Well, thank you, Rudy. Welcome everyone. Great to see all of you. And I really want to emphasize the point Rudy made. We work very hard at the institute to have these open sessions of our council meetings as available to the community as possible. And so that's why we stream them live. And we also record them and make them permanently available on our website genome.gov. That includes not only the presentations themselves, but also all the various documents associated with those presentations. That includes my director's report. And for those of you who are new to council meetings, I just want to make you aware that we create a pretty comprehensive electronic resource that's routinely developed each time we put together a director's report. This is analogous to supplemental materials associated with a published paper. We give the URL, a convenient URL, as shown there. The slides that I'm going to show during my director's report are also available electronically. You can see you can get them either as the native PowerPoint file or as you prefer as a PDF file. When we cross-reference documents or relevant websites for a particular slide, you'll see a document number on the bottom right of that slide. Those document numbers reference materials that can be accessed or downloaded, in some cases at the website, if you go to the website shown here and go to a particular document number. And all of these materials and websites and everything will be permanently archived as a historic record of this meeting. There's going to be a number of other presentations during the open session of this council meeting. And I'm going to deliberately tailor my presentation around these other presentations so I'm not going to discuss in any detail the topics that others will cover. Immediately after my director's report, we'll be joined by my good friend and colleague, John Lorsch, who's director of the National Institute of General Medical Sciences, who's here to talk not about his institute, but rather to talk about NIH's strategic plan for data science. Then after lunch, there's going to be two concept clearances. First, Nicole Lockhart will present a concept clearance for a center for ELSI resources and analysis. And then Lisa Brooks will present a concept clearance for the Genomic Innovator Award. After that, we will have an update about a part of the institute that is not really the responsibility of this council, but is an important part of the institute. Dan Kastner, who's the institute's scientific director, in which he serves as the director of our division of intramural research, will be here to give a report and an update, if you will, about the NHGRI intramural research program. And then we're going to have two extramural program reports to follow. Adam Felsenfeld and Chris Wellington will talk about the NHGRI genome sequencing program and then Anastasia Wise will talk about the Undiagnosed Diseases Network. So that's the plan for the open session. What I'm going to do in my director's report is to cover these seven areas that are listed here, which have proven to provide a nice framework for the topics that I want to cover. And I'll start with one and actually only one update about a general institute update, but it's an important one because it relates to our new strategic planning process. So at the February council meeting, all of you hopefully remember that I announced and kicked off, if you will, the beginning of a new round of strategic planning for NHGRI, one that will establish a 2020 vision for genomics by publishing a new strategic plan in late 2020. Now there have been a number of developments since that time that I want to briefly summarize for you. So earlier this month we held our first public town hall, in this case it was a virtual one in which participants joined by webcast and audio conference. The emphasis of this first town hall was to get input about the strategic planning process itself and a recording of this town hall and the materials presented during it are available at the dedicated Genomics 2020 website. Now there's going to actually be two in-person town halls over the summer that will take place before this council meets again. One will take place in Seattle, Washington in June and then one will take place in Palo Alto, California in July. We welcome those of you living in those general geographic locations to participate in these first two of what will be a series of traveling town halls, including town halls that will take place in place other than the West Coast and we have some of these already being lined up and we'll have more to say about that at future council meetings. Now details about these upcoming town halls as well as various other past and future strategic planning events will always be available on a dedicated news and events calendar that's also available on the Genomics 2020 website. Finally, I was recently interviewed for an Illumina Genomics podcast in which I spoke about our nascent strategic planning process and how it will play out over the next couple of years. So that's the main update for NHGRI, let me move on to NIH updates. On June 1st, coming up in a few short days, Jim Batty will be retiring as the director of the National Institute on Deafness and Other Communication Disorders or NIDCD. Jim came to NIH in 1983 and has served as NIDCD director for 20 years. He also served as a member of the U.S. Public Health Service Commission Corps for more than 21 years, retiring as a Rear Admiral in 2008. Under Jim's leadership, NIDCD supported researchers who developed the tools and programs necessary to implement universal screening for newborn hearing loss. Now over the years, Jim has been an important NHGRI partner, most notably helping to provide oversight of the Center for Inherited Disease Research or CIDR and also the Common Fund's knockout mouse projects, both COMP and COMP2. Judith Cooper will serve as acting director while NIH conducts a national search for a new NIDCD director. Another retirement, Richard Nakamura, will also soon retire as director of the NIH Center for Scientific Review or CSR. Richard has devoted 39 years to NIH starting as a postdoctoral fellow and later serving as deputy director and then scientific director of the National Institute of Mental Health. While serving as CSR director, Richard has dealt with historic increase in applications, multiple policy changes, and a host of other challenges, including recovery from the 2014 government shutdown. Noni Burns has been selected to serve as acting director of CSR while NIH conducts a national search for a new director. In terms of other recruitments, I want to bring to your attention something I know is of great interest to this council, a recently launched recruitment for an important NIH leadership position that is really highly relevant to this institute. The position is called the NIH Chief Data Strategist. This individual will report directly to the NIH director and will serve as the principal advisor to the NIH director and other NIH leadership in all things data science. This person will also serve as director of the newly formed NIH Office of Data Science Strategy. This individual will play a key leadership role in the arena of data science, both in building trans-NIH programs and coordinating data science efforts at individual institutes and centers. Applications for this position are due on July 9th. I can tell you that I'm actually a member of the search committee for this position and I would personally welcome any suggestions you have of potential candidates. In March, Robert Redfield became the 18th director of the U.S. Centers for Disease Control and Prevention, or CDC, a sister agency of the NIH. Dr. Redfield has been a public health leader actively engaged in clinical research and clinical care of chronic human viral infections and infectious diseases, especially HIV, for more than 30 years. In terms of relevant policy developments, you may recall that an interim final rule was previously issued to delay implementation of the revised common rule from January to July of this year. Now, the common rule agencies have issued a notice of proposed rulemaking, or an NPRM, that proposes an additional six-month delay, meaning that the revised common rule would be implemented in January of 2019. Now the NPRN is asking for feedback about the ability of institutions to comply with three burden-reducing provisions beginning in July of 2018. These provisions include, first, the updated definition of research under which certain activities are no longer considered research, second, the provision that no longer requires annual review for some types of research, and third, the provision that eliminates the requirement that grant applications undergo institutional review board review and approval. The NPRN is open for comments until May 21st. On the legislative front, a bill recently proposed in Congress is of interest to NHGRI and the genomics community more broadly. Specifically, HR 5062, titled the Advancing Access to Precision Medicine Act, was introduced in the House of Representatives by Eric Stallwell, the Democrat from California, in February. The bill has been referred to the House Committee on Energy and Commerce. The stated purpose of the bill is to, quote, to provide for a study by the National Academy of Medicine on the use of genetic and genomic testing to improve health care and for other purposes, end of quote. The bill, if passed, would primarily accomplish two things. First, let me just get rid of that, first, the bill would charge the National Academy of Medicine to conduct a study of how genomics can improve preventive care and precision medicine. And second, it would amend Medicaid to allow states to offer whole genome sequencing clinical services for children with undiagnosed diseases. In March, President Trump signed the Fiscal Year 2018 Amnibus Appropriations Bill into law. Needless to say, this was of great interest to NIH. The bill provides an 8.8 percent or a $3 billion increase for NIH. Of this $3 billion, about $1.2 billion is set aside for specific areas that include but are not limited to $414 million for Alzheimer's disease research, $500 million for opioids research, and $60 million for the All of Us Research Program. I am pleased that NHRI received a 5.4 percent or a $28.5 million increase putting our Fiscal Year 2018 budget at $556 million. These funds have already started to be dispersed to NHGRI and the Institute is working extremely hard to utilize these additional funds in an efficient and effective manner. All of us at NHGRI and I am sure the entire biomedical research community are appreciative of the continued support of the U.S. Congress in our ongoing work. Well, now that we have our Fiscal Year 2018 budget in place, budget attention is turned to preparing for the start of Fiscal Year 2019, which is now just over four months away. Well, to get things started, the President released his proposed Fiscal Year 2019 budget for the federal government back in February. Now, this budget was a bit complicated for a number of reasons, including the timing for finalizing the Fiscal 2018 budget and the