20 Burst results for "Journal Club"

"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

04:56 min | 4 months ago

"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

"Of course you can also calculate a number needed to treat or number needed to harm as as you know what those terms mean and you can interpret them if asked but oftentimes you have to actually calculate these on your own you know. Some articles will prison this in the discussion section. But if they don't you should be able to calculate it and it. It looks good. If you include that to put into perspective in terms of How many patients you'd have to give your drug two for one patient benefit and then you know kind of the number needed to harm similar concept as you're looking at maybe in the secondary The side effect of the drug or the eighty yards. No if it's alarming really would like to see the number needed to harm if it's too small than likelihood of having that side fact it's higher to in that something pertinent your patient or earned the population. You were working with Until really the last part in arguably the most important part of that journal club is too heavy discussion. That's why Journal club discussion. This is why we evaluate primary literature is to figure out how to improve our practice in that comes from discussion among people who read the article in decide whether this should be implemented in their practice or not just because an article is published. Doesn't mean that you must accept the results in do whatever the travel did you know that comes from discussion and thinking about the other body of literature out there guidelines and things like that absolutely and again if you are including the summary of art parent article make sure it's very small ones to sing to bring everybody on the same page to carry out the actual discussion in what you're focusing. Rodion is critiquing the article you're focusing on. What was the study population wallace. The design in the interventions were statistics. We talked about earlier. And what were the end points. And how the findings at this article would make an impact to your practice and you know wanted..

Rodion eighty yards one patient two secondary
"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

04:40 min | 4 months ago

"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

"You don't have to necessarily put it in your document although you could. But you can always say referring to figure two. You can see blah blah blah blah blah of that the article that you're presenting so you know when appropriate you can leverage what is already in article to get a point across to show a result for the audience and also rising results to you. You don't have to write the entire statements of the result. Just put a little table. You know as we said you don't have to go into each and every secondary endpoint or outcome but like us the primary ones you can put him in a table format in. It's a little bit more visually appealing. And it won't look like you're reading off because you're actually explaining the results until the next step. Is you know as students are talking about the methods and things like that. It's very common that biostatistics come up. And i know that students absolutely hate talking about the section. Because they aren't confident in terms of what the different terms mean it's also very common area where receptors ask questions of the students about the methods section or interpretation of certain biostatistics that are presented in the manuscript. So we don't have time to have a full scope review of biostatistics in literature evaluation. But i think we can probably cover a couple common elements most journal clubs will at least touch on so that the audience can have a better sense of those common pitfalls and that you i completely relate to segment because i used to be one of those students in. Obviously they're much better place but we can understand. That students are generally nervous about this area. So if you if you know that that weaker area you have ahead of it and you wanna make sure what you're presenting and what the article includes you have a good handle of those biostatistics methods so for example doctor tele common thing that comes up is type one and type two air no matter what you are always at risk for one or the other type one error where you have a significant p value..

one each type one type common secondary endpoint figure two
"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

04:23 min | 4 months ago

"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

"Template you need to be concise only include the most pertinent information. You're not taking the article. In converting everything comprehensively into a word document. You want to make sure that you know you're expecting your audience to have read the article right and so even though that sticks vacation because it's kind of like a book club. Your audience may not have done that. And so that's where you need to present or summarizing article comes from but summary should actually garner much much smaller attention in that critiquing the discussion at the end. It should be the larger off the the presentation yet. You're just trying to get everyone on the same page. Were if they read the article a week ago they can some pertinent details and if they didn't have the opportunity to read it yet but they wanted to attend your presentation then they can be up to speed in terms of what was the core stuff about the article in terms of methods results. Things like that. So you're trying to be comprehensive. You're just trying to get everyone on the same page so that everyone can participate in that really high quality discussion. That you're gonna have later so again just to reemphasize. The common pitfall here is that you have way too much stuff in that journal club document. So doctor told what are some things that tend to be like excessive in the journal clubs that you have on your rotation..

a week ago
"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

02:56 min | 4 months ago

"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

"And i wanted to know more about what would that benefit be patient like mr jones. That's an awesome way to setup that presentation where people are automatically entrusted because it's relevant to that rotation. Maybe other people in that room even knew who mr jones was in this potentially could impact mr jones's care. I think that's a great way to kind of tie everything together. Before you start that presentation and of going along with that declaration. I think it also helps generate that discussion at the end to. You can use mr john. As a case for those who weren't involved in his care to engage them in the at the end it's all i think it's very important one thing not to do even though you might be comfortable but this is present your didactic years journal of into an app Tation your role. Find out to make sure you're going with the fresher article fresher topic something that you can increase your knowledge and that being said i would usually want my students to pick something more recent or things that are still relevant. My recent definition is no more than two years old Just because if the article is too old than likely that everybody in the audience knows about that article you not really adding to that knowledge. It's been presented already. And then you you wanna make sure it's relevant because if a new guidelines come out of your treatment comes out that trump's the standard of care in the standard of care is no longer standard of care than you. Don't wanna present that article you wanna present what's new and what's part of the deadline or potentially what's new that could change the guidelines. Because it's so impactful i think that's great and you know dr patel once you figure out that perfect article even if you're precept your doesn't require it you really should be asking them for permission for that particular article most rotations. They're going to the precept. Allow you to pick your article. They're gonna want to approve if they don't as if i was a student. Absolutely go to the precept and make sure that the article that i picked is consistent with what their expectations are so that everyone's happy at the end of the day. Your this is kind of like getting the lineup. Before you start your article draft you wanna make sure that it's because then all that work is going to be basted exactly. What will you know once you pick that perfect article. The next step is to likely summarize the article in journal club. Template format different preceptory. Different sites may have a template or they may ask you to use your universities template. And i think the this is where journal club start to get their bad rap. Is that students. Have this perception that everything needs to go in this template in your converting a ten page. Pdf manuscript into a five page uber. Small text word document. That has all of the information. That's in the manuscript and at that point..

ten page five page mr jones mr john trump uber dr patel two years old one thing more than
"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

05:45 min | 4 months ago

"journal club" Discussed on HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

"I'm your host actor kane in the title of today's episode is the first rule of journal club is that we don't talk about journal club today. We're talking about basically from a student. Perspective had excelled in your next journal club presentation or discussion. All while avoiding some of those all too common pitfalls that dr patel and i commonly see in students when they do present on their p. for appier rotations so As abbot receptors. We have these students with do journal clubs and really you know these general clubs or something that we learned off of to want to make this a very good learning experience for everyone but make students successful as well so in this episode. Today you're hoping to kind of focus on you. Know what makes you like a superstar of and you're presenting your journal club and kind of some of the common pitfalls to avoid that every precept or or even the audience member who attend would want you to avoid the dr patel. I'll be honest with you. Know the word journal club depending on what hospital system. You're in sometimes is almost a dirty word. Because it's synonymous with a student generating a four page word document in reading every word of it that summarizes another article. You know historically. I used to bring coffee to these journal clubs attend because they would get so boring because a student would just talk and read off of a document for forty minutes and there was no discussion or very little discussion. So one one thing. That i think everyone precept. Students can do better is making this more of an interactive experience and active learning experience. And we're going to go through some tips and tricks with respect to that today. I love that. And i think the first thing we need to do is making sure we have the right journal article to talk about so. I usually advise my students to make sure that they kind of tried to go with the randomized controlled trials. It could be either placebo or active control. Depending on the disease or the treatment you're dealing with but these will be the best articles all the other ones such as the observational trials or meta analyses are not just the best to discuss in journal club format and i found dr patel with those non randomized observational trial. Students sometimes jump to conclusions inappropriately so because of the lack of innovation these are intended to be hypothesis generating and they're not really intended to influence. Your clinical practice in students wrongly conclude that association means causation in these trials in are so many other limitations to these non randomized trials. That students don't pick up on so it tends to be a little bit more of a minefield. The same is true with meta analyses so most of pharmacy schools will emphasize these randomized controlled trials. And we'll talk about meta-analysis but if you as a student or a precept your don't know what awaiting means or is square to random effects models in meta analyses than you may not fully understand the methods used in that meta-analysis and again it's kind of a minefield for student where you're more prone to having a misunderstanding of the methods of the study or even the conclusions and another thing. I always try to ask students to try to pick a topic that you're interested in or you want to learn more about because this is also an opportunity for the students to grow their knowledge rate and so pick a topic satisfy time when the nabet studying category because it's gonna presentations requires students to dine into reviewing guidelines other articles that are similar to The article they're presenting. And i was the other pertinent literature about the topic in general..

