Good morning, everyone. Welcome to today's session. We're going to study on the book of the major prophets starting with prophet Isaiah. Our recording has been started. So, even before we could begin with our class, can I request one of us to please lead us in prayer? Can I request Leah Lama or Anita or Aradna, anyone can lead us in prayer. Okay, Sid, please go ahead. Father, we come to the throne of grace. Thank you for this day, Lord. You have given us short as the first day of the week and we are going to learn about the prophets a lot and their prophecies a lot. The book we are going to start a lot, made this learning and not made the prophets a lot. Whatever we are going to learn there will be a blessing and we are adding to the knowledge of Christ in our life. So, thank you for this day, Lord. You have given us. Thank you for all the blessings you have given us and the time we are going to spend learning about the prophet and prophecies, Lord. In Jesus' name, you pray Amen. Amen. I'll just present a PowerPoint presentation for the class. I hope everyone can see this presentation. Okay. So, in Old Testament, we have 39 books out of which we studied on the book of Torah or the Pentateuch. There is the first five books of the Old Testament. And then later, we moved on to the book of history where we had, we studied, we studied on the 12 books of the history. And then from there, we moved on to the wisdom and the poetry books, which is five from the book of Job to song of songs. And now we are starting with the five major prophets book, starting with Isaiah. And then we will move on to Jeremiah, Lamentation, Ezekiel and Daniel, after which we will be covering the minor prophet books, which are 12 books from the book of Hosea till Malachi. So, with this, we will move on to the book of Isaiah. Yeah. So, the book of Isaiah compromising 66 chapters and is one of the most profound theological and the literary expressive works in the Bible, which is compiled over a period of two centuries, like later half of the eighth century and also the later half of the sixth century BC. So, the book of Isaiah is generally divided by the scholars into three major sections, which are called the first Isaiah. Let me move on to the next slide. The first Isaiah that is from chapter one to 39. And then it is called as the Deutero. Isaiah covers from chapter 40 to 55 and Trito Isaiah chapters 56 to 66. Well, the first Isaiah, which covers from chapter one to 39, they believe, you know, the scholars say that it is written by Isaiah himself. Well, the Deutero Isaiah from 40 to 55 and Trito Isaiah from 56 to 66. They believe to be written by the disciples of Isaiah from the school of prophets. Well, all this were written, believed to be written in Judah.  There's very little information given about Isaiah that he was married to women. The prophetess, which has been mentioned in Isaiah chapter eight verse three, and she bore two sons. Isaiah has two sons, which is also listed in Isaiah chapter seven verse three and Isaiah chapter eight verse three. And according to the Jewish tradition, or in Old Testament, it is known as the Hebrew tradition, Isaiah was martyred by the wicked king Manasseh, who placed him in the hallowed trunk of a carrot tree and was sown into two. And many believe the book of Hebrews in the New Testament in Hebrew chapter 11 verse 37, where in the list of heroes of faith, he says, sown ascender, where it refers to the prophet of Isaiah. Well, Isaiah was also a Hebrew poet, a prophet who was believed to have lived about 700 years before Christ birth. He was also born in Jerusalem, and he was said to have found his calling as a prophet when he saw a vision in the year of King Uzziah. Okay, one second, somebody has logged in, I'll just admit them. Yeah, so Isaiah prophesied the coming of the Messiah, Jesus Christ, and he spoke on God's behalf to the leaders of Jerusalem and Judah. He spoke first of all on the message of God's judgment. And later, he warned Israel corrupt leaders that their rebellion against the covenant with God would come at a cost. And that God was going to use the great empires of Assyria. And after them, Babylon would judge Israel, sorry, yeah, judge Jerusalem, if they persisted in the idolatry and into their sin nature. But that announcement combined also with the message of hope in the later part. So as I talk about the judgment, as I talk about the judgment, the way Isaiah put it across and later the hope, it also talks about in the book of Isaiah, if you see how the books have been arranged, the first 39 books of the Old Testament, which is talking about the judgment and immorality and the idolatry of men, you know, it compares, we can compare that to the 39 books of the Old Testament. And later, the remaining 27 chapters in the book of Isaiah gives a message of hope. And we can compare that to the 27 books of the New Testament, where the Messiah is coming as a savior and sovereign Lord to bear a cross and to wear a crown on himself. So here the complete, the total 66 chapters of Isaiah is been compared with the books of the Old Testament and also with the books of the New Testament. We also see that Isaiah believed deeply that God would one day fulfill all of his covenant promise that he would send a king from David's line to establish God's kingdom. And we also see that in 2 Samuel chapter 7, that he would lead Israel in obedience of the law of the covenant made at Mount Sinai. The law that was given to Moses, we see that in Exodus 19 and all of this was so that God's blessing and salvation would flow outward to all of the nations to whom God had promised to Abraham. And it's this hope that compelled Isaiah to speak out the corruption, the idolatry of Israel in his day to warn them, to ask the people to repent and come back. And later he delivers a message of hope to the people who have received who can hope for the Messiah. I'm sorry. With this, we will move on to the notes as well. Before we could move on to the notes, I just project this slide. Here we see the same thing. Whatever I just explained from chapter 1 to 66, we see that the first books are compared to the Old Testament, which talks about the day of the Lord, the judgment. And later 27 books are being compared with the New Testament, where it talks about the messianic and also about the hope that we have with the coming Messiah. And also, the first 36 books, the prophecies were directly written by Isaiah. And later, from chapter 37 to 66, we see his disciples, where the prophets from his school wrote, compiled it together. The scholars believe that way. With this, we will move on to our notes. I'll just stop presenting this and we can directly go to our notes. We just saw the background. We saw this. The authors, we know, Isaiah is also known as Saint Paul of the Old Testament. The New Testament quotes from all parts of the book were crediting to Isaiah from many passages. We see that in the book of John, quotes from Isaiah 6, chapter 6, verse 9 to 10. And also we see some of the quotes from the book of Matthew, chapter 3 and 4. And also from the book of Romans, we see the quotes from the book of Isaiah. And they are the quotations from the second part of Isaiah by the other Old Testament prophets who wrote prior to the exile and the situation Christian traditional views are only one, Isaiah. We see that and Isaiah as a man, he was a writer, he wrote history that reigns from among the four kings from Uzziah, Ahas. And he was also a statesman, patriot denouncing all foreign alliance. And he was a reformer like Noah preached righteousness and exposed the formalism as a poor substitute for spirituality. He was also a major prophet, teacher and a theologian during his time. And Isaiah has been called as the prince of the Old Testament prophets, the great messianic prophet, the fifth evangelist after Matthew, Mark, Luke and John. He's been recognized as the fifth evangelist who talks about the messiah and the prophet of redemption, the evangelical prophet, Saint Paul of the Old Testament, the gospel according to Isaiah after Matthew, Mark and Luke and John's gospel, the prophet of the sons as he speaks more of messiah than any other prophet. And well, the purpose of this book is to show that Judah has a form of godliness, yet it is corrupt, immoral and social and political. So he is warning them to come out of the idolatry and the very purpose of this and also he gives a great promise of messiah delivering a message of hope to the Israel. And there's some additional information that has been mentioned in the book of Isaiah with with law of course from the New Testament. And there is a detailed background. I would encourage each of us to please go through it. There's some unique features in the comparison with the other books of the Bible with this as an outline. Okay, so we will get back to our notes. So we will turn to our Bible from chapter one to 12. The main section focuses on Isaiah's vision of judgment and hope for Jerusalem. And it begins as Isaiah accuses the city leaders of the covenant rebellion and idolatry injustice. And God says he's going to judge the city by sending a nation to conquer Israel. And Isaiah says that this will be like a purifying fire that burns away all that worthless in Israel in order to create a new Jerusalem that's populated by a remnant that has repented and turned back to God. And we also see that Isaiah, what happened? So we also see that Isaiah says that when God's kingdom will come that all the nation will come to the temple in Jerusalem and learn of God's justice, bringing about the age of universal peace and harmony. Now it's this basic storyline of the old Jerusalem purifying judgment into the new Jerusalem. This is going to get repeated over and over throughout the book getting filled in with, you know, in increasing detail so that at the center of the section in Israel's grand vision of God sitting is on the throne in the temple and the surrounded by this heavenly creatures that are shouting that God is holy, holy, holy. And Isaiah suddenly realizes just how corrupt that he and his people Israel are.  