Now, this is the one example I am trying to tell you, again you do not have to worry about few things, let me get it very clear. You should not be worrying about these drawing, these are the protein backbone, protein backbone means amino acid put together it is forming, it is a huge polymer. Polymer means let us say it is a huge length, it could be a lot of things together a lot of amino acid together and that is how this sort of different orientations are given, because that is how they look like different, different you know way of their structural aspects that is going on over here structure are different. So, you do not have to worry about all these protein backbone or the peptide backbone, if you zoom on over here you see that amino acid backbone, these are from different amino acid, all those amino acid if you look at you can see their structure, they are nothing but organic compound ok.  Tyrosine oxygen can bind with the iron center, another tyrosine oxygen phenol phenol oxygen can bind with the iron center, this is histidine and this is aspartate, aspartate is having carboxylic acid CO2H, carboxylic acid that can bind with the iron center, this is having histidine unit ok, just nothing but imidazole, imidazole you have heard of imidazole phenol carboxylic acid these are the side chain of amino acid, all those amino acid we know which it is having some side chain which can bind with the iron center or any other metal center. So, this is the one let us say it is transport iron that is what I was telling this is a PIDJA delivery guy, it is a delivery guy iron delivery guy right. Now, it picks up iron from different side and it essentially see it is not like they have to move they can just pass on also, you can I can take I can give it is a it can be a relay process as well right. Overall this is where it picks up or that is how one of the example we are showing how the metal center is going to be picked up. It binds with the amino acid backbone and it gets picked up and then delivered at a certain point where it can be stored pick up iron from storage iron protein ok, you can read, but usually what we see is iron centers during this movement when it is moving this is pick up and delivery time it is going to be plus 2 during transport and storage it is stabilized in plus 3 state. Because plus 3 are the one which is oxidized state little bit stable state during this storage it has to be stable. So, their redox chemistry is used for their transport as well right. Storing is in plus 3 form and during transport also it is in plus 3 form, during picking up and during delivery it is in plus 2 form ok. So, what essentially we are trying to tell you is a metal ion gets delivered by different approach. One of the main approach is simply different protein backbone that is nothing, but amino acid backbone protein backbone is nothing, but amino acid backbone. Amino acid has this phenol unit this imidazole unit carboxylic acid unit these are ligand these usually acts as a mono dented ligand and thereby can bind with either let us say iron 2 plus or iron 3 plus or zinc 2 plus or copper 1 plus copper 2 plus of course, you have to also understand that hard soft I told you hard soft acid base when you have a harder one for example. So, harder anion will come right when you have let us say you have copper 1 plus versus copper 2 plus copper 2 plus is harder one. So, if copper 2 plus has to be delivered it and let us say the ligands are very hard copper 2 plus is hard. So, the ligands associated with it during the delivery time it is let us say very hard right hard anions are bound. Now, the place where it is going to get delivered it is not having the harder anion what copper has to do or copper has to undergo is reduction copper 2 plus will undergo reduction to come to copper 1 plus since copper 1 plus is soft that side previously which was having hard ligand it will not bind it very tightly. Now, that softer copper 1 can be exchanged from one place to another let us say storage place if you say or that or the delivery place wherever it is delivering. So, that is how things gets also delivered you have very hard situation very strong situation hard anion all the oxides let us say are bound let us say carboxylate O minus or phenolate pH O minus differ whatever you know as hard, hard ligands are bound with a hard cation. Now, then you want to deliver it to a softer place. So, the metal center has to undergo a reduction and thereby softer center will pick it up and the reverse is true also the other case soft 2 going to hard. So, all these simple principle actually matters what ligands is there what ligand environment is there what oxidation state is there and thereby you can deliver in a particular manner. So, this is another enzyme I am just giving again you do not try to memorize too much because you may not be able to get into too much detail we do not want you also at this point these are protein backbone it looks quite funky and big, but if you nail it down if you zoom it down what you see is this. So, different protein backbone is coordinated with metal center and another different protein backbone is coordinated with another center. Essentially once again hard soft acid base principle will be followed of course, also another thing you have to see what is available sometime whatever is available they can still go with it if there is no competition between hard and soft center. Even if it is in a soft center hard if metal center is soft, but hard anions are the one which is available it is ok it will go with it it is not it is not like they cannot bind binding efficiency may not be great that is it. Overall I think the what we are trying to say is this enzyme is able to function since copper can undergo oxidation state blah blah blah you read it I think I explained it copper 1 plus and copper 2 plus iron 2 plus and iron 3 plus these oxidation state change help you to do a lot of chemistry 1 or 2 chemistry we will discuss today that is number 1. Now, zinc plus does not undergo usually these oxidation state change they can give the structural aspect they hold things together and thereby provide some chemistry to be done at that center let us move on. Now, I think the major part of the syllabus is on hemoglobin and myoglobin or so called the porphyrin centers right. I do not know whether you have studied little bit before fine. So, porphyrin center is something this is one thing I would ask you to remember and draw it again and again. Usually what people do is they cannot provide this double bond in a rational manner you try to draw it usually in the exam it is given ok draw porphyrin or you will be asking a question in a way that you have to draw porphyrin draw the porphyrin what is not important is these are what substituents are there. Of course, these substituents these R group will determine whether a complex is going to be soluble or how soluble they have a role, but for this class you do not have to understand or know what the role they are actually playing. By changing the R group you can change or modulate the properties to some extent ok. Now, this is the porphyrin you should be very familiar with this is nothing, but a ligand this is a kilator it kilates the metal center actually it is a tetradentate ligand usually what we have seen so far in the amino acid backbone is mono dentate ligand usually right means only one coordination sites are there. One let us say phenol phenol oxygen can bind right imidazole imidazole nitrogen can bind, but porphyrin these 1 2 3 4 4 nitrogen can bind and if you put a metal center over there you can see 1 2 3 4 5 6, 6 membered metal that ring will be formed. You have seen the bidentate ligand how they are forming dent I mean how they are biting it bidentate they are biting it this is like tetradentate and this is a very good kilate. It can you know it is almost like those EDTA we were talking EDTA can extract out porphyrin is a strong ligand it can extract out iron let us say or any metal center very easily ok not I mean of course, not neutral form let us say iron 2 plus or iron 3 plus these are these can be extracted or these can be put very easily over here of course, there is a size right there is a cavity. So, anything that does not fit into that cavity will not have strong binding with the porphyrin. So, the size of the iron let us say iron 2 plus versus iron 3 plus will matter whether it can fit in here or not properly ok. High spin and low spin will matter and thereby of course, high spin low spin size will be different right and thereby you can see whether metal can be sitting over there or not ok. Now, this is what I was talking about iron binding you see 6 membered rings 6 membered rings 6 membered ring and 6 membered ring it is holding it very tightly you do not have to memorize this side chain you have to just remember the core structure core structure includes these pinhole ring right. So, these side chain whether this is a double bond or a methyl double bond or methyl methyl or carboxylic acid these are the one you do not have to remember anything ok, but the porphyrin ring itself porphyrin ring means without those substituent that is the simple porphyrin ok you can then substitute. So, you should be very familiar with this this is the imidazole which also binds at the. So, the if porphyrin ring is actually flat like this flat. So, iron is right let us say in the middle of my pump and then imidazole is right over here in the middle. So, below this plane this is a plane below this plane imidazole is bind like that is bound like that ok. So, it is a tetradentate ligand porphyrin is a tetradentate ligand this is the fifth coordination imidazole ok. The sixth coordination is over here which is open or almost let us say something is there very far interacting not too close this is the center where oxygen binds when we are inhaling right oxygen gets in this is the site on top of it on top of the flat porphyrin ring that binds the oxygen and that determines the life. You can now imagine I will come to that if this oxygen binding site this is imidazole this is oxygen binding site if this oxygen binding site is occupied by carbon monoxide or cyanide I will see you again after life ok. So, that is what happens those bindings are going to be stronger right compared to oxygen binding those bindings are very strong. So, oxygen cannot displace them the ligand exchange between oxygen and CO will not happen other or cyanide will not happen other way around will may happen oxygen can go off cyanide can come in that is why it becomes so poisonous. So, deadly carbon monoxide cyan and so on it is also one of your tutorial question ok. Now, I will go into again once again do not get I mean sometime we do get very well there is feedback also right. Do not please give your feedback not at the end of the class at the usually I think at the end of the semester or something you are allowed to evaluate us as a teacher. The way we do also get an opportunity to evaluate your performance by taking exam I think that is kind of our exam it determines a lot of things for us. So, take it seriously for all of all of you or for all of the teachers because it determines of course, you know not too serious it is not life threatening, but it did determines something ok. So, the major one of the major objective or topic of this chapter is myoglobin and hemoglobin how molecular oxygen or oxygen which is in the air how it binds in the blood. In the blood we have porphyrin center the porphyrin center we were discussing over here right. So, this is there in the blood and how oxygen from air binds with this center and what happens during this binding what happens when oxygen gets released ok. So, as you know usually what we have learned or what happens oxygen goes in for our body we are showing just human it goes in in the lungs it gets in and then it gets delivered from all of body parts right. Now, let us say in the muscles it gets stored right it gets stored in muscle. So, how oxygen is going to get transported and then how it is get stored in the muscle that is the one kind of the major things we will be discussing today. So, the storage protein let us say in muscle what we have is myoglobin where that is what we are trying to say iron storage is there some other metal storage is there then oxygen storage is there oxygen transport is there right. So, hemoglobin is the one which transports