Today forty minutes first today kane four page one dr patel first rule one thing patel
"journal club" Discussed on a16z

a16z

04:52 min | 7 months ago

"journal club" Discussed on a16z

"I'm on all editor-in-chief at Hendrickson Horowitz and what follows is the very first episode of Journal Club would you actually heard me introduced to the stroh feed much earlier this year, but it is now part of our separate show bio eats world a podcast all about how biology is technology as a reminder journal club dives deep into a new scientific article with the authors of said article and or. A six Z, and other experts on the implications of the breakthroughs, as well as how to translate them from paper to practice if you'd like to continue receiving Journal club episodes produced and hosted by ESIASON'S Z. Bio editor. Lauren Richardson please subscribe to bio eats world wherever you get your podcasts and if you'd like to learn more about the expanding a six Z podcast network, please visit a six dot com slash pod network. Thank you for listening. Tie I'm Hannah and welcome to bio eats world I'm Lauren, and this is the first episode of Journal Club so tell me, what's Journal club all about. So Journal clubs on Thursdays, and this is where we take a recent scientific article and discuss it either with the authors of the paper or with our own internal experts here at a sixteen Z, and we highlight what the paper shows, what new opportunities it presents an how to. Take those research findings from paper to practice. Okay. So tell me what's this first paper? All about the first paper is titled License on Targeting Cameras For degradation of extra cellular proteins and it was published in nature. That's a lot of words what they actually means. The basic idea is that diseases are often caused by proteins that have gone haywire in some way. So there's either too much of them or their present in the wrong place. At the wrong time and the idea here is to create a new kind.

Journal Club Hendrickson Horowitz Lauren Richardson stroh editor Hannah
"journal club" Discussed on a16z

a16z

03:21 min | 8 months ago

"journal club" Discussed on a16z

"Unless we're storing a youthful phenotype kier immune system's ability to target these cells. We've talked a lot about how effective this was, but let's talk about what the limitations of actually using these therapies and getting them into people are. First of all studying anything in the field of aging and finding clinical benefit of removing the Essen cells poses its own challenges in terms of how you study this in the human population as well. Understood, you can't really have clinical trials for aging per se because they would literally take a lifetime to conduct, and so then the question becomes like right? What are the right and two points what of the Wright markers that you should be looking for to demonstrate and determine whether there's clinical benefit for removing senescence cells, some of these complex chronic conditions so that wouldn't be without its challenges. And then the second one from a very practical standpoint, it's you're looking at. Using complex modalities like Kartini therapy to treat a broad range of diseases. It presupposes that we're going to be able to address a lot of the challenges that are inherent developing Kartini rt therapies like the cost of manufacturing like whether or not these needs to be autologous. In other words, the T. cells are engineered from the patient themselves or can they be allogeneic where you can have a universal donor that would reduce the cost of developing these therapies and increase their ability to scale from a manufacturing standpoint there's a lot of challenges associated with these kinds of new modalities would have to be addressed if we do eventually want. To See this more broadly applied across a range of diseases. Right. Perhaps, if we're able to show that car T. cells can be transformative in so many different diseases that will drive innovation in this area, and if they were just for blood cancers, which is such a small portion of cancers than you could see it staying really expensive in each. But whereas if it's for a lot of different things, you know then perhaps they'll be enough of drive to really make this feasible from a cost standpoint and from a scientific standpoint I think another thing is. Of course, in this paper, we saw a lot of promising in Vivo. But we also saw that mice treated at the super therapeutic dose. Did see rising serums at a guy owns this really typical for Cardi therapies in having cytokine release syndrome spots, and so for cartoon therapy to be really translated from the lobster clinic getting the dosing right for humans is non trivial. A key nextstep actually spend time to refine the sal engineering component and then also incorporate different things like safety switches. combinatorial strategies, other types of synthetic promoters that might drive safer expression. All of these things are going to be key for the Gen, two version of this innate a Cartesian out before actually makes its way all the way to human.

cytokine release syndrome Essen Wright
"journal club" Discussed on a16z

a16z

03:29 min | 9 months ago

"journal club" Discussed on a16z

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cancer clarence tencent Yori Natalie Tinker T. Therapy grimes Doug
"journal club" Discussed on a16z

a16z

10:07 min | 9 months ago

"journal club" Discussed on a16z

"Hello and welcome to the a Sixteen Journal club I'm Lauren Richardson this is podcasts where we cover recent scientific advances why they matter and how to take them from proof of principle to practice. Antibiotic Resistance is an urgent problem, but many aspects of how bacteria acquired this ability to evade the drugs designed to target them. The steriods and is not always clear whether the conditions that drive the evolution of resistance in the lab occur in patients suffering from bacterial infections. This is where the work of Natalie, Balabagn a professor at the Hebrew University and my guest. Today comes in. She joins me to discuss her article published in science titled Effective Tolerance on the evolution of antibiotic resistance under drug combinations. The work is based off of previous research done in her laboratory and importantly uses samples from a patient with a life, threatening bacterial infection to understand the conditions that lead to multi-drug resistance in a hospital setting. The work reveals how the ability of bacteria to develop tolerance, which we also refer to as dormancy or slow growth can act as a steppingstone to assistance and can. With the efficacy of drug combinations. Our conversation covers what tolerance is the conditions that promote tolerance how it leads to resistance and impacts, drug combination therapies, and lastly integrating this new understanding into clinical microbiology protocols years our conversation. How. Would you describe the big question that this work had to address what we are seeing on? Their other medications are occurring before when but cer exposed to onto badly, actually promoting the fixation of resistance mutation, and this will typically go completely undetected, because they don't really unfair resistance, but they are making the resistance mutation. Develop a much easier so their mutations that happened before resistance is developing that promote resistance exactly, and then we found that it was more general that that was not only mutation because a behavior of Bardiya. Can Be concerned by mutation, but can those from third by external edition, this behavior of his ability to become domains old more slower in wants to enter the state of. Dormancy all slow gross, it turns out that they have the ability to become resistance too much higher rates than if they don't.

