kraken 2 does is it tries to, in this report that we're going to see, give us some sense as to whether the species is predicted to be mycobacterium tuberculosis. I said earlier that mycobacterium tuberculosis doesn't have a huge amount of diversity within the species. So that makes sorting out specific different mycobacteria quite difficult. I should have said it doesn't have a lot of diversity within the genus. There's more similarity than you might find in some other species. But yeah, let's set this running and then we'll run after the Traumatic. And Kraken 2 is quite a resource intensive process. So that'll run for quite a while. If you want to skip this step and just work the tutorial faster, I will make a saved history of this tutorial available for you to download. So you can just see what the Kraken 2 output looks like. So at this point, Kraken 2 is busy running. Traumatic is run. There's not much to see here because this is just Farscue files. But if we have a look at them, we'll see that the two paired-end files, 257 megabytes each, if we compare that to the input files, we see there is some change in size. Let me just go back to confirm that. And then at the unpaid, it's a very small amount of reads in the unpaid section. But we see that there has been some trimming down of our data to get our Traumatic Farscue. While Kraken 2 is still running, I'm going to go back to my regional uploaded data and I'm going to change some names. So I'm going to just remove the prefix to this mycobacterium tuberculosis ancestralreference.genbank and do the same with the .fasta file. Now what is this file that I'm looking at? As I mentioned previously, the standard reference genome for mycobacterium tuberculosis is H37RV. So I'm going to do the same with this chromosome file. And H37RV belongs to lineage 4 tuberculosis. Inarchicomas and colleagues worked with the diversity of mycobacterium tuberculosis genomes to infer what the ancestral reference genome should look like, but only inserting single nucleotide substitutions. So the inferred ancestral reference genome is exactly the same size as H37RV. That means the annotation still works the same. But in terms of the sequence content, it is more neutral when it comes to the sequence being closer to what we think the ancestor to all lineages of tuberculosis looked like. So it's quite useful for building phylogenies, especially because you no longer getting bias from comparing your samples against a lineage 4 reference. And so now Kraken has finished running. So let's have a look at the output files from Kraken. This is the classification of each individual read, many, many millions of lines. And this is the report generated. So it starts here by saying, well, 95% of all reads could be classified as something. So there's only 4% so it could unclassified. Then we go down and read it down. And we see that 94% are classified as mycobacterium. Mycobacterium tuberculosis itself, the complex can only count for 14% of the reads. But that's because it's not able to unambiguously classify further down than mycobacterium. But that suggests that we are looking at a mycobacterium tuberculosis sample without significant contamination. So now that we've finished with our quality control work, we can map these reads against the mycobacterium tuberculosis genome. And for that, we're going to use a tool called Snippy. Snippy is essentially a pipeline written in Pearl by Torsten Siemen that does mapping, some cleaning up of the mapping and then variant calling. It does mapping with BWA and BWMM and it does variant calling with Freebase. So let's look at the options. We're going to use a genome from the history and build the index. Now here I'm going to choose the GenBank file because if I use a GenBank file, Snippy will generate a VCF that also has information about which genes the variants were founded. Now I'm going to use the R1 and R2 paired reads. Then in the advanced parameters, I'm just going to drop this down to 0.1. So normally at 0.9, in other words, finding variants only if 90% of the reads agree, I'm going to say 0.1 to see even rare variants. And finally, I want the VCF format. I want the tab separated summary of all variants. I want the alignment in BAM format. I'm not interested in Snippy Core because I'm not analyzing multiple samples at this point. Just checking my tutorial. And those three outputs are the only ones that I care about. Then I hit execute and the mapping will now commit. Mapping and variant calling. So now that Snippy has finished running, that should take about 20 minutes. You can see what our output looks like. OK, this is the alignments in BAM format. Then we have VCF format. We see here various variants. And because of how we used a GenBank reference, then we can see that the variants annotated in terms of their location on the genome and what genes are happening in that region. So let's have a look, 1,087 lines in this tabular format output. And this means that we've basically got 1,086 variants, not different types, SNPs, deletions, and so on. And this is what we should expect from a typical macrobacterium tuberculosis sample. We have approximately in the range of between some hundreds and maximum maybe 2,000 variants compared to the reference genome. So we've done various steps of quality control to get this point. We've looked at the sequence quality with FastQC and MultiQC. We've checked for contamination with Garkin2. And internally Snippy does its own quality controls. To make sure that we get good alignments specifically, you might have noticed in the advanced parameters section, there is a parameter for minimum mapping quality, which is used internally by Snippy to ensure that we have good quality alignments coming out. And then finally, we've used the inferred ancestral reference genome, which, as I described earlier, has some advantages for variant calling in macrobacterium tuberculosis. So one of the challenges with macrobacterium tuberculosis is that the genome has some repetitive regions in social sequence sites and also the PEPP, PGRS gene family. So there is a tool specifically for filtering out these problematic regions and just doing in general VCF filtering for M tuberculosis. And it's called TB variant filter, and I found it now. And we're going to run it on the VCF file. And let's see which filter should we use. So filter out variants by region. So that looks, if we just look at the options available here, the default regions that are filtered out of the PEPP regions and the tool UVP has a useful list of repeats and insertion sequence sites. So those regions are also filtered out. And then some other filters we might want to use is remove variants close to indels. It's still being debated whether this is still necessary, but in general, when an indel happens, then alignment around it, a few bases around it. And by default, that is five bases can get a bit uncertain. So then there could be false variants around indel. So that's why that photo is there. And then very commonly used photos, photo sites by alignment depth. So the default here is read depth of 30. We want at least 30 reads supporting each variant. Not going to change any of the default options for the specific photos. Just use those. Just use those photos as they are. OK, a TV variant filter is busy running. So now let's do something else in parallel. TV Profiler is a tool to infer drug resistance from the mycobacterium tuberculosis sequence data. And it can take input straight from the Illumina sequences or you can feed it the aligned BAM, which we snippy already produced an aligned BAM. And it can either output in text or PDF and just checking the minimum allele frequency is 0.1, which is the same frequency that I was using in snippy for its variant calling. And let's hit. OK, so this takes the output from the snippy and it's running in parallel with TV variant filter. It is not using the output for TV variant photo. You can run it on VCS, but because it has its own variant calling, I prefer to run it on the BAM. When you are using an aligned BAM for TV Profiler, then it is useful to keep the... Well, it's not useful. It's necessary to use a alignment against 837RV chromosome so that TV Profiler is able to understand the variants in terms of the coordinate scheme of 837RV. TV Profiler has now finished running. This one took only a few minutes for me. And what does it give us? So TV Profiler gives us output in JSON format, which is a format that is