And he prays, he seeks God for God's holiness. And he says that we are not holy. And when he asked God to cleanse, so God's holiness in the form of this burning cold comes and burns him, but not destroying him. It burns his lips, but not destroying him, but rather it purifies him from his sin. And as Isaiah ponders the strange experience that God commissions him in a vision with this very difficult task to keep announcing the coming judgment. But because of Israel has reached a point of no return as warnings are going to have a serious effect on hardening of people if they don't repent. At the same time, Isaiah is trusting on God's plan that Israel is going to is comparing it to a chopped tree. Like if the tree is chopped and left like the stump in a field and itself is scorched, burnt, but all of that burning, God says that this stump is a holy seed that will survive into the future. And it is a small sign of hope that who or what is that holy seed? So the stump has been compared with that holy seed and now we may think who is this holy seed? The rest of the section will give us that answer. Who is this holy seed? Where we will talk about it in the later section. Well, Isaiah confronts a has a descendant of a king of from the David's line. Just give me a minute, please. He has was a descendant of king and the king of Jerusalem and he announced his downfall because God said that his great empire of Assyria will first chop Israel down and devastate the land. But there is a hope because of God's promise to David that he is going to send a new king named Emmanuel, which means God with us and Emmanuel kingdom is going to set God's people free from this violent oppressive empire. And also Isaiah describes that the coming king as a small shoot or a new growth that will emerge from that stump that was cut off that is from the David's family. It's this king that is known as the holy seed, which has been stated in chapter six in this book of Isaiah. And the king is going to be empowered by God's spirit to rule over a new Jerusalem and bring justice for the poor and all the nations will look to this messianic king for guidance and his king will transform his kingdom will transform all the creations and bringing peace with this. We will move on. We will move on to the next chapter. We see that Isaiah saw another empire rising after Assyria, that is Babylon would also attack Jerusalem and actually succeed in destroying it completely along with the temple and we see that from chapter 13 to 27 where he says that with the large collection of poems he explores God's judgment over Israel. Like a year we learn about the fall of Babylon and Israel's neighbor and we also see that Isaiah could see that a very serious world power would one day be replaced by the empire of Babylon, nation even more destructive and arrogant. And Babylon's king claimed that they were higher than all other gods and so God was to bring Babylon down because of the pride that they carried within them and not only Babylon but Isaiah also goes on to list Israel's neighbors accusing them all of the same kind of pride and injustice and here we see that Isaiah predicts their ultimate ruin but he remembers for God's judgment is never the final word for Israel or the nations. With this we will move on to chapter 24 to 27. Here we see again a list of poems that tells us a tale of two cities their lofty that has exalted itself above God and they corrupt nature and unjust which you know which stirred God's anger and this city is an rebellious in in nature and it described with the language that's all bored from Isaiah's earlier description of Jerusalem and then later Assyrian and then later Babylon which is all put together. Well now this city is destined for ruin and one day is going to be replaced by the new Jerusalem where God will reign as a king over the redeemed humanity from all the nations and there's no more death no more suffering and here Isaiah is also portraying a message pointing far beyond his own day it was a message for all who are waiting for God to bring a justice on this violent oppressive kingdoms and kings and also the injustice with the with the injustice nature of people and to bring the kingdom of justice and peace and healing love among all the people around them they are looking forward for that messianic king to reign and the following section in chapter 26 to 38 we see Isaiah is predicting that the Assyrian armies come and try to attack the city and so Ezekiah humbles himself before God and he prays for divine deliverance and the city is miraculously saved by overnight but Ezekiah rises and immediately followed by his own fall also as he hosted a delegation from the Babylon and he tried to impress them by showing everything whatever he had the position israel's treasury he showed them the temple the palace everything to the Babylon kings and it clearly made an effort for them you know or he thought he can impress them with political alliance and protection but then later it turns to be his own fall and Isaiah hears about this and he confronts Ezekiah for his foolishness he predicts that his partner will one day betray him and return as an enemy to conquer Jerusalem and we know that in second kings chapter 24 and 25 that Isaiah was right what happened to Ezekiah was Babylon plundered Jerusalem and it destroyed everything and it brought Israel temple and the kingdom into ruins over a hundred years later this happened yeah and we see Isaiah also warns of his divine judgment which led he shows to be a true prophet because all that e-prophesy was fulfilled and remember the purpose of God's judgment to purify Jerusalem and bring the holy seed that is the messianic kingdom over all the nation and it's that hope that gets explored in the next check section that is from chapter 40 onwards we see the first main section of 40 through 48 opens with the announcement of hope and comfort for Israel that people are told that Babylonian exile is over and Israel's sin has been dealt with and the new era is going to begin so that they would return back home to Jerusalem where God himself will bring his kingdom and all the nations will see the glory now we can we can ask a question like who was saying all this to us whose voice are we hearing in these words of hope well the prophet in these chapters is that somebody who's living after the exile in other words the time period described by Ezra and Nehemiah but Isaiah died in 150 years before any of that so what are we supposed to make this year it is the it is the prophets who were from his school who were there who who actually noted all Isaiah's prophecies and they saw the fulfillment started you know writing it started noting and you know recording it for later purpose for us so 200 years into the future that he's speaking to the future generation as if the exile has passed over and you know it gives a deliverance message of hope so here we see the prophets from the school have been recorded all that Isaiah has been said so in chapter 8 to 29 and then 30 we were told that Isaiah was rejected by the Israel leaders that he wrote and sealed up a scroll of his message of judgment and hope that he passed it on to his disciples as a witness for the days to come yeah so now the chapters are one to 30 line way designed to show the judgment talks about the prediction of judgment that was that they fulfilled in the exile and it also says that Isaiah was a true prophet now we are moving to the next section of the 27 chapters which is describing or giving us a hope talks about the Messiah and so after exile is over Isaiah's disciple have treasured his words so long and open up the scroll and began applying his words of hope to their own days so on this view the book of Isaiah consists of the first collection of Isaiah words as well the writings of his prophet a prophetic disciples and then and then we also see a view that end up everybody agrees that these chapters were announcing that the future hope has come so God is fulfilling Isaiah's prophetic promises and so the prophet gives us a hope that Israel will respond by becoming God's servant that is after experiencing God's justice and mercy through history that they will now begin to share with the nations who God truly is but that's not what's happening in Israel instead we are we are seeing the witness to the nation is actually we see actually they are complaining and accusing God here he says first that the exile to Babylon was not divine neglect rather it was divinely orchestrated as a judgment for israel sin and second we see that israel's uh it was for the israel's sake that God raised a persia to conquer Babylon so that they would come back fulfilling Isaiah's words so the right conclusion that we see that we see that israel would draw is that their god is a king of history not the idols of the nation so in fall of Babylon and the rays of persian king cyrus israel should see god's hand at work so it becomes a servant telling the nation who god is but the end of the trial in chapter 48 we find that israel is still as rebellion or hard hearted as they were before so they are now so god disqualifies them has a servant but god god's uh but god is still on his mission to bless the nation but we'll see how we will fulfill that so the prophet says one second some days a lot and i'll just admit them yeah so the prophet is saying god's going to do a new thing to solve this problem which moves into the next section from 149 to 55 so here we see the introduction to a figure who's called god's servant who's going to fulfill god's mission and do what israel has failed to do and god gives his servant the title israel and sends this person on a mission to first of all restore the people of israel back to their god but second to become god's light to the nation and here we are told that his servant is empowered by god's spirit to announce good news and to bring god's kingdom over all the nation it sounds just like the messianic king from chapter 9 and 11 but then we learn um we also see that in chapter 61 as we see that he's been empowered by god's spirit to announce the good news and we see that fulfillment being when jesus came on this earth when he started his ministry we see him go into the synagogue open the scroll of isiah and start from isiah 61 saying that the spirit of the lord is upon me he has anointed me to proclaim the good news to the poor we see the whole few of the verses been narrated by jesus himself and we see that has also been recorded in the book of look but then later we learn the surprising way of how this servant will bring god's kingdom that he is going to be rejected beaten and ultimately killed by his own people in reality as he's been accused and sentenced sentenced to death and he's also going to die on behalf of the sin of his own people so the prophet here we see that he's been prophesying completely on the messiah who is jesus who actually we can see the fulfillment of the prophecy which was been prophesied by isiah that time in the new testament and then after his death all of a sudden he also says about he also prophesies about his resurrection servant is just alive again and he hears that his death he provided a way to make people righteous that is to put them in a right relationship with god the restoration of human back to god we see the prophecy been fulfilled in the new testament and with this section concludes by describing the two ways people can respond to the servant some will respond with humility and turn from their sin and accept god servant did on the behalf the work that he did on the cross and these people are called the servants or the children of god and also the seed remember the holy seed that we spoke before in chapter 6 is the seed and these are the ones who will experience the blessings of the messianic kingdom but there are others who are called simply the wicked who rejects the servant that is rejects jesus and this teaching which brings us to the final section of this book from chapter 56 to 