"journal club" Discussed on a16z

a16z

05:55 min | 10 months ago

"journal club" Discussed on a16z

"Hello I'm Lauren Richardson and this is the a sixteen z Journal club our podcast where we cover recent scientific advances why they matter and how to take them from proof of principle to practice. For this special holiday weekend edition. We've got something a little bit different. In this snack size as the showed a sixteen general partners Vj Ponte. Conde. Join me to discuss an opinion piece published in nature reviews, drug discovery called breaking. Even law even saw. Is Moore's law spelled backwards? Whereas Moore's law describes technologies becoming exponentially faster and cheaper over time, even slot describes the trend of drug development, becoming exponentially more and more expensive overtime. In breaking a rooms law, the authors analyzed the data since two thousand ten and find that 'cause appear to have stabilized over the last ten years. What has contributed to this critical and exciting trend shift? In our conversation or hey and VJ discussed their views on the technologies and policies impacting this trend and their opinion on whether even saw is broken for good. We start by discussing the three possible factors for the shift cited in the breaking, even saw article with the first being quote better information in my mind. There's sort of three vectors that are converging that. I think become increasingly important. When it comes to impacting productivity in there for rooms law, the first one is the fact that we can generate increasingly broad array of data across the various ways in which biology transmits information, so we can do genomics transcript. Oh, mix, we can do. Proteome mix all of these things that increasing scale. The second point we can also do them at increasing resolution. Go now increasingly down to a single cell level, which in many cases the sort of the functional unit of disease that single level. Effect that we can query biology at that level of resolution, I think also makes a big difference. And thirdly we can take all of these various streams of information. And make better sense of.

Vj Ponte Moore Lauren Richardson
Therapeutic Video Game on Trial

a16z

05:56 min | 10 months ago

Therapeutic Video Game on Trial

"Today's episode covers the topic of Digital. Therapeutics given that earlier this month. The FDA approved its first ever prescription video game. And since this is journal, club, we go into one of the key clinical trials, underpinning this historic decision published recently in Lancet digital health by Scott Collins and colleagues, which evaluated this games ability to improve attention and kids with attention, deficit, hyperactivity, disorder, or adhd. Are Sister podcast. Sixteen minutes on the news also covered this topic debating the bigger picture. Questions of what is an isn't a digital therapeutic and where pricing and regulation comes in. You can find that episode at a Sixteen Zero Dot. com forward slash sixteen minutes. A sixteen. Biodiesel Team Partner Former MD entrepreneur. Justin Larkin joins me in this discussion where we cover the pros and cons of this video game compared to traditional pharmacological therapies. The game specifically targets the attention impairments in twelve year. Olds by having them help an Avatar navigate digital environment in the face of other distractions. We also discussed how the randomized controlled clinical trial or are. CT was designed the limitations of the study and the open questions to be addressed. Will you begin with what question this paper answers? Video game via digital therapeutic and I think this paper resoundingly answers that question of yes, a video game target, a specific mechanism of action can have advocacy to cross that threshold of being considered at their pubic, but then I think more importantly is. Can this specific video game have an impact on a child with Adhd? To the point where it could be considered a tool in the toolkit of physician, treating this patient and I would argue the resounding answer from this is certainly this is considered, both because it there's an obvious benefit, but also the risks associated with it proved to be pretty minimal. There's plenty more research to be done, but I think this does a great job at answering that in the subsequent FDA decision just went on to reinforce study further. My favorite part of the paper was getting to watch that supplemental file, showing the kids video game and see what the kid seems and being able to connect that to kind of the goals of the game. If you're to watch that video outside of. The context of knowing that this was coming from a digital therapeutic company or clinical trial. You probably wouldn't know that it was a digital therapeutic. You'd probably think it was any other game that our kids are playing these days, but I think the opportunity for digital therapeutics that creates an environment where a therapeutic can actually be enjoyable, can actually be entertaining, and the really cool thing about this program is that it learns it's able to know what the kids ability is, and then Taylor the game, and how hard it is based on how quickly they pick it up and it's always responding to that level of engagement as a kid learns to adopt those skills. If you think about nutritional therapeutic lake uphill. There's opportunity for real time iteration of the therapeutic. There's no ability to say hey. This person is responding great, so we're going to cut the sing off. This person isn't responding, so let's up titrate the dose. Where in the game there's this ability in real time to iterative on how the person's experiencing that there. Yeah. I've known kids with ADHD and some days. They have good days and some days. They have days where it's more difficult being able to have that happen. Real time seems really appropriate for this type of condition. I think it's a really great match. Between kind of underlying mechanism, underlying patient characteristics in the method of delivery of the therapeutic, so there's proof of concept evidence from previous studies. This therapeutic video game can help kids with Adhd, but this particular study really test that hypothesis with sophisticated and careful clinical trial design, so let's dig in now to some of the important details of the study, the built upon the pita studies by having truly randomized controlled trials. So this is where there's a control group women interventional group getting developed intervention, but then also importantly, all of the researchers involved were blinded to the intervention. Of Selves and the patients themselves are blinded to whether in the intervention group or not, so the control group also got a video game, and it was a word search game that it also learned was also rewarding, and also had a lot of the same kind of game design elements, but that video games doesn't target those same pathways that are issues. ADHD, an important is also used a method called the intention to treat meaning all of the people that were initially stratified into the two groups were included in a statistical analysis, regardless of whether they completed or not so really meeting at the top level criteria what it means to be a rigorous are ct for therapy. Yeah. This study is pre registered, and so the idea behind Predrag distraction. Is that you as a researcher? Lay Out exactly what you're going to do before you ever do the study how you're going to collect the data how you're going to analyze that data, and importantly you determined to be a significant outcome before you look at any of the data and that really help prevent that kind of post talk. We looked at the data. We see this as significant. Therefore, this is important. You're saying from the start. This is important and will only know if our study is successful if it meets this particular endpoint. To Study Island, importance of having got foresight in the design, but also another thing that was interesting in the study was the choice of outcome metrics traditionally adhd research. A lot of the outcomes have been focused on the number of different metrics and batteries of surveys, subjective measures to assess symptoms of adhd whereas this particular study use a measure called the Tova Api. That's Te'o via API, which is really focused on assessing objectively attention. They picked an outcome that really got out. Some of the core impairment comes along with Adhd and then a lot of circumstances is equated with some of the challenges. Kids have in the classroom and other settings.

Adhd FDA Sixteen Zero Dot. Study Island Researcher Scott Collins Mechanism Of Action Biodiesel Team Partner Former Justin Larkin Taylor
"journal club" Discussed on a16z

a16z

02:04 min | 10 months ago

"journal club" Discussed on a16z

"Hello and welcome to the as Sixteen Journal club.