designed for computer programs to read. It does its own VCF calling, but this is only focusing on regions that it considers of interest for drag resistance. So you see it's only 43 lines, quite a bit smaller than the VCF from snippy or TV filter. And TV variant filter. And then it produces a report. So let's have a look at its report. This report can be in PDF. This one is a text format. Firstly, it tells us what lineage we're looking at. So this is a lineage for the so-called Euro-American lineage. To be closer, sample that we're looking at. Despite the name, Euro-American lineage is common worldwide, at least in part due to colonialism spread of Europeans around the world. It gives us a predicted Spoligotype. And then it talks about predicted drag resistance. So here are some characteristic variants, RPI-B, SERR 450LEU. And this is the percentage of region in which that was confirmed. And so we know with Rampus and Resistance is largely associated with mutations in RPI gene. Isonizid resistance, we have here a change in the KG gene and so on and so forth. So unfortunately, this is showing that this sample is predicting resistance against all the first line. Typicalosis drags and it's classified as multi-drag resistance. And then there are variants in other positions which TV Profiler did not associate with resistance. Now, before we finish off this analysis, I just want to look at a detail here in the VCF. So when we use Snippy with a GenBank reference to create the VCF, then all of the gene names have a prefix gene in front of them. Now the tool which I'm going to use next does not handle that prefix very well. So I'm going to use the set tool or text replacement to remove those prefixes from the VCF. So my set program is simply take gene, remove it across the entire line, and I'm going to run it on the output of TV variant filter. Execute. Now that I've got filtered VCF and I have the output from running TV Profiler, I can use the TV variant report tool which uses the Combat TV Explorer database and the data we've generated thus far to produce a nice to read report on variants that we found within our sample. So my output is the JSON. In the second option here, the drag resistance reports, I'm going to use the JSON output from TV Profiler, and I'm going to use the text transformation on the VCF as an input. And then I'm not going to, I'm going to filter out some of these variants between in the intergenic regions because the annotation sometimes shows us that a variant is intergenic when it actually is in a gene. Anyway, it's just a snippy of it gives us multiple reports for the same variant. Just going to have a look at the advanced options which database to use. We will use the one back at Sanby. Okay, so that is waiting for text transformation with said to complete running. A later version of the TV variant report tool might not need this step. So now my set has finished running. If I look here, I still see the same variant report, but now the RV locus numbers rather than gene underscore, etc. I'm going to just look, this is sample 0042, and I'm going to just change the name here to variants so that this is a meaningful name in my history rather than what it was before. And now we can see that TV variant report has also finished running. Now this uses the Combat TV Explorer database to annotate the variants, but that database is currently running on a server in Cape Town, South Africa. It is an open source project though. So you can actually run a local copy of the database if you want to, and if you don't want to rely on our infrastructure. Again, I'm going to make the window a bit bigger to see the outputs. Here we can see just the HTML slightly prettier version of the same drug resistance report that we got from TB Profiler. But here is the interesting output, which is the TB variant report, where instead of looking at VCF, each variant is now annotated in terms of its gene, which protein it is associated with what the expected impact is. So we've got here, this is a synonymous variant, so the expected impact is low, pathways if they're known that this protein is involved in, and the position in the genome. So if we control click on this position, it'll open a window on Explorer at Sanbi, which, sorry, it's taking a little while to load, there it is, which is J-Prowse, genome browser, and this variant is in this position. This is showing us that synonymous variant in that position at that locus. This is a locus in question. If I right click this, and I say search for DNA in, then it will open a window on top, which will load the results page for DNA in or here at the top, there's a link, I can just control click that, and then I get a full page for you. And this is what is known about this gene. It's a DNA polymerase, it's a sequence and so on and so forth. So then if I take this position and I control click it, it loads the J-Prowse and it shows specifically where in the genome this variant is happening. So you can look at the genomic context of the variant. Finally, for this tutorial, we might want to see the alignment that underlies our variants. So we can do that within Galaxy using J-Prowse. The advantage of J-Prowse is that we don't need to download the alignment to our local computers to visualize. The alternative is using ITV and doing the download. So we're going to use the genome from the history and then we want a new J-Prowse interest. We want us to be the bacterial code. I'm going to refer to the tutorial for these settings. So a new J-Prowse instance and then we want to insert track group and I'm going to call this sequence reads and the first thing that I want on the annotation track is the pile apps from the BAM that is from Snippy. I'm going to leave the auto-generate snip track. I'm going to say yes and I'm going to put this on for new users and the next annotation track I want is the variants. So that's VCF format. So this is BAM then we have the variants and we're going to use the VCF variants, the most recent one in our history and we're also going to put this on for new users and finally I'm going to insert a new annotation track group and I'm going to insert the annotation track for micrometric tuberculosis TFF annotation and then I want that to be a canvas feature that's in the track type. That is a canvas feature and style.label I'm just going to call that product and style.descriptor I'm going to also call that product and then I'm going to say that this should be on for new users. Execute and now it will go and build J-Prowse for us. This is somewhat of a time consuming process. Okay, our J-Prowse has completed. So let's have a look again. I'm going to hide the side bars here despite what I asked for. It is not showing the annotation in our first load so I'm just going to have a look look for a variant of interest. VCF variants. It looks like there's something interesting around this position on the chromosome so let's zoom into there and here is the deletion that we heard about and I'm going to zoom out a little bit just to give us a bit more context. There is the BAM alignment and there definitely appears to be some kind of a gap going on here which Freebase has classified as a deletion. I'm going to zoom out a little bit further and a little bit further so that I can see the read context. In here we see the reads. Paid end reads around this part of the genome. Zoom out quite a bit further and I'm now going to hide the actual read track so I can just see the coverage plot and we can see a dip in the coverage over there. Let's take another example. So this is the CATG mutation that we are interested in for drug resistance so I'm going to have a look here in the report from DP variant report. Search for CATG. This is the problem of the annotation using RV numbers. So CATG must just remember what is the RV number for it. This is RV1908C and so that shows us that the variant is at this position in the genome and I will go back to my J-brows. Look at that position and now zoom out some and there we can see very clear evidence that there is a variant at that position which is the one associated with drug resistance. That brings me to the end of the tutorial on mycobacterium tuberculosis. Variant calling and analysis with Galaxy. Look at the end of the tutorial for some examples of samples that are not as straightforward to analyze. It is always useful to know what kind of problems you can encounter in sequencing and bioinformatics. I hope you enjoyed the tutorial.


