Here we go now. Hey get them now get that sucker out of that tree. That's a good one Welcome back to the channel everybody welcome back to a beautiful glorious day calm Water elk bugling in the background my goodness. It's outdoor greatness. I've got Parker and cutter here with me today How did you guys get here? Why are you here? Oh? we won a giveaway, I guess you call it to get a private fishing trip with y'all and We haven't even made our first cast yet, but it is Gorgeous the guys over at fun and sun they hook us up with boats and a lot of our geared stuff They're they're big on high school bass fishing and these guys are from Roy City. Is there right? Roy City bass fishing team and we've got one over their team over there with Rob And we are gonna dangle hard today, and it looks like we're gonna get some top water action in Let's commence the first cast Although we're kind of out in the middle of nowhere. Sorry, and here we go. I'm gonna be starting out with the Hummer the buzz bait with the saucy swimmer on it Beautiful little combo. It's gonna happen. This water is clear. Make sure your drags are set mine was not first guy little Little weak attack wasn't a full blown What's going on here?  I'd certainly enjoy that. That's the best That's kind. There's one swirl right there You have to break out the swim bait on them on this point just to clarify what's going on So weird to hear elk bugly. Have y'all ever heard that before? Oh my gosh, this water is clear y'all I can see my bait way down there. Boy, that should just be getting Slopped on gosh. He's elk man. This is ridiculous the first The first big one we'll say mid-size Falls victim to the old whopper plop as the elk Bugle in the background There we go nice one clear water top water action I would take five of those any day we may have to Have to break out some worms and jigs and stuff. Oh boy. There he is Oh, no, you did not sir Oh, he's coming back. Look at him. Oh, it's a five pounder. Amazing That was a glorious That was a big one He bamboozled my worm, man six pounder.  That's a beautiful fish Nicely done man on a spinner bait. I love it I love it right between those the two little trees. Yep Good job, dude a brute and a butte On an awesome lure. It's a little slow, but Fish like that that keeps me motivated right there. I see Definitely shied away from the boat. There's another one Hey, come on now. I think I may switch to A jig Not yet. I'm not convinced Wow Okay, if this guy doesn't have it There we go I only got one to Stay on On the mondo the old tree pounder Nice I think I have another bite Might be worm time He absolutely had it too It's just a just a good old bass right there. Just a good old bass There's not a whole lot I could say about that one except it's just a good profile nice bass See you buddy How do you rig your zed? Time to switch tactics. Okay. This is Show you this hook is kind of interesting So it's kind of a hybrid hook.  I just I want old hog We're entering into some serious stumps here five offset worm hook Stick that in the plastic there five 16 ounce bullet weight hook or bullet weight bullet weight hooks have never Been a thing 20 pound gs flurro We're ready to dangle out here in the trenches with the trench hog All these trees just follow a creek channel. I'm assuming Oh my dad's out fishing again Hey, uh, gilip g. Good morning. I thought I'd give you a quick update Of the fish got it. I've never had that happen with a Nice Oh, there he is.  That's a new word just came out Donkler Yeah, it was a tap tap tap aroo It's happening right on that point. Absolutely inhaled The trench aroo come on big mama Oh, yeah, just got a collar in That's not a big one but To do someone right on the very end of the extended point big fatty That one about pulled the rod out of my hand Dear goodness very nice another one on the old trench hog Oh, yeah, you can actually see the bottom right here guys We should break out our top waters again though and just run through here See if there's any that are chasing Chasing bait like all the way up here yet Dang right on that big stop. I don't feel I'm just keeping pressure in mind to get off Do you see some I hadn't okay, that's good Y'all one. Oh, yeah, dude. Nice one up in the shallows Heck, yeah Nice No Now's not the time Should be a fish there So far we've been catching them on plastics Kind of out in the timber a little bit deeper We decided to roll up in this little creek right here just to see if they're chasing bait Oh, do you break your blade? Yeah, he broke it off Dude, that's when your spinnerbaits at its peak is like right before it breaks He probably heard it coming. He was like, I got to have that deliciousness We're just gonna fish all the way back see if there's any more fish in the super shallows But you can literally see the bottom That fish came out of that shallow water Just now heard that one blow up. Does that get you pretty excited? Yeah, a little bit a little bit What gets you more excited A 10 pounder. Okay. Let's see right now. We probably have Working on we're probably like 18 pounds What would you say that's a nice fish Oh my gosh Dude, there's a big one swimming right in the gut of this thing. There's another one right there, dude They're stacked.   Holy cow Oh man Nice fish right there. Nice Just go go far and beyond There it is No No The dreaded hang up.  