Good morning. My name is James Coulomb, and I have the honor of serving as the NIH Working Group Coordinator for the Gabriella Miller Kids First Pediatric Research Program. I'm here to give you a brief overview of the program and a progress report, and also talk a bit about a very recent collaboration with COMP. Excuse me if I read this. I want to stick to the time, and I want to not skip over a lot of salient points. So the Gabriella Miller Kids First Pediatric Research Program was initiated in response to a congressional act, the 2014 Gabriella Miller Kids First Research Act. Both the program and the act are named in honor of a 10 year old Virginia girl who in her short lifetime became a very forceful advocate for pediatric research. The act did a number of things. It ended taxpayer contributions to presidential nominating conventions, and it transferred $126 million that had been accumulated into a pediatric research initiative fund and authorized an appropriation of $12.6 million per year for 10 years to the NIH Common Fund for Pediatric Research. The first appropriation was for fiscal year 2015. This is separate normally from NIH's other budget, so it's an additional chunk of money for NIH to advance research with. The vision of the program is to alleviate suffering from childhood cancer and structural birth defects by fostering collaborative research to uncover the etiology of these diseases and supporting data sharing within the pediatric research community. And notice the emphasis is really on collaborative research and data sharing. We're operationalizing this vision by building a pediatric data resource to provide access to high quality genomic and clinical and phenotypic data and in order to facilitate collaborative research. The intent is to accelerate gene discovery and ultimately to improve diagnostics and therapy. Kids First is a trans-NIH effort supported by the NIH Common Fund, and the institutes that chair the Kids First working group are, well, it's basically program institute leadership from NICHD, NHLBI, NCI, and NHGRI. In the working group, there are also representatives from a variety of other institutes and the CDC, basically everyone who's interested in pediatric research, we try to rope into our program. The list of members can be found on the Common Fund's NIH.gov Kids First website. The working group, which puts together and organizes and thinks up and puts together the nuts and bolts of the program, is led by a smaller leadership team, which is named here mostly their program officers, but we also have grants management specialists, a team from the Common Fund, and since all of us have other jobs, sometimes a little too many jobs, we have Valerie Cotton as a program manager to ride herd and keep us in line and make sure the program doesn't go off track. We also have a governance structure, as it were. This is an overview of the basically four elements of the program, the working group, the data resource center, sequencing centers, and again, X01 investigators who all have representation on a steering committee that's chaired by Virginia Papiano. We also have a group, we've recruited a group of five outside experts to independently or individually give us advice about the program. The program initially was conceived of as three major initiatives. One, we wanted to identify cohorts of children with cancer and or structural birth defects and their families and provide whole genome DNA sequencing and in order to build a database with the phenotypic, the genomic, and clinical data that the community could then use. The second initiative was to build that data resource and make it available to the community. And a third initiative, which is still in the planning stages for the future, is basically demonstration programs to show Congress that this is a good approach and we've managed to do something with the money. In the first year of the program, we had sequencing done by Baylor and WashU's sequencing centers. Subsequently, and for the last three years, we've been working with Hudson Alpha and the Broad Institute for sequencing our cohorts. As Charlene said, we use the X01 mechanism, which is not really a grant. It's a grant, I don't want to say the word grant. It's to provide access to NIH funded centers, in this case sequencing centers. And in the first three years of the program, we've put into our pipeline the following, the named here cohorts for sequencing. This represents about 6,000 cases. And since most of the studies are in TRIO's design with the affected child and their parents, this represents over 18,000 genomes. Five of these studies are available now to the public. The rest are somewhere in the pipeline and more should be available soon. In this last year, 2018, the fourth year of the program, we were able to add 11 cohorts representing over 8,000 genomes. And this is an expansion of what we expected to be able to do with the money. And we were able to expand our sequencing scope by collaborating with other programs at NIH. These include the Include Program for Studying Down Syndrome and NIAAA, who've provided additional funds for sequencing, and the data will go into the Kids First program. These are great examples of how NIH programs can work together to amplify our effects. So some of this is going to seem like down in the weeds administrative trivia, but in the four years of cohort sequencing, we've faced a number of surprising challenges and come up with solutions. And basically, this program has sort of been a wild ride with one problem after another, kind of surprising because other programs have gone here before, but we seem to be facing new problems all the time, but we're managing with a dedicated staff and dedicated folks at the sequencing and data resource centers. So I'm going to tell you about three of those problems. The first was not really a surprise. XO1s don't come with any funds for analysis support. So we repeatedly heard from our XO1 investigators that, wow, it's great you've given us hundreds of thousands of dollars for sequencing, but now what can we do with the data? We don't have money, and it's hard to get funding for analysis support through NIH regular grant mechanisms and the review process. So in