So good morning everybody, a welcome to the BioXL webinar series. Now we have a webinar number 48, we start again with this Atom section, and the talk of today will be on computational biomolecular simulation workflow with BioXL building blocks. Our speaker of today is Adam Hospital, from the Institute for Research in Biomedicine Barcelona. Today's speaker and the person that will start the new The Atom series of the BioXL webinar is Adam Hospital. Adam is a postdoctoral fellow in molecular modeling and bioinformatics unit at the Institute for Research in Biomedicine in Barcelona. But in the meantime, he's also a researcher software engineering at the Spanish National Institute for Bioinformatics. So we can say that Adam start from a computer science background, and then he moved to bioinformatics world, and then he was fascinated by the structural aspect of the bioinformatics. He's involved in different projects, both at the Institute for Research in Biomedicine in Barcelona, but also in the supercomputer center in Barcelona. And he's leading the workflow team at BioXL. So he got also in the meantime, he was working in as a software engineering. He got his PhD in biotechnology at the University of Barcelona. We can say that he's also developer of public web server database. Among those we can do, we can see, we can find empty web, naflaps, big na sim. And now I will be happy to see what he will tell us. Okay, fantastic. So thank you, Alessandra. And welcome to all the attendees. And thank you for being here today with us in this webinar. I will talk about the computational biomolecular simulation workflows that we are building with the BioXL Building Blocks Library. I have divided the presentation in these different sections that you see here. I will start with a brief introduction on the BioXL Center of Excellence for the ones that are still not familiar with it. I will give an update on what we understand the current work on the biomolecular workflows, what we are developing our library, the BioXL Building Blocks Library. And then I will show you examples of biomolecular workflows using this library, built using this library. Two different, really different kind of workflows, demonstration workflows built with Jupyter Notebooks and pre-exescaled HPC workflows built or managed by Com Software in supercomputers. And if we have time, I will show you an example of a work that we are doing with these pre-exescaled workflows in the COVID-19 related research. So starting from the beginning, we started in the BioXL Center of Excellence. This Center of Excellence is a project, an European Horizon 2020 project that started in the year 2016, so four years ago. With the motto of becoming the central hub for biomolecular modeling and simulations. And for that, and I hope that you can see my pointer, more than 15 different European partners joined together, all of us coordinated by the KTH in Sweden, to work on the connection between the life science and HPC. And basically working on this area of expertise, so going from the atomistic models to small molecules, macromolecules and reaching the cell unit. Using tools such as molecular mechanics, quantum mechanics and this kind of biomolecular research. Our main objective is to enable better science and we are doing that basically improving the performance and functionality of a set of key applications that I will introduce in the next slide, providing support to non-experts and advanced users. And finally, developing user-friendly and computational workflows. At this point, it's the one that we are more interested on and this is why we have created this library and we are today all together in this webinar. So the key applications that we have in our Bioxial Center of Excellence are very popular tools in this field. I'm sure that you will recognize them. For molecular dynamics, we have GROMACs for the free energy calculations. We have PMX for the docking, not only protein protein but also protein ligand and protein DNA. We have Hadoq and for the QMM and QMM calculations, we have CPMD and CP2K. All of these key applications are developed by partners that are involved in the Bioxial Project. We also have supports, we have a lot of webinars these one training events, conferences, workshops, industry visits and we have a forum where you can this ask.bioxial.eu where you can place and formulate any kind of questions that you want in this key application but also in general in the biomolecular computational field. And of course, using these key applications, what we want is to design, deploy and make available biomolecular workflows. And when we started the project, we thought that we should do that looking at the usability. So we wanted to change the way that we were building these biomolecular workflows. And for that, we partnered with this Elixir European, big European project to start trying to follow a set of best practices in software development to build these workflows. So that means that our workflows should be easy to use, available in different platforms, in different infrastructures, able to be reproduced in different machines in an easy way. And for that, a set of these partners in Bioxial started to work on the library that I will present today. So a little bit about the information about biomolecular workflows and what we think that biomolecular workflows are when we started the project, we sit and start brainstorming with all our colleagues. And I'm sure that you also share this thing with me. The biomolecular simulation workflows are usually built from a number of tools that perform different tasks. And if you think about one workflow that you are now using in your everyday work, you can maybe, you have maybe to download the structure from using a REST API. You maybe need to convert between different formats. You need some kind of modeling if you want to start the molecular dynamics or maybe you are interested in quantum mechanics, you will need to choose which of the programs available you will, you are interested in using. Maybe you are performing QMM on the resulting trajectories. You for sure want to analyze something, extract information from these trajectories. Maybe you are thinking about doing some docking, free energy, et cetera, et cetera. There's a lot of different functionalities. And when you think about these functionalities, I'm sure that you, in the reality, what you are thinking about is something like that. Yes, I'm going to work with molecular dynamics and I'm going to use amber for that or maybe grommax for that or maybe NAMD. And on the resulting trajectory, I'm going to visualize it using VMD. Maybe extracting information also with VMD or maybe using CPP track from amber tools. Or maybe I'm interested in small molecules and I'm going to use open bubble as a chemoinformatics package, parametrize the small molecule using ACPAP. A lot of different tools that we are familiar with because we are working with them every day and many, many more, this is just an example. And at the end, what we are doing, most of the scientists working in this field, what we are doing is to build a shell script like this. So in the step one, I'm running a command line, one of the tools performing one particular functionality, something that I'm interested on. For example, a REST API, I'm downloading a PDB file from the PDB database. In the second step, maybe I am generating a topology using one of these molecular dynamics programs, et cetera, until we end up in the last step of our workflow. Of course, this has a lot of problems, a lot of problems. And you can think about the usability, the one that develops this shell script understands this script, but it's really difficult to teach how this shell script works and why the step one is doing what he's doing and the step two is doing what he's doing. Even if you put a lot of comments between the different steps, interoperability is another big, big problem here. So the upwards of the first step don't need to be compatible with the step two. You need to maybe change the formats and make them compatible with the second step and the same can happen with the other ones. Portability and reproducibility, as you can imagine, you take this shell script and you move this shell script to another computer. If you don't have the same versions of the same programs installed with the same libraries, these will not work the same way that it's working in your computer. And finally, scalability. If you want to take this script that is working really well in your laptop, but with just micro dynamics of 10 nanoseconds, if you want to go to the one microsecond or maybe run that 100 times, you need to move that to another computer, maybe a supercomputer and you will have a lot of scalability problems there. So with all these keywords in mind, we started the development of a new software library that is called BioXL Building Blocks and I will explain you a little bit about this library in this webinar today. So BioXL Building Blocks is basically a Python wrapper, a set of Python wrappers on top of biomolecular simulation tools or biomolecular computational tools. For example, if you think about a particular execution of a particular functionality of a program, for example, build a system box on top of a protein to perform molecular dynamics simulation with these books, with the system. For example, we can choose to work with Gromach molecular dynamics package. We know how to execute that. We know the command line to do that and we know the local input parameters for this command line. But what we are adding here is a Python compatibility layer. And this Python compatibility layer what it's doing is to adapt a set of him output files and configuration files, which are always the same. They have always the same syntax no matter what program is here in the middle. And it does the same. It adapts these inputs to local input parameters and it does the same with the local output parameters. It adapts these output parameters to a set of output files and log files which are always the same syntax for all the different building blocks no matter what is the program that is being executed. And I will give you examples of that. Don't worry if you don't understand now exactly what I mean by that but you will understand that for sure at the end of this presentation. And on top of that, we are building an external layer which is called workflow manager adaptation layer. And this new layer is making these building blocks compatible with different workflow managers. And you will also see examples of that during this presentation. This is important. You have all the information that you need in this web page here. And you will see this URL in different slides in this presentation. So this is a kind of a summary. We start with the building blocks which are wrappers on top of functionalities on different biomolecular tools. And we put together these building blocks which are really easy to interconnect because of this interoperability layer that we are adding and we build our biomolecular workflows. And once we have the biomolecular workflows we launch, we execute these workflows using different workflow managers. And that's thanks to the external layer of compatibility with these workflow managers which can be grown on graphical user interfaces such as this NIME or Galaxy if you know about these graphical user interfaces or Jupyter. But we can also work with HPC focus so more workflow managers focused on supercomputers such as Pycoms or Toil for example. So different ways to execute and control our workflows. As I was telling you at the beginning for that we started this collaboration with Elixir and I don't want you to recognize all of these different logos here but just briefly introduce you that the library is completely fair. That means that it's findable, accessible, interoperable and reusable. And just as an example you can find the library in the Elixir Bio Tools repository, software repository. We have a webpage where you can find all the different information. It is indexed in the OpenEvenge Elixir platform for benchmarking of different software tools. All the source code you can find it in GitHub. We have bio schemas behind all the web pages that we are developing and also the documentation. So you can find our library easily with