oxygen myoglobin is a single unit means one porphyrin center is there only one hemoglobin is the one where 4 units are there 4 iron centers are there 4 porphyrins are there ok. Where are they roughly again you do not have to even attempt to memorize any of this structure please do not ok. This is a hem center hem center this is another hem center this is another hem center this is another hem center. Hem means porphyrin ring plus iron that is called hem that porphyrin ring flat plus iron that is the hem. So, we have a hem center in here we have 4 hem centers are in there how they are connected they are connected by this protein backbone ok. It could be let us say I mean hem center is here another hem center is here in between hem center is there another hem center is there in between there is those protein backbone amino acid side chain lots of amino acid side chain putting together of course, is peptide backbone those protein backbone peptide put together is forming protein those protein backbones are together. It is not like all of them has to be covalently linked covalent bond we know some of them are covalent bond some of them are just linked by hydrogen bonding. Let us say this is a protein this is another protein they are linked by hydrogen bonding right. So, hem center hem center they are linked by let us say simply said amino acid amino acid residue which is having let us say your covalent bonding ok. So, all of them are connected if not directly none of them are directly connected like iron center bound with nitrogen that is a direct coordination ok, but there is indirect coordination such as hydrogen bonding and other loose forces which becomes important. So, they are connected they can communicate with each other they can talk it is just like we can communicate they can communicate with each other that is essential ok. Communicate means what happens to this center when something happens to this center this center comes to know. If something happens to this center this center comes to know and it relays that is that relay of information will be learning in form of cooperativity. They cooperate with each other ok that is the cooperativity that thing is missing from myoglobin because they have nothing to no one to communicate they are isolated kind of system one porphyrin center it is not like they are unhappy just they do not want to communicate ok. Now, of course, if you want to compare hemoglobin and myoglobin first thing I said is this is the myoglobin one hemoglobin one having 4 iron center. So, 4 unit versus 1 unit of course, their molecular weight is going to be you know related by 4 times. So, myoglobin sorry hemoglobin is approximately 4 times compared to myoglobin ok. Of course, both of them are having porphyrin both of them are red in color in the oxy form. What is oxy form? Oxy form simply means that oxygen is bound deoxy form means that oxygen is not bound period ok oxy hemoglobin deoxy hemoglobin deoxy hemoglobin oxy myoglobin deoxy myoglobin these terms will be used deoxy means no oxygen is there ok. What is there to remember? I do not see anything to remember it is this what I am saying you remember this nothing to remember this is a porphyrin center iron is there porphyrin you have to remember yes porphyrin you have to remember that is the only thing I am asking you to remember rest of the things you can just read or you know understand as a story I think that is good enough story we do remember I guess we can tell a tale right. Now, so the color as you know the blood color is red it is simple right it is going to be red. Now, deoxy form when if you do not have any oxygen in it it is going to be red purple if you do not want to remember do not remember ok. Now, I did not mean in that way of course, iron is in reduced form you are going to add oxygen. So, iron will be in reduced form what will not be discussing today is the redox chemistry what happens to the iron is it going to iron 3 plus yes it goes, but that information we will not be discussing for the class. What we will discuss is initially what happens initially redox chemistry does not happen redox chemistry happen right after it we do not need to know this. We will discuss that oxygen comes and binds with iron center that is it that is the syllabus right after that binding oxygen actually gets reduced iron gets oxidized that is not part of the syllabus do not even write in the exam ok. I will be discussing whatever part in the syllabus ok this is the same thing again 1, 2, 3, 4 iron center nothing else ok 1, 2, 3, 4 iron center we are discussing myoglobin no hemoglobin see you understand by now ok. Now, see something like if you put a lot of oxygen in a lot of oxygen if or other way around if lot of oxygen is not there you will be suffocating right you feel breathless that means oxygen is not there breathless situation is less oxygen right that situation and then if you compare to breathless situation if you want to pressurize oxygen too much oxygen is there that oxygen pressure you can vary and then you can measure how oxygen is uptake uptake means how it is taking how porphyrin center in hemoglobin and myoglobin is taking up oxygen with respect to oxygen pressure. You pressurize oxygen say gas cylinder let us say you can pressurize gas cylinder you can have not so pressurize gas cylinder with respect to partial pressure of oxygen as you increasing the pressure of oxygen and you see how oxygen pickup is happening at the myoglobin and hemoglobin. What you do this is the curve for hemoglobin this is the curve for myoglobin and this is the curve for hemoglobin at pH 7.6 hemoglobin pH 6.8 is red curve lot of things are red this one sigmoidal curve is at pH 6.8 hemoglobin pH 6.8 hemoglobin 7.6 is the blue curve for hemoglobin and then myoglobin that is the curve. Now, so what we are seeing as you increase the partial pressure of oxygen uptake goes up percentage saturation means you can keep on bind up iron center you have more oxygen pressure it will go up sigmoidal curve you are saying it will go up and after certain point it will saturate it will not take up any more oxygen that means that is the maximum that is that is almost like the equilibrium is reached after that no more oxygen pickup will happen. So, you pressurize you know you take pure oxygen we have 16 percent oxygen pure oxygen you can take or pressurized oxygen you can take. So, therefore, what we have measured here is oxygen pressure is going up how saturation level is going how our hemoglobin and myoglobin is up taking. Now, in lungs what happens in lungs we have this is the partial pressure we have this is the partial pressure. Now, it is almost the it is very, very high oxygen amount we can take it up at the at the at the low pressure if you see at the low pressure you see the myoglobin is having higher affinity that is in the muscles where low pressure of oxygen is there oxygen is going to transfer transfer from hemoglobin to myoglobin in muscles because firstly because at a low pressure of or you know myoglobin has a higher affinity or higher affinity for oxygen compared to hemoglobin. And you know myoglobin also has pH something like 6.8 at a lower pH. So, at a lower pH this is the pH curve with respect to pH hemoglobin oxygen uptake is shown in here at higher pH oxygen uptake is shown in there since in in muscles pH is pH is low then what happens from hemoglobin. So, hemoglobin is over here that much oxygen it can pick up myoglobin right over there is having high affinity for oxygen. Therefore, hemoglobin to myoglobin transfer will happen that is how the transfer mainly happens both at a lower pressure hemoglobin has higher binding and the pH for pH 6.8 this is pH 6.8 curve you see hemoglobin binding is over here myoglobin binding is over there. And therefore, hemoglobin to myoglobin oxygen transfer occurs it is very beautifully written in this here we you can read it is a Stiver Atkins book which is your textbook you can read in there in detail. Now let us go on. So, what is what is essential for oxygen binding irrespective of myoglobin and hemoglobin what is essential? The thing that is most essential is we have to prevent reduction of oxygen. Oxygen can get reduced by 2 electron that is oxygen to peroxo formation can happen iron center can give 1 electron another electron the second electron can also come from either that iron center or from another iron center. Since you are seeing that 2 iron centers are really far apart from each other although they communicate, but the electron transfer will not be that very fast. So, therefore, what happens is oxygen to peroxo formation does not happen that would have been a irreversible thing. So, what all happens in our body is a reversible oxygen binding oxygen does not get reduced completely to peroxide hydrogen peroxide let us say that that reduce reduction does not happen fully. Oxygen to peroxide level reduction is prevented by default by design because the 2 electrons are required oxygen to peroxo that 2 electron reduction cannot be possible because this that reducing equivalent means that you need something to give electron right that is how you will reduce. Reducing equivalent is not available readily there is nothing to reduce very readily right over there that is one aspect. Another aspect is you of course, you have to prevent the oxygen from going out it has to bind those binding even though it is not that very strong what happens over here is let us say it binds over here for example, oxygen is over here this oxygen by will have after binding oxygen will have hydrogen bonding some sort of. So, let us say this is my porphyrin this is my iron center oxygen binds this lone pair right and this is the axial position top the below is again your histidine or histidine unit right this is your porphyrin. Now, this oxygen you will see there is a hydrogen bonding from another histidine. So, this hydrogen bonding also gives the stability to the structure overall it is a bent oxygen geometry and it prevents it prevents the reduction oxygen to peroxide this is peroxide reduction that is what happens in our body when you try to synthesize porphyrin which I have done let us say actually I have done if you take porphyrin and iron synthetically prepared. So, that is why synthetic blood is very difficult to prepare why because the moment you have porphyrin it reacts with oxygen if you have porphyrin synthetically made it reacts with oxygen overall what you get is here iron 3 see what happens here is porphyrin is too far oxygen can come over here it is it cannot bridge between two porphyrin, but in synthetic system two porphyrin can come very close because there is no restriction there is your globular protein that is again another tutorial question which is preventing the dimerization and also providing the stability for the monomeric structure in synthetic system what is happening is or what can happen invariably 99.99 percent cases it happens that porphyrin P means porphyrin oxygen reacts and overall you do not have to remember all these again this one iron 3 iron 3 each iron is giving one electron therefore, iron 2 plus going to iron 3 plus oxygen is getting reduced by 2 unit oxygen 2 peroxo is forming this reaction is killing the porphyrin or the oxygen binding this is not too much of a reversible reaction. So, in our body what happens is it is a reversible oxygen binding oxygen can bind and pop up it can go it can be delivered to myoglobin hemoglobin takes up transport and deliver in synthetic system it is very very rare to deliver how you can deliver that can be done in synthetic system it requires if you put some steric bulk steric bulk means let us say you have you put an umbrella you put an umbrella on top of porphyrin of course, that will take a lot of synthetic effort to put an umbrella on porphyrin if you put an umbrella another umbrella will not be able to come very close and affect. So, another umbrella even if it comes it will come over here, but iron site is here iron site is here. So, they too cannot communicate. So, these are called steric effect you put bulk and thereby you prevent, but that is very very expensive I mean it is a lot of synthetic effort, but by default nature has it in our body we do have that by default we do have what we do have these protein backbone protein backbone prevent these two porphyrin to come close and thereby we do not have any problem to deal with right.