response, we have been issuing funding opportunity announcements for RO3s that are dedicated to support analyses of Kids First data sets and the development of appropriate methods for analyzing those data sets. These are not using Kids First monies, but instead we've gotten a number of institutes to agree that if they get funding, if they get review scores that meet their pay lines, that they'll pony up the money. The combined direct budget for these two-year projects is twice the normal RO3 budget. So it does give you a little bit of leeway for at least hiring bioinformatics personnel and getting started with analysis. If you're interested in this, you can contact myself, my e-mails there, or the IC representatives that are named as scientific contacts in the program announcements. We're soon going to be reissuing this announcement, so this number is going to change, but there will be an announcement for continuing the RO3 support. Oh, and by the way, these are program announcements with referral or PARs, and that means that they should get a more targeted than normal review, and the reviewers should be well aware of what the intent of the program is and review accordingly. Okay, another challenge that was a bit of a surprise was that the cohorts often had data use limitations that interfered with the intent of the program. Our mandate is to make data generated by kids first accessible to the research community and to facilitate collaborative research by enabling researchers to easily combine and compare data sets for cross-data set analyses. We found that many of the data use limitations were restricting the ability to use these data sets fully, and we also were under the impression that I've got to be careful here because Valerie's going to kill me if I say this wrong. We were under the impression that possibly some of these data use limitations were misinterpretations of the original consent language that the participants had agreed to. So we undertook about a four-month exercise to educate our cohort PIs in what the data use limitations really meant, and in this last selection of cohorts, we were able to specify our expectations of broad data sharing. Didn't say anything wrong? Thanks. Another challenge was that when you go through a DB gap to apply for access to these controlled access data sets, your application for access is reviewed by a data access committee typically, and up till now, requests for access to kids' first data sets have been sprinkled about the different institute-specific data access committees, and we foresaw that as being a problem both in terms of consistency and possibly in terms of timing. So we've formed our own data access committee just for requests for kids' first data, and that committee is being chaired out of NCI's Office of Data Sharing. We think this is going to streamline the process and make it consistent and hopefully speed up the processing of these data access requests, making our data sets more available to the community, more easily available. I talked about cohort data sequencing, and we're building a set of data, but that's not very useful unless people can access it. So we funded, in the third year of the program, a data resource center. That data resource center is really a consortium of five different sites and investigators at those sites with CHOP, the Children's Hospital of Philadelphia, as the lead institute. The overall PI is Adam Reznik, and he and his team were funded just a little over a year ago as of last July. The work of constructing this data resource center was divided into three cores, a data coordination center, administrative and outreach center, and a data research and a team working on a data research portal. Their stated goals are in this slide, but I'm just going to touch on some of the accomplishments that they've done in this brief last year. OK, the data coordinating center is charged with taking in the genomic, phenotypic, and clinical data, and that's surprisingly difficult. These are huge data sets, as you probably know. And so just piping over data to a cloud resource and having control of it is actually quite a challenge to arrange. They also were charged with and have constructed a phenotypic clinical data harmonization framework using controlled ontologies. And this is a, like in all this field, this is a source of continued improvement and a lot of interest and hopefully powerful tools for analysis. The genomic data coming into the kids first data resource is being harmonized against the latest reference build of the human genome. And they're using an optimized and scalable pipeline. So all the data sets are harmonized the same way and that makes it easier to bio analytically compare and search data sets. Again, that's actually a pretty huge project. Well, the data resource center as a whole recognized that the patient and clinical communities can and should be able to access and contribute to the research. So they recognize that we have partners, not only the researchers, but also health care professionals, the patients and family members, and the interested community. So they've done outreach both to help design the data portal and the website. They went through a process of having community meetings, at least three with the interested community, getting feedback on what features were desired. One of those features or features of the data resource center was a call for more outreach. People in the, especially the advocacy community, really wanted to know about the researchers. They wanted to know about the projects. They wanted to know about the data resource center itself. And they wanted to know about scientific progress. So the administration and outreach core has developed flyers and handouts and posters for meetings explaining the program, as well as reaching out through social media with investigator spotlights and spotlights for the community interested advocacy community groups so that some of their efforts can be better coordinated. OK, finally, again, the data is great to assemble and index and put together phenotypic frameworks. But it's not very useful if you can't access it. And it's not easily accessible. So an important part is the data resource portal. This is the