need to then include an addendum for the released Fiscal Year 2019 budget proposal. But putting those nuances aside, the bottom line is that the President has called for an overall budget reduction for NIH, which would involve a proposed 8.1 percent reduction for NHGRI over Fiscal Year 2018. Now, of course, the proposed budget has now moved onward to Congress for their consideration, and we will see how this plays out in the coming months. Well, with the President's Fiscal Year 2019 budget now proposed, the Senate and House are currently working on appropriations bills, including multiple hearings, such as shown here. There have been various developments in the budgeting process. These are happening in real time, including hearings that took place late last week, and they're likely to continue to do so throughout the summer and probably well into the fall. Now, it's useful to note that while the two-year budget deal was reached earlier this year, that deal established top-line numbers only. Lawmakers now need to hammer out the details of how those numbers are divvied up, including how much money will go to the Department of Health and Human Services, and then in turn how much money comes to NIH. So we're obviously tracking all of these events carefully, and we hope to have more positive budget news at future council meetings. So moving on now to general genomics updates. Starting with some sad notes, the first of which is the genomics community recently lost, a true pioneer and a legend. Sir John Sulston, founder of the Wellcome Trust Sanger Institute in the United Kingdom, passed away all too soon at the age of 75. John received the Nobel Prize in Physiology or Medicine, along with Sidney Brenner and Robert Horvitz, for mapping out the cellular development of C. elegans and nematode flatworm. Of particular relevance to NHGRI, John was a key leader in the human genome project, someone who was an outstanding partner with NHGRI in all aspects of this historic effort. In addition to his scientific excellence, he was a strong leader in advocating for open and rapid data sharing. John will be sorely missed. NHGRI is also mourning the loss of Congresswoman Louise Slaughter, who recently passed away at the age of 88. Mrs. Slaughter served in the House of Representatives for over three decades and most recently represented the 25th District of New York. She was the lead author of the Genetic Information Non-Discrimination Act, or GINA, which was signed into law in 2008 and a strong advocate for genomics research in general. Her work on GINA protects patients and research participants who undergo genetic and genomic testing from discrimination in health insurance and employment. And interestingly, in an appointment way, it was pointed out to me this weekend that this photograph you see here of the President signing in to law, GINA, literally took place precisely 10 years ago today. Just happened to work out. And so a truly historic time exactly happening. And sadly, Congresswoman did not live long enough to celebrate this 10th year anniversary. Well, several of us here at NHGRI had the pleasure of meeting and working with Mrs. Slaughter over the years. And so to honor her legacy of leadership in genomics and science, we have renamed our annual National DNA Day Lecture, which takes place every year on April 25th. We'll now be called the Louise M. Slaughter National DNA Day Lecture. Representative Slaughter's commitment to genomics and leadership in Congress will be deeply missed. Our NHGRI K99-R00 grantee, Neville Sanjana, received the AAAS Martin and Rose Wachal Cancer Research Award. This award honors early career investigators who have performed outstanding work in the field of cancer research. And all of the work cited for this award was published during this investigator's K99-R00 funding period. So congratulations to him. And also, congratulations are due for newly elected members of the National Academy of Sciences. The NIS recently announced their newly elected members, and of particular relevance to the genomics community and to NHGRI are the individuals listed here. We extend our heartfelt congratulations to these colleagues. Historians will note that Michael Gottesman, listed second here, was at one time acting director of NHGRI between Jim Watson and Francis Collins, and has always been a great supporter of NHGRI. But congratulations to all the individuals listed here. Also, congratulations to someone who the genomics community knows well. Earlier this month, Magdalena Skipper, who's currently editor-in-chief of Nature Communications, was named the new editor-in-chief of Nature. She will be the eighth editor-in-chief in Nature's 149-year history. She's the first woman editor, and she's the first editor to come from a life sciences background. Dr. Skipper is well known to the genomics community, having major editorial responsibilities in the genomics area for many years at Nature. She will succeed Phil Campbell, and she will start in the position in July. We look forward to her new role with Nature. And lastly, of course, I have to give you the update of genomes in the news, because there have, as always, been a number of recently generated genome sequences reported since the last council meeting, including, and here we go, the marbled crayfish, 30 different citrus species, the sydney funnel web spider, the eastern Australian mouse spider, the lovely cockroach, solodendon, the sweet wormwood, the Egyptian rosette bat, the California yellowtail, and here we go, the fin whale, the humpback whale, the gray whale, the say whale, the mink whale, and the blue whale. So once again, genomics finds its way throughout the world of animals and other life species. Okay, moving on to the extramural research program and starting with our genome sequencing program. Well, the genome sequencing program, as many of you know, is composed of a coordinating center, three analysis centers, four centers for common disease genomics and four centers for Mendelian genomics. The program is supported by other organizations, in addition to NHGRI, as we broaden our net of support. These include the National Heart, Lung and Blood Institute, the National Institute of Aging, the National Eye Institute, and also the Simons Foundation. Now, the genome sequencing program recently held its annual consortium meeting, and the various centers discussed research updates, sequencing progress, and their goals and strategies documents, which will guide their plans for the rest of the current grant cycle. Additional meeting highlights included scientific talks from outside researchers, updates from collaborations with the Knockout Mouse Project, or COMP, Transomics for Precision Medicine, or TopMed, and the Undiagnosed Diseases Network, as well as clinical laboratories. And finally, they had opportunities within the program to build common resources. In terms of some numerical updates, go through each program, the centers for common disease genomics are using large-scale genome sequencing to discover genomic variants underlying common diseases, including rare risk and protective variants. The centers also aim to understand common disease architectures and ascertain optimal study designs. As of May of 2018, the centers had sequenced over 101,000 samples. 58,000 reflect whole genome sequences, and about 43,000 reflect whole exome sequences. The centers aim to sequence about 200,000 samples by December of 2019. Freeze one of these data, which includes 20,000 whole genome sequences, was made available in November of 2017. The centers are currently working on Freeze Two, which will include whole genome sequences generated as of May 1st of 2018. Freeze Two is intended for release this coming summer. Moving then to our Centers for Mendelian Genomics, these centers use genome sequencing analysis to discover the genomic basis of as many Mendelian diseases as possible. Now, by sequencing the genomes of roughly 45,000 individuals, these centers have discovered more than 3,000 disease gene associations. Over 2,100 of these associations meet the conservative Tier One criteria, while the remaining 1,000 meet the suggestive Tier Two criteria. Other accomplishments of these centers include helping to accelerate discoveries globally by releasing tools and methods that others can use to acquire samples, analyze data, and share results. Through courses and training, the centers are empowering researchers to bring cutting-edge genomics to the study of Mendelian diseases. As a result of both their discovery and outreach efforts, the centers have been involved in more than 450 publications to date. Now, a subset of key collaborators within these centers include the Knockout Mouse Project, the Undiagnosed Diseases Network, a matchmaker exchange, thousands of sample providers, and tens of thousands of patients and family members. NHGRI staff recently convened a four-hour webinar in March to discuss the Human Genome Reference Sequence. Specifically, over 65 stakeholders were asked to discuss the future of NHGRI-funded components of the Genome Reference Consortium. Topics included how the reference, which currently includes 261 alternate loci, 70 fixed patches, and 70 novel patches as shown on this figure, how best these things should be represented, how to include haplotype-resolved data, what additional data sets are needed, what bioinformatics tools should be developed in conjunction with the reference, and how the consortium can improve education and outreach opportunities for the basic science and clinical communities. Also affiliated with our Genome Sequencing Program, the Cancer Genome Atlas, or TCGA, is a coordinated effort between NHGRI and NCI to better understand the molecular basis of cancer. This project completed data generation in 2016 and has two noteworthy capstone activities this year. First, the PAN Cancer Atlas was published last month as a collection of 27 papers across a suite of cell journals. The project provides a unique, comprehensive, and interconnected understanding of how, where, and why tumors arise in humans, focusing not on cancer genome sequencing, but also on different types of data analyses, such as investigating gene and protein expression profiles and associating them with clinical and imaging data. Second, there will be a three-day cell symposium in Washington, D.C. in late September to discuss future research enabled by the TCGA legacy and to mark the end of this decade-long effort. Abstracts are due June 15th and the registration deadline is August 10th. Moving on, NHGRI's Technology Development Program continues to move forward, paving the way to new technologies and discoveries in genomics. After the success of the previous funding announcement, NHGRI is again soliciting applications for novel nucleic acid sequencing technology development that involves both DNA and RNA direct RNA sequencing. The first application due date for this new request for applications is June 27th. An advanced genomic technology development meeting will be held at Northeastern University later this month. Novel DNA sequencing and genomic technology developers from the program will come together over