"journal club" Discussed on a16z

a16z

03:05 min | 10 months ago

"journal club" Discussed on a16z

"Explore entirely <Speech_Female> new <SpeakerChange> chemistry that <Speech_Female> we've never seen. <Speech_Female> Yeah, in this kind of <Speech_Female> can even get us <Speech_Female> back to what we were talking <Speech_Female> about at the beginning, <Speech_Female> which was like how <Speech_Female> bad <Speech_Female> re Bisco is <Speech_Female> as an enzyme, <Speech_Female> reb iskoe originally <Speech_Female> evolved <Speech_Female> in <Speech_Female> environments <Speech_Female> where there was not <Speech_Female> a lot of oxygen, <Speech_Female> so as before the <Speech_Female> great oxygenation <Speech_Female> of the atmosphere, <Speech_Female> and so <Speech_Female> this problem <Speech_Female> with substituting <Speech_Female> oxygen <Speech_Female> for carbon dioxide. <Speech_Female> Just wasn't a thing <Speech_Female> when it first of all. <Speech_Female> And <Speech_Female> as Oxigen, <Speech_Female> increased in an <Speech_Female> atmosphere, it <Speech_Female> had to start making <Speech_Female> trade offs between <Speech_Female> the specificity <Speech_Female> of <Speech_Female> whether it chose <Speech_Female> oxygen <Speech_Female> or carbon dioxide, <Speech_Female> and it's efficiency, <Speech_Female> so it <Silence> could be more efficient, <Speech_Female> but <Speech_Female> then it would incorporate <Speech_Female> oxygen more often, <Speech_Female> versus <Speech_Female> it could be <Speech_Female> more specific, but <Speech_Female> then it would be even <Speech_Female> slower. <Speech_Female> So if <Speech_Female> you're designing <Speech_Female> a system to <Speech_Female> Novo. <Speech_Music_Female> Is there a way <Speech_Female> to <Speech_Female> bypass <Speech_Female> some of the <Speech_Female> evolutionary <Speech_Female> inherited <Speech_Female> trade-offs <Speech_Female> and make something that's <Speech_Female> just more <Speech_Female> finely tuned <Speech_Female> to the situation <Speech_Female> that you want to design <Speech_Female> so evolution's <Speech_Female> always lagging <Speech_Female> behind how the world <Speech_Female> is changing, which <Speech_Female> is exactly why we're <Speech_Female> Bisco has evolved <Speech_Female> for a world that <Speech_Female> we no longer live in, <Speech_Female> but <Speech_Female> but humans <SpeakerChange> can adopt <Speech_Female> much faster. <Speech_Female> That's like an <Speech_Female> interesting philosophical <Speech_Female> idea that people <Speech_Female> will say. <Speech_Female> Evolution <Speech_Female> has on <Speech_Female> infinite creativity <Speech_Female> like we could never <Speech_Female> think <Speech_Female> of the things. <SpeakerChange> Abolition <Silence> <Advertisement> has created and. <Speech_Female> I <Speech_Female> think that's true to some <Speech_Female> extent, <Speech_Female> but. Is Fundamentally <Speech_Female> Limited <Speech_Female> to be <Speech_Female> designs <Speech_Female> <Speech_Female> that are within of <Speech_Female> certain <Speech_Female> distance of <Speech_Female> the designs that <Speech_Female> are out there nature today <Speech_Female> you're not going to get <Speech_Female> a really huge <Speech_Female> rapid change <Speech_Female> in an organism, <Speech_Female> just because it wouldn't survive <Speech_Female> that sort of transition <Speech_Female> period, <Speech_Female> so there's all <Speech_Female> of these transitions. <Speech_Music_Female> Evolution <Speech_Female> can't pass through, <Speech_Female> but we can <Speech_Female> as humans, <SpeakerChange> so <Speech_Female> I actually think <Speech_Female> in a lot <Speech_Female> of ways human creativity <Speech_Female> can go way <Speech_Female> beyond what <Speech_Female> evolution has made <Speech_Female> and I think there's a ton <Speech_Female> of opportunity <SpeakerChange> <Speech_Female> here. Yeah, it's I. <Speech_Female> Don't think it's necessarily <Speech_Female> about <Speech_Female> being better than <Speech_Female> evolution. It's <Speech_Female> learning from evolution <Speech_Female> <Speech_Female> and seeing <Speech_Female> all the different <Speech_Female> ways that <Speech_Female> evolution has <Speech_Female> functioned and <Speech_Female> then kind of taking <Speech_Female> you. You know the best <Speech_Female> of the best in matching <Speech_Female> our own <Speech_Female> our own <Speech_Female> knowledge <Speech_Female> and you know <Speech_Female> what a I will <Speech_Female> be able to provide to us <Speech_Female> as like even <Speech_Female> beyond our knowledge <Speech_Female> is like new <Silence> ways of looking at <Speech_Female> these problems <Speech_Female> in these solutions <Speech_Music_Female> and say and <Speech_Music_Female> like being able to input <Speech_Music_Female> them in completely <Speech_Music_Female> creative <Speech_Female> ways that you <Speech_Female> know evolution <Speech_Female> hasn't hasn't <Speech_Female> found yet and neither <Speech_Female> people. <Speech_Female> Thank you, judy <Speech_Female> for joining me on. Turtle <Speech_Female> Club this week <Speech_Female> to sum up. We are <Speech_Female> excited about this work. <Speech_Music_Female> As it demonstrates <Speech_Female> that you can improve <Speech_Female> the process of carbon <Speech_Female> fixation <Speech_Female> and link it to the natural <Speech_Female> photosynthesis <Silence> machinery from plants. <Speech_Female> This <Speech_Female> bio engineering solution <Speech_Female> could be applied <Speech_Music_Female> to our crops to improve <Speech_Female> growth, efficiency <Speech_Music_Female> and carbon <Silence> dioxide sequestration. <Speech_Female> That's <Speech_Female> it for Journal club <Speech_Female> this week. <Speech_Female> You can find all these <Speech_Female> episodes at A16. <Speech_Female> Z Dot, com <Speech_Female> forward Slash Journal club. Thanks for listening.

Oxigen Novo.
"journal club" Discussed on a16z

a16z

03:48 min | 10 months ago

"journal club" Discussed on a16z

"Enzyme evolving to be better, there's entirely mechanical systems of all like open, and these pores in the plant cells to be able to let in more or less oxygen at different times of the day, and it's this highly complex thing that has evolved to make up for the just poor efficiency of one enzyme. The Tobias Herb lab developed essentially a synthetic calvin cycle so. So it's a different method for fixing co two into some sort of carbon containing substance icee dark cycle, you say Calvin Cycle Fun factoid is that it's actually the Calvin Benson Bassim Cycle, but Bassam doesn't want his name. Include it because he thinks it's a disservice to all the students that worked with him on the project, so he has requested that it be called. Called the Calvin Benson Cycle in the two thousand sixteen article that you mentioned authors developed this very cool synthetic pathway for Co, two fixation that did not use for Bisco instead. It used a combination of seventeen different enzymes from nine different organisms. That could do this dark face half of the reaction ten times faster than the plant version that does rely on were Bisco. And they called this the catch cycle or the C. E. T. C. H. Cycle in the previous paper. They sort of cheated by in these enzymes that would just produce an ADP H. and ADP as starting points for bear, synthetic carbon fixation cycle so that they can kick start the part of the experiment that they really cared about in this new paper, whether doing is adding in a module to create that any deep in that. ATP That is light driven, so it doesn't require at the experimentalist to add in these enzymes or to add in the substrates for these enzymes. Yeah, what they're doing here is. They're linking the light cycle so the photosynthetic. To dark cycle, the carbon fixation part, so the goal is to have this own self sustaining reaction. That's what plants are, so let's talk about the implications of this research. The biggest and most interesting implication here is that you could use some of the insights from these papers to upgrade plants perform in the idea to basically counteract some of the evolutionary pressures that were present when we weren't using these plans for crops or to sort of make up for some of the inefficiencies of natural selection like for example, re Bisco being about enzyme. This entirely new cycle for doing carbon fixation could really dramatically increase the rate of carbon fixation and the rate of growth for plants that we use crops, these synthetic chloroplast that they created are actually more efficient than natural chloroplast, and that's because they don't. They don't have Bisco which is slow, and they also don't suffer from photo respiration, which is wasteful process. You're talking about where we're Bisco uses. Oxygen instead of carbon. Carbon, dioxide, and in most plants they waste about twenty five percent of their energy from photosynthesis on photo respiration. So there's this way in which you kind of get around the photo respiration problem with something like these synthetic class when we think about on a global scale, the carbon cycle, and if we're concerned about release of too much carbon the atmosphere, there's sort of an interesting class of solutions here which is. is to increase the rate at which are crops poll carbon dioxide out of the atmosphere, and that kills two birds with one stone. One is that it increases your efficiency of of food production, and at the same time you're removing more carbon dioxide from the air. You're actually using it for something useful. Yeah, that's possibly a very elegant solution. Let's dig into these methods and results now so in plants. Photosynthesis happens in..