PI of this part is Vincent Ferati. And they've developed their charge with, and I believe have been successful in a very short time, in developing a compelling user interface that will let users of all skill levels browse, visualize, and perform in-place analytics across the kids' first and related data sets. Of course, these are controlled access data sets. So it was necessary to integrate into this a framework from the Gen 3 platform that allows controlled access of the data sets. And they also integrated in Kovatica, which is sort of a, now I'm not a bioinformatics person, but I sort of view this as a Santa's workshop where you can import power tools, as it were, into the workshop and set the L's on working on your data sets. It really looks intriguing to me. And you'll see a little bit of glance of it in a minute. I can't really convey how this data portal looks and feels and how useful it might be. So what we're going to try and do is show a, and I can't see, oh, I've got to use that, sorry. So what I want to do is show a quick demonstration of the portal. You can do this yourself. You go to the kidsfirstdrc.org website, click on support, go to support, oops, and getting started. I'm not sure why that scrolled. Oh, yeah, yeah, forgot about that. Got to scroll down. And down here is a quick demo of this first, now they only had a year to work on this, so this is their first iteration, and it will certainly be improved upon. But it's pretty impressive, I think. And I'm supposed to go, OK, sorry. Hello, and welcome to the kidsfirst.org center demo of the website and portal system. The goals of the kidsfirstdrc website are to increase research, collaborations, partnerships, and engagement in the research, health, patient, and foundation communities, as well as provide a centralized location for the dissemination of information and resources to support the overall research goals of the kidsfirstdrc and kidsfirst program. The website will provide user support, news, and information, as well as encourage people to use the portal. It will provide real-time summary data for updates, as well as news to keep the community informed about study updates and research. Once users are navigated to the portal, they'll see this landing page where they can log in with popular identity providers like Facebook and Google. Let the pro you do it. Can you get rid of the feedback? Once users are logged into the portal, they'll be navigated to a wizard to orient them. They can select a self-identified role and then are navigated to the terms and conditions for data access. After reading through these, they are required to check off that they have read and agreed to it and then can enter the portal system. I'm just going to navigate to a user that has a little more information filled in. From here, you can see that the user dashboard has information about things that have been saved and interaction points. Users can also edit their profile with some information about themselves and interests. The next major setting is the partner integration area. Right now, there's two integrations. From the University of Chicago, the Gen 3 data comments, which allows people to gain access to data through the NIH and DBGAP program. And then the second partner, Seven Bridges, Kovatica workflow platform, which will allow you to quickly analyze data from the kid's first file set in an online cloud environment. The last page that users can interact with is the file repository. You can see on the left data features highlighted that you can browse through, as well as a table of files with some summary stats and actions that you can take on those, including downloading a manifest or a report. Once you've identified a study of interest, you can download that information. You can see that the download has started there. Another thing that you can do is identify multiple studies of information and then push those files onto the Kovatica platform to analyze data in the cloud. Before we do that, we'll always make sure that users have the permission to access these files. You can see I don't have access to one study, so I won't be able to copy those. But I do have access to CBTCC, so I will be able to copy those. And select my Kovatica project and copy the files right over. Once I'm in Kovatica, I can check and see that all of the files are listed there for me, that I just copied over. In addition to any other files I might need for workflow usage, like reference genomes or input data sets that would supplement that. In Kovatica app area, I can add apps to my workflow area. I can search through public apps, add them to my projects, or I can create my own app. So for Kids First, a custom joint genotyping workflow app has been created. I've already set up a demo task that shows what this would look like. So from the task tab in Kovatica, you can see the Kids First joint genotype workflow that's already been set up. Going into that workflow, you can see all of the steps are here with their files attached. I'm going to select the files that we chose from the portal. So I'm going to be looking for GVCF files that are harmonized. Once I've found the correct files, I can select them and save them to the workflow, which you can now see that's resolved. And then I need to name the output. And I can kick off the workflow with Kids First data. You can see that it has queued up. In my task tab, I can see a list of all the running tasks. In my collaborative environment, I can see there are other tasks that are running as well. And even one that has failed that I might need to go in and fix something about one of the preset inputs or the files I selected. I was supposed to stop that. And if I can get back to my on the bottom. OK, so I don't know about you, but I'm pretty impressed in what they've built in one year. It's time. And looking forward to the future, this is a very dedicated team. And I think they're doing fantastic work. OK, back. This is a timeline sort of overview of the Kids First program. In the first couple of years, we only did sequencing. And then we've continued that and expect to continue it through physical year 2012, building the data sets, the data resource. We funded a data resource center. And that funding