Uh, there's some little flare fish back here. I'm telling you I saw some on those creeping in here But I think we we spooked them Got another one definitely bigger Nice, uh Is there anything better than that? slapping spitter baits you guys You guys got to work on that landing, man You ever had a big tournament fish flop out of the boat? Not yet Actually when I was really little I watched my dad and one of his friends and they had like a seven pounder go out of the boat Oh, dude, I like form tackling when they hit the carpet so far. We've amassed about 30 bass soft plastic speed of the key trenchhog Mondo worm biggest bass has come on a spinner bait, which I mean wind is a big bass not common on a spinner bait, but right now we're gonna actually load up this place that we're at I believe this place is called the high top range or something like that. This is a unique place They literally have deer hunting elk hunting lots of lakes. There's 22 lakes out here And we're going to go explore a couple of A couple more of them sun is getting high Sometimes the schooling up action Actually happens like later in the day three four o'clock and we are sitting at noon right now So time to grab a little bite to eat and then get back to dangling, but we're doing pretty good so far This is a good time Lake number two we are dumping in That's monnie right there. He's the owner of fun and sun He's orchestrated this deal That's a great man He's also gonna back me in here He's fished these lakes before they've uh, they've done some shows and things like that And he's saying this one Should be just as good round two going for the megalodons. You guys is pbs. We're looking at Seven pounders. I think what you guys said sixes or sevens Got the opportunity here close the gap shallow by the tree Tree pounder by the tree on the bank a little windy bank action here. Oh, I'm getting one too I think we're done Yeah, I got a bigger one on the swim bait. Are we tripled right now guys? Really? Triple chunkers Saucy swimmer You got it big one on the old saucy Tripled up. That's our first triple of the day. Should we get a triple selfie? Hey, we're doing it See baby. That's what it's all about You guys giving up right now. What's going on? What's happening right now? Take some more Advil We got a we got a man down right here.  It's gonna get gobbled So you don't have to get your tattoo today No, I just hammered down on the five Nice I don't know if the zingers are doing the massive work Get that sucker down on that tree. That's a good one. That was a nice one. That was a foreski for sure Give me the play-by-play what happened So threw it in there Twished it once He hammered it Got caught up in the tree and came off Such as life Maybe a body game They're in that tree Getting that fall action always got it Slammed I got one little guy. Yeah, the triple man the triple threat I don't think we have a big one on this This round though the old tag team on that guy beautiful fish You did the old reel in trick till it got heavy. BAM got that big and see Oh, yeah, dude that thing is gone. Absolutely gone saucy That one's been eating good. Hold on one's back in here. Time has come School is back in tomorrow The dreaded class What would you rather do go to first period or catch an eight inch largemouth Okay, that's pretty evident there pretty clear question there What would you rather do graduate from high school or catch a 28 pound bass? 28 pound bass 28 pound bass would probably make you a lot of money. You'd probably get a lot of endorsements there Stay at school kids stay at school. We probably we definitely caught over 50 Even though the wind was high we came to the southern lake I think that the better average size was there And uh, they were they were just eating the meat potatoes baits They were eating the saucy swimmer. They were eating a spinnerbait. They were eating a crankbait. You were catching them on crankbaits So they were eating the good stuff. Okay, unfortunately We gotta we gotta go in because they have to go back to school So we're not gonna get an evening bite session in but it's been a pretty good dangle today Come here pumpkin. You're gonna say hi your dad You took a hard ride. Alrighty all I'm gonna go spend the rest of my weekend With the family at a really good time fishing with parker and cutter today. We learned some things. We had some good times I wish there was high school fishing around when I was that age But I'm glad they're getting to experience it the saucy swimmer y'all now available I'll link it down below that was a key component on that second lake to getting bites And it was kind of different between the two. I cannot believe There was 22 lakes on that place. We only fished two of them It was a majestic place that we went to today. So go ahead smash the like button for outdoor greatness today lfg signing off until the next dangle soon


Thank you, Neil. So I would like to thank the organizers for giving me the opportunity to speak here. And that's a picture of me jumping from joy because I heard that my abstract would accept it for a talk. And I'll be talking about a pan-cancer proteomic perspective on the cancer genome atlas. We at MD Anderson generate RPPA data, protein expression data for TCGA. So we analyzed, in this particular study, we analyzed 3,467 samples across 11 different tumor types. Those are the tumor types listed there. We did not receive any AML samples, so as opposed to pan-can 12, we had pan-can 11. We had 181 proteins in total, 128 of them were total proteins, one cleaved, one acetylated, and 51 phosphorylated forms. And the data were produced in six reverse-phase protein array or RPPA batches. This is a platform for generating protein expression data. So the first step we did was we developed an algorithm called replicates-based normalization to reduce batch effects between the six batches. After correcting for batch effects, then we performed protein versus other platform comparisons. So the first one was