several days to facilitate collaborations and interactions. Meanwhile, an adjacent public meeting will allow broader community participation and also discussion of NHGRI's next phase of strategic planning. The goal of the Encyclopedia of DNA Elements or ENCODE project is to create catalogs of all functional elements in the human and mouse genomes and to make those catalogs freely available as a resource to the biomedical research community. In this effort, ENCODE has produced its Registry of Candidate CIST Regulatory Elements, or CCREs, that is at the core of the project's encyclopedia. This registry integrates data produced by the ENCODE and the NIH Common Fund Roadmap Epigenomics Consortium to identify regions of the genome with potential functional activity. Now, ENCODE's new online visualization tool provides the means necessary to search candidate CIST regulatory elements by ENCODE, otherwise known as SCREEN. In other words, to screen this registry to make it easier to annotate genomic data. For example, one can enter a single nucleotide polymorphism or genomic coordinate of interest indicated by the upper red arrow, and SCREEN will attempt to find candidate regulatory regions, such as the one indicated by the lower red arrow. One can also find out about the expression of a gene of interest by entering that gene name indicated by the upper left green arrow, and then clicking on the Gene Expression tab indicated by the upper middle green arrow, which then reveals the gene expression results indicated by the bottom green arrow. ENCODE tutorials, including a recent tutorial about using SCREEN, can be found on the NHGRI website, genome.gov. Altogether, SCREEN consolidates in one website information important to understanding gene regulation and expression and its relationship to human health and disease. ENCODE data are widely used, and they're now about 2,000 community publications from groups without ENCODE funding who use ENCODE data for their published work. ENCODE consortia members have produced more than 600 publications themselves. Three recent publications from ENCODE and related projects deserve highlighting. So for example, in November of 2017, the ENCODE Data Coordination Center published a description of the ENCODE portal database and website as a source for data and metadata generated by the ENCODE consortium, as well as hosting data and metadata from related projects, including the Genomics of Gene Regulation, Roadmap Epigenomic Project, Model Organism ENCODE or ModENCODE, and the Model Organism Encyclopedia of Regulatory Networks, or MODERN. An update of MODERN, an extension of the MODENCODE project, was published online in January of 2018. This paper provides a description of the catalog of regulatory elements identified by mapping Drosophila and C. elegans transcription factors and how to access those data and resources. And meanwhile, council member Jonathan Pritchard's group, funded through an ENCODE Computational Analysis Award, published this paper in genome research in January 2018. The paper describes a deep neural network to predict open chromatin regions from DNA sequence only and discusses how this can help predict the effects of common genomic variants and cell-type specific chromatin accessibility. The NHGRI Computational Genomics and Data Science program supports research and development of data science methods, resources and tools that maximize the integration of genomics data into biomedical research. The program hosted a workshop in the fall of 2016, which yielded recommendations for NHGRI to pursue in bioinformatics and data science research over the next three to five years. The workshop's outcome was discussed at the May 2017 council meeting. Now, the program plans to release funding opportunity announcement in summer 2018, which will aim to increase the pool of investigator-initiated applications covering a broad range of innovative research efforts in computational genomics, data science, statistics and bioinformatics. The second homomorphic encryption standards workshop was held in March in Boston. Organized by Microsoft Research, this workshop was part of an effort to set community standards for broad use and to put this privacy technology to practical use in many different settings. Homomorphic encryption is a type of cryptography that allows analysis tools to be used directly on encrypted data, thus making it possible to extract results while keeping private or proprietary information in an approvably safe fashion. This privacy technology has gone from theoretical interest to practical utility in just a few years due to a major investment by other agencies with a strong mandate to protect sensitive data. NHGRI is supporting a few grants in the early application of homomorphic encryption in genomics and clinical research, including an SBIR small business grant for secure distributed genome-wide association study data. Ongoing support by NHGRI has allowed the development of MedCo, a homomorphic encryption module in I2B2 that is now being tested in an international setting as part of the Swiss Precision Medicine Initiative. The NHGRI EBI Genome-Wide Association Studies or GWAS Catalog is an online resource providing curated results from GWAS-related papers and user-provided summary statistics. On April 28th of this year, the GWAS Catalog celebrated its 10th anniversary. Its iconic diagram launched in 2008 with a single GWAS finding related to age-related macular degeneration, as shown by the red circle. Look how it's changed in 10 years. Now, 10 years later, curators have added information about over 3,300 publications and over 59,000 associations filling out the chromosomal map of the human genome. Additionally, the catalog and its associated papers at references have been cited over 3,100 times in the literature. The numbers of studies and associations have continued to increase over time, suggesting that the initial investment in GWAS continues to yield dividends, even as more advanced DNA sequencing technologies are becoming widespread. And in honor of its 10th anniversary, the GWAS Catalog team has created a video of the time series available at the GWAS Catalog homepage. The clinical genome resource, or ClinGen, defines and disseminates the clinical relevance and genomic variants for use in precision medicine and research. ClinGen was a very active participant at the American College of Medical Genetics and Genomics annual meeting. The ClinGen variant curation workshop drew over 280 attendees and provided guidance for groups interested in launching new variant expert curation committees using the ClinGen curation frameworks and tools. ClinGen investigators were featured in a scientific session that emphasized the need for creating quality and consistency in genomic variant interpretation. Given the community's interest in this topic, the session was streamed live for remote meeting access. And finally, Dr. Jonathan Berg delivered a ClinGen overview during the presidential plenary session and encouraged the community to join ClinGen's curation efforts. ClinGen joined a number of U.S. and international partners to form the Gene Curation Coalition, or GenCC, with the overarching goal to standardize curation processes, terminologies, and the results from gene disease curation efforts. In addition to ClinGen, partners include the Genetics Home Reference, Decipher's Developmental Disorders, Genotype Phenotype Database, OMIM, Genomics England Panel App, Transforming Genetic Medicine Initiative, or TGMI, and also Orphanet. Now, this coalition will next meet on Wednesday, actually, of this week, so in two days in Hingston, England, in advance of the 2018 curating the Clinical Genome Conference co-hosted by ClinGen and Decipher. Several new ClinGen papers have been published in the last few months. The ClinGen-inherited cardiomyopathy expert panel summarized their adaptation and validation of the ACMG-AMP variant classification framework for the MYH7 gene associated inherited cardiomyopathies. The ClinGen Sequence Variant Interpretation Working Group published a letter to the editors of genetics and medicine, providing a rationale for the removal of two criteria, including in the ACMG-AMP Sequence Variant Interpretation Framework. And finally, a commentary in Cold Spring Harbor molecular case studies outlined points to consider for sharing genomic variant level information from clinical genetic testing with ClinVar. And a full list of ClinGen publications can be found on the ClinGen website. Meanwhile, the Clinical Sequencing Evidence Generating Research, or CSER program, aims to generate evidence related to the clinical utility of genome sequencing with a major emphasis on recruiting ancestrally diverse and medically underserved populations. Now work from phase one of CSER was prominently featured at the recent American College of Medical Genetics and Genomics meeting. In total, there were 10 CSER-related posters and presentations addressing secondary findings and complex genomic results, economic perspectives, and sharing genomic results with family members. And a recent paper from the first phase of CSER looked at the reasons that patients declined, study participation. The decline rate ranged from 12% to 64% across seven sites, with a median of 28%. Commonly cited reasons were similar to those reported for clinical single gene testing and non-genomic sequencing genetics research. The most frequently cited reason for decline was time commitment and study logistics at about 35%, followed by no reason given or unknown at 16%, and privacy and discrimination concerns at about 13%. A small percentage of potential participants cited psychological impact at 8% or not wanting to receive secondary findings at 2% as reasons to decline, suggesting that these concerns were not major barriers for participation in genome sequencing studies. Since the start of funding for the second phase of CSER last summer, investigators have established six working groups to collaborate across multiple program areas, including clinical utility, education, and return of results, ethical, legal, and social implication and diversity, stakeholder engagement, survey measures and outcomes, and sequence analysis and diagnostic yield. The working groups have been focusing on harmonizing measures and outcomes and study patients and providers to be measured at baseline and at follow-up. These harmonized measures will be developed and shared with other NHGRI genomic medicine consortia, including Emerge and Ignite. Investigators are also preparing for satellite stakeholder workshop during the next CSER in-person meeting in September. The newborn sequencing and genomic medicine and public health or NSITE program explore is in a limited but deliberative fashion. The implications, challenges, and opportunities associated with the possible use of genomic sequence information for the care of newborns. In January of 2018, Jennifer Pucks Group published a paper in Human Mutation showing that dried blood spot DNA from samples archive over 20 years ago can be used without whole genome amplification for exome and genome sequencing. Shown here on the right is actually an agarose gel image revealing tight bands of high molecular weight with no observable degradation of the DNA extracted from dried blood spots. This demonstrates that when properly stored, dried blood spots can yield DNA of sufficient quantity and quality for exome and genome sequencing without amplification. In February of this year, Stephen Kingsmore's group published a paper in Genomic Medicine showing that genome sequencing can accelerate the diagnosis of critically ill infants. In the figures shown here, time to diagnosis on the left and age of diagnosis on the right were both decreased for infants receiving genome sequencing in addition to standard genetic testing. Standard genetic testing was added, was shown in red. As compared to just standard genetic testing alone shown in blue. Now, many of you might remember, quote, the case of misinheritability that was popularized by Brendan Maher's article in Nature in 2008. That article led to NHGRI workshop that produced this nature paper now with nearly 3,800 citations and this diagram of the then understanding of where the heritability of complex traits unexplained by GWAS might be found. Well, 10 years later, NHGRI reconvened many of the original workshop participants to revisit this issue and ask, what have we learned since 2008? What has been or will be the value of identifying the sources of misinheritability and what research can or should be pursued to determine these sources? Workshop participants concluded that using all associated SNPs or even all genotype SNPs explains much more heritability than genome-wide significant SNPs alone. 