66 where the servant inherits god's kingdom and these chapters are beautifully designed as a designed and which brings together all of the themes of this book together at the very center and there are three beautiful points that describes how spirit empowered servant is announcing the good news of god's kingdom to the poor and he reaffirms all of the promises of hope from earlier in the book of the new Jerusalem which is inhabited by god servant will be the place from which god's justice and mercy and blessing will flow out to all the nation of the world and and which will surround the points and our two long long prayers of repentance have been recorded in these chapters where the servant confesses israel sin and they grieve over all the evil they see in the world and around them and they ask god to forgive them and that his kingdom would come here on earth as it is on heaven now on each side of these prayer are the collections of more poems that contrast the destiny of the servants with that the wicked who has been who persecuted them god is saying that he's going to bring justice to all who pollute his good world with their evil and selfishness and idolatry and it's going to remove them from his city forever but the servant but the servant those who are humble before god and who repent and their own evil they are forgiven and they will inherit the new jerusalem because they have repented and asked for forgiveness which we discover in an image for an entire renewed new creation will be in the new jerusalem and this brings us to the very outer frame of this part of the book in this renewed world of god's kingdom god's people from all the nations have been invited to come and join the servants of god's covenant family so that everyone would know that their creator and redeemer is the messiah is a servant so the book of isiah ends with a very grand vision of the fulfillment of all god's covenant promise through the suffering servant that god has created a covenant family of all the nations who are waiting with hope for god's justice and you know to bring that messiah through whom they will be delivered through whom they will be set free through whom they can see experience the peace and love of god so here we see god's kingdom finally come here on earth as it is in heaven and that's the very powerful hope that the book of isiah is actually declaring or or prophesying to the people of israel where there was a turmoil and a loss of hope but here in the last 27 chapters we see that isiah is giving us a message of hope giving them a promise that this is just not the end but then we have god's mercy and love on us that god will never cut off the promise that he made to david but then he will give us the messiah who will reign from david's line and he will be obedient until his death and he come and he prophesies over jesus and how we'll be birthed and how his life will be led and till his death and ascension and how we will redeem israel and set us back into the new generously new world with full of hope and love so this message just then stir the people of israel who were in exile or after the exile but then it also gives us a hope to us as we read the book of isiah we see the prophecy of isiah which has been fulfilled and it it also gives us a hope that as we are also waiting just like them for the second coming of jesus that with all hope we can wait because those prophecies will come true so that even though we die even we can believe that we will be we will live alive with jesus within the new jerusalem this is the hope of message with isiah delivered to the people in israel and today this book is also gives us stirs the same kind of hope to us that as we wait on the second coming of jesus with this i end with the book of isiah and i'll keep it open to our class to to share on on the book of isiah what personally you have learned from this book you can take this time to share your learnings open to class as you can share about what you learn from the book of isiah how it has impacted you i think as we already mentioned that there are quite a lot of prophecies which we can take for our personal lives as well um one of which which one of the prophecies which really encouraged me these days was chapter 32 was 18 isiah chapter 32 was 18 then my people will live in a peaceful habitation and in secure dwellings and in undisturbed resting places which i think we can declare it over our families and any relationship that is broken or any place where any houses which we feel like there are there is discomfort there is disturbances we can apply these promises and declare god's favor amen thank you thank you john anyone else who'd like to share your experience from the book of isiah yes please thank you so i say as even you were mentioning like there's a lot of comfort that promises that give us so much comfort and now for me there are lots of favorites in isiah one is especially isiah 4110 i think i had already mentioned it once like where god assures his presence with us and asks us not to be afraid do not fear from with you do not be dismayed for i'm your god i'll strengthen you and help you i'll uphold you with my righteous right hand so it's there has been you know our times in my life that this verse has really helped me get over you know difficulties that assurance of god's presence also these days here the waiting on the lord especially the words that says those who wait on the lord will renew their strength leave them on wings like eagles so those verses yeah we as you were mentioning also like the even though in the beginning we see the judgment but we see a god who cannot you know just leave his children by themselves like orphans even in isiah i think 49 there's a verse which says i have engraved you on the palm of my hands like even if your mother forgets you i'll not forget you so these are promises to the nation of israel but yeah yet it is promised to us individually as well individually as well yes yes yeah this reminds me about isiah 43 also individually when we read it it brings so much of comfort to us yes yes thank you thank you thank you so much yeah anyone else pastor yes i found the the book of israel to be one of the most profited books in the bible and they realized that most of the prophecies that go through the prophet israel were fulfilled in christ jesus it gives us the hope that whatever god has said concerning our lives will also be fulfilled in its due in its due time and i also realized that the people went into activity because of their own sin so you must not blame god for the predicament that comes to us as a result of our own willful sins you must humbly surrender to god and ask for his forgiveness so that he can restore us to our lost glory i also realized that god does not give up on his children he always wants to win the hearts of his children back to himself so through his prophets he speaks to us and he calls us to repentance similarly he is speaking through jesus christ in our in the new testament era calling us all back into repentance so that we will be restored to the lost glory of humanity these are the few thoughts i want to share from the book of israel thank you thank you thank you laisha thank you anyone else who'd like to add on to this book brother lubega brother subhashish yes first of all actually this book is a prophetic book and a long time before jesus actually came to this earth uh isai prophesized that uh jesus will be pierced for our translations and uh in isaac 53 verse 5 to 6 and it's really wonderful that god has uh revealed a huge word through isa long long time before and um we really thank god and that god opened the doors for our translations through jesus and and it's really amazing that how uh isa actually revealed and um really means so i praise god that how actually that time will be that people they uh they were with isa because these are the days we have many prophets and and it's really challenging for us to believe who is the real and who is the false prophets because sometimes they prophesize and happen sometimes they prophesize and and they maybe uh they denied okay maybe some other things but this is a really i really like i said the whatever the things actually god has uh spoken through him and it and it actually had happened and uh he said that uh with his wound we are healed and it happened that jesus actually because of his wound that we are healed many times we yeah thank you so much thank you thank you brother okay anyone would like to go share their experience or the worst that has been impacted in their life from the book of isaia if not we can dismiss with a word of prayer okay zellie would you like to dismiss us with a word of prayer you're still on mute elasha would you like to lead us in prayer i think there's some problem that zellies might thank you we are praying i want to thank you and bless your name for this great opportunity you have granted us all through the study of your way that we pray in the name of jesus that as we have discarded discovered from the book of isaia that your promises are yet and amen and surely they will come to pass at the right time we pray that lord all prophets is concerning the son of god jesus rise forth where fulfilled we pray that may you fulfill whatever that you have said concerning our lives in the name of jesus but we pray that lord whenever we are falling off your grace may your mercy continue to uphold as as you have held the people of isaia in your mighty arms we pray that lord oh god continue to guide us with your words speak to us each and every moment as you spoke through the prophet isaia when we are going astray lord speak to us by your spirit in jesus mighty name we thank you and we want to bless you for the lives of each and every person in this session in jesus mighty amen amen amen thank you god bless thank you in laisha thank you all for joining in today's session see you all tomorrow god bless have a wonderful day thank you god bless


Hi everybody. Thank you Yash for talking to me. My name is Daya. My dad is a patient here. His name is Suraj Vaan. You know, the only reason I wanted to talk to you is I wanted to really recognize and appreciate Ritika Sharma.  Every time, not only when I have come, you know, being a service industry, I always see the people. Six months ago, three months ago even today, but I've always seen her behavior with everybody, you know, being very patient. Not only that, she's very thorough. She wants to make sure she gets done. Even I've seen that sometimes she will pick up her phone and try to accommodate a patient even though the doctor is available if he's not there. And I've seen it a few times. So I really wanted to recognize you, Ritika. You know, if you're listening to this, you've done an amazing job. Incredible. It's not easy to work in a hospital setting when everybody's stressed, everybody's in on top of you, but you always keep your composure and I appreciate it and I just wanted to acknowledge that. Thank you and keep doing what you're doing and I wish you the very best. Thank you.