Calvin Benson Bassim Cycle Bisco C. E. T. C. H. Cycle Bassam Co ADP
"journal club" Discussed on a16z

a16z

02:29 min | 10 months ago

"journal club" Discussed on a16z

"These are hugely powerful processes have generated essentially all the organic matter on earth from the wooden trees to our own bodies. But these processes also aren't perfect and scientists have for decades been trying to make them more efficient. The two articles that we discussed today we're both published in the journal Science and are both from the lab of Tobias at the Max Planck Institute for Terrestrial Microbiology. The first article published in twenty sixteen develops synthetic pathway for the fixation of carbon dioxide in vitro. The second article, which was published in. May combines this synthetic carbon fixation pathway with the natural photosynthetic pathway isolated from spinach to create a synthetic chloroplast. This combination of natural and synthetic components to improve the efficiency of these pathways as a number of potential applications, including engineering our crops to grow faster. Judy and I discuss these exciting applications of evolution has restricted the efficiency of carbon fixation, and how these bio engineered solutions get around that problem and the use of micro fluids for vastly improved experimental design. The first we start with a discussion of why the dark cycle this process of carbon fixation is not as efficient as it could be. The key thing here is that the dark phase has this great limiting step, which is this enzyme known as Rube? ISKOE is just super slow, and that's the first enzyme in the pathway that binds carbon dioxide, poor older, Bisco, when I imagine it, it's like an old man enzyme with like a long white beard, and it makes a lot of mistakes, and it goes really slow but it. It evolved really early on, and then was a key requirement for these organisms to live. Furthermore Rib makes a lot of mistakes, which is that it often subs in oxygen molecules for carbon dioxide molecules said there's huge body of work trying to evolve risk to better, but as it stands. Our plants are stuck with this really old enzymes that is not as efficient as it could be. Yeah instead of evolving rube, Iskoe, it seems like plants have evolved kind of everything around it, so there's all different classes of plants that have modified to support the slow cycling of Rubik's going to be efficacious in different environments, and to limit the air as you call it of of Bisco which is also known as photo respiration kind of crazy that rather than this enzyme..

Bisco Rube Max Planck Institute for Terre Iskoe Tobias Judy Rubik
"journal club" Discussed on a16z

a16z

06:26 min | 11 months ago

"journal club" Discussed on a16z

"Inhaler go about your day instead of wearing a mask. And what do we think about safety for these things and safety for delivery and safety for the Crisper Part? The crisper part seems utterly straightforward. Because is going after Arne. It's not editing. Your genome could be the delivery. Part now becomes the real question. Can we come up with delivery where it could be done multiple times in weight of safe so AV is typically the gold standard for gene therapy delivery? These ADN associated viruses are approved therapies. Right now these are what we call one and done treatments because your body will develop immunity against this gaps. If this all works out well this could be a universal krona virus or Flu Vaccine. But if you think about re administration every single year you'd probably want something that is less mutagenic. The other big problem is immunity. Necessity of Christopher nucleus is a lot of the common crisper nucleus that we use do come from pathogenic sources. There are people that are developing new forms of New Claes's Cassocks for instance that might have come from non pathogenic sources that could be used in the less committed. Jennifer Fashion Crisper cast. Nuclear is definitely a a hardware platform? If you think of it in the molecular sense all of the concepts that they showed here in this paper you can apply it not only to cast their team but also differ. Nucleus or even liber- nanoparticles non viral approaches. Different ethic peptides. That also shown to deliver cast. Nine nucleus is really well could be combined here and so we can also think about. How do we engineer better crisper system that utilize the same platform but a lot of the stuff and the foundation? That they've developed can be play. Do you think that the hurdles that we just discussed with safety delivery immuno-genetic city we easier faster or more feasible to clear than the hurdles facing a vaccine for copay nineteen or is it just anyone's guess right? Now there's a couple different scenario. So one scenario is were antibody dependent enhancement. Ad is actually a real serious difficult problem. That can't be cracked if that's the case then this looking pretty good. In comparison there's another scenario where Vaccine becomes much more to like an influenza vaccine and so a more traditional approaches work and then this might be harder unfortunately with Kovin. A lot is still unknown. One I'm thinking about is not just planning for what we can do to help. Covert in two thousand twenty and twenty one. But what would we do about the pandemic that could be in twenty thirty or twenty five if you look at the timing between these pandemics using about SARS and Murs and covert the years between them becoming fewer and fewer? If that's the case having a broad spectrum sort of programmable ish approach that could be brought out very quickly. That's particularly intriguing. Though validating crisper approach my take longer and it might span this current one. You know if we get this moonshot right. We can dramatically save time for all future bendix basically sidestep. There's really linear passive vaccine development. Okay so we've discussed the scientific hurdles that therapy like this would still have to overcome but assuming they were overcome. Are there strong business models and incentives for prophylactic treatments or does it suffer from some of the same headwinds as antibiotics and traditional accedes? Yeah I think if you think about the modern record of producing vaccines. It doesn't really inspire that much confidence because if you think about SARS Cov one Mersey Coppola all really provoked these similar arms race to make vaccine if you will and today only if the bowl effort has been successful and the vaccine was approved basically last year five years after the epidemic really happened. Well learn you talked about. Comparing this to antibiotics thing about. Antibiotics is said we intentionally don't give them out because we want avoid resistance and that's what's economics event novel antibiotic so challenging because If you have a great antibiotic it goes lock box and doesn't get used. This is actually upside down for a couple of reasons. One it inherently is engineered to grafter resistance in that a few mutations. And they're going to make a big deal and then secondly I imagine that it would be the type of thing going lock box. It would be heavily manufacturing distributed such that everyone would have available so that I think there would be a real commercial vantage doing something like this so for those two reasons. I think this becomes almost opposite of what we're seeing antibiotics. I think you know thinking about this. Whole economic context governments and institutions spent billions of dollars every year on nuclear weapons that they hope to never use how about we spent a couple of billion to build these plants and teams who equip ourselves to handle the next upper pandemic. Think that's excellent point. Turn it into a national defense issue and not just a health. Market health demands issue. It's interesting to think about. What can we do either to have a response? Already or to engineer something rapidly in response to something being a threat I think the old style sort of military topgun like war where it's GonNa be our fighter jets against other fighter jets becomes less and less of a reality. Bioterrorism becomes probably a much more insidious threat I mean. These vaccines remained the best. Virtually only weapon against these viruses and bioterrorism. So it's GonNa be a mission critical defense mechanism going forward so one last thing and this may be more SCI FI. It's interesting to ask. Could sort of a crisper approach a true broad spectrum antiviral for like all viruses and especially given the nature viruses and how they spread with a population the ability to tackle these things early means that they don't spread which means that we don't have these crazy pandemics anymore that would be the ultimate fantasy. Thank you both. And thank you for joining the A sixteen Z Journal. Club this week to recap. This research shows that it is possible to program a crisper based system to target both krona viruses and influence to prevent infection. There are a number of challenges still to overcome especially as these results are only in a cell culture model but there is huge potential here to create a broad range kroth electic treatment for viral infection and advances in engineering. Biology will take us. There will continue to discuss related themes other a sixteen Z podcast episodes..