45% for height, for example, compared to 5% for genome-wide significant SNPs. They also proposed that increase in the proportion of heritability explained remains important for improving the reliability of prediction algorithms and they recognized the critical need for this and so many other genomics research questions for expanding the study of African and other non-European populations to enhance characterization of human genomic variation and leverage subpopulation differences for finding associated genomic variants. In March, Terry Minolio and Laura Rodriguez and I participated in an international summit of cohorts and biobanks with 100,000 or more participants. The summit was organized by the NHGRI-initiated Global Genomic Medicine Collaborative, or G2MC, in collaboration with the Global Alliance for Genomics and Health, or GA4GH. Representatives of over 50 very large cohorts for more than 30 countries, as shown here, convened at Duke University in March and in total, these studies account for over 25 million participants. The summit was conceived by the heads of international research organizations, so the Heroes Group, and the group leads, specifically Jeremy Ferrar of the Welcome Trust and NIH's Francis Collins, seen as a means to bring together very large cohorts and explore the potential for collaboration and harmonization among these international cohorts. Participating cohorts agreed to develop a searchable registry of cohorts and their key details, explore the potential for a common IT infrastructure, and develop a strategy for large-scale collaborative genome sequencing and the use of other omics technologies. The group is currently identifying other relevant cohorts through G2MC and GA4GH in hopes to reconvene the group within the next year. And in April, NHGRI released two program announcements to stimulate investigator-initiated genomic medicine research. The PARs, one for R01s and one for R21s, aim to support research that will advance our understanding and implementation of the use of genomic information about an individual to inform clinical care, as well as the health outcomes of that clinical use. And the PARs will have six application dates over three years, the first of which is June 20th of this year and the other ones listed here on the slide for convenience. The ethical, legal, and social implications or LC research program supports research on the implications of genomics for individuals, families, and communities. The program Centers for Excellence in LC Research, or CIRS, had their annual meeting this April. In addition to plenary presentations and panels, roundtable discussions featured topics including data sharing, health equity, and privacy. This format emphasized transdisciplinary dialogue and trainee interactions. The genomics and society working group of this council provides guidance to the LC research program. At their next in-person meeting on May 23rd, later this week, the working group will welcome new members, Pat Deverka, Consuela Wilkins, and Vardit Ravinsky, as well as Bid farewell to working group member and former council member, Shanita Hughes-Halbert. Lastly, two recent webinars reached out to the community to gather ideas and needs and resources to increase the reach, impact, and transparency of LC research. Over 75 participants joined the webinars and there's now an executive summary of those discussions available online. Thanks to everybody who participated in those webinars. The NHGRI research training and career development program continues to grow and evolve. We recently awarded a new institutional T32 training program focused on LC research. Scott Roberts of the University of Michigan will lead the new program which will complement the 18 currently funded NHGRI T32 programs. This new program will support both pre and postdoctoral trainees and will incorporate a mix of coursework, research opportunities, and mentoring to provide practical knowledge on the current state of genomic science and medicine. Core principles and bioethics, also grant writing and manuscript preparation, as well as interdisciplinary LC research projects. Our diversity action plan or DAP program seeks to expose underrepresented minority students to genomic research experiences and a new NHGRI DAP award has been made. The new program at Duke University which focuses on genomic medicine is led by Suzanne Haga and Gregory Way will consist of a 10 week mentored research project with undergraduate students from Duke and North Carolina Central University. The program will focus on a variety of areas including translational genomic medicine, bioinformatics, engineering, and statistics. And then our NHGRI Research Training and Career Development program held its third annual meeting which took place in UCLA in March. This annual meeting continues to provide a venue for all trainees supported by NHGRI to come together, present their research, form collaborations with other trainees and established investigators. And pictured on the left are the attendees of the meeting. Of the 274 attendees, 194 trainees presented abstracts as either a poster, a lightning talk, or an oral platform presentation. Trainees came from the Diversity Action Plan programs, the T32 training programs, the Centers of Excellence in LC Research Program and also the NHGRI Intramural Research Program and individual awardees, in addition to individual awardees of fellowships and career development awards. Pictured on the right are the poster award winners which included trainees from the undergraduate, post-baccalaureate, graduate and post-graduate career levels. And the next annual training meeting will take place in St. Louis next April. Now, as a new item for my director's report, I will be including a new section every time in director's report on NHGRI Extramural Research Highlights. Because the other slides and material that I typically go through for the extramural program tend to emphasize updates and accomplishments from the institute's managed programs and initiatives. So in contrast, the next two slides feature four papers nominated by NHGRI program directors that exemplify the spectrum of exciting genomics research funded by NHGRI Investigator-Initiated Awards. First, Diane Dickle and her collaborators used genome editing to knock out single and multiple ultra-conserved enhancers. They found that these enhancers are required for normal development. Often the actual function is detectable only when sets of elements are actually perturbed. Second, Nila Ioannidis and her collaborators developed fire or functional inference of regulators of expression, a tool to score both coding and non-coding single nucleotide variants and their potential to regulate the expression of nearby genes. This tool should help in evaluating genomic variants of unknown significance. Third, Jean-Louis Rosero and his collaborators in conjunction with the Global Alliance for Genomics and Health proposed practical strategies to reduce re-identification risks in beacons of databases of genomic data. These include obscuring the presence of rare alleles and limiting the number of accesses per user. Finally, Gaye Bizarro-Munez and his collaborators proposed that psychiatric genomics researchers offer findings to psychiatric patients similar to those with other medical conditions. This would include return of medically actionable findings as well as, if possible, clinically valuable findings in genomic variants of unknown significance related to a participant's symptoms. These findings may corroborate psychiatric diagnoses or indicate important health risks. So that wraps up the section on our extramural program. Let me move on to NIH Common Fund and other trans-NIH efforts, starting with the Human Heredity and Health in Africa or H3 Africa program who has as a central goal to develop a sustainable and collaborative African genetics and genomics research enterprise. This past March, H3 Africa held its 11th consortium meeting in Uganda. This was the first consortium meeting for the second stage of the program, both new and returning grantees as well as H3 Africa trainees and fellows presented to the more than 215 participants, making this the largest consortium meeting in H3 Africa history. Consortium members have authored several recent publications in scientific areas including the genetics of blood pressure in South Africa, cohort, the modifiable risk factors of stroke in Nigeria and Ghanaian populations. And of particular note, the H3 Africa Ethics and Community Engagement Working Group recently released the Ethics and Governance Framework for best practice in genomic research and biobanking in Africa. And this framework was featured actually as in nature news. Looking forward to the summer, we're anticipating adding the final H3 Africa LC research awards as we start the next five years of the initiative. Now, the NIH Common Fund is launching a new program called Sematic Cell Genome Editing which aims to develop quality tools to perform effective and safe genome editing in human patients. The program elements will include improved delivery systems and genome editors as well as in vitro and in vivo assay platforms to test safety and efficacy. The information and materials will constitute a genome editing toolkit that will be disseminated through a data coordination center. Now, almost 100 applications were received this past April in response to six FOAs and the Common Fund expects to issue approximately $18 million towards this program in fiscal year 2018. And the kickoff meeting for this