Hi everyone, Sean with jaspyscasebreaks.com here doing 2020 Panini Absolute Football six box inner case break pick your team number four Pretty straightforward all card ship No random buyers. No nothing. No fillers in this one everything up straight up. So here is the full list for us and Here's our case Marked pick your team four since this is the second inner case from a master box Pick your team three was for the first part of this And here is our list last spot mojo Nick Galvin in the Detroit Lions Good luck. I don't know What was pulled in 15 three that was a little bit earlier today, I think with Joe But I do know we have not seen a boom yet So obviously that's One of the things we're hoping to see right here There we go. There is our six boxes So I don't think we've hit a kaboom at all today from what everybody was saying earlier Maybe pick your team four is the one What do we think? They do max all card ship says on the break itself I'm not sure Pat is agreeing that all card ship or if he's saying yes, we're gonna see a kaboom But either way I agree with him. He's right Good luck everyone Donovan people's Jones to 199 For the Cleveland Browns and Serenity IG did neither We got a redemption any guesses AJ Green 36 out of 75 For the Bengals and Joshua Oh, no, you're good Max. It's all good. Trust me an easy answer like a yes on that. All good Kenny Moore Relic or sorry auto 39 out of 99 for the Colts and Mike Grosinski Deandre swift relic 5 out of 199 for the Lions and Nick Galvin and Levy on Bell 60 out of 100 For the Jets and David chant Max is saying Cole Comet or Edward to layer Pat's saying a one-of-one of something on the redemption Willis McGay. He won the last time we saw his name 32 out of 99 Denver Broncos Eric Ainge Dual Relic team tandem DD Westbrook DJ shark Jr. 177 of 199 Going to the Jaguars and Robert Garicki and Travis Kelsey star gazing 31 out of 100 For the Chiefs and Josh right Redemption, so it's got to be the RPA right? rookie premiere materials autos spectrum anybody know what spectrum is out of Or have that up Card number 216 Starts with a C H a s e Y O U N G chase young Going to the Washington football team and Mark I'm not sure what the spectrum parallel is numbered out of but Maybe we'll look that up for you a little bit Pat. It's out of 99 Pat So Washington football team it says rookie premiere materials autos Spectrum so I think spectrum is the parallel Pat I think the premiere materials is like the is the base version to 99 It is out of 99 Red spectrum It doesn't have a color interesting Why why would it have But this just says spectrum. It doesn't say any color I'm very confused by that Cam Acres rookie auto 20 out of 35 Going to the Rams and Richard for autos Chase young Ryan Kerrigan dual relic 162 out of 199 for the Washington football team and Mark mature and Kenny Galladay 18 out of 75 for the Lions and Nick Galvin last spot mojo. Okay, Pat. Make sense Trayvon digs 47 out of 199 going to the Cowboys and Matt meddling Cam Acres triple relic auto 228 out of 399 for the Rams and Richard for autos and Marlon Davidson 96 out of 100 for the Falcons and Matt meddling Jalen Johnson rookie auto 111 out of 149 for the Bears and Max Lesky Erlasky dual relic delvin cook Kirk Cousins 92 out of 199 for the Vikings and Comer Conrad bots and Thurman Thomas 65 out of 100 going to the Bills and Tracy Murray Tristan, there's still a bunch of stuff we can do Check the site. There's a At least three more breaks that have less than nine or nine spots or less We still got 35 people in here too guys, so Trust me nine spots on a break. It's nothing when you got 35 people That's one in every four people buying a spot So even those breaks that have 17 spots left Very doable guys very very doable. So figure out what you want to do Buy a spot and then let everybody else in the chat know that you bought a spot So they can follow suit Let's start a little push Rookie Auto 2 out of 50 Lynn Bowden, Jr. For the Raiders and Robert Runkel dual relic Isaac Bruce Steven Jackson 16 out of 99 for the Rams and Richard Farrott us Jordan Love introductions red 22 out of 100 For the Green Bay Packers and Mike AJ Dylan rookie to 199 For the Packers and Mike Krasinski triple relic auto rookie 61 out of 399 for Darrington Evans and the Tennessee Titans Zach And say Quan Barkley red to 100 for the Giants and Juan Escobby Deontay Johnson dual relic in auto tools of the trade 40 out of 99 For the Pitchfork Steelers and Michael Galucci Drew lock relic 68 out of 99 absolute heroes for the Denver Broncos and Eric Ainge and Alvin Kamara blue four out of 50 Going to the Saints and Brian Croft Joshua Kelly rookie auto 72 out of 75 for the Chargers Patrick Cologne Paris Campbell six out of 99 dual relic for the Colts and Mike Krasinski and 29 out of 100 Isaac Bruce for the Rams and Richard Farrott us very nice triple relic drew lock one out of 25 Triple relic and auto for the Denver Broncos Eric Ainge CD lamb 27 out of 199 single relic for the Dallas Cowboys and Matt Medlin and Melvin Gordon 79 out of 100 for the Broncos and Eric Ainge Daryl Taylor rookie to 199 For the Seahawks and Juan Escobby, Pena triple relic auto Lynn Bowden, Jr. 161 of 399 for the Raiders and Robert Runkle and Derek Brown rookie blue to 50 for the Carolina Panthers and Matt Medlin Willie Gay, Jr. Rookie auto red 54 out of 60 for the Kansas City Chiefs and Josh Reich Dual relic team tandem 10 out of 49 some nice patches there for the Bangles and Joshua I'd let's Tyler Boyd and Joe mixed in Brandon I you rookie to 25 For the 49ers Raymond Day Jesus Derek Brown to 199 for the Panthers and Matt Medlin and very nice Triple relic auto to 99 JK Dobbins That's going to the Baltimore Ravens and Aaron Billingsley and Jake Lutton 59 out of 75 for the Jaguars and Robert Ricky Christian Fulton auto 55 out of 149 for the Titans and Zach Erb Cam Acres relic 60 out of 199 for the Rams go into Richard Farradis and 14 out of 75 Barry Sanders and the Detroit Lions for Nick Galvin It's an acres inner max Cool last box guys Good luck everyone Let's see something nice. That's what I'm hoping for max and it was something great, right? Derek Brown rookie auto 55 out of 75 for the Carolina Panthers and Matt Medlin Paris Campbell triple relic 66 out of 99 for the Colts and Mike Graczynski and Dalvin Cook red zone three out of 25 Going to the Vikings and Conrad bots Henry rugs to 199 For the Raiders and Robert Runkle Antonio Gandhi Golden rookie triple relic auto 375 out of 399 For the Washington football team mark measure Joe borough blue 19 out of 50 going to the Bengals and Joshua Idlitz and last inner Good luck. Let's see something nice Anthony Miller dual relic auto 30 out of 99 For the Chicago Bears and Max Lasky There you go max dual relic 36 out of 50 Ezekiel Elliott Dallas cool cowboys Matt Medlin and AJ F. Vanessa 83 out of 100 for the Buffalo Bills and Tracy Murray There you go guys that was our break That was 2020 Panini absolute football six box inner case break pick your team number four Pick your teams five and six in the store now both from a fresh case So let's see Jasper's case breaks calm. I'm Sean. Thank you guys very much, and we'll see you next time


Hey, did you guys have an invite law? Hold on, I gotta get Drippie out? Yeah! Oh, we're getting Drippie out! Okay, okay! Where the store is that? Oh my god. Yeah, I don't know if you guys knew this, but the more money you spend at swags, the higher your hot zones go. I was walking behind the agent, I seen them walking to the store, and I'm like, wait, I can't even buy nothing. Hey, wait, wait, we'll leave. Play the sad music. Guys, look at Nick's clip. Look, he's so poor. Please guys, help. Help now. Go to his channel and donate. Click I'm gonna need you to rate my drip against Lowe's drip. All right. There's no bias. You can't like there's nobody paid you, right? No, have you paid him? Why are you saying it like that? What the hell's going on? Oh my god? Why are do rags 15,000? Oh, are these designer do rags? You mean to tell me it costs more to buy us a do rag in NBA 2k then it doesn't realize Holy yo look at me. I'm a little like if I came out of a cold range over you just be like Like a wide-body slam Everybody's great blobs. That's exactly what you look like. You just like riffraff. Yeah Yes, look at the intricacies. No, no, no, no, please. What you need me looking at is your cash?  It's not very varied.  That's not a cup. That's the real deal down there You both look insane, but he looks a little bit like less insane, right? Maybe you don't screw if we go and based on insanity. He got like a cool 8.4 But no, we're going on what no, that's not it's worth. Oh, is this the record? Yeah, I'm trying to get that 100% win percentage so I could tell all the YouTube Hey, that's all the team was good with y'all Oh There's no way there's just no way I refuse to believe it That's early my bad run it back. That was a mistake Where you going it is work bro, so why don't you stop getting off my Oh Man oh man, oh man, oh man. Oh man. Oh man. Oh man. Oh man. Oh man. Oh man. Oh man. Oh man. Oh Shooting is too easy Mike. Why don't you change that bit Mike? We're gonna have to leave this park due to the fact that we are cloutless. Yo agent. No, bro.  Appreciate you turn the music up Yes, I'm being a little fanboy man Yo, click what bad did you get where you thought that was like a I got this green up green up Yeah, you guys from New York, you're from the Bronx, right? Oh I got a question for you. Did he people sound familiar? You know who that is I have no idea. I was hoping you knew Hilarious What That's clean what I just did right there is clean and let's end it like that right there I got whole clip Let's leave guys, I don't want to get those those guys like another chance feel me I want them to like wake up tomorrow knowing that like There's no way they could ever play us again, and they lost the first time I'm gonna hear you span the circle to that's a People just come in here to take a screenshot so they could pretend like did I just go through this door? Good Where am I right now? Oh my god. This is what death must look like I'm just in a black abyss right now behind the map All right Well, let me show you guys a tour of the ante up if you come over here. It's a nice little In my screen guys, I'm behind the map. I've done it. All right. Well, this is there you go You've achieved good content, so you don't need to worry about nothing You I'm just walking through the walls guys. This is incredible. Can I walk on the courts? Oh my god. I Can what the they're letting me walk on the course. Is that Iggy? Oh, I know these guys I'm gonna play defense right here D up D up Mike Wang is probably like man agent You just been so like great for the community stuff like that I'm gonna give you this new feature where you could disrupt everybody's experience for your own enjoyment This is the worst experience. Why does anybody come on the ones? This is garbage Hey, how far do you guys think I can get away from the ante up? But what do you want me to give you like a measurement?  We'll just say 8,000 The answer is forever by the way guys you can do this forever. I'm I've been going for a while. Goodbye world It's what 2k team must look like.  She has to be at zero So green up man. It's so automatic. Thanks Mike Wang. Could you buff it more? I want everyone to do that all the time. Are we out here with it? You don't shoot those. What is wrong with this guy?   Hey, can we talk about the guy who's designed the UI for the phone? Doesn't he need to be fired like I'm just trying to think to myself.  There's just no way Shot good board Oh This one's it Hit me in the dome. He's at off the easy Get him off the court sweep him up man mop him up get it. What's the thing called a jumboni? I'm not Canadian. Hey, if y'all enjoyed the video man Have no where to make sure to drop a like subscribe to the channel Lowe's link and Nick's link in the description down below Make sure go check him out. We'll catch you guys in the next one, man