engineer Flu Vaccine Christopher nucleus Arne influenza Kovin Jennifer Fashion Murs Z Journal Coppola
"journal club" Discussed on The A&P Professor

The A&P Professor

02:46 min | 1 year ago

"journal club" Discussed on The A&P Professor

"Hey I have some exciting news. We have a new kind of segment plan for the next episode. Or maybe the one after that these days. I've learned that one must not make plans based on the world staying on. Anyone assumed trajectory but soon I hope what is it I can tell you. It's not a book club we already have one of those and won't be getting a new book club recommendation soon. So now it's not a book club. It's a journal. Club the ADP Professor Journal Club. And we have a new voice joining in for that one. It's a voice that we've heard before on this podcast and a voice that you may have heard before if you've been active in town hall meetings or in Triple A. Or any of a number of other venues including her own journal articles on teaching and learning. It's my friend. Krista Room Polski who is an associate professor at Moravian College in Bethlehem Pennsylvania and part of the ANC authoring team over at McGraw Hill? Every other month or so she'll be bringing us a journal Article She's found. That helps enlighten us about evidence based approaches to teaching amp. I have a link to the first journal. Article in the show notes in the episode. Page if you WANNA read ahead and perhaps send in your recorded reaction but you don't have to read ahead. Don't worry about that. Crystal will be summarizing. The article in the Journal Club segment. And then she and I will be discussing it a bit as always if you have any ideas to share about that or any other feature of this podcast or perhaps a new feature. You'd like to suggest. Please let us know so that we can better meet your needs. Hey let's have a peer review. Wait we already have that. It's called the listener survey. I don't have nearly as many of those in is. I'd like to have so why not go to the? Ap Professor Dot Org Slash Survey Right now and tell me what you think anonymously. Of course this is professional peer review or after all right searchable transcript and a captioned audio Graham. This episode are funded by AAA the American Association for Anatomy at Anatomy Dot Org. Did you know that if you're looking microscopic images to use remote teaching triple a? Has You covered? They have something called the virtual microscopy database or Vm. De.

ADP Professor Journal Club Article Krista Room Polski Journal Club associate professor Professor ANC Bethlehem Pennsylvania McGraw Hill Moravian College American Association Graham
"journal club" Discussed on a16z

a16z

12:44 min | 1 year ago

"journal club" Discussed on a16z

"Featuring senior author Jim Collins called all about synthetic biology in this next segment a sixteen Z by odeal partner. Judy Savitskaya and I discussed two articles on the novel. Corona virus causing the cove in nineteen pandemic. The first article is structure function and anti jesty of the SARS. Cove to spike glycoprotein by Alexandra Walls David Visa and colleagues published in cell. We refer to this article throughout as walls at all or the walls paper. The second article is cry. Em Structure of the 2019 NCO vs spike in the pre fusion. Confirmation by David Rob Neon Chong Wang Jason McClellan and colleagues published in science. We refer to this article as rap at all note that these two articles use different names for the novel. Current virus SARS co V. Two versus two thousand Nineteen NCO V. Which was the original name for the novel Corona Virus but it has now been settled officially as SARS Cova too and this is a bit confusing because the virus that caused the pandemic SARS which is an acronym for Severe Acute Respiratory Syndrome primarily in Asia. In two thousand to two thousand four is called. Sars. Co V. They're both CORONA VIRUSES. And they're both closely related and each of these articles that we discuss compare SAR cove which we informally refer to as two thousand and two SARS with SAR cove to which we refer to as twenty nine thousand nine SARS finally one last bit of important context sell the two papers also have similar experimental designs. Were they investigate? How this protein binds to the host cell and whether antibodies that recognize two thousand and two SARS Spike Protein will recognize twenty nineteen SAR spike protein? This is important because it helps guide vaccine and drug design since the results of the two papers are not identical. We discuss why this might be and what we can learn but first we start with the similarities. Both of these articles are comparing and contrasting these spike proteins on the current corona virus with two thousand and two SARS virus this really important of the structure of the Spike version. Because that's the part of the virus that is actually gonNA find to. The host cell is really important to know where it binds on the host cell what protein it's using which has been discovered to be ace to. That's the same protein that the two thousand and two SARS virus used to infect human cells so once we know the structure of the spike protein. We can start to understand how it's actually entering cells and have some hypotheses for what types of drugs or what particular molecules could be used to disrupt that interaction and actually treat this disease or prevent the ability of the virus to initiate an infection into new cells. This protein is also really important because it's exposed to the immune system and so that's where antibodies will probably bind to the virus so speaking of the immune system one of the really interesting aspects of these viruses the spike proteins are covered in different sugar like molecules and those are actually sometimes called. The glide can shield which is Glen for sugars and then shield because they actually prevent the immune system from recognizing the viral proteins as easily as otherwise. Could both these papers showed that there are a lot of like ends on the spike protein of the two thousand nineteen SARS virus but that they actually differ very slightly from the two thousand and two SARS virus overall? The structure was super similar. But there is one key difference. Do you WanNa talk about the fear cleavage site. This cleavage a really key part of the mechanism for viral entry. So the mechanism for the virus to get into the cell is actually a sequence of about four steps the first just the virus arriving at the lungs once it arrives at the lungs the spike protein will bind to the ace two receptor which has been now shown in multiple different papers and then proteins that are on. The surface of the salad called proteases will reach over and cleave a piece of this spike protein. And that helps to pull the virus in closer to the cell to the point where a fusion can occur between the members and so at that point the viruses inside the solid it can replicate why has been found in the SARS twenty nineteen virus versus the two thousand and two virus is that there's an additional cleavage site an additional set of amino acids in the protein that are cleaved and that's called a fuhr insight and that is not present in the two thousand two virus so there's some hypotheses out there that this fewer in cleavage occurs. I actually enhances the probability in the success of the second cleavage in subsequent viral entry. So there's some theories that the reason this virus is actually more effective at infecting cells than the two thousand. Two SARS virus is because of this fearing cleavage site. I think that's so interesting. And one of the facts mentioned in the discussion of both papers was that a similar fearing cleavage site is seen in an analogous protein in highly virulent avian and human influenza strains let's talk more about how the virus binds the host. Sal What happens next? Told me about this ace to molecule as to as a really common protein found on the surface of many different cell types in the human body it stands for Aga tencent converting enzyme and this is a receptor that is involved in regulating blood pressure so it has nothing to do with viral entry in definitely didn't evolve for that but many of these viruses have found to be a sort of convenient receptor that they can co ops to be able to get into the cell and. I think one of the reasons for this. Is that the protease activity that the virus is using the sort of cut in Poland mechanism that we talked about before. That's part of the natural mechanism of how as two functions. What's important here is that this receptor is the exact same one that was discovered to be involved in the two thousand and two sizes entry mechanism. And that's important because if we have a good understanding of how to drug the as two receptor following on the two thousand and two stars work we can potentially apply that to treatments for this current corona virus. Yeah the downside of that would be that. Since two is involved in extremely critical human physiology that it might be almost impossible to drug without having some kind of adverse side effect. Yeah both sets of papers look at the strength of the interaction between two thousand nine hundred nine SARS in two thousand two SARS with the ace two receptors. What did they find here? So using different methods the walls paper found that the two thousand nineteen SARS virus in the two thousand two stars viruses bind to as to with roughly the same affinity but then wrap at all showed that the two thousand eighteen stars virus binds with ten to twenty times higher affinity which is a huge difference. They conjecture that this tighter binding is part of what makes us so virulent because it's able to more successfully get into cells following that binding event. It's interesting you know they're publishing. These studies one right after the other. They don't discuss why this might be different. Yeah and I think it's hard to say they're using different techniques in this scientists happening so live. It's actually really cool to think about this from the perspective of being at the bench. You're working on something and if a paper comes out that contradicts what you're finding while you're still working on that affects your work because it changes how you trust your own work and it changes war kind of data. You're going to be looking for but in this case. This is all happening so quickly that they're finding what they're finding in their publishing it and I think it's really cool to see it side by side you get to see the of the field and the thinking kind of at the moment it's happening and of course that really bolsters the findings that do concurred like finding that ace two is the receptor and not the spike protein is really similar since those groups got those same answers without influencing each other. That really is kind of the gold. Standard of replication in scientific publishing is having to independent groups finding things in parallel. Okay let's talk about the next area where we saw differences between these two articles so this was in the section where they looked at whether antibodies against two thousand two SARS combined to twenty nineteen SARS. There were key differences between these two papers in the types of antibodies. They were looking at in the walls at all paper. They are looking at poly cloning. Antibodies which were generated by injecting mice with the purified protein from the virus. So the mice's immune system saw this protein generated. Antibodies in response. The researchers then took a blood sample purified. The Sierra that Sierra contains all sorts of different antibodies that bind to all different regions of the spike protein rap at all used three monoclonal antibodies which had already been previously characterized as binding to just a sub domain within the two thousand two SARS spike protein so whereas in the walls at all paper. There's all sorts of antibodies in this mix that combined all over the spike protein and rapid. All these are three highly specific. Antibodies bind to three highly specific sites. In just one tiny portion. There's also a big difference in what they measure using the monoclonal. Antibodies in rap. They're measuring just binding. So do the monoclonal. Antibodies bind to the spike protein at all whereas in walls what they're measuring is weather. The polyclinic antibody set prevents the virus from entering into human cells. This is more of a fina typic- it's more of like a does the entire mechanism that you're trying to stop not happen versus just the binding alone which has a piece of the process. In this case. I'd say the two papers show opposite results walls shows that you can stop viral entry using these polyvinyl. Antibodies and rap shows that there's no binding of the monoclonal antibodies from two thousand to SARS to the two nineteen SARS virus. There opposite results. But they're not necessarily mutually exclusive results because rapid all's only looking at three antibodies. You know there's an absolutely enormous number of possible. Antibodies against these viruses and even just the spike protein. So the fact. That three didn't work. You know that could just be scientific bad luck. There's also the fact that we read other papers to prepare for this segment that supported both the rap conclusion that there is no cross reactivity and the walls conclusion that there is cross reactivity so the jury is still very much out and the fact that all these studies are using slightly different designs. Different sources of. Antibodies different kinds of antibodies. Different readouts. This is still definitely evolving. And it's part of what makes the research right now. So interesting is that so. Many groups are applying their expertise their backgrounds their favorite techniques to this problem and my gut feeling is that there's some kind of nuance into cross reactivity here that we just haven't appreciated yet. Why do you think they basically ended up doing the same set of experiments? I think that what we have here is a demonstration of the types of science that you can get data on really quickly in the past to get a structure of this quality. You would have had to do x Ray crystallography which requires I getting the protein to crystallize in this very specific manner. And it's a tricky thing to do but with you just get the protein samples super super cold and shoot a beam of electrons off it then chairman the structure based off how the electrons bounced off. There has been a real revolution in Cro. Yom recently making this method capable of determining the structure of very large protein complexes also the results of both of these papers are in vitro. So we're getting really important information that can help. Vaccine Design and therapeutics design. These are also the fastest type of research that can be done on these as the publication cycles continue in the research continues will get different insights coming out with experiments at take longer and that require mouse work or that require kind of more complex. Experimental design seeing these two papers side by side really speaks to what can be done. What can we learn? That's important and valuable in the shortest amount of time. Thanks Judy for discussing these articles with me. And that's it for Journal club this week you can find all episodes A16 DOT COM. Thanks for listening..