Hi, I'm Zor. Welcome to a new Zor education. Today's lecture is about motion on the inclined plane. Well, this lecture is part of the course, which is called Physics for Teens. It's basically a high school level course of physics, which I am recording right now, one lecture at a time. Right now we are in the middle of Mechanics part and there are others. This course is presented on the Unisor.com website. If you find this lecture on Unitube or anywhere else, I do suggest you actually to switch to Unisor.com. It's a free site without any advertisement and the advantages of listening to this lecture through this website is that, number one, you have a complete picture of whatever the topics will be provided. Number two, every lecture has detailed notes. Number three, there is an educational process if you would like to get involved in it for either self-study or supervised study. And it allows you basically to take exams and if you are working just by yourself or with a supervisor, you can take a look at the results of your exams and do something about it. Anyway, let's get back to our motion on the inclined plane. First, let me just draw a picture which would probably explain everything. This is something which we call inclined plane and this is an angle phi. So it's a plane which is not horizontal but at a certain angle. And there is an object there which obviously has certain weight and it slides down this inclined plane. Well, sometimes I use the word inclined plane, sometimes I'm using the word slide because it really looks like a slide on the children's playground. So on the slide, this object is sliding under its own weight. So my task is to determine how fast it will go down. Now, obviously, if the angle phi is greater, it's steeper, it should go faster, right? And if angle phi is 90 degree, which means basically there is no inclined plane because there is nothing which holds the object from underneath, the object should fall down with acceleration of the free fall, which is on planet Earth called G, which is approximately 9.8 meters per second square. Alright, so let's see. So in our extreme case, this would be the maximum. Now, in our other extreme case, when phi is equal to zero, basically we have a horizontal plane, right? Then the object will just sit by itself, right? You just put something in the horizontal plane and nothing happens. It just does not move. The weight is completely compensated with the reaction of the supporting plane, right? So in this particular case, in the middle between these two extremes, we understand that there should be some kind of reaction force which should force our object to slide exactly on this plane, on an inclined plane. So the combination of this force and this force, the weight and the reaction of the supporting plane are the only two forces which are acting on our object. And their resultant force should be directed along the slope, right? So this is supposed to be parallelogram. This, this, this and this is supposed to be parallelogram, right? Because if it's not, then our object either would fly off the inclined plane, which does not happen. Now, if it's turned this way, it should actually go through the plane, which also doesn't happen. The reaction force is exactly of such a value that this is parallelogram and the diagonal is directed along the slope, right? Okay, now we do know that this angle is straight, right angle, sorry, right, right angle, right? Why? Because the reaction force is always perpendicular to the supporting plane. So no matter how the plane is positioned at angle or whatever, the reaction of this supporting plane always on a perpendicular or we're saying normal to the plane. Okay, so this is normal to this plane. So this angle is right angle. Alright, now if this angle is right angle, then this angle is also right angle, right? This one. Which means if this is w, this is the right triangle and we can actually determine two different forces. One is the resulting force, this one, which actually pushes the object down the slope, right? Well, if this is phi and this is the right angle, then obviously this is phi as well, right? Because this is perpendicular to this, this is perpendicular to that. So if two sides of one angle are corresponding with perpendicular of two sides and other, then the angles are the same. So this is angle phi. This is w. Now when I'm talking about the value w, obviously it's a vector, but if I don't put this vector thing on the top, I actually mean that we all know the direction of this vector and I'm talking only about its absolute value, about its magnitude. And this positive, because if it's directed somewhere else, then I will use not in the positive direction of some axis, but in the negative direction I will use the minus sign basically. So we're assuming that all values are positive, but we do know that their direction is such and such. In this case, this goes down and this goes this way. Alright, fine. So in theory, we can very easily determine the strength of this force, the magnitude of this force, because it's just the right triangle and this obviously w times sine of phi, right? This ketitus is hypotenuse times the sine of this angle. Alright, fine. Now this is the force which moves, let's call it wf. Now what other forces are involved here, which I didn't really mention before. Now obviously if this is a reaction force, it's supposed to be a reaction on something, on what? Obviously on the pressure which this object exhorts on the plane, which must be exactly equal to in magnitude to this r. Well, it's not equal maybe on my drawing, but in any case, it's supposed to be equal. So this is wr. So this force which goes down can always be represented as the sum of this, which is wf, and this, which is wr. Which is r, I'm talking about again magnitude, that's w times cosine of phi, right? Obviously. Because this is w, so this is w, this is also angle phi, so r is equal to w times the cosine of this angle. Well, basically that's quite sufficient to determine how our object will move, because if I have the force which moves it down the slope and I have the mass, well, if I have the mass, I don't have the mass, but if I have the mass, then this force must be equal to the mass times acceleration, right? That's the second law of Newton. Now on the other hand, since I know what wf is, it's w times sine f, fine, and I know that the weight is related to mass and free acceleration, because weight is basically the force which forces the object of mass m to go down, vertically down with acceleration g, right? So it's mg times sine f, fine, sine phi. So from this and this, we deduce that a is equal to g times sine of phi. So it doesn't depend actually on mass, which we don't know. The acceleration depends only on some constant and the slope. Now let's just analyze. If phi is equal to zero, which means my slope is not really slow, but the horizontal plane, sine is equal to, zero is equal to zero, so I have no acceleration, right? Which is right. I mean, the object will just lie on the flat surface. If my sine is equal to one for angle equal to 90 degree, right? Then my acceleration will be just free falling, g. And that's exactly what corresponds. Now let me just make a little logical deviation. I did not talk about the reference frame. I'm kind of assuming that the reference frame is my y-axis goes down and my x-axis goes to the right, right? I mean, not down, but vertically. So I assume basically this is my directions. This is x and this is y, which is fine. In this particular case, it's fine. However, I would like to mention one might actually be a simplification, if you wish. You see, there are usually many forces which are acting on the object. Now in this case we have two forces, right? Now the reference frame might actually result in easier approach if the reference frame is catering to the movement of the object, not to the forces. Now a major force is the gravity. So my system of coordinates is basically catering to the fact that my gravity looks simpler. It has only the y-direction and no x, right? So it's vertically, so there is a y-coordinate. So if I'm talking about the vectors, it's basically zero comma w, right? So no projection on the x-axis and there is only projection on the y-axis, which is equal to an absolute value of w. And if I'm using w as my absolute value, the magnitude, then I really should put minus here because the force of the gravitation is directed downwards, right? And my y goes up. So that's kind of a natural thing. However, it's not the simplest thing. You might consider slightly different system of coordinates. And here is the one which I prefer in this particular case. And when we will talk about the next problem, you will see how much more important this is. I prefer to simplify the movement of our object. For this, knowing that the object is moving parallel to the slope, I will use this slope as my x-coordinate. And perpendicular to this would be y. It seems a little unnatural from the first viewpoint. However, it greatly simplifies the movement of our body. Now, I was calculating the acceleration along the slope. What if I would like to measure acceleration as a vector which has certain coordinates? Well, it would have two coordinates in the old system of coordinates, right? Because it goes under angle, so it will have some acceleration along the x-axis and some acceleration along the y-axis. Now, in this particular case, with this particular coordinate system, I do have only movement along the x-axis. And there is no movement along the y-axis. It's always equal to zero, which is a little bit more convenient. Now, what's less convenient is our weight. Now, the weight becomes a little bit more complicated. But reaction force is not. So, if I'm talking about real vector algebra, I'm simplifying a little bit