Driven in from the right-hand side by Tealum. It's a great looking ball, headed away by the cherries at the near post. Mevin' my peak. Driven back into a cluster of players, and then in the back of the net from Dhaka. It was pinging around everywhere. The cherries couldn't get it clear. And Patsen Dhaka, the Zambian International, spot on a six-points in the six-yard box and planted it into the bottom right-hand corner down the right-hand side. Salanki now might try and change that after a mistake by Faze. Salanki into the penalty here, onto his left foot. Blocked away, and it's gone in there! Now onto bed. Salanki did the hard work. Creshing the mistake, and as of all, spun up in the penalty area. Peel-billing with a crunching left foot finish. Third goal of the season for him. And the cherries with the corner of the game left are back on terms with their first home goal since the opening day of the season. One-one. Lerma plays it to Christy in the centre-circle. Fredericks, if he has got any gas left in his tank, is now trying to race on around the outside and support Ryan Christy. Here's Fredericks, level of the edge of the box. Early ball in towards Salanki. And ball! Was there a hand in there? Referee says no. Billing edge of the box, chipped in towards the back post. Salanki does it down. Here's Christy! Two-one! Couple of opportunities at the other end. This time, poached the goal from close range. And Bournemouth from being behind. Just three or four minutes later, by themselves, two-one in front. Well, absolutely fantastic. And I wonder if Christy was going to be one of the nominations to come off. But he stayed on, he stuck to the task. He's had a couple of chances all game. But that one, I think he just flustered it into the ground and passed the keeper.


Good afternoon everybody, thanks for your your patience in grabbing your box lunches and bringing them in so that we can take advantage of Commissioner Stein's very short time in Ann Arbor.  We're glad to have her here. Dick Berner I know joins me in welcoming Commissioner Stein to this conference. Dick and I spent a good bit of time tag-teaming on Commissioner Stein to get her here so we're thrilled that it was able to to work. Karestine was appointed by President Barack Obama to the U.S. Securities and Exchange Commission. It was sworn in on August 9th of 2013. Anybody who has paid any attention to the SEC since then knows that one of Commissioner Stein's singular focus for her time on the Commission has been promoting and encouraging and demanding accountability in the financial sector. Miss Stein joined the Commission after serving as legal counsel and senior policy advisor for securities and banking matters to Senator Jack Reed. From 2009 to 2013 she was staff director of the Securities, Insurance and Investment Subcommittee of the Senate Banking Committee and during that time Stein played a really central role in drafting and negotiating significant provisions of the Dodd-Frank Act. I'll just say Commissioner Stein's role on the derivatives title was really quite central and it also was resulted in one of the rare bipartisan moments during the legislative process and also one of the funniest but I will leave that story for another day. And for our purposes today Commissioner Stein was also really quite central I would say indispensable in the creation of the Office of Financial Research. There's no no staffer on Capitol Hill who did more to draft, build, support for, create and and enliven, enrich, empower the Office of Financial Research so all of us here today I think are very much in her debt. Prior to that Commissioner Stein spent quite a long time in roles on the Senate Banking Committee with jurisdiction over the banking agencies and the SEC. She worked for quite a while in as legal counsel and senior policy advisor to Senator Reed as majority and minority staff director on the Banking Subcommittee on Housing where she played an especially important role in calling attention to the foreclosure crisis early on in that process and in working on solutions across the aisle to try and address it. Before going to Capitol Hill Commissioner Stein was an associate at the law firm of Wilmer Cutler and Pickering. She was a Scadden Public Interest Fellow, an Advocacy Fellow at Georgetown University Law Center, an assistant professor down the street at the University of Dayton School of Law. Commissioner Stein received her BA from Yale College and her JD from Yale Law School. We got our start working together on housing discrimination in Connecticut a gazillion years ago and so I am just thrilled and honored and humbled to have a chance to introduce Commissioner Stein to you today. Please join me in welcoming her. I have a low type presentation here. Got it? Okay. Low of stature and low tech. It's an absolute pleasure to be here and I want to thank Mike for the kind introduction. We actually wrote a paper together in law school when he I was a third year and he was a second year on housing discrimination so sort of amazing where we are now. I also want to thank the University of Michigan and the Office of Financial Research which is near and dear to my heart for organizing this important conference. I'm pleased to be with you today. I actually think it's a really important time to be discussing some of the forces that are shaping financial markets and regulation. I wanted to start my remarks with a quote. What hath God wrought? That message was sent from Washington to Baltimore in 1844 and it signaled the arrival of the telegraph. Originally an exclamation but sometimes it's written as a question. It captures I think both the wonder and the uncertainty that new technologies can inspire. The telegraph proved to be a transformative technology. Information was no longer limited by the speed of a horse but could spread almost instantaneously. Farmers in one part of the country could learn about prices and distant markets and an expanding country would soon communicate from one coast to another. The transformation of knowledge that began with the telegraph has continued for more than a century. Over the last several decades in particular data and our capacity to store and process it has grown at an astounding rate. These technologies have touched nearly every endeavor including science, health care and of course finance. Even the Bard has felt the effect thanks to text analysis. Shakespeare will now have to share credit for several plays with Christopher Marlow. Railroads and telegraphs and automobiles and telephones fundamentally reshaped society. By connecting distant locations with greater speed they created new avenues for spreading goods and knowledge and the result was increased prosperity, convenience and efficiency. I think the current revolution in data similarly allows us to make novel connections. However instead of connecting physical locations we're connecting data points to uncover new insights and the result may be another leap forward in how knowledge develops and spreads but you know all of this. You are the data geeks. So today I actually wanted to drill down a little and talk about how these developments are affecting the financial markets and the Securities and Exchange Commission in particular. Specifically I wanted to discuss four broad themes. I thought I could lecture right? One, two, three, four. One, the new opportunity that data provides. Two, why the Commission must keep up with data's growing role in the markets. Three, some of the challenges to keeping up and four, some ideas for overcoming these challenges. It won't surprise you I'm going to focus on my perspective as a commissioner at the Securities and Exchange Commission but these themes likely have relevance to other financial regulators as well. Ultimately regulators are being disrupted by new technology and it is important to focus on what we should be doing about it. However before going further let me say that my remarks today and the views I express are my own and they do not necessarily reflect those of the Commission, the views of my fellow commissioners or the staff of the Commission. You'll see you'll hear that disclaimer whenever you have a Securities and Exchange Commissioner speaking to you. Let's start out with the new opportunity and information particularly fast and reliable information has always been central to the financial markets. For example shortly after the development of the telegraph, brokers began leasing their own telegraph lines so they could receive pricing information faster. The securities laws in large part can be understood as a set of rules about information. What information is useful for public dissemination? How should we ensure that it's accurate and it's reliable? Does fairness require everyone to have the information at the same time? How do you protect non-public information? What information is necessary for price discovery? The federal securities laws speak to all of these questions. I think in this sense big data is actually a continuation of an old theme. In another sense the developments in the past 10 to 15 years represent a totally new phenomenon in the same way that satellite imaging is completely different from surveying a landscape from the top of the hill. At that scale patterns become evident that would have been impossible to piece together by considering one plot at a time. This means that both market participants and regulators have new opportunities for developing knowledge. Moreover this is a qualitatively different kind of knowledge encompassing entire data sets in one pass rather than a slowly accumulating insight from individual experience. Market participants have already seized this opportunity. They are using a wide range of data sources to call signals about possible market movements. Among these data sources is actually information that the Securities and Exchange Commission makes available. The demand for which is actually enormous. In the last year our website received over 7 billion page views. That's more than some major media sites. We also delivered more than two petabytes of data to visitors. I recall not long ago when a gigabyte seemed like a lot of data. The commission itself is also beginning to realize some of the potential of new data tools. In a recent case we obtained a settlement against a large broker dealer for its failure to adequately train its representatives when they were selling certain complex debt instruments. What made the case unique was that instead of traditional investigative techniques it was actually built on custom analytics. SEC industry specialist working with a team of tech experts developed tools to sift millions of trading records. Using this technique they were able to identify over 8,000 retail customers for whom the investment in the complex debt instruments was inappropriate. A case like this may not have been possible in the past. I believe, however, that enforcement is not the most important potential use of data for the commission. By the time we start building a case the harm has already been done. I am much more interested in establishing rules of the road that can help prevent crashes than in waiting to deal with the aftermath. Better investor protection is avoiding fraud and misconduct in the first place. So the key question is how can we design policies and monitoring systems that support healthy market