gene versus mRNA versus protein matched comparisons. So what we found that on average, the mRNA versus protein correlations was on the order of 0.3. That sounds a bit on the low side, but this is common for patient samples. In cell lines, we see much higher correlations, 0.7, 0.8. But for patient samples, this is common. But what's interesting is that when we looked at the individual mean correlations within the 11 disease types, we found that the correlation was not uniform across diseases. In colon cancer, for instance, the average correlation between mRNA and protein was on the order of 0.16. However, in ovarian cancer, the correlation was much higher, was 0.33. So we didn't see a uniform distribution of the correlations across disease types. When we compared copy number variations with protein, we found that, on average, amplifications resulted in only a 5% increase in protein levels, whereas deletions resulted in only a 5% decrease in protein expression levels. Now, there is a caveat here that this may be due to the large number of passenger amplifications and deletions that we often see in copy number data. So those might be diluting the results for the copy number data. For mutation versus protein, we saw that, on average, elevating mutations, those that result in higher expression levels, increase protein expression levels by about 20%. Whereas suppressive mutations decrease protein levels by about 10%. So those numbers are more than the copy number numbers. And, again, we think that's because there are fewer passenger mutations than there are passenger copy number variations, so that might possibly explain why we see this discrepancy. Other comparisons we made were between microRNA and protein, so every microRNA versus every protein, mean spearmint correlation was on the order of plus or minus 0.07. And protein versus protein, mean spearmint correlation was on the order of plus or minus 0.15. I'm going to focus on herb B2 as a use case. So what we did was we used breast cancer, HER2 positive versus everything else as our benchmark. And using HER2 positive versus all the remaining breast cancers, we identified thresholds for copy number, mRNA, and RPPA that would separate HER2 positive from HER2 negatives. Then we applied those same thresholds and other disease types to see what comes out. And what's interesting is that, not surprisingly in many diseases, we don't see protein expression level, you know, it's high in, let's say, less than 5% of the samples. But in some of the diseases, what we saw in those diseases where more than 5% of the samples had HER2 positive protein expression levels, we saw that by comparison with copy number and mRNA, proteins predicted a much higher level of samples, a much greater number of samples that had high HER2 levels. So for example, in bladder cancer, we saw that only 7% of the samples were HER2 positive by copy number, 8% by mRNA, but 22% by protein. Similarly, for colorectal cancer, only 7% by copy number, 3% by mRNA, but 37% by protein, and so on. So we saw discrepancies in lung adeno and endometrial as well. So why is this important? This is important because many of the therapies that are currently being used, for example, Herceptin and the new drug that's about to come out, TDM1, they work at a protein level and they actually target the protein on the cell surface. However, many of the tests that we use today to check for HER2 positive versus HER2 negative patients, they rely on copy number versus or mRNA platforms. So this finding is interesting in that we should probably, you know, try to measure a protein directly when trying to assess HER2 positive versus HER2 negative patients and who could possibly benefit from the therapy. Moving on, this is the clustered heat map for the 3467 samples by 181 antibodies. And using unsupervised clustering, we got eight different clusters. We nicely got the women's cancers, that's luminal breast, endometrial and ovarian in one major cluster on the left-hand side. Basil breast and HER2 breast were not in that cluster. They were quite distinct from the remaining samples. And the URL is given there. If anybody wants to look at this in much greater detail, the URL is provided. This is using the tool called Next Generation Clustered Heat Maps that was developed at MD Anderson. It allows you to navigate and zoom and search the entire heat map. So zooming in on this heat map, we see that most of the clusters, they cluster by tumor type. But there are a few exceptions. So for example, cluster F has a mixture of many different tumor types in there.  Some of the squamous bladders are also in there. The other cluster that didn't have a one-to-one correspondence with tumor type was colorect, was cluster E, in fact. And cluster E had basil breast, HER2 breast, and ironically, a few bladder samples. Those bladder samples were the HER2 high bladder samples. And if you look at bladder, that's a very different animal altogether in this particular picture. What we see is bladder is spread out across four different clusters. This is not in a single cluster. That's in contrary to mRNA clusters where we do see bladder in a single cluster for the most part. But here we have bladder in four different clusters. If you look at outcome differences, so bladder that looks like endometrile, so the ones that clustered with endometrial cancers, they have a much worse prognosis than the remaining bladders. And it's interesting that we found any difference whatsoever because bladder data isn't, you know, there are many examples with sensor data, so it's not the best outcome data that we have. Similarly, in kidney cancer, we found that the squamous-like kidney cancers have worse prognosis than the remaining kidney cancers.  