more. I'm simplifying movement and the reaction force. And I'm still a little bit more complicated with the weight. And it does make sense, because in this particular case, now I can say that my acceleration has only x-component, and it's equal to whatever I was just calculating, which is g times sine of phi. And my y-component is zero. So that's my vector of acceleration of this object. And it's a little bit easier to represent it this way. And now, well, basically, that's it about this particular problem. And I would like to switch to a little bit more complicated, where these coordinates will be really important. Now, consider we have exactly the same setting. However, there is one important consideration. This is not an inclined plane or a slide, which is, well, fixed on the surface of the earth anymore. Let's consider that it sits on some kind of a table. Table is fixed, but this thing can slide without friction along this table. Now, why is it more complicated? Well, just think about it. If the object forces the whole thing down, well, it means that this slide might slide from under the object to the right. So the object will not move exactly parallel to the x-axis, and I'm still retaining this coordinate system because it will be easier for me. So the object is not moving this way. It's moving basically under some kind of an angle. Why? Because on one hand, it slides the slope, and on the other hand, the slope goes from under it. So the movement would be like this, basically, right? So that complicates the picture, significantly complicates. But we can say now that the reaction force is no longer, the reaction force is no longer the WR with a minus sign, where WR is basically W times sine of this angle. Fine. And because of this imbalance, you see, if you are pressing something on the plane and it's not moving, then the weight is actually exactly equal to the reaction force. But if you press something on the plane and the plane by itself is moving down, the pressure would be less on the plane, and that's why the reaction force would be less. Now, if this is an incline plane, again, I'm not only slowing down by sliding down, my plane goes this way, and that basically weakens the pressure, because the plane goes from under the object. So, R now, by its absolute value, is less than W sine pi. So if this is WR, like here, you know what, let me just draw it a little bit better. So, again, we have this thing on the table. I'm still using this as an x-axis, and perpendicularly to this would be y. Now, this is my object. So this is the W, and this would be my WR. This is the real R, and this is minus R. It's smaller by magnitude than this, because the plane slides out. Well, that complicates the picture, because right now I don't have the reaction force. I know that reaction force and the weight are two components, and now this thing goes this way. The resultant of this force and this goes this way, and that's the real trajectory in my system of coordinates of the object, because, again, object goes down, but slope goes to the right, and that would be the real trajectory. Again, that complicates the picture. It's still parallelogram, but it's no longer right triangles here. So, what do we do? Okay, let's just think about it. And here my system of coordinates plays a very important role. Let's just think about the movement of this object separately as a projection to the x-axis and as a projection to the y-axis. Actually, my first is how it's projected to the y-axis. Well, let's just think about the forces which are acting along the y-coordinates. Now, what are these forces? Well, actually I have this force, reaction force, right? And I have a projection of the weight on this line which is parallel to the y-axis, which is WR. So WR is acting along the y-axis and WR is acting along the y-axis, right? So along the y-axis, my forces are to the negative side, it goes WR and this is negative, right? Because, again, I'm assuming that all these numbers, numerical values are just magnitude and that's why I put minus because it's to the negative direction of the y-axis. Y-axis goes this way, my force goes this way. Now, R, on the other hand, is a positive and my acceleration is negative actually, right? My AY is negative, so if all these numbers M, AY, WR and R are positive then I have to put these numbers, these minus signs to compensate. Okay. Now, what is WR? Well, WR I know what it is because this is really projection on the y-axis so this angle is right angle. So I know that WR is equal to WR times cosine phi, right? This is phi, this is phi and WR is WR times cosine of this angle. Well, R is R, I can't say anything about R right now but I do can say something about AY. Well, let's just think about it. By how much in the direction of the y-axis my object moves if my entire plane slides this way? So let's consider my entire plane slides this way. So from this it goes to this. So this is the movement of the plane. Now, what is the vertical, what is the component of the movement of this object in this particular direction? So if this moves by D, how much this is moved? So this is D, this is the same as this, this is phi so this is D times sine of phi. So for every movement of the plane to the right by distance D my object, if it does not have this component along the x if it has only y-component, I'm talking only about its y-component the y-component moves by this. Now, if the distances are related this way so the speeds are related because they are derivatives from the distance and the acceleration are related this way. So this is equal to a plane times sine of phi but this should actually be very clear because it's very important for everything else. If a is acceleration of the plane and we are talking about only in this direction because this is a table on which it slides and the table is horizontal, it doesn't move anywhere so there is a reaction force which prevents it to jump up or down it's only to the right. So as this slide moves from this position to this position vertical component of the movement of this object only vertical, I'm not talking about because any movement like this one has two components along the x-component which is this and along the y-component which is this perpendicular to the plane. That's why it's important to have this system of co-ordinate one is along the plane and another is perpendicular because this is really very important we are projecting everything on the y-axis which is perpendicular to this plane. So this would be my acceleration of the object the y-component of acceleration of the object in terms of acceleration of the plane and again its angle. So let's just leave the letter p here that would be easier and now I can write this particular equation in the following form minus m A p sin phi equals 2 r minus r minus w r and w r is w times cos i. Okay, this is a very important equation and we will call it equation number one. Now what's wrong about this equation but there is nothing wrong about this but what's insufficient because we have two different unknowns r and acceleration of the plane. Well let's assume we have to determine acceleration of the plane and this is the whole problem actually. What is my acceleration of the plane as the object pulls down? Well obviously I don't know mass that's important and I don't know the mass of the plane this slide because obviously it's important consider it this way if the slide itself is very massive well most likely the small object which is on its surface it will slide down but it will move only slightly the slide acceleration will be very small because the force is basically the same right so acceleration will be smaller so it actually depends on mass it depends on the mass of the slide itself well we'll see what we will need for complete solution but actually these are kind of complicating factors now let's move on now since I'm actually talking about acceleration of the entire plane I have to somehow relate it to again the second law of Newton I need the force which is actually pushing it in this direction well let's just think about which force is this well obviously it's related to the force exorted by this object and related to its weight but the force actually is only the pressure which is equal to minus r as far as the vector is concerned so the pressure from the object is basically the same as the reaction force of the plane itself into that direction so all I can say is that we are pushing with the force r but in this direction that's why it's minus okay but plane goes this way now how is it supposed to be working well let's just forget about the object and let's just think about only the plane so this is my inclined plane this is my object which is pushing this with the force equal in magnitude of r now obviously this is support why would my slide go this way well obviously I have to represent this as perpendicular and horizontal and the horizontal component pushes the slide to the right and the vertical component is balanced by the reaction force of the table now this is still an angle phi and this is angle phi so my horizontal component is my force of pushing the pressure force which is equal to r in magnitude and the horizontal component would be times what? times sine and phi this is just right triangles so the horizontal component this is phi, this is phi so it's hypotenuse times sine would be the catheters and this is equal to what? well this is equal to mass of this inclined plane the slide itself times its acceleration in this direction the same thing as this one we are talking about this horizontal acceleration now it's much easier now we should really assume that we must know mass and mass so remaining unknown are acceleration of the plane and the reaction force so we have two equations with two unknowns and all we have to do is to