function and aid and compliance on the front end? Improved data tools have the potential to be uniquely powerful in this way. They can allow us to make better more tailored policy choices that focus on actual risks to investors and the market. This approach will never replace humans or human judgment, but it can improve the markets and help us make smart use of what are always going to be limited resources. Data and technology, they present tremendous opportunities and benefits. But as you know they've also opened the door to new and exceedingly complicated risks. Data is distributed across a range of electronic platforms, complicating the task of monitoring and examining market participants. Moreover, the variety of data has increased dramatically. This includes highly structured derivative transactions that are reported in competing taxonomies such as FYX and FPML, as well as unstructured information like social media posts and narrative reports. As a result, in addition to being an exciting opportunity, the spread of data and data tools also requires the commission to make changes to keep up. A number of recent developments highlight this need. As you know, today's electronic trading environment has significantly changed the capital markets. Algorithms called matching engines match electronic limit orders with electronic market orders. High-speed trading dominates representing over 55% of United States equity markets. And liquidity provision has largely shifted from traditional market makers to computerized systems that trade in fractions of a second across different trading venues and securities. When the flash crash happened on May 6, 2010, equity markets suddenly plunged and then rebounded. In contrast to the incredible speed of this disruption, it was months before the SEC and the CFTC were able to gather the necessary information, turn through the data and produce an analysis of the trading on that one day. I was actually working in the Senate at the time, and I remembered the uncertainty as we waited to understand whether the disruption signaled vulnerability and whether it could happen again. Since then, the financial markets have experienced other temporary disruptions and many flash crashes. These events implicate data both in their causes and in the ability of regulators to understand and respond. I think they also highlight the risk of driving a carriage in the age of Tesla. By the time you're pulling out of the stable, everyone else's autopilot has passed you by. Since the flash crash, the commission has made some steps towards developing enhanced monitoring capabilities. The SEC has, for instance, created what we call the Market Information Data Analytics System. It's fondly known as MIDUS. MIDUS combines information from the consolidated tape and separate proprietary feeds to create a more complete picture of equity market activity. We need to go further, though. The SEC will soon consider a plan to create the largest data repository of securities trading activity that has ever existed. This is widely known as the Consolidated Audit Trail, or the CAT. This unprecedented data effort will help us finally move at highway speeds. The SEC's statutory mission involves three core objectives, which protect investors to maintain fair and orderly markets and to facilitate capital formation. Our mission is not changing in the digital age, but our tools for carrying out that mission must. We simply can't be effective or efficient without a more strategic approach to our mission, to financial markets and data. So what are the challenges in keeping up? I'll go back to recognizing that the growth in data, it represents both an opportunity and a necessity. How can the SEC best position ourselves to respond? There are a number of challenges, and I'm not going to address all of these exhaustively, but I want to talk about several that are critical. I think the first condition to success is acquiring the right data. We need data that's relevant, timely, and high quality. So this is not simply about increasing the volume of data. There's already a lot of volume out there. This requires being smart about the data that we collect. When you want an apple, chopping up the tree usually isn't the most efficient way to get it. So we must instead, I think, carefully consider our possible sources, actual data gaps, and reporting methods. Where we, as a commission mandate reporting, how can we ensure that our requirements keep pace with a quickly evolving market? Can we design reporting requirements so that our resources are spent on analysis instead of cleaning up data sets? These are challenging, but important questions, I think that require a forward-looking approach. Another condition to success is ensuring that computers can quickly and reliably interpret the data. Structured data can be an important part of this. SEC reporting in the last few years has begun to embrace better practices for structured data. For instance, we recently adopted reporting requirements for mutual funds and ETFs that will require the use of XML. Our existing form PF, on which hedge fund managers report, also uses XML. Where structured data is not available or reliable, we should continue to explore techniques that allow better parsing of unstructured data. We should also, and anyone who's heard me talk before knows how much I love LEI, we should also embrace identifiers like the legal entity identifier. I remember vividly the uncertainty following Lehman's collapse. Regulators and counterparties were left to sort through the rubble, trying to piece together the consequences. It was a problem of modern complexity, but without an equivalent modern solution. LEI helped solve that problem by providing a uniform and reliable way to identify counterparties. This should free regulators and others, right, to focus on the financial risks instead of the data issues. The new mutual fund reporting forms also include an important new requirement for funds to obtain an LEI. Growing use of XML and LEI are important steps. However, we can still do more to ensure that we have data that is ready for efficient analysis. Another significant challenge is limited resources. Using data effectively depends both on having people with specialized skills and having sophisticated systems. In addition to our excellent staff of lawyers and accountants, we need more professionals with the right technical skills. Our systems and software also need to keep up with the speed and the volume of today's markets. Our main information reporting system, Edgar, was a huge leap forward 20 years ago, but it is ancient in tech years. With a limited budget and an ever evolving market, we may never drive the latest model, but we must, however, find a way to keep pace. We also need to remain vigilant about protecting proprietary information. Cyber security is a constantly evolving risk. The latest large scale attacks on the news directed at certain internet utilities may have been launched using webcams. As a result, we have to be creative and dynamic in developing responses. I think we also need to ask how new data tools can improve our ability to deliver decision useful information to investors. I have spoken before on the need to create a digital disclosure task force to help us reimagine how the commission acquires and provides data to investors and market participants. I believe that we have an opportunity to reduce the burden on companies and those who are submitting data to us, while at the same time providing better disclosure to investors. I don't say this in my speeches, but if Amazon can pick up and you can look at three different toasters at one time and compare them, can you imagine if you could do that with three companies that are selling similar types of products and actually decide what you want to invest in? Thinking about companies submitting data to us and we use it to populate interactions with investors on our website. We're very tech centric at the commission that goes back to having lots of lawyers and not as folk, not data centric. So again, we're being disrupted. And it's hard for people to shift gears. Another condition to success is that we never lose sight of the human element. No matter how powerful the processor at the end of the day, humans develop the assumptions and the metrics. They design the analyses, they program the algorithms, and they interpret the results. I think for me, the housing crisis forcefully brought this home. As models were built from assumptions that were chosen by humans, and were fallible, that no, you know, three housing markets in the entire country could go down at the same time, you know, you had inputs that were being put into algorithms that ultimately were fallible. Human biases are as much a part of digital databases and computer analysis as they are of any other source of knowledge. Accordingly, we must approach them with the same judgment and caution and safeguards. The final challenge I want to touch on is one of leadership. Success here depends on drawing together an array of expertise. And always you're making decisions with limited resources and within limited budgets. This cannot be done without vision. The vision needs to be accompanied by a detailed roadmap and effective management. Without these, we risk missing the opportunity that data can provide. So meeting the challenge. How can the SEC meet the challenges of developing and using data effectively? In recent years, we've made some progress. An important part of this has been the growth of our Division of Economic Research and Analysis, or DRRA, as well as several other groups that include analysts, quants and economists. We even have a physicist. These include talented folks in the risk and examinations office, in investment management, the risk analysis examination team. We have acronyms for all of these, the RAE, so I don't usually say all of them. In our exams office and the Center for Risk and Quantitative Analytics in our Enforcement Division. These groups have advanced our ability to handle data with rigor. They've also played an important role in everything from identifying risk to informing policy and conducting investigations. In addition, as I mentioned previously, we've made some progress on the systems front with the development of Midas and hopefully in the near future, the advancement of CAT. But more needs to be done and it needs to be smart. An important part of defining our vision should be the creation of an Office of Data Strategy. For some time, I've asked that the SEC develop an executive team responsible for creating and overseeing such an office. The office would be responsible for coordinating the creation of a data strategy, addressing how we collect, manage, use and provide data. I just think it's like project management. This is a critical step from turning our sort of ad hoc growth in this area as data users into a more deliberate plan. The office also could lend its expertise to and we coordinate with our policy exam and enforcement offices. Having a data strategy and a team dedicated to it is especially important in the light of our limited resources. So just as the telegraph ushered in a new information era, the spread of data and data tools is changing how information is used and shared. The promise of this is tremendous. And if the commission can successfully harness the new technology, I think investor protection, financial stability and the markets will all benefit. Thank you again for inviting me to talk with you on this beautiful day in Ann Arbor. You're engaged in a fascinating and I think very productive conversation and I look forward to hearing about some of your ideas in this area. Thank you.