It's hard to describe, but there's something about a leather jacket that just makes you feel different. And I'm not talking about the, oh, you feel like a badass when you wear one kind of thing because that kind of style isn't for everyone. A leather jacket can elevate your look. It can be elegant. It can be sophisticated. And it will transform how you feel when you wear one. If you've been looking for a leather jacket to upgrade your style in that way, I've got five options that I think really fit the bill along with five different outfits for some fall, winter inspiration. I'm Brian Sakawa. This is He Spoke Style. Advice and inspiration to help you dress well, develop your personal style, and be more confident. Today's video is sponsored by the Jacket Maker and all the leather jackets I'll be featuring are from the Jacket Maker. Jacket Maker has a wide range of men's outerwear essentials, all at a really fantastic price point. Bomber jackets, biker jackets, trucker jackets, and more, all classic designs that are a great addition to any wardrobe, whether you consider your style more timeless or if you're more on the contemporary or trendy side of things. Every jacket from the Jacket Maker is made from the finest quality full green leather, which means that it's got that natural green, it's durable, and will improve with age. And they also use high grade hardware such as YKK zippers and all that attention to detail just helps to ensure that the product is going to last. I mentioned the price. Most jackets from the Jacket Maker retail for $300 or less. And you can also opt for a made to measure option that's around $50 to really help dial in the fit even more, which is perfect if you often find yourself in between sizes or if you prefer a very specific kind of fit. I've personally owned a few jackets from the Jacket Maker in the past. If you follow me on Instagram, you've seen them before and you may remember a video I did last year featuring those pieces as well. They look great. They fit great. And the price point is very affordable. If you're thinking about pulling the trigger, go to that link down in the description and use code Brian10 for an extra 10% off your order. Thanks to the Jacket Maker for sponsoring this video. Now let's take a look at five leather jackets to upgrade your fall and winter style. Up first, one of my all time favorites, we have a classic G1 bomber jacket. The G1, which is what this military flight jacket came to be known as is a revised version of the 1930s US Navy jacket known as the M422 Alpha. It was updated in 1947 and is still the current issue jacket for commissioned and enlisted aviation personnel on flying status in the US Navy, Marine Corps, and Coast Guard. This version is made with a great looking dark brown sheepskin leather, two outer pockets with button closures, quilted lining to inner pockets. It's got a knit rib cuff and knit rib around the bottom as well, zip up front and a fur collar that is removable. Obviously many, many ways to wear this, but let's take a look at how I styled it for this video. So very classic, not unexpected. I've got a mock neck sweater that I paired with some medium blue jeans, suede chukkas, and then giving a nod to the G1's history with both the vintage aviators and the IWC Spitfire on the wrist. When I wear a leather jacket, I generally like it to be the focal point of the outfit, but I tried to make this a little more interesting with the addition of some texture. The mock neck sweater has a great texture to it, which really sets it apart from the smooth leather. And then the suede chukkas as well, unlike matching your belt finish to your shoes, totally fine to wear suede shoes with a smooth leather jacket. It breaks it up visually, it makes it look less perfect, and I think it's overall a more interesting look. Up next we have another bomber jacket, this one a bit more simple than the previous, still a very classic look made with black sheepskin leather. It's very soft and supple, two outer pockets, quilted inner lining, two inner pockets. It's got knit rib cuffs and same on the bottom as well, a zip up front, and then the collar is actually lined on the inside. So if you wanted to zip it up all the way, it would be a bit more comfortable around the neck. So this look is perhaps a little unexpected, wanted to show that it is possible to dress up a black leather jacket. Again, it's just very simple cashmere cable knit sweater paired with some mid gray flannel pants.  I always think it smartens up an evening look like this. Dressing monochromatically like this, easy way to make a statement by doing less, and also a statement that's not going to call a ton of attention to yourself. To do it well, just make sure you're not matching colors exactly. I've got two shades of gray here along with the black, and then adding in some texture as I've done with the cable knit is another great way to keep it interesting. Here we have another bomber jacket in a beautiful mocha brown suede. It's a goat skin leather, and you can see the really nice suede finish. This is a really simple and elegant design, which I love. It's got two outer pockets, quilted inner lining with two inner pockets. The collar is a knit rib, which gives it a little more of a sporty feel. It's got a zip up closure and snap closures on the cuffs. Going monochromatic once again with this look, got a tan cashmere turtleneck paired with some cream colored cotton trousers, brown suede belt to go with the suede penny loafers, also cream colored socks, and finished off with the Vacheron traditionnelle on my wrist. Pretty much exactly the same concept as the previous look where we're dealing with a variety of shades of brown as well as some texture. Great example of how a leather jacket, in this case suede, can be more sophisticated than you might think. Here is our fourth jacket. This one is in a beautiful cognac light brown color. Once again, it's made with sheepskin leather, two outer pockets, a quilted viscose lining, two inner pockets. It's got a button up front, which gives it a much different look and feel than a zip up front. Cuffs are buttoned as well, and it's got a simple well proportioned collar. Styling it here with a little more contrast. I've got a cream crew neck sweater paired with some black jeans, brown chelsea boots, and a speedy on the wrist. Here, I have decided to kind of color match the boots and the jacket. You know, with a higher contrast foundation of cream and black, it really helps balance the look as a whole. I really do love the color of this jacket. Just pops. And as I said, the button up front just makes it different than most leather jackets, and as a result, a real standout piece. So if you have been a longtime fan of HSS, I think you're really going to be excited about this last jacket. It is very similar to one that I have worn a lot in videos over the years. And pretty much anytime I wear this jacket, you guys ask me where you can get it. And I always feel bad because it's really old and no longer available. But this one is the closest thing I have ever found to that jacket. And not only is it very similar, but the price is way better than the other jacket. So this is a light brown suede trucker jacket. It's goat skin leather. It's just super soft and supple. It feels great in the hand. It's got four outer pockets, two down low, and two breast pockets with snap closures. Inside is a quilted lining as well as two inner pockets. It's a snap closure up the front, simple collar. And it's also got snap closures on the cuffs, as well as on the two waist adjustment straps. Going super casual with this look, a cashmere hoodie paired with some light wash jeans, white leather sneakers, and speedy on the wrist. Once again, you've probably noticed that I like to pair a cashmere with leather jackets. I think especially as an older guy, it's a very easy way to showcase a little more sophistication and make the look more grown up. Also, you know, investing in pieces like that, you're going to get more out of them. So over time, financially, it makes sense as well. Thanks once again to the jacket maker for sponsoring this video. Links to all the jackets featured here are down below in the description. And remember that you can save 10% off your next purchase by using code BRYANTEN at checkout.


Hi folks, it's Jen with opensource.com bringing you the top five articles from this week, September 5th. As always, you can find the articles in the description below the video and also on opensource.com every Sunday. First up, we have Trying Out WordPress 4.0 on OpenStack. Jason Baker shares with us his experience of getting the new WordPress 4.0 up and running on an OpenStack instance. WordPress 4.0, called Benny, was officially released yesterday, but it was a few days ago that Jason used the TriStack site to test out the release candidate version. In this step-by-step, see how Jason launches a virtual machine, connects his OpenStack instance to the outside world, and creates a WordPress database. At number four, we have the next open-source frontier is the farm. Michael Thiemann brings us a story about the plight of what big agriculture is doing to farmlands and to our food. He asks, what can open-source do about it? Thiemann first explains that industrial agriculture evolved around the assumption that total uniformity was the key to efficiency. But what if large-scale processes could tolerate medium-scale diversity, restoring the benefits of ecological diversity to improve farm health? One open-source answer that has come about so far is FarmBot, a universal agricultural tool based on 3D printing technologies that can make crops economically feasible that were not feasible before by automating tasks that are too labor-intensive for humans to do. But on a small scale, allowing for diversity where large-scale farming cannot. At number three, we have top four open-source invoicing tools for freelancers and small businesses. Scott Nesbitt reviews these four tools, Simple Invoices, InvoiceNinja, CWAP or SIWAP, and open-source billing. Scott also gives readers tips on what to look for in an invoicing tool. At number two, we have Canvas Free Software Company, Secure the Future of Linux for the City of Munich. George Greve, founder and CEO of Colab Systems, addresses the concerns of City of Munich officials over a Linux distribution government workers have been using called Linux. George points out that Linux is not to blame for their problems with the calendar and email systems, and that going back to Windows is an unnecessary step. George tells us, and we're hoping the City of Munich is listening, that the newest release of Colab 3.3 alleviates these issues and is the fix everyone is looking for. Finally, at number one, we have Bringing New Security Features to Docker. Dan Walsh has been working on container technology for several years and runs the Red Hat Enterprise Linux Docker Enablement Team. He also works closely with SE Linux and frequently writes on topics of security for open-source.com. In the second part of a series on Docker and security, Dan addresses the misconception that containers contain, and walks readers through what security measures should be taken to protect the host from the processes within the container, and also to protect containers from each other. That's it for the top five this week, everyone. Thanks so much. See you next time.