solve these two equations to find out what is my r what is my acceleration of the plane and r as well so how can we do that? well it's simple, it's linear anyway so r is equal to from here m a p divided by sine of phi putting it into this we will have minus m a p sine phi equals to m a p divided by sine phi minus now w is again m g because w is a weight this is a mass this is a free fall acceleration times cosine phi well from this we obviously have to multiply it by sine that would be square that would be sine here now what is my a p? a p is here and here so a p is equal to this goes to the right this goes to the left so it would be my m g sine phi cos sine phi divided by m plus this minus goes this way m sine squared phi alright so this is my a r I mean a p from this we can obviously find the r if you want r is equal to m a p divided by sine phi so it would be m m g we will divide by sine phi so it's only cos sine phi and m plus m sine phi squared phi so we have found the reaction force and that's very important now this is the reaction force if you remember from in the y direction right this is reaction force and this is my system of coordinates this is x and this is y this is r so we have found the magnitude of the reaction force what's the x component x component is 0 because it's perpendicular to this particular line right the reaction force is perpendicular to a slope so that's why it's very important actually to use this particular system of coordinates it would be probably possible to do a little bit more I would say habitual system of coordinates like this one vertical y and horizontal x but it's easier in this case that's all I'm saying so we have found these guys and since we have completely expression of r in this coordinates and we obviously have the weight as well it's time sine and sine times cosine we have two real forces so we can find not only the horizontal but also the vertical horizontal in this system along the slope and perpendicular to the slope so we can find the real movement which I'm not going to do it it's kind of a simple thing anyway but the most important is basically this to find the acceleration of the slide because that's what's new about this problem relative to the previous one where the slide was fixed alright so this was a presentation of a little bit more complicated mechanical problem and you know what are probably complicated even further in one of the future lectures when I will introduce the friction we will have some friction friction of this object on the surface of the slope and then the friction of the slide on the surface of the table so with these complications that would be a really big formula as a result in any case that's it for today I suggest you to look at the website dot com go to the physics 14 and to mechanics and to dynamics and this is super position of forces that's one of the lectures in that particular part of this course read the explanation I think it's like textbook basically so you have the advantage of having a textbook and the video lecture together so I do suggest to go again through all this material that's it, thanks a lot and good luck


So the point of this exercise was to kill a company to reinforce U.S. consulate in order to support the farm and estate and then secure a key terrain to allow follow-up operations for the battalion. So we had actors in the town, but the role was to provide a more realistic feel in the Maltown and also provide some stress for the Marines that they're likely to encounter within country later on this year without deployment. So initially coming to the town, the Marines faced a lot of hostility from the actors. As we went on, they faced a lot of adversity. They encountered a couple of IEDs. We also had some Marines out here playing an outpour. Those guys increased the stress, not necessarily hostile actors, but definitely just guys thrown into the mix to make sure we kept on our toes. Subsequently, the actors or the Marine counterplanned to throw at us to continue to make us to develop our decision-making, update our METTC, and I find a new solution. The Marines did a great job today being very flexible, definitely be proud of the Marines Gila Company.


Day 29 of 31 days of story Wanted to share with you the story that you want to tell for a pre-screen interview The pre-screen interview is a way of the hiring person to check if you are you know The kind of person that they want to meet in person Really, that's it Sometimes, you know the HR will get Or the hiring people like whichever whoever the decision-makers are will get resumes that seem really polished And then when they call the person it becomes quite obvious very very very soon into the call that You know the person who they're speaking to didn't write their resume because they are speaking a completely different kind of language Which is you know that could be a resume issue But you know as long as you are using your own words and your resume sounds like you and you're going to sound the Same on the phone then there's nothing to be worried about because you're telling a consistent story about yourself So it's that it's that they're calling because they don't you know It can be a real waste of your time and their time and other people who are involved in the hiring process is time if You know, you're not the right person like why waste the time of all that traveling and getting together If you're really not even going to be considered So it's just like a pre-screen to see if you know everything that you said on your resume is true if you're available if you're still interested and that's you know the story that you want to tell is a story of being interested in the role of being available of Showing them why you want to work for them in that role and in that company and a little bit about why you're qualified and it's not Huge memorized speeches that you want to be giving but those that's it is you're telling the story when you answer the phone You're in the role of a character who is telling the story about being excited and prepared and qualified for the role that they're talking about And that is that is the through line of your story Things you know stories that you want to have is you want to know why you applied for the job So, you know if they say hey, why'd you apply for the job? You can tell them exactly why what interested you about the role If they ask you why you are available for the job, then you want to have the story about why you're available So why are you thinking about leaving your current company or why you're no longer working? And you can phrase those both in really positive ways where you're not Putting down your current employer and you're not You know if you experience job loss, you're not putting down your current employer And you're not showing you know desperation or like you're still attached when you answer that question. So work on your leaving story The last one of those is you know what qualifies you for this job And so having an example about any education or experience and again not five minutes But a really short bit of like here's why and here's a little example of work that I've done and Usually those calls are only, you know, like 15 to half hour calls And so you don't need to to add, you know, a whole lot more They might ask you some questions that are extra screening ones and then those ones It's okay to not be prepared for them You just want to be open and present and tell them the truth when they ask the question And then hopefully if you're telling the right story, then they'll invite you in to meet them in person So thanks for watching. I'll be back with video number 30. Thank you


from Orlando, Florida. It's theCUBE, covering Cisco Live 2018. Brought to you by Cisco, NetApp, and theCUBE's ecosystem partners. Hello, everyone, welcome back to the live coverage here at theCUBE here in Orlando, Florida for Cisco Live 2018. I'm John Furrier with my co-student and for the next three days of wall-to-wall live coverage, we have the co-founders of the network collective here, Yvonne Sharp and Jordan Martin. Thanks for joining us today, network collective. Sounds great, sounds like it's a collection of networks. Sir, what's going on? What do you guys do? First, let's talk about what you guys do. I saw you guys doing a lot of podcasting, a lot of digging into the tech. What is network collective?  