Hello everyone and welcome to the next edition of the BioExcel webinar series. My name is Rossin Apostolov and I will be today's host. Today we will have a presentation of a new open source tool, CWXAC, which allows you to run common workflow language workflows on LSF and it will be presented by Ching Da Wang. Today we have as a co-host Michael Kruso, which many of you know as the co-founder and the leader of the CWL project. First to let you know that this webinar is being recorded and we will upload the recording of this webinar to the BioExcel YouTube video channel and you can share it later with your colleagues or friends if they have not been able to attend today's event. Just a few words about BioExcel. For those of you who are not familiar with our center, BioExcel is a center of excellence for computational biomolecular research. We are over two years old now and we work in three main directions. One is to improve the performance, efficiency and scalability of several important applications for molecular dynamic simulations such as GROMACS for docking an integrative modeling HADOC and QMMM simulations, CPMD. Another main aspect of our work and this is also the topic of today's webinar is our work on efficient workflow environments with associated data integration. And there we work with a number of platforms and CWL is one of the projects that we have been working with and supporting. We also work a lot on training and providing consultancy to academia and also industry examples such as pharma companies. We have a number of activities centered around several interest groups. One of the interest groups that might be of interest to you is the workflows IG. You can find more information about them on our website and you can get in touch with us, various platforms in the forums that we have. We have a chat channel and a video channel. You have recordings of our previous webinars and events. At the end of today's webinar, we will have questions and answer session where each of you can ask whatever questions you have in mind to change them. While the presentation is going, you can use the questions tab on the GoToWebinar control panel. And after the presentation, I will let each of you speak directly to CINGDA and ask your question. If you have problems with the audio, if you don't have a working microphone, I will read the question on your behalf. If you have any other follow-up questions or points that you would like to discuss, you can always go to our forums at ask.bioxcel.io where we will further follow-up. And with that is the small introduction that I gave. Now I would let Michael Kruzo take over with hosting and presenting CINGDA to the audience. Hi, Michael, can you hear us? Yeah, I can hear you. Hi, everybody. I'm really excited to be introducing a new vendor into the CWL ecosystem today. CINGDA Long, as we see here, has a lot of experience in software development and grid cluster in cloud. And so we saw their blood post from the LSF group about their experiences running CWL using toil last summer. I'm quite intrigued to read at the end that they were developing their own implementation directly on LSF. So in this sort of deeper integration between a workflow language and a specific scheduler, hopefully yielding special optimizations or just a better experience, has always been something we've been anticipating and hopeful for as a project. Looking at the number of attendees, it looks like the Rails is quite interested. So I'll stop talking and let CINGDA continue with this presentation. Okay. Thank you, Rosen and Michael, for your introduction. I'm very happy to have this opportunity to present to BIOXCEL users today. My topic is, as Michael mentioned, CWL exec, a new open source tool to run CWL workflows in LSF. Can everyone hear me properly? Yeah, you sound great. Okay, thanks. So before I start, maybe I can say a few more words about myself. So I'm the principal architect at IBM working on IBM Spectrum LSF family of products. I have worked on a product called LSF Process Manager for many years. It is an enterprise workflow software running on top of LSF. And we have a lot of customers in the life science vertical. So we know a lot of use cases and requirements from life science. Hopefully this helps us to develop CWL except better for life science users. Okay, so because I'm going to make many forward looking statements on our project and loader map. So I'm required to show this disclaimer. With that out of the way, here's a gender for today's presentation. First, I'm going to introduce IBM Spectrum LSF and LSF Suite. Next, I will briefly go over common workflow language and its implementation. And then I will cover CWL exact in detail and then talk a little bit about what is ahead of our loader map. So I know there are LSF users in today's audience, but many of you may not know or not that familiar with LSF. IBM Spectrum LSF is a batch scheduler for the HPC environment. So it is a workload management software that helps you to optimize your computing resources. Whether you have a small or large cluster. And it provides efficient scheduling and also sharing policies for maximum job throughput. LSF also has a few add-on products that helps you to improve the user experience and provide additional functionalities. For example, IBM Spectrum LSF application center is a web-based user portal for users to submit and monitor their workload. And the process manager automates workflows that runs on top of LSF. We also have other products to monitor your cluster usage and generate reports. So LSF together with these add-on products, we package them into IBM Spectrum LSF Suite. I should mention the LSF Suite for HPC is available for free under the IBM Academic Initiative. So next I will briefly go over common workflow language. As Rosen has said, Michael Kruso is the founder and the leader for the CWL project. And he has done a bio Excel webinar before covering CWL. Hopefully you have attended his webinar or have watched the video. Briefly, as you know, there are many open source workflow tools available today. And many of them are very widely used in life science. But one issue with these tools is each tool has its own specification or format for the workflow definition. So it becomes difficult for scientists and users to share or collaborate on designing the workflows. CWL is an open standard developed by an informal and multi-vendor working group. It's led by the community and there are many participating organizations in academic research and industry. And it basically designs the CWL specification in such a way that makes the workflow definition portable and scalable across various software and hardware environments. So as long as the open source software implements the support for the CWL and conforms, passes the conformance test, then the CWL workflows can run in these different software. And if you have the same definition and the same input parameters and data, then the result is repeatable. And also CWL workflows can run in different computing environments such as running locally or in a cluster or on the cloud. And CWL also has prominence in mind, so you can always get the same result. So it becomes a documentation of your workflow. There are already many implementations of CWL on the right of this screen. You can see a list of the software. I copied this from the CWL website. And if you check periodically, you can actually see more and more software implementing CWL. On the platform support, you can see software supporting local execution or in HPC environments such as Slurm, Grid Engine, and LSS. And they can also run on the cloud including AWS, Azure, and Google computing platform and so on. So as CWL grows in popularity, we have LSEF users asking us to support running CWL workflows on LSEF. And even though there are already many open source implementations of running CWL workflows on the HPC environments for batch schedulers, these integration are often generally relatively basic. So this is not just for LSEF, it's pretty much most batch schedulers. So they are usually limited to the simplest or the most common functionality. So you cannot take advantage of some of the rich features from these batch schedulers. And the implementation can be inefficient. I will talk about this later in more detail. And they are often limited or no ongoing testing or enhancement. Even though these batch schedulers continue to release new versions. And there's pretty much just the best effort community support. So in order to overcome these limitations, we started working on this new project we call CWLExec. And it will be an open source tool to run for now with LSEF. And we will have tight integration with LSEF and it will be fully supported by IBM as long as you have LSEF support. And we will leverage many LSEF features such as native container support to take advantage of the LSEF features. The versions we are going to support is CWL draft 3 and the version 1.0. There will be a few exceptions. Some of the features we may not support in the first release. This includes software requirement, expression tool. They include the directive and the remote location in the file and the directory specifications. This primary is due to the effort required. We can certainly add them in CWLExec in a later phase. We actually looked at all the CWL workflow definitions in the public repository. And we kind of find that these features are not that widely used. So maybe this will not be a big limitation. CWLExec will require LSEF version 10.103 or above. If you use LSEF suite 10.2 community edition, then the LSEF version inside will be sufficient. And I need to point out the community edition for LSEF suite is free and downloadable. You can download it from IBM website. I should also point out CWLExec will be a standalone package. So aside from the fact that you need LSEF, it will not rely on any other IBM product. So this makes it easier for people to use it. We plan to release it in the second quarter as part of LSEF suite. We will put the source code on GitHub under Apache license. The source code will be written in Java. So here's a look at the CWLExec command line. This is similar to CWLRunner. And we don't have a lot of options like CWLRunner. It's basically you provide the CWL workflow definition file and input setting file. Then this command will execute the workflow. The command line options are consistent with the CWL conformance test. So we can use this command to run the conformance test. The parameters include the output directory, the working directory. And we have a new parameter called exact config that I will talk about in more detail. And when you run the CWLExec, you will get a unique workflow ID, which you can use later on to query the workflow status or to rerun the workflow. So now I'm going to talk about more details of the features in CWLExec. I will talk about how we check job completion efficiently with maximum parallelism, how we support LSF submission options, self-healing of workflows, Docker integration, cloud bursting, and I will also talk about how you rerun and interrupt CWL workflow. So first, efficient checking of job completion with maximum parallelism. Like I mentioned in the open source implementation, often to check whether a job has completed the existing tool, often just pull the status of the job periodically. For example, in LSF, there's a command called bejobs. You