the search engines like Google for example. All the documentation is made with this standard initiative. Read the docs, OpenAPI, Swagger for the REST API, Interfaces, common workflow language for our workflows descriptions. We are using packaging and this is really, really important for the reusable and reproducibility of our library. Conda packages, Docker containers and also singularity containers. And as you could see in the previous slide we can run and launch our workflows with different workflow managers. I'm not going into details about that but just for you to know that the software best practices that we are following in this library. One of these best practices that is really important for us is the conda environments. And if you are not familiar with this software I will strongly recommend you to take a look at it because it's really powerful. In just one minute what this conda software lets you do is a closed environment inside within one particular computer with a set collection of software libraries and tools installed with particular versions. And you can reproduce in a really easy way the same closed environment in another computer. And that of course gives you the possibility to run a particular workflow. In our case we are interested in workflows using these programs with these versions in the same way in this computer as you do in the other in the second computer using the same conda environment. So I will not extend on that but please take a look at the conda if you are not familiar with it because it's really, really important. And for us it's really important for the reproducibility of our workflows. And you will see examples of that. So at the end of the day what we have is a collection of modules which gather together different building blocks with a particular functionality. So for example, the common is a base package required for all the different building blocks library but we have a bioVV input output module which is a collection of building blocks to fetch data from biological databases. We have a molecular dynamism collection to perform setup and run molecular dynamic simulations. In this case we are using Gromax as it's one of our key applications in BioXL but we are thinking about adding different packages. We have an analysis collection to perform analysis over the molecular dynamic simulations that we are running with this module here. We have a collection to perform free energy calculations wrapping the PMX tool. Also one of our key applications in BioXL we have structure utils to modify or extract information from a PDB and also to convert to in different formats We have a collection to check a model structures, chemistry collection with chemoinformatic analysis, a machine learning one, wrapping popular machine learning algorithms like Psyche-Learn, TensorFlow, etc. And we are finishing a virtual skinning one, a molecular interaction potential one and we are thinking about different modules. So we are extending the library and it's good to know that every time I explain these BioXL building blocks I have more and more of these modules so I will need to extend this slide in two different slides. So we are extending these modules and you can find all the information about these modules in the web page. Those are all the different modules but if you click on one of these plus icons here you will find all the building blocks that you can find inside of this particular module which is the analysis one and you can see clustering, RMS, RDS, etc, all different functionalities which are basically building blocks. If you click on one of these names of the building blocks you will go to the documentation that will explain you everything that you need to know about this building block and what is important is that you have here links to the source code in GitHub, the Python code, documentation and read the docs, the bio-contact package, the Docker container and the singularity container that contains all not just the Python wrappers folder for the building blocks but for example, in this case it also contains the dependencies needed for this building block to run. So in this case in the analysis that means that the Amber Tools 19 and Gromax will be installed if you just type in the install in your terminal. So this is important, really important for reproducibility. Examples about the syntax. I was telling you before that we have this Python compatibility layer. We have these input files and configuration that are then adapted. So these input files and configuration basically are these inputs, outputs and properties that we need every time we want to launch one of our building blocks. So this is repeated every time we want to use the building blocks. We need to import the module, define inputs, outputs and properties which are the parameters of the function for the building blocks and to launch a building block. The example is always easy to see. So import the module. We are importing in this case the particular building block which builds this system box on top of the protein. We define the inputs and outputs files. In this case you can see that this is just a path, a string with a path with the name or in this case of the output file that we want to produce. And here we define as a Python dictionary the properties which are basically the parameters that we need in this particular case. We want the box to be cubic and we want the distance to module to be one nanometer. And then we launch the building block. Inputs, outputs and properties. Inputs in this case is taken the output of the previous step on the workflow. This is basically what we do when we develop workflows. We use as an input for a particular building block the output of the previous building block. And for the output we take this output that we have defined here and the properties, the dictionary of properties. It is really not complicated but if you see examples of how we do that, for example, for a mutation, you can see importing the building block that we need, defining inputs, outputs and properties. You see that it's exactly the same and launching the building block. In this case, we are mutating a residue using Modeler. In this case, we are running a cluster, a clusterization on top of a trajectory. So again, importing the building block, defining inputs, outputs and properties and launching the building block. And here what we are doing is obtaining this cluster centroids and we can represent them. So it's exactly the same. And basically if we join together four different building blocks like these ones that you will understand because this is not difficult. The first one, I can remember importing the library, defining input, outputs and properties, launching the building block. We are downloading using a REST API, a small molecule in PDB format, in this case, the ibuprofen one. Here we are adding hydrogens to this structure with the same syntax as before but now using a building block which is called bubble at hydrogens which is using open bubble. It's wrapping open bubble. We can take a look at the intermediate structure using Jupyter Notebook. You will see that in the next slides when I will show you examples on Jupyter Notebooks. The third step that we are doing here is to minimize the structure of these hydrogens and atoms that we have added in the previous step. Again, importing the library, defining inputs, outputs and properties. In this case, we don't have properties launching the building block. Again, looking at the intermediate results and finally we want to parametrize the small molecule using AC pipe. We import the library. We define inputs, outputs and properties and we launch this. So we have been using in this mini workflow three different tools but the syntax of the building blocks as you could see is exactly the same. So it's very easy to use. Where you can find information about which inputs and outputs I need to define and which properties and which parameters can I use for a particular functionality or for a particular building block. You can find that in the documentation. So each one of our building blocks has a read the docs, a standard documentation with the parameters that they did accept, inputs, outputs and the different properties that you could use. I cannot extend more on that because of the time that we have for this webinar but you can find all the information that you need in the scientific data paper that we published a year ago. And just to tell you that the European Commission has identified this library as one of the high potential innovations from innovation tools from European funded research such as the BioXL Center of Excellence. As I was telling you before, the workflows that we are producing with this library can be launched in many different workflow managers. Here you have just examples of them, common workflow language, using a REST API, using command line, using graphical usage interfaces such as Galaxy or NIME. And even we are developing a web server so that you can use pre-configured workflows and run them with a connection with HPC machines. We don't have time again in this webinar to take a look at all of the different versatility workflow managers that we can use. But I have centered this presentation in two examples. The first one, demonstration workflows, workflows to play, to start with the library using Jupyter notebooks. And the second one, completely different from the previous one, pre-exascale workflows or workflows designed to be used in supercomputers like this Marinostrum one from the Barcelona Supercomputing Center which are controlled by a software that is called Pycoms and are able to use thousands of cores in one single job. You will see. We start with the first one. So demonstration workflows using Jupyter notebooks. Why we chose Jupyter notebooks? I think that they are really, it is a great tool in general because it's a fantastic tool for training. You can inspect intermediate results. In our case, we can inspect the molecules in 3D with interactive tools like NGL. We can interactively modify the parameters of the different steps of the workflow.  If you are not familiar with Jupyter notebooks, you have different cells, independent cells that you can run in an independent way. And you have also the possibility to run the complete Jupyter notebook in my binder infrastructure. I will tell you something about that in a couple of slides. But in particular, for the BIOXL building blocks, it is a really good tool, I think, to be familiar to start playing with the syntax that I have just shown you in the previous slides and to learn how to build these workflows. And for that, we have developed a set of tutorials that are the ones that you have here and you can find them in our webpage to start looking at the syntax in how you can join together the different building blocks and build your own workflows. And this is also important. It's an easy way to see how you can package your workflow using the Conda packages and export this workflow to another machine, infrastructure, et cetera. And using Conda, you will see examples of this. So this is how Jupyter notebook one of these demonstration tutorials that we have in the webpage looked like. There's a lot of information, as you can see, this is marked down in the Jupyter notebook that you can add information about the building blocks that we use, the libraries, actual libraries that we need. When you go to a particular cell which is running a particular building block, you can now identify import of the library inputs and output definition and launching. Remember that it's always the same. So here, you have, for example, generating the topology for Gromax MD package, here information about the force field and the water type that is used, here the cell that you can execute and here is the lock that the building block is producing. As I was telling you before, you can check intermediate results. In this case, this is NGLB where you can rotate and zoom and take a look at the structure, intermediate structure. And this is inside the Jupyter, really nice. But you can also take a look or generate plots like this one, which is showing you how the energy is decreasing during the energy minimization process, the step of energy minimization inside one of the demonstration workflows, which is the