will at least continue through 2012. We've issued RO3s for data analysis and we'll continue to do that at least through 2012. Pardon? Oh, 2021, sorry, a little dyslexia time here. The last three years of the program, however, are sort of terra incognita. We have no idea what we're gonna do. That's not true. We know a lot of possibilities that we could do, but we're just now embarking on planning for that, for those years. One thing we know is that it will be important to demonstrate the value of the data resource we have built and some possible projects to consider are funds to support phenotypic curation, funds to recruit and or re-consent cohorts of affected children, data mining or demonstration projects. And of course, developing animal models will be important or is likely to be important. And your suggestions are solicited and very much wanted. Finally, I want, since this is a comp collaboration day, I wanna talk about a very recent collaboration. I think we found out about this less than three weeks ago. So it's pretty fresh. We're trying to move it for NIH standards, the speed of light here to get this up and running. The project, the collaboration is to develop mouse strains to study phenotype and validate coding and non-coding genetic variants identified from kids' first whole genome data sets. We want the community to invite and to nominate variants identified through analysis of kids' first data sets for mouse model production and phenotyping to take advantage of the powerful production pipelines and phenotyping pipelines that comps developed. We've put together a team of NIH program officers to evaluate these. We call that an administrative review to evaluate the nominations.  If you have a series of variants to nominate, you don't need to fill out three pages for each variant, but what we came up with brainstorming was this set of information. It's likely to involve as we see what comes in. And if we need more information, we'll come back to you with additional questions. As I said, in order to get this moving quickly, well, the nominations will be reviewed by a subcommittee of NIH staff from the kids' first working group. The variants will be prioritized basically based on the strength and breadth of the supporting evidence. In other words, whatever you tell us is important. Make your best case. And decisions will be finalized in consultation with the Comp2 staff. So again, we're moving very rapidly. Our first deadline will be October 26th. And if we need more information, it'll be requested after our preliminary review. If you have technical questions about the variant production, you can go to this email and Comp staff will answer those questions. Okay, we at kids' first want to use this as a pilot for how to evaluate nominations and pilot a process here for feedback to see how this program evolves and how to go about best accumulating nominations with the idea of maybe in the future having support for model producing model organisms using kids' first variants. Mouse aren't pictured here, but certainly in the mix already as it were. So finally, I want to put in a plug. We're going to be at the AS American Society of Human Genetics annual meeting. We'll have an evening poster session and social as it were so that you can meet kids' first cohort PIs. We can talk about collaborations. We can get your feedback on what you think we should be doing with the program. And data resource center staff will be there as well as people from the kids' first program. And we're hoping that this will be a truly interactive meeting and another way we're hoping to have meeting structures that are maximally productive. I have to say, I haven't encountered an NIH group that is as motivated as this group and we're constantly trying to innovate and tailor our program to use the money Congress has given us to the best effect and we'd love your feedback. So you can catch me here or you can contact me. You can find out more about the program on the Common Fund website for kids' first. And I guess we're not going to take questions but you can get to your break now.


Start the presentation, good luck. OK, thank you. Well, hello, everyone. I'm Matias Vara. I am here to talk about some of the work I did in the last couple of months regarding some work I did to improve the booting time of the Toro kernel, which is a kernel dedicated to running built-in machines. Can you hear me well? I mean. So in general, there are no speakers here. OK. OK, cool. So what is exactly Toro is application-oriented kernel, which is made of, more or less, a five-mainly unit, which are a process memories, file system, networking, and these components, these units provide a simple API for the user application. For example, if you see the process unit, we'll see machines thread, three-thread, all the manipulation of the thread. If you see a file system unit, we'll see some API to manipulate files and so on. In the case of microservice, which is a user application, we propose to compile the microservice together with the kernel, and this results in a single binary. The microservice can decide which are the components going to include in this binary. And that is done directly from the syntax of the microservice. So for example, in this case, I say, OK, I will include memory, file system, the extensive driver, and the Intel Gigabit driver. After the rest of this, we generate a binary, which is a ELF. From this binary, we have a set of tools in which we can first generate a Dmash by relying on another tool called a Clody. We can then launch a built-in machine. To demonstrate all this work, I will just show a simple demonstration. Here, for example, we have a total running in a simple microservice, which is serving index HTML. For example, here, you see the results. What you see here is more or less the initialization of all the drivers. Sorry, we're just here, the initialization of all the drivers, the network key, and so on. And then from here, you see the user application start to execute. If you come back to the slide. So actually, we spend some time to first compile the kernel and the user and the microservice. And this takes more or less one second, because it's only compilation, and then generate