So now I'd like to start us off with a illustrious researcher with a remarkable career in comparative and functional genomics. So Harris Lewin, I am going to read this to make sure I get it right, is the... Can you hear me now? Okay. So Harris Lewin is the Robert and Roosevelt Osborne Endowed Chair and Distinguished Professor of Evolution and Ecology at UC Davis in his latest carnation of his career. He is also the chair of the Earth Bio Genome Project and a member of the National Academy. And as I said, he is probably known to everybody here because he is one of the guiding lights in this field, so we're very lucky to have Harris. Well, I'd like to thank Jen for that very nice introduction. And I'd like to thank the organizers for inviting me to the workshop and specifically for the honor of allowing me to give the keynote address to this group. My assignment from Jen and the organizers was to help to set the stage for the workshop to provide a very broad view of comparative genomics across all of life's domains with an emphasis on forward thinking for the development of NHGRI's strategic next 10-year strategic plan. Before moving forward, I'd like to take a brief historical dive into the past to see how we got to where we are today. So the method of comparison, we just heard this very nicely from Adele, the method of comparison has been a very critical methodology to philosophers, to biologists, and to medicine for more than 2,000 years. And of course, Aristotle in his very early classification system for life on Earth recognized that before you can understand the differences between species, what makes this individual organisms different, you have to be able to group them by their commonalities. And that was really the roots of 2,000 years of what then in the early 1700s, Linnaean used the same system of comparison to create the Linnaean system of taxonomy, which we are still using 300 years later today. Of course, Zuma had another 150 years and Darwin, of course, used the power of comparison both within species and between species in his exposition of the theory of evolution by natural selection. And more recently, maybe 150 years from Darwin, we have the first example of the use of genetic techniques by Carl Woze, who compared 16S ribosomal DNA sequences, those DNA sequences encoding the 16S ribosomal RNA subunit, and was able to forever change our view of the evolution and history of life on Earth by recognizing that what were then called the archaebacteria were not bacteria at all. In fact, they were a separate domain of life, the third domain of life, distinguishing them clearly from the bacteria and the eukaryotes. And so these very powerful tools of molecular phylogenetics across the different groups of organisms shed great light on our understanding of the history and evolution of life on Earth. But the term genomics, this is the mid-70s. The term genomics wasn't even invented until 10 years later. And those of you who've been around long enough remember that this term was put out by, first suggested by Tom Roderick, a biologist at the Jackson Laboratory at a pub not far from here in Bethesda. And this was written up, this story, in beer Bethesda in biology, on how genomics came to being. Genomics as a field, as a discipline, was born not far from here. And the early practitioners of the field of genomics, particularly comparative genomics, were the mappers, the comparative mappers. And we're very fortunate that some of those folks are still around with us and still very active. I didn't know my friend Steve O'Brien would be here today. But that's his picture there, and that's the real thing right there, one of our founders. And we're so fortunate to have people like Steve and Jim Womack, again, those of you at USDA will remember Jim, and people like Jenny Graves in Australia, studying the weird mammals of Australia and trying to understand the evolution of sex through the study of the evolution of sex chromosomes. So Steve with his cats, and Jim with his cows, and Jenny with her weird animals, this was really the beginning in 1984. And that's about when I came along, little Harris, as Steve used to call me in those days. And I heard a talk, I was trained as an immunogeneticist and I was working on the genetic control of disease resistance. And I heard a talk by Jim Womack in 1985, and Jim put up this slide that showed a comparison of the organization of the cow, the human, and the mouse genomes. And the markers in those days were biochemical markers and serological markers. There weren't really molecular markers in those days. But I became completely, you know, enthralled with this idea because I was working on the Majestic Compatibility Complex and I just thought, you know, a cow was the MHC with another, you know, and others thought that a mouse was the chromosome 17 with hair. I mean, we had a very limited view of comparative genetics because we had very few loci that we can study in those days. And in that interest, you know, that interest at that time eventually over the period of the next 10 or 15 years led to my own interest in comparative genomics and evolution as we recognized that these same techniques we were using in comparative genetics could be used across the entire genome. And it was only, we believed a matter of time before markers went from, maps went with markers of tens and 20 organism, 20 markers to hundreds if not thousands of markers, not even anticipating the kinds of things that we think about today. We just didn't even think it was possible. But after 30 years, my love affair with chromosomes is still going on and I'm still as passionate about chromosome evolution as I was when we began 30 years ago. So what is comparative genomics? What is this new field? This new field is a field of biological research in which genomic features of different organisms are compared. The genomic features may include DNA sequences, genes, gene order, regulatory sequences and other genomic structural landmarks such as three-dimensional structure. I think you can find this definition on Google. It's there. The field of comparative genomics is absolutely exploded. If you go back the most recent publication to summarize this was Mulligan in 2004, I happened to do just a little search before I came over to see what has happened since 2014, I said 2004, 2014, and what we see now is over 4,000 titles and abstracts with the word genomics in it and more than 650 titles and abstracts with the words comparative genomics. So in the last six years, we have had more than doubling of the scientific output in this very new discipline. And this is a good sign. This field is really expanding logarithmically and building or linearly and bringing in many talented new investigators. And so comparative genomics can be grouped into sort of three broad areas, interspecies such as comparing of maps as we talked about a moment ago, of sequences, identification of conserved regulatory elements, introspecies comparative genomics or within a species such as identification of population level genetic variation using SNPs and GWAS studies, within individuals such as the identification of cancer genomes, within individual patients, and even whole ecosystems, the identification of organisms in complex ecosystems and how they respond to their changes in their environment. And many of you, those in the room today, have been very important developers of the tools that we use for comparative genomics which span everything from DNA sequence comparison tools to annotation tools for annotating genes and functional annotation of genes, evolutionary and population genomics tools for doing epigenetic analysis and epigenomic analysis, tools for understanding the microbe and host microbe interactions, as well as the data visualization tools which and analysis tools which have become so critical to our field as the data have been rapidly expanding. Genomics and comparative genomics has contributed tremendously to important applications as well. This is not just a fundamental scientific discipline but is a discipline that is yielded important practical results in agriculture and in medicine and environmental sciences and in conservation. And I won't go through all of those things. This is well known to most of you, genetic diagnosis, identification of genes responsible for diseases and complex traits and this spans across all really of the important, economically important eukaryotic taxa, species of plants, animals in particular. So I won't go through all of these things. These are well known to most of you in the room. But what we should realize is all of these advances that we've had in the past 20 years has been accomplished with the knowledge of the genomic biology of very, very few organisms. If we look across the entire universe of known eukaryotic organisms, about one and a half million species, if you go to GenBank you will find genome sequences for only about now about 4,000 and 2018 about 3,300 unique species. And what is absolutely shocking is if you parse these into taxonomic classification, yes, we have a representative from each of the three domains of life. Yes, we have a representative species sequence from each of the five, if you will, major kingdoms of life. But once you get past the kingdoms, even at these higher taxonomic levels, such as phylum, 37 of the 71 phylum, we don't even know how many phyla there are. But 37 of the 71, only 52 percent, have been sampled as a representative organization at the phylum level. And it gets worse after that. At the class level, 41.5 percent. If you look in the, in the chordates, chordates is a phylum and you take our own lineage that would be equivalent to a mammal, 41 percent only sampled, 31 percent of the orders, 10 percent of the families, 0.89 percent of the genera and 0.22 percent of the species. This is rather humbling, I think, for most people and when we think about the future, we must think about what we're going to be able to learn if we understand and if we sample the blueprints of life from the remaining 99.8 percent of the known eukaryotes. And remember what we know is only 10 percent, perhaps, of what's there. So you can multiply that by 0.1. And that's probably the representation that we have for known life on the planet. It is, we are just at the beginning of this journey. And then you have 3,311 sequences. Well, how good are those sequences? You know, these are the genome sequences. That's the next question you're going to ask. And these data are summarized, we're summarized together, myself, John Coddington and Mike Trizna at the Smithsonian Institution. And I'll just explain a little bit of what this diagram shows, if I can figure out this little laser pointer here, yeah. Okay, so this bottom number here corresponds to sort of the level of saying these are contig assemblies, the twos are all scaffold assemblies, the threes are all chromosome assemblies, and four are complete genomes. The next number is the log, okay, is the log of the contig N50, okay. So a value of 6 here means a contig N50 of a million base pairs. The next number is the log of the scaffold N50. So a log there of 7 would be 10 million base pairs. So if you look here where the majority of sequences across all of life, first thing you'll notice is like half of what's been sequenced are fungi, okay. And then animals of all types, not just vertebrates, and then the plants and produce, and I love the other category, which is really the biggest category of eukaryotic life, and there's 30 of them there. And then we look at the distribution here of these