SARS Judy Savitskaya David Rob Neon Chong Wang Jaso Jim Collins Cove Cova David Visa Asia partner Severe Poland Journal club Glen Yom chairman Ray tencent
Finding New Antibiotics with Machine Learning

a16z

06:07 min | 1 year ago

Finding New Antibiotics with Machine Learning

"Don't you break down for me? What the machine learning approach that they used here. And what kind of advanced does this represent took this machine learning model that they made and they traded on about twenty five hundred molecules and use that to train binary classification models to predict probability of whether it new compound would inhibit the growth of e coli or not and then turn to the truck library Library of six thousand compounds. That are ready in human clinical development for wide variety of indications and at this point the compared several different models and after narrowing down there's molecules and actually predicting toxicity using different neural networks. They've came up with this particular molecule and Howson and then thirdly lastly in the process they went on to apply machine learning motto after iteration and optimization too much broader set zinc fifteen data set with over a billion a half structures and under machine learning side. What's key here's the deep learning network that the US didn't really rely on any information about the chemical structures of molecules. It actually really built new representations called for years. A lot of people represented molecules with these fingerprint factors reflected things like presence or absence of functional. Groups are descriptors and comparable properties but relying on known fingerprints. Didn't really work that well. And that's why you know. A lot of the old antibiotic screening process gives you a lot of the same classes of molecules over and over again and what they did here they actually have these fingerprint descriptors that were built from. Scratch well you know. What you're describing is still a fingerprint. Right into dimensional vector to describe molecules. I think perhaps what's different is at deep learning approach. You can try to infer what the right descriptors should be. That's the hallmark of all of the deep. Learning approaches for drug design is at the end deep learning in general that recall even when we're just talking about conventional neural nets for image recognition the ideas that CNN's for image. Recognition versus classical computational vision. Is that in the classical approach? That person's defines what the right features are and so similarly. You know it's interesting that you can feed any representation of molecule into computer which parts of the interesting ones. You can have just like old school computer version. You could have a human being say all these in the important ones but a a beauty of DNA approach which is Ucla but also in many precursor works. That helps understand. What are the key aspects? And what are the interesting ones? And that is really. I think the big difference between what you can get in modern deep learning with machine learning versus classical machine learning with like random forest or something like that right so deep learning helps us figure out what we don't know versus focusing only on what we already know or what we think we know what makes Alison an attractive candidate for further research and development. What are some of the properties that they discovered without a doubt certainly a really potent inhibitor of e? Coli and you know. Further investigation showed that Halston has strong growth. Inhibitory effects on a wide following spectrum of pathogens. They tried it on. C. Money and which is one of the highest priority pathogens that is urgently required for in terms of antibiotics and then more. Interestingly it was even able to eradicate equal I persist yourselves that remained after episode and treatment so pretty strong efficacy and pretty low talked based on their screen. It also checks the box of something that is really structurally divergent from conventional antibiotics. And so certainly a very powerful new class of antibiotics that could potentially be strong candidate for further development. Yeah the fact that they found the antibiotic they showed it worked in vitro they showed. It worked in Vivo. And then they also did some experiments together this mechanism of action suggesting that Howson selectively disrupts the Ph potential across the bacterial membrane this saps the Proton motive force which is like the battery of the cell so all antibiotics. It's disrupting an essential cellular function but this appears to be a distinct and new function. That's being targeted super elegant work such a complete well rounded story. Yeah well I mean I think one of the things that really stands out here. Is that full stack of experiments. That they've done where it goes. All the way from looking at they might see in a dish to going through mice and one of the appealing things about studying antibiotics. And this often even pertain. Santa Viral that the animal models are pretty good with something like alzheimers. On the far extreme where animals are generally not very good. And so it's appealing that one could go. Do all of this. You know. Probably not requiring huge budget and therefore get something on the other side of that. Looks kind of intriguing beyond initial discovery? Can this kind of machine? Learning based approach be applied to other aspects of either earlier late stage drug development. Yeah it's it's brought Tommy with the fun thing about it. There's a reason why it's a broad topic because there's a broad range of things you can do. I mean you could talk about identifying targets and there's a lot of work to do there an extra shooting novel targets. It's really interesting. Time to go after novel targets. You could talk about identifying leads. Basically what's been done here that identification leads and then the testing of them. These compounds are leads but presumably. They're not drug like so they have to be optimized so there's these methods helping lead optimization and then along the way hopefully you'd want to also be screening for talks and so there's a ton of methods that are getting really surprisingly accurate basically the beautiful thing about a machine learning approach like this is at the approach for the most part is pretty agnostic to what you're predicting and that the processes you're building up can be useful one last thing and this is maybe the holy grail dream is that if you're predicting a lot of properties for a lot of different systems with a whole bunch of molecules in some multitask like framework where one model is predicting all of it. You can learn from all of it and that you develop even though you might not have a lot of data in any single project or any single area here. The sum of all this data now is huge and helps to regularise your predictions to make them less over fit and more