the Dmash. We take another one second and a half, more or less, to boot the built-in machine. Here, I'm taking into account the time the door is open. And here, this time, it shows that the kernel starts to execute, but not after that. It's just until the kernel mine starts to execute, for example. The Dmash in the current state is around four megabytes. So what we figure out, but I figure out that this time limits a lot, if you wanted to use kernel, for example, continuous deployment of microservice, or if you wanted to instantiation on the mine of microservice, because we need a fast instantiation. So if we see more in detail how is the booting process of Toro, you see, first, the built-in machine monitoring instantiation, which includes, for example, instantiation of the device model, bias, and other stuff. I'm not pretty sure about this. Then you have the bootloader that is already part of the kernel, which is instantiation of most of the hardware, the processor, and two log-mode, an APG in, well, read the kernel from the disk, and then put it on memory. So this talk, I'm only going to talk about the word I did, which is what focuses on these two first steps. In the next slide, I'm going to talk about how we try to improve this time. So yes, I will start talking about how I improve the bootloader, then the visualization of the built-in machine monitor. I will present some tests that I did, and then we conclude. What the problem that I had at the beginning was that, as you can see, the generated image that includes the user application and the kernel was very big. And this was like this, because in order to make the bootloader simpler, what we say is the image will be the copy of the kernel in the memory. So the whole, I mean, an image of the kernel in memory. And we did it like this, because it makes it seem a little bit bootloader, because you just need to read the image, put it in memory, you don't need any compression or something like this. And the main problem of this, first, you end up with a mesh that is huge, as you can see, what's four megabytes. The bootloader is still complex, because you still need to initialize some hardware, any paging, and so on. So the proposal, what I'm working on, was to use the minus kernel option, which is proposed in QAMEM, to load the kernel. And I will explain a bit what is exactly this. Actually, what you can tell QEMU is to pass the binary, which must be a multiboot kernel. And what is exactly going to do? Well, this is not exactly like how the binary is, but I'm using these pictures just to illustrate a bit. So actually, the binary, which must be ILF32, you have for sure all the sections, and you need some sort of special header that QEMU is going to read. From this header, it's going to read all the sections of the binary, and then put it on memory. I mean, this is the memory of the virtual machine on the guest. When QEMU starts to execute the multiboot mind, which is a point in the x-text section, the processor is already in protect mode. So most of the hardware is already initialized. So all that feature that you need to implement the model to install a hardware you don't need anymore, because you already have it here. And then, at some point, you want to start to execute the kernel. So the benefits of using this option that have QEMU were many. For example, I could reduce the size of the mesh from 4 megabytes to 130 kilobytes, because only include the binary, right? That reduces a lot of the complexity of the bootloader, because you don't need to jump to protect more the names on the stuff, because QEMU is already doing this for you. And also, since you don't have to read the whole image from this and put it on memory, because QEMU is doing this, you release a lot the boot in time. I started with 1 and 1 half, and I end up with half second to boot the kernel. The main drawback of this is that, well, not all virtual machine monitors support the use of the feature. So at the end, you're porting your kernel to that virtual machine monitor. Second, QEMU only support ELF32, so you need some sort of magic to put ELF64 inside ELF32, which is extra work that you have to do. And still, when the kernel starts to execute, it still is in protected mode. If you want to use 64-bit, you have to go to log mode, and you still have to do such initialization in the boot loader, so it is not that you can just start to execute the kernel. Some people were working on this more precisely in a project called QEMU Lite. We tried to add these features to QEMU, so you don't need to enable log mode, because when you jump to the kernel, it's already in log mode, so they use a lot of also the composite of the boot loader. But they stopped it to work on this, I think, one year ago. If you see the port that I did for Toro, you can find it in that issue in GitHub. I stopped in that one year ago, I think. So the next topic that I want to talk is how I work around the virtual machine monitor to try to improve the initialization. So actually what I did was, I saw three approaches to try to improve the virtual machine monitor. These approaches are based on QEMU and QEMU, and these are Keywood, Nimu, and Firecracker, maybe you know already then. The big picture of these approaches is that they try to improve some aspect of the virtual machine monitor, for example, simplify the load of the kernel or some reduce the device model. So I think they tackle different aspect of the whole virtual machine monitor. And to talk about these approaches, I wanted to first introduce some concept here. When you have the kernel, the Linux kernel, the Kavi driver, which provides all the virtualization features. Then you have the virtual machine monitor, which provides, for example, device simulation bias to the guest, and then you have, for sure, the guest in guest model. So the first approach I want to talk is Keywood, which is also based on QEMU. And the idea that proposes a firmware, which is much more optimized. The only drawback that they present, they are not a lot of information about how exactly is the optimization, but one of the drawbacks that they present is, for example, they limit the size of the kernel that you can load. It is 8 megabytes, and you can find