program will occur in December of this year. The NIH Data Commons is a cloud-based platform for storing, sharing, accessing and computing on fare or findable, accessible, interoperable and reusable biomedical research data. During the pilot phase of the project, test case data sets from the Alliance of Genome Resources, from GTECs and from TopMed projects will be stored on Amazon and Google Cloud platforms and shared with the scientific community. The pilot started in September of 2017 with awards made to a consortium of investigators charged with the design and initial implementation of Data Commons infrastructure. The initial accomplishments of the pilot include establishing a governance structure and developing a project execution plan. In addition, NIH staff collaborated with the consortium to establish processes for making data, including controlled access data available to approved consortium users. The implementation of the project execution plan for the NIH Data Commons pilot began in early April and will continue for approximately six months. During this period, awardees will design innovative solutions to test key capabilities of the Data Commons with the end goal of producing demos, prototypes and basic training modules. The second stage of the pilot will start in October of 2018 and will continue for approximately three years. During this lighter stage, awardees will work to fully develop the capabilities produced during the first implementation period. Another trans-NIH program, the All of Us Research Program, aims to gather data from one million or more people living in the United States to accelerate research and improve health by advancing precision medicine. All of Us hosted a workshop in March and a broad array of stakeholders, including some members of this council, gathered in Bethesda and participated in plenary talks and active breakout sessions focused on identifying research questions and associated data measures that could capitalize on the program's unique characteristics. Over 500 use cases were generated and those use cases will be synthesized along with those generated in advance of the workshop to help inform future protocol development and scientific priorities. Now, of particular interest to the genomics community, All of Us intends to solicit applications for large genome centers. The centers will generate genotyping and whole genome sequence data, develop workflows for high confidence, genomic variant calling and securely processing and transmitting the data. The funding announcement itself is expected to be published this month with a start date in September of 2018. Meanwhile, the All of Us Research Program had its official launch earlier this month. This included seven simulcasted events around the country with speakers, participant engagement activities and a community art experience. Enrollment in this program is now open to all eligible adults who live in the United States. Taking part is simple. If you want to enroll, just join, just visit joinofus.org and create an account. You could then, if selected, create your health information online to this program and then some people will be asked to then visit a local partner site to collect physical measurements and provide blood and urine samples. So we're excited that All of Us has reached this important milestone and look forward to continued development of this historic and important NIH research program. So let me move on to our division of policy communication and education. And as I mentioned earlier, April 25th is National DNA Day and every year NHGRI plans celebrations to mark the occasion. This year we celebrated the 15th anniversary of National DNA Day and the 15th anniversary of the completion of the Human Genome Project with a plethora of activities. To kick off NHGRI's DNA Day events, we hosted a six-part Ask Me Anything or AMA series on the popular online discussion forum Reddit. Prominent genomics experts participating in these AMAs included Dr. Francis Collins, as well as NHGRI council member, Dr. Aviv Raghav, who answered questions posed by the public. Then on National DNA Day itself, NHGRI hosted Dr. Oliver Noel, who's founder and CEO of DNA Simple for the newly renamed, and as I mentioned earlier, Luis M. Slaughter, National DNA Day Lecture. Dr. Noel spoke about his interesting career path and his experience as an entrepreneur, including his appearance on the TV show Shark Tank. We also broadcast this talk through Facebook Live. To close out DNA Day celebrations, NHGRI partnered with the Smithsonian's National Museum of Natural History and NHGRI's Dr. Lita Proctor gave a human origins topic, or I'm sorry, human origins today, or hot topic talk about the human microbiome. Lastly, our DNA Day event map featured 93 DNA Day events, and I'm also pleased to report that five states this year signed proclamations, declaring April 25th, 2018 as National DNA Day, reflected by the red stars on the map. Now it was the 15th anniversary of the completion of the Human Genome Project, so to commemorate that, NHGRI enlisted partners from academia, industry, government, K through 12 education, patient advocacy, and various other organizations to launch the 15 for 15 celebration. The celebration involved a 15 day countdown leading up to National DNA Day on April 25th, together enumerating 15 ways that genomics has influenced in our world since the completion of the Human Genome Project. Topics range from technology advances in DNA sequencing to pharmacogenomics and rare diseases to DNA forensics and agricultural genomics. In addition, the celebration was promoted through daily newsletters via social media and involving the help of our national network of partners. All the content and communication assets were shared in a 15 for 15 celebrations partner toolkit in early March. The Genetic Science Learning Center at the University of Utah promoted the celebration at its website, which is the most highly used genetics teaching website in the world. Other partners, such as the St. Louis Academy of Science shared the daily feed through their own organizations mailing lists and communications channels. And in total, 45 partners participated and we reached about 60 million people through the social media campaign. Our outreach didn't stop there. Other outreach activities included in March, NHGRI engaged with the Washington DC community at the NBC4 Health and Fitness Expo, the largest free consumer health event in the country. The Expo featured celebrity guests, cooking classes, fitness classes, and more. With 200 exhibitors and over 87,000 visitors attending, NHGRI staff interacted with about 600 people in conversations about genomic medicine, family health history, and participation in genomics research and clinical trials. In addition, as shown in the photo on the bottom left, Division of Medicine Director, Dr. Terry Minolio participated in an interview with NBC4 Anchor Dureen Gensler and NIAID Director, Dr. Tony Fauci, speaking about advances in genomic medicine. In a video of the interview, can be found on NBC4's Facebook page. Then in another event, in April, NHGRI was one of the 19 NIH institutes and centers to participate in the USA Science and Engineering Festival. NHGRI led activities such as extracting DNA from strawberries and developing a genetic treat tree. The festival was attended by over 370,000 people with approximately 1,500 people interacting and engaging in the hands-on activities at the NHGRI booth. And then, of course, the genome unlocking lights code exhibition continues to make stops across North America as it continues its roadshow during 2018. The exhibition completed. It's stay at the Rochester Museum and Science Center in New York at the end of April, and it will then open on June 23rd at the Rochester's Art Center in Rochester, Minnesota, being sponsored by the Mayo Clinic Center for Individualized Medicine. And then in September, it will travel to Florida for a stint at the Orange County History Museum in Orlando. Please continue to check the exhibition's website and follow it on social media for the most up-to-date program information. Now, related to this exhibition, it's interesting to note that back in 2012, when we were developing content for the Genome Unlocking Lights Code exhibition, the History Channel agreed to contribute video interviews of luminaries in genomics as in-kind contribution to the exhibition. And they further enlisted producer Kate Reyes of the 42 Degrees North Media Organization to create four videos that chronicled the history of the human genome project and speculated on the future of genomics. Those videos were prominently featured and continued to be prominently featured within the exhibition itself, and they included very short video clips of people like President Bill Clinton, Jim Watson, Francis Collins, Maynard Olson, John Sulston. And the actual video interviews when they were actually conducted in preparation for the exhibition were well over an hour each, but had to reduce what could actually be shown in the exhibition itself to just a small number of sound bites at best. Well, knowing that we had this incredibly valuable and remaining footage as valuable content, we thought about was there a way to sort of repurpose some of it and use it since such a small amount was actually used in the exhibition. And so we recently contracted with Kate again in 42 Degrees North Media to create an additional set of educational videos. That wonderful collaboration then yielded the five new videos that are shown here, two of which actually use footage that got us started on this from those original interviews. The other three new videos actually harness the incredible creative talent of Kate and 42 Degrees North Media, especially in storytelling and animation. And actually we unveiled these five new videos in one or more ways during the 15 for 15 celebration. And you can find and could watch each of these videos if you just go to the 15 for 15 celebration website. In addition, you can now of course go to Genome TV channel on YouTube where we have these videos now posted as well. And I would encourage all of you to look at all five of them at some point and perhaps even use them as an educational tool. But since these are really great videos and since I knew my director's report would be a little bit on the short side, this side in terms of length, I thought it might be fun if we actually showed one of these videos so all of you could see what they're like and it was one of the ones that used the video clips from the exhibition. So we're gonna do that now. In 1989, a group of scientists was assembled to decode the human genome under the direction of Dr. James Watson. One of Watson's big motivations here was to try to recruit the best and brightest from many different disciplines, biology, but also physics, chemistry, engineering, because all of those would have to get together if this was going to work. Many of the biologists, and I love them dearly, of course, were dragged into it, kicking or screaming in the beginning because they failed to see the tremendous value that such an enterprise would provide the field. The talent