can use to query the job detail and status. And often it is used to, you use run bejobs say every 10 seconds to pull for the job status until the job finishes. This is not efficient because first of all, you can have up to 10 seconds delay. You don't get the job status in real time. And secondly, if you have many workflows in the system and many jobs, then running bejobs on these many jobs over and over can generate a lot of network traffic. Even though LSF can handle high volume of queries without problems, these commands can still generate a lot of network traffic, which can have an impact on your environment. So in CWL exec, we use a command called bewait instead. This command was introduced in LSF 10102. Basically it waits for the job completion through a callback or notification mechanism. So you can get the job status in real time without delay. And at the same time, you don't generate those kind of network traffic. And we run bewait in a separate thread so that we can ensure we have the maximum parallelism. So on the screen, there's an example. In the beginning, we have four jobs, J1, J2, J3, J4, which don't have any dependencies. And potentially the first job, let's say it's a scattered job, you can have thousands of jobs that can run immediately. So we will submit these four jobs right away to LSF so that they can run concurrently in the cluster, depending on the capacity of the cluster. And then there's a job, J5, that depends on the output from J1 and J2. So we will run bewait to wait for J1 and J2 to finish in a separate thread. As soon as J1 and J2 are finished, the bewait command will return and the main thread will gather the notification and then start the job J5. So same thing with job J6. So in this way, we will be able to check job completion efficiently and ensures the maximum parallelism. Next, I will talk about how we support the LSF submission options. In LSF, you use the command bsub to submit a batch job to LSF cluster. And bsub has a lot of options, dozens of options. And our users pretty much consider it mandatory to be able to specify these submission options when they run LSF, run CWL workflows on LSF. Some of the examples for these submission options say resource requirement. In CWL specification, the resource requirement is limited to CPU memory and the disk only. This is understandable because CWL specification is supposed to keep the flow definitions portable. They don't necessarily run on LSF or any workload manager. They can run locally or on the cloud. So these kind of options, workflow manager specific options may not apply in other environments. So back to the resource requirement. In LSF, the resource requirement can be much more than just CPU memory and disk. For example, a user can specify the preference on what types of hosts. Do you want hosts with least load or more free slots? And for parallel jobs, you may want to specify how these parallel jobs should span across multiple hosts. So a user can specify very complex resource requirements to match their jobs to the optimal compute hosts. And another fundamental thing users want to specify is which queue they want to submit their jobs to. The queue can reflect policies like priorities and how groups of users should share the cluster and so on. And other options can be what project, application profile or whether a job should be runnable. And as I mentioned, the CWL workflow definition is supposed to be portable. So in order to support these submission options while keeping the workflow definition portable, we will introduce a separate configuration file that you can specify for the submission option when you run the CWL workflow. So as shown here, we use the parameter exact config to specify this file which will be in JSON format. And these LSF options can be specified at step level or workflow level. Options at the workflow level applies to every step in the workflow. And if an option, a same option is specified at a step level, then that the one at the step level will overwrite what's specified at the workflow level. And on the right, there's an example. The user has specified a queue called high, and this will apply to every job in this workflow. And he has also specified that all the jobs should be runnable. And then in the steps, for example, main step one, the user again specifies the runnable to be false which overwrites the one at the workflow level. And he also specified a resource requirement for this step which says what type of host he wants and he prefer hosts with least CPU utilization. And also it will require 500 meg of memory and there's a requirement for swap memory and temp space and so on. So he can just use this file when he run the execute the CWL workflow. And currently we will support a queue project, a runnable application profile and the resource requirement, these options for when you execute the CWL workflow and we can easily add more later on. So next I will talk about self-healing of workflows. What do I mean by self-healing? It really means when a step fails in a workflow, we try to let the job recover itself without user intervention. So we will do this in two parts. One is the runnable job that is a feature from LSF as long as you enable runnable then when the execution host for the job goes down, LSF will rerun the job automatically on different hosts so the user doesn't have to worry about this part. And the second thing is we will provide a custom post-fader script. So when a job fails in a workflow, often it is recoverable after you take some action. Ideally you may want to have a script to check and fix the problem automatically whenever possible then the script can recue the job and let the workflow continue. For example, a job may fail due to insufficient memory and you can have a script that detects the job failure reason then modify the job submission parameter to increase the memory requirement. You can do this through the demod command in LSF and then recue the job. Here's a command called beRetue and then the job will run again with more memory requirement. As you know, it's always very difficult to estimate a job's memory requirement accurately. If you specify too high a requirement then you may overuse your resources. So it's best you make the best effort, best estimate and then if occasionally the job fails then this kind of script can recue the job and the job can still succeed. And the script may potentially also just check a job log and if it can fix certain problems then it can fix the problem and then recue the job. We will support this kind of custom post failure script and through the exact config file we talked about before. And on the right there's an example you can specify the path to your script and you can specify a time out value in case the script is not written properly and it can run for a long time or even half. And you can also specify how many times you want to retry. So if a user has configured the post failure script and then when the job fails CWLExec will run the script. When it runs the script it will pass the job ID, the sub-command and job command all the necessary information to the script so that the script can do the check and take actions properly. If the script runs successfully then CWLExec will consider the job has been recued and it will go back to wait for the job to finish. If the script fails then CWLExec will consider the job has really failed and then it will stop the workflow. So this makes it possible for the workflow to be self-heating as much as possible and hopefully this is a useful feature. And next I will talk about the Docker integration. So CWL specification supports dockerized jobs and there are some security issues when you use dockerized applications. This is not specific to CWL, it's a generic issue. For you to run Docker jobs in order to avoid a seal-do often the users need to be placed in the Docker user group and the Docker job will run as root so these Docker group members get root equivalent privileges. This is not really an issue when Docker is used to run services started by root but it can be a potentially serious issue when the users are allowed to run arbitrary jobs like in this kind of HPC environment. Second issue is many businesses often have concerns about users being able to arbitrarily using a container from external registries such as the public Docker Hub. There could be concerns on security and provenance or auditability of these Docker images. And LSF has integration with containers including Docker. Actually LSF also integrates with other container technologies like shifter singularity and so on. And LSF addresses these security issues for dockerized applications. First we let administrator to use application profiles to configure dockerized applications. Application profiles are some configuration in LSF they are used to define the common requirements and parameters for the same types of jobs. For example for a certain application they want to specify some common requirements such as memory CPU limits pre-post execution scripts and so on. And for dockerized applications LSF administrator can have the ability to approve and configure what registries and what images can be used. And he also has control on what docker options that can be used through the application profiles. And LSF will start those docker containers as LSF administrator removing the need for all the HPC users to be in the docker user group. So that means those end users never gain elevated privileges. The only user ID you need to put in the docker user group is the LSF administrator. Of course there's a configuration that you can specify a different user ID to start the docker jobs. So this diagram basically illustrates the points I've just mentioned. The administrator will be able to manage what registries and images can be used through the application profile which is defined in the lst.applications file. And the user just needs to specify a dash app which means what application profile I want to use. And LSF will then pull the image and run the docker job. So regarding the CWL exact integration we allow the administrator we expect the administrator to configure the application profile for the docker jobs. Typically for now we expect one profile per registry. So here in the configuration there's a line container which specifies which images can be used. So in this example the administrator has specified the key.io as the registry and the image name is passed in through an environment variable called the lst container image. So this will be passed in when user actually CWL exact runs the bsub command. And this pretty much limits the docker images have to come from the registry key.io. And in the docker options the user as the administrator has specified a script. He can specify hardcoded docker options but LSF provides the flexibility to use a script to generate the docker options. So we have a sample script here basically you pass seeing multiple docker options through the lst container options in one variable. And the last parameter is the starter which is the user ID who will start the docker job. After the administrator configures these application profiles the user just need to specify this application profile in the exact config for the docker job in his CWL workflow definition. He just need to make sure the registry matches the application profile. And CWL will then submit the docker job and automatically