more information there, which is cool with this is that you can just compile it and then use it by passing the minus bias with the firmware. The next approach that I tried was NEMU, which is based on QEMU, but they only focus on two platforms. And the idea of this project, at this idea that they gave me, was that they tried to reduce all the device model in order to reduce the texture phase and also the, for example, memory footprint of the virtual machine monitor. Also, they propose a new type of machine, which is named Beard, and to use this virtual machine, you can only boot from USB. I did not work too much on this, but you can find more there in that link that I used. And the last approach that I tried was Firecracker, which is, I think they started to be public on December, I think. The nice thing here is that they don't have any device emulation, all the hardware is based on Viewtio. What is also nice is that you don't have this multi-boot feature that has NEMU, but you can, for example, use Firecracker and ELF64 binary, and it's going just to start the kernel, and the processor is already with patient-enabled and 64-long model, which is quite nice. So that reduced a lot of the hardware initiation I had to do before I secured the kernel. So how I compare these approaches, well, the test was quite simple. Well, I'm sure it was the time from I launched the VN until the VN is shut down, and to shut down the VN, I just added some code in the kernel mine, and then I did this for three approaches, and then compared the time. If you want to see more about the script that I used, you can see here. For sure, you can give me some comment about the script, because it's just sort of a sketch. So that is the test, the rest of that I have. This is the hardware that I use it, and one interesting thing, but there are many interesting things that you can see here, for example. Here you have Kimu, where I use the four megabyte image, and then you can see the difference when you start to just use the binary. I mean, that is rational, because you're using a lot of the binary. I had to load on memory, and then you can see that you have 300 milliseconds that you get if you use Kimu. Then you have Nimu, where you see a difference of 152 milliseconds for Kimu. I don't know why, but then you have a lot of difference when you use Kimu, and this is really interesting what you get by using Firecracker, because it's only take 27 milliseconds to start to execute the kernel of mine. And it's just a note that I leave here just to compare as far in mind the times. For example, if you follow this blog and you check how much time spent in Echo is more or less two and a half milliseconds. And here you have a whole built-in machine, a sort of micro-built-in machine, how they call it. So, yeah, I'm going to conclude. So what I get is when we use a solution that is a combination between a multi-boot kernel and key-boot, which is a framework which is optimized, you see an improvement of my current boot loader of 11, yeah, a factor of 11. I agree that my old boot loader was a bit crap, but still. Then we have a factor of 85% when we try with Firecracker. My impression is that the choice of one solution over and over is just a trade-off between the need that we have to do to adapt the kernel to that solution and the resulting boot-in time that we want to expect. So, yeah, that's me. I don't know if someone had any questions. Maybe it was too fast. Yeah, that's it. Yeah, sorry? No, I didn't try. Ah, sorry. If I had tried a KBM tool, no, I haven't. They told me to do it a couple of days ago, but I had no time, but I will do it next time. Implementation of what? Sorry, yeah, the question was if the implementation was in Assembler and Pascal, the implementation of what? Well, they have, yeah, a part of Assembler, a part of Pascal, yeah. I mean, all the work that I present here is most on the boot loader, so it's most Assembler. So, if you have no questions, that's all.


Hello, and welcome to Newsclick. We have with us our editor-in-chief, Mr. Prabir Purkayasta. We are going to discuss the ongoing military situation in Syria. Welcome, Prabir. For over one and a half months, the government forces have made serious advances towards the east of the country in Syria. They are now in Derazor province. So how do you see this advance? I think there have been very, very significant changes that has taken place in Syria over the last six months. It's probably good to have an overview of what's happened. They have liberated Aleppo. Half of Aleppo was under the siege or in the occupation of the Al-Qaeda other forces, allied to Al-Qaeda. That siege was lifted sometime back. As you know, the Christmas for the first time after a couple of years was celebrated in Aleppo. Now they have lifted the siege of Derazor. Now this was a siege which has been continuing for almost 30 months, two and a half years. They have lifted the siege. This is a very, very significant change. If we look at the map of Syria and particularly the changes that have taken place over the last six to seven months, you will see what was originally a small region under the Syrian government's control, probably about 25 to 30% of the territory of Syria, though 80% of its population, was under the Syrian government forces. Now issue is that it is quite different and you see that they have gained by all accounts at least three times the territory that it had at that point of time. So at the moment, there are still pockets which are not under its control. They have come to those pockets, but there has been a significant enlargement of the territory that it has held, particularly the east, which is largely desert. So not very well populated, but has oil wells over there and two major cities. One of course is Derazor, the other is Raqqa and both were strongholds, the areas with the strongholds of ISIS. The Derazor Syrian government never lost the city. It was isolated. It was at the siege, but nevertheless they held on to it using various air lifting, air bridge, supplying it with food and other weapons, etc. So this, they had a three-pronged attack towards Derazor in order to lift the siege. One was across the desert, which was really the Pamirah, Sukhna, Derazor