molecular dynamic setup tutorial. And this is just to show you that you can integrate in the middle of the building blocks, Python code, just to extract information in this case from an energy values output from Gromax and use these values to plot this information in an interactive flow like this one, using the plot library. And this is important. Once you have the Jupyter notebook finished, your workflow in the Jupyter notebook finished, you can export this Jupyter notebook using this code packages. So for that, you just need to create this kind of YAML file, which is called environment dot YAML. And you just need to tell here the dependencies of this workflow, which are these three different building blocks modules, common input, output, and chemistry, apart from some auxiliary libraries that is needed to inspect the intermediate results. You put all of these in one single file and then just doing this, which is Konda environment create with this file, you will, so the Konda software will install everything that is needed to run this particular Jupyter notebook, this particular workflow in another computer. So these seven really easy steps here that you can find in the demonstration workflows that we have in the webpage are the ones, the only ones that you need to reproduce, in this case, this particular workflow, which is the one that I have shown you to automatically parametrize a ligand. You can also use this environment dot YAML, these files too, and these Konda packages to automatically deploy these Jupyter notebooks in the MyBinder infrastructure. If you are not familiar with that, it's an infrastructure that lets you deploy automatically in the cloud, your Jupyter notebooks, install all the dependencies, and you can let you play with the Jupyter notebook as if it was installed in your own machine, just using a browser. You have four demonstration workflows and we are working on more different workflows in our webpage. You can click on execute in binder if you want to directly play with them, but also I invite you to take a look at the tutorial, try to install using these Konda packages in your own machine and try to play with these different demonstration workflows. And now changing to the second part of the examples, which are the HPC workflows. In this case, these workflows, as I was telling you before, are prepared to work on thousands, of course, at the same time, so nothing to do with these Jupyter notebooks that I have just showed you. Starting yet from the Jupyter notebooks, what we can do is to export this Python code that is coded inside the Jupyter notebook to a particular Python file, and you can run this Python file in a command line interface. So you can just with little modifications, you can have the command line interface from this Jupyter notebook, but of course you have these advantages. The graphical cells are not showing, of course. You are losing interactivity, but you gain high throughput. So you can start using this to automate processes, to repeat the processes with different input files, with different parameters. And the problem basically is that this Python file needs to be modified every time you need to modify a certain parameter for a certain step of the workflow. So we thought that a good approximation to run command line interface workflows using the bytes of building blocks would be to split this Python script in two. So we have, on one hand, the workflow script in Python, and on the other hand, a YAML configuration file with a workflow parameter. So here we have the building blocks, the workflow, the Python codes, loops and condition, and so on, what defines the workflow, and here what defines the parameters of the workflow. So inputs and outputs of the step, dependencies between the steps, and the properties which are the configuration files that you saw in the previous slides. And you have also global workflow inputs and parameters. Examples that is always easy to understand with examples, this is a very easy sequential empty setup where you download the PDB, fix the missing side chain atoms, generate the topology, all of that with grommats, generate the system box, solve the box, generate the counter ions and add the counter ions and minimize the structure. So all of these are building blocks from the BioXL building block library. And this, which is a separated file, which is a YAML file, are all the inputs needed. So inputs are just a PDB code that we want to use for the particular step one, dependencies on different steps. So the input of the second step, it's a dependency on the output of the second step. So the input of the second, sorry, of the first step, the input of the second step will be the output of the first step, and here you are defining all these things, which are the parameters of the workflow. We can have more difficult workflow like this one, a little bit more difficult. In this case, we have a loop on different mutations that we want to model on the mutations list and these mutations list is defined in the YAML file as you can see here. So we can run this basically in the terminal and it will produce something like that, which is step one and two are common for all the different mutations, but then when you start modeling the different mutations, you have three different folders. Each one of the folders has 24 different steps, which are the steps defining the MD setup and the run of the simulation. We are, if you remember from our diagram of the building blocks, we have this adaptation layer on top of our Python compatibility layer that makes our building blocks and our workflows compatible with different workflow managers. In this case, we are using for the HPC pre-exascale workflows. We are using PyCons, which is a framework developed in the Barcelona Supercomputing Center. These PyCons, what it does is automatically identify these kind of loops like this one that you have here. So for all the mutations in our list of mutations do something in this case a molecular dynamic setup, PyCons is generating a dependency graph like this one that you can see here is identifying that we have in this case five different mutations which are completely independent, one from the other. So we can run these branches totally in parallel and basically what it ends up doing is something like that, which is using 100% of the CPU of all the nodes that we have reserved for a particular job in the Marine Austin Supercomputer. This is what PyCons is doing and this is the approximation that we are taking for our pre-exascale workflows, PyCons together with the BioXL building blocks workflows. And just to finish, I will finish with an example of how we are applying that in a pre-exascale workflow. In a COVID-19 related study, I will go really fast because we don't have time but I'm sure that you will identify the COVID-19 virus, the spike proteins in red, the RBD receptor binding domain protein coming out of the spike, which is the receptor that is docking to the humanase protein here. This interface here, one where the RBD is attaching the humanase protein is the one that we are interested on. This particular interface here, what we are doing is using our chemical free energy calculations of relative protein binding, free energy difference. Check the influence of particular mutations on the RBD of the virus or on the humanase protein, on the free energy of the binding of the two proteins. So basically what we end up doing is this complex workflow that I have no time to go into details. We are selecting two different deltages. We are subtracting the deltages and obtaining the binding free energy. This can be transformed to pre-exascale workflows. And again, I'm not going to enter into details, but we have pre-exascale workflow to simulate molecular dynamics for different mutations on the RBD, on the humanase and on the complex and all the different structures. And with these molecular dynamics simulations, we are running free energy calculations that it means that we are running this non-equilibrium molecular free energy calculations that involves running 1,000 independent short molecular dynamics simulations using Gromax and BMX. This is extremely parallelizable and we can transform that into this kind of workflows. This is the first one, equilibrium MD simulations that you can see here. This is the reality, is how we are using it in the Marinostrum. We call a Python script, which launches molecular dynamics simulations and models of particular mutations that we are stating here. So we want to run the wild type and this particular mutation. And this, what it's doing is using algorithmic blocks and picons is running all the mutations in all of these nodes. This is a real example 12 mutations, 10 nanoseconds molecular dynamics simulations in more than 2,000 nodes in the Marinostrum supercomputer with just eight hours of time. And the same with the free energy calculations on top of this equilibrium simulations that we have performed in the previous using this workflow. In this case, we can do exactly the same. You can see that the approximation is the same, really easy to understand. And here, again, we are using 100% of the CPU of, in this case, 1,500 different nodes. As a summary, the Bioxial Building Blocks software library offers a new layer of interoperability on biomolecular software tools. The workflows that we are building with this library are portable and reproducible, and can be easily built using this library. And the external additional software workflow manager compatibility layer allows these workflows to be launched and controlled with different frameworks and be used in different infrastructures. And I have shown you a couple of examples, really quick about the demonstration workflow with Jupyter Notebooks, and the pre-exascale HPC workflows, completely different, two different approaches, but using exactly the same workflows behind using the Bioxial Building Blocks. Just as a bonus track and before finishing, you can build your own building block if you are interested on that, and you have a particular tool that is not integrated in our library, or a particular tool that you have developed and you think is interesting for us to have it in our collection. Take a look at this particular section of the web page, and you can find all the information that you need to build your own building block that we will check, of course, and make the appropriate arrangement if needed, and then we will integrate it in our library. Remember, if you don't know that we have a lot of training in the Bioxial Center of Excellence, so we will have a remote Bioxial Winter School on Biomolecular Simulation. We will have a new virtual training related to building blocks in November this year. You have the YouTube channel in Bioxial where you will find different examples of how to build workflows using the Bioxial Building Blocks with the Jupyter Notebooks, in particular this demonstration workflow. So in one hour, there's no time for everything, but please, if you are interested, take a look at these resources because they are really interesting and useful. Finally, just acknowledgments. Those are the people which really make the work here. So the Bioxial Building Blocks developers, Paul, Janice, Laya, and Luis, the Bicom developers, Jorge and Rosa, that is the boss, and the coordinators of all of these library and the Bioxial Workflows Modesto and User-US. And now I would be really happy to take questions from you. We have a first question from Henry Whitler. Henry, I have unmuted your microphone. If you would like to ask your question, please go right ahead. Thank you. Yes, very inspiring talk. I was wondering if this BioBuilding Blocks available in Orgithub, I was wondering which license does it have, and is anyone able to, can anyone adapt the workflow to work with any programs and software, for example, like material research software? Is it possible to adapt? The thinking by copying the code from GitHub? Yes, absolutely. The license that we have is Apache 2 in all the different building blocks and all the different modules. So you can take a look at the GitHub repo of Bioxial, and you will find all the different modules there. So yes. I guess I will have a look, so thank you. Thank you for that answer. The next question we have is from Leonardo de