turned out to be all over the world, so you have to basically make it possible for those bright minds to get engaged where they are. They're not gonna all move to join this effort. Genomics has fundamentally changed the way we do science. It brought the notion of team science and collaboration to biology. Curiously about collaboration, it's also intensely competitive. Each person wants to achieve something personal. They want to make their hit on the problem, but then immediately they want to share it with the other and the other learns immediately, and so you ratchet each other up. From the beginning of the genome project, there was a fairly strong sense of enthusiasm in the public sector, the private and academia. We had lots of support from Republicans, partly because Newt Gingrich was interested in science, and I knew it. There's no partisan difference in everybody wanting to live as long as they can. I think there's a lesson there. It isn't a being a monolithic project. It was a big challenge, but it brought people together, and I think that's what we have to do in the future. And the human genome project would start it. It's important to note that technology of sequencing was not developed yet, so it's in a sense a project that was launched with a wing and a prayer. We couldn't sequence it at that time. The machines were nothing like fast enough. There were no machines even. It was sequencing that was done by hand. I thought we might have to do it before, so I was quite unprepared to use the old-fashioned technology just because it was so important to get it done. There are a lot of things that would make life easier that just hadn't been invented yet. It would be a 100-year project like monks working the copy of book at best. We got into a more and more large-scale sequencing, but the sequencing is enormously important because it provides the possibility of searching by computer. When I showed up at the Washington University one day with a computer terminal under my arm, people looked at it and said, what are you gonna do with that? This is a genetics department. Genomes were supposed to be too complex to be able to reassemble them in the computer. Without computers, we simply would be dead in the water. Computers and genomics were made for each other. Genetic information is digital. It's like binary code. It just happens to use four digits instead of two. It is amazingly accurate, and that's what biology gets from digital information. The Human Genome Project contributed a cultural change about data sharing because the Genome Project was about sharing data almost immediately. While it seems obvious now, it wasn't obvious then. That required significant effort.  The community around me, the genomics community, the worm and fly communities as well. It's just a default that you're gonna share everything. You're gonna share the code.  You're gonna share half-coded ideas. And in fact, this is a wonderful thing. It's liberating. That would then virtually criminal to try to hoard discoveries that meant the difference in life and death in people. This is information which we'll be using for centuries. The sooner we get it, and everybody has access to it who wants it, the faster we can move in terms of understanding how life works and how disease occurs. Patients invest a certain degree of fear about genetics. Who's going to find this out? How will it be used against me? So a lot of the ethical and social considerations that we're struggling with today really have historical roots in the early 1900s in the United States where we had many states that had laws that allowed us to forcibly sterilize people and prevent them from having children based on whether we as a society felt that they were genetically fit. So at the beginning of the Human Genome Project, we got it right of bringing in the social scientists, the ethicists, the lawyers, and we now have helped to provide a whole generation of scientists that are focusing on the ethical and social issues of genomics. Human genome was a monumental achievement. Decades of work, thousands of scientists, billions of dollars, and we get this first roadmap for what makes up the human genome. It's an incredibly exciting moment. At the same time, it's just the beginning of what's really a much longer voyage. And let's again be audacious, but let's not be unrealistic about what's possible. I think the next 10 years are gonna see some exciting developments in genomics, particularly those where we start to use genomic information as part of routine medical care, and that'll be applied to dealing with diseases like cancer, hypertension, diabetes, and Alzheimer's disease. I dream of the day when every young mother brings a young girl or young boy home from a hospital with a little gene card and they say, this is the way you should prepare this child's health care. It's exhilarating. I would encourage you to look at the other four. They're all, I think they're all great, but, and all very different. So again, when you have a chance, these are five new contributions, videos from our education group, collaboration with this outside group, which is wonderful collaborators. So I will move on, wrap things up, just say a few things about the institutes intramural research program, including some impressive developments, later in the afternoon, after lunch, you're actually gonna be hearing from Dan Kaster, but I should also point out that Dan, who's our scientific director, has been selected as a finalist for the 2018 Samuel J. Hyman Service to America Medals, or SAMHIs. You may not be familiar with the SAMHIs, but those of us in government service are. The SAMHIs are also known as the Oscars of government service, and they're highly respective and highly competitive honor given each year, selected from across the government, to government employees for their outstanding, oftentimes long-term contributions. And Dan has received this honor as being a finalist for identifying a new class of rare genetic diseases related to inflammation and developing treatments for those disorders, all part of a many decade career he's had in the intramural program at NIH, first at NIH National Institute of Arthritis and Musculoskeletal Disorders, and now more recently at our institute. And the final medal recipients will be announced in the fall and October. Hudson Alpha Institute for Biotechnology has awarded the 2018 Hudson Alpha Life Science Prize to Dr. Charles Rotimi for his genomics-based research in health disparities. The Life Sciences Prize recognizes research and the Life Sciences that seeks to improve human or environmental health or agricultural yields while elevating research careers and endeavors for current and future students in biotechnology. And then just a few brief highlights that I always like to give about the intramural research program. They've always been productive, but since the last council meeting, there's three papers I'd like to highlight. In a study of sickle cell disease, Dr. Charles Rotimi and colleagues investigated the origin and clinical classification of the disease, issues that have been debated for over 40 years. The researchers used whole genome sequence data to pinpoint the single origin of the sickle cell mutation to the wet period of this Sahara 7,300 years ago. Dr. Bill Paven and colleagues discovered a connection between the genes that contribute to hair color and the genes that control the body's immune system. The new mouse study offers insights into why some people's hair goes gray in response to serious illness or chronic stresses. And finally, Dr. Julie Segre and collaborators conducted whole genome analyses on antibiotic resistant organisms in hospitals to study the bacterial plasmids that can confer resistance to antibiotics. And that concludes the content in my director's report. I always like to wrap up by saying, as always, and put in a plug for anyone wishing to receive my monthly email update called the Genomics Landscape. You can simply go to NHRI website and subscribe under email updates. And then a final thanks to the 50 to 60 people, most of which sit in this room who contributed, put together this director's report and all the materials that go with it. As always, it's a group effort and it takes weeks and weeks of preparation for each council meeting. And also a special thanks to the communications group and the web team for making that electronic resource available. And of course, a special thanks to Chris Watterstran who's the ringleader and coordinator for putting my director's report together. Now this is an interesting photo. Here is Chris celebrating National DNA Day. Not with me, but with a cardboard replica of me. Seriously, that is not me in the photo. You can tell from the handshake. It's a very unnatural looking handshake. That is a cardboard replica of me and just don't ask why is there a cardboard replica of me. It's just one of these things I don't wanna have to admit to. So I will stop there, thank all of you and take any immediate questions you may have before I introduce our next speaker. We're good? Okay.


Stafford, looking right, comes back to the middle under some pressure hit. Sack! Taniko Autry! Stafford, pressure up the middle again, he's in trouble. He's hit, he is sacked! Jeffrey Simmons coming right up the gut. Stafford, looking under pressure hit. Sack! He's got a lot of more! Jeffrey Simmons!


Good morning friends, I am Purva and today we will work out the following question. Form a differential equation representing the given family of curves by eliminating arbitrary constants a and b and we have x upon a plus y upon b is equal to 1. Now as the order of a differential equation representing a family of curve is same as the number of arbitrary constants present in the equation corresponding to the family of curves so here we shall differentiate the equation two times. So this is the key idea behind our question. Let us now begin with the solution. So here we are given x upon a plus y upon b is equal to 1. Let us mark this as equation 1. Now since the above equation consists of two arbitrary constants so for eliminating them we shall differentiate equation one two times. So differentiating 1 with respect to x we get, differentiating x upon a with respect to x we get, 1 upon a plus differentiating y upon b with respect to x we get, 1 upon b into dy by dx is equal to differentiating 1 with respect to x we get, 0. This implies 1 upon a plus 1 upon b into, now dy by dx can be written as y dash is equal to 0 and this can also be written as this implies 1 upon b into y dash is equal to minus 1 upon a which further implies y dash is equal to minus b upon a and we mark this as equation 2. Now differentiating equation 2 with respect to x we get, differentiating y dash with respect to x we get y double dash is equal to differentiating minus b upon a with respect to x gives 0 so we get y double dash is equal to 0. And this equation does not contain the constants a and b therefore the required differential equation is y double dash is equal to 0. Hence we write our answer as y double dash is equal to 0, hope you have understood the solution, bye and take care.