Howson United States Truck Library Library CNN Ucla Alzheimers Halston Alison Mechanism Of Action Tommy
The Care and Feeding of Data Scientists

Linear Digressions

07:47 min | 1 year ago

The Care and Feeding of Data Scientists

"Talking about data signs management. This is something we've been China about for a while leading wrote and a Riley report together on this very topic a few months ago and and thought it would be worthwhile to get in and talking through. So that's what we're doing today talking about once. You have a data science team in place. How do you keep those learning? How do you keep them growing? How do you think about moving along in their careers? All that good stuff. So you're listening to the year diversions in our last couple of episodes which listen to strongly recommend that you go back and pick goes up by a little bit of recap here so we talked a little bit about getting into data science and the different types of data scientists. How you assemble a team and why it's so important to get the right blood in your team once you have? The team assembled or you. How kind of critical mass us most of your time? These days is not your managerial time by not beyond hiring. But it's instead on growing your not making sure that they're learning and they're sticking around. They're happy hair progressing in their careers. You say yes yes yes sorry you can't you can't you can't hear me now so and this was something that we it's your three chapters to talk about if I recall correctly because it's really important and it's a for me this the the stuff. That's not always obvious because sometimes if you're a good manager you're working super hard and but people don't see the things that you're you know fighting for the process of the you're putting in place two two happy I don't know maybe maybe it's a little bit cynical but sometimes given the only time you hear about is when people are unhappy with their happy sounds about right. Yeah I I think that's just as of nature of the beast so but when we were together we together for a couple of years. I remember even when I started at that job. There was a lot of. There's a lot of stuff that was in place when I write the action that you were part of starting some of this certainly part of of continuing the things that have been started before your time of that created a really nice learning environment and so I think that now upon on reflection I realized how important that was for me as a younger data scientist as a way of learning and and stay happy so if as you can get a little bit of detail about what was the you put in place out of things April so yeah it's funny. I actually don't know that I can take credit for having put in place a lot of the good things that we had But I can't take credit for stealing them and putting them in place in my current company actually But there's actually I think one of my favorite topics at least one of my favorite topics from the book and the way the way we talk about it in the book is kind of this idea of like foam. Oh like fear of missing out that like data scientists really have this feeling that like if they're not using cool new techniques learning things that they're like falling behind and just again anecdotally like I think a Lotta people quit jobs or go from company to company because they feel like they're getting stagnant or they're not learning anything anything or doing anything interesting at their company so some of these things that we had in place to help combat that that feeling that people can have so. What kinds of things are we talking about so we're big fans of of just a simple idea of having a journal Club where folks get together? Read a paper of blog posts. It's like something like that. Maybe they've ideally they've read the paper of the blog post but that's not necessarily mandatory and get together and discuss it Someone who has like selected the paper could maybe give the short presentation but really you can just do it over lunch and spend an hour talking about a paper blog post like learning something new dirty secret. You never read the paper. I know what I was GONNA say. Everyone has been very often but every once in a while I'll realized that Journal Club is on a topic that I wanted to do on podcast anyway and then I'll make sure gotta check. Oh all your listeners. Know the secret purchase but and we have like A. I think we find that a great way for people to keep learning stuff but it's also a good opportunity for the company because a lot of interested engineers or analytics people. Oh Com people who are a little bit Interested in getting into the field and it's just a good rates like socialized data science. Like around your your company One thing we've done a few times he's like when we forgot to select paper is to have like a cold. Like Davis is movie night where we will find a talk from an interesting conference. Like Pie de puts video video online a lot of conferences. But there'd be online and we'll just like sit for the hour and like watch talk a conference talk together and I think people often accumulate these lists of things they wanNA watch and they don't have the time for it and that's just another way to get people like watching something Learning something so journal Club thing. That were a big fan of the second one I think is like some sort of dedicated halftime and I definitely did not start this at our previous job and I definitely didn't even come up with the best iteration that I think that we've landed John so I've never three companies that have done halftime we've and seeing many flavors like one flavors like that we at a previous company was like half of every he Friday. You got to do whatever you wanted. Essentially another one has been like what is like a full day full day once a month. I think that's where we're doing a full day once a week at some point either way like that in those like short increments I find. They often don't work very well for two reasons. One people don't aren't able to at the time Apart like it was just half a day every week like you just get pulled in a meeting. So you'd get normal work like you can't actually. You can't actually do it even if it's like a day every other very hard at at the time aside so then we've tried whole team accolades and spending two days like working on something a team. We did cagle competition as a team wants. It's an and that has been fun has advantages but I think the the downside of that is that people can't work on the particular thing that they're interested or they want to learn about. Yeah Yeah So. That's a problem so I think both what we did at Civis and what we do now. Here is the idea of of individual hack weeks. And how often you do them depends is on your company. And what you what you can do. We do them quarterly. But you can. You can even do them once or twice a year but the idea is basically that each person gets to spend a dedicated week on like a hack project and because it's a whole week retire them to treat it like it's a vacation and plan for it like way out in advance and you know people can take a week advocation and get out of meetings and projects so do the same thing with this hack week actually set time aside a week as long enough to make meaningful progress on projects. It's like to actually get end to end on a prototype or try a new software package or open source somethin- and then the last bit is like some kind of bit of accountability to make sure people are actually doing something so Having a slight plan in place ahead of time that people can look at and then doing a presentation to the rest of the team at the end is super important so We do it on Friday as well help like a forty five minute presentation where the person that was on Hack Week. We'll walk the rest the team through what what they've done and so the rest of the team also gets to learn something new and cool but then that person realizes actually have to do something. Because I'm going to get off in embarrassments off. I have nothing to show for my

China Riley Civis Scientist Journal Club Davis Cagle John Forty Five Minute Two Days