We really felt like there was a need to build community around network engineers and that really a lot of network engineers are very isolated in their job. There's only a couple of people where they work that know what they know and they don't have a lot of peers. And so we see network collective as a way to bring network engineers together to learn about their craft and also share with one another in a community that's more than a once-a-year conference like Cisco Live. That's awesome, I love the video podcasting. More than ever now, the need for kind of peer review, conversations around learning because the world's shifting, the keynote today, the CEO of Cisco talked about the old way and the new networks that are coming. We've been talking about no perimeters for years but now security threats are real, got to keep that screen solid, keep managing that. But also bringing a new kind of a cloud, hybrid, multi-cloud world requires real skill adoption, new things. What are you guys seeing? What's your thoughts and what's some things that you guys are exploring on your video podcast around these trends? Do you want to take that, Jordan? Sure, so I think the rate of change in networking is faster than it's been in a very long time. So we've kind of not had a whole lot of churn in the things that we've had to learn. I mean, it's been complex and difficult and there's been challenges in getting up to speed but with the transition to a more developer-focused and developer-centric model of deploying equipment, it is, and the integration of cloud into what is essentially our infrastructure, it's changing so much that it's good to get together and have those conversations because it's very difficult to navigate this by yourself, it's a lot to learn. Yeah, I want to push back a little bit on that because I've been in networking my whole career when I used to speak at Interop and I put down, here's the rate of change and here are the decades. It's like, okay, 10 gig, here's where the standards are, here's where the first pieces are, it's going to take years for us to deploy this. I don't disagree that change is happening overall faster but how are people keeping up with it? Are the enterprises that the networking people work for allowing them to roll out some of these change a little faster, so it gives a little insight as to what you're hearing from the community. I think, I mean, technology, we've got Moore's Law, right? I mean, technology has always been changing rapidly. I think the thing that is different is the way network engineers need to interact with their environment. Five to 10 years ago, you could still operate in an environment where you still did a lot of static routing, for example. Now, with the cloud, with workloads moving around, there is no way to run a multi-cloud enterprise network without some serious dynamic routing chops, whether that's BGP or EIGRP or OSPF or all of the above and a lot of network engineers are still catching up with some of those technologies. They're used to being able to do things the way that they've always done them and I think there needs to be a mind shift where we start thinking about things dynamically and that an IP address may not live in the same geography. It may move from on-premises to the cloud to another cloud and we have to be able to build networks that are resilient enough and flexible enough to be able to support that kind of mobility. Yeah, I love that, Yvonne, you're right. You talk about the multi-cloud world. Jordan, a follow-up question I have for you. How does the networking person look at things when there's a lot of the networking that are really outside of their control when you talk about really the cloud world today? Sure, before we jump there, I want to say the change that we're talking about though is a bit different than what's happened. So what we've seen traditionally, we mean speeds and feeds, but what's changing is the way we operate networks and that hasn't changed a lot. Now as for how do you view it when you don't, well that's a challenge that everyone is facing. We see networking getting further and closer to the host and when we see networking inside of VMware, I mean this has been something around for a while now, but we're just getting comfortable with the idea of hypervisor and now we've got containers and we've got networking in third-party services that we don't necessarily have access to, we don't have full control over and it's a completely different nomenclature. We have to relearn all the terms because of course no one reused the stuff we're familiar with because this all started from a developer mindset. It all makes sense where it came from, but now we're catching up. And so the challenge is not only understanding what needs to be done in all these different environments but also understanding just the terminology and what it means, what is a VPC? Well VPC means something completely different to a networker that has never touched Amazon than it does to somebody who has worked in Amazon completely. There's overlapping terms and confusion around that and it's just a matter of, I think you need some broader coordination. There's been discussion about something like a full-stack engineer. I think that's a pretty rare thing. I don't know how likely it is that you're going to be expert level in all different disciplines. But you do need cross-team collaboration more than you have traditionally. We've had these silos that no longer work in a multi-cloud world. It just doesn't work anymore. One of the things that came up in the keynote was the Networks Next Act was the main theme as they talked about this new way. They used secure intelligent platform for digital business, a little marketing there. More complex than a few years ago and then the onslaught of new things coming, AI, augmented reality machine learning and I put blockchain in there because I thought they would have put blockchain in the keynote to hype it up a bit. But then they introduced the multi-cloud concept at that point. So in the keynote, multi-cloud didn't come up until the next act came up. So obviously that is a key part of what we're seeing. We saw Google Cloud's CEO, Diane Green come on. How are network engineers looking at the multi-cloud? Because, I mean, are they toe in the water? Are they putting the toe in the water? What is multi-cloud to them? Because we talk about Kubernetes all the time from an app standpoint, but networks have been locked down for many, many years. You talked about some of the chops they need. What are those next chops for a network engineer when it comes to taking the road to multi-cloud? Sure, I mean, I think if you are going to do any kind of multi-cloud interconnect, you've got to know BGP. But at the same time, you need to understand some of those fundamental concepts that the reason developers are pushing to the cloud is not cost, although I've heard that a lot, that, well, this cloud thing can't be cheaper, but it's really about enabling the business to move faster, and so we need to start thinking that way as network engineers more too. We have, I think, historically, our mentality, and we've even trained our network engineers to go slow, to be very deliberate, to plan out your changes, to have these really complex change windows, and we need to start thinking differently. We need to think about how to make modular changes and to be able to allow our workloads to move and shift in ways that don't provide a lot of risk, and I think that's a new way of thinking for network engineers. Yeah, well, we're sitting here in the DevNet zone, and that was one of the highlights in the keynote talking that there are over 500,000 developers now registered on this platform that they've built here. Bring us inside a little bit, you know, is it, what was it, John? DevNet, Sec, you know, there's all of these acronyms as to, you know, how developers can... NetOps was their big thing. Yeah, how the network and the operations go together. What are you seeing? What's working? What are some of the challenges? I think this is a shift of necessity. As we see more problems solved in the network, we're adding complexity at that layer that hasn't been seen before, before it was routing. We just had to get traffic from one place to another. Then we added security. So, okay, we've got security going to security where we can send all the traffic through this place and just, like, we can do filtering or some sort of identification there. Well, then we start moving to cloud and we talk about dynamic workloads and we talk about things that can just shift anywhere in the world. Well, now our choke point is gone and so now we have to manage all the pieces, all the solutions, all the things we're putting into the network. We've got to manage it in a distributed way and so that's where I think the automation is white. It's such a big push right now is because we have to do it that way. There's no way to manually put these features in the network and be able to manage them at any type of scale without automating that process and that's why I think we see the growth of DevNet. I mean, we've been here the past few years. It's gone from a little thing to a much, much bigger thing. There's a lot of people looking at automation specifically that 500,000 number is rather large. That is really impressive that there's that many people looking at networks from a programmatic way. But in the meantime, I think that there's also a bit of a divide here because I think that there's, a lot of people are looking this way but I think there's, we talk about this on the show pretty often, there's really two types of networks. There's the networks of companies where it really is, they see their network as a competitive advantage and those places are definitely looking at automation and they're looking at multi-cloud. But we also see another trend in networking and that is to, I want some simple push button, just put it out, get packets A to B and I don't want to mess with it, I don't want expensive engineers on staff, I don't want, so I feel like the industry's almost coming to a divide that we're going to have like two different types of networks. We're going to have the network for the place that they just want packets going A to B and they really don't want much and the other side of that divide is going to be very complex networks that have to be managed with automation. Tell me about that other divide, I love that conversation because that almost kind of comes into like the notion of networks as a service because if you want to have less expensive people there but yet have the reliability, how do those companies grow and maintain the robust resiliency of these networks and have the high performance take advantage of the goodness, or does it matter? I mean, how are they, how is that demographic of the network evolving because either they're stunted for growth or they have an enabler, how do you view that and how do you take that apart? I think we have to look at our business needs and evaluate the technologies that we use appropriate to that, there are times for complexity, I think we pushed as Jordan very eloquently described a lot of complexity down into the network and we're working I think now as the entire industry to maybe back some