Good day, fellow investors. This week's big news is a new letter from Ray Dalio and please read it on LinkedIn. He has written an article talking about paradigm shifts, how what we have lived through over the last 10 years might be completely different over the next 10 years and how people don't expect that. And how people invest in equities, stocks, index funds because that has been the best investment over the last 45 years and I think it will be the best investment over the next 45 years but that's not usually so and things will change. And his message is to be diversified with gold because, to sum up his letter, central banks will print more money to keep interest rates low, equities degrading the past but not anymore as valuations don't justify pushing prices higher, so there is a new paradigm. Debt burdens are higher and income is smaller from assets as prices are higher because as interest rates go down, the prices of assets go up and the yield on those assets goes down, so it increases debt burdens. So the solution is that currencies, he doesn't know when, currencies will be sacrificed so we will see devaluations, debasements of currencies and he says that each portfolio should be better diversified holding gold and I really think that someone that has index funds and has been following the trend over the last 10 years that he should look into diversification of his assets of his portfolio because what did well in the past might not be so good in the future. The worst thing you can do is to own bonds, currencies and hope it be a safer because usually savers are those that get screwed when central banks print more and more money and we have seen a lot of pain with pension funds which don't have the option to invest 100% into equities and they missed out on a lot of gains over the last 10 years because they invested in bonds with very very low or even negative interest rates. 13 trillion of assets is invested with sub zero or zero interest rates on it. So that's the amount of money that is happy sitting aside not earning anything with real negative returns. In any case just to comment on gold you have to see how that fits you. Gold is a non-productive asset it is just a hedge so you won't make any money while you are holding gold because it will just protect you from gold doesn't go up in price is the currency that loses its value. So it will give you protection on currency depreciation. So it is up to you whether you just want to be diversified with gold and keep up the non-thinking investment environment like investing in index funds etc. Or you will start to look for assets that have yields assets that will give you yields over the long term no matter the currency environment that will have the pricing power to adjust their prices in an inflationary environment because when central banks print money and that will not be enough like we have seen now with the Fed not increasing interest rates because higher interest rates are too much to stimulate the economy they will print money and give it directly to the government to invest in infrastructure projects to build new roads new train rails etc. And that will need a lot of commodities so perhaps commodities are a way to have a producing assets that will give you also protection in case of currency devaluation. So I'm thinking of gold and I'm here going with Buffet just because okay it's not productive you have to be a trader you have to be a speculator and if you own gold yes you have to own it but then you have to sell as it goes up and buy as it goes down something very few are doing and if you look at my gold video that I published two years ago now that gold prices are higher now the video gets views now the interest is there for gold but when gold prices were lower and lingering nobody cared but that was the time to buy now it is the time to sell a part of what you bought in the past. So you have to keep that in mind and constantly rebalance which is Ray Dalio's message and he will make an article on it in the future. So this is the news for today please read Ray Dalio's article see how it fits your investment style and then see how to go about it it's not just investing in gold is just like investing in index funds so the simplest option and that's what he is selling in his article but I think there are many many other options a little bit more sophisticated that offer you both offer you both protection and both yields on real assets that will in the long term prevail over any other asset strategy please subscribe if you want to hear more about this business like investing assets where we look for both protection value investing with a margin of safety and a high return on the assets that we own thank you and I'll see you in the next video


Ooh, hold on. Good night, these videos. Yeah. Well done. Very on-brand. Hey, welcome back to our stupidly-rexed idiots. I'm Corbin. Who cut the cheese? And you can follow us on Instagram and Twitter on all of our juicy content. It's so cheap. You can follow us on Patreon, follow us on Twitter, and on our attempt to make you as uncomfortable and cringe-fest as possible, we have more nineties for you. Uh, and this one, I believe, for what I've been told, is quite cheesy. Mmm, yeah. Which is our favorite. We love us some cheese. Apparently, there's a 90s Bollywood dance here in LA. Oh, oh, joke. We just found out about it. He sent me the text. He's like, there's this thing in here that's about to celebrate the Bollywood 90s stuff in LA.  He's like, no, it's legit. Yeah. So I'm researching that. So hopefully, we'll be able to go. Who knows? But, American? Great. Yes. Great. And this is a subversion, but this is called Atikai Kandala. Atikai Kandala.  Yeah, I know. I'm sorry. I don't do them on purpose, guys. Exactly. That's what makes them so great. And now they're even better, because they're more rare. They're like precious pink diamonds. But, uh, I believe this is from, I believe, you haven't seen it if you're not on Patreon, but I believe this is from that train scene we reacted to, a long time ago. Oh, his running against the giant. He did his own stunt. I believe this is from that film. That's a Patreon exclusive. We reacted to the scene from this film about him running and doing the stunt thing. Right. It was a while back. Yeah, a long time ago. Yeah. But I believe this is from this exact film. From that same film? Okay. So he'll be very young here. Yup. Here we go. Oh, here. Do you want some cheese? I do want some cheese. I'll never turn down some cheese. Would you wash your hands? No. Pig. Last week? The dirtiest part of your body. Here we go. Stonewashed. That's late 80s, man. Oh. I feel it. That bass? Mm-hmm. I love that. That workout. Trying to show you. That was cheesy. That was very cheesy. Thank you so much for that. Because sometimes these night, the song was actually quite good. I enjoyed that. The song wasn't bad. The song was like, I'm kind of digging that, man. It's got a nice groove. It said the amount of cheese that I was looking for. It's satisfying the palette. It has a ridiculously cheesy outfit. Yeah. There are certain qualities that have to fall to a 90s for it to reach the cheese level. First and foremost is cheese? Yes. What they're wearing. She doesn't qualify. He makes up for whatever she doesn't qualify in. Oh, yeah. But the girls usually are never really outside of them and the dudes. It's the dudes. Outside of the girls in the Akshay Saif one, the first one that we did with the girls in the peacock. And Akshay's still the king. Oh, yeah. He's got three, I think, that are still at the top of everything. But, oh, yeah. Amir is number two. Because he did the other one where he did the number with the handkerchief thing. Yeah. The scarf. Yeah. That scarf number. So, yeah. The mood. Okay. So you got to have the cheesy clothes. You got to have... When we say cheese, we enjoy this. Oh. Some people mistake what we're saying and they're like, you're disrespecting. No, not at all. Like, we really enjoy this. It actually qualifies because it's the era. Yeah. That era was cheesy. So if you're capturing the era right, it's going to be cheesy. So the clothing. Yeah. The dance moves. That's number two. Mm-hmm. If you've just got the clothing and the dance moves, you've got the cheese. Everything else is gravy on top of that. Then it's the scenario. What's going on? What are they doing together? Ridiculous pants that are leather and uber tight with a chain... With a stone wash with the chain... Chain belt? That's like... And the neon yellow... Helping you crush. And the neon yellow tight shirt. He has a ring on every finger. Yeah. He's got a hanger chip. He's licking a... What is it called? A match. A match. And then the goofy, silly running away. This definitely qualifies. Thank you. That was fantastic. We love that. Yep. That was quite enjoyable. I hope you cringed a lot. And I don't understand when people say, oh, cringe. I'm like, that was... That's fun. That's fantastic. Like, it's not like it's a new film that has come out and it's like way under budget and it's all cringy. Like, films in this era of Hollywood and Bollywood, wherever, are just... That's how they were. Yeah. You're allowed to laugh at them. Yeah. And there is something about the late 80s into the 90s era that has cheese that you don't find in any other decades where you... You can be nostalgic, you can be old, you can be goofy, but there's a cheesiness about the 80s and 90s that's just... It's the post-MTV era when they're making these things that they think they're so cool and it's so cheesy. I love it. Let us know what other cheesy songs there are. Octray is still the king. Yeah. Yeah. Obviously, there are some 90s ones that are just good songs. There's been a couple that was like, that was a great song and it wasn't really cheesy. We've reacted to a couple of big B's that are just fun. And I think probably it was a couple where we were like, that was just freaking cool. Yeah. It wasn't cheesy at all. SRK, we've reacted to a couple of those 90s but I don't know if they're cheesy. Well, they gave us one that we thought was going to be cheesy. It was the China, China, that was a great song. That's on our playlist. Oh, yeah. A great video. So, there's a couple that we can't, so if you send some in their YRF, I will not do it. Can't do it. They'll block it. Yeah. Sorry. That's just what happens. So, I know they have a lot of the rights to a lot of them. A lot of them. But if there's other ones, I know the Godiva, what is his name? Yeah, Govinda. Govinda. Yeah. People love him. Yeah. We still get to see and need to. We got, there were a lot of comments in the last one we did with him. Just over and over, non-stop comments on, yeah, you guys, it reminded me of when we first started Yeah. You don't even, then we saw him a couple of times and I'm like, yeah, don't insult him by comparing him to Michael because also we know he's not a dancer like probably. No. Yeah. No, we're not making that comparison. What we're saying is I know somebody will misunderstand. Yeah. He's a guy we obviously didn't know about and we're learning about and we still have yet to see him unleash. He's the king of 90s. He was holding back with Big B. Yeah. But you have to. If you're a great dancer, you've got to hold back when you're with someone who's not a good dancer. Yeah. Great cheese. One of the greatest dancers. Michael Jackson. Did you know? Yeah, it's true. He was underrated. No, what I was going to talk about is that Gene Kelly and Fred Astaire always match their dance to the partners they dance with. Murdered the 90s cheese.