genome quality metrics, metric if you would like to call it. And you could see the vast majority of sequences bunch up here in this group in the middle, which have contig N50s of somewhere around between 10,000 bases and 100,000 bases and scaffold N50s between 100,000 and a million. And if you go out here to the right, which are the really good high quality genomes, you'll see most of those are fungi again, and very few of them are plants or animals. And I want to point this out because Eric Jarvis is going to talk about this, I'm sure. The metric for the vertebrate genomes project, the newest and best genomes that we're able to produce are right here. This is the metric, chromosome assignments, contig N50s of a million, scaffold N50s of 10 million or greater. And the contribution just last year of 14, just in the last year of 14 genomes of this quality is quite a contribution really to our overall, you know, overall knowledge and collection of very high quality reference genomes, which is what you would consider here. So as we move through the next two days, we need to ask ourselves the following questions. First of all, what should we do when we are thinking about producing reference genomes? Do we produce reference genomes to ask a specific biological question? Or do we produce reference genomes to ask those questions and in addition questions that we have not even thought of yet? And I think I'll argue, and I'm sure that Eric's going to argue, that we should do the latter. Do the best we can now, do it once, and you don't have to do it again. Okay. And so what enables then comparative genomes, we need more genomes, you know? We don't have very many to compare. We need more genomes and what enables comparative genomics is high quality genomes to compare and the tools to compare them. And so I'm going to spend a few minutes because this is really the thinking that led to the Earth Biogenome Project. And you know, it was, it's clear that having more genomes, better genomes, you're going to be able to address a broad set of scientific health and environmental and conservation issues. And the idea for this project arose about four years ago at, and the first time it was discussed was at a meeting at the Smithsonian Institution, several of you were there, I know Paula Mayby from who was at NSF, at the time she was there representing NSF. And there were, Lakshmi I think was there as well for USDA. And we had a very intense discussion. We presented this idea for the first time and everybody felt in 2015 that it was a good idea to explore this idea further. Two years later, the project was sort of framed in this way as a grand challenge. The Earth Biogenome Project, what it is, is a confederate confederated network of networks that has a common goal of sequencing and annotating the genomes of all 1.5 million known species in a period of 10 years. Not very ambitious, but this is what we have proposed. And we have outlined this in a paper published in 2018, in April of 2018, in PNAS, Pam Soltis is here, Eric several of the authors of this article are in the room. And this perspective article laid out the goals, the challenges, and the potential benefits of this project. And since that time, the response really from the scientific community has been overwhelmingly positive. Very much unlike what happened with the human genome at the beginning, we only get your nuts or something like that, or it's overly ambitious, but we rarely get criticized in saying that the value of a project like this to science and to the world would not be worth the cost. And so a little bit about where we are because if we need genomes, we have to be organized to produce them. The project officially launched last year at the Wellcome Trust in London, I think unless you've been hiding under a rock, you haven't heard about this. Extremely wide media coverage endorsed in nature and even in the times of London. The project really got a boost in moving forward when the under the leadership of Mike Stratton at the Wellcome Trust Sanger Institute committed 50 million pounds or approximately $65 million to producing genomes at scale over a five-year period to organize this project. They've already hired their director, Mark Blackster, a very prominent evolutionary genomicist from the University of Edinburgh, and they're seeking another $100 million with the goal of sequencing all 66,000 species that have been found in the United Kingdom. That's the stated goal of the Darwin Tree of Life project. An organized national project to sequence the entire biodiversity in the United Kingdom. And they're about to announce further commitments to this project. There are also ongoing national projects in China and Chile. Has their 1000 Genomes Project, India, Korea, Australia, where there are Oz mammals and there are plant genomics in Canada, where there's 150, can 150. This is starting to get going and it's becoming a global movement. Something I think that's been mildly disappointing to many of us in the United States and it's in large part due to the way science is funded in the United States, and I'm going to talk about this at the end, is that there is no comprehensive national project as there is now in several other countries. Just two weeks ago it was announced in California that we have a $10 million program called the California Conservation Genomics Program, which will contribute at least 100 genomes to the Earth Biogenome Project. This is headed by Brad Schaefer at UCLA at the Lerkratz Center there. And the USDA has a very, very nice project for sequencing 100-ag pests. In terms of large-scale sequencing of eukaryotes in a coordinated fashion, there's not much and we aim to address that. The project has 25 participating institutions that have signed the Memorandum of Understanding in 13 countries that commit these institutions to the principles of the Earth Biogenome Project as outlined in the Memorandum of Understanding. For open data access and sharing and commitment to the principles of the Convention on Biodiversity Nagoya Protocols for Access and Benefit Sharing, there are over 20 communities that have now voluntarily affiliated with the Earth Biogenome Project, many of them represented here today. And this has been really important to us because some of these communities, as you'll hear from Eric's talk, have been really leading the way in producing high-quality reference genomes. That's the vertebrate genomes project, which I've been a part of since 2009 when the project was founded. And how would we go about doing this? You can't do it all at once. Again, I mentioned this was over a 10-year period. And the first strategy we call it the phylogenomic wave. And the proposal is to get the framework backbone, the outline of the Tree of the Life by first sequencing all of the known 9,300 known eukaryotic families, one representative of each of the eukaryotic families, to reference quality in the first three years. In phase two, it would be 200,000, approximately 200,000 genera. In phase three, it would be all known 1.5 million species. And if you want to have an idea of what that really scales to and how achievable and doable phase one is today with the technology that we have, that would be 60 genomes a week worldwide, 60 genomes a week worldwide over a three-year period. If there were 10 laboratories around the world, that would be six genomes a week. And Eric tells me that this is about exactly what he's being able to produce right now. And so this is clearly scalable. Phase one is achievable. In the United States alone, we have somewhere between 2,000 to 3,000 of the families represented. We could do a third of all the families, just with species here in the United States. Very achievable. Phase two and phase three require more genomes, 865 a week, and eventually to phase three in the out years, probably sequencing technology in year seven through ten that we don't even have or can imagine maybe today. That would be 9,000 genomes a week, which with instruments like ONT and the new pack biotechnology may not be that far fetched if we're talking about high quality draft processes and not reference genome quality for every species. We're talking about reference genome quality just at the family level. And that's the wave. Did I not have the right slide up? I don't know. Okay. And the second strategy, complementary strategy, and to be done in parallel is what we call the Google Life Strategy or sequencing of entire ecosystems, which is essentially of all organisms in a particular geographical area. For example, within biodiversity hotspots, everything in the soil, land, and water. This is already being done to some extent with some of the EDNA technologies, but anybody who's using EDNA technology knows that if you go out and sequence, at least half of the thing, half of the reeds don't map to anything. And so until you have the organisms identified, you really are shooting in the dark with these kinds of studies and trying to understand complex ecosystems. And so technologies can easily be adopted once you have the sequence for being able to assay at very low cost entire ecosystems over periods of time to understand then the impacts of environmental change on biodiversity and eventually to produce a multi-dimensional dynamic view of all life on Earth. And this strategy is being employed by the Darwin Tree of Life program, and it is part of what we're planning to do in the California Conservation Genomics Program. So what's all this going to cost? I swallowed hard there, but it's really not too bad. It's $4.7 billion. And these numbers were rigorously tested. This was two years ago, $4.7 billion over 10 years. And, well, how does that compare to the Human Genome Project? If you look at what it cost in about 1990 dollars when the Human Genome Project was initiated, that's about $3 billion. Today, or in 2012 dollars, is $5.4 billion. Today, this is probably close to $6 billion. And we had pretty firm estimates less than two years ago that I think have been very well tested that all million and a half known eukaryotes can be sequenced at a cost of under $5 billion. Now, the initial calculation I did on the way back from a flight in 2014 was about 2.7 when we added all the costs in. It turned out to be right. And at that cost, we're going to get better genomes. Better genomes than we initially anticipated because the cost of long reads is going down. And the return on the investment to the United States economy alone, as outlined in the Battelle report, was a trillion dollars. And if that's what returned from one species, what's going to be the return on investment for another million and a half species? It's going to be likely to be many times more. But it's not, you know, just about the money. It's about our understanding and the rules of life as was just talked about. And so this is where we are. $4.7 billion, it is a lot. I don't know. The Lodge Hadron Collider has a budget of $1 billion a year. It costs $13.2 billion to identify the Higgs boson. And I would argue that the value of knowledge that we're going to gain from a million and a half species to the average person on this planet is going to be far greater than what we have from some of these very large science projects, both very fundamental knowledge but very little applied knowledge. And so this type of project is going to, no doubt, it's going to happen. It's going to happen sooner. It's going to happen later. But it's not going to happen if we don't have a systematic way of doing it. But what happens when we come together across agencies and across projects is we have the ability to completely revolutionize the life sciences. We have right now the loss of 50% of the vertebrate population in the world in the last 40 years, 27,000 species that are on the threatened and endangered list no matter what they do to the legislation for the Endangered Species Act. It's very important that we move on this because by the end of the century it's predicted that we're going to lose half the biodiversity on Earth if we don't do something about it. And having a repository, a digital library of life and making sure that we have a representation of every species that we have on this planet at this point in time, the most biodiverse period in the history of this planet would be a huge mistake to pass on to our descendants. We need to do this. But out there lies new resources for the improvement of plant and animals in plant and animal agriculture. New sources of genetic variation that have yet to be exploited. New drugs to be discovered. 