of that out but one of the things that I hear a lot when we talk about automation and things like DevNet and developers is, I believe a lot of network engineers are afraid their jobs are going away but if you look at what's going on we have more connected devices than we've ever had before and that's not going to stop and all of those connected devices need networks and so really what's happened is we've reached a complexity inflection point which means we have to have better tools and I think that's really what we're talking about is how do we, instead of doing everything manually how do we look at the network as a system and manage it as a system with tools to manage it that way? You pointed about the jobs going away, I love that comment because that's a fallacy because there's so much other stuff happening tell us security, so that begs the question, I mean first of all, guys your job's not going away Jack, it's only, well Ken if you don't like stay current so there's all the learning issues the progression for learning but really it's the role of the network engineers and the people running the networks I mean I remember back in the old way the network guys were the top dogs they were kicking butt, taking names they ran the show, lot was riding on the network but as we go into this new dynamic environment what are the roles of the network? Is it security, I mean what are some of the things that people are pivoting to or are laddering up to from a role standpoint that you see in terms of a progression of new discovery, new skills is there a path, have you seen any patterns for the growth of the person? I really think network engineers need to at least understand what the cloud is and why it exists and they need to understand more about the applications and what they mean to the business I think we have created a divide sometimes where my job is just to get packets from point A to B and I don't really need to understand what we do as an organization and I think that those days are going to be behind us we need to understand what applications are critical why do we need to build the systems the way that we need to build them and use that information from the business so I think for network engineers I think cloud security, understanding applications and learning the business and being able to talk that language is what's going to be most valuable to them and their career in the future. Yeah and you know we've heard the term many times I'm a plumber, well I mean applying that moving packets from A to B it gets interesting with containers policy based stuff is known concept of networking QOS, these are things that are well known but when you start looking at the trends up the stack you're seeing that kind of thing going on service meshes for instance they talk about services from a policy standpoint up the stack that's always been the challenge for Cisco over the past 20 years is how to move up the stack should they move up the stack but I think now seems to be a good time your reaction guys to that notion of moving up the stack while maintaining the purity and the goodness of good networking I mean that's a big challenge right now right? The more that we mesh it all together and we don't really define the layers that we've traditionally used the more challenging it is to have experts in that domain because the domain just grows so incredibly large and so there's got to be a balance here and I think we're trying to find that I don't know that we've hit that yet you know where we understand where networking fits into all these pieces how far into the host or how far into the application does networking go we've seen certain applications not using the host TCP-IP stack right just to find some sort of performance benefit and to me that seems like we're pushing really far into this idea of you know well if we don't have standards and define places where these things exist it's going to be very much the Wild Wild West for a little while until we figure out where everything is going to be and so I think it just presents challenges and opportunities I don't know that we have the answer about how far it goes yet well let me ask you a question a good point by the way we agree I mean it's evolving it's a moving train as they say but as people that might be watching that might be a Cisco customer or someone deploying a lot of Cisco networks and products in this portfolio what's your advice to them what are you hearing that's a good first three steps to take today obviously the show's going on here the multicloud is the center of the focus this new network age is here for the CEO what are some things that people can do now that are safe and good first steps to continue on the journey to whatever this evolves into I think as you're building your network you need to think about modularization you need to think about how to build it in small manageable pieces and even if you're not ready to take the automation step today you need to think about what that's going to look like in the future so if you really want to automate your network you have to have consistency, consistent policy consistent configuration across your environment and it's never too late to start that or too early to start that right and so you can think about if I wanted to take these 10 sites and I wanted to manage them as one how would I build it and you can use that kind of mental framework to help guide the decisions you make even if you're not ready to jump into full scale automation from soup to nuts and also I think it's important to start playing around with automation technology there are all kinds of tools to do that and you can start in an area that's either dev or QA it's not going to be production impacting but you really need to wrap your hands around some of the tools that exist to automate to start playing with that Stay where you're comfortable get learned, get hands on Jordan, your thoughts Yeah, so I was over here like knotting my head furiously because everything she said that I was going to agree with Yes, ditto, exactly The only thing I would add is that we think about automation a lot in the method of config push or the idea of configuring your device and automating away but that's not the only avenue for automation start by pulling information from your devices it is really, really low risk way to start looking at your network programmatically is to be able to go out to all of your switches all of your routers all of your networking devices and pull the same information and correlate that data and get yourself some information that's with a broader view does nothing to affect the change or state of your network but you are now starting to look at your network that way and I will reiterate Yvonne's point you cannot automate a network if it's not repeatable if every design, every topology every location is a special snowflake you will never be able to automate anything because you're going to have a hundred unique automation scrims to run a hundred unique sites It's going to be chasing your tail It's going to be chasing your tail and so it is critical if you're not in that state now what you need to do is start looking at how to modularize and make repeatable config blocks in your network Well guys, thanks for coming on Yvonne George, thanks for coming on I appreciate you taking the time Final question, I know it's day one we've got two more days of live coverage here but if you can kind of project in your mind's eye, see the development of the show what's bubbling up as the most important story that's going to come out of Cisco Live? Have you had to look at some early indications from the keynotes and some of the conversations in the hallway? What do you think is the biggest story this year for Cisco Live? I think for me personally I want to understand what Cisco's cloud strategy looks like to know where they're going with the cloud and how they're going to help stitch together all the different services that we have the clouds are becoming their own monolith they each do things their own way and still the network is what is stitching all those services together to provide access and so I think it's important to understand that strategy and where Cisco's going Jordan, your thoughts? My, what I'm really looking for from the show this year is how Cisco's going to make orchestration approachable we've seen this process of automation where only the hardcore programmers could do it then we've got some tools and these tools and as we watch as more of Cisco's product platforms start to integrate with each other I think the key piece for enterprise shops that don't have that type of resource on staff is what tools are they going to give them to make this orchestration between the WAN and the enterprise campus and into the cloud and in the data center how do we tie all that together and make that like a nice seamless way to operate your network? Hey what a great opportunity to have another podcast called Under the Hood and see what's going on a lot of chops needed, thanks for coming on give a quick plug for your address for your podcast where do we find it, what's the site? Network Collective obviously you guys doing great things share the coordinates. Sure you can find us at thenetworkcollective.com we usually use the hashtag network collective I'm on Twitter at Sharp Network Jordan you want to tell people to find you? Sure, I'm at B.C. Jordan on Twitter and obviously if you want to interact with Network Collective at Net Collective PC on Twitter as well. All right thanks so much for the commentary and great to have a little shared a little podcast here live on theCUBE here in Orlando I'm John Furrier Stu Miniman for our coverage at Cisco Live 2018, stay with us for more we got two more days of this got day one just getting started be right back after this short break.