I'm from San Francisco, California, extracting the signal from the noise. It's theCUBE, covering DockerCon 2015, brought to you by SiliconANGLE Media, with special thanks to Docker. Now your hosts, Stu Miniman and Jeff Frick. Hi, Jeff Frick here. We're with theCUBE and we're at DockerCon 2015 in downtown San Francisco. I think under here we're playing a garden long haul walk from Hilton San Francisco. Excited to be here. We're joined in this segment by Stu Miniman, who's been getting the low down, studying hard, a lot of information, and John Gosman, architect from Microsoft. John, welcome. Thank you. So what do you think? You were here last year at DockerCon 2014? Yeah, it's amazing to see how these things grow.  I remember when Ben first came and visited us last year, and there were four of them. We brought 10% of the company, how many people did you bring? Yeah. And yet there's 2,000 people coming to these conferences already. Yeah.  There's a huge line behind you of people at the Docker booth getting their t-shirts. I have a few friends in Microsoft that have even said that they've spotted Docker t-shirts inside the company, people wearing them.  Well, there's a lot of Docker t-shirts around. We've been coming to these conferences now. It's the third one, and it's been spreading the love. And the Docker guys, we meet with them regularly, and they always come bearing gifts. That's awesome. So can you give us a little bit insight, you know, what you're working on, you're part of the Azure team, my understanding, you know, and how does Docker fit into what you're building there? Okay. I am an architect in the Azure Core team. The Azure Core team builds the core network storage and compute services. And so, you know, and then other parts of Azure are built upon the services and software that we write. And so, part of that is just getting whatever the customer wants to run on Azure, because you can't be a Windows-only or a .NET-only cloud or Linux-only cloud. Every enterprise has a wide range of software that they want to run, and they want to bring it all. And so, we look a lot at what it is that customers are asking for. And for, you know, well over a year now, one of the biggest types of things that people are very interested in is running Docker. And then internally also, I like to say that everybody in the industry has been doing containers before containers were cool. So inside our services, inside services like Bing, we've been running container technologies for a long time. There's bits of pieces of Windows, there's a thing called a job object that is basically a container technology. I'm sorry, when you say a long time, can you quantify, I mean, is it five years, ten years? Well, the job object was introduced into Windows in Vista, to give you an idea how long, and a bunch of other bits of technology were put in at that time. But like most people in the industry, we thought of containers as an advanced topic. This is something that's really fancy, and you get a hyper cool kernel engineer, and they can work on containers. And what Docker did was say, oh, look, there's a really easy to use developer experience here that anybody can use and deploy quickly. And that was what they basically taught the whole industry. So when we saw that, we knew that wanted that same capability. Our customers are asking for us, and we wanted both for Azure and for Windows. So John, was that a point of view from a design decision, or was there a breakthrough technology that enabled them to make it from that which was complex to that which is really easier for a much broader kind of developer ecosystem? So it's my opinion that these breakthroughs that are aesthetic ones, that are designed to use the ability ones, are actually the ones that are rarer and harder to land. And like look at the web browser, I was working on a hyper media system at the time, and when I first saw it, I was like, ah, no big deal. But the key was it was so simple to use, and because the technology was already fairly mature, then it just took off. And that's the same sort of thing we're seeing now with Docker, is that the technology, and like I say, people are doing, it's containers are cool. 15 years, all the technology is there. And then putting it together and the right combination of usability is the key. Yeah, interesting. People, I think, often discount packaging. Packaging UI is very, very important. And I don't know why we do that, because the industry tends to be revolutionized not by somebody come up with some incredible algorithm, but by making it really easy to use. Yeah, John, can you give us an update on Microsoft's support of Docker? I really thought it was one of the really important moments of the ecosystem building when Microsoft said, OK, we're going to containerize Windows, it's going to be management compatible with what Docker is doing. When we had the whole, almost container wars broke out over the last kind of six months or so, I said, well, this is momentum going forward. And then, you know, then when we get past that, we'll talk about the OCP announcement today, which hopefully gets us past some of that war discussion. Yeah, so our strategy is twofold and it's completely the same sort of experience that the Docker people wanted and our customers wanted, which one is to bring Docker to Azure, Docker for Linux, Docker for Windows, and then also bring Windows to the Docker ecosystem. So about a year ago at DockerCon last time, we announced that we had to integrate Docker into Azure so that we could really easy to launch a VM with Docker and launch containers. And we continued to add support for that. So this spring, we added the ability to take a compose file and launch it on Docker very easily. And then the other thing we announced last fall was the flip side of this thing, which putting the Docker work onto Windows. And the goal there again is just like Docker unifies to some degree the ability to run, say, a Debian and a CentOS, why should Windows be the same way if you want. And so we wanted people to be able to, if they're, you know, want to use containers, but they're using Windows not to be limited to having to switch operating systems and vice versa. And so that work is underway. You can see it actually live going into the Docker engine, GitHub repository, Microsoft, Windows, kernel and Hyper-V team people. The people you might think they were almost the last people to be working on some sort of open source project that started out on Linux, contributing code into this open source project to unify the experience.  You know, can you sum up for us, you know, what are customers asking for, what's the key value and, you know, why is this whole Docker wave so important? So the key value, I think, like I said earlier, is it's a developer experience, it's very attractive. So you develop on your laptop and then you get kind of this teleport to where it suddenly magically shows up on the cloud and on any cloud and it can run on top of all of us. So the ease of use of the experience is the key reason that it's taken off. But the second part is, as I alluded to earlier, we, the, you know, the operating system elitists have known for a long time that containers are a good way to run things at high density, you know, like I, so even though right now developers are just starting out with small clusters and putting an application into a container and then uploading the cloud, they know that long-term they're going to get these other benefits in cogs and density and that sort of stuff. So it's, it's still a fairly early thing, but that's what we're seeing the interest from for customers. All right, so John, last question I have for you. There's some that would say that containers lessen my reliance on the operating system. So Microsoft is much more than operating systems. I mean, your cloud platform, you've got lots of applications.  So I think Solomon actually gives a really great analogy between how container ecosystem works and the internet works, where at the top you have large range of different applications. At the bottom you have a lot of different devices and then there's a narrow waste of the ITF protocols that enable those things to run all these different types of devices. And I think there's a similar layering of operating system, hypervisor, container, and then that thing that's, that's going to be the narrow waste of how compute works. And then each of those layers can be optimized. And sometimes maybe you don't need the application layer, you just need the transport layer, something like that. And that's what's going on. And a lot of the stuff they said today with plumbing fits totally into that, that these lower levels of plumbing and then there'll be more opinionated layers as you go up. So I don't think operating systems aren't going to go away. I don't believe hypervisor's going to go away. And I know that people are going to use a lot of containers in the future. Excellent. Well, John, nice summary of what's going on. Thanks for stopping by theCUBE, sharing your insight with us. You got a busy schedule. They're giving us the hook. So again, thanks for stopping by. I'm Jeff Frick with Stu Miniman. We are at DockerCon 2015. You're watching theCUBE. We'll be back with our next segment after this short break. Thanks for watching.