80% of the pharmaceuticals that we consume today in the world have its origin in a natural product, 80%. And finally, the value of basic science. Most of you are familiar with the Linnaean taxonomic view of a hierarchical tree of life, but this is our current view of the eukaryotic tree of life. And for those of you who want to be humbled, you are here, right there. That's humans in this vast new way of looking at eukaryotic life in these five supergroups in which we're more closely related to fungi than we are to many of the other eukaryotic life forms that he've evolved over the last two billion years.  And the value here is going to be enormous. Let me see. So in the last few minutes, I just want to give you a few examples from my own research on how chromosome-scale assemblies can assist in understanding very deep and complex problems in evolution. And the area that I've been interested in is chromosome evolution. And this field was really dead, which is why I went into administration for five years, because there just weren't enough genomes for us to analyze. Chromosome evolution is a process by which chromosomes change in the order and orientation of genes, regulatory elements, and three-dimensional structure over time. This is a paper that we published in 2019 that schematizes sort of the main discoveries. First thing you need are these chromosome-scale assemblies so that you can define the lineage-specific breakpoints in chromosome evolution over time. We discovered that the evolutionary breakpoint regions that flank the boundaries of the rearrangements are enriched in lineage-specific transposable elements. Lineage-specific transposable elements contain more transcription factor binding sites, and these transcription factor binding sites, if there are more of them, lead to higher affinity for transcription factors, all shown here. And those lead to stronger enhancers, and these stronger enhancers can lead to the change in gene expression. And some of these changes in gene expression are no doubt related to adaptation and speciation, as has been known for some time. And so what we really need, the framework for doing all of this kind of work, which was published in Genome Research, is having a really good understanding of the comparative organization of chromosomes across evolutionary taxes. So, back in 2015, we first set out to do a much more extensive computational reconstruction of the ancestral genome of all placental mammals. The most recent one before that was 2005, which we published with Mr. O'Brien there, and has then post-doc Bill Murphy, and we had a handful of genomes. We only had three sequences, and we learned, we figured out how to integrate maps and sequences to look at, you know, do a reconstruction. And we reconstructed the Boreo-Eutherian ancestor, but with only about 50% coverage related to the human genome. With the genomes that we have available, I'll talk about it in a moment. Our goal was to define all of the evolutionary breakpoint regions, conserved blocks along the lineage, Eutherian lineage leading to primates. And this is an area that we now call Paleogenomics. And again, in setting the stage, this is an area I think that Beth Shapiro will cover tomorrow. Now, the way this study was done was using 19 Eutherian species representing 10 orders. We didn't even have four of the major, all four of the major super orders represented. We had three of the four. And for the first time, we learned how to use scaffold-based assemblies. There were seven of those, and two out-group species. And the descrambler algorithm, which we developed and described, was developed by J. Boom Kim, and described in this paper was applied to this dataset. And we reconstructed seven ancestors, including the Eutherian ancestor, the ancestor of all Eutherian mammals, and then six other ancestral genomes leading to the human genome. And the kinds of information that you can get from a reconstruction like this is that you can define all of the fusions and the fusions and inversions and complex rearrangements along the 105 million-year evolutionary time span between the Eutherian ancestor and the human and other Eutherian mammals. And as you can see from this table, we could define eight fusions, 12 fusions, 59 inversions, 38 complex rearrangements for a total of 117 rearrangements over a period of 105 million years. That's about one rearrangement every million years. You think about the number of myosis. So large-scale rearrangements are quite common, but stable rearrangements are very rare. And we're very interested in the rates of rearrangements, and as you can see, the rates differ. This confirmed our 2005 study early before the K-PG boundary. The rates of chromosome evolution were very low. And then after the gritaceous paleogene boundary, after the asteroid impact, it seemed that chromosome evolution speeded up. We showed this in the murid lineages and confirmed this in the primate lineages in this study. And so why is this important? Why would this be important to NHGRI? The first example of a genetic mutation associated with a human cancer was a chromosome rearrangement. 1959, the Philadelphia chromosome was discovered. Janet Rowley, in the mid-70s, was the first to demonstrate that the etiology of these small chromosome 22s was actually a reciprocal translocation between chromosome 9 and chromosome 22. Later, it was shown that this translocation produced a fusion of the V-able gene and the BCL gene, producing a tyrosine kinase signaling molecule that was constitutively expressed in all cells that had this particular rearrangement. And that tyrosine kinase could be shown to directly transform cells. This rearrangement is found of 95% of all patients with CML, chronic illocytic leukemia. And what we showed in 2005 was that this breakpoint, in fact, on chromosome 22 was an evolutionary breakpoint region, a region that we could define as a breakpoint as far back as the ancestor of the U-archontagliar ancestor. And so, here it shows the examples of good annotation, high-quality genome sequences, in being able to unravel a very important problem. And that's not the end of the story. This beautiful story is that, as a result of this knowledge of what the fusion protein was, a drug was developed, GLEVAC. So, this is a complete story from rearrangement to drug to treatment, and a very effective treatment, indeed, for the treatment of CML and other cancers of the hematolymphoid system. And, yeah, she's gonna... Yes. And so, I'm going to just wrap up in the next few minutes to say, we've now expanded these studies. The 200 Mammals project has been incredibly important to us. We're collaborating with Eleanor here and Kirsten, Bruce, the folks at the Broad Institute. And our chromosome evolution collaborative, getting a representative species from each of the 19 Euthyrian orders plus representatives of the marsupials, the metatherians, and the platypus, the protherians. And we're doing a complete reconstruction, the first reconstruction of a mammal genome. And when I saw this just last week, unpublished data, the only unpublished data I'm showing you, I practically cried because I've been waiting for 20 years to see something like this. This is an evolution highway image showing an overlay of 30 different chromosome scale assemblies on the reconstructed mammalian ancestral chromosome 8a. And to me, this is one of the most beautiful things.  But in this beautiful mosaic of genome evolution, you can see so many interesting and important features. Features that have been conserved when you compare to the outgroups, the chicken, and you know, the most recent common ancestor of the Euthyrians, of all the mammals, 312 million years ago, synthetic relationships that have been conserved over vast evolutionary time scales. And in certain lineages, rearrangements are speeding up, and other lineages, these arrangements are stable over hundreds of millions of years of evolutionary time. So I just want to wrap it up and say, you've given us our charge, Jen, identify the areas of synergy across all taxa, identify gaps in knowledge and resources and recommend areas that we should focus on. I've made a list of things that I think would be cool to talk about over the next few days, especially the areas of synergy across all taxa. I think these things are important, no matter what tax you work on, high-quality reference genomes, functional annotation, things that why June is doing with FANG, functional annotation across taxa. How nutrition affects, yes. It is time to get off. Host defense, wellness and disease, all of these things are across taxa, and gaps in our knowledge, how 3D genome structure affects genome evolution and function I'm working with. There is Lieberman who's in the crowd on that problem. Many different problems that are important no matter what group of organisms you're working in. And, oops, I went the wrong way. And finally, we'll leave it for the last few days to work out strategies for NIH. But I just want to say this last thing, is that what we really need from NHGRI and from NSF and from the representatives here is to have strong interagency support and coordination of funding for a national large-scale genomics initiative. We are being left behind by our colleagues around the world and many of our scientific competitors. And it's because of this mission. If I go to NIH, you'll sequence anything that kills you. DoSDA will sequence anything you can eat. DOE will sequence anything that you can create energy from. But there are lots of organisms in between. And, you know, NSF really does have this broad mandate. And so we looked at NSF, really. But NSF is a hypothesis-driven type research organization. And what we're talking about with Earth Biogenome Project is an infrastructure project. An infrastructure for the future of biology. And until we start thinking about it as an infrastructure project, it's going to be very difficult to get this kind of project funding. So that's my plea. We are going to the moon, and we're not going to stop halfway. People say, well, why do you need to do all of them? Maybe evolution happens at the species level, not at the genus level or the family level. You need to go all the way. And we can talk about that, not halfway. And we're going to do it. It's not going to be easy. We don't have all the answers. But we're well on our way. And so now is the time to really think about this. And to go forth and sequence, and to annotate as well. And to do all the things that we're here over the next three days to discuss. Thank you very much. Really hard person to kick off. So.