So in breast cancer, for those of you familiar with the marker paper for breast, we had identified a reactive group. This is based on protein expression levels in breast cancer. And that reactive group had good prognosis. Some of the markers of the reactive, breast cancer reactive group were caveolin, collagen, MYH11, and Richtor. Some of the marker proteins that were identified, so what we did was we did a differential analysis to see which proteins were differentially expressed in different clusters. So in women's cancers, we saw ER alpha and AR. Now, AR was a surprise. Now, prostate cancer was not included in Pancana 11, but regardless of that, AR was pretty high in women's cancers. In luminal breast, we found AR, BCL2, FAS, and ACC1 and phosphoACC. They were high. In ovarian cancer, we had CMIC. They were high. So these are potential targets. Not all of them have targeted therapies as of right now, but some of them are under development. So these are potential targets. All of them, except women's cancers, had phosphosarct elevated. And in head and neck, phosphosarct is a downstream target of EGFR. So perhaps we can use EGFR therapies for head and neck. And HER2 was high in a number of cancers including endometrial, bladder, breast, and colorectal. HER3 was high in kidney cancer. And phosphoEGFR, notch 1, HER3, they were all high in GBM. So maybe it could be amenable to combination therapy. The next step we did then was, well, so we find clusters that are mainly thereby tumor type. Those clusters have almost a one-to-one correspondence with tumor type. Can we go ahead and reduce tissue-specific effects so that we can see clusters that span multiple tumors instead of having a one-to-one correspondence for the most part? We did that using a technique called MC that we developed. And I don't have time to go into the details of that, but here's the zoomed-in view of the clusters that come out. So we came up with seven clusters. And as you can see from the top bar, the tumor types are all spread out among the different clusters. There's no single dominant tumor type that's there in each of those clusters. Cluster 1 had PEA and HER2 elevations. Then we divided cluster 2 into two parts, 2A and 2B. 2A had HER2 elevation. 2B had EGFR elevation. Then we had a cluster with AKT pathway high, a cluster with AKT pathway low. Wind signaling high, wind signaling low.  So the reactive cluster had predominantly breast cancers, but also other disease types were there in this cluster. So let me talk a little bit about this. This is the reactive cluster right there. This is the zoomed-in view of the same clustered heat map that I showed earlier. And we can see caviolin 1, MYH11, Richtor, collagen 6, those are the markers for the reactive cluster. So we can clearly see this is a reactive cluster. What is interesting about that cluster is that, like I said, in breast cancer, reactives have good prognosis. And the same is true for colon cancer and kidney cancer. So in colon and kidney, reactive samples have good prognosis. However, if you look at lung squamous, ovarian, and bladder cancers, then in those, the reactives tend to do worse. Now, we don't know why that's the case. All we see is an observation here that the reactives do distinguish from the others, and they can either have good prognosis or bad prognosis. And that's not just true for reactive, but ironically, that's also true for some well-known pathways. So, for example, the AKT pathway, one would expect that when the AKT pathway is suppressed, you would have better prognosis. AKT pathway is responsible for proliferation. And that is indeed what we see in ovarian cancer, that those samples where AKT pathway suppressed do better. But in kidney cancer, that's not the case. It's the other way around. In kidney cancer, when AKT pathway suppressed, those patients do worse. And as a sanity check, we tried the other way around. So when the AKT pathway is activated, we indeed see a trend where the ovarians are doing worse. But kidney is actually doing better. So this is somewhat of an enigma right now that some of the pathways, you know, they don't behave as expected in some of the tumor types. So it looks like pathway activity is dependent on tumor type. This is interesting because there are some studies or some trials that actually try to silo different samples by pathway activity rather than by tumor type. If we're going to, you know, do studies like those, then we should be mindful of such observations. And this is my no means conclusive, but it just raises a possibility that pathways may not be agnostic to tumor type. So to summarize, the take home findings are, when we did cross-platform comparisons, we found that mutations on average have greater meaning, have greater fold changes than copy number variations, possibly due to the larger number of passenger events in copy number domain. mRNA protein correlations can vary widely by disease. They are by no means uniform across disease. Her two protein levels are not predicted well by copy number or mRNA in certain diseases like colorectal, lung adenu and bladder cancer, but they are predicted well in breast cancer. And then several novel markers were identified. There were outcome differences seen across clusters, possibly driven by pathway differences. Pathway effects are not equal by disease. Certain pathway activations may have good or bad prognosis depending on disease. And not shown here, we also looked at protein-protein correlations, and even they vary by disease. So for example, P10 versus phospho-AKT, it was found to have a strong correlation in lung