pass in the image name and docker options such as volumes because the CWL exact knows what work directory or output directory and other temporary directory potentially to be mounted for the docker. So this way it should be pretty simple the administrator to configure and the end user doesn't need to know all these details he just need to specify the correct application profile and this makes it more secure to use docker jobs. And the next feature I'm going to talk about is the cloud bursting capability from LSF. So LSF has a component called the resource connector that adds the cloud bursting capability to LSF. This will enable LSF to automatically borrow and launch hosts from a cloud provider to join the cluster when the workload demand is high in the LSF cluster. So the cloud provider we support include AWS, IBM cloud, Microsoft Azure Google computing cloud pretty much all the main cloud providers and the resource connector is able to automatically flex resources up and down based on the workload in your cluster. So when the workload is high it will borrow resources from the cloud provider to join the cluster and when the workload goes down these borrowed hosts become idle for a certain amount of time the resource connector will return these hosts to the cloud provider. So this pretty much you will be able to leverage the on-demand capability from the cloud infrastructure to borrow resources as many as you want as you need and you will be able to only pay for what you use. And the resource connector also has policies for you to configure when you want to start bursting and also for example the maximum number of hosts you can borrow and so on. So this is mainly the execution effort by the administrator the end user just need to specify the queue or resource requirement to be able to borrow resources from the cloud and in this way CWR workflows can run in the cloud when your on-prem cluster does not have enough resources. So finally I will talk about the rerun and interruption so if a workflow fails it exists with non-zero code because some jobs have failed you can rerun the flow through the CWL exact command with the rerun option and the rerun will start from the failed steps not from the beginning because the user's workflow can be long running and has hundreds of steps the user don't want to rerun the flow from the beginning. Usually you only want to rerun from failed steps and also you can interrupt running CWL workflow by pressing Ctrl C the CWL exact will stop it will not submit new jobs and although it will let the submitted jobs to continue to run. So this is all the features I want to cover and next I want to talk about our load map looking ahead. So the previous slide basically talked about how you use CWL exact to execute CWL workflow. It is pretty much in the CRI mode we will add a server mode to CWL exact and the server will run as a web server that provides RESTful API and points. In the server mode it pretty much acts as a central server to execute and manage flows from many users and it will be a central place to manage all the flows and you can achieve scalability and so on and the RESTful API will include the APIs to execute a CWL workflow or get a list of the finished and running workflows optionally with the filter you can also use API to query details of a specific workflow like the details of each step and so on we will also provide the APIs to control CWL workflows including kill, suspend, resume and rerun a workflow and we intend to include the server mode in the open source project and use the CWL exact server mode as back end we will also implement a GUI interface for CWL workflows and the GUI will be done in IBM Spectrum LSF application center to integrate the environment for users to visualize, manage and monitor all the workflows so the abilities include managers of CWL workflow definitions visualize the definitions and the instances, the running instances so visualization will be similar to the CWL viewer measurement by University of Manchester and you can also monitor the progress of the workflow instance visually and additionally you will be able to select input and output data and view its content as well as the work directory of the workflow instances and jobs in this single integrated environment you can also control the workflow instances you can select the workflow instance to kill, suspend, resume or rerun many of these capabilities are implemented in the LSF process manager we are just going to port or migrate many functionalities to support the CWL workflows so these are illustration of these abilities this is the LSF application center so you will be able to see a list of the CWL workflow definitions all the definitions in your system and you can pick one of them and say I want to view its graph then we will show a chart similar to CWL viewer and you will see all the steps and their relationships and if there are subflows you can select it and then expand or drill into its details and you can also select a workflow definition and then execute it by providing input the settings file then you can have a list of all the running workflows and then you can select one of them and say I want to see its chart and then we will show the progress of this workflow instance and the status of the steps will be shown in the graph through color coded states the color gray indicates that step has finished green means the step is running and yellow means the step has not started yet and you can also click on the input or output file and then say I want to tail or view the content and you can actually, when you tail, you can gather the content at a real time so this is pretty much our roadmap and I have I think coming to the end of the presentation I want to thank everyone for joining the webinar and you are encouraged to download and try CWL EXEC when it's available in second quarter and we are always welcome collaboration and contribution from you if you want to be informed of further developments feel free to just drop me an email and you can also just give me feedback so I think that's end of my presentation and I will be open for questions thank you I would like to see what you've accomplished so far and your vision for the future so I just want to invite everybody to send in any questions you may have we've got some time set aside for this we have one question already it's a kind of straightforward one asking if there's going to be a recording of this talk available and yes, the recording is being made and hopefully in a couple of days it will be public in fact there will be another opportunity to ask questions in a sort of virtual face to face format next week at the CWL community call which will be on Tuesday at let me get the time zones right because we're also going to do a little bit a half hour earlier than we normally do today at 1500 UTC and the email about that will go out to the CWL community mailing list so great time for questions let's see here if there's any others available yet I have a question for you have you tested the CWL exec with any of the publicly available CWL workflows that's our plan actually we looked at the CWL definitions available on the public website and we have picked a few to want to make sure it can run with our tool great all right Maxine Sherman writes will the slides be shared yeah this slide will be shared I think it will be downloadable from the file excel website great and we've got a question here from new to this interface looks like somebody unmuted me am I speaking now I guess my question is if we have not yet upgraded to <IP_ADDRESS> how can we use CWL exec okay yeah so as I mentioned we need the B-weight B-weight is actually on 10102 so if you have 10102 then majority of the functionality should work we need a 10103 mainly for the Docker options and of course for LSF if you have the LSF the upgrade is always available okay so if we if we are not looking at using the containerization right off the bat and if we are able to implement our own B-weight command will that work or is it using B-weight through if you implement B-weight it should work but make sure it actually we basically do B-weight W and the list of job IDs and the relationship for now so if you satisfy that then it can work this isn't something we're hoping to do long term but just until we get that upgrade if we want to try things out theoretically if we write our own B-weight command it should be able to find it in the path and then work correct yeah okay cool thank you so Michael actually I can read the questions sorry my DM rebooted so thanks for doing that no problem so I will just go on to the next question yeah from Igor Kosin yeah so the question is is PAC needed for Docker integration or is it integrated directly into LSEF so the answer is it integrated directly into LSEF so you don't need to have PAC Igor you'll need to speak up a bit we can hear you Igor I can't yeah Igor doesn't have a mic Igor if you'd like to respond in the chat or ask another question to reply okay he's good thank you Igor for your question so we've got the next questions from Manabu Ishii are features like post-failure script are they valid would they be seen as valid by the schema-solid tool I think I can answer that one so the post-failure script as shown in the example Manabu was in that external configuration file that's pasted separately so it's not part of the CWL description if it was implemented as an extension to the spec which is totally allowable and that was supported by CWLExact then schema-solid tool would be fine with it as long as it had a namespace and a schema-specified just like other extensions Manabu does that answer your question thank you I understand any other questions is if anybody else has anything you said Shindo that your LifeScience customers had asked for CWL support did you have interest from customers in other segments for now I'm only aware of customers from LifeScience I think a CWL is I know it probably has already expanded beyond the LifeScience but from our customers from LifeScience great so in your Docker integration with the dash app support so that means that Docker containers can only be specified by this sort of parallel configuration is that correct or will you be able to translate CWL's Docker requirements to see if they're supported actually we have a fallback so if you don't specify the application profile we will just assume the user is in the Docker user group and we will run the Docker run directly okay and then there's a technology called UDocker that kind of gives a fake Docker experience and we've had success using it at the European Informatics Institute has your team played with UDocker yet? we haven't looked at it yet it's in the reference runner if you want to take a look at that and that flows into your toil yep we will have a look we've got a few more minutes one more minute for questions if anybody else has any just want to take another opportunity to thank you again Chinda I am really excited to play with this myself I know a lot of customers and users out there are as well so Q2 can't come soon enough thank you Michael as well well that's all for now so look forward to on the biocell mailing list and website for the recording of this webinar and again we'll be emailing shortly to the community group about another Q&A session as part of the CBL Community Call next Tuesday take care all cheers thank you bye