highway. Other was along the Euphrates from the north and the other was an attempt from the south along again the Iraqi border and then bending towards Al-Bukamal to and then via Mayadin to Derazor. These are the three axes in which it was advancing. It is very clear that the major thrust for them was the desert because here you can take over the major cities, then you can quickly cover the distance. Unlike the Euphrates river where the terrain is much more difficult and the ISIS was able to mount offensives from the east of Euphrates. You can see the map is very clear that they were vulnerable to attacks from the east or from the ISIS. So given that these three axes meant that the ISIS was under pressure from all sides and finally what has worked is essentially breakthrough straight down the Pamirah, Derazor highway and they have now broken the siege. It also means that when you look at the maps, the maps are a little misleading. We see them colored red or black, which is normally what ISIS areas are colored and then you have the blue or green, whatever colors. There is idlib is shown as a province of the Al Qaeda. Essentially in the east, which is the desert region, the towns and villages are held but the territory is largely empty. So therefore, if the main towns are taken over then others get into what would be called pockets and those pockets can be reduced over a period of time. In the east it does look like those pockets are going to be now slowly squeezed out, fragmented, squeezed out and Syria will be soon really in control of the region of the entire eastern region which is the west of the Euphrates river. That opens up the question what happens south of Derazor which is still an ISIS occupied area and across Euphrates which is also occupied by ISIS which is at the moment a two front war. In fact a three front war. ISIS is fighting Syria on this side of the Euphrates on the other side. It is fighting the Iraqi forces which are also converging on that area from the other side because they have liberated parts of, after Mosul they have liberated parts of the region which are contiguous to Syria and are in a position now to advance on this side as well. On the north they are also facing, ISIS is also facing pressure from the Kurds who are now being supported by the Americans as well as what's called the SDF which are really some of the Arab forces which have joined with the Kurds against ISIS. So it's facing a three front war. West of Euphrates there are oil fields, just the south of Derazor there are oil fields. Now who controls these oil fields is the next issue. The month of September is going to be actually very significant in terms of how we can see ISIS controlling and losing its territory. Also in the west of the Syria we are witnessing a simmering conflict between, rising tensions actually between Israel and Hezbollah. Israel just held its biggest military exercise in the last two decades. So how do you see, how do you read this simmering conflict between Israel and Hezbollah towards the west of the country? You know there are two sets of issues involved here. One is of course Lebanon and Lebanon for Israel has been a major issue because Hezbollah is the only force which has held it to a military draw in 2006 when they had crossed over into Lebanon and tried to come up to the Lethany river and as well as in earlier times when it had physically been thrown out of southern Lebanon and had to retreat back to Israel. So Israel has never recovered from the fact that militarily Hezbollah is the only force in West Asia, the only Arab force in West Asia which has fought it to a draw and if not forced to a draw from certain occupied territories. It's something Egypt didn't succeed, something Syria didn't succeed in Jolan for instance. So therefore they do look upon Hezbollah as a serious military threat. Hezbollah also has accumulated a lot of rocket and other designs and is capable of launching by conservative figures something like 10 to 30,000 rockets into Israel including up to Tel Aviv. So Israel has always held that this to be a major threat both in terms of its offensive capabilities and as well as its defensive capabilities which allows Hezbollah then to confront militarily Israel. With the Syrian war Hezbollah has actually also gained a lot of military experience now it's linked directly to Iran, Iraq, Iran, Syria, Hezbollah. The link is now complete, there is a possibility of supplies being actually increased. They don't have to fly, they don't have to go by ship, they can directly go to Lebanon from Iran. So this is a serious, shall be said, strategic weakness not developing for Israel that it does not seem to be able to control militarily the region as it could in the past. Now Hezbollah has concentrated its force outside the demilitarized zone which is between Lebanon and Israel which is right now controlled by the United Nations forces over there. They are in supervisory capacity watching the ceasefire. Now Israel tried to the United States to say Hezbollah should be disarmed even outside this part of the zone, even refused to do so. Israel's problem is just after the UN controlled zone at the moment where the UN observers are there is a concentration of Hezbollah forces including rockets and other missiles which are capable of being launched to Israel. So Syria was a possibility for them to march through Syria after Jolan, go past this line as it were which Lebanon, in Lebanon is held by the Hezbollah and take it from the rear almost like what the Germans did to the French Majino line and this was something they were planning for a long time that this is a possibility whether they do it or they don't do it is not the issue. The military plans included march into Syria from Jolan, bank left and then take Hezbollah in the rear in the area confronting the Israeli forces. That was also foiled recently because both the Lebanese army, Hezbollah and the Syrian forces with support from other countries like Iran and Russia they cleaned out first the Al-Qaeda and the ISIS forces from that region. This is a border region between Lebanon and Syria in which ISIS and Al-Qaeda were there. They were repeatedly given support by Israel to keep this part