squamous cancers, but not so much in any of the other cancers. Finally, I would like to acknowledge my co-authors. This is the paper that is due to come out in nature communications in about two weeks. The title is Pancancer Proteomic Perspective on Cancer Genome Atlas. I also have poster number one, so anybody who wants to talk to me further is welcome to attend the poster session. And I would like to thank specifically Gordon Mills and the rest of my team. And that's a picture of us celebrating the acceptance of the Pancan paper over dinner. Thank you. Very nice work. Just one comment. The reason you are seeing the AKT pathway in kidney cancer when it's low, the behavior is better, it's because the mTOR pathway is activated, and just a feedback. Because kidney is very, very mTOR-driven disease. You see 6% of mTOR activation mutation, you see TSC mutation. I think that's the reason why you're seeing it. The other question I really have is between F and G, you're talking about kidney cancer, they are squamous type. What are the markers that differentiate them from the most of the G-type kidney cancer that you separate them? So I think you're talking about the very early years, because the main lineage. Right. Let me get back to that slide. Okay. So you're talking about this particular figure, right? So in squamous like, oh, there we go. So in this figure we can see some of the markers in kidney cancer in the squamous type. Those are the markers for the squamous type. So we have phospho-soc, for example, that's elevated in this cluster versus the others. There's also a fast N that is differentially expressed, and also AMPK-alpha. So those are some of the markers that we see between the two clusters. Great. Thank you. Thank you. Thank you very much. Our next speaker is John Martinetti from Mount Sinai, who's going to talk to us about data mining TCGA breast and ovarian exomes for novel susceptibility markers.


The use of dietary and metabolic therapies to treat various neurological diseases has been attempted, including epilepsy, headache, neurotrauma, Alzheimer's disease, Parkinson's disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The motivation for using these treatments stems from the lack of effectiveness of pharmacological therapies and the appeal of a more natural treatment. However, the spectrum of pathophysiological mechanisms underlying these diseases suggests that dietary interventions may not be effective universally. Nonetheless, it is possible that alterations in certain dietary constituents could affect the course and outcome of these brain disorders. The ketogenic diet, KD, has been shown to be effective against medically intractable epilepsy by normalizing aberrant energy metabolism. This concept suggests that many neurological conditions may be linked pathophysiologically to energy dysregulation, providing a common research and experimental therapeutics platform for influencing the course of several neurological diseases through dietary means. This article was authored by John Monroe and Carl E. Staffstrom. We are article.tv. Links in the description below.


Hi, my name is Minar and today I'm going to be telling you what it's like to study international sociology at Tilbury University. First, what is sociology? Well, it's an academic discipline that studies the dynamics between humanity and society. By studying international sociology at Tilbury University, you learn to see and make sense of social problems with global impact. Through this understanding, you are able to analyze social phenomena in contemporary society. You also learn that social problems such as poverty, migration, and cultural differences are related to policy, politics, law, and so much more. International sociology uses a comparative perspective on the Western world, meaning that our personal experiences and backgrounds are of great value in the international classroom. The small scale of this classroom allows for vibrant discussion and debates with their classmates. International sociology is a three-year international bachelor degree. In your first year, you take introductory courses in the field of sociology, as well as courses such as political science, economics, and psychology. You also take courses in academic skills, which is used to develop your academic writing and research methods, all of which are used in your first research project. In your second year, you choose a major in either culture or social risks. You also further develop your academic skills so that you are able to read and think critically and scientifically. The methods and statistics courses further develop your scientific researching skills. All of these are used in your second research project. In your final year, you are now given the room to develop your education according to your ambitions, talents, and interests. Alongside your minor electives and courses, you take a practical internship at an organization of your choice. This is also the time to develop your cultural experiences by taking a semester abroad.  As an international sociologist, you are an expert in social issues, which occur in every sphere of society. You can now follow a career path in several directions, such as a policy advisor at a municipality. If you are interested in broadening your social impact, you can follow the footsteps of trainees at European organizations. You can of course also follow a career path in scientific organizations, or even broaden your horizons by becoming a journalist or an opinion maker. If you are interested in how society works and how it is related to various global challenges, then international sociology might be the right fit for you.