Maria. Leonardo, I have unmuted your microphone. If you would like to ask your question, please go right ahead. Yeah, hi, Adam. Thanks very much for the very nice presentation. I was wondering, you for obvious reasons have started with a selected number of applications, like for example, using Gromax heavily as your MD engine, but can you comment, you know, how easy would it be to have other engines there, like for example, let's say NAMD? Yes, yes, that's a very good question. I mean, in my experience, I developed a web server that was able to, like 10 years ago, that was able to run a setup, to perform setup and run simulations for amber, for NAMD, and for Gromax. So it's all, it's just the only thing that we need is to understand how to prepare everything, all the steps that we need. And once we have that, I would say that integrating that in the Bioshoel Building Logs is really straightforward. We actually have a template. I haven't said anything about that, but we have a template in the GitHub repo that you can, well, everybody can use. You can download the template and just modify what is the tool execution. That means that the command line interface that basically you are wrapping. So once you have this line, I would say that integrate that in the Bioshoel Building Logs is really easy. So yes, of course we are thinking about NAMD, we're thinking about amber now. The thing about amber is the license, which is another thing that we need to discuss another day. We don't have time for that, but yes, we have problems with BioCon and the Konda packages because we can not distribute that, but we can use and we can build this kind of Bioshoel Building Logs anyway, because we are prepared to use software which is compiled in a particular infrastructure. So in the supercomputers, we are not using the Gromach installation that comes from the Konda package, but we are using the installation that it's compiled for the particular infrastructure. So yes, there's a lot of things to discuss here. Yep, thank you. Thank you. Thank you for that answer. The next question we have is from Giorgio Tambo. Giorgio, I have unmuted your microphone if you would like to ask your question. Please go right ahead. Okay, well, thank you very much. First of all, for the very nice talk. I'm sure if I had this during my PhD, that would have saved me a lot of hours and a lot of wrangling with the bar scripts. Well, now currently I'm working in the industry and so I know that it's quite difficult to get access to most software simply because you have to pay for them. And so are all of the Building Blocks free to use also for industry or is some of them to come at the price? For instance, NAMDI, I know it's not free to use in the industry. Yeah, well, the only thing that we are doing in this library is wrapping this kind of software. So if NAMDI is not free to use for industry, we cannot do anything about that. We just can write the wrappers on that so that you can use workflows on top of this. So using the Building Blocks, but you still need this license if the software that is wrapped behind needs a license. So we have, for example, excuse me, we have a wrapper on top of Modeler and in this case, we can even share, distribute the software because they have a conda package for that.  So this is a kind of a problem in reproducibility, but we cannot do anything about that. We have started just selecting all the tools that we know that are free to use. You can imagine as Gromax, PMX, all of these workflows, sorry, tools, but yes, we can use these, we are compatible with this kind of software, but we cannot do anything about the licenses that are behind. Of course, of course. Okay, well, thank you very much. Welcome. Thanks again for that answer. The last questions we have are from Dikeos Sumpassis. Let me try that again. Dikeos, I cannot seem to, I seem to not be able to unmute your microphone. I apologize. So in that case, I will ask the questions for you. Dikeos wanted to know, can any Anaconda install work with these building blocks? So for instance, specifically, does the Anaconda installed on Windows 10 PC work? That's a good question. It works. We have tested that in the virtual machine inside the Windows 10. If that is what he or she is referring to, yes. The thing is that of course, you need these Anaconda 3, and then if you have like this kind of a mini-Conda or the different approximations which has a less number of packages installed, the packages that are needed will be installed anyway. But the short answer is yes, as far as I know. We have tested that in the virtual machine, Linux virtual machine inside the Windows 10 Operative System. Great, thank you very much. With that, we have no more questions. I'd like to take a moment to thank Adam again for this very interesting presentation and also to mention that there are a couple of other BioXL webinars coming up. I believe, Adam, you have a slide showing upcoming seminars. Yes, let me see if I can hold for that. Yes. Yeah, so for instance, next week on Tuesday, we have a special edition. We're running a summer school and the students, there will be a student webinar for that summer school happening on Tuesday at 1500 CESD, so European time. And then in October, we have a talk about Molywood streamlining the design and rendering of molecular movies. The method for joining us for these talks is much like the method for joining us for the talk that Adam has just given. With that, thank you again, Adam, for this very good talk and thank you everyone for coming to this webinar.


A lot of players they get the ball and they don't know what to do with it, so they overcomplicate or they take too much time.  So maybe for the first few minutes of the game, until you build this confidence, you just want to think about playing very simple. Do not give the ball away. So play me a pass again. So as that ball comes, I'm just thinking about, boom, receive it, pass it to my teammate. Move into space to support him and get it back again. I will send the better in one day soccer blueprint to anyone who comments hashtag soccer on this video. Okay, if you are overcomplicating the play, you're losing the ball far too often, you have to start building up your confidence. And you can do that by playing very simple. So play them all again. So focus on that good first touch, pass it to your teammate.  I want you to be creative. If you like this content, check out the Soccer Success Planner. You can download it for free. There's a link in the description below. And for advanced training, check out the Online Soccer Academy.


The Central Analytical Facility, or CAF, is a group of tools that allow us to characterize materials from the atomic scale up to hundreds of microns, and it gives us the ability to understand materials in both one, two, and three dimensions. The center is really unique, you know, to me it's really world-class. We've worked very hard to assemble a group of instruments that would allow us to characterize materials from the atomic scale all the way up to the bulk scale. The instruments that we have, and the access that we have to the instruments, there's really no comparison to any other place that I've been. Sitting behind me here is an atom probe, which allows us to characterize the atomic scale of materials, but around us are tools such as TMS, scanning electron microscopes, x-ray diffractometers, and a whole range of different tools. And the collection of all these tools together is what really provides the type of tools that have helped a lot of students, particularly graduate school, to advance their science and their projects, because they're able to capture what they need to at the right length scale. Graduate students are quite different from undergraduates, and you need to find a very good supervisor to lead you into the field. And Professor Thompson is a very good source to solve my problems. And he gives me a very large freedom to do the research I want. It's very enjoyable. I'm listening to Dr. Thompson talk at the seminar. He had a lot of really good research, he was really energetic, and he really, he could tell you could really care about his students. He gave students credit whenever he could. He's like, I didn't do this part of the research my students did, and I'm just here talking about it. And that just really impressed me. The University of Alabama has got something that's really special here, and we just need more and more students that have the desire and drive to come and take advantage of it.


Hey Psych2Goers and welcome back to another video. Before we start, we want to give a huge thanks for all of the love and support that you've given us. Psych2Go's mission is to make psychology and mental health more accessible to everyone, and you help us do that. Now, let's begin. How do you describe someone important in your life? Supportive? Caring? Understanding? These are the people with whom you've fostered deep connections. You look forward to spending quality time with them because you have such a mutually enriching and positive relationship.  Here are six signs that you're emotionally attached to someone. 1. You find it difficult to let go of them When you're emotionally attached to someone, they become important to you. As you progress in your relationship, slowly but steadily, you find it hard to imagine your life without them. If things get rough between the two of you, the process of having to let them go is very difficult. You're so attached to them that you can't imagine your life without them in it, and that notion scares you to the bone. 2. You really understand them and vice versa Creating a special bond with someone is the hallmark of an emotional attachment. Over time, you become more and more attuned to each other. As you learn more things about them, you get a better understanding of who they are as a person. When you both feel understood and mutually respected in a relationship, you feel like you both are being seen, heard, and accepted for who you are. 3. You absorb their emotions Do you possibly find yourself taking on their different moods without even realizing it? People who are empathetic and highly sensitive often take on the moods and emotional states of the people around them, especially those they're emotionally attached to. This can lead to emotional and mental fatigue, which can be extremely detrimental to your mental health in the long run. If you can relate to this, it's important to remember to maintain your boundaries and learn to regulate your own emotions. 4. You want your family and friends to know about them Do you wish for this special person to meet the other most important people in your life? Your closest friends and family's opinions about your partner matter a lot to you. You have a strong desire for them to like this person just as much as you do. You want both parties to get along with each other and make good impressions on the other. 5. You take interest in the things they like Have you taken renewed interest in writing or music or find yourself deep in a hobby you've never thought of before? Having an interest in their hobbies shows how much you care about them. Maybe you've never finished reading a book in your life, but then because this person has offered you to read their favorite book, you want to finish it to impress them. You start listening to their favorite songs and watch the TV shows and movies they happen to recommend. 6.  No matter how long you talk on the phone or get to hang out together, you don't ever get bored. The conversation never goes to jail. You make plans to meet up when you're both busy. You call or text each other whenever you can. You spend so much time talking that sometimes you're having three completely different conversations simultaneously on three different social media platforms. Do you associate any of these signs of emotional attachment to someone in your life? Tell us about your important relationships and why they're special to you in the comments below. If you enjoyed this video, please hit the like button and share it with someone who would find it helpful. Don't forget to hit the subscribe button and the notification bell icon for more Psych2Go content. The references and studies used in this video are added in the description Thanks for watching and we'll see you soon.