Hello. All right. Thanks for the introduction. So today, I will be talking about explicit rate 1 non-medical code for local tempering. So this is joint work with Stevia Gupta and Hamata Maji. So let me first tell you what is non-medical code. So you have already seen some of this from Marshall's talk, but let me just quickly remind you. So non-medical code is a primitive introduced by Zimbofsky, PyTrak, and Witz back in 2010. So this primitive is originally motivated by temper resilient cryptography. So imagine you have signature schemes where the adversary might be able to temper the internal state of the challenger and then obtain a signature under some tempered secret key and then try to forge the signature under the original secret key. Under such tempering attacks, the classical security guarantee of the signature schemes does not say anything about whether the adversary could succeed or not. So the idea is that if we use non-medical code to encode the secret key, this could help preserve the security of the signature schemes, even in the presence of such tempering attacks. So intuitively, non-medical code is a coding scheme such that if some tempering happened on the code word, then the tempered code word either encodes the original message or some message that is completely unrelated with the original message. Specifically, let's say you have a message that is first being encoded and then tempered by some function F and then you get the tempered code word and then you decode this tempered code word to get the tempered message. So we want to say that this tempered message, message tilde could only be related with the original message in three following ways. The first way is by identity function, meaning that the tempered message is identical to the original message. The second way is a special symbol, but simply means that the tempered code word is an invalid encoding. And finally, the third way is a constant function, meaning that this tempered message is being fixed to some constant no matter what the original message is. More formally, non-manable code ensures that for this tempering function F, we can, there exists a simulator that outputs a distribution over these three types of functions such that the distribution of the tempered message in the real word is indistinguishable from this simulated distribution. So note that this simulator only takes the tempering function as the input and is oblivious to the original message. So if you think about this definition for a while, you will quickly realize that this tempering function cannot be an arbitrary function. The reason is very simple. So since this is a coding scheme, the tempering function can always first decode the code word first and then flip a bit of the message and then re-encode. In this way, the tempered message, message tilde will always be the original message with one bit flipped. Then there cannot be any simulator that simulates this process. Therefore, non-manable code is always defined with respect to a fixed set of tempering functions. And just like error correcting codes, we define the rate as the ratio between the length of the message and the length of the code word. So intuitively, high rate here implies that the overhead of achieving non-manability is low. So since the introduction of non-manable codes, after many years of research, we find that non-manable code is actually closely related with many other primitives in crypto. For example, in the field of privacy amplification, we have this primitive called non-manable extractors and it turns out that non-manable extractors and non-manable codes are very closely related. And we have many excellent research going on in this area. Next, in the setting of multi-party computation, we also have found constructions of non-manable commitments using non-manable codes as building blocks. In relatively new primitives, called non-manable secret sharing, many of those constructions of non-manable secret sharing also use non-manable code as a building block. So the research objective of this line of research is to find explicit construction of non-manable codes with high rate against sophisticated tempering families. So high rate directly translate into high efficiency in those applications and reductions. And the sophistication of such tempering families implies a stronger security guarantee. So in this talk, we will be focusing on local tempering. So let me first tell you what is local tempering using a very simple example. So here, we have a code word that consists of four bits, a one, two, three, four. So this tempering function will take these four bits as input and output a tempered code word. So here, the first input bit will depend on, the first output bits will only depend on the first input bit and the second input bit. And the second output bit will depend on the first input bit and the third input bit, and so on. So we say a tempering function F has delta output locality if every output bits depends on at most delta input bits. So here in this example here, every output bits depends on precisely two input bits. So F has two output locality. Analogously, we say that F has delta input locality if every input bits influence on at most delta output bits. So in this example here, the first bit actually influence on all the output bits. Therefore, this function F has four input locality. So we say a tempering function F is delta local if it has delta output locality. So do note that for delta local tempering functions, this function can actually have arbitrarily large input locality, just like this example here. And this fact actually turns out to present significant technical challenges when designing non-mailable code. So in this work, we gave a compiler that compiles a low rate non-mailable code into a rate one non-mailable code. So specifically, for any constant C between zero and one, we gave a compiler that compiles a low rate non-mailable code against local tempering with an appropriate leakage resilience property into a rate one non-mailable code against this constant C times log n local tempering. So ball at all gives the first feasibility result of non-mailable code against the local tempering. Our compiler instantiated with ball at all construction gives us a rate one non-mailable code against C times log n local tempering. And as a corollary of our results, we obtain a rate one non-mailable code against NC0 tempering. This is because NC0 tempering is all the tempering with constant locality. So to give you a more detailed comparison, when the locality is a constant or NC0 tempering, ball at all construction has a rate, has constant rate while our work has rate one. When the locality goes beyond constant and is smaller than the threshold we set here, our ball at all construction has a decaying rate while our work still has rate one. When the locality goes beyond the log n, ball at all construction, the rate of their construction is linearly dependent on the inverse of the locality. Unfortunately, our work does not extend to this case. So as a very cool application of non-mailable code against local tempering, ball at all construct non-mailable code against AC0 tempering. So in this application here, they actually requires the building block, the non-mailable code against local tempering to have a very high locality. So our work here does not improve the rate of their AC tempering here. So before I go into our compiler, let me tell you a bit more about what do we know about non-mailable code against local tempering. So we have very nice Monte Carlo constructions that tells us when does rate one non-mailable code exist based on how large the tempering family is. Such Monte Carlo constructions implies construction in the common reference ring model. So firstly, fourth at all tells us that when the tempering family has size two to the polyn, rate one non-mailable code exists. And the more over, their construction is efficient. When the tempering family size goes beyond that and it's actually two to the small of n, Chilachi and Gruswamy's results tells us that even in this case, rate one non-mailable code still exists. However, their construction is inefficient. So a quick calculation will show you that for a delta local tempering family, the size of this family is roughly two to the two to the delta times n. So if you plug in delta with order of log n, fourth at all results tells us that efficient rate one non-mailable code exist in this case. When delta goes beyond log n and is still small of n, Chilachi and Gruswamy tells us that rate one non-mailable code exist. However, it remains unclear if efficient rate one non-mailable code exist in this case. So as a reminder, our work here shows that we can get explicit efficient rate one non-mailable code when delta is smaller than some constant times log n. So before our work in a plain model, all the known explicit rate one constructions are actually against functions that has input locality one and output locality one. Such tempering families is referred to as speed level tempering in the literature. So now let me tell you about our compiler. So fix any constant c between zero and one, our compiler will use the following ingredients with appropriate parameters. First, we will be using error correcting secret sharing schemes that has rate one and the near linear distance and also near linear independence. Such error correcting secret sharing schemes could be based on standard read Solomon code. Secondly, we will be using a base non-mailable code that is secure against order of log n local tempering. So this base non-mailable code could possibly have very low rate and in addition to non-mailability, we require it to be resilient to a constant fraction of leakage. Finally, we will also be using a pseudo random generator against a finite stain machine by Nissan. So we remark that other alternative pseudo random objects potentially also suffice here. So given these three ingredients, our error correcting secret sharing schemes, a base non-mailable code and a suitable pseudo random objects, our compiler will use these three ingredients in a black box way to output a rate one non-mailable code against the c times log n local tempering families. So our construction draws inspiration from the following two components. The first is a rate amplification techniques by Agarwa at all. And second is a PRG techniques by Boyd all. So let me tell you a bit about both of them. So Agarwa at all constructed a rate one non-mailable code against a bit level tempering. So here is just a very simple example of what a bit level tempering looks like. So such functions has input locality one and output locality one. So their compiler is constructed in the following way. So given any message, the first they first encoded this message using error correcting secret sharing schemes to obtain a code word A. Next, they will sample a subset of those indices from code word A. And for roughly half of those indices, they intentionally introduce errors into this code word. And for the other, roughly other half of those indices, they will keep those bits untouched. Next, they were encoded this consistency check information using a base non-mailable code. So their final code word consists of two parts. The main code word C, the main code word C, which is error correcting code with arrow introduced, and then a tag which contains, excuse me, contains the consistent check information. So to decode this code word, one first decode the erroneous error correcting code and then cross check the information of those errors with the tag to see if they are consistent. So unfortunately, their techniques here does not extend to tampering functions with high input locality. Actually their compiler does not even extend to functions with input locality too. So in order to deal with this technical challenge, we use the PRG technique by Boydor to circumvent the technical challenges posed by input bits with high input locality. So on a very, very high level, imagine you have a code word that has two parts, the left part and right part. So these techniques will keep the left part as it is and then hide the right part among many, many redundant bits. And the position of those informative bits from the right part is hide among the string pseudo-randomly. So using this, one can argue that it is very unlikely that an informative bits from the string actually have a high input locality. So this property turns out to be very useful for our proof. So given, so our compiler first follows the framework by Agawa at all. We also encoded the message using an error correcting code and then introduced some errors and also keep some bits untouched and record this information using a base non-manable code. And after that, we will be using a PRG to hide this tag among a list of strings that contain both the redundant bits and the informative bits from the tag. So our final code word consists of three parts. The main code word, which is an error correcting code with errors introduced, then a seed for the PRG and then this string here that contains both redundant bits and informative bits from tag. So the length of this code word is roughly same as the length of the main code word. So let me give you a very brief sketch of our proof. So our proof roughly falls from the following way. So we first argue that the tampering happens on the tag is actually independent of the message here. Then given this observation, we can say that the tampering on the tag either keeps the consistent check information identical or fix this consistent check information to a constant. So this is given by the property of the base non-manable code. So finally, our intuition is that if the adversary keeps this tag identical, then the only valid tampering is to also keep the main code word identical. Conversely, if the adversary fixed the tags to be some constant string, then the only valid tampering is to also fix the main code word to some constant. So the idea is that if the adversary does not tamper this code word in this way, then with probability one minus negligible, he will always fail the consistency check. So the hardness of this proof completely lies in how do we prove this intuition? So unfortunately, I don't have time to go into the details of this proof. I would be happy to discuss this offline and I will end my talk here. Thank you. Questions? Yeah, you said that there was a previous result that supported log locality. I think one of the authors was Faust and it was efficient. So can you explain again what is the difference? So they show that it's a probabilistic construction. They show that actually with probability one, their probabilistic construction will be secure against that tampering family. However, we cannot de-randomize such Monte Carlo construct. So it's not an explicit construction? No, it's not explicit. More questions? Let's thank the speaker again.