out of the control of the Syrian and the Lebanese forces particularly the Hezbollah and they therefore were supporting Israel, supporting them with both air cover as well as money as well as with medical relief. So all this was being done in Israel in order to keep it out of the control of the Syrian government on one side and Hezbollah's presence on the other. Recently the Lebanese army, the Hezbollah and Syrian army moved together to squeeze out Al-Qaeda as well as ISIS from this regions and now after the Russia-American agreement there is an understanding that Iranian forces and Hezbollah forces will not come up to the Jolan border remember Jolan is still occupied territory. It's really that part of Jolan which is under the control of Israel still as an occupying power after the 67th war. So this part of it that which is under Syrian government's occupation still that part of Jolan they will come up to the border but this shall we say the ceasefire line. They will come up to 8 kilometers of the ceasefire line in Jolan and they will not cross that but that means they are dug in over there they are militarily going to prepare over there, make it impossible for Israel to go past the Syrian forces bank left and take Hezbollah in the rear. So both Hezbollah and Iranian forces are going to be there they are staying there in order to prevent this break from happening. So I think this is a major development. One is taking out the ISIS and the Al Qaeda from this from that area will not go into the details of how they did it but also preventing Israel from making this maneuver and that's one of the reasons the United States is so unhappy with the Lebanese government particularly because it has broken ranks with Saudi Arabia and the United States and joined with Hezbollah and the Syrian army in order to clear its own territory. So given the current situation, what can we expect from now on? I think it's an interesting situation where we can expect mopping up in rest of the country that you are going to see the south and east you are going to see mopping up in the west you are going to see mopping up operations continue for the next 2 to 3 months. I expect the Euphrates River to be crossed by the Syrian forces I expect most of the oil fields in that region also to fall to the Syrian government forces that's the next I would say 2 to 3 months target for Syria really take away all the small enclaves that still exist with Al Qaeda the so called Free Syrian Army forces some of them backed by the United States like in Al-Tanaf I think those enclaves will shrink or fragment and will slowly disappear Thank you Prabir that's all the time that we have today keep watching news click for more updates


The Clinical and Translational Science Award, CTSA, Consortium and the National Centre for Advancing Translular Science, NCATS, undertook a common metrics initiative to improve research processes across the National CTSA consortium. The implementation programme included training on the metric operational guidelines, data collection, data reporting system, and performance improvement framework. This article was authored by Denise H. Daudelin, Laura E. Peterson, Lisa C. Wells, and others.


Hi this is Matt McDonald with CalTV Entertainment News and I'm here at the 2017 Sundance Film Festival for the world premiere of Don't Swallow My Heart Alligator Girl. Your film is a love story but there's also the historical background of colonialism and indigenous justice so can you please explain a little bit about the historical context and the importance that it has in the film? Yeah the film is shot exactly in the border between Brazil and Paraguay and in a small city where like really violent battles happened in the past and so like a hundred years ago but since today people in this region has all these memories of these violence in the past so the relationship in the social relationship and even the more like personal relationship there is all a future by this memory so this film is this love story between a Brazilian teenager and Paraguayan teenager but they have to deal with all these past violence and how to try to transform it in something new or try to go through it and and leave what they they can maybe it's an impossible love but they are going to fight for this. I work with Glauco Fipu, he's a Brazilian DOP, it's my first time working with him. We had this idea to work with the natural light of the region but also creating some kind of mysterious atmosphere there because one of the references of the film is some like American film from the 80s like the warriors and so this kind of action film that has some it's not just action had a lot of ideas and concept behind some this mix of realism and some magical and gen-gen atmosphere so it was really fun to get all these old not old 80s gen-hub movies from the United States and bring into the South American reality and there's some elements of magical realism in the film. Can you talk about how that adds to the story? All the film is like narrated through the eyes and the imagination or the narration of this Joker the young boy so the idea was everything in the film has some some centimeters higher you know the four so this is the idea like it's not like fantasy but you're telling a story through the eyes of a 13 year old boy who has all this pop reference all this imaginary of adventure and pop reference and how some way he's bringing this story to us so when I was writing my own filming I was trying to always imagine the scenes through his eyes so I think the magic comes from him.


And the believer is not simply someone who has belief, but is the one who lives according to belief. Allah is the one who points out the distinction between simply having belief and living that belief. He tells us, for example, in the Qur'an, All you who believe, believe, meaning that all you who accept belief live according to that belief. And if one lives according to that belief, then as the Prophet SAW said, everything that happens to the believer is for their good. If pleasing things happen to them, they are thankful. And if distressful things happen to them, they remain contentedly patient. This will be a means to their earning the pleasure of Allah SWT.