Do you like history? Well, you should. So if you're not reading history, start. Hello everyone, Dylan Schumacher, Citadel Defense, and we are back with another edition of Tactical Book Review. And today's book is Tactical Leadership by Paul de Le Favore. I have no idea how to pronounce Paul's last name, so Paul, if you ever see this, I'm sorry. So this book is exactly what it sounds like. It is about tactical leadership. And in this book, Paul breaks down 12 leadership traits that he thinks are important and that you should try to garner if you're gonna be a tactical combat leader. And the way he does it is pretty interesting because there's a lot of leadership books out there. There's a lot in business. There's a lot in combat, tactical reading, whatever you wanna call that. There's a lot of leadership books out there. But this one's unique in that he takes these 12 traits and then he goes through one or two historical examples of a person and how they embodied that trait. And so it's this really fun mishmash of history and learning about these leadership traits and seeing them play out in history. Leadership, in case you don't know, is universal. Meaning that what motivates people has been the same since we left the Garden of Eden. That's just true. That's how it is. Our people, across generations, across time, across regions, across cultures, people need to be led. That's why we have leaders and that's one of the ways that history moves forward. So he does a really good job again of saying, okay, this is a leadership trait, like I think tenacity is one of his leadership traits. So let's see here what he's got. Tenacity is one of the leadership traits. So he takes an example of tenacity, right? And he'll explain a little bit about what it is and then he'll say, okay, here's an historical example of tenacity and we'll go through that. So for tenacity he covered, for tenacity he talked a lot about John Mosby from the Civil War and kind of did a little historical lesson on John Mosby and what made him tenacious. So again, it's this really fun mishmash of history and historical battles and historical people and learning about these leadership traits and how you can better garner them in your life. And you can see what you do have, what you don't have, what you're missing, you know, all that kind of thing. So big fan of this book in that regard, it's written again entirely towards military people, not for everyday people, but like I said earlier, leadership is universal, so it really doesn't matter. If you wanted to read this book to learn how to lead your team at work better in your little corporate office, you could learn some things from this. So I would highly recommend this book if you're at all interested in leadership, particularly tactical leadership, this book is gonna help you out and it's really one of the better leadership books that I've read that I can think of. I've ever had a handful. The reason I like this one in particular is again, it's that fun combination of history and when you can see a trait and you can relate it to a historical example, a real life historical example of something someone did or didn't do well, you can look at that and say, ah, I see it now or I see where if they would have had that trait, that would have gone better for them. But because they didn't and they made that glaring mistake or had that huge character flaw, right, that caused them an issue. So I would again, recommend tactical leadership by Paul D. Lafavore. And if you're watching this channel, chances are you consider yourself or want to consider yourself or want to be some kind of tactical leader, right? Because who else is reading the books? The people who read will lead. That's been universal throughout human history. So read the books, be a better leader. We're gonna need you. Do brave deeds and endure.


Hi there. Welcome back to History and Philosophy of Science and Medicine. I'm Matt Brown. Today is part three of our discussion of Fireobbin's book, Against Method. We're talking primarily about chapters 15 and 16 and the interstitial appendices there. So, in these chapters, Fireobbin is attempting to sort of wrap up the main argument of the first part of the book, really the primary focus of the book, which is the argument against method, against the notion that there's a single scientific method that unites all of the diverse activities that we call science. And he's trying to do so by responding to some ideas that might be used against the main part of his argument, right? So, just to remind you, the main part of Fireobbin's argument against method stems from, on the one hand, the Galileo case. Galileo violates a variety of empiricist prescriptions of scientific method by essentially using what Fireobbin calls counter-inductive approaches. And Fireobbin also provides sort of scaffolding or supplementary theoretical abstract arguments that go along with the historical arguments that this is a reasonable set of things for Galileo to do. And in the background, of course, is the idea that Galileo is an important figure in modern science. And so we should regard, sort of by default, the things that Galileo is doing as at least permissible aspects of science, if not exemplary. So, in Chapter 15, Fireobbin considers some responses to his argument. The main one is based in a classic logical empiricist distinction between the context of discovery and the context of justification. So, the context of discovery is supposed to be that part of science where scientists discover new phenomena, pose new theories, come up with new theories, and do all of the messy things that scientists do to arrive at their ideas and conclusions. And then the context of justification is supposed to be that part of science where those results, those theories, hypotheses are logically justified on the basis of the evidence that is gathered. Now, many thinkers at Fireobbin's time and since have questioned this distinction between the context of discovery and the context of justification, and Fireobbin is no different here. And he largely points to the fact that these processes are entangled in practice, right, as the main argument. But he also points out, as he's done throughout the book, that the strict sort of application of the methods that are supposed to apply just to the context of justification would still wipe out broad swaths of science, including Galileo's innovations, right? The practical impossibility of making the distinction, the overly restrictive notions of what happens in the context of discovery, and also the need for the close interaction between the two in order to criticize abstract theories of method are all parts of Fireobbin's argument against this distinction. There is, I think, a distinction in the neighborhood that's relevant to think about. I wouldn't call it the context of discovery versus justification, but there are two processes that tend to be somewhat separable in science, and that's what you might call the context of inquiry when a scientist or more likely a team of researchers in a laboratory conduct experiments, propose theories, and then publish their results. In the context of certification where those publications are peer-reviewed, published, and then potentially taken up by other members of the scientific community. So I think that there is an interesting difference there, but it's not one that lines up with the philosopher's attempt to draw a difference between the historical process, the messy history of science that happens in the context of discovery, and the philosophically interesting process of justification. Justification happens in both of the real-world context of inquiry and the context of credibility. In attempting to oppose the context distinction, Fireobbin also raises an objection to a similar distinction between prescription and description. Particularly thinking of methodological prescription for science and historical description of how science actually works. Now, I think Fireobbin doesn't mean to say that there's no meaningful distinction to be had there. Rather, what I think Fireobbin says is that there's an important way in which the descriptive and the prescriptive interact. So philosophical prescriptions are tested in the history of science and by the history of science in a sense. And there are important ways in which not only can you criticize happenings in the history of science based on methodological prescriptions, you can criticize methodological prescriptions as unrealistic or inapplicable or irrelevant by looking at how they would work out in the history. So of course there is some kind of distinction between ought and is, but it's not as fundamental as some philosophers have led us to believe. There's also a lengthy discussion rather of critical rationalism, which I won't try to repeat here, but rather I think what's most interesting about it is the way in which Fireobbin talks about different conceptions of scientific progress from one theory to the next. So he has this diagram. It's on page 159 in the fourth edition. It looks like this. So the top diagram here is sort of how Fireobbin thinks we tend to think of the history of science, right? So we tend to think, you know, the old theory was okay, but it wasn't as good as the new theory. The new theory has increased content and the relationship between the two is one of growth. The knowledge has increased, right? But in fact, what Fireobbin points out is that this version of the old theory is kind of a fiction. It's kind of a construction from the perspective of the new theory. So the old theory wasn't... This isn't really what the old theory was. This is a version of the old theory, which has been kind of sanitized and rendered compatible with the new theory. Another version of that is one where we admit, okay, there were some things that the old theory got wrong, but still there were parts that it got right and the parts that it got right here are explained by the place of those sort of predictions in the new theory, right? And so it's still a matter of empirical growth, right? Growth of empirical content, right? In fact, on Fireobbin's conception, it really works more like this, right? First, theories are much more open-ended on Fireobbin's conception. So, you know, we know to some extent what the old theory and the new theory say, but they have a kind of open-ended content, a kind of variety of different ways in which the basic commitments can be developed by further research. So the fact that they're not closed here in the diagram, that's what that represents is the open-endedness. The other is that the shared content, such as it is, is also kind of a distortion, kind of a construction, right? So there is stuff that the old theory predicted that seemed fairly successful and this gets shoehorned into the new theory, but because in part of what Fireobbin calls the incommensurability between the two theories, it's not, you know, the idea that it's shared content is a little bit of a fiction as well, right? So what you have is sort of a replacement of the old theory and the new theory, some shared content, but only sort of, and really it's more of a replacement of focus and emphasis going on there. Now I just used the word incommensurability. We've talked about it a little bit before, but this is really a major focus of these chapters. So let's talk about it for a moment. Incommensurability for Fireobbin means, to some extent, incomparability, right? That's where the word comes from, right? So one of the original uses of the word, or the home uses of the word incommensurability is in mathematics to describe, for example, the relationship between the length of the side of a square and the length of a diagonal, okay? The length of the side of the square and the length of the diagonal are incommensurable. In