It's such a joy to click with a novel. Those initial pages which plunge you into the world and characters. The expectations you build of who the central cast might be. To then see those expectations continually undermined by the changing circumstances of Anthony Rand's protagonist, Alwyn Scribe. That's a ride-and-a-half. The storytelling mode adopted in the Covenant of Steel. Trilogy is from the point of view of an older Alwyn, scribbling down his youthful experiences. I'm particularly partial to this narrative model. Recent and hallowed examples of it include Richard Swann's Empire of the Wolf, and of course Gene Wolf's Book of the New Sun, among many others. The sense of dramatic irony and foreboding a capable author can work into a story with this literary device is potent. Anthony Ryan proves himself adept with it time and again. As here, I quote, I like to think I learned more from Declan Scowd that day than I did throughout the preceding years of our association. However, the principal lesson he would teach me in very short order would be this. All ambition is folly when it fails to be matched by reason. This is but one example that stands out among many. Often, we as readers are given the contours of an idea as to where events may soon go, yet that doesn't take away from seeing the events unravel on the page. Rather interest is heightened. It's one of those strategies that invites readers to speculate as they read along. That's why I love this method of storytelling. It makes the reading of a novel even more explicitly collaborative between author and audience. This pet passion out of the way. Let's turn our attention to another element of this work that simply delights me. I love fantasy novels that take their cue from historical events before going in widely fun new directions. In some ways, the pariah is such a novel. Several characters and cultures have roots in popular archetypal figures from history. Olwin's first leader and benefactor, the outlaw Deccan Scowl, is a de-romanticised version of Robin Hood. While he certainly steals from the rich, he's likely to give to the poor only if that serves his aims or increases his reputation for largesse with the common folk. Similarly, Captain Everdeen Curlayne, one of the main characters of the book, will send your Joan of Arc radar pinging. And the Ascarlians, a people to the far-off north, are quintessential worshippers of an asgard adjacent pantheon if I ever saw one. Similar comments can be made about the tenets of the Covenant of the Martyr, the chief religion of Olwin's homeland, and its likeness to a certain Christianity that we may be familiar with. What makes each of these elements so gratifying to read about is the way Ryan makes them his own. I'd be doing this novel of this service if I didn't stop to consider the protagonist. Olwin's cry of sparse throughout the pariah is a spectacular one. In the span of 560 pages, Anthony Ryan portrays a young outlaw turned jaded prisoner, turned soldier in a complex relationship with a Joan of Arc figure, and really isn't that every young man's truest aspiration. To see a character grow and learn from their mistakes, only to make various new ones. To see them develop down a path that, if you're lucky, you are partial to and enjoy. On both accounts, Olwin's development spoke to me. He is intelligent and perceptive, but brush, qualities that make for a character as likely to get into trouble as he is to get out of them, or coast by just before they ever come calling. Often Olwin knows better than to do a thing, almost as often he does it anyway. This is a believable and relatable lead, even in those moments of color's disregard for another's life, perhaps because Ryan imbues him with a potent sense of guilt. What's a great leading man without a support cast to watch his back, or at least put a dagger or two in it? Well, you'll have to make do with the first. Let me calm you. While there is little in the way of people backstabbing Olwin, he's more than happy to backstab a former teacher or two, whether to survive or to deliver vengeance. As for his friends, there are several notable ones. Toria is one of the first people that Olwin chooses to save at his own expense, and one of the finest friends you could make. Toria is caustic, competent, and short-fused, but steadfast. The way she sticks with Olwin through thick and thin is great, and I hope to get more of that dynamic in the sequel, even as the two's parts begin to diverge. When Olwin joins Covenant Company after his imprisonment, Toria joins too, as there's another prisoner of the pit mines, Brewer. In gaming terms, a tree would make for an excellent tankant DPS group. To the closest thing they have to a healer is a freelancer, a curious spell worker known as the Sackwitch. If you love your characters' clothes in an abundance of mystery, you will love the Sackwitch. I know I did. If you're in for a taste of gauntry and nightly deeds, there's even a turncoat knight with a death wish whose acquaintance you might enjoy. Look for Wilhelm Dornmel. I couldn't even get started on Everdeen Corlaine, the captain of Covenant Company, and the figure out which I suspect much of the next two books will revolve, in addition to the better part of this one. I have talked about the Anointed Captain, this holly figure that goes through her own share of travails in this first book, and I hope to voice them another time. The prior scratched my itch for a complex and adult work of fantasy, one that succeeds as much on strength of character as it does on the appeal of its low magic setting. You'll particularly enjoy this novel if you'd like an intimate read that has deep political dimensions. I think this would appeal to a lot of George RR Martin fans, in fact, Anthony Ryan starts off a trilogy that doesn't lack phrasing, not bone-crunching battles in unexpected defeats, not even the occasional miracle. I'm ever so eager to jump into the second book in the series. If you would enjoy listening to my thoughts on that one, don't forget to subscribe to the channel, smash that like button and let me know, have you read anything by Anthony Ryan? For me, he is a brand new author, although I know he has quite a few fantasy novels under his belt, I'm very excited to look out for all of them. At some point, especially once I'm done with the Covenant of Steel trilogy, which wrapped up just a few months ago in terms of publication, so it's all out there, all available, and I'm making my way through it as fast as can be. I'm Philip Magnus, I look forward to seeing you next time, bye!