the sense that the length of the side of the square is one, right? The length of the diagonal is the square root of two and there's no finite number or a decimal or fraction that you can use to express those numbers in the same system, right? If you switch to treating the diagonal as a whole number, then you're going to get an irrational number for the sides. Of course, they're comparable in a sense, like you can mark the approximate lengths on one ruler and you can see one is longer than the other. They're comparable in that sense, but they're not rationally comparable. They can't be made part of the same sort of accounting system, right? Insofar as that means, you know, having a finite representation in the same numerical system, right? So, Too-Fire-Oven thinks that scientific theories are incommensurable and so far as there's no rational, logical way to line up all of the concepts, laws, claims, predictions, evidence, experiments for one theory and another theory to compare them one to one, right? The conceptual change that accompanies the move from one theory to another means that there is some ambiguity, some slippage between the two, right? Some change of not only theoretical but also perceptual content. In fact, in these chapters, Fire-Oven tells us that it's not just that our perceptions or our observations are influenced by theory to some extent. They're actually fully theoretical, right? And observational claims are fully informed by our theoretical commitments, right? We can, of course, within a framework on a pragmatic basis distinguish between something that's an observation and something that's a theoretical claim, but there's no sort of in-principle difference between the two, right? Any kind of commitment is on the same ground as another kind of commitment. So that's incommensurability. Fire-Oven tells us incommensurability is a philosopher's problem, not so much a scientific problem, right? It has to do with the way that philosophers want to rationally reconstruct, logically reconstruct scientific activity and not so much with the activities that actually scientists engage with. Scientists are more comfortable with ambiguity. They can make these comparisons just like an engineer, right? Can compare the side and the diagonal of a square for length, right? So it's a sort of artificial problem, but it is one that helps to undermine rationalist conceptions of scientific method. In Chapter 16, Fire-Oven has a very long description of ancient cosmology. He's really in the sense of the ancient worldview in relation to art, mythology, science, language. And his argument there is that one's conceptual system is influential on not only what one believes about the world, but the way one sees the world, right? A tight connection between concepts and conceptions and perceptions, right? And so it's a rather long description of that, but the key idea, I think, to connect it to scientific method, the key idea is that when you change from one theory to another, when you change from one language to another, and all of these associated conceptual changes that go with that, to a certain extent, one is perceiving a different world. The facts that one believes, right? One's beliefs about what the evidence says, what the facts are, will change. In effect, to use language from Thomas Kuhn, when you move from one conceptual framework to another, you're living in a different world. So that's what's going on, I think, in this third part of the book to sort of sum up, you know, scientific practice is much more complex than the philosophical rationalist would have you believe. Plurality, variety, creativity, you might say, complexity are all important parts of science. From the perspective of the philosophical rationalist, disorder and chaos are essential to knowledge and its progress, according to Fireabend. And the way to really understand science is to look at how it unfolds historically and to some extent to give space for the scientists to proceed creatively. And, you know, one of the things that Fireabend, I think, is trying to get us out of is rigid conceptual systems that impede the progress of science. That's a big part of what's going on in the first three quarters of the book. Part four, we'll start to get outside of science, per se, and into a broader view, but we'll save that for the next video. All right, see you next time.


All right guys so in today's video we're going to be talking about the 14 highest paying freelance jobs that you can land online in 2024 and many of these you can actually land relatively easily without having that much experience or at the very least you can learn them relatively quickly and relatively inexpensively without having to get a college degree so without further ado right after you gently cheers the like button we're going to jump into it with number one on the list which is going to be a Google merchant expert. And these are basically the middlemen in the online shopping frenzy. So Google Merchant is very similar to Amazon but it's Google's version of it and this is all part of Google's evil plan to take over the world and rule just about every industry out there.  YouTube is owned by Google. Please don't delete my YouTube channel Google. But yeah very powerful company. Also honestly a really good company they have a lot of great products. But Google Merchant Services is getting more and more popular and more people are starting to use Google Store and considering there's so many searches every single day on Google and YouTube and Google has access to pretty much all of the internet's data probably a pretty good idea to learn how to do this and there's not that many people who are familiar with how to use these platforms. So just as an example here's somebody who basically specializes as a freelancer in Google Shopping Ads and the Merchant Center. And they charge about 75 to 125 dollars an hour to do their work. Here's another one on Fiverr and they typically charge about 60 to 150 dollars per gig.  I believe that Google Merchant and Google Shopping is going to be more and more popular in the near future. And so it's probably a great idea to learn this as a skill as more and more people are going to be searching for people who are good at running these types of ads. And the coolest thing is Google actually offers entire classes on how to do this for free. So they literally just train people on how to use their platform. So yeah I think this one is an incredible opportunity. It's going to be even bigger in the future. So it's probably a good idea to get in early while you still can and it's still a really good opportunity. I'm going to give this one a 9 out of 10 opportunity score. And by the way I just want to let you know that I'm going to be doing a free training on how to grow and monetize your YouTube channel. And it's going to be on Tuesday at 9 p.m. Eastern time. It'll be a live interactive zoom call with me where I can answer questions that you have about YouTube. And I'll also be revealing the five biggest secrets when it comes to growing and making money from YouTube. And this is what you can do to either add a couple thousand dollars a month to your income or even grow a full time income purely from making content on YouTube. And when I started out on YouTube I was working as a pharmacist full time but within a few months of starting I was getting messages like this in my inbox. And all of a sudden I was adding thousands of dollars on top of my full time job. Now if you want to do the same make sure to join the live training because I'll also be giving away a free mini course only to the people who show up to it. This is not going to happen anywhere else. There will be no replays and there's limited seating. So make sure you sign up by clicking the link down in the description as well as the pinned comment below. And I look forward to seeing you there. Next is going to be a Pinterest manager. So Pinterest is one of the most popular social media apps for women and women make 70 to 80% of all purchasing decisions. And right now just because of the fact that this is not one of the platforms that people focus on a lot. Buying ads on Pinterest is actually relatively cheap and selling products on Pinterest is relatively easy to do as well. And so if you can learn how to properly use Pinterest, if you can learn how to use Pinterest ads, and if you can learn how to manage a Pinterest account and post on it, that can be an incredibly good opportunity. And it looks like the average salary per hour for Pinterest managers is about $15 to $30 an hour right now. This seller for instance charges about $10 to $25 an hour and this freelancer charges about $15 to $50 an hour. And full time Pinterest marketing managers will make around $90,000 a year according to comparably. And even if you're brand new and you have no experience, you just have an interest in Pinterest. Maybe you use it yourself. You can still charge around $15 to $20 an hour as a newbie just to get some experience, get that work in and basically get your foot in the door. So like I said, we do a ton of research on these videos. We try to kind of like predict what opportunities are sort of not saturated yet, but they're going to get even bigger in the future. And this is another one of those where I see it as a great opportunity right now. It's going to get even bigger in the future. And it's at that point where not that many people have gotten into it. And this is the perfect time for you to basically enter the market, learn these skills, get familiar with the platform, get familiar with how to use it, and you can make a ton of money in the future. So with this one, it's a little bit less high paying than the other one, but I do think there's also more opportunities right now. So I'm going to go ahead and give it an 8 out of 10 opportunity score. All right. So the next freelance job on the list is going to be digital designer, but you need to niche down. Okay. So digital design in general is very similar to graphic design, but it's done in the digital world. And you might be thinking, oh, those two are the exact same thing, right? Well, not exactly because graphic design could be designing things digitally, but then they're actually put out in the real world, whereas digital design is designed to only be in the digital world. And there are certain niches within digital design that can be incredibly profitable. For instance, there are digital designers that are making millions from in game fashion. And these are on games such as Roblox and Fortnite. For instance, there's a 22 year old from Florida named Samuel, who made over a million dollars in sales in 2021 alone. So here's the thing about niches like this where it's sort of a common skill set. If you just advertise yourself as a digital designer or a graphic designer, you're probably not going to get that many gigs and the gigs you do get are going to be relatively cheap, right? So you're not going to get paid that much per hour, unless you're just insanely good. So what you want to do is you want to pick a specific niche such as in-game design, maybe even pick a specific game that you design for, and that is going to be your gig and your niche that you offer, right? And digital graphic designers that get paid full-time make about $27 an hour, which is already pretty good, and graphic designers on Upwork cost around $15 to $35 an hour on average. But if you specialize and niche down, you can get paid much, much higher than this, right? This is one of those things where you want to keep your finger on the pulse of all of these different things that are happening, look for these different niches that are emerging, and then specialize in that type of design. So yeah, this one is really good as long as you niche down and as long as you specialize, I'm going to go ahead and give it an 8 out of 10 opportunity score. Next is going to be a YouTube channel manager, and this also falls under the category of a YouTube creative director or a YouTube content strategist. And this is kind of like being the backstage maestro of a YouTube channel, orchestrating every aspect of the channel's performance with finesse. And in this position, you'd be responsible for strategizing, creating and optimizing content for a YouTube channel to maximize viewership and engagement. Now, as you probably know, YouTube is incredibly profitable. It's by far the most profitable platform. It's the only platform where creators are making over $100 million a year, and people like MrBeast are getting far more exposure than entire news networks. And YouTube channel managers make about $68 an hour, which is $142,000 a year according to Zippercruiter. So these content creators are making a ton of money, but they're also stressed out, right? They need someone to come in and take some of the stress and some of the work off of their plate. And that's where the YouTube channel manager comes in. So yeah, I think this one is an incredible opportunity. You can make some top tier content. Like if you accidentally get a little bit of water in your eye, you'd make a video like this. Definitely got to give this one a 10 out of 10 opportunity score, although I am biased. YouTube has completely changed my life. I grew up watching YouTube. I started a bunch of random channels. Like my first channel was on RuneScape. I was basically just fighting people on RuneScape and then uploading videos. And it was always my dream to be a YouTuber and I made it. You know, I made it a reality. And I actually started coaching my friends and then random people that reached out to me and I started getting them results as well. And now I do accept a few people every month into my coaching program and I also have a free training which you can check out down in the description as well as the pinned comment below. I will warn you, we are pretty picky about who we accept into the coaching program. We only accept people who take it very seriously because we don't have that much time and we can't waste any time on people who don't take YouTube seriously. But yeah, if you think you're a good fit for the coaching program or if you just want to check out the free training, go ahead and check that link down in the description as well as the pinned comment below. Next is going to be a media buyer. So this is basically somebody who purchases advertising spots or advertising space and time to promote products or services across various different media channels. So for instance, you might promote products on Facebook. You'd be a Facebook media ads buyer. You might promote products on YouTube. You'd be a YouTube media ads buyer. And these types of positions you're usually going to charge between $50 and $200 per hour on a site like Upwork. And if you work a full-time job, you'll typically get paid between $63 and $101,000 a year. Now again, this is one of those where if you specialize and you get really good at a particular platform, you're probably going to be able to make a lot more money. I know media buyers that make half a million dollars a year, for instance. So yeah, this one is really good. I'm going to go ahead and give it a 9 out of 10 opportunity score. Another one that's relatively similar is a digital marketing consultant. So media buying is of course a type of digital marketing. There's a lot of other different types of digital marketing out there as well. For instance, SEO or search engine optimization. This is how you get blogs or news articles or content to rank at the top of Google. And you'd basically just be consulting different businesses on how to do their digital marketing strategy. So just as an example, right now, what's working really well in digital marketing is content, right? So quality content is the king of digital marketing. 70% of internet users want to get information about products through content instead of traditional advertisements. That's one of the reasons why YouTube, for instance, is one of the best ways to make money. Another really good way of making money is, of course, running paid ads. As a digital marketing consultant on Upwork, they're typically going to make between $15 and $45 an hour. But again, if you specialize, you can make a lot more than that. However, if you get a full-time job, digital marketing consultants make between $81 and $140,000 a year. So yeah, this is another really good one. As always, make sure you specialize, make sure you have a specific thing that you like to consult on, a specific thing that you are very, very good at getting people results with, and good things will happen. So yeah, this one is great. I'm going to go ahead and give it an 8.5 out of 10 opportunity score. And by the way, if you want to get a job in digital marketing, because that's what a lot of people do at first, they just get a job, learn the skills, basically get paid to learn the skills. And then later on, move into freelancing, start their own business or get a better job. I've actually interviewed a bunch of people on this channel that have been able to get entry-level jobs in digital marketing without needing a college degree or previous experience. And they were all able to do this by my good friend and business partner, Seth. And Seth is basically the goat of getting people jobs in digital marketing. And Seth actually does have a free masterclass where he's going to explain exactly what digital marketing is, the different types of jobs that he recommends you get in digital marketing, which one might be the best for you, and whether digital marketing in general is going to be a good fit for your personality. And you can check that out by clicking the link down in the description as well as the pinned comment below. Next is going to be a Google ads specialist. And Google ads is basically the platform that people spend the most money on out of all the different platforms out there. And you've probably seen Google ads thousands of times before. You search something on Google and there's an ad that pops up at the top. So this is a type of digital marketing like I talked about before. It's one of the better ones as well. Again, this is an example of you specializing. And Google ads experts make about $15 to $40 an hour on Upwork. So yeah, not going to go too deep into this one because I already talked about it a lot, but this is a really good one. I'm going to go ahead and give it an 8.5 out of 10 opportunity score. Now another job that's relatively similar to this is going to be a social media manager.  So typically this is going to be where you coordinate the content that gets posted, make sure it gets posted on time, make sure it doesn't have any mistakes, it has the right links in it, all that kind of thing. Sometimes in different types of positions you might also strategize on the content. You might also be the one who helps to create the content. It really depends on the position that you're in. Generally speaking on Upwork, social media managers make about $14 to $35 an hour. Again, really helps if you specialize in a particular platform and full-time social media managers make about $65,000 a year. So these digital marketing jobs are great because they actually prefer to hire younger people for these jobs. And it makes sense because younger people grew up using social media so they understand the platforms on a deeper level. And so it's much easier for you to get a job in a lot of these different digital marketing-related careers than many other types of careers out there like coding or something in technology. So yeah, this one's pretty good. I'm going to go ahead and give it an 8 out of 10 opportunity score.  Go ahead and subscribe to the video down below. I think only 15 to 20% of you are subscribed. I can see it in the analytics guys. Don't be a lurker. Go ahead and subscribe if you appreciate this. All right, so next one is going to be a YouTube scriptwriter. And this is one that I am seeing. I'm predicting it right now. This one is going to blow up in the next few years because one of the biggest pain points I hear when I meet with other YouTubers, when I talk with other YouTubers is they have a lot of trouble writing scripts. It's one of those things where it's very difficult to have someone else to help you research and write the scripts. So if you can be somebody who can go in there, you understand how YouTube works. You understand how to make scripts easily readable by the person who's actually presenting them. This can be a very lucrative career for you. Now, according to Glassdoor, YouTube scriptwriters make about $24 an hour. There's also a lot of opportunities for scriptwriters on websites like ytjobs.co. And yeah, this is one of those careers that I foresee blowing up in the near future. If you can even save the creator an hour or two on every single video he creates. If it's a creator that's making a ton of money like $100,000 a month, you are going to be saving them a significant amount of time and money. So yeah, this one's really good. I will say it's still in the infancy stage right now. And there's positives to that, but there's also negatives to that. So the positives are you can get in early, you can learn how to do this right now and you're going to be one of the best in the world in a very short period of time because not that many people are doing it. The negatives are the infrastructure for getting into this type of thing is not really developed. And so it can be kind of hard to get a job here. But with that being said, this one is still good. I'm going to go ahead and give it an eight out of 10 opportunity score. Next is going to be a course writer. So this is where you would help people create info products. So this could be anything from an online course or a coaching program where there's basically information that people are consuming online. Now, according to Glassdoor, course writers make about 56 to $92,000 a year. Curriculum writers make about $27 an hour according to Zip Recruiter. So that's very similar. And here's a story of somebody who made $20,000 in one two week Upwork freelance writing project. So yeah, you can definitely make money doing this. Now, if you were to combine this skill with instructional design, which is basically where you design online courses as well, you can make a ton of money doing that. I'm talking like as a freelancer, you could probably make $200, $300,000 a year. So yeah, this one's really good, especially if you combine it with instructional design and especially if you sort of specialize like I talked about before. I'm going to go ahead and give this one a nine out of 10 opportunity score. By the way, if you're enjoying any of these, let me know which one was your favorite. Also, if you don't like some of them, let me know as well. And if you think I should have included different ones on the video, go ahead, comment down below and let me know which ones I should have included. And of course, I always read your comments and there's a good chance that I'll either include it in a future video or if there's one you really liked, I'll go in more detail on it. Next is going to be a project manager. And they basically oversee the planning, execution, and delivery of projects within specified constraints such as time, budget, and scope. And this one works really well with freelancing because a lot of the time, a company will want to launch a project, but they don't necessarily want to hire someone full-time because for one, they don't know whether the project is going to work or not. They also know that it might be just like a one-quarter or a two-quarter project and then they're going to make the decision on whether they're going to continue with it or not. And then sometimes they just want somebody to come in and help them launch the project and then once it's afloat, once it's kind of like working on its own, they don't necessarily need a project manager anymore. And project managers typically make about $19 to $45 an hour on upward. Again, if you specialize in something, you can make a lot more than this. Project managers that work full-time jobs typically make about $49 an hour according to Zip Recruiter. So yeah, this one can be really good as well. I'll go ahead and give it an 8 out of 10 opportunity score. All right, so next one is going to be a bookkeeper. And this one is oftentimes mixed up with an accountant. And there are a lot of similarities and overlaps, but as a bookkeeper, at least in the United States, you don't have to get an accounting degree or become a certified accountant in order to do it. And this is basically somebody who maintains financial records, including purchases, sales, receipts, and payments for individuals or businesses. Now this one can be really good, especially at certain times of the year. And bookkeepers in general on upward charge about $11 to $25 an hour, but during tax season, they typically charge more than this. And according to Glassdoor, bookkeepers make about $24 an hour. So this one's pretty good. It's not amazing, but it's one where it's relatively easy to get into. Doesn't require a whole lot of training or anything like that. So I'm going to go ahead and give it an opportunity score of 7 out of 10. Next is going to be a podcast host or a podcast assistant. Basically anything related to podcasts. So podcasts are incredibly profitable right now. And the great thing about podcasts is you can kind of just put them on in the background if you're cleaning your house or if you're driving somewhere. And if you can specialize in podcasting and just understand how the industry works and how the different jobs work, you can get paid a ton of money to do this. And there's all kinds of different podcasts related gigs. Anything from setting up a podcast, because honestly the technology is a little bit complicated, all the way to advertising the podcast or being a podcast host. So for instance, podcast hosts get paid about $15 to $25 an hour. And you can make much more than that if you specialize in something when it comes to podcasts. And this is one, again, where there's a lot of podcasters out there making a lot of money, but they're also spending a lot of time making their content. And if you can just save them even a few hours per week, that's probably worth it for them to hire you full time and pay you a very good salary. So yeah, this one is really good. I'll go ahead and give it a 7.5 out of 10 opportunity score. Next is going to be an oldie but a goodie and that is email marketing. So email marketing has been around for over 20 years now. And it's basically been one of the kings or the queens of marketing the entire time. And although it seems like it might be boring, it is still incredibly effective. In fact, in terms of ROI, just about nothing else out there beats email marketing. They estimate that you'll make about $35 to $40 for every $1 you spend on email marketing. Pretty hard to beat those numbers. And email marketers on websites like Upwork make about $15 to $40 per hour. Now of course, there's specialized types of email marketers. So for instance, e-com email marketing where you sell physical products is completely different than information product email marketing. So you'd want to specialize, right? Always niche down, always specialize. And you'll get paid a lot more if you do that. Other websites, for instance, email marketers that freelance get paid about $75 to $125 an hour. So yeah, email marketing is incredible. It's still one of the best ways of marketing out there. I'm going to go ahead and give this one an 8.5 out of 10 opportunity score. Now by the way, I did a video that went viral. Got a couple hundred thousand views. And it's basically the freelancing for beginners tier list that talks about a bunch of different types of freelancings and which ones are the best. And you can check that video out by clicking right here.


Hello everybody, E here. Welcome back to another Thursday Theorist Review. Today we are talking about Stephen King's newest Billy Summers. If you don't know what the Thursday Theorist series is, it's where I connect all of Stephen King's books ever since Carrie, all the way up to the most latest, to the Dark Tower series by way of theories or by way of actual factual content from the book that references specifically the Dark Tower or the Stephen King universe as a whole. But let's get right into the video. First up, we have Billy referencing himself as the outsider. I know this is a very small, I mean I'm reaching here, but I did want to mention this because Billy says it at least three times within I think three or four paragraphs toward the beginning of the book and I think that's important. There is another section where Stephen King talks about you never know what's coming around the corner, around the bend. That seems to reference, that section specifically, seems to reference his van accident. Again, I could be reaching, I like to throw the reaching parts up front and then get to the stuff that I have, that I feel are valid claims. If you've been watching the Thursday Thiers video, there's over 60 of them at this point. I'm sure you know, but for those of you new before I go any farther, this video is going to be loaded with spoilers for this book and his entire catalog. So if you have not read all of his books and you're worried about spoilers, I suggest you click away. Next up is something that I found for whatever reason this name not spoke to me, but this name, you know, caught my interest, piqued my interest, whatever you want to say. So I went and looked up, my friend Patrick Costin has a database of all of King's books. I'm not going to share it because technically it's piracy if we share it, but I was able to do a search through, I own all of his books anyways in multiple different formats. So I don't consider it piracy me looking at it, but I'm not going to share it with you is what I'm getting at. And Patrick, I don't think Patrick's sharing it with anybody either. But there was a character, let's see here, let me check my notes. There was a character, Mr. Stepanik and Dalton Smith. The reason why this, well, I don't know why it piqued my interest. I don't even know why I remember it. But there is a character named Stephanie Stepanik, nay Dalton. In fact, I may have got that backward. One might be in one in the midst and one might be in Billy Summers. But I thought it was, I don't know, sometimes King just reuses names like like Traylani in I think it was the outsider and there was a Traylani in the Mercedes trilogy. But again, this stuff up front is reaching. I just want to throw these thoughts out that I had while I was reading the book. Next up, we have Midwood, which is a location in Billy Summers. It's where he spends the majority of his time. And yes, I'm going to mention it because it does sound a lot like Midworld. I'm not going to. That's not my connection to the Dark Tower series. I just wanted to make note of it. Now on to actual references in the book to other Stephen King works. The very first one that I'm going to talk about is the mention of, I believe it was Billy's mother working the Mangle or the Mangler, the laundry press folding machine. Stephen King wrote about very early on in his career. I'm not sure if it was Skeleton Crew or Night Shift. I forgot to check before I shot the video. But it's a short story called the Mangler that was made into an adaptation with Robert England, I believe, and some other folks. It's a pretty decent adaptation. It was a lot of fun. I felt, but it is a cheesy low budget horror movie. Next up, and this is my hard tie into the Dark Tower series because numerous, numerous times is Inside View mentioned in the Dark Tower series. And it is mentioned here. I always forget the guy's name from Night Flyer, but he worked for for Inside View. And I've I've tied all that stuff. I mean, it's literally mentioned in the Dark Tower books. Inside View is mentioned many times. So there's your hard connect. But I have another one that I enjoy a bit more, but we'll get to that in a second. Next up, we have another connection to the Dark Tower by way of Stephen King himself referencing himself or putting himself in books as a character. Of course, he is a character in Song of Susanna. I can't remember if he's in Wolves of the Kala or the last book, The Dark Tower. But he references himself. He does not he he does not mention that this this quote is from Stephen King. But if you listen to the audiobook, Stephen King actually quotes himself. They bring him in as a narrator for one line. And that line is I always keep two things in mind, myself and the stranger. So that that's a Stephen King quote. It was interesting that they would bring him in just for that little small section. I thought it was a really cool Easter egg to to add to the audiobook. And what I want to know is did any of you catch that in the text? Because I didn't catch it in the text. I caught it in the audiobook and last but certainly not least, the most important piece of the puzzle in this one is Sidewinder, Colorado. And the Overlook Hotel are referenced numerous times. In fact, Billy actually visits Sidewinder. On top of that, there is a painting, a picture in his. I believe it's the apartment he's hiding in. It has to be because it's after the assassination attempt. And the hedge animals in the picture move. I've already connected the shining to the Stephen King universe. I believe that the shining was a thinny and the creature or the shapes and everything that you see at the end of the book. I believe those are creatures from the prim or something like a like not really a penny wise, but more of an ethereal type of creature. I know I know I didn't like this book and I appreciate and respect you guys who came forward and said that you did like the book.  You want your comments won't show up anymore. It'll look like they're there, but they won't show up anymore. All I ask is that you be respectful when we talk about these things.  But did you find anything that I missed here? I don't think I left anything out this time.  I did not do that this time, but I might next time. I don't know, but I'll tell you any time that I do. Did you find anything? Let me know down there in the doobly-doo. Also, let me know whether or not you like this book, whether or not you loved it, hated it, felt mad about it. Let me know if you haven't already. You don't have to repeat yourself if you already commented on the review. But let me know these things and let me know why you felt these things so that we can have a discussion. But until next time, I have been E, you have been U. This has been another Thursday theorist review. I'll talk to you guys later. Bye bye. And for those of you who hang around or watch the community posts, those of you still watching the video, there is a on my Twitter account. The link's down there in the doobly-doo. There is a contest right now to win a copy of I think it's right here. Night Shift, the Cemetery Dance Gift Edition. All you have to do is retweet the my pinned tweet and make sure that you are following me on Twitter and that you subscribe to me here on YouTube. That's all you got to do. Good luck.


Let me, let me get a good listen. Let me hear the textures of that crunch. Here we go again. What did he do now? He's really good at just subtle. See, I get to put my handset and I'm just like, you got that gas